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[ "We are a GIS platform-as-a-service company, connecting people, their location, their need at a particular time. ", "We believe in developing rock solid, highly performing, scalable and stable platform for our customers.", "\n\nMenu\n\nMonthly Archives: October 2012\n\nJersey is suppose to make things easier. ", "Well, it does, but also add’s its own set of challenges along the way. ", "A bunch of crazy exceptions that our developer community out there is completely unclear on how to solve. ", "So with this blog, I hope to document some common causes and fixes for most of the exceptions that I have got.", "\n\nSelf Advertisement\n—–Start of Advertisement——-\nBUILD CAR POOL SOLUTIONS ON ANY DEVICE TO RUN ANYWHERE (www.mcruiseon.com). ", "Introducing mCruiseOn, the java library /json api’s that you can use to build a car pool solution. ", "Be the next avego.com, carpooling.com, zimride.com. ", "mCruiseOn is your one stop API on EC2.", "\n——End of Advertisement——-\n\nThats the point right, if something ain’t that easy to understand, how easy will it be to implement and maintain ? ", "The challenge is to understand it in one go.", "\n\nMemcached is a distributed memory object caching system. ", "No, that is not the way I am going to explain it, so chill :).", "\n\nWe all know that our webservers have web applications that run database query’s to get data. ", "They also call query’s to insert, delete and update data. ", "As simple as it sounds, its crazy to get such a system working when millions of connections on the webserver get requests. ", "Webservers need to be added in parallel to handle load, databases need to be replicated so that in parallel data can be accessed, and then starts the complication of ensuring that data is consistent across all the requests. ", "Then comes the challenge of ensuring data is available quickly enough.", "\n\nBad examples are http://www.irctc.co.in. ", "But its important to understand how difficult it is to get it right. ", "Especially if your data is as complex as the Indian Railways. ", "If this site is down, the nation stops.", "\n\nNow, for some basic computer fundamentals. ", "Just as a quick reminder. ", "We all know that tape drives are slower than floppy disks. ", "Floppy disks are slower than hard disks. ", "Hard disks are slower than memory. ", "And memory is slower than CPU memory. ", "CPU memory is much more expensive than memory, and the story continues. ", "Faster the memory the more expensive it will be.", "\n\nWhat is serialization ? ", "A object that can be stored on a disk byte by byte, and read back to form that object again, is called a Serializable object.", "\n\nNow, imagine. ", "If I store a file on a harddisk, and read it. ", "Will it be faster if I read it from the memory ? ", "Obviously. ", "We dont use fread (file read, File.read()) for every operation we want to perform. ", "We first read it into a String, and then read it from that String. ", "Memcached does something similar. ", "It stores all data given to it in memory. ", "So that you can read from it faster as compared to a harddisk.", "\n\nSo, if you have a piece of code doing a lot of read from harddisks, (mind you databases are also stored in big harddisks), AND if that data is needed to be read multiple times, then you can write that data to memcached. ", "So instead of reading data from the harddisk all reads can goto memcached. ", "There by preventing the harddisk from the extra effort for each read. ", "It can do something more important in that time.", "\n\nMemcached provides you with a way to identify the data that you just wrote with a identifier, a name or a key. ", "We call it key value pair.", "\n\nWhen you load memcached, you need to specify the amount of memory that this machine will dedicate for memcached. ", "And memcached reserves that much memory for itself (the -m command). ", "So, what happens when u run out of memory.", "\n\nSimple load memcached on another machine, and get both these memcached machines to know each other (this is called a cluster). ", "Then you can refer to the cluster and add objects. ", "Memcached will store objects in round robin between the servers on the cluster.", "\n\nNow, your application needs to identify from its request if similar data is being requested between its clients. ", "If it is, then the first call can save that common data on memcached, and subsequent calls can retrieve the data from memcached.", "\n\nJust remember, that memcached is a “explicit cache”. ", "Which means you need to add stuff to memcached, remove it, updated it. ", "It does “nothing” automatically. ", "At this point many people get turned off, but the concept of memcached is to save your trip to the database, and reduce the need for clustering a database and webservers. ", "Since clustering memcached is very cheap, as compared to database and webservers." ]

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[ "Senate Democrats seek to drive wedge between business and Republicans\n\nSenate Democrats, who are desperate to stimulate the economy but don’t have the money to pass traditional stimulus legislation, will turn to cutting business taxes when they return to Washington this fall.", "\n\nIn doing so, they will try to drive a wedge between business interests and the GOP leadership, who has tried to block almost every element of the Democratic agenda, by pushing a round of corporate tax breaks, say Senate Democratic aides.", "\n\nThe strategy has appeal on two grounds.", "\n\nADVERTISEMENT\n\nThe legislation would stimulate the economy at a time when many economists argue the government must step in to revive demand despite it not being politically feasible to pass traditional infrastructure spending bills.", "\nIt would also force Republican leaders to either endorse the Democratic agenda or block proposals that are popular among corporate leaders and domestic manufacturers.", "\n\nBut the plan is not without pitfalls. ", "Democratic leaders could find centrists and liberals within their caucus divided over how to structure the tax cuts and whether they must be paired with infrastructure spending programs, as some liberals might demand.", "\n\nDemocrats have found themselves at odds with the business lobby for much of their reign in the majority, fighting over healthcare, cap-and-trade and other regulations.", "\nAnd they were disappointed businesses did little to help them in their standoff with House Republicans over raising the debt limit, even though business leaders saw the mere threat of a default as dangerous.", "\n\nTheir new plan could net them the support of groups like the U.S. Chamber of Commerce, which traditionally supports Republicans — both politically and financially.", "\n\nTheir first tax proposal is to make the corporate research and development tax credit permanent. ", "The second is to pass an Advanced Energy Manufacturing Tax Credit. ", "This would create a 30 percent tax credit for companies that manufacture new clean-energy technologies, which Democratic aides say would help create thousands of new jobs around the country.", "\n\nA third idea is to extend the payroll tax cut Congress enacted in December and expand it to employers, reducing the cost of labor. ", "And a fourth option is to give employers tax breaks for hiring new employees, an idea Democratic members of the Senate Finance Committee panned in 2009 but now seems more attractive.", "\n\n“We’ll be looking at things in the tax-cut variety. ", "All will be proposals that have a history of bipartisan support or animate the business community in a way that Republicans will go along,” said a Senate Democratic leadership aide.", "\n\nThe aide said other proposals might include tax incentives for people who make their homes more energy efficient.", "\nSome of these ideas will be included in a jobs agenda Senate Democrats plan to unveil upon their return in September.", "\nLegislation to make permanent the research and development (R&D) tax credit is expected from Senate Finance Committee Chairman Max Baucus (D-Mont.).", "\n\n“Chairman Baucus is always working to find ways to boost the economy and help businesses create jobs, and he supports a permanent extension of the R&D credit as a part of that effort,” said a committee aide. “", "He has, on a bipartisan basis, sought expansions and improvements to the credit to spur growth at home and boost American competitiveness abroad, and he remains committed to that end.”", "\n\nA spokeswoman for Sen. Orrin Hatch (Utah), the senior Republican on the finance panel, said her boss would support making the research and development tax credit permanent.", "\n\n“Senator Hatch has long championed the R&D tax credit — a credit that is so effective at encouraging investment and growth that the deficit commission endorsed it by keeping it in place last December,” said Julia Lawless, a Republican spokeswoman on the Finance Committee. “", "He's working on legislation extending this critical job-creating tax incentive and is discussing how to move forward with it with his colleagues.”", "\n\nBut the Democratic plan to advance legislation making the research and development tax credit permanent could become ensnared in internal caucus politics.", "\nThe R&D tax break now stands at 14 percent, and businesses want to increase it to 20 percent, according to Monica McGuire, senior policy director at the National Association of Manufacturers (NAM).", "\n\nBut some Democrats want any increase in the tax credit to be contingent on a company basing a high proportion of its manufacturing within the United States.", "\n\n“We have a proposal that would increase the R&D tax credit for companies that would do most of their manufacturing here,” said Ryan McConaghy, director of the economic program at Third Way, a centrist Democratic think tank.", "\n\nNAM rejects this idea.", "\n\n“Those proposals penalize U.S. multinational companies,” said McGuire, who also serves as executive secretary of the R&D Credit Coalition. “", "Only 6 percent of world’s population lives in the U.S. I think it’s pretty well understood that for U.S. companies to grow they need to expand their markets. ", "There are a lot of reasons a U.S. company is going to manufacture abroad.”", "\n\nSens. ", "Debbie Stabenow (D-Mich.), Sherrod Brown (D-Ohio) and Jeff Bingaman (D-N.M.) are pushing the Advanced Energy Manufacturing Tax Credit. ", "The credit was first enacted as part of the economic stimulus legislation Congress passed in 2009, which set aside $2.3 billion for companies that build new clean energy technologies. ", "That amount was quickly exhausted as companies applied for $7 billion worth of tax breaks under the law.", "\n\nA Senate Democratic aide said NAM supports the proposal and Democratic leaders had discussed including it in the September jobs agenda." ]

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[ "Category Archives: Uncategorized\n\nCross-posted from HOPE This article first appeared on the Deakin University website. ", "Professor Johnstone has been a consistent critic of what she says is the ‘Alzheimerisation’ of the euthanasia debate: The way Alzheimer’s disease is portrayed by advocacy groups and the media is having undue influence on the euthanasia debate, according to a Deakin University nursing ethics\n\nCross-posted from ProLife NZ, originally appears in Princeton ProLife In the ongoing debate about cloning human embryos for research, and about destroying them in order to harvest their stem cells, it is important to keep some basic facts in mind. ", "Our moral analysis must be built upon fundamental scientific truths. ", "If we obscure the facts,\n\nCross-posted from BioEdge with modification It is illegal in Australia, taboo across Asia, and a political and moral minefield to boot, yet poll after poll shows 80 percent of Australians want voluntary euthanasia introduced. ", "The nation shocked the world in the 1990s when the Northern Territory became the first place in the world to permit" ]

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[ "Corning Incorporated, Corning, N.Y., has marketed glass lenses which polarize radiation in the red to near infrared portion of the radiation spectrum for a number of years under the trademark POLARCOR.RTM.. Those lenses are prepared in accordance with the method described in U.S. Pat. ", "No. ", "4,479,819 (Borrelli et al.). ", "As is explained in that patent, the method involves four fundamental steps:\n(a) a glass article of a desired configuration is fashioned from a composition containing silver and at least one halide from the group of chloride, bromide, and iodide;\n(b) that glass article is heated to a temperature above the strain point, but not higher than about 50.degree. ", "C. above the softening point of the glass, for a sufficient period of time to generate crystals therein of AgCl, AgBr, and/or AgI;\n(c) that crystal-containing article is elongated under stress at a temperature above the annealing point, but below that at which the glass exhibits a viscosity of about 10.sup.8 poises, such that the crystals are elongated to an aspect ratio of at least 5:1, and thereafter;\n(d) that article is exposed to a reducing environment at a temperature above about 250.degree. ", "C., but no higher than about 25.degree. ", "C. above the annealing point of the glass, for a sufficient length of time to develop a chemically reduced surface layer on the article wherein at least a portion of the elongated silver halide particles is reduced to elemental silver.", "\nThree different general base types of silver halide-containing glass compositions are disclosed therein: (1) glasses containing copper which exhibit photochromic behavior; (2) glasses having similar base compositions, but wherein copper is absent so that the glasses do not exhibit photochromic behavior; and (3) glasses having compositions in the alkali metal oxide borosilicate system containing high levels of B.sub.2 O.sub.3 which do not display photochromic behavior. ", "Readily-reducible metal oxides, such as PbO and Bi.sub.2 O.sub.3 will be avoided.", "\nIn the preferred embodiment of the first two types of glasses, each had a base composition consisting essentially, expressed in terms of weight percent on the oxide basis, of 6-20% R.sub.2 O, wherein R.sub.2 O consists of 0-2.5% Li.sub.2 O, 0-9% Na.sub.2 O, 0-17% K.sub.2 O, and 0-6% Cs.sub.2 O, 14-23% B.sub.2 O.sub.3, 5-25% Al.sub.2 O.sub.3, 0-25% P.sub.2 O.sub.5, 20-65% SiO.sub.2, 0.004-0.02% CuO, 0.15-0.3% Ag, 0.1-0.25% Cl, and 0.1-0.2% Br, the molar ratio R.sub.2 O:B.sub.2 O.sub.3 ranging between about 0.55-0.85, where the composition is essentially free from divalent metal oxides other than CuO, and the weight ratio Ag:(Cl+Br) ranging about 0.65-0.95. ", "In the second type of glass, CuO is omitted from the composition such that the glass does not demonstrate photochromism.", "\nThe third type of glass containing silver halide crystals may contain copper and consists essentially, expressed in terms of weight percent on the oxide basis, of 5-12 alkali metal oxides, 1-15% Al.sub.2 O.sub.3, 27-35% B.sub.2 O.sub.3, and the remainder SiO.sub.2, the molar ratio (R.sub.2 O--Al.sub.2 O.sub.3):B.sub.2 O.sub.3 preferably being less than 0.25.", "\nThe elongated metallic silver particles can polarize light in the visible and/or near infrared regions of the radiation spectrum depending upon the size and aspect ratio of the elongated silver halide crystals. ", "Nevertheless, inasmuch as the preferred reducing treatment penetrates the glass only to a depth of about 20 microns, a large population of photochromic silver halide crystals will be left in the glass matrix of the first type of glass described above. (", "The depth to which the reducing heat treatment penetrates is controlled by the time and temperature of the treatment.) ", "The phenomenon of photochromic behavior is of no consequence when the polarizing effect takes place in the infrared regime of the radiation spectrum. ", "Photochromism becomes a problem, however, where polarization in the visible portion of the radiation spectrum is desired.", "\nAs was discussed above, copper-free, silver halide-containing glasses which display no photochromic behavior have been prepared. ", "Unfortunately, whereas photochromism was not displayed by the glasses, the silver was reduced to the metallic state during melting of the glass batch or during the subsequent heat treatment to generate silver halide crystals. ", "That action is evidenced in the formation of a red colored glass. ", "This premature reduction of the silver precludes the formation of silver halide crystals in the subsequent heat treatment. ", "As indicated in U.S. Pat. ", "No. ", "4,479,819, supra, the elongated silver halide crystals, wherein at least a portion thereof is reduced to elemental silver, imparts the polarizing capability to the glass.", "\nThe mechanism via which the inclusion of copper inhibits the reduction of Ag.sup.+ ions to Ag.degree. ", "metal has been explained as follows. ", "The presence of Cu.sup.+2 ions in the glass composition provides protection against the reduction of Ag.sup.+ ions to Ag.degree. ", "by the reaction Cu.sup.+2 .fwdarw.", "Cu.sup.+. ", "Hence, the elimination of copper from the glass removes this protection, thereby allowing the reaction Ag.sup.+ .fwdarw.", "Ag.degree. ", "to take place.", "\nTherefore, the primary objective of the present invention was to develop glass compositions containing silver halides which, when heat treated to generate silver halide crystals that can be elongated to impart polarizing properties to the glasses, would not exhibit photochromism when exposed to radiation in the ultraviolet/visible portions of the radiation spectrum, and wherein silver ions present in the glasses would not be reduced to metallic silver during the melting process or the heat treatment step." ]

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[ "Live in Buenos Aires (Coldplay album)\n\nLive in Buenos Aires is the sixth live album by Coldplay, released on 7 December 2018. ", "The album was recorded on 14 and 15 November 2017 in La Plata, which was the final concert of the A Head Full of Dreams Tour. ", "\n\nLive in Buenos Aires and Live in São Paulo are both featured in Coldplay's seventh compilation album, The Butterfly Package. ", "Live in São Paulo was filmed on 7 and 8 November 2017. ", "The set also includes the documentary Coldplay: A Head Full of Dreams, directed by Mat Whitecross, about the album of the same name. ", "Its release marks the first time a Coldplay concert has been released in full.", "\n\nPackaging\nThe album was made available as a two-DVD/two-CD set and a two-DVD/three gold vinyl set. ", "The package has been labelled \"The Butterfly Package\". ", "A two-CD set featuring only Live in Buenos Aires was also made available. ", "Digitally, the album was made available to stream and download, while the concert film is only available to download. ", "The Icelandic artist Kristjana S. Williams created the artwork for the package.", "\n\nPromotion\nThe band had announced the release of the A Head Full of Dreams documentary in mid-October. ", "The following week, the set was announced by the band on social media with a clip of them performing \"Viva la Vida\", on November 2 live performance of \"Fix You\" and on November 29, \"A Head Full of Dreams\" To promote the premiere of A Head Full of Dreams on Amazon Prime Video, Coldplay premiered three live tracks through Amazon Music from 26 October: \"Stayin' Alive\" (live at Glastonbury) with Barry Gibb; \"Us Against the World\" (live in Leipzig) and \"Don't Panic\" (live in Paris).", "\n\nControversy\nThe newspaper El Día of La Plata, the city where the concert took place in Argentina, questioned the album's/video's title for including the city name Buenos Aires, which is located a distant 60 kilometers away from La Plata. ", "According to the article, \"Although for many this situation is a trifle, for others it is a great disappointment when their idols do not name their city, especially after years and years of having crossed the highway to go see these great events. ", "That's why the disappointment, being local, is greater, they feel ignored.\"", "\n\nTrack listing\nAll tracks written by Guy Berryman, Jonny Buckland, Will Champion, and Chris Martin, except where noted.", "\n\n2 CDs / Digital download\n\nPersonnel\n Guy Berryman – bass guitar, keyboard, backing vocals\n Jonny Buckland – electric guitar, keyboard, backing vocals\n Will Champion – drums, electronic drums, backing vocals, percussion, acoustic guitar, piano; lead vocals on \"In My Place\"\n Chris Martin – lead vocals, keyboards, acoustic guitar, piano; backing vocals on \"In My Place\"\n\nCharts\n\nWeekly charts\n\nYear-end charts\n\nCertifications\n\nReferences\n\nCategory:2018 live albums\nCategory:2018 video albums\nCategory:Coldplay live albums\nCategory:Coldplay video albums\nCategory:Parlophone live albums\nCategory:Parlophone video albums" ]

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[ "Q:\n\nIs it possible to become a vampire because you consume vampire dust\n\nCould it be possible that i became a vampire by consuming too much vampire dust? ", "\nI was never hit by a vampire (sneaking thief bastard) but i contracted it after the morthal mission and consuming the various vampire dust ingredient i found on site.", "\nObviously i noticed it and reloaded and cured the disease before getting my final vampire form...\n\nA:\n\nWhen they do their life drain effect you have a chance to contract it I believe. ", " Shouldn't be anything related to the dust, least nothing that I've ever read.", "\n\n" ]

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[ "- food - go visit any restaurant or mall, see how people leave their food untouched,\n\n- secure place to sleep - i actually think, this one is a bit harder, because this is our weakest point, the moment people dare to rob us, and continually stay alert would have impact to our own body,\n\n- commitment - this is one of the harder part too, because you cant choose what lifestyle you want as you wish when you already involved others inside your life, your wife, your parent, etc, kids,\n\n-\n\n- this is another story, about the logicomix\n\nQuote:\n\nLogicomix: An Epic Search for Truth is a graphic novel about the foundational quest in mathematics, written by Apostolos Doxiadis, author of Uncle Petros and Goldbach's Conjecture, and theoretical computer scientist Christos Papadimitriou of the University of California, Berkeley. ", "Character design and artwork are by Alecos Papadatos and color is by Annie Di Donna.", "\n\n- the graphics are so beautiful,\n\n-\n\nQuote:\n\nIn philosophy and logic, the classical liar paradox or liar's paradox is the statement of a liar who states that they are lying: for instance, declaring that \"I am lying\" or \"everything I say is false\". ", "If they are indeed lying, they are telling the truth, which means they are lying.", "\n\n- the struggle to find truth, to find something that we could hold,\n\n- the logic of infinity,\n\n- imagine about infinity could cause me so much excitement, the very large number,\n\n- actually, pondering about circle is kinda excitement too,\n\n- lying on coach, let the mind imagines, and entertain those inputs, damn, what a great moment,\n\nDude that's 3 different operational modes, it doesn't count that way Since the currently running mode is what counts as RISC. (", "I mean, all the basic operations are shared anyway, just different encodings, an add is still an add, etc)\n\nI was talking about instructions; otherwise, there's way too many encodings for the \"same\" instruction even in x86 (actually even more so due to memory operands which RISC don't have except on dedicated instructions). ", "Also, Thumb fewer than what? ", "You said X + Y + Z, I simply said, pick one, not necessarily Thumb.", "\n\nI know you'll say \"instructions\" is vague, but from the point of what it actually does, it's not really \"vague\".", "\n\nUhm, I mean actual effects of the instruction (in general, not special case). ", "sub reg, reg and xor reg, reg are different since they are only identical with \"reg, reg\" combination etc (just to clarify). ", "Of course, stuff like \"cmov\" I consider as one instruction with different suffixes/modes/prefixes etc. ", "More like \"common sense\" than not. ", "It's not super technically precise, but then, neither is the RISC/CISC definition anyway.", "\n\nI wouldn't consider \"add eax, ebx\" and \"add al, bl\" as two different instructions though... even if they have different opcodes (not even override prefix).", "\n\nUltimately these instructions does have a \"logic\" behind being labeled like this: they likely share the same hardware under-the-hood too.", "\n\nThe German-born physicist had won the Nobel and was in Japan on a lecture tour.", "\n\nWhen the courier came to his room to make a delivery, he did not have any money to reward him.", "\n\nInstead, he handed the messenger a signed note - using stationery of the Imperial Hotel Tokyo - with one sentence, written in German: \"A calm and humble life will bring more happiness than the pursuit of success and the constant restlessness that comes with it.\"", "\n\nA second note written at the same time simply reads: \"Where there's a will, there's a way.\" ", "It sold for $240,000, Winner's auction house said.", "\n\nSince there's always an opcode followed by extra bytes (mod R/M, imm, disp, SIB, etc) or preceeded by prefixes. ", "Or an opcode extension. ", "Either way, the only thing \"add al\" and \"add eax\" differ in is the opcode byte, thus their opcode is different.", "\n\nYou cannot post new topics in this forumYou cannot reply to topics in this forumYou cannot edit your posts in this forumYou cannot delete your posts in this forumYou cannot vote in polls in this forumYou can attach files in this forumYou can download files in this forum" ]

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[ "/*\n * Copyright (C) 2015 Kaspar Schleiser <[email protected]>\n * 2015 Freie Universität Berlin\n *\n * This file is subject to the terms and conditions of the GNU Lesser\n * General Public License v2.1. ", "See the file LICENSE in the top level\n * directory for more details.", "\n *\n */\n\n/**\n * @ingroup sys_auto_init_gnrc_netif\n * @{\n *\n * @file\n * @brief Auto initialization for ENC28j60 Ethernet devices\n *\n * @author Kaspar Schleiser <[email protected]>\n * @author Hauke Petersen <[email protected]>\n */\n\n#include \"log.h\"\n#include \"enc28j60.h\"\n#include \"enc28j60_params.h\"\n#include \"net/gnrc/netif/ethernet.h\"\n\n/**\n * @brief Define stack parameters for the MAC layer thread\n * @{\n */\n#define ENC28J60_MAC_STACKSIZE (THREAD_STACKSIZE_DEFAULT)\n#ifndef ENC28J60_MAC_PRIO\n#define ENC28J60_MAC_PRIO (GNRC_NETIF_PRIO)\n#endif\n/*** @} */\n\n/**\n * @brief Find out how many of these devices we need to care for\n */\n#define ENC28J60_NUM ARRAY_SIZE(enc28j60_params)\n\n/**\n * @brief Allocate memory for the device descriptors\n * @{\n */\nstatic enc28j60_t dev[ENC28J60_NUM];\n/** @} */\n\nstatic gnrc_netif_t _netif[ENC28J60_NUM];\n\n/**\n * @brief Stacks for the MAC layer threads\n */\nstatic char stack[ENC28J60_NUM][ENC28J60_MAC_STACKSIZE];\n\n\nvoid auto_init_enc28j60(void)\n{\n for (unsigned i = 0; i < ENC28J60_NUM; i++) {\n LOG_DEBUG(\"[auto_init_netif] initializing enc28j60 #%u\\n\", i);\n\n /* setup netdev device */\n enc28j60_setup(&dev[i], &enc28j60_params[i]);\n gnrc_netif_ethernet_create(&_netif[i], stack[i], ENC28J60_MAC_STACKSIZE,\n ENC28J60_MAC_PRIO, \"enc28j60\",\n (netdev_t *)&dev[i]);\n }\n}\n/** @} */\n" ]

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[ "Executive functions, depressive symptoms, and college adjustment in women.", "\nMany students have difficulty adjusting to college, and the contribution of academic and relational factors have been considered in previous research. ", "In particular, depression commonly emerges among college women at this time and could be related to poor adjustment to college. ", "This study examined the relationship between executive functions, depressive symptoms, and college adjustment in college women. ", "Seventy-seven female participants from a midsize urban university completed the Wechsler Abbreviated Scale of Intelligence, College Adjustment Scale, Beck Depression Inventory-Second Edition, Behavior Rating Inventory of Executive Function-Adult Version, and four subtests from the Delis-Kaplan Executive Function System: the Trail-Making Test, Design Fluency Test, Verbal Fluency Test, and Color-Word Interference Test. ", "After controlling for IQ score, hierarchical regression analyses showed that subjective and objective measures of executive functioning and depressive symptoms were significantly related to college adjustment problems in academic, relational, and psychological areas. ", "The current study provides evidence for a relationship between cognitive abilities, psychiatric symptoms, and college adjustment." ]

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[ "I don’t understand why people want to continue kicking down Penn State and the State College Community. ", "The outrage is justified, make no mistake about it. ", "But it has reached such a magnified state of frenzy that a mob with pitchforks and torches are descending upon Happy Valley. ", "The “guilty by association” argument is too simplistic.", "\n\nExtrapolate that argument, and you have some really tough questions:\n\nShould we bankrupt the city of Boston, tear down Fenway Park, and destroy the busts of the great Red Sox players in the HOF for the twenty years (1971-1990) they knowingly hid Donald Fitzpatrick and his acts of child molestation?", "\n\nShould we dismantle the Democratic Party for its role in the Japanese internment and subsequent work to suppress it from the history books?", "\n\nShould we dismantle the Republican Party for its role in covering up Watergate?", "\n\nShould we bankrupt and tear down the Citadel, for knowingly covering-up sexual assaults in the 2000’s?", "\n\nShould we bankrupt Rome and tear down every cathedral for its cover-up of child molestation over the last century?", "\n\nShould we bankrupt the military and tear down every military memorial in D.C. in light of the many lawsuits of rape cover-ups (years unknown)?", "\n\nShould we bankrupt the FBI for it’s cover-up of flawed 1990s investigations once promised to reveal the innocently convicted, but instead led to not one single report?", "\n\nIf a critic says yes to all of these questions, and will fight tooth-and-nail to destroy the Red Sox, both political parties, the Catholic Church, the U.S. Military, and the FBI, then we will have to agree to disagree. ", "The argument stops here, and we should simply part ways.", "\n\nPerhaps he or she has never worked for a bureaucracy, and in that context, cannot identify with what went on at Penn State, or the fact that what went on here has sociological implications beyond simply discussing who’s a bad or good guy. ", "Bureaucracies dehumanize workers and officials alike. ", "Organizational Theorists have known that fact for decades and still struggle to develop an antidote for it. ", "But to destroy an entire organization, like Penn State’s, would amount to the destruction of innocent people — people with families and livelihoods, human beings like you and me who also have dreams. ", "Such would render more innocent victims, and although the violation is not sexual, the economic and educational impact will be significant enough to affect many for a lifetime.", "\n\nDashed dreams are dashed dreams. ", "Many locals depend on the economic power from the university. ", "Many people would never have been able to receive a college education, or the chance to strive for a better future, if it was not for the discount offered to parents working as faculty and staff at the university. ", "To be a defender of children is to be a defender of ALL children. ", "A scorch-Earth policy will render more children’s dreams dashed, and more victims pondering what might have been. ", "Let us not forget that many people here in this region are those very same victims of child sex abuse. ", "Has it not occurred to critics that many of Sandusky’s own victims are members of our community too?", "\n\nIt is way too easy for a less-well-thought-out critic to dismiss somebody like me as one who cares nothing about children and sex abuse, or that I have drunk the “Kool-aid” of power worship. ", "That sort of dismissal is precisely what led people not to truly study and understand the underlying issues at Penn State, a large bureaucratic organization.", "\n\nPenn Staters and State Collegians, like me, have every reasonable motive (a term borrowed from the Freeh report) to make sense of the tragedy that occurred. ", "We have every reasonable motive to read each article and report with a critical eye. ", "The sweeping generalizations and calls to punish even the most innocent people in my town and my school, yes even the children, are leveled by those with less connections, those who would think nothing of destroying the livelihood of others (but would hypocritically fight tooth-and-nail if they themselves felt wrongfully persecuted).", "\n\nFor them, there is no reasonable motive to read reports with a critical eye. ", "Collateral damage means little to them. ", "Ironically, with this sort of thinking, there is a need for the very same sort of face-saving, that years ago led to tragic decisions at PSU, but today only leads to the never-ending competition to show that one can be more against child abuse than the next person. ", "Let’s not manufacture a competition about who’s more or less against child abuse and just accept that practically everyone is disgusted by it.", "\n\nThe same pride that led to the downfall of Penn State administrators is now leading to the mindlessness of condemners worldwide who drink the “kool-aid” of media sensationalism. ", "Penn Staters and State Collegians are actively seeking to go through the phases of grief and betrayal (anger and denial are included). ", "Unhealthily, some critics remain stuck in the stage of anger.", "\n\nThere are many flavors of kool-aid, and just because Penn Staters have been called out for drinking theirs, does not mean that the condemners have not already picked out to drink another flavor. ", "We all know what a “mob mentality” is.", "\n\nSome critics who claim, “I would never mindlessly join a mob,” have real reason to pause and consider if, right now, they have been caught up in one anyway? ", "Some officials at Penn State should have stood up against temptations not to challenge the organizational culture. ", "Today, some critics are faced with the dilemma of whether they too have the strength to face down a media culture of indiscriminate vengeance.", "\n\nJoe Paterno should have considered going against the dominant narrative. ", "Spanier should have considered going against the dominant narrative. ", "Curley should have considered going against the dominant narrative. ", "Schultz should have considered going against the dominant narrative. ", "So too should the critics calling for the destruction of all of Central Pennsylvania consider going against the dominant narrative." ]

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[ "Introduction\n============\n\n*Streptococcus pneumoniae* (the pneumococcus) is a pathobiont mainly colonizing the nasal passages but capable of causing invasive disease ([@B1]). ", "Thus it is exposed to a variety of nutrient profiles in its environment, such as a glucose-dominated environment in the blood or a galactose (and GlcNAc)-dominated environment in the respiratory mucus of the nasopharynx ([@B2]). ", "Recent studies have investigated the host glycan sugar-specific pathways in *S. pneumoniae* ([@B3], [@B4]). ", "This has provided an accurate map of the biochemical pathways for the pneumococcal galactose, mannose, and GlcNAc catabolism. ", "It also has been shown that the transcriptional response to glucose is strong and that in the central carbon metabolism, glucose exerts mostly negative regulation ([@B5]). ", "Recently, the growth and metabolism of *S. pneumoniae* has been studied by *in vivo* NMR techniques, which has paved the way to a better understanding of central metabolism regulation ([@B6]) ([Fig. ", "1](#F1){ref-type=\"fig\"}). ", "The central carbon metabolism of *S. pneumoniae* has also been studied by isotopologue profiling, which allowed investigation of the biosynthesis of amino acids ([@B7]).", "\n\n![**", "Schematic illustration of metabolic pathways in *S. pneumoniae*.** ", "Adapted from Refs. [", "@B3], [@B11], [@B14], and [@B53]. *", "I*: *fruA* fructose uptake phosphotransferase transporter (*red*); *II*: *manLMN* monosaccharide uptake phosphotransferase transporter (*red*); *III*: membrane-spanning protein able to take up free fructose, PtsG analog (*red*); *1,3-DPG*, 1,3-diphosphoglycerate; *3-PG*, 3-phosphoglycerate; *6-PGL*, 6-phosphogluconolactonase; *DHAP*, dihydroxyacetone phosphate; *fba,* fructose-bisphosphate aldolase; *fki,* fructokinase; *Frc-1,6bP*, fructose 1,6-bisphosphate; *Frc-1P*, fructose 1-phosphate; *Frc-6P*, fructose 6-phosphate; *G6PDH*, glucose 6-phosphate dehydrogenase; *gale,* UDP-glucose 4-epimerase; *galU,* glucose 1-phosphate uridyltransferase; GAP, glyceraldehyde 3-phosphate; *gapA,* glyceraldehyde 3-phosphate dehydrogenase; *gapN,* glyceraldehyde 3-phosphate dehydrogenase (NADP+); *gki,* glucokinase (*orange*); *Glc-1,5lac-6P*, glucono-1,5-lactone 6-phosphate; *Glc-1P*, glucose 1-phosphate; *Glc-6P*, glucose 6-phosphate; *GlcN-1P*, glucosamine 1-phosphate; *GlcN-6P*, glucosamine 6-phosphate; *GlcNAc-1P*, GlcNAc 1-phosphate; *GlcNAc-6P*, GlcNAc 6-phosphate; *glmM,* phosphoglucosamine mutase; *glmS,* glutamine-fructose 6-phosphate aminotransferase; *glmU,* bifunctional protein (acetyltransferase, uridyltransferase); *gnd,* 6-phosphogluconate dehydrogenase; *manLMN,* monosaccharide uptake phosphotransferase (*orange*); *murA,* UDP-GlcNAc enolpyruvyl transferase; *murB,* UDP-*N*-acetylenolpyruvoylglucosamine reductase; *murC-F,* peptide ligases; *nagA,* α-*N*-acetylgalactosaminidase; *nagB,* glucosamine 6-phosphate deaminase; *pfkA,* ATP-dependent 6-phosphofructokinase; *pfkB,* 1-phosphofructokinase; *pgi,* glucose 6-phosphate isomerase; *pgk,* phosphoglycerate kinase; *pgm,* phosphoglucomutase; *rpiA,* ribose-5-phosphate isomerase; *ScrT,* sucrose phosphotransferase transporter (*green*); *tkt1,* transketolase; *tpiA,* triose-phosphate isomerase; *UDP-Gal*, uridine diphosphate galactose; *UDP-Glc*, uridine diphosphate glucose; *UDP-GlcNAc*, uridine diphosphate GlcNAc; *UDP-MurNAc*, uridine diphosphate *N*-acetylmuramate; *UDP-MurNAc-p5*, uridine diphosphate *N*-acetylmuramate pentapeptide. ", "Hypothetical fructose-1,6-bisphosphatase (*FBPase*) is indicated in *gray*.](zbc9991914660001){#F1}\n\nIt is believed that the nutritional environment may not only influence the metabolism but is also relevant for the expression of one of the main pneumococcal virulence factors, its polysaccharide capsule. ", "It has been shown that changes in availability of oxygen accentuate differences in capsular polysaccharide expression ([@B8]). ", "In addition, we have studied the capsule type in pneumococcal strains grown in nutrient-restricted Lacks medium (MLM) and in rich undefined brain heart infusion broth supplemented with 5% fetal calf serum (BHI + FCS) and have shown that certain pneumococcal strains produce less exopolysaccharide if grown in nutrient-restricted conditions ([@B9]). ", "Different carbon sources present in the environment may also affect capsule expression differently. ", "Using chemically defined media (CDM),[^2^](#FN1){ref-type=\"fn\"} it has been shown that *S. pneumoniae* grown on fructose produce less capsule polysaccharide than those grown on glucose as the sole carbon source ([@B10]). ", "The effect of other carbon sources on the capsule is less clear, although it has been speculated that in medium containing galactose, the amount of capsule produced is higher than compared with glucose ([@B11]).", "\n\nCarbohydrates enter the pneumococcal cell via different transporters, and many of them have been investigated ([@B12]). ", "There is complexity to the pneumococcal sugar uptake, as many transporters accept multiple substrates, and many sugars are transported by more than one system ([@B12]). ", "The principal glucose transporter in *S. pneumoniae* is the mannose type PTS *manLMN*. ", "It has been shown by mutant analyses that the deletion of this PTS was the only one to affect the utilization of glucose ([@B12]) ([Fig. ", "1](#F1){ref-type=\"fig\"}). ", "However, other routes of glucose importation are hypothesized including uptake by ABC transporters ([@B11]). ", "As for fructose, the relevance of the *fruRBA* operon as a phosphoenolpyruvate-phosphotransferase system (PTS) has been described for *S. pneumoniae* but also for Group A Streptococci ([@B12], [@B13]). ", "However, again, the PTS *manLMN* or non-PTS as illustrated for *Escherichia coli* could hypothetically import fructose ([@B12], [@B14]). ", "On the other hand, sucrose (disaccharide glucose-fructose) is probably taken up via a different PTS transporter (*ScrT*) and afterward processed to glucose 6-phosphate and fructose ([@B4]).", "\n\nIn this study, we elucidate the influence of three different saccharides (glucose, fructose, and sucrose) on the capsule biosynthesis in various strains of *S. pneumoniae*, both commensal and invasive. ", "For investigating the influence of the different carbon sources on gene expression, RNA-Sequencing (Seq) was conducted and phosphorylated metabolites, which are important for capsule composition were quantified by ^31^P NMR. ", "In addition, isotopologue profiling was performed to study ^13^C-labeled glucose and sucrose incorporation into the pneumococcal capsule and to better understand the mechanism behind the capsule expression.", "\n\nResults\n=======\n\nPolysaccharide capsule thickness and growth curves are specific for glucose, fructose, and sucrose\n--------------------------------------------------------------------------------------------------\n\nIt has been previously hypothesized that exopolysaccharide production is reduced in *S. pneumoniae* in the presence of fructose as the only carbon source ([@B10]). ", "Therefore, we first aimed at determining the influence of glucose, fructose, and sucrose (disaccharide glucose-fructose) on capsule thickness. ", "Six wildtype (WT) strains with different serotypes were selected from our collection ([Table 1](#T1){ref-type=\"table\"}). ", "The structures of the chosen serotypes have been shown and can be found in the supporting material ([@B15]) ([Table S1](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)).", "\n\n###### \n\n***S. pneumoniae* strains used in this study**\n\n ID Serotype Capsule size RFLP*^[a](#TF1-1){ref-type=\"table-fn\"}^* MLST*^[b](#TF1-2){ref-type=\"table-fn\"}^*\n -------------------------------------------------------------- ---------- -------------- ------------------------------------------ ------------------------------------------\n *bp* \n **Wildtypes** \n     106.66 6B 17,506 3 2244\n     203.24 6C 17,677 11 NA*^[c](#TF1-3){ref-type=\"table-fn\"}^*\n     208.41 7F 24,127 8 191\n     B109.15 7F 24,127 8 191\n     201.38 9V 20,856 1 644\n     207.31 15 18,626 1 199\n     103.57 23F 22,330 11 507\n     110.58*^[d](#TF1-4){ref-type=\"table-fn\"}^* nt \\- 344\n **Δ*cps* Janus KO mutants** \n     106.66 Δ*cps* Janus*^[e](#TF1-5){ref-type=\"table-fn\"}^* nt \\- 3 2244\n     208.41 Δ*cps* Janus*^[e](#TF1-5){ref-type=\"table-fn\"}^* nt \\- 8 191\n     B109.15 Δ*cps* Janus*^[e](#TF1-5){ref-type=\"table-fn\"}^* nt \\- 8 191\n **Backtransformants** \n     106.66 cps 106.66*^[e](#TF1-5){ref-type=\"table-fn\"}^* 6B 17,506 3 2244\n     208.41 cps 208.41*^[e](#TF1-5){ref-type=\"table-fn\"}^* 7F 24,127 8 191\n ***cps* switch mutants** \n     208.41 cps 106.66*^[e](#TF1-5){ref-type=\"table-fn\"}^* 6B 17,506 8 191\n     106.66 cps 203.24*^[e](#TF1-5){ref-type=\"table-fn\"}^* 6C 17,677 3 2,244\n     106.66 cps 208.41*^[e](#TF1-5){ref-type=\"table-fn\"}^* 7F 24,127 3 2,244\n     106.66 cps 201.38*^[e](#TF1-5){ref-type=\"table-fn\"}^* 9V 20,856 3 2,244\n     106.66 cps 207.31*^[e](#TF1-5){ref-type=\"table-fn\"}^* 15 18,626 3 2,244\n     106.66 cps 103.57*^[e](#TF1-5){ref-type=\"table-fn\"}^* 23F 22,330 3 2,244\n\n*^a^* Restriction fragment length polymorphism (RFLP) type according to Ref. [", "@B9].", "\n\n*^b^* Multi-locus sequence type (MLST).", "\n\n*^c^* NA, not applicable.", "\n\n*^d^* Whole genome sequencing of nt (non-typeable) strain has been described ([@B52]).", "\n\n*^e^* From the collection of strains created by Hathaway *et al.* ([", "@B9]).", "\n\nCapsule thickness was determined by FITC-dextran exclusion assay during mid-log phase of growth in a chemically defined medium (CDM) ([Fig. ", "2](#F2){ref-type=\"fig\"}). ", "A clear decrease in capsule production was observed for the six chosen strains grown on fructose as compared with glucose-fed strains ([Fig. ", "2](#F2){ref-type=\"fig\"}*A*). ", "Findings were confirmed in capsule switch mutants with a 106.66 (MLST 2244) background and above mentioned, six serotypes ([Fig. ", "2](#F2){ref-type=\"fig\"}*B*). ", "In addition, serotype 7F WT (208.41) and cps switch mutant strains (106.66cps208.41) produced the thinnest capsule of all the strains when grown on glucose. ", "We therefore chose 106.66 (a strain with a thick capsule) and 208.41 (a strain with a thin capsule) and their mutants for further experiments. ", "Although capsule thickness was measured at mid-log phase, [Fig. ", "2](#F2){ref-type=\"fig\"}*C* shows that the growth phase in which the bacteria were harvested did not generally have a large influence on capsule thickness despite two significant findings.", "\n\n{#F2}\n\nInspection of the growth curves revealed that whereas bacteria grown on fructose did not reach logarithmic phase any later than when growing on glucose ([Fig. ", "2](#F2){ref-type=\"fig\"}, *D* and *E*), there was a reduction in the amount of time before the beginning of autolysis. ", "Sucrose on the other hand had the opposite effect, significantly lengthening the time before autolysis in strain 106.66. ", "Both these effects were reduced in the Δ*cps* knockout strains ([Fig. ", "2](#F2){ref-type=\"fig\"}, *D* and *E*), indicating an effect of the presence of capsular polysaccharide on the longevity of the bacteria. ", "The maximum OD~600\\ nm~ was significantly different for different serotypes and accordingly, the point of harvest was adjusted to OD~600\\ nm~ = 0.15 for Serotype 7F strains and OD~600\\ nm~ = 0.25 for other strains.", "\n\nCapsule thickness under the influence of glucose, fructose, and sucrose as the carbon source was also measured by transmission EM for 106.66 and 208.41 wildtypes as well as their *cps* switch mutants (TEM, [Fig. ", "3](#F3){ref-type=\"fig\"}, *A--G*) and showed a reduction in exopolysaccharide production to almost zero when grown on fructose. ", "Capsule thickness of strains grown on sucrose as a combination of the glucose and fructose monosaccharides was also assessed. ", "The sucrose-fed bacteria were not negatively influenced by the presence of the fructose moiety and produced thick exopolysaccharide capsules. ", "In fact, strain 106.66 WT produced larger amounts of CPS when fed sucrose than when grown on glucose.", "\n\n{#F3}\n\nRNA-Seq reveals fructose-specific changes that do not occur in the capsule region\n---------------------------------------------------------------------------------\n\nWe then performed RNA-Seq of the WT strains 106.66 and 208.41, *cps* mutants, and their back transformants. ", "The total number of paired-reads per sample ranged from 4.79 to 39.65 million paired-reads (average: 20 million reads).", "\n\nIn average 99.03% of reads were mapped onto the pneumococcal genome. ", "Between 54.02 and 93.93% of reads (average: 81.47%) mapped to annotated features. ", "Most of these reads aligned to rRNA. ", "Overall 73.5 or 75.5% of reads aligned to rRNA or tRNA in strain 106.66 or 208.41, respectively.", "\n\nThe [Fig. ", "4](#F4){ref-type=\"fig\"}, *A* and *B*, show the principal component analysis (PCA) of all the samples. ", "For the strain 106.66 there is one outlier for one replicate for the mutant with the 7f capsule from strain 208.41. ", "The samples clearly separate by media and capsule for both strains. ", "PCA1 (55--58% of variance) separates data by \"capsule,\" PCA2 (18--19% of variance) separates data by medium. ", "However, the separation by capsule seems to be driven by expression of genes of capsule region, after removing these genes, there is no separation by capsule in PCA (data not shown).", "\n\n{ref-type=\"table\"} for more information). ", "Heat maps show the fold-change values for the top 50 genes for each pairwise comparison of the samples according to the strain background 106.66 (*C*) and 208.41 (*D*). ", "Genes that were up- or down-regulated within both are indicated in *bold*. ", "Full gene names and expression values of strains with 106.66 and 208.41 background can be found as [Tables S2 and S3](http://www.jbc.org/cgi/content/full/RA119.010764/DC1), respectively.](zbc9991914660004){#F4}\n\n[Fig. ", "4](#F4){ref-type=\"fig\"}, *C* and *D,* show the heat maps of the fold-change values for the top 50 genes for each pairwise comparison of the samples. ", "We then more closely inspected genes that were part of or subsequent to the central carbon metabolism of *S. pneumoniae*. ", "In both the 106.66 and the 208.41 strains, we observed that compared to glucose, the *glmS* and *nagA* genes (relevant for peptidoglycan synthesis) are respectively up- and down-regulated in fructose-grown bacteria. ", "The latter was not as significant for 208.41 as in 106.66 but similar log-fold values were received ([Tables S2 and S3](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)). ", "RNA-Seq results of *glmS* and *nagA* has been subsequently confirmed with RT-PCR for 106.66 and 208.41 (data not shown). ", "In addition, a number of genes related to PRPP and subsequent pyrimidine synthesis were also increasingly expressed in fructose for both strains (*carA, carB, pyrB*, and *pyrR*). ", "Finally and as expected, fructose transporters fructose transporter genes and Phosphofructokinase (pfk1) were the genes with the highest log-fold differences. ", "Expression values and full names for genes of strains after filtering with 106.66 and 208.41 background can be found as [Tables S2 and S3](http://www.jbc.org/cgi/content/full/RA119.010764/DC1), respectively.", "\n\nAnalysis of polysaccharide capsule metabolites by ^31^P NMR\n-----------------------------------------------------------\n\nWe hypothesized that the lack of capsule polysaccharide in CDM-fructose was due to fructose not being catabolized to the capsule precursors such as UDP-glucose or UDP-galactose ([Fig. ", "1](#F1){ref-type=\"fig\"}). ", "We therefore compared the intracellular metabolite profiles of *S. pneumoniae* strains grown in CDM supplemented with either glucose, fructose, or sucrose. ", "Because phosphorylated monosaccharide precursors like UDP-glucose and UDP-galactose play a very significant role in capsule biosynthesis ([@B16]), we decided to use ^31^P NMR to identify and quantify the phosphorylated metabolites. [", "Fig. ", "5](#F5){ref-type=\"fig\"}, *A--C*, show the relevant regions of a whole cell extract ^31^P NMR spectrum of *S. pneumoniae*, including the diphosphodiester region ([Fig. ", "5](#F5){ref-type=\"fig\"}*C*). ", "UDP-glucose, UDP-galactose, UDP-GlcNAc, ATP, PRPP, and fructose 1,6-bisphosphate (FBP) were identified by addition of pure compounds to the samples (spiking). ", "UDP-glucosamine and UDP-*N*-acetylmuramate-pentapeptide were not available or expensive for spiking and therefore, peaks were assigned by comparison to spectra from previous studies ([@B11], [@B16]). ", "Other precursor molecules like TDP-rhamnose and CDP-choline could not be identified.", "\n\n![**", "Excerpt from ^31^P NMR spectra of pneumococcal whole cell ethanol extract (strain 208.41, type 7F).** ", "Metabolite peaks for ATP (*A*) and FBP (*B*) have been identified by spiking. ", "Furthermore, PRPP, UDP-Glc, UDP-Gal, and UDP-GlcNAc have been identified by spiking, whereas UDP-MurNAc-p5 and UDP-GlcN were identified by comparison to previous studies ([@B31]) (*C*).](zbc9991914660005){#F5}\n\nThe experiments were then conducted for WT strains and capsule switch mutants (to exclude any effects of the genetic background) as well as Δ*cps* (knockout) strains ([Fig. ", "6](#F6){ref-type=\"fig\"} and [Fig. ", "S1](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)). ", "We also conducted the experiments using an additional serotype 7F strain (B109.15) and a naturally nonencapsulated strain (110.58) ([Table 1](#T1){ref-type=\"table\"} and [Fig. ", "S2](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)).", "\n\n![**", "Metabolite levels observed in *S. pneumoniae* whole cell extracts, biological triplicates from separate cultures.** ", "Overall absolute values were similar to those obtained in a previous study ([@B11]). *", "Red,* CDM-glucose; *blue,* CDM-fructose; *purple,* CDM-sucrose. ", "Differences between conditions were analyzed by unpaired *t* test to determine the significance of results. ", "Significance levels are attributed as not significant (*ns*, *p* \\> 0.05); \\*, *p* ≤ 0.05; \\*\\*, *p* ≤ 0.01; \\*\\*\\*, *p* ≤ 0.001; or \\*\\*\\*\\*, *p* ≤ 0.0001.](zbc9991914660006){#F6}\n\nOverall, extracts from Δ*cps* (knockout) strains growing in media supplemented with glucose or sucrose contained a much larger amount of UDP-monosaccharide capsule precursors than their WT counterparts, indicating that the lack of exopolysaccharide biosynthetic mechanism leads to the accumulation of the precursors in the cytoplasm ([Fig. ", "6](#F6){ref-type=\"fig\"}). ", "In addition, serotype 7F WT isolates accumulated more precursor molecules as compared with 6B strains, which may indicate a less efficient conversion of precursor metabolites into CPS by the exopolysaccharide biosynthetic mechanism. ", "This interpretation is also consistent with the transferability of the effect with the serotype in a *cps* switch mutant (106.66cps208.41), indicating that it is specific to the *cps* operon ([Fig. ", "S1](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)). ", "The resulting decreased exopolysaccharide production may explain to some degree the generally thinner capsule of the serotype 7F strains.", "\n\nFurthermore, Δ*cps* knockout strains growing in CDM supplemented with fructose as the only carbon source produced lower amounts of UDP-glucose and UDP-galactose compared with CDM supplemented with other carbon sources ([Fig. ", "6](#F6){ref-type=\"fig\"}). ", "This is also true for the naturally nonencapsulated strain but absolute values were lower as compared with Δ*cps* knockout strains ([Fig. ", "S2](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)). ", "FBP production, on the other hand, was increased in the presence of fructose as compared with glucose. ", "Another interesting effect was the significant increase of PRPP production in serotype 6B WT bacteria, which is consistent with the observed up-regulation of related genes (*carA, carB, pyrB,* and *pyrR*; [Fig. ", "4](#F4){ref-type=\"fig\"}). ", "In addition, UDP-*N*-acetylglucosamine was significantly decreased if grown in fructose in WT and capsule switch strains for serotype 7F but not 6B. The combination of both glucose and fructose monosaccharides in a disaccharide (sucrose) resulted in a metabolite pattern resembling a mixture of the two conditions, with the UDP-monosaccharides reaching levels comparable with those reached in CDM-glucose, whereas FBP levels approached or even exceeded those of the fructose-fed bacteria.", "\n\nUtilization of fructose subunit of the disaccharide sucrose\n-----------------------------------------------------------\n\nThere are several pathways of fructose and sucrose transport and utilization in bacteria ([@B14]) ([Fig. ", "1](#F1){ref-type=\"fig\"}). ", "Because growth of *S. pneumoniae* in CDM-fructose yielded no capsule, but growth in CDM-sucrose resulted in a thick polysaccharide capsule, we hypothesized that the fructose subunit of the disaccharide was mostly metabolized through the glycolysis pathway, allowing the glucose subunit to be catabolized in capsule production. ", "To study the metabolic flux of the fructose subunit of sucrose into the polysaccharide capsule we first cultured the pneumococcal strain 106.66 (serotype 6B) in media containing carbon 13-labeled \\[^13^C\\]glucose-1 or sucrose-(\\[^13^C\\]fructose-1) as the only carbon source. ", "In ^1^H NMR spectroscopy, protons attached to ^13^C display a different peak pattern than protons attached to ^12^C due to the different spin quantum numbers between those two nuclei ([Fig. ", "7](#F7){ref-type=\"fig\"}, *A* and *B*). ", "Exopolysaccharide from bacteria fed ^13^C-labeled glucose showed distinct and complete splitting of the CPS anomeric proton resonances in ^1^H NMR spectra and strongly increased signals at the relevant chemical shifts in ^13^C NMR spectra. ", "The changes observed in the NMR spectra are characteristic of a complete ^13^C replacement at the relevant positions in the capsule, confirming the incorporation of the labeled monosaccharide into the capsule. ", "The proportion of ^13^C in polysaccharide labeled with \\[^13^C\\]glucose was between 81.7 and 91.2% in all three CPS anomeric proton resonances, indicating a very efficient labeling ([Fig. ", "7](#F7){ref-type=\"fig\"}*B*). ", "Subsequently, we performed an experiment with the labeled fructose moiety of sucrose-(\\[^13^C\\]fructose-1) and only observed small ^13^C satellite resonances, indicating that its use in capsule biosynthesis is not very efficient ([Fig. ", "7](#F7){ref-type=\"fig\"}*A*). ", "More specifically, the proportion of ^13^C in polysaccharide labeled on \\[^13^C\\]sucrose only contained 4.5% ^13^C for the galactose resonance at 5.53 ppm, 4.7% for the rhamnose resonance at 5.07 ppm, and 6.2% for the glucose resonance at 5.05 ppm ([Fig. ", "7](#F7){ref-type=\"fig\"}*B*). ", "This finding supports our hypothesis that the polysaccharide capsule is biosynthesized from mostly the glucose subunit of sucrose, whereas the fructose subunit is mostly metabolized through the glycolysis pathway.", "\n\n and is depicted from Ref. [", "@B52]). ", "Peak splitting due to the heteronuclear coupling between ^1^H and ^13^C nuclei is clearly visible in the extract from pneumococci grown on glucose-1-^13^C. Only minute split peaks are visible in the extract from bacteria grown on sucrose-(fructose-1-^13^C) for identical ppm as compared with glucose-1-^13^C (*red dotted lines*). *", "B,* quantitative representation of integrals of ^13^C coupling peaks in % of the total capsule extract from three separate cultures under each condition (repeat measurements for sucrose-^13^C were not done due to high pricing of the sugar).](zbc9991914660007){#F7}\n\nDiscussion\n==========\n\nThe polysaccharide capsule is a major virulence factor and surrounds most clinical strains of the Gram-positive human pathogen *S. pneumoniae*. ", "It functions as a shield protecting underlying bacterial structures from recognition by the immune system, interfering with complement deposition, phagocytosis, and mucus-mediated clearance ([@B17][@B18][@B22]). *", "S. pneumoniae* regulates the thickness of the polysaccharide capsule in response to its environment and this is key in colonization and invasion of epithelial host cells ([@B23]). ", "However, despite the importance of the capsule, the mechanisms and environmental conditions that influence capsular polysaccharide expression are not yet very well-understood ([@B23]). ", "It has been previously hypothesized that CPS production in *S. pneumoniae* is reduced when grown on fructose as compared with glucose as the carbon source but the mechanism was unclear ([@B10]). ", "Within this study, we confirmed that this phenomenon is indeed true for a large number of pneumococcal strains and assessed the mechanism for this phenotypic phenomenon by measuring the intracellular phosphorylated metabolites. ", "In addition, we describe the relevant transcriptional changes from RNA-Seq data if *S. pneumoniae* is grown in fructose as compared with glucose. ", "Finally, we reveal that labeled glucose rather than fructose is incorporated into the capsule if grown in sucrose by stable isotope tracing. ", "Understanding the expression of the capsule in response to the environment is important to future vaccine design.", "\n\nPneumococci metabolize carbohydrates such as the monosaccharides fructose, mannose, glucose, galactose, GlcNAc, disaccharides such as sucrose, lactose, and cellobiose, or trisaccharides such as raffinose, which all enter the glycolytic pathway ([@B12]). ", "In addition, carbohydrates are involved in the biosynthetic pathways of housekeeping and nonhousekeeping (CPS-specific) components of *S. pneumoniae* CPS ([@B24]). ", "Phosphorylated metabolites such as UDP-glucose and UDP-galactose are especially important as precursor molecules for capsule production ([@B11]). ", "We therefore focused on quantifying phosphorylated metabolites by ^31^P NMR within this study. ", "This method has been used previously to investigate the effect of *ccpA* deletion on intracellular concentrations of phosphorylated metabolites during growth on glucose or galactose ([@B11]). ", "To our knowledge, it has not yet been used to study capsule biosynthesis within *S. pneumoniae.* ", "As compared with HPLC-MS and GC-MS methods for characterizing the pneumococcal metabolome ([@B25]), ^31^P NMR only reveals a small subset of (phosphorylated) metabolites. ", "However, ^31^P NMR can distinguish metabolites with identical mass (like the important capsule precursor UDP-glucose *versus* UDP-galactose), which may not be as straightforward with HPLC-MS and GC-MS methods.", "\n\nBy quantifying phosphorylated metabolites, we show that the intracellular concentrations of UDP-glucose and UDP-galactose are drastically decreased in Δ*cps* pneumococcal strains if grown in fructose compared with glucose. ", "This reveals that the pneumococcus is not able to produce the relevant precursors for the biosynthesis of the pneumococcal capsule under fructose conditions. ", "In contrast, exopolysaccharide (EPS) production in *Bifidobacterium longum* has been shown to remain similar when grown on fructose, galactose, and glucose ([@B26]). ", "In accordance with our findings, the concentrations of the same two EPS precursors, UDP-glucose and UDP-galactose, were significantly lower in a *Lactococcus lactis* strain containing the EPS gene cluster (Eps+) than in the nonproducer strain MG5267 (Eps−) ([@B16]). ", "In a further study focusing on *L. lactis* subsp. *", "cremoris*, it has been shown that fructose is taken up mainly via the fructose PTS resulting in fructose 1-phosphate ([@B27]). ", "In addition, combined actions of 1-phosphofructokinase and FBPase would be required to form essential biomass precursors ([@B27]). ", "We hypothesize that the same is true for *S. pneumoniae* due to the following two reasons. ", "First, we revealed that the relevant PTS transporter and *pfk1* are highly up-regulated in fructose from our RNA-Seq data. ", "Considering earlier findings suggesting the presence of *fruA* is essential for growth on fructose ([@B12]), we assume that fructose is indeed primarily imported by this PTS transporter. ", "Second, due to the absence of UDP-glucose and UDP-galactose if grown in fructose, FBPase activity seems to be nearly absent in *S. pneumoniae*. ", "However, the product of FBPase, fructose 6-phosphate is essential for polysaccharide capsule production but also peptidoglycan synthesis. ", "Two additional routes for the utilization of fructose have been suggested for *E. coli* ([@B14]). ", "Although much less predominant, the additional routes facilitate the production of fructose 6-phosphate. ", "We do not know if they are also the two additional routes for fructose utilization within *S. pneumoniae* at this point. ", "However, we noted an up- and down-regulation of *glmS* and *nagB/nagA*, respectively. ", "These genes are essential for the production of UDP-GlcNAc to build the cell wall, which has been described to be tightly regulated ([@B28], [@B29]). ", "More specifically, *glmS* RNA-specific degradation through the possible participation of a *glmS* riboswitch mechanism has been described ([@B28], [@B29]). ", "Based on our expression results, such degradation might be more abundant if grown on glucose than on fructose, but more detailed experiments will be necessary.", "\n\nRecently, a mechanism of regulation of the *pyr* operon by the *pyrR* RNA element has been proposed for *S. pneumoniae* ([@B30]). ", "It has been shown that in the presence of high UMP but low PRPP, PyrR binds to the *pyrR* RNA and results in the formation of a premature terminator, disrupting the anti-terminator formed when UMP is low (and PRPP high), resulting in transcription termination ([@B30]). ", "Within our study, we found both increased intercellular PRPP and expression of genes of the *pyr* operon if grown on fructose. ", "This therefore suggests a tight regulation of this operon as suggested by Warrier *et al.* ([", "@B30]).", "\n\nHaving analyzed the mechanism of CPS biosynthesis and nonbiosynthesis of *S. pneumoniae* grown on glucose and fructose, respectively, we then were wondering how the disaccharide sucrose (fructose-glucose) would be incorporated into the capsule. ", "Sucrose is an important dietary glycan ([@B4]) and sucrose metabolism contributes to *in vivo* fitness of *S. pneumoniae* ([@B31]). ", "Sucrose is probably imported mainly via a PTS transporters (*ScrT*) and subsequently degraded/hydrolyzed (by *ScrH*) to glucose 6-phosphate and fructose ([@B4]). ", "It is hypothesized that a putative fructokinase (*scrK*) produces fructose 6-phosphate ([@B31]), which, like glucose 6-phosphate, could be used as substrate for the production of CPS precursor molecules, such as UDP-glucose and UDP-galactose, and, subsequently, capsule biosynthesis ([Fig. ", "1](#F1){ref-type=\"fig\"}). ", "However, in contrast to labeled glucose, we only noted an incorporation of less than 10% of labeled fructose into the capsule of our serotype 6B strain. ", "More specifically, we received a very reduced labeling of the anomeric protons of rhamnose, galactose, and glucose, which have been previously shown to be characteristic of serotype 6B isolates in NMR spectra ([@B32]). ", "Our results are therefore able to quantify the proportion of metabolites used for CPS production within the central carbon metabolism if glucose and fructose monosaccharides are present in equal concentrations within *S. pneumoniae* (as derived from the disaccharide sucrose). ", "We did not consistently detect a decreased production in UDP-*N*-acetylmuramate-pentapeptide in non-EPS producing strains as reported previously ([@B16]).", "\n\nA major strength of our study is the implementation and usage of ^31^P NMR for quantifying phosphorylated (including capsule precursor) metabolites. ", "Doing this for strains grown on glucose as compared with fructose, we were able to provide mechanistic evidence for the absence of the capsule in the latter condition. ", "By additionally performing RNA-Seq, we were also able to reveal relevant gene expression differences. ", "Another particular strength of our study is the usage of isotopologue profiling, which offers the possibility to decipher the incorporation of the distinct carbon sources into the capsule. ", "This may seem less important for monosaccharides such as glucose (as incorporation of ^13^C-labeled glucose is nearly 100%) but, in contrast, is very relevant for di- and oligosaccharides (such as sucrose), as the proportion of utilization of the different monosaccharides in CPS biosynthesis is unknown.", "\n\nA limitation of the study is the fact that we did not yet check the influence of larger fructooligosaccharides (FOS) on the expression of the capsule. ", "FOS are taken up by different (ABC) transporters ([@B4], [@B33]) and, once imported, are thought to be degraded by *FusH* ([@B4]). ", "The exact products of this enzymatic reaction and their effects on CPS biosynthesis are unknown. ", "Also, we did not investigate the effects of other monosaccharides, such as galactose, mannose, and GlcNAc on CPS production, as our main aim in this study was to elucidate the cause of the absence of CPS in strains grown on fructose. ", "It is known that pneumococcal strains without capsule are more prone to opsonophagocytosis and, therefore, it remains to be analyzed if increased concentrations of fructose and/or FOS could potentially be used as prebiotic for preventing pneumococcal colonization and/or subsequent invasive disease.", "\n\nWe did not detect UDP-GalNac in the ^31^P spectra of the strains with 7F serotype, which was also not reported for pneumococcal strain D39 in a recent study ([@B11]). ", "This is perhaps surprising considering that the serotype 7F strains possess GalNac within the capsule structure ([Table S1](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)) but the building of UDP-GalNac is probably important for all pneumococcal strains for the biosynthesis of teichoic acids ([@B34]). ", "We may only speculate if UDP-GalNAc is generally consumed very rapidly in *S. pneumoniae* and therefore difficult to detect using the methods presented.", "\n\nHowever, we observed a less efficient conversion of precursor metabolites into the CPS in 7F. The accumulation of UDP-precursors could be the result of a relative bottle-neck step in epimerization done by the GalE enzyme ([Fig. ", "1](#F1){ref-type=\"fig\"}), which has been shown to be able to epimerize both, UDP-glucose/UDP-galactose, and UDP-GlcNAc-UDP-Gal-NAc in *S. pneumoniae* ([@B35]).", "\n\nIn summary, this study reveals and quantifies the dual utilization of carbohydrates for capsule production and glycolysis. ", "It further shows that some serotypes (*e.g.* 6B) are more efficient in the conversion of precursor molecules to capsular polysaccharide than others (*e.g.* 7F). ", "Understanding the metabolic flux of different carbohydrates and their relationship to capsule expression is important considering the wide range of host-derived glycans the pneumococcus encounters during its interaction in the human host ([@B4], [@B7]). ", "Knowledge about the pneumococcal metabolism and mechanism of capsule biosynthesis is also important to recognize potential new drug targets.", "\n\nExperimental procedures\n=======================\n\nBacterial strains and growth conditions\n---------------------------------------\n\nThe bacterial strains for this study were selected from the collection of the Swiss National Reference Centre for Pneumococci. ", "Strains for the preliminary experiments were chosen to include a variety of serotypes. ", "This included strains of serotypes 6B, 6C, 7F, 9V, 15, and 23F and their capsule switch mutants. ", "The structures of the serotypes have been shown and can be found in the supporting material ([@B15]) ([Table S1](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)). ", "For the more detailed analyses, strains 106.66 (serotype 6B) and 208.41 (serotype 7F) were chosen as examples of serotypes more commonly associated with commensal colonization of the nasopharynx and invasive disease, respectively, as well as representing one strain with a thick polysaccharide capsule and one with a thin capsule ([Table 1](#T1){ref-type=\"table\"}). ", "Bacteria were cultured as described previously ([@B36]). ", "Briefly, bacteria were streaked out on CSBA plates and grown for ∼10 h at 37 °C in a 5% CO~2~ atmosphere. ", "They were then inoculated into tubes containing modified Lacks medium ([@B37][@B38][@B39]) supplemented with glucose and grown to an OD~600\\ nm~ of 0.5. ", "After centrifugation and washing, 3 ml of bacterial suspension at OD~600\\ nm~ 0.5 were added to 150 ml of CDM supplemented with a single carbon source at a concentration of 5.5 m[m]{.smallcaps} (5.5 m[m]{.smallcaps} glucose is approximately naturally found in the blood). ", "For the isotopologue profiling experiments, CDM containing 5.5 m[m]{.smallcaps} of either 100% labeled or unlabeled carbohydrates were used. ", "The cultures were then grown further to mid-logarithmic phase. ", "Bacterial growth was tracked by measuring the optical density at a wavelength of 600 nm (OD~600\\ nm~) using a Thermo Scientific Helios Epsilon UV-visible spectrophotometer with an adapter to allow measurement of OD~600\\ nm~ directly in the culture tubes.", "\n\nFITC dextran capsule thickness measurements\n-------------------------------------------\n\nCapsule thickness was evaluated in biological triplicate by fluorescence microscopy according to a method previously described ([@B10], [@B40], [@B41]). ", "Briefly, cells were harvested by centrifugation at mid-log phase, washed, and resuspended. ", "Cells were prepared for visualization on a microscope slide and imaged as described before ([@B9]). ", "At least 5 brightfield and fluorescence images per sample were recorded and the area of fluorescence occlusion per cell was calculated using free ImageJ software as previously described ([@B40]). ", "The experiments were done three times on different days and a total of 15 pictures (=15 values) per strains and carbon source were taken.", "\n\nTEM imaging\n-----------\n\nCells were grown using the methods described above and harvested at mid-log phase. ", "Samples for TEM imaging were prepared as described before ([@B40], [@B42]). ", "In brief, bacteria were pelleted by centrifugation (5000 rpm for 5 min) and the supernatant was discarded. ", "Bacteria were then cryopreserved by high-pressure freezing (HPF) as described by Studer *et al.* ([", "@B42]) using 1.4 × 0.1-mm membrane carriers (Leica Microsystems, Vienna) coated with [l]{.smallcaps}-α-phosphatidylcholine (Fluka, Buchs, Switzerland). ", "Acetone containing 2% osmium tetroxide, 0.1% uranyl acetate, 0.2% ruthenium hexamine trichloride and a total of 4% H~2~O served as the medium for freeze substitution. ", "The ruthenium hexamine trichloride was added to improve capsule resolution ([@B43]). ", "After substitution, bacteria were washed in acetone (Merck, Darmstadt, Germany) four times for 30 min each, they were then incubated for 2 h and 30 min in acetone:Epon (2:1) and 4 h in acetone:Epon (1:1) followed by an overnight incubation with acetone:Epon (1:2) at room temperature. ", "The next day, samples were embedded in Epon (Sigma) and left to harden at 60 °C for 5 days. ", "Ultrathin sections (75 nm) were produced with an ultramicrotome UC6 (Leica Microsystems, Vienna, Austria). ", "The sections, mounted on Formvar® (Ted Pella Inc. USA)-coated single slot copper grids, were stained with uranyl acetate (Electron Microscopy Sciences, Hatfield, PA) and lead citrate (Leica Microsystems, Vienna, Austria) with an ultrostainer (Leica Microsystems). ", "Sections were examined with a transmission electron microscope (CM12, Philips, Eindhoven) equipped with a digital camera (Morada, Soft Imaging System, Münster, Germany) and image analysis software (iTEM). ", "Measurements of capsule thickness were conducted on several images and several points on cell bodies perpendicular to the pneumococcal cell wall using the software ImageJ. For each strain and carbon source, a total of between 37 and 67 measurements were conducted.", "\n\nWhole genome and RNA-Seq of WT and mutant strains\n-------------------------------------------------\n\nWe first sequenced the reference genomes (106.66 and 208.41) by Illumina HiSeq 2000 (Illumina Inc.). ", "The resulting reads were *de novo* assembled using SPAdes ([@B44]). ", "Gene prediction was performed with Prodigal ([@B45]) and annotation was a carry-over from strain 23F. The assembled genomes are available under PRJNA554545.", "\n\nOverall for each strain 7 samples each in 3 replicates were analyzed with RNA-sequencing with the accession number PRJNA554543. ", "The 7 samples were the original strain, a mutant with transformed capsule from the other stain and a mutant with the back transformed capsule in two media; with fructose or glucose; and a mutant without a capsule in medium with glucose. ", "RNA libraries were sequenced as paired-end reads on Illumina. ", "Reads from RNA-sequencing were mapped to the reference genomes with bowtie2 ([@B46], [@B47]) and following counting of the reads was performed with featureCounts ([@B48]).", "\n\nGenes annotated as rRNA, tRNA, transposases, and manually confirmed hypothetical proteins were excluded from the analysis. ", "After this step 2095 and 1944 genes from 2163 and 1997 genes were left for strains 106.66 and 208.41, respectively. ", "Reads were then normalized as a regularized log (rlog), a data transformation method in DESeq2 ([@B49]), and as transcripts per million (TPM) ([@B50]). ", "Low expression genes were categorized from TPM values. ", "Decile values were used to partition expression values of genes into 10 classes. ", "The first decile was used as the maximum limit for low expressed genes. ", "2.1 TPM for strain 106.66 and 2.9 TPM for strain 208.41 were set as the minimum expression value, 1966 for strain 106.66 and 1829 genes for strain 208.41 were left for further analysis. ", "The very short genes were also removed from the analysis. ", "The same parameters as for low expressed genes were used: the first decile was used to define the short genes. ", "With these criteria all genes shorter than 225 bases (strain 106.66) or 240 bases (strain 208.41) were removed from further analysis. ", "Overall 145 genes in strain 106.66 and 148 genes in strain 208.41 were removed. ", "After all filtering 86% of genes were left for the analysis (1821 of2163 genes for strain 106.66, and 1681 of1997 genes for strain 208.41) ([Tables S2 and S3](http://www.jbc.org/cgi/content/full/RA119.010764/DC1)).", "\n\nFold-changes were calculated for each pair of conditions, resulting in a total of 21 comparisons. ", "Fold-changes of genes for which significance could not be calculated confidently, defined as adjusted *p* value greater than 0.01, were set to 0. ", "Then the fold-changes were calculated over all conditions comparing the values in glucose and fructose media. ", "The fold-changes of genes with an adjusted *p* value bigger than 0.01 were set to 0. ", "The ranking was made based on this comparison. ", "For the ranking, the absolute value of the fold-change was taken. ", "The capsule genes were analyzed separately. ", "The fold-changes of genes for which none of the pairwise comparisons was significant were also set to 0. ", "Overall 737 genes for strain 106.66 and 756 genes for strain 208.41 had significant fold-changes and 41 genes for strain 106.66 and 47 genes for strain 208.41 had fold-changes bigger than 2. ", "The top 50 genes with the highest absolute fold-change were used for further analysis.", "\n\nIntracellular metabolite extraction\n-----------------------------------\n\nWhole cell EtOH extracts were prepared using a slight modification of the method of Ramos *et al.* ([", "@B16]). ", "In brief, the bacteria cultured in chemically defined medium were harvested by centrifugation and washed once each with ice-cold 0.8% NaCl and ice-cold H~2~O. They were then resuspended in ice-cold H~2~O and diluted with absolute EtOH at −20 °C to a concentration of 60% EtOH. ", "Cells were disrupted via vigorous shaking for 2 h at 0 °C. ", "Cell debris was removed by ultracentrifugation and ultrafiltration (Amicon 10-kDa centrifuge filter) and the solvent was evaporated under reduced pressure. ", "Dried samples were weighed and dissolved in 100 μl of NMR buffer (20 m[m]{.smallcaps} MOPS, 5 m[m]{.smallcaps} NaOAc, and 1 m[m]{.smallcaps} EDTA in D~2~O with 0.1% phosphonoacetic acid (PPA), and 0.1% TSP, pH 7.4) transferred into 1.7-mm NMR microtubes and submitted for measurement of ^31^P NMR spectra.", "\n\nCapsular polysaccharide extraction and analysis\n-----------------------------------------------\n\nExtracts of the capsular polysaccharide were obtained as described previously ([@B9], [@B36]). ", "For isotopologue profiling experiments, the pneumococci were provided a single carbon source, either unlabeled or labeled with ^13^C in the 1-position at 100% concentration (5.5 m[m]{.smallcaps}). ", "For serotype analysis, regular unlabeled saccharides were used. ", "Bacterial cultures were grown as described above, harvested by centrifugation, and washed with ice-cold H~2~O. After resuspension, capsule polysaccharide was separated from the cells by addition of buffer-saturated phenol to a concentration of 1% and incubation overnight at room temperature. ", "Cell debris was removed by centrifugation and nucleotides and peptides were digested by addition of nuclease and proteinase K, respectively. ", "CPS was separated from smaller molecules using Millipore Amicon Ultra 30-kDa cut off membrane centrifugal filter units and the solvent was removed under reduced pressure. ", "Dried capsule polysaccharide samples were dissolved in 100 μl of D~2~O transferred into 1.7-mm NMR microtubes and submitted for NMR measurements.", "\n\nMetabolic flux analysis by isotopologue profiling\n-------------------------------------------------\n\nMetabolic flux analysis of carbohydrate uptake was based on the principle of ^13^C-based isotopologue profiling ([@B51]). ", "Bacteria were grown as described above using ^13^C-labeled monosaccharides as the carbon source. ", "In particular, \\[^13^C\\]glucose-1 was used to create completely labeled capsular polysaccharides as a reference point. ", "To track the metabolic flux of different monosaccharides, sucrose with an unlabeled glucose subunit and a labeled fructose 1-^13^C subunit was used. ", "By extracting the capsule and analyzing it by NMR as described, it was possible to determine the proportions of labeled and unlabeled saccharides in the polysaccharide capsule.", "\n\nNMR measurements\n----------------\n\nNMR data were collected on a Bruker Avance II (500 MHz; ^1^H) spectrometer equipped with a 1.7-mm triple-resonance (^1^H, ^13^C, ^31^P) microprobe head. ", "The samples were prepared as follows. ", "The full amount of each capsule extract (∼5--10 mg) was dissolved in 100 μl of NMR buffer (MOPS/EDTA in D~2~O with 0.1% PPA and 0.1% TSP, pH 7.4) or pure D~2~O and 65 μl of the resulting mixtures were transferred into 1.7-mm NMR tubes. ", "^31^P spectra were acquired using 4096 scans with a spectral width of 40760.9 Hz, a recycling delay of 2 s, and an acquisition time of 0.402 s. ^1^H spectra were recorded using 1024 scans with a spectral width of 12500.0 Hz, a recycling delay of 1 s, and an acquisition time of 1.311 s. All spectra were acquired at a regulated temperature of 298 K. All experiments were recorded using the TopSpin® software, version 3.2 (Bruker Biospin), and processed using TopSpin® version 4.0.5. ", "For the intracellular metabolite extracts, one-dimensional ^31^P NMR was used, whereas for the capsule extracts, one-dimensional ^1^H NMR as well as two-dimensional ^1^H/^13^C-heteronuclear single quantum coherence spectra were recorded.", "\n\nIdentification and quantification of metabolite signals\n-------------------------------------------------------\n\n^31^P NMR resonances were assigned to metabolites by spiking samples with specific metabolites in known concentrations and comparison to previous studies. ", "Quantification of the metabolites was achieved by comparison to the quantity of the internal PPA standard following a classical calibration procedure. ", "A specific conversion factor was obtained from this calibration for each metabolite and was used to calculate absolute amounts from the NMR integrals of the metabolites and PPA. ", "To ensure consistency of the results, all metabolite extract samples were dissolved in NMR buffer from the same batch. ", "Metabolite concentration data were analyzed by unpaired *t* test to determine the significance of results.", "\n\nAuthor contributions\n====================\n\nL. J. T., J. F., and M. H. data curation; L. J. T., J. P. W., T. O. S., N. M., C. S., S. D. B., and M. H. investigation; L. J. T., N. M., and J. F. visualization; L. J. T., J. P. W., T. O. S., P. V., M. V., D. W., C. S., R. B., L. J. H., J. F., and M. H. methodology; L. J. T. writing-original draft; N. M., D. W., and C. S. software; P. V., M. V., D. W., S. D. B., L. J. H., and J. F. writing-review and editing; C. S. resources; S. D. B. and M. H. conceptualization; L. J. H. and M. H. supervision; M. H. validation; M. H. project administration.", "\n\nSupplementary Material\n======================\n\n###### Supporting Information\n\nThis work was supported by Promedica Foundation Grant 1449/M (to S. D. B.) and Swiss National Science Foundation Grant 31003A_133157 (to L. J. H.). ", "The authors declare that they have no conflicts of interest with the contents of this article.", "\n\nThis article contains [Figs. ", "S1 and S2 and Tables S1--S3](http://www.jbc.org/cgi/content/full/RA119.010764/DC1).", "\n\nThe nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBank^TM^/EBI Data Bank with accession number(s) [PRJNA554543](PRJNA554543).", "\n\nThe abbreviations used are: CDMchemically defined mediumCPScapsular polysaccharideFBPfructose 1,6-bisphosphateFITCfluorescein isothiocyanateFOSfructooligosaccharidesGlcAglucuronic acidGlc-NglucosamineMurNAc-p5*N*-acetylmuramate-pentapeptidePRPPphosphoribosyl pyrophosphatePTSphosphotransferase transport systemTEMtransmission electron microscopyUDPuridine diphosphatePCAprincipal component analysisEPSexopolysaccharideTPMtranscripts per millionPPAphosphonoacetic acidntnucleotide.", "\n\nWe thank Prof. Wolfgang Thormann for advice and help with analytical questions and Suzanne Aebi for excellent technical assistance. ", "We also express our thanks to Stefan Weissen for technical support and NMR work. ", "TEM sample preparation and imaging were performed with devices supported by the Microscopy Imaging Center (MIC) of the University of Bern.", "\n\n[^1]: Edited by Chris Whitfield\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "gtx ltd seat cover\n\nim in the process of picking up a new seat cover from the forum store.. however.. im having the hardest time trying to figure out the color which would best match my \"blue\" on my gtx limited. ", "does anyone know exactly what this color is called?? ", "I would like to contact the company to see if they carry anything similar to this color. ", "if not I might have to stay with the old, faded cover for a while." ]

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[ "The Servicecenter for young researchers is the central place to go/contact point for all Postdocs, PhDs, and for students who are interested in doing a PhD.\nAlso as an international PhD the Servicecenter can give you a piece of advice abput Your Doctorate." ]

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[ "The Rugby League World Cup 2017 announced the draw for the tournament to be co-hosted by Australia and New Zealand and Papua New Guinea on Tuesday.", "\n\nWorld Cup pool breakdown\n\n10 Must-see experiences at the World Cup\n\nHave a World Cup every two years: Voss\n\nMelbourne Rectangular Stadium will host a blockbuster opening match of the RLWC2017, when the home nation – the Kangaroos – begin their campaign under lights against England on Friday, October 27.", "\n\nThe following day the Kiwis first pool match will be played at the home of Rugby League in New Zealand – Auckland's Mt Smart Stadium – when they take on Pacific rivals Samoa.", "\n\nPort Moresby will host the PNG Kumuls' three pool matches against two European Qualifiers and the USA. ", "The first match is scheduled for Saturday, October 28 and in a country where Rugby League is the national sport, the passionate fans of PNG are sure to embrace the sport's pinnacle event.", "\n\nThe World Cup Final will be decided at Brisbane Stadium on Saturday December 2, as the two finalists battle it out for the right to hold aloft the Paul Barrière trophy and claim the title of World Champions.", "\n\nRLWC2017 chief executive officer Michael Brown said the Organising Committee made a deliberate decision to take the Rugby League World Cup to more fans than any World Cup has done before.", "\n\n\"The Tournament Draw demonstrates how far and wide we are taking matches, from established Rugby League communities, to those new and emerging fan bases in all three countries,\" he said.", "\n\n\"Over the course of the pool stages we have looked to position matches in strong Rugby League communities and where large populations of ex-pats, Pacifica and indigenous fans live, to give those who love the sport and their national teams the chance to see some World Cup action.", "\n\n\"The decision to take matches to places like Darwin, Perth, Christchurch and Port Moresby were made with the future of the game in mind. ", "They are matches we believe will give profile to the sport in markets that have already shown an appetite for rugby league.\"", "\n\nThe RLWC2017 Tournament Draw is family-friendly by intention, with all matches to be played across the weekend including Friday night games. ", "There will be three double-headers in Cairns, Perth and Townsville, providing additional value for money for fans.", "\n\nWhen not attending games, fans will experience some of the most iconic sporting destinations in the world. ", "Sports enthusiasts will be able to explore the diversity of the eight host cities across Australia to New Zealand's compact nature that simplifies travel and makes it easy for visitors to access all venues while experiencing a variety of tourist attractions along the way. ", "The welcome and hospitality supporters will receive when visiting all three host nations will make the RLWC2017 a bucket list item for sports fans worldwide.", "\n\n\"We not only want to see traditional rugby league fans come out to support their national team, we aim to engage with the local communities of all participating teams to deliver an event that will entertain the world, inspire communities and celebrate rugby league,\" continued Brown.", "\n\n“Rugby league is truly a game for everyone. ", "We hope the Rugby League World Cup 2017 leaves a legacy for the game that sees it continue to grow and dominate the sporting landscape.\"", "\n\nTournament Pools\n\nWith 11 teams already confirmed, the final three teams will come from the European Qualifying Tournament to be played in October and November this year.", "\n\nThe pool structure reflects that of the successful 2013 Tournament. ", "The composition of the pools for RLWC2017 were shaped by a number of considerations, including the final placings from the 2013 World Cup and current world rankings\n\nPool A: Australia, England, France, Lebanon\n\nPool B: New Zealand, Samoa, Scotland, Tonga\n\nPool C: Papua New Guinea, European Qualifier 1, European Qualifier 2\n\nPool D: Fiji, USA, European Qualifier 3\n\nWorld Cup Draw - Pool matches\n\nDate Match Type Match-Up Venue Oct-27 Pool – Round 1 Australia vs England Melbourne Rectangular Stadium Oct-28 Pool – Round 1 PNG v Euro Q1 Port Moresby (venue TBA) Oct-28 Pool – Round 1 New Zealand vs Samoa Mt Smart, Auckland Oct-28 Pool – Round 1 Fiji vs USA Townsville Stadium Oct-29 Pool – Round 1 Scotland vs Tonga Barlow Park, Cairns Oct-29 Pool – Round 1 Euro Q2 vs Euro Q3 Barlow Park, Cairns Oct-29 Pool – Round 1 France vs Lebanon Canberra Stadium Nov-03 Pool – Round 2 Australia vs France Canberra Stadium Nov-04 Pool – Round 2 New Zealand vs Scotland Christchurch Stadium Nov-04 Pool – Round 2 Samoa vs Tonga Waikato Stadium, Hamilton Nov-04 Pool – Round 2 England vs Lebanon Sydney Football Stadium Nov-05 Pool – Round 2 PNG vs Euro Q2 Port Moresby (venue TBA) Nov-05 Pool – Round 2 Euro Q3 vs USA Townsville Stadium Nov-05 Pool – Round 2 Fiji vs Euro Q1 Townsville Stadium Nov-10 Pool – Round 3 Fiji vs Euro Q3 Canberra Stadium Nov-11 Pool – Round 3 Samoa vs Scotland Barlow Park, Cairns Nov-11 Pool – Round 3 New Zealand vs Tonga Waikato Stadium, Hamilton Nov-11 Pool – Round 3 Australia vs Lebanon Sydney Football Stadium Nov-12 Pool – Round 3 PNG vs USA Port Moresby (venue TBA) Nov-12 Pool – Round 3 Euro Q1 vs Euro Q2 Perth Rectangular Stadium Nov-12 Pool – Round 3 England vs France Perth Rectangular Stadium\n\nWorld Cup Finals\n\n\n\nDate Match Venue Nov-17 Quarter Final 1 Darwin Stadium Nov-18 Quarter Final 2 Christchurch Stadium Nov-18 Quarter Final 3 Wellington Regional Stadium Nov-19 Quarter Final 4 Melbourne Rectangular Stadium Nov-24 Semi Final 1: QF1 v QF2 Brisbane Stadium Nov-25 Semi Final 2: QF3 v QF 4 Mt Smart, Auckland Dec-02 Final: SF1 v SF2 Brisbane Stadium\n\nFor more information, please visit RLWC2017.com" ]

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[ "Q:\n\nBroadcastReceiver not called\n\nI found lots of threads about this topic, however I'm not able to solve my problem. ", "Here is the code:\nThe manifest file:\n<service\n android:name=\"com.xxx.player.", "MediaPlayerService.", "MediaPlayerService\"\n android:enabled=\"true\" >\n <intent-filter>\n <action android:name=\"android.media.", "AUDIO_BECOMING_NOISY\" />\n </intent-filter>\n\n <receiver android:name=\"com.xxx.player.", "MediaPlayerService.", "MediaPlayerService$ServiceBroadcastReceiver\"\n android:enabled=\"true\"\n android:exported=\"false\">\n <intent-filter>\n <action android:name=\"@string/ACTION_PREPARE_AND_PLAY_NEW_FILE\"/>\n <action android:name=\"@string/ACTION_PREPARE_NEW_FILE\"/>\n <action android:name=\"@string/ACTION_START\"/>\n <action android:name=\"@string/ACTION_STOP\"/>\n <action android:name=\"@string/ACTION_PAUSE\"/>\n <action android:name=\"@string/ACTION_SEEK_TO\"/>\n <action android:name=\"@string/ACTION_RELEASE\"/>\n </intent-filter>\n </receiver>\n </service>\n\nThe broadcast class:\npublic class MediaPlayerService extends Service implements\n MediaPlayer.", "OnErrorListener, \n AudioManager.", "OnAudioFocusChangeListener,\n Runnable,\n SeekBar.", "OnSeekBarChangeListener {\n\n ... \n\n public class ServiceBroadcastReceiver extends BroadcastReceiver {\n\n @Override\n public void onReceive(Context context, Intent intent) {\n\n String action = intent.getAction();\n\n Toast.makeText(getApplicationContext(), \"action: \" + action, 30000000).show();\n\n if (action.equals(Resources.getSystem().getString(R.string.", "ACTION_PREPARE_AND_PLAY_NEW_FILE))) {\n prepareAndPlayNewFile(intent.getStringExtra(\"mediaData\"));\n }\n\n }\n\n }\n\n}\n\nThe way I submit the intent:\nprivate void prepareAndPlayNewFile(String mediaData) {\n Intent myIntent = new Intent();\n myIntent.setAction(context.getString(R.string.", "ACTION_PREPARE_AND_PLAY_NEW_FILE));\n myIntent.putExtra(\"mediaData\", mediaData);\n context.sendBroadcast(myIntent);\n }\n\nA:\n\nInstead of approaching your playing of media this way, you should instead bind your Service to your Activity instead of using a broadcast receiver for message passing. ", "\nAlso you shouldn't be using @string/VAR1 (which I'm not sure if intent filters work with that kind of string definition) for your intent actions it ALWAYS should be the constant string such as:\nandroid.intent.action.", "BLAH\n\n" ]

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[ "Effects of compression tights on calf muscle oxygenation and venous pooling during quiet resting in supine and standing positions.", "\nWe applied near-infrared spectroscopy (NIRS) to evaluate in resting conditions the effects of compression tights (CT) on calf muscle oxygenation and venous pooling compared with Lycra(R) elastic tights (ET) and shorts (no compression) according to the body posture (supine vs standing). ", "Twelve sportsmen regularly involved in endurance training volunteered to this study. ", "Their average age, height and weight (+/-SD) were 26.5+/-2.6 years, 177+/-6 cm and 70.1+/-4 kg, respectively. ", "Tissue oxygenation index (TOI), deoxyhemoglobin (HHb), and blood pooling (Hbtot) of the right gastrocnemius medialis were continuously monitored at 2 Hz using a NIRS device (NIRO-300, Hamamatsu Photonics, Japan). ", "A home made transducer was used to measure applied pressure at the interface between skin and clothing over the calf area. ", "Subjects were asked to realize a supine-standing protocol (5 min for each position) by wearing CT, ET or shorts in a counterbalanced order on the same day. ", "HHb and Hbtot concentration changes were significantly lower whereas TOI was significantly higher by wearing CT compared with shorts and ET (P<0.001) as did supine compared to upright postures. ", "The mean pressures applied over the calf were 5.6 and 23.2 mmHg during supine and 5 and 24.1 mmHg during standing for ET and CT, respectively. ", "Pressures were significantly different among clothing according to the following rank order: CT>ET>shorts (P<0.001). ", "CT compared to ET have positive effects on calf muscle oxygenation and venous pooling in quiet resting positions." ]

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[ "From Mike Lofgren, best-selling author of The Party Is Over , long-time staffer for Republicans on Capitol Hill. ", "He writes in an email:\n\nBeginning with the dethronement of Jim Wright and the House banking scandal, and achieving escape velocity in the mid-1990s with Matt Drudge becoming the virtual assignment editor of the mainstream press during the Clinton impeachment, the Washington press corps has become increasingly \"wired\" to accept the Republican view of what constitutes a scandal. ", "The public has been ignoring Benghazi for 8 months; as for the Washington press, we saw how Jonathan Karl got played by Republican staffers' misrepresentations of the administration's e-mails.", "\n\nThe three Obama \"scandals\" have varying characteristics and varying levels of legitimacy, but all three share a meta-story. ", "And I think I know whereof I speak as a former GOP staffer.", "\n\nTake Two. ", "From a middling-selling author and long-ago, one-time Democratic White House aide:\n\nLet's think about the modern history of \"the scandal,\" and how such episodes emerge.", "\n\n\n\n\n\nThe modern saga all starts with Nixon. ", "Obviously there have been scandals throughout political history, and in the immediate pre-Nixon era you had Bobby Baker, Billy Sol Estes and Walter Jenkins with LBJ; Sherman Adams under Eisenhower; and such different political dramas as the Army-McCarthy hearings in the early Eisenhower era and the Bay of Pigs aftermath under JFK. ", "But Nixon marked the beginning of the modern scandal era. ", "That is because the phenomena of the televised high-stakes public inquiries (as with the Watergate hearings and impeachment preparations) really dates to then, as does modern press-consciousness of how coverage of a big, exciting scandal looks and feels.", "\n\n\n\nI. The main stops along the way:\n\nNixon: Watergate -> hearings -> dramatic revelations -> Supreme Court hearing -> impeachment -> resignation.", "\n\nAlso under Nixon: Spiro Agnew taking a brown paper bag full of bribery money, in his Vice Presidential office, and having to resign, something barely remembered now.", "\n\nNixon era: Teddy Kennedy and Chappaquiddick.", "\n\n\n\n\n\n\n\nFord: None really.", "\n\n\n\n\n\nCarter: No long-running ones, despite flaps about his budget director and his chief of staff. ", "But his era marks a major change, since round-the-clock news coverage was just getting going then, and Ted Koppel's Nightline, originally known as America Held Hostage, pioneered what we now think of as scandal-style coverage, of the American captives in Teheran.", "\n\n\n\n\n\nReagan: The Iran-contra mess, complete with Fawn Hall and Oliver North.", "\n\n\n\n\n\n\n\nGHW Bush: None, really, though the Clarence Thomas nomination got scandal-style coverage because of the charges against him and the dramatic hearings.", "\n\n\n\n\n\nClinton: First the phony scandals of Whitewater and Vince Foster. ", "Then the real problems via Monica Lewinsky. ", "Clinton era notable for the creation/revelation of something like a permanent-scandal mentality in politics and the press.", "\n\n\n\n\n\nGW Bush: Few scandals in the technical sense. ", "But the election, recount, and judicial overreach known as Bush v. Gore got scandal-style coverage. ", "Then Abu Ghraib, waterboarding and torture, and the war as a whole.", "\n\n\n\nObama: In his first term, the phony scandals of birtherism and Shirley Sherrod. ", "Now the three-\"scandal\" combo made of elements that have nothing whatsoever to do with one another and don't necessarily have anything to do with Obama himself but that nonetheless satisfy that phantom-limb craving for a good exciting scandal.", "\n\n\n\n\n\nII. ", "What a Scandal Takes, to Take Off\n\n\n\n1. ", "An underlying offense people can understand. ", "Clinton and Monica meet this test. ", "Also Nixon ordering wiretaps, or Agnew taking a bag of money. ", "Iran-Contra was always sort of a struggle on this front -- for people to grasp what exactly the offense was. ", "Today's IRS/Tea Party accusation meets the test (despite complexity of the underlying reality); Benghazi, less so.", "\n\n\n\n\n\n2. ", "Evidence of president's personal involvement. ", "The Watergate tapes again lead the way here -- Nixon's own voice, cursing and swearing. ", "Monica and Clinton -- whew. ", "Obama \"scandals\" lacking here.", "\n\n\n\n\n\n\n\n3. ", "A formal hearing/ investigative structure that guarantees an ongoing daily drip-drip-drip coverage. ", "When there is a schedule of witnesses for a hearing, an upcoming set of votes, or a sequence of new revelations, then the story can keep going for weeks, months, even years. ", "Darrel Issa, listen up!", "\n\n\n\n\n\n\n\n4. ", "A press culture and DC culture that is now wired to swing into \"scandal mode,\" and start writing stories and giving commentary reflecting that \"narrative.\"", "\n\n\n\n\n\n5. ", "A structure of news coverage that keeps the scandal narrative going. ", "This was probably at its strongest in the era of the weekly news magazines (Time, Newsweek, etc.) ", "Then you would have: daily coverage in the papers; nightly coverage on TV news; weekly advancing of the narrative by news mags (and Sunday talk shows); analysis of \"Administration in crisis\" and \"President under pressure\"; and it would all keep going. ", "Now, in a sense, the hourly / minute-by-minute cycle can make scandals \"burn out\" too fast." ]

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[ "Sometimes the media misses the elephant in the room, and this is clearly one of those occasions.", "\n\nBuried within several news reports is the stunning revelation that Pope Francis, then Jesuit Cardinal Jorge Mario Bergoglio, may have quietly backed gay civil unions as an alternative to the gay marriage law that passed in Argentina in July 2010.", "\n\nAccording to the new pope’s authorized biographer, Sergio Rubin, Bergoglio was politically wise enough to know the church couldn’t win a straight-on fight against gay marriage, so he urged his bishops to lobby for gay civil unions instead. ", "It wasn’t until his proposal was shot down by the bishops’ conference that he publicly declared what Paulon described as the “war of God” — and the church lost the issue altogether.", "\n\nDespite his conservatism, “Bergoglio is known for being moderate and finding a balance between reactionary and progressive sectors,” Paulon said. “", "When he came out strongly against gay marriage, he did it under pressure from the conservatives.”", "\n\n…\n\nFreyre, executive director of the Buenos Aires AIDS Foundation, wrote on his Twitter account this week that Pope Francis “knows that gay marriage isn’t the end of the world or the species.”", "\n\nWhen it became clear that stopping the marriage law would be impossible, the church may have tacitly given its backing to a civil union law as a way to head off the marriage bill. ", "Senator Liliana Negre de Alonso, a member of Opus Dei and one of the politicians most closely linked to the Catholic Church, sponsored the civil union bill. (", "This would be like Rick Santorum having endorsed a civil union law in the United States.) ", "It went nowhere. ", "During the debate, the leader of the majority party reduced her to tears while calling her a “Nazi” for backing legislation that would create a “separate-but-equal” status for same-sex couples.", "\n\nMore information is coming in. ", "This Spanish-language transcript was provided to me by an Argentinian friend Natalia Jacovkis. ", "It comes from Federico Wals, Cardinal Bergoglio’s spokesman in response to the 2010 proposal to legalize gay marriage in Argentina:\n\n[My translation to English] We are not searching to discriminate against same-sex unions. ", "We don’t have a fanatic vision. ", "What we are asking is that the laws are respected. ", "We believe that we must propose more comprehensive civil union [rights] than currently exist, but not [gay] marriage" ]

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[ "Q:\n\nLooking for an open source PDF Framework for iPad\n\nMy customer wants a pdf reader which has a page curl effect. ", "Also, he wants it to be zoomable as well. ", "I tried using the UIPageViewController but it doesn't support zooming (as far as I know). ", "I also tried using both UIScrollViewController and UIPageViewController by switching between these 2, but it's not so smooth. ", "\nDoes anyone know any free framework that meets my requirements?", "\nI don't want any content searching, highlighting or anything, just the reader and thumbnail view.", "\n\nA:\n\nHave a look at this:\nhttps://www.cocoacontrols.com/controls/pdf-reader-core\nhttps://www.cocoacontrols.com/controls/pdfreportkit\nHope this helps...\n\n" ]

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[ "Gumstix has updated its wireless enabled, Linux-oriented Overo Storm modules with new “Storm-Y” models that add WiFi access point and BLE 4.1 functions.", "\n\n\n\nLast summer, when Gumstix announced a Storm-P version of its wireless-enabled Overo Storm computer-on-modules, the company said the Storm was its most popular model. ", "Whereas the Storm-P added WiFi Direct support via Wi2Wi’s W2CBW0015 wireless module, the new Storm-Y, which appears to supersede it, goes with a Texas Instruments WiLink 8 module.", "\n\n\n\n\n\n\n\nOvero Storm-Y with antenna\n\n(click image to enlarge)\n\n\n\nThe key enhancement here is the addition of WiFi access point support. ", "This enables the Overo COM to serve simultaneously as client and host, “critical for Internet of Things (IoT) gateway applications,” says Gumstix. ", "The WiLink 8 module stays with 802.11b/g/n rather than the newer 802.11ac technology, but boosts Bluetooth to version 4.1 with BLE (Bluetooth Low Energy) support. ", "A single antenna connector is also provided,\n\nThe Storm-Y modules retain the Overo’s 58 x 17mm dimensions and optimized Yocto Linux build running on TI Cortex-A8 processors clocked at 800MHz to 1GHz. ", "The COMs continue to ship with 512MB RAM, 512MB flash, a microSD slot, and a 27-pin camera connector. ", "Other standard features include dual 70-pin AVX connectors with support for interfaces including, USB OTG, GPIO, GPMC, LCD, ADC, I2C, SPI, UART, and audio I/O.\n\nAs before, three versions — Air, Fire, and Iron — are provided for the Storm-Y models, with the following differences and prices:\n\n— ADVERTISEMENT —\n\n\n\nAirStorm-Y — TI Sitara AM3703 — $139\n\nFireStorm-Y — TI DM3730 with PowerVR SGX530 GPU and DSP — $159\n\nIronStorm-Y — TI DM3730 with PowerVR SGX530 GPU and DSP, plus extended temperature operation — $179\n\nGumstix recently released an updated Linux distribution for the modules in the form of a Yocto Project 1.7 “Dizzy” image that adds driver support for the WiLink 8. ", "The Overo Storm-Y series COMs are fully compatible with the existing Gumstix Overo expansion boards, says the company.", "\n\n\n\nFurther information\n\nThe new Overo Storm-Y modules should be available today at the prices listed above, at Gumstix’s online store.", "\n\n" ]

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[ "Q:\n\nbuild real time dashboard using google apps script\n\nI want to be able to update my web app constantly (in real time) such that anytime there's an update on my Google Sheet (via a webhook configured using apps script's doGet function), the same is shown in the HTML dashboard that I've built.", "\nI don't need help with setting up my sheet, or the webhook or the HTML dashboard - I have all of that already setup.", "\nI do need help / advise on how can I update my HTML dashboard (web app) any time there's an update either on my doGet function or on the sheet (that part doesn't really matter).", "\nThe best example would be the way Google Analytics realtime dashboard changes, every time there's a new user who lands on your website.", "\nPS. ", "I know I'm supposed to share some code but everything I have has nothing to do with what I actually want; hope that's clear but should there be a need for any of you to see my code/sheet, I'd be happy to create a dummy version.", "\n\nA:\n\nYou'll need to use:\n\ngoogle.script.run.withSuccessHandler which is a JavaScript, asynchronous, Client-side API that allows you to interact with server side functions (references could be found here).", "\nsetInterval function to invoke the aforementioned client-side API at a frequency you see fit\n\n3000/3500 milliseconds is what I've been using so far and the service quotas don't specifically talk about its limitations\n\nServer side\nThis is pretty much the code that gets written in the code.gs part of the script; where all your functions reside that interact perhaps with your Spreadsheets or act as the webhook\nClient side\nThat's the code that runs from your *.html file and, post loading, on your web browser. ", "This is where you get to use the \"asynchronous\" API\nExample\nIn my dummy setup, I'm -\n\nFetching random quotes from thesimpsonsquoteapi\nDisplaying a timer that changes every second\n\nCode.gs (server-side code)\nfunction doGet(e) {\n return HtmlService.createHtmlOutputFromFile('Index').setTitle('Realtime Data');\n}\n\nfunction randomQuotes() {\n var baseURL = 'https://thesimpsonsquoteapi.glitch.me/quotes';\n var quotesData = UrlFetchApp.fetch(baseURL, { muteHttpExceptions: true });\n var quote;\n var imageURL;\n if (quotesData.getResponseCode() == 200 || quotesData.getResponseCode() == 201) {\n var response = quotesData.getContentText();\n var data = JSON.parse(response)[0];\n quote = data[\"quote\"];\n imageURL = data[\"image\"];\n } else {\n quote = 'Random Quote Generator is broken!';", "\n imageURL = 'https://cdn.shopify.com/s/files/1/1061/1924/products/Sad_Face_Emoji_large.png?v=1480481055';\n }\n var randomQuote = {\n \"quote\": quote,\n \"imageTag\": '<img class=\"responsive-img\" src=\"' + imageURL + '\">'\n }\n return randomQuote;\n}\n\nfunction getTime() {\n var now = new Date();\n return now;\n}\n\nIndex.html (client-side code)\nI'm only highlighting the relevant aspects of the code\nThe following fetches random quotes every 10 seconds (10000 ms)\n<script>\n function onSuccess1(quotedata) {\n var quoteactual = document.getElementById('quote');\n quoteactual.innerhtml = quotedata.quote;\n var quoteimg = document.getElementById('quoteImage');\n quoteimg.innerhtml = quotedata.imagetag;\n }\n\n setInterval(function() {\n console.log(\"getting quote...\")\n google.script.run.withSuccessHandler(onsuccess1).randomQuotes();\n }, 10000);\n</script>\n\nThis fetches time every 1 second (1000 ms)\n<script>\n function onSuccess2(now) {\n var div = document.getElementById('time');\n var today = new Date();\n var time = today.getHours() + \" : \" + today.getMinutes() + \" : \" + today.getSeconds();\n div.innerhtml = time;\n }\n\n setInterval(function() {\n console.log(\"getting time...\")\n google.script.run.withSuccessHandler(onsuccess2).getTime();\n }, 1000);\n</script>\n\nYou can access the entire script on my github repository or make a copy from the original script.", "\nOutput\nThe image here is supposed to change every 10s and timer, every 1s\n\nThe browser console log can be viewed here -\n\nI wrote this article a couple weeks ago that outlines most aspects of what everyone has been answering/commenting so far but I'm hoping my explanation here helps as well.", "\n\n" ]

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[ "Q:\n\nDo not work socket.io-client with Angular2 when server emit event to specific client (different angular2 service)\n\nI created two service send-message.service.ts\nimport { Injectable } from \"@angular/core\";\nimport * as io from 'socket.io-client';\n\n@Injectable()\nexport class SendMessageService {\n\n private url = 'http://localhost:4000';\n private socket = io(this.url);\n\n saveUser(user) {\n this.socket.emit('joining-to-chat', user);\n }\n\n sendMessage(data) {\n this.socket.emit('send-message', data);\n }\n\n}\n\nand receive-message.service.ts\nimport { Injectable } from \"@angular/core\";\nimport { Subject } from 'rxjs/Subject';\nimport { Observable } from 'rxjs/Observable';\nimport * as io from 'socket.io-client';\n\n@Injectable()\nexport class ReceiveMessageService {\n\n private url = 'http://localhost:4000';\n private socket = io(this.url);\n\n getMessage() {\n let observable = new Observable(observer => {\n this.socket.on('getMessage', (data) => {\n observer.next(data);\n });\n return () => {\n this.socket.disconnect();\n };\n })\n return observable;\n }\n}\n\nAnd my server code is look like following: \nexport default (io) => {\n\n io.on('connect', (socket) => {\n\n var users = [];\n\n socket.on('send-message', (data) => {\n io.sockets.in(data.message_to).emit('getMessage', {\n text: data.message,\n from: data.message_from\n })\n })\n\n socket.on('joining-to-chat', (data) => {\n socket.join(data.username);\n users.push(data.username);\n io.emit('new-user', users)\n })\n\n socket.on('disconnect', () => {\n console.log('a user disconnected');\n })\n\n })\n\n}\n\nWhen send-message and getMessage event in same service server code and client code everything work perfectly as my expectation. ", "But if these to event placed in different service I can't emit event two specific client. ", "Only io.emit('getMessage', 'msg') and socket.emit('getMessage', 'msg') work correctly. ", "I am using: \nAngula2 v4.3.1 \n\"@types/socket.io-client\": \"1.4.30\", \n\"socket.io-client\": \"2.0.3\", \n\"socket.io\": \"2.0.3\",\n\nI want to know how to use socket.io-client in angular2 and what is the best structure of socket.io-client when my app contain lots of different independent module and services?", "\n\nA:\n\nThe server side code for socket joining and emitting event to specific user is pretty well.", "\nBut in client side there have two different instance of socket in two different service. ", "\nFirst instance of socket which has been created in SendMessageService that joined with socket and another new socket instance in ReceiveMessageService are not same. ", "So it would not broadcast event as expected.", "\nTo make it workable two socket in\ngetMessage() {\n let observable = new Observable(observer => {\n this.socket.on('getMessage', (data) => {\n observer.next(data);\n });\n return () => {\n this.socket.disconnect();\n };\n })\n return observable;\n }\n\nand \nsaveUser(user) {\n this.socket.emit('joining-to-chat', user);\n }\n\nshould be same instance of socket.", "Though the angular component or module are different those will use getMessage and saveUser service methods should be use a common service or a global service.", "\nTo create a global service follow the link Making global service \n\n" ]

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[ "The term “farm murders” has become fundamentally politicised, associated with false right-wing claims about “white genocide”. ", "Farmers say they are under siege, that farm attacks are on the rise and that both the media and the government prefer to turn a blind eye to their plight rather than take them seriously. ", "A recent report about farm attacks reaching record levels over January and February failed to make it much beyond the Afrikaans press. ", "REBECCA DAVIS takes a look at a deeply emotive topic.", "\n\nIn the early hours of February 19, 64-year-old Sue Howarth and her 66 year-old partner Robin Lynn were woken by three intruders on their farm in Dullstroom. ", "When money was demanded, Lynn emptied his wallet and gave the attackers his bank card and PIN number. ", "Reportedly unsatisfied with these spoils, the men tied up Howarth and Lynn, stabbed them, and burned the two with a blow torch. ", "A plastic bag was then tied tightly around Lynn’s head, while another bag was stuffed down Howarth’s throat.", "\n\nHaving loaded the two into the couple’s bakkie, the attackers drove down the R33 before shooting their victims in the head and dumping them near the side of the road. ", "Lynn survived. ", "Howarth died of her injuries in hospital.", "\n\nHowarth’s death brings the number of murders on South African farms to 26 within two months this year, says Bennie van Zyl, general manager of the archaically-named Transvaal Agricultural Union (TAU). ", "The issue of farm murder numbers is heavily contested, but TAU’s figures are used by independent bodies such as the Institute for Security Studies.", "\n\nThe union compiles its data on farm attacks by cross-checking media reports, police cases and reports from its own network. “", "If we cannot confirm the [victim’s] name, place and police [case] number we do not record it,” Van Zyl explains. ", "He says that the first two months of 2017 have been the bloodiest yet experienced.", "\n\nFarm murders are now such a political hot potato that some think it best to avoid the term altogether. ", "A 2008 report by the South African Human Rights Commission (SAHRC) found that “the use of the nomenclature of ‘farm killings’” was “stereotypical and divisive”.", "\n\nOne reason for this in recent years has been the co-option of the issue by the right wing, led by singer Steve Hofmeyr, to support false claims about “white genocide” in South Africa. ", "Factchecking website Africa Check has previously established that whites make up 1.8% of total murder victims in South Africa, while forming 8.85% of the total population.", "\n\nBut there is little doubt that farmers are being killed at higher rates than other sections of the population. ", "The Institute for Security Studies’ Dr Johan Burger says that the general murder ratio for South Africa was 34 people per 100,000 in 2015/2016. “", "For farmers, this figure was 97 per 100,000,” Burger says. “", "To put this into perspective, the ratio for another high risk group – police – is 52 per 100,000.”", "\n\nThe definition of “farm attacks” has been as follows since 2003: “Acts aimed at the person of residents, workers and visitors to farms and smallholdings, whether with the intent to murder, rape, rob or inflict bodily harm.” ", "It excludes “cases related to domestic violence, drunkenness, or resulting from commonplace social interaction between people”. ", "This is a selective focus which has come in for some criticism, given that farmers have historically often been the perpetrators of human rights abuses rather than the victims.", "\n\nThe reasons why farms are targeted for robberies are that they are often isolated, in places where police services are patchy, frequently house elderly individuals, and are perceived as sites where weapons can be stolen.", "\n\nWhat is less easy to explain, however, is the level of brutality meted out in some of the attacks. ", "The ordeal experienced by Howarth and Lynn is not an isolated incident. ", "Also in February, Trevor Rees, a farmer in the southern Drakensberg, hid from intruders in a cupboard. ", "When found, he was tortured with pliers, made to drink Jik, shot twice, and beaten over the course of two days. ", "Rees subsequently died in hospital.", "\n\n“Some people say [farm attacks] are only normal crime that goes overboard,” says Van Zyl. “", "But if a person says they want to steal some food, they don’t break in, wait for hours, burn [victims] with irons, beat them… People shouldn’t tell me this is normal crime. ", "We have a lot of questions.”", "\n\nBurger describes the type of violence increasingly seen in farm attacks as “a very difficult phenomenon to explain”. ", "He says that researchers in the past have interviewed incarcerated farm attackers in an attempt to understand more. ", "They found that torture is sometimes used in situations when intruders suspect money or possessions are being kept from them, for instance in a secret safe.", "\n\nBut there may be other factors at play.", "\n\n“Older farmers in particular come from a period where they are the bosses and black people in general are expected to be respectful,” Burger says. “", "Suddenly [black] robbers enter their house and act in a totally different way. ", "Farmers then still treat them as if they are nothing – they do not acknowledge the fact that the roles have changed.”", "\n\nIn response to this demeaning treatment, Burger suggests, attackers may escalate violence out of anger.", "\n\nThe notion that some farm attacks are motivated by hatred and anger is politically sensitive, but cannot be dismissed. ", "When Knowledge Paulus Mandlazi went on trial last year for murder and robbery on farms in the Brits area in 2014, he openly told the court that he “hated white people and wanted their money”.", "\n\nAfriforum deputy CEO Ernst Roets told Daily Maverick that the organisation is considering releasing a report on the issue soon, but that it would be irresponsible to generalise about all cases.", "\n\nSome political figures see farm attacks as a form of retribution for the injustices and dispossession of the past. ", "Black First Land First leader Andile Mngxitama was recently quoted as saying: “If you look at the gruesome manner in which farmers are attacked, it is more like a response or revenge. ", "Even the farmers that are not involved in brutality end up becoming victims because of the culture of violence. ", "The death of these farmers is minuscule compared to the horrors that black people face.”", "\n\nMngxitama added: “The murders of black people on farms are not counted. ", "Occasionally people react when white farmers are slain.”", "\n\nWhite farmers’ rights activists maintain the opposite: that both the mainstream media and the government prefer to turn a blind eye to the issue. ", "Facebook and other private channels have become the major conduits to share information about farm attacks and pool ideas and resources to deal with the problem.", "\n\n“We are now doing it by ourselves,” says Van Zyl. “", "The closest helping hand you can get is on your own arm. ", "We are creating farm watches, and carrying out training and reconnaissance. ", "We are gathering intelligence by ourselves with our farmworkers. ", "The farming population has its own plans.”", "\n\nIt is often assumed that only white farmers are targeted in attacks, but this is not the case. ", "A 2003 police inquiry into farm attacks found that 38.4% of farm attack victims were black, coloured or Asian. ", "On Sunday, a black family was attacked on their smallholding east of Pretoria. ", "Mosima Molefe was shot twice as she defended her baby, but survived. ", "Tellingly, Netwerk24 reported the victim’s husband as saying: “[Security] initially thought I was one of the suspects.”", "\n\nBlack farmers’ union ASAFA (the African Farmers Association of South Africa) says farm attacks are not a major preoccupation for its members, however. “", "We take it as normal crime, like any other crime in the republic,” secretary general Aggrey Mahanjana says. ", "He does describe farms as “soft targets”, though, and rues the fact that police resources have been drained from rural areas.", "\n\n“We as black farmers regard the issue as serious, but we cannot single it out as if it must be given special attention,” Mahanjana says. “", "For us, bigger daily issues are stock theft, vandalism of property, people removing irrigation systems from our farms…”\n\nAt the end of February, the Freedom Front Plus wrote to the Speaker of Parliament to ask the House to hold a debate on farm murders. ", "Speaker Baleka Mbete responded by acknowledging that the issue was serious, but also said that it did not justify an urgent debate.", "\n\nThis has been greeted as further evidence of the government’s wilful obliviousness on the issue, but the truth is that violence against farmers and farmworkers has been on the agenda for two decades. ", "Former President Nelson Mandela requested the staging of a Summit on Rural Safety as far back as 1998, in response to concerns from the SA Agricultural Union. ", "At that summit, Mandela warned: “Beyond the immediate human suffering, lack of security and stability in our rural and farming community causes serious disruption to our economy.”", "\n\nMandela’s words there provide the argument which farmers present when asked why farm attacks should be viewed as a special category of crime in South Africa.", "\n\n“The biggest asset any government can have is a productive commercial farmer,” argues Van Zyl. “", "You cannot spread politics over bread and feed the nation.” ", "DM\n\nPhoto: A farm windmill. ", "EPA/KIM LUDBROOK" ]

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[ "Q:\n\n$_GET[] doesn't work in included file?", "\n\nI have a webpage which holds the number of the page to display:\nmydomain.net/index.php?page=42\n\nThis works alright. ", "Now I want to display the page only when a particular cookie is set, and I moved most of the body to an include file, so that index.php only has\n<?", "php \n if ($cookie_ok):\n include(\"http://mydomain.net/index_d6skrif9.php\"); \n else:\n include(\"http://mydomain.net/noaccess.inc\"); \n endif \n?", ">\n\nand now the $_GET[\"page\"] in the include file, which is supposed to retrieve the page number returns nothing. ", "\nI read that $_GET[] is a superglobal and that superglobals' scopes are across include files. ", "So what's wrong here, and how can I use the page number in the include file?", "\n\nA:\n\n$_GET works in included files, it does not work in included HTTP resources.", "\nThe PHP in index_d6skrif9.php will be executed by mydomain.net before it gets to the PHP program with the include statement in it.", "\nUse a local file path, not an HTTP URL.", "\ninclude(\"index_d6skrif9.php\"); \n\nAlternatively, pass the value to the server you are pulling the include from:\ninclude(\"http://mydomain.net/index_d6skrif9.php?page=\" + urlencode($_GET['page'])); \n\nNote that the latter approach has far more opportunity for things to go wrong and is much less efficient than a local file included, so it isn't recommended if you can help it.", "\n\nA:\n\nYou'll need to include them locally, not over-the-web:\nif ($cookie_ok) \n include(\"index_d6skrif9.php\"); \nelse\n include(\"noaccess.inc\"); \nendif \n\nBy using URLs, you're making a web-request and the server executes the PHP in the file and returns the contents (making it have its own set of super-globals).", "\n\n" ]

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[ "Clare Jones (front row, centre) with her Wales team-mates\n\nWales netballer Clare Jones wants greater understanding of the potentially debilitating impact of periods on female athletes.", "\n\nThe wing defence or centre from Swansea, who plays for Premier Division 2 champions Hucclecote, says it is a subject that is often ignored.", "\n\n\"It's a massive topic within sport and it's definitely not given focus,\" said Jones, an assistant psychologist.", "\n\n\"The way it affects an individual is different from month to month.\"", "\n\nJones says that a woman's natural cycle can have an impact on not just her performance come competition day, but also hamper training schedules and motivation.", "\n\n\"Personally I've had months where fatigue has really kicked in and I've definitely been guilty of not wanting to say to my coach that... this is having an affect on my performance or how I feel,\" she told BBC Sport Wales.", "\n\n\"I don't like being hindered by anything that would stop me getting a good result or developing as an athlete.", "\n\n\"So there is a bit of stubbornness and a bit of pride over... something you can't really control, it's going to happen month by month.", "\n\n\"But that's why I feel quite passionate that coaches should be aware of the effects it can have on us and also to ensure our... training is looked at and modified a bit to get the best out of us at that time.\"", "\n\n'Some months are just horrendous'\n\nIs it that time of the month again? - ", "Hockey players talk periods\n\nJones believes her chosen sport is good at dealing with women's issues including the impact of periods, but realises athletes in other sports may not feel so supported.", "\n\n\"I've had previous coaches that have just seen the colour absolutely drain from me and... they've been able to say, 'right, get some fluids onboard or get some salts down you, whatever you need to',\" she said.", "\n\n\"You might assume that the male coaches in particular might be a bit uncomfortable talking about it to their female athletes, but actually in my experience [that's not the case].", "\n\n\"I never take for granted the advantages of being within a team sport; being a netballer I'm surrounded by girls going through exactly the same as me.", "\n\n\"Some months are just horrendous and you can really help each other and you've got those people to talk to.", "\n\n\"Obviously it's been mental health awareness week all last week - I'm a huge advocate for mental health through my job - and you can only really encourage people who don't feel supported to go to someone and just let off some steam, or explain to someone that they just don't feel right.\"", "\n\nAs well as reaching out to someone to deal with any emotional problems, her advice to offset any physical changes is to do the simple things: get plenty of sleep, keep hydrated and eat properly.", "\n\nBBC Sport has launched #ChangeTheGame this summer to showcase female athletes in a way they never have been before. ", "Through more live women's sport available to watch across the BBC this summer, complemented by our journalism, we are aiming to turn up the volume on women's sport and alter perceptions. ", "Find out more here." ]

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[ "Q:\n\nSave OneHot Encoder object python\n\nIs there anyway of saving OneHotencoder object in python? . ", "Reason is being I used that object in preprocessing of training data and test data and we are building a API containing the same trained model and that will be injected by real data from the website when user created. ", "So first that data needs to be preprocessed and then model can predict o/p for the same.", "\nThanks\n\nA:\n\nsimple use of pickel for OHE will do for me.", "\n\n" ]

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[ "The objective of this study in postmenopausal women is to determine if a) hormone replacement therapy (HRT) or endurance exercise training independently result in improvements in cardiovascular (CV) function, CV disease risk factors, body composition & bone density and b)combining HRT and exercise training results in even greater beneficial adaptations in these same variables." ]

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[ "1. ", "Technical Field\nThe present invention relates to the MMI (Man-machine interface) interaction, and in particular, to methods for generating and manipulating the grouped photos and apparatuses using the same.", "\n2. ", "Description of the Related Art\nTypically, photos that are shot are stored in a storage device in sequence according to the time the photo was taken or serial numbers which generate by camera automatically. ", "However, this can make it difficult for users to search for a desired photo. ", "Specifically, with the aforementioned photo organization, users need to search for photos by referring to the images icons along their shooting time from the beginning. ", "It consumes excessive time to conduct a search due to the stored photos are in the thousands or even more. ", "Thus, it is desirable to have methods for generating and manipulating grouped photos and apparatuses using the same to reduce search time, thereby improving the user satisfaction." ]

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[ "---\nabstract: 'We demonstrate the growth of Co-doped BaFe$_2$As$_2$ (Ba-122) thin films on [*A*E]{}F$_2$ (001) ([*A*E]{}:Ca, Sr, Ba) single crystal substrates using pulsed laser deposition. ", "All films are grown epitaxially despite of a large misfit of -10.6 % for BaF$_2$ substrate. ", "For all films a reaction layer is formed at the interface confirmed by X-ray diffraction and by transmission electron microscopy. ", "The superconducting transition temperature of the film on CaF$_2$ is around 27 K, whereas the corresponding values of the other films are around 21 K. The Ba-122 on CaF$_2$ shows identical crystalline quality and superconducting properties as films on Fe-buffered MgO.'\nauthor:\n- 'F. Kurth'\n- 'E. Reich'\n- 'J. Hänisch'\n- 'A. Ichinose'\n- 'I. Tsukada'\n- 'R. Hühne'\n- 'S. Trommler'\n- 'J. Engelmann'\n- 'L. Schultz'\n- 'B. Holzapfel'\n- 'K. Iida'\ntitle: 'Versatile fluoride substrates for Fe-based superconducting thin films'\n---\n\nSince the discovery of superconductivity in K-doped BaFe$_2$As$_2$ (Ba-122) [@Rotter2008a] many efforts have been made to investigate the physical properties and to understand the physics in these superconducting materials. ", "Compared to single crystals, thin films are suitable for investigating transport and optical properties due to their dimensionality. ", "Additionally, thin films are favourable for superconducting electronics applications. ", "The symmetry of the superconducting order parameter has been investigated by means of hybrid Josephson junctions using Co-doped Ba-122 thin films realizing S’NS-type Josephson junctions as well as SQUID using bicrystal junctions.[@Katasesquid; @ISI:000284233600037; @0953-2048-25-8-084020; @2012arXiv1211.3879S]\\\nMany groups have prepared thin films of the so called “122” family with *AE*Fe$_2$As$_2$ (*AE*: alkali earth elements, Sr and Ba) by means of pulsed laser deposition (PLD) and molecular beam epitaxy (MBE).[@leeKdopedfilms; @TakedaMBESrBa; @APEX.1.101702; @HiramatsuWaterindsc; @lee:212505; @Katase20092121; @iida:192501; @Katase20092121; @Adachi:2012:0953-2048:105015] We have proposed the usage of Fe as a buffer layer on a MgO (001) substrate for growing Co-doped Ba-122 thin films, which yields high crystalline quality as well as improved superconducting properties under our deposition conditions.[@Thersleff2010]\n\n![", "RHEED images of the $in\\ situ$ growth of the Co-doped Ba-122 phase on (a) CaF$_2$, (b) SrF$_2$, (c) BaF$_2$ and (d) Fe-buffered MgO substrates. ", "The pictures were taken after the deposition. ", "The incident electron beam is along the substrates \\[110\\] azimuth. ", "Since Ba-122 is grown with a 45 rotation on the fluoride substrates, the incident electron beam for (a), (b) and (c) is along the Ba-122 \\[100\\] azimuth. ", "For (d) along the Ba-122 \\[110\\] azimuth.[]{data-label=\"RHEED_all\"}](RHEED_all.eps){width=\"\\columnwidth\"}\n\nHowever, the Fe buffer has some disadvantages, such as the shunting of the current in the normal state which necessitates a recalculation of the superconducting transition temperature, $T_\\mathrm{c}$.[@tro2012] Additionally, measurements of the normal state properties are always hindered by the Fe buffer layer. ", "For instance, the parent compound of Ba-122 has shown a spin density wave anomaly in $R(T)$ curves at around 140 K,[@Rotter2008] however, this transition is hardly recognized in the corresponding thin films on Fe-buffered MgO substrates. ", "Furthermore, the intrinsic physical properties may be influenced by the ferromagnetism of the Fe or FeCo buffer layer, which is currently topic of investigation.[@italysalerno] Another significant influence of the Fe buffer is the observation of Co diffusion from the film into the Fe buffer layer, which leads to off-stoichiometry of the films.[@kurth1] In order to avoid such problems without compromising crystalline quality and superconducting properties, new types of substrates should be explored.\\\nRecently, epitaxial Fe(Se,Te) thin films as well as *RE*FeAs(O,F) (*RE*: Nd and Sm) thin films have been prepared on CaF$_2$ (001) substrates by PLD and MBE respectively.[@JJAP.51.010104; @APEX.4.053101; @Ueda2011; @Uemura2012735] These films show high crystalline quality as well as excellent superconducting properties. ", "Hence, fluorides may be versatile substrates for Fe-based superconducting thin films. ", "In this letter, we demonstrate the epitaxial growth of Co-doped Ba-122 on various fluoride substrates and discuss the influence of substrate materials on the structural and superconducting properties.\\\nFor the deposition process a BaFe$_{1.84}$Co$_{0.16}$As$_2$ bulk target prepared by a solid-state-reaction was used ($T_\\mathrm{c}$ = 23.7 K, measured by magnetization method). ", "The phase purity of the target material was studied by powder X-ray diffraction (XRD) in Bragg-Brentano geometry (CoK$_{\\alpha}$ radiation with $\\lambda$ = 1.7889 Å), showing high phase purity. ", "The detailed preparation procedure and analysis can be found in Ref.[@kurth1]\\\n\n![", "$\\theta$ - 2 $\\theta$ scans for the Ba-122 thin films deposited on (a) CaF$_2$ (001), (b) SrF$_2$ (001) and (c) BaF$_2$ (001) substrates, respectively. ", "A weak BaF$_2$ (002) reflection appears in the film deposited on CaF$_2$ and SrF$_2$.[]{data-label=\"xrd\"}](XRD.eps){width=\"\\columnwidth\"}\n\nThe fluoride substrates were cleaned in an ultrasonic bath using acetone and isopropanol and subsequently transferred into the ultra high vacuum chamber (base pressure 10$^{-9}$ mbar). ", "Co-doped Ba-122 layers were deposited on (001) *AE*F$_2$ (*AE*: Ca, Sr and Ba) single crystalline substrates using a KrF excimer laser ($\\lambda$ = 248 nm, pulse duration = 25 ns) at a frequency of 7 Hz with an energy density of around 2.5 J/cm$^2$ at the target. ", "The samples investigated in this study are summarized in Table \\[tab:dep\\].", "\n\n [**Substrate**]{} [**Deposition temp.**]{} ", " [**Layer thickness**]{}\n ------------------- -------------------------- -------------------------\n CaF$_2$ 750  85 nm\n CaF$_2$ 700  50 nm\n SrF$_2$ 700  40 nm\n BaF$_2$ 700  40 nm\n\n : Deposition temperature and layer thickness of the Co-doped Ba-122 thin films.[]{data-label=\"tab:dep\"}\n\nThe deposition process was monitored $in\\ situ$ by reflection high energy electron diffraction (RHEED). ", "In all cases streak like patterns were observed during film growth pointing to an epitaxial growth with low surface roughness. ", "The spacing between streaks indicates the formation of a superstructure during the growth of the Co-doped Ba-122 on CaF$_2$ and SrF$_2$, i.e. a surface reconstruction that is also observed in single crystals (Fig.\\[RHEED\\_all\\](a), (b)).[@PhysRevLett.106.027002] These RHEED patterns are very similar to Co-doped Ba-122 thin films on Fe-buffered MgO (Fig.\\[RHEED\\_all\\](d)).[@Iida:2011:0953-2048:125009] For Co-doped Ba-122 on BaF$_2$, despite the observation of streaks, however, no sign of this superstructure is observed, presumably due to a relatively large misfit of -10.6%. ", "Therefore we assume a lower surface quality for the film grown on BaF$_2$.\\\nThe phase purity of the thin films was confirmed by X-ray diffraction (Fig.", " \\[xrd\\]). ", "The scans showed no additional reflections of other phases except for the films deposited on both, CaF$_2$ and SrF$_2$, where a small peak at 2$\\theta$ = 33.6 is visible, which can be assigned to the (002) plane of BaF$_2$. The origin of this reflection will be discussed below.\\\nThe determination of the epitaxial relationship between films and substrates was conducted by XRD texture measurements. ", "The (103) and (202) planes have been used for Co-doped Ba-122 and fluoride substrates, respectively. ", "All films showed a clear fourfold symmetry without any additional peaks. ", "The film reflections are rotated 45 with respect to the substrate. ", "Accordingly the films are grown epitaxially with the relation (001)\\[110\\]Ba-122$||$(001)\\[100\\]*AE*F$_2$. The corresponding $\\phi$ scan of Co-doped Ba-122 and substrates are displayed in Fig. ", "\\[phiscan\\]. ", "The average full width at half maximum ($\\Delta\\phi$) values of films grown on CaF$_2$, SrF$_2$ and BaF$_2$ are 1.31, 1.41 and 1.62, respectively. ", "Values were not corrected for device broadening. ", "We assume that the large lattice misfit (Table \\[tab:misfit\\]) leads to a relatively large $\\Delta\\phi$ value. ", "Measurements on a thicker Co-doped Ba-122 film (85 nm) on CaF$_2$ showed an even higher crystalline quality with a $\\Delta\\phi$ value of 0.95, which is almost the same value of layers grown on Fe-buffered MgO.[@Iida:2011:0953-2048:125009]\n\n --------------------- ------------------- -------- --------------- --------\n [Misfit in]{} \n Ba-122 thickness a-axis/$\\sqrt{2}$ a-axis c-axis a-axis\n **CaF$_2$** - 85 nm 3.854 Å 3.89 Å 13.19 Å +2.7%\n **CaF$_2$** - 50 nm 3.854 Å 3.91 Å 13.17 Å +2.7%\n **SrF$_2$** - 40 nm 4.100 Å 3.94 Å 12.97 Å -3.2%\n **BaF$_2$** - 40 nm 4.381 Å 3.96 Å 13.02 Å -10.6%\n --------------------- ------------------- -------- --------------- --------\n\n : Lattice parameters and misfit data of the Ba-122 on different substrates.[]{data-label=\"tab:misfit\"}\n\n![", "$\\phi$ scans of the (103) reflection of the Ba-122 phase on (a) CaF$_2$, (b) SrF$_2$ and (c) BaF$_2$ showing sharp reflections with a four-fold symmetry. ", "No rotated grains are observed.[]{data-label=\"phiscan\"}](phi.eps){width=\"\\columnwidth\"}\n\nAs stated earlier, Co-doped Ba-122 films have been grown rotated 45 in-plane on the substrates. ", "Therefore, the lattice misfit between film and substrate is defined as $((a_{Ba-122}\\times\\sqrt{2})-a_{substrate})/(a_{Ba-122}\\times\\sqrt{2})$. In this calculation, the lattice parameter $\\textit{a}$ = 3.96 Å of bulk (i.e. PLD target) was used. ", "In Table \\[tab:misfit\\], the in-plane and out-of-plane lattice parameters of Co-doped Ba-122 evaluated through high resolution reciprocal space maps (RSM) are also summarized. ", "The out-of-plane lattice parameter evaluated by the Nelson-Riley extrapolation from $\\theta-2\\theta$ scans are in good agreement with the values of the RSM measurements. ", "Clearly, negative misfit values of films on SrF$_2$ and BaF$_2$ lead to a slightly larger in-plane lattice parameter compared to the one on CaF$_2$. However, a change in lattice parameter *a* is small even for large misfit, in particular, BaF$_2$ substrate, whereas a significant change in lattice parameter *c* is observed. ", "Additionally, a reaction layer between Co-doped Ba-122 and substrates is observed, which will be discussed later. ", "Hence, such a change in lattice parameters can not be explained by the simple misfit scenario indicative of another mechanism such as F intercalation into the Co-doped Ba-122 lattice. ", "Possible diffusion of F from the fluoride substrate has been discussed in both the SmFeAs(O,F) and the Fe(Se,Te) systems.[@Takeda:2012:0953-2048:35007; @2012arXiv1208.3287I] Further investigations are underway.", "\n\n![", "TEM bright field monograph of the (a) Ba-122/CaF$_2$ (thickness about 50 nm) and the (b) Ba-122/BaF$_2$ thin film (thickness about 40 nm) showing high structural quality of the Ba-122 layer. ", "However a reaction at the interface is observed.[]{data-label=\"tem_baf2\"}](tem_BaF2_CaF2.eps){width=\"\\columnwidth\"}\n\n![", "HRTEM investigations of the Ba-122 film (thickness about 85 nm) deposited on CaF$_2$ (a). ", "A closer look at the Ba-122-CaF$_2$-substrate interface (b) reveals a reaction layer which can be assumed to be BaF$_2$ due to XRD and EELS data.[]{data-label=\"tem_caf2\"}](Fritz_KI_NEW_104_TEM.eps){width=\"\\columnwidth\"}\n\nTEM investigations of the films grown on CaF$_2$ and BaF$_2$ showed no appreciable defects in the Co-doped Ba-122 layers (Figs. ", "\\[tem\\_baf2\\]). ", "However a reaction at the interface is observed. ", "The respective film thickness on CaF$_2$ and BaF$_2$ substrates are 40 nm and 50 nm. ", "For the film on SrF$_2$, a layer thickness of 40 nm was determined by a cross-sectional focused ion cut on the sample.\\\n\n![(", "a) Resistance measured curves for the Co-doped Ba-122 deposited upon BaF$_2$ (red round), SrF$_2$ (blue star) and CaF$_2$ (green triangle). [*", "T$_\\mathrm{c,90}$*]{} is 21.4 K for the film deposited on BaF$_2$, 22.1 K for the film on SrF$_2$, 26.9 K on CaF$_2$ and 27.9 K for the thicker film on CaF$_2$ (green half-filled triangle). (", "b) T$_{c,90}$ over *c/a* shows almost linear dependence. ", "The film with the highest *c/a* ratio shows the highest [*T$_\\mathrm{c,90}$*]{} (green half-filled triangle). ", "The data from oxide substrates are also plotted on the same figure.[@iida:192501][]{data-label=\"rt\"}](rt_tc_o_ca.eps){width=\"\\columnwidth\"}\n\nMicrostructual investigations on a thicker film (i.e. better crystalline quality) by high resolution TEM (HRTEM), high resolution scanning TEM (HRSTEM), and electron energy loss spectroscopy (EELS) have also been conducted. ", "Although a possible fluorine diffusion into the Co-doped Ba-122 has been discussed earlier, a trace of fluorine in the layer cannot be detected by EELS due presumably to the high volatility of the fluorine under the influence of the electron beam. ", "An interfacial layer ($\\sim$10 nm) between the Co-doped Ba-122 and the CaF$_2$ substrate is clearly observed (Figs. ", "\\[tem\\_caf2\\]). ", "A HRSTEM linescan over the interface with combined Ba detection using EELS revealed a small diffusion of Ba into the CaF$_2$ substrate. ", "As stated earlier, a small BaF$_2$ signal was detected in $\\theta$-2$\\theta$ scans (Fig. ", "\\[xrd\\]). ", "Accordingly, we assume this reaction layer to be BaF$_2$.\n\nThe $T_\\mathrm{c,90}$, which is defined as 90 % of the resistance in the normal state at 30 K, of the thin films was determined through resistance measurements with a four point probe method using a Physical Properties Measurement System (Fig. ", "\\[rt\\](a)). ", "The film deposited on BaF$_2$ shows a $T_\\mathrm{c,90}$ of 21.4 K and the film on SrF$_2$ shows 22.1 K whereby the film deposited on CaF$_2$ has the highest value of 26.9 K. It is worth mentioning that the highest $T_\\mathrm{c}$ of over 28 K has been realized in thick Co-doped Ba-122 on CaF$_2$. Additionally, this film shows a high self-field critical current density ($J_\\mathrm{c}$) of over 1 MA/cm$^2$ even at 10 K and good in-field $J_\\mathrm{c}$ performances (not shown in this letter). ", "Hence fluoride substrates, in particular CaF$_2$, offer a clear benefit for growing epitaxial Co-doped Ba-122 with good crystalline quality and superconducting properties. ", "Fig. ", "\\[rt\\](b) shows the relationship between $T_\\mathrm{c}$ and the *c/a* ratio. ", "For comparison, the films on various oxide substrates are also plotted in the same figure.[@iida:192501] It is clear from fig. ", "\\[rt\\](b) that $T_\\mathrm{c}$ is increasing with increasing *c/a*. ", "From the above results we conclude that the lattice distortion clearly affects the superconducting properties. ", "The origin of the trend of the $T_\\mathrm{c,90}$(*c/a*) needs further investigations.", "\n\nHere we emphasize that the crystalline quality of the thicker films grown on CaF$_2$ is almost identical if not superior to the films on Fe-buffered MgO. Additionally, several advantages over the use of Fe buffer layers are highly expected such as the absence of current shunting due to the Fe layer.[@tro2012] Most importantly, the stoichiometry of the Co-doped Ba-122 film, in particular, the Co concentration, can be more stable, since Co diffusion into the Fe-buffer is avoidable.\\\nTo conclude, Co-doped Ba-122 thin films have been grown on various (001) fluoride substrates by PLD. ", "Despite the presence of a possible BaF$_2$ reaction layer, all films have been grown epitaxially with good crystalline quality. ", "In particular, the crystalline quality of the Co-doped Ba-122 on CaF$_2$ substrate is almost identical if not superior to that on Fe-buffered MgO substrate. ", "The lattice distortion of the Co-doped Ba-122, which influences the $T_\\mathrm{c}$ significantly, is confirmed by RSM. ", "The highest $T_\\mathrm{c}$ of about 28 K has been achieved on CaF$_2$. Therefore the CaF$_2$ substrate offers a clear benefit for growing high-quality, epitaxial Fe-based superconducting thin films.\\\nThe authors thank S.Fähler and V.Grinenko for valuable discussions as well as U.Besold, J.Scheiter, M.Langer and M.Kühnel for technical support. ", "The research leading to these results has received funding from European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 283141 (IRON-SEA) and by Strategic International Collaborative Research Program (SICORP), Japan Science and Technology Agency.", "\n\n[26]{}ifxundefined \\[1\\][ ifx[\\#1]{} ]{}ifnum \\[1\\][ \\#1firstoftwo secondoftwo ]{}ifx \\[1\\][ \\#1firstoftwo secondoftwo ]{}““\\#1””@noop \\[0\\][secondoftwo]{}sanitize@url \\[0\\][‘\\\n12‘\\$12 ‘&12‘\\#12‘12‘\\_12‘%12]{}@startlink\\[1\\]@endlink\\[0\\]@bib@innerbibempty [****,  ()](http://link.aps.org/doi/10.1103/PhysRevLett.101.107006) [****,  ()](http://stacks.iop.org/0953-2048/23/i=8/a=082001) [****,  ()](\\doibase 10.1063/1.3505526) [****,  ()](http://stacks.iop.org/0953-2048/25/i=8/a=084020) [****, ()](\\doibase 10.1109/TASC.2012.2226861) [****,  ()](\\doibase 10.1063/1.3431583) [****,  ()](\\doibase 10.1143/APEX.3.093101) [****,  ()](\\doibase\n 10.1143/APEX.1.101702) [****,  ()](\\doibase\n 10.1103/PhysRevB.80.052501) [****,  ()](\\doibase 10.1063/1.3262953) [****,  ()](\\doibase\n 10.1016/j.ssc.2009.10.001) [****,  ()](\\doibase 10.1063/1.3259922) [****, ()](\\doibase\n doi:10.1088/0953-2048/25/10/105015) [****,  ()](\\doibase 10.1063/1.3457432) [****,  ()](\\doibase 10.1063/1.3696888) [****, ()](http://link.aps.org/doi/10.1103/PhysRevB.78.020503) @noop [“,” ]{} [****,  ()](http://stacks.iop.org/0953-2048/26/i=2/a=025014) [****,  ()](\\doibase\n 10.1143/JJAP.51.010104) [****,  ()](\\doibase 10.1143/APEX.4.053101) [****,  ()](\\doibase\n 10.1063/1.3664632) [****,  ()](\\doibase 10.1016/j.ssc.2012.01.037) [****,  ()](\\doibase\n 10.1103/PhysRevLett.106.027002) [****, ()](\\doibase\n doi:10.1088/0953-2048/24/12/125009) [****,  ()](\\doibase\n doi:10.1088/0953-2048/25/3/035007) @noop [ ()]{},\n" ]

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[ "\"Cauliflower Ear\", while a badge of honor for some, can be an embarrassing disfigurement for others. ", "Fortunately CauliCure can help to restore your ears to their natural shape!", "\n\nIn 2015, CauliCure™introduced the First CauliCure™ Compression System. ", "Since then, thousands of Grapplers, Wrestlers, Boxers and Rugby Players have used CauliCure™ to Manage, Treat and Prevent the painful and disfiguring effects of Cauliflower Ear.", "\n\nNow in 2019 Caulicure™️proudly introduces a 2nd Generation of the system in one easy and reusable product.", "\n\nCaulicure™ RESTORE:\n\nThe system has been re-introduced with a few key changes providing an even better outcome in maintaining the shape of the ear.", "\n\nWe now have a proprietary magnet manufactured specifically for improving the comfort and pull strength required to safely compress the ear tissues almost effortlessly. ", "In addition, the medical grade silicone has been modified to be more durable and softer than ever before.", "\n\nThe compression band has been altered to fit more comfortably, while offering the same reliability in keeping the discs in place while you sleep.", "\n\nLastly, the small disc has been modified to be slightly larger in diameter, lower profile, while allowing a more stable fit during daytime and nighttime use.", "\n\nCaulicure™ ACTIVE:\n\nThe Caulicure™ACTIVE compression discs were designed to allow continued compression while training, competing, or practicing on the mats or on the field.", "\n\nCreating a system to allow for uninterrupted compression from the very onset of ear damage to complete resolution, is the single most important requirement for any grappler, wrestler or rugby player.", "\n\nThe Caulicure™ACTIVE discs are low profile, strong, very durable, and are designed to be worn under the provided headgear.", "\n\nThe Caulicure™ ACTIVE discs REQUIRE headgear to work effectively. ", "Use your own or add one to your cart with any kit for only $10\n\nWhat’s in the box?", "\n\nRESTORE - 4 compression discs including 1 Large, 2 medium and 1 small. ", "These can be applied before or after the ear fills with fluid and are designed to be worn all day and night.", "\n\nACTIVE - 4 compression discs including 2 large and 2 small. ", "These are to be applied during training, competition or practice only. ", "You must use these discs under headgear at all times. ", "Remove these discs after activity is over, and apply the RESTORE compression discs immediately." ]

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[ "Q:\n\nWhy Subsection at top-bar in fancyhdr?", "\n\nCode \n\\documentclass{article}\n\n\\usepackage{fancyhdr}\n\n\\pagestyle{fancy}\n\\rhead{\\textsc{Department}}\n\\cfoot{\\thepage}\n\n\\begin{document}\n\n% \\section{Objective Data} % nothing at left top when this active\n\n\\subsection{Status localis}\n\nHello world\n\n\\end{document}\n\nOutput\n\nExpected output: without 0.1 Status localis at the top-left bar. ", "\n\nHow can you have no subsection at top-left bar? ", "\n\nA:\n\nJust say \\lhead{}, i.e. an empty left page heading, because this is used by \\leftmark{} normally, which prints a section etc. ", "title. ", "\n\\documentclass{article}\n\n\\usepackage{fancyhdr}\n\n\\pagestyle{fancy}\n\\rhead{\\textsc{Department}}\n\\lhead{}%\n\\cfoot{\\thepage}\n\n\\begin{document}\n\n%\\section{Objective Data} % nothing at left top when this active\n\n\\subsection{Status localis}\n\nHello world\n\n\\end{document}\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Q:\n\nHow much citric acid is safe to use?", "\n\nI am using citric acid as a preservative for peanut sauce. ", "The 1tsp per quart is not strong enough. ", "Is it safe to use a higher concentration? ", "My peanut sauce is currently at a pH of 4.5, I need <4.3. ", "I don't want to water down the sauce any more than it already is. ", "I will be hot pack bottling, maybe.", "\n\nA:\n\nAccording to (US) Code of Federal Regulations on Citric acid:\n\n(c) In accordance with § 184.1(b)(1), the ingredient is used in food with no limitations other than current good manufacturing practice. (", "d) Prior sanctions for this ingredient different from the uses established in this section do not exist or have been waived. ", "\n\nBasically, you can eat the stuff by the spoon-full if you can stand the sour.", "\nIf you're adding a lot compared to how much you think you should have to add, you might consider Phosphoric acid instead. ", "You get a little more bang per mole pH-wise with that, and it too, within limits, is generally regarded as safe (GRAS). ", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "[Comparison of various methods of correction of QT intervals during exercise in familial long QT interval syndrome].", "\nPathologic prolongation of QT interval is related to increased risk of arrhythmias. ", "Changes of this parameter are influenced by many conditions, the most important is heart rate. ", "Several formulas have been proposed for mathematical description of QT interval/heart rate relationship. ", "The aim of this study was comparison of different QT interval correction formulas in families with congenital long QT syndrome (LQTS). ", "In 28 members of 6 families with LQTS occurrence bicycle ergometry testings were performed. ", "QT and RR intervals were measured before exercise, at peak exercise and in the 1st and the 6th minute of restitution. ", "For QT interval correction single-parameter formulas by Bazett, Fridericia, Malik and Framingham study were used. ", "In 3 families the results could be correlated with genetically proved diagnosis (KCNQ1 gene mutations in 2 families, HERG-KCNH2 gene mutation in the other). ", "In the described group the genetically established diagnosis of LQTS correlated at best with values obtained with correction by Bazett. ", "All the mutation carriers were correctly identified only by this method. ", "The Fridericia, Malik and Framingham formulas failed to identify 2 patients--mutation carriers (both KCNQ1 and HERG-KCNH2 mutations). ", "Because of simplicity the Bazett formula remains the most common method of QT interval correction. ", "Moreover, in our study this formula appeared to be the most sensitive for clinical diagnosis of LQTS." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "TNF-α exerts cytotoxic effects on multidrug resistant breast cancer MCF-7/MX cells via a non-apoptotic death pathway.", "\nTumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. ", "Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. ", "In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed. ", "Although, treatment of MCF-7 cells with TNF-α activated NF-kB and caused RIP1 ubiquitination, TNF-α exposure led to JNK and RIP1 phosphorylation in MCF-7/MX cells. ", "In both cell lines TNF-α did not activate the caspase cascade. ", "Moreover, AnexinV/PI analysis showed that cytotoxic effects of TNF-α on MCF-7/MX is mediated via apoptosis independent mechanisms and inhibition of RIP1 kinase activity using necrostatin-1 revealed that kinase activity of RIP1 plays role in the production of ROS, activation of JNK and cellular death following exposure of MCF-7/MX cells to TNF-α. ", "Overall, it seems that RIP1 ubiquitination and NF-kB activation are prosurvival signaling mediators protecting MCF-7 cells against cytotoxic effects of TNF-α while TNF-α drives MCF-7/MX cells to non-apoptotic cellular death via kinase activity of RIP1, activation of JNK and ROS production." ]

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[ "2/10/13 11:53 AM EST\n\n\"The president and I spoke about this visit and agreed that we would discuss three main issues,” Netanyahu said, according to a Reuters report. “", "Iran's attempt to arm itself with nuclear weapons, the unstable situation in Syria ... and the efforts to advance the diplomatic process of peace between the Palestinians and us.”", "\n\nThe White House has yet to confirm the dates of Obama’s visit to Israel, which press secretary Jay Carney said Tuesday that Obama’s trip will also take the president to the West Bank and Jordan.", "\n\n\"It is a very important visit that will emphasize the strong alliance between Israel and the United States,\" Netanyahu said." ]

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[ "Prime Minister David Cameron has vowed to hunt down and bring to justice the Islamic State fighters responsible for the killing of a British aid worker.", "\n\n\n\nCameron's comments on Sunday came after an emergency meeting with his top security advisers in response to an online video that purports to show the beheading of David Haines who was abducted while working in Syria.", "\n\n\n\n\"David has been murdered in the most callus and brutal way by an organisation, which is the embodiment of evil,\" Cameron said.", "\n\n\n\n\"The fact that an aid worker was taken, held and brutally murdered at the hand of ISIL sums up what this organisation stands for,\" Cameron added.", "\n\n\n\n\"They are killing and slaughtering thousands of people; Muslims, Christians and minorities across Iraq and Syria. ", "They boast of their brutality. ", "They claim to do this in the name if Islam. ", "That is nonsense. ", "Islam is a religion of peace. ", "They are not Muslims, they are monsters.\"", "\n\n\n\nCameron said that the UK could not afford to ignore the threat of IS and would continue to support the international coalition that is fighting the group.", "\n\n\n\n\"There is no option of keeping our heads down that would keep us safe… We have to confront this menace. ", "We must drive back, dismantle and ultimately destroy ISIL and what it stands for. ", "We will do so in a clam deliberate way but with an iron determination.", "\n\nFourth hostage threatened\n\nIt was the third apparent beheading of a Western hostage in less than a month and an Islamic State member seen apparently killing Haines in the video threatened to execute a fourth, another Briton.", "\n\nThe video blamed Cameron for joining forces with the United States, which has said it is at \"war\" with the group and is currently hitting it with air strikes in Iraq.", "\n\nThe government in London faces accusations of confusion over its policy towards the Islamic State after conflicting comments from Downing Street and the Foreign Office last week.", "\n\nDuring a visit to Berlin, Foreign Secretary Philip Hammond said Britain would not take part in strikes against IS in Syria, after parliament last year voted against taking military action in that country.", "\n\nBut just hours later, a spokesman for Cameron's Downing Street office insisted the prime minister was not ruling anything out.", "\n\n'Degrade and destroy'\n\nIn a statement issued on Saturday night, US President Barrack Obama said the hearts of Americans go out to Haines' family and the people of the United Kingdom.", "\n\n\"The United States stands shoulder to shoulder tonight with our close friend and ally in grief and resolve,\" Obama said.", "\n\n\"We will work with the United Kingdom and a broad coalition of nations from the region and around the world to bring the perpetrators of this outrageous act to justice, and to degrade and destroy this threat to the people of our countries, the region and the world,\" he said.", "\n\nIn his statement, Obama repeated the pledge he made on Wednesday night in a nationally televised address in which he laid out a strategy to respond to the threat from IS, which is also referred to as ISIL.", "\n\n\"Our objective is clear,\" he told the nation earlier this week.", "\n\n\"We will degrade, and ultimately destroy, ISIL through a comprehensive and sustained counter-terrorism strategy.\"", "\n\nAs part of that effort, US Secretary of State John Kerry announced on Saturday that retired Marine General John Allen was joining the State Department as a special presidential envoy to coordinate the international coalition.", "\n\nThe Australian prime minister, Tony Abbot, said on Sunday said his country would contribute 600 troops and up to 10 military aircraft to the coalition." ]

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[ "It has been known for many years that cellulose can be synthesized by certain bacteria, particularly those of the genus Acetobacter. ", "However, taxonomists have been unable to agree upon a consistent classification of the cellulose producing species of Acetobacter. ", "For example, the cellulose producing microorganisms listed in the 15th Edition of the Catalog of the American Type Culture Collection under accession numbers 10245, 10821 and 23769 are classified both as Acetobacter aceti subsp. ", "xylinum and as Acetobacter pasteurianus. ", "For the purposes of the present invention any species or variety of bacterium within the genus Acetobacter that will produce cellulose under agitated conditions should be regarded as a suitable cellulose producer for the purposes of the present invention.", "\nAcetobactor aceti subsp. ", "xylinum is normally cultured under static conditions with the cellulose microfibrils being produced at the air medium interface. ", "A normal cellulose pellicle produced in a static culture tends to have a lamellar structure with significantly less branching. ", "Most bacteria of this species are very poor cellulose producers when grown in agitated culture. ", "One reason proposed for such poor production is that an agitated culture induces a tendency to mutation to noncellulose producing strains. ", "In contrast, the Acetobacter strains according to the present invention are characterized by an ability to produce large amounts of cellulose in agitated culture without manifesting instability leading to loss of cellulose production in culture.", "\nThe present invention involves the processing and use of bacterial cellulose produced by such microorganisms under agitated conditions. ", "U.S. Pat. ", "No. ", "4,863,565, granted Sep. 5, 1989 discloses Acetobacter varieties which are vigorous cellulose producers under agitated culture conditions. ", "The cellulose produced by the microorganisms and culture conditions disclosed in this application appears to be a unique type, physically quite different from the bacterial cellulose produced in static cultures. ", "It has a highly branched, three dimensional reticulated structure.", "\nBacterial cellulose fibers formed from an agitated mixture is in the form of pellets or pellet fragments. ", "These pellets may be on the order of 1 mm. ", "in size. ", "The pellets or pellet fragments are then formed in a cake which is typically between 10 and 20% solids. ", "Before use the reticulated bacterial cellulose is diluted to the desired solids content, and soluble or insoluble materials are added to preserve or enhance the properties of the final product.", "\nU.S. Pat. ", "No. ", "4,861,427 discloses the use of such a bacterial cellulose as a surface treatment for fibrous webs.", "\nU.S. Pat. ", "No. ", "4,374,702 discloses a process in which a Gaulin homogenizer is used to convert wood pulp fibers to microfibrillated cellulose." ]

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[ "Parts of Highway 1 in Santa Cruz will be closed for emergency repairs on Tuesday. ", "According to Caltrans, northbound lanes of Highway 1 at Bay Street in Santa Cruz to be closed Tuesday, May 21 from 9 a.m. to 5 p.m.All traffic heading northbound on Highway 1 will be detoured onto Bay Street. ", "Motorists can expect delays of up to 20 minutes to access and get through the detour. ", "The closure is because of an \"emergency electrical project\" to replace a damaged signal pole following a recent crash.", "\n\nSANTA CRUZ, Calif. —\n\nParts of Highway 1 in Santa Cruz will be closed for emergency repairs on Tuesday.", "\n\nAccording to Caltrans, northbound lanes of Highway 1 at Bay Street in Santa Cruz to be closed Tuesday, May 21 from 9 a.m. to 5 p.m.\n\nAdvertisement\n\nAll traffic heading northbound on Highway 1 will be detoured onto Bay Street. ", "Motorists can expect delays of up to 20 minutes to access and get through the detour.", "\n\nTraffic backed up from Highway 1 road closure.", "\n\nThe closure is because of an \"emergency electrical project\" to replace a damaged signal pole following a recent crash." ]

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[ "Third year Bengals cornerback Darqueze Dennard is more than familiar when it comes to lofty praise. ", "The former Michigan State prospect was projected to be selected in the top half of the first round of the 2014 NFL Draft. ", "When the Bengals selected him at the 24th spot, defensive coordinator Paul Guenther and then co-defensive backs coach Vance Joseph chose another Big 10 alum to compare him to:\n\nNone other than former Bengal and current free agent cornerback Leon Hall.", "\n\nThey couldn’t really give any higher acclimation to the rookie two years ago.", "\n\nThere may not be a tougher position in the modern NFL than being a slot cornerback. ", "Sure, the most recognizable corners in the game spend the vast majority of their snaps on the outside. ", "But with offenses transitioning to more three wide receiver looks, and slot receivers being used in more creative ways than ever before, the task of being just a serviceable slot cornerback requires supreme quickness and a vast amount of trust in your eyes and footwork.", "\n\nFor many years, Hall exhibited these traits better than practically anyone else in the league. ", "And even after two achilles injuries in the last five years, he still managed to perform like his old self in spurts last year.", "\n\nReactionary skills are by far the most vital for any defensive back, but the need for it is unmatched for slot corners. ", "Since the majority of routes they cover occur in short areas, the margin for error is so small where a misstep is answered with an easy completion. ", "Not to mention they have to be athletic to at least mirror the route.", "\n\nThis play came from last year’s Week 9 Thursday night encounter with the Cleveland Browns. ", "While quarterback Johnny Manziel has four different targets to go for against this cover 1 man look from the Bengals, this play is designed to have a single read. ", "The other three routes of the play call is to get Y receiver Taylor Gabriel isolated. ", "The only thing Gabriel has to do is sell the slant and transition to a flat route to beat Hall. ", "Too bad he was lined up against the wrong cornerback: (BTW, that’s Dennard at the top of the GIF)\n\nIt’s almost impossible to play it better than that if you’re the cornerback.", "\n\nWith countless plays like this under his belt, Hall has enjoyed a distinguished nine year career here in the Queen City, and is somewhat of an unsung hero around the league. ", "His All-Pro Team exposure consists of only 2009 AP and PFF Second Team honors, and he has never been voted to a Pro Bowl. ", "But this is not to slander the media’s and fan’s ignorance to Hall’s skill, it’s a testament to how unappreciated any nickel corner has been in recent memory, if arguably the very best of a generation has been snubbed of recognition so many times.", "\n\nThe long and short of it: Dennard has some very large and underrated shoes to fill if Hall has indeed played his final games in black and orange. ", "Has he shown he can live up to his hype so far in his short career? ", "Let’s go back to the tape.", "\n\nLate in the fourth quarter, back in Week 4 last year against the Kansas City Chiefs, we see another cover 1 man look from the Bengals, with a three wide receiver set from the Chiefs. ", "Dennard and Dre Kirkpatrick on the opposite boundary are playing off man coverage, which is understandable in this scenario where the Bengals were leading by 18 points with less than five minutes remaining in the game. ", "The simple objective is to not get beaten deep and allow any big plays.", "\n\nRemember those reactionary skills? ", "It’s a pretty broad term, but having quick hips is a monumental part of it. ", "Dennard learned this the hard way:\n\nThis is what technique can look like from a lack of snaps. ", "Dennard is sold by wide receiver Chris Conley’s fake go route, where he turns his hips to the right to keep Conley outside and give him less sideline room to run. ", "Conley uses a simple dig and completely turns Dennard around.", "\n\nThis is a prime example of having stiff hips, which isn’t promising for someone whose projected to play significant time covering the slot. ", "Speaking of which, Dennard had two notable snaps covering the slot this past season, let’s diagnose them.", "\n\nWe’ve seen a couple of cover 1 looks, now we see the Bengals cover 0 concept with no safety over top. ", "It’s an eight man blitz with three corners playing man. ", "There’s not a whole lot of margin for error for any of them if the pass gets off, and unfortunately for Dennard, quarterback Russell Wilson does just that:\n\nNow, Doug Baldwin, the wide receiver who made this catch, didn’t have a career-year last year by not burning most of the corners he lined up against. ", "This is a veteran stop and go route from the Seahawk standout, and Dennard is caught flat footed and left out to dry. ", "Defensive end Carlos Dunlap was a split second away from flattening Wilson for a sack, and the pressure he created caused Wilson’s throw to be under-thrown, bailing out Dennard to an extent by giving him more time to catch up to Baldwin, but the aftermath of the double move and the difference in speed is too much for him.", "\n\nOf course, the game of football is predicated on mismatches, and in the pre snap phase, Wilson and Baldwin were on the same page. ", "The signal caller moved Baldwin inside to create a more favorable matchup against Dennard, while also moving tight end Jimmy Graham next to the line of scrimmage to help against the pending blitz:\n\nThis tactic is normal to do against an inexperienced player like Dennard, and the very next week, the Buffalo Bills probably thought they could have some success on a similar play.", "\n\nOn a third and short, the Bengals added some short zone coverage to their ever appearing cover 1 man coverage. ", "Quarterback E.J. Manuel had three short yardage options designed to mask wide receiver Chris Hogan’s go route from the slot. ", "Dennard had solid positioning throughout the entirety of the route and instead of throwing Hogan open, Manuel hesitated and ended up under throwing the pass; giving Dennard an opportunity to show off his hands for the very first time in his career:\n\nWhether you’re playing the slot or the boundary, the ability to find the ball is crucial when playing man coverage downfield. ", "Dennard displayed he could do just that here.", "\n\nLast but not least, playing the run and making plays behind the line of scrimmage is imperative as a corner, and most of that starts from disengaging from the block the receiver gives. ", "The best example from Dennard last year is this play from the Sunday night game at Arizona:\n\nIt’s a play action reverse handoff to wide receiver Jon Brown, who motioned all the way from the Z spot on the far boundary. ", "Weak side defensive end Michael Johnson does a good job of getting off the line quickly and is in position to maintain backside containment, but the reverse catches him in a bad spot to make a play in the backfield. ", "Brown, being the athlete he is, makes his way around Johnson and begins accelerating up field. ", "He would’ve left Johnson in the dust had Dennard been blocked out of the play:\n\nDennard does a superb job of shedding the receiver’s block and using his hands to push back towards Brown. ", "Had the block been effective, Brown would have had ample room to run for a much greater yardage on the play, but Dennard’s presence turned Brown back towards the middle of the field and Johnson and Dennard finished the stop for a short gain. ", "The less effective trick plays are for the opposing squad, the more one dimensional they become over the course of the game.", "\n\nSo we’ve seen Dennard have issues with his hips in off coverage and letting his lack of proper footwork get the best of him. ", "We also saw him utilize good ball skills and great reactionary block shedding. ", "It was a very up and down second year for the \"Leon clone\" that was eventually halted by injury, but this doesn’t mean that the words his coaches used back in 2014 carry any less weight. ", "More than anything, with a first Round investment looking to make a bigger impact in his third year, it’s time to really see what he can do in a starters role.", "\n\nThe modern day NFL defense has evolved to where three corners are playing the majority of the time, and with Hall still a free agent, Dennard is in line to replace his role as that third corner, where Hall has thrived. ", "We don’t quite know yet if Dennard can prove to be a worthy predecessor, what we do know, is that now is the time to truly find out." ]

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[ "Fear not, I'm coming! ", "I Garen-Tee it. ", "Guide for Garen Crownguard\n\nGaren Build\n\nTable of Contents\n\nIntro\n\nWelcome to Loiri's Garen guide, feat. ", "Linnala!", "\n\nFirst of all, english isn't my first language, so my spelling and grammar may look weird sometimes, im sorry. ", "Also, this is my first guide. :)", "\n\nI play Garen as a \"CDR Off-tank\". ", "I have never seen any Garen with this build, thats why i am showing you my personal Garen playstyle, because, atleast for me, it's working perfectly. ", "This is going to be a short and simply guide (mostly because of my weak english writing skills) that contains all basic information with some tips and video clips.", "\n\n!!! ", "This guide Is based on 5v5 map Summoner's Rift. ", "Don't try this on other maps, it won't work !!!", "\n\nLet's end this quickly!", "\n\nYou need to use the little soldier's room? ", "Don't worry, here's the shortened guide that contains all you need to know in simple way!", "\n\nAbilities\n\nGaren's best skill imo. ", "Crazy damage and silence (2.5s) at lvl 1, awesome scale, speed boost and short cooldown. ", "Also good for chasing and escaping.", "\n\nDecisive strike resets your basic attack timer, so it's wise to use it immediately after basic attack. ", "That way you can hit 3 attacks in row. ", "This method really hurts at lvl 1! ", "Deceive Strike is also good for last hitting since it's free to cast and doesn't have long cooldown, even at early levels.", "\n\nYour main damage ability. ", "The slow remove thing is often ignored, but for real, it's damn useful! ", "It often makes your escaping easier and makes you one step harder to kite. ", "Simply example:\n1. ", "You are casing Teemo. ", "Teemo places shroom behind him. ", "You step on the shroom and immediately after you use Judgment to remove the slow and continue the chase!", "\n2. ", "Enemies are chasing you. ", "You step on a shroom and get slowed and immediately after you use Judgment (and Courage to reduce it's damage if needed) and continue your escape with full speed!", "\n\nFinisher of your killer-combo and a fihishing move in general. ", "Damage of this skill is often underestimated and that allow you to surprise your enemy, like killing them from half health under their own tower (video coming!). ", "Awesome combined with Ignite/ Flash (video coming!) ", "or just finish escaping enemies in fights.", "\n\nNote: It deals magic damage.", "\n\nScales from: Magic penetration\n\nLaning\n\nGaren is a very bad jungler, so you have to lane with him. ", "Don't worry, because Garen is very good on every lane! ", "Solotop (recommended), bot with support or any other champion or even solomid.", "\n\nAgressive laneplaying is often very good strategy for Garen, because there is not many champions that can beat you in fair 1v1 at early game (especially when you get your The Brutalizer. ", "Still, some tanky champions that can heal or absorb big amount of damage (example: Warwick) can be very problematic.", "\n\nGaren's 2v2 lane damage output is also godlike. ", "Other melee fighter are normally very good lanepartner for aggressive playing. ", "Heres some examples:\n\nXin Zhao, very durable melee fighter and deals tons of damage on early game and also has some CC, exactly like you.", "\n\nYorick, same as Xin Zhao. (", "see above)\n\nRenekton (see above)\n\nJarvan 4 (see above)\n\nGaren + Ranged AD is also pain in the ass for your opponent.", "\n(more info coming!)", "\n\nSkilling Order\n\nPretty basic skilling order for any Garen. ", "Some Garen players still start with Judgment, but Decisive Strike is just superior. ", "Decisive Strike does more damage at lvl 1, it has silence, speed boost and it resets your basic attack timer, which allow you to do some burst. ", "Slow remove on Judgment is rarely needed at lvl 1, because not many champions pick their slows first and even if they would, Decisive Strike is still overall better choice.", "\n\nSummoner Spells\n\nPersonally i always use Ignite & Flash on Garen. ", "The reason i take Ignite over Exhaust is because you can kill squishies from half health with your Ignite/ulti combo (video coming!). ", "Also i take Flash over Ghost for epic jukes and Flash+Q, E or Ulti can surprise anyone!", "\nIt's just what you like to take. ", "Exhaust and Ghost are very good choises for Garen too. ", "One \"offensive\" and one \"defencive\" is good for alsmot every champion and Garen isn't deviant!", "\n\nMasteries\n\nI like those masteries alot on Garen! ", "21/9 & 9/21 are very viable for Garen too, as well as Utility+Defense/Offense hybrid too. ", "I have tried many mastery setups on Garen, but 12/16+2 fits my playstyle best. ", "Give it a try!", "\n\nIf you are not using Ghost, replace [mastery=Haste] wiht something else. ", "Viable choices would be: [mastery=Defensive Mastery],[mastery=Offensive Mastery] or Brute Force. ", "You can also take one point away from Resistance if you want to put an additional point to one of those masteries. [", "mastery=Cripple] is just a filler, even if u don't use Exhaust, because you don't get any benefit from [mastery=Archmage's Savvy].", "\n\nWith [mastery=Sunder], armor penetration marks and quints and The Brutalizer you have 46 armor penetration. ", "That allows you to deal true damage to most champions early game especially to the shuishy ones!", "\n\n(More info coming!)", "\n\nItems\n\nAs i said before, i build Garen as \"CDR Off-tank\" and here's my build:\n\nI always start with Boots of Speed and 3x Health Potion. ", "Why? ", "Because Garen HAVE to outrun his target at every point of game. ", "With my runes and masteries i still have 599 health, 40 armor and 35 magic resist at lvl 1. ", "3 Health Potions you can afford by buying Boots first are also very good for aggressive laneplaying.", "\n\nOptimal starting item: Doran's Blade. ", "Personally i never use this on Garen, but it still can be very effective, especially if you are using movement speed quints.", "\n\nWhy not Doran's Shield? ", "I see many Garen players start with Doran's Shield. ", "Imo it's just not good item for him. ", "You don't need early health regen because of your passive and with my mastery and rune setup i have very good defense early without Shield. ", "Health is OK, but you get almost same amount from Blade.", "\n\nAim to get 1337 gold before going back, so you can build The Brutalizer as early as possible. ", "The Brutalizer increaser your damage output ALOT and it's your first CDR item too.", "\n\nIf you can't get those 1337 gold before going back and your lane is terrible, you can get Doran's Blade or two. ", "I normally trying to avoid this option, but sometimes it's MUST, because Garen's mid game depents on his lane dominace, and his late game depents on his mid game. ", "So if you are not winning your lane or even get good amount of last hits you are going to be, well, can't say useless, but just \"not that good\" at the rest of the game.", "\n\nThis is what i use almost every time on Garen. ", "Aim for Ionian Boots of Lucidity. ", "Why not Mercury's Treads? ", "Well, they are other viable choice, but i like to rush as much CDR as possible early on and there is no other really good CRD items for Garen. ", "And imo Garen doesn't really \"need\" those, because in teamfights enemy shouldn't focus their CC's on Garen, but if they do, well, good job off-tank Garen! ", "For smaller fights where is more kiting etc. ", "you have your Judgment, which removes/reduces duration of slows. ", "If you are getting stunned while chasing someone, the enemy most likey getting away with or without Mercury's Treads.", "\n\nI don't really recommend this one, but if you still want to build CDR Off-tank Garen with Mercury's Treads, this is the build for you:\n\n[builder=Garen/37812a6ee8d092460f216849d97db584]\n\n103 Magic resist(!)", "\n67 Armor\n28% CDR\n\nWhy Spirit Visage? ", "It may look dump item for Garen, but it's a good item overall for him. ", "It gives good amount of CDR and some defensive stats and it isn't very expensive. ", "Even the healing bonus isn't useless, since it improves your passive and [item=Force of Nature]'s healing.", "\n\nNext item depents on enemy team and specially who you are laning against if laning phase seems to last forever:\n\n[item=Force of Nature], Sunfire Cape, Atma's Impaler and Infinity Edge or Frozen Mallet. ", "Normally in that order. ", "Why those items and that building order?", "\n[item=Force of Nature] is overall awesome item for Garen. ", "It offers you tons of magic resist and health regen (even more if you are using Mercury build) and movement speed what is VERY important for Garen. ", "The main reason im building this first after the core build is the movement speed bonus on it. ", "Im not normally running with movement speed quints on Garen, so movement speed from items are important to get as soon as possible. [", "item=Force of Nature] makes your movement speed 420 with tier 2 boots. ", "Of course if you are facing heavy AD team you should get Sunfire Cape first.", "\n\nAfter [item=Force of Nature] i always build Sunfire Cape to balance my defesive stats. ", "Magic damage aura synergies very well with your Judgment and health and armor on it is just awesome. ", "Very cost effective item imo.", "\n\nGames rarely last this long, but if game is still running on you should aim for Infinity Edge or Frozen Mallet\nIf you think you have enough damage at this point, you should build Frozen Mallet to get even more tanky and for it's slow. ", "Almost every time i build Infinity Edge instead, the damage increase is just that big. ", "Crit, crit damage and attack damage are awesome on it. ", "Best damage item for Garen.", "\n\nFinal Build:\n\n[builder=Garen/028aac0f844f02dc32f7d1d1c3cfac04]\n\n\"more detals\" thing seems to be bugged or something, it doesn't show real stats. ", "Click \"more detals\" buttom second time and it takes you to builder site where is the correct stats. ", "Im trying to fix this.", "\n\nMallet Build:\n\nRush Frozen Mallet after your core build. ", "You can start with Phage or Giant's Belt, whatever you need. ", "Normally i take Phage first. ", "Then build your Chain Vest into Atma's Impaler and Negatron Cloak into [item=Force of Nature]. ", "I lake to take [item=Force of Nature] first, because of it's movement speed boost and it will balance your defensive stats. ", "It's about what you like. ", "Last item is Infinity Edge. ", "As i said before, it's best damage item for Garen, and if game will last this long, damage is exactly what you need!", "\n\nPersonally i don't like atmogs on any champion, but in certain situations it's very effective build. ", "If you can easily farm to get Warmog's Armor and the extra bonuses for it early and if team fights are not starting before you got it, then it's safe to build atmongs." ]

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[ "The present invention relates to a process for desulphurising crude iron in a ladle containing the hot metal, in particular in a torpedo ladle, having a submerged lance, wherein first aluminum is added and then, by means of the carrier gas, lime is blown into the hot metal.", "\nThe blowing of fine-grain desulphurising agents into hot metal has gained increasing importance in recent years. ", "In this process, mainly agents based on calcium carbide and magnesium are used. ", "Although these desulphurising agents are highly effective, they are relatively expensive.", "\nSince lime is a relatively cheap agent, desulphurising agents based on lime have therefore also been proposed. ", "They have the disadvantage, however, that large quantities are necessary in order to obtain the desired desulphurisation effect. ", "In practice, this leads to considerable difficulties because of the resulting large quantities of slag. ", "The considerable volume of the large quantities of slag in the ladle causes a corresponding reduction in the transport capacity of the ladle. ", "Moreover, the slags tend to deposit on the ladle walls, whereby the transport capacity is yet further restricted. ", "In addition, the slags contain large quantities of iron droplets, which leads to considerable losses of iron.", "\nThe desulphurising agent which consists mainly of lime and, in addition, also proportions of 10-40% by weight of alkaline earth metal carbonate or hydroxide, 2-20% by weight of carbon, 2-10% by weight of at least one fluoride selected from the group comprising alkali metal fluorides, alkaline earth metal fluorides, cryolite and sodium silicofluoride, and 0.015-1.0% by weight of a silicone oil surface-active agent, is known from German Patent Specification No. ", "3.004.973.", "\nIn a further development of the use of lime as a desulphurising agent, aluminum is admixed to the desulphurising agent (German Auslegeschrift No. ", "2.531.047) or first aluminum and then lime are blown into the hot metal by means of high rates of conveying gas. ", "The high rates of a non-oxidising gas, such as, for example, nitrogen, for conveying the lime also serve for dispersing the lime particles in the hot metal and for generating a circulation in the bath. ", "However, this causes considerable disadvantages since, due to incomplete dispersion, the lime cannot deploy its full effect and considerable splashing of the hot metal occurs due to the high conveying gas rates (SDS process of Nippon Steel Corporation). ", "Extensive progressive wear of the refractory lining of the ladle in the inlet region must also be taken into account.", "\nIn known desulphurisation processes which operate with lime as the desulphurising agent, the oxygen formed by the reaction CaO+S=CaS+O is bound by the silicon of the hot metal to give SiO.sub.2. ", "With the lime blown in, this silica forms dicalcium silicate which surrounds the lime grain with a solid layer. ", "As a result, the desulphurisation effect of the lime grain is adversely effected.", "\nIn the known desulphurisation processes with lime, wherein aluminum is additionally blown in to the melt, the oxygen formed by the desulphurisation reaction CaO+S is bound by the aluminum particles blown into the melt, to give Al.sub.2 O.sub.3. ", "The alumina formed is bound by the lime blown in, to give a layer of calcium aluminates n.CaO.Al.sub.2 O.sub.3. ", "In contrast to the solid dicalcium silicate, this layer is predominatly in liquid state above 1350.degree. ", "C., having a good desulphurising capacity.", "\nIt was the object of the present invention to reduce both the required rate of conveying gas and the consumption of lime-containing desulphurising agent." ]

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[ "Russia: U.S. FIFA Investigation Is Illegal, Extraterritorial Use of Law\n\nLess than 24 hours after U.S. and Swiss authorities unveiled a sweeping investigation into corruption at the highest ranks of FIFA, including how the 2018 World Cup was awarded to Russia, Moscow is hitting back.", "\n\nIn a statement Wednesday, Moscow accused Washington of illegally applying its laws around the world. “", "Once again we are calling on Washington to stop attempts to make justice far beyond its borders using its legal norms and to follow the generally accepted international legal procedures,” said Alexander Lukashevich, a Russian Foreign Ministry spokesman, adding that the recently announced investigation is “clearly another case of illegal exterritorial use of U.S. law.”", "\n\nThe charges are particularly sensitive for Moscow, which has found its moment in the World Cup spotlight tarnished by allegations of mismanagement, accusations of human rights abuses, and international calls for a boycott following the Ukraine crisis. ", "With national pride at stake, Russia is sparing no time in voicing its displeasure about the long arm of American justice.", "\n\nThe latest controversy comes after the United States announced corruption charges against 14 FIFA members, including seven who were arrested in a dawn raid in Zurich on Wednesday. ", "No Russians are among those detained on suspicion of paying bribes and kickbacks over the past two decades. ", "But allegations of corruption have swirled around the Kremlin’s courting of FIFA officials in the run-up to the 2018 World Cup vote, and authorities in Switzerland say they are investigating how that tournament and the 2022 World Cup in Qatar were awarded.", "\n\nDespite controversy over Russia hosting the World Cup, FIFA President Sepp Blatter has defended the decision. ", "Following the annexation of Crimea, Blatter told reporters at an April 2014 meeting with Russian President Vladimir Putin that “if a few politicians are not particularly happy that we are hosting the World Cup in Russia, then I always tell them: ‘Well then, stay at home.’”", "\n\nIn November 2014, Putin allegedly offered an original Picasso painting to Union of European Football Associations (UEFA) President Michel Platini, according to a report from Britain’s Sunday Times. ", "The allegations were made by England’s 2018 World Cup bid committee, which lost out to Russia. ", "The report goes on to detail that Putin, then the Russian prime minister, had allegedly tasked trusted oligarchs with the task of doing “deniable” deals to win over FIFA voters months before the secret ballot.", "\n\nAccording to the Sunday Times, the allegations were based on leaked documents from intelligence gathered by “a network of British embassies and private intelligence firms staffed by former MI6 officers” over two years. ", "The allegations were firmly denied by the Russian government and Platini.", "\n\nPhoto credit: PEDRO UGARTE/AFP/Getty Images" ]

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[ "Six reasons to become an urban beekeeper\n\nUrban beekeeping will help boost the UK's declining bee population. ", "Here are six reasons to get involved\n\nHealthy bees make a healthy planet\n\nBees play a crucial role in the Earth's ecosystem. ", "They are essential for biodiversity, as they have a symbiotic relationship with flowering plants, and they are an important part of the food chain. ", "They pollinate plants and trees, crops that we rely on as food sources, and the cotton we wear against our skins. ", "It's even thought that they contribute to reducing exhaust fumes in cities by filtering them out of the atmosphere.", "\n\nBee populations are on the decline\n\nColony Collapse Disorder has been causing mass bee deaths over recent years and it is a widely-discussed phenomenon today, however most people who are concerned about CCD and bee health feel helpless when it comes to reducing the plight of the bees.", "\n\nWhen asked why bees are dying prematurely and in vast numbers, experts point to a combination of the varroa mite and other viruses, however the root of the problem can be attributed to a variety of factors including the way bees are currently ‘farmed', and the use of pesticides and insecticides used in modern-day agricultural practices, which have inevitably entered the bee food chain..\n\nBees need a break from being farmed like cattle\n\nIn modern agricultural practices bees are treated like commodities in the same way that factory farm animals are used for maximum output using minimal resources and space. ", "In many countries today bees are fed sugar-water in place of their own nutrient-rich honey and confined to small, compact hives which are stacked on top of one another and designed to allow constant interference from their farmers. ", "These large-scale bee‘keepers' use bee colonies to pollinate vast quantities of the same crop in one sitting, for example a single almond plantation, then they package them up again to let loose on the next field. ", "Like cattle, their natural feeding habits and freedoms are restricted, and they succumb to health problems as a consequence of these unnatural practices.", "\n\nUrban beekeeping is necessary for strengthening bee populations\n\nThe primary aim of natural beekeeping is not to harvest the products bees create, such as honey and beeswax, but to help colonies to maintain optimum health by giving them a safe, non-invasive space to ‘bee'.", "\n\nOne of the best ways you can do this is by offering a small space in your garden to the bees. ", "Due to the vastly differing plants available within small spaces in urban areas, bees actually thrive in busy cities and towns. ", "According to Parisian bee artist Olivier Darne, in ‘an analysis of the honey we made here in Paris...it contained more than 250 different pollens. ", "In the countryside there can be as few as 15 or 20 pollens'.", "A backyard space in a city provides an ideal habitat for a bee colony. ", "Bees can travel large radiuses to access further nutritious plant nectar, and bees kept in urban areas are also less likely to encounter large amounts of pesticides and insecticides which are commonly used to treat crops en masse in countryside fields.", "\n\nBackyard beekeeping doesn't cost you anything\n\nIt can cost virtually nothing to provide a rich habitat for a colony of bees, but the value of this colony to our planet is immense. ", "Natural beekeeping does not require the use of the expensive equipment that is used to interfere with bee patterns, such as smoking them out to get to their honey, or donning protective suits to avoid attacks triggered by this honey ‘harvesting' (stealing). ", "The Top-Bar beehive is designed to minimise how much the bees are disturbed by the keeper, as it allows maximum visibility of bee life without forcing them to evacuate the hive in order to observe them. ", "With a Top-Bar hive you can get to know your bees and even closely study them without ever having to open the hive up completely. ", "You can make your own Top-Bar beehive for free using this guide, thanks to champion bee guardian Phil Chandler.", "\n\nBees have much to teach us\n\nChandler wrote The Barefoot Beekeeper as a guide to natural beekeeping without a protective suit. ", "He advocates learning the way of the bees by observing them and literally listening to them to work out their natural patterns, for example when they are most busy and should therefore be left alone, and when they might welcome a visit from the keeper.", "\n\nLeft to themselves, bees are harmless creatures, busy running the hive in their various allocated roles, working all day long, and serving and protecting the queen bee. ", "All they need from you is a safe base to come back to at the end of a working day, and in return for this you get to watch the fascinating way in which these insects work together. ", "The bee dance is simply amazing to witness first-hand.", "\n\nWhen you ‘keep' bees in this manner you come to realise that these humble, hardworking insects keep the natural order of things buzzing in a way that humans can only partially understand, but that we can certainly learn to appreciate more. ", "Have you ever used the phrase ‘the bee's knees' to describe something of high quality or excellence? ", "Such is the world of the bees. ", "When you become a backyard beekeeper, you open up a complex, beautiful facet of the natural world. ", "And you'll never want to look back." ]

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[ "Morphologic detection of blast cells in the cerebrospinal fluid at diagnosis of adult acute lymphoblastic leukemia appears to be associated with adverse prognosis.", "\nAppropriate treatment of central nervous system (CNS) involvement in adult acute lymphoblastic leukemia (ALL) is important for patient prognosis, but the diagnostic criteria of CNS involvement has not been established. ", "The significance of blast cells in the cerebrospinal fluid (CSF) at diagnosis was evaluated in 81 adults newly diagnosed with ALL. ", "Patients with unequivocal morphologic evidence of lymphoblasts in the cytocentrifuged CSF slide were considered to have CNS involvement regardless of the leukocyte count. ", "The outcomes of the patients were analyzed. ", "Four of the 81 patients (5%) had detectable blast cells, and three of these four patients had less than five leukocytes/μL of CSF. ", "One-year event-free survival (EFS) was 25.0% and 53.2% (P = 0.008) and overall survival (OS) was 50.0% and 68.8% (P = 0.001) in patients with and without CNS involvement, respectively. ", "CNS involvement had prognostic impact on EFS (P = 0.047) and OS (P = 0.009) after adjusting for sex, age, leukocyte count, Philadelphia chromosome status, and immunophenotype. ", "This study suggests that morphologic detection of blast cells in the CSF at diagnosis of adult ALL, regardless of the leukocyte count, is associated with adverse prognosis." ]

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[ "The Future of the World ‘Wired’ Mind?", "\n\nBy Pete MacKay\n\nI never thought neurophysiology could be made so interesting – or blended with philosophy for that matter – but this is what author Michael Chorost does in his book World Wide Mind. ", "Recently one of our Project Managers forwarded a link to an interesting PBS News Hour piece pondering “Will ‘Bionic Bodies’ Offer High-Tech Hope to the Disabled?”. ", "The clip covered the exoskeleton from Berkeley Bionics, coincidentally featuring John Fogelin, former CTO of Wind River and an original author of the VxWorks RTOS. ", "It also featured one of my personal heroes, Dean Kamen, as well as an interview with writer and cochlear implant recipient Chorost, who discussed his latest book, World Wide Mind.", "\n\nWind River Blog Network\n\nThe Wind River Blog Network is made up of a variety of voices: executives, technologists and industry enthusiasts. ", "We hope to foster conversations and encourage the sharing of insights regarding the evolving landscape of intelligent, connected systems with our ecosystem of customers, partners and colleagues." ]

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[ "After a failed coup in 2016, the Turkish government closed 169 newspapers, publishers, and TV and radio stations. ", "Thousands of reporters lost their jobs, or worse. ", "Currently Turkey has more journalists in jail than any other country in the world.", "\n\nThis is on top of recent terrorist attacks, millions of refugees entering the country, and a president who has been consolidating more and more power.", "\n\nBut one Istanbul radio station remains a beacon of free speech: Açık Radyo. ", "That’s “Open Radio” in English.", "\n\nI spent the fall in Istanbul, and I wanted to see what it was like to make radio in a country that shuts down media outlets.", "\n\nA lone voice\n\nAfter I take a ferry across the Bosphorus — that’s the waterway that divides Istanbul — I walk up the hill to the station. ", "It’s noon, and a music program called “Rambo Mozart” is playing from one of the two small recording studios.", "\n\nThere are years of old framed station schedules and posters all over the building, featuring the station’s frequency, 94.9.", "\n\nAs I walk into the kitchen, I find Utku Zırığ relaxing with a coffee.", "\n\nHis show Yeşil Bülten (Green Bulletin in English) just ended. ", "Today they were talking about the effect of a new coal power plant in northwestern Turkey.", "\n\nHe says most locals are opposed to the government project because of its environmental impacts.", "\n\nI ask if other places are talking about the issue.", "\n\nZırığ thinks. “", "No TV, no radio. ", "But three opposition newspapers. ", "That’s all.”", "\n\nThose three papers are some of the few remaining independent news sources that are fighting for survival in the country. ", "The rest are one-sided in favor of the government led by President Recep Erdoğan.", "\n\n“The government says: if you against a power plant project or mine project, you are terrorist,” Zırığ complains. “", "They always say this about every issue, about every project.”", "\n\nMedia restrictions aren’t new in Turkey. ", "For example, it has been illegal since 2005 to “insult Turkishness.” ", "That’s been used to silence people from talking about things like the Armenian Genocide.", "\n\nBut in recent years, the restrictions have gotten worse. ", "Much, much worse.", "\n\nBack in 2013, tens of thousands of demonstrators pushed back during the Gezi Park protests in Istanbul’s Taksim Square. ", "During that spring of demonstrations, Açık Radyo was one of the main sources of information.", "\n\nWhen other reporters were restricted at their home outlets, they could speak freely on the station. ", "Once the protests ended, the government continued to tighten restrictions. ", "After the failed coup in 2016, all but a few independent media sources were silenced.", "\n\nZırığ hosts his show here for an hour every Thursday as a volunteer, but he used to be a full-time journalist.", "\n\n“In TV I was doing four hours of live show daily,” he says proudly. “", "I liked it.”", "\n\nThat was on IMC TV, a station that had Turkey’s first transgender TV reporter. ", "It was shut down by the government in October 2016.", "\n\nSince then he’s been writing corporate PR; that’s what he says many journalists have had to do to make money. ", "Açık Radyo gives him a place to stay on top of issues, hoping that he’ll eventually be able to get back to work.", "\n\n“In these days in Turkey, Açık Radyo is like a island,” explains Zırığ. “", "Staying together makes us more strong. ", "That's why it's important.”", "\n\n\"Hey dad, why don't we start our own radio station?\"", "\n\nUpstairs is General Manager Ömer Madra. ", "His desk is filled with Turkish periodicals and pamphlets from the station. ", "Madra hosts their flagship current affairs show: Açık Gazte (Open Newspaper).", "\n\nThe program is “intergenerational, in between the lines, and intercontinental. ", "Always in between,” he says.", "\n\nFor the last 20 years, Madra spent two hours every weekday morning interviewing people about what’s going on in Turkish politics and around the world.", "\n\nThis morning, they talked about how the Turkish courts aren’t independent from the authoritarian government.", "\n\n“I talk about wars, you know genocides, and whatever,” he explains. “", "I throw all these things upon the listeners. ", "And there you are: let them solve it!” ", "He starts laughing. “", "You know, global warming!”", "\n\nMadra is always smiling, always telling stories. ", "And if you stick around long enough, he’ll likely end up roping you into hosting a show on-air.", "\n\nHe starts telling the story of how he started the station back in 1995. “", "It was totally accidental, as very many things in life are.”", "\n\nThis is Madra’s second career. ", "Before running a radio station, he had spent years as a professor researching international law and human rights. ", "But he grew disillusioned with restrictions on academic freedoms in Turkey.", "\n\nThe airwaves were opening up, though. ", "Before 1993, the government had a monopoly on all radio and TV, but then they let private groups start their own stations.", "\n\nIt was his son who came up with the idea. “", "My son said: ‘Hey dad why don't we found our own radio station?’ ", "And, being even crazier than he is I said: ‘OK, why not! ", "It will be a free independent radio station. ", "It would be progressive. ", "This is crazy.’”", "\n\nThere had never been a listener-supported station in Turkey before. ", "Like public radio stations in the United States, this one also holds regular fundraising drives. ", "Staff at the radio station say they’re still the only one in Turkey that does this.", "\n\n“Probably the highest priority goes to being independent,” says Madra. ", "Without financial independence, they wouldn’t have control over what went on air. ", "One of the ways the government has controlled or shut down other media outlets is by finding ways to limit their funding.", "\n\nFuture of Açık\n\nIn the United States, NPR stations have each other to get content and support from. ", "They’re part of a network.", "\n\nFor Açık Radyo — it’s just them.", "\n\nThere is a government-run national radio and TV network, similar to the BBC, but editor Ilksen Mavituna says they only support president Erdoğan’s government.", "\n\nHe calls it “propaganda.”", "\n\nMavituna has been at the station since 2005, and hosts their other main daily program: Açık Dergi (Open Magazine). ", "It’s two hours of arts and culture every weekday afternoon.", "\n\nI asked Mavituna if things had changed for the station over the past five years.", "\n\nHe hesitates, then says, “Looks the same to me.”", "\n\nHe says that many radio stations have been closed, but that Açık Radyo has largely escaped that fate — so far. (", "The station was temporarily closed down by the government for 15 days a decade ago because they read a Charles Bukowski poem on air.)", "\n\nWhen I mention Açık Radyo to people around town, everyone first says that they love the station, then they say they’re surprised it hasn’t been shut down yet.", "\n\nMativuna tries to brush off those fears. “", "We hear that very very often. ", "I don't get it— why people are just that pessimistic. ", "But they're right as well. ", "I don't know, maybe we're waiting our turn? ", "We'll see.”", "\n\nI ask him if he’s scared it might happen.", "\n\n“Of course,\" he says. \"", "As a person? ", "Yes. ", "But as a part of Açık Radyo? ", "No. ", "I'm not afraid. ", "Why should I be afraid? ", "They can stop the broadcast, but that doesn't mean the end of Açık Radyo. ", "We have books, we have big electronic archives, we have a memory shared with the listener.”", "\n\nBut then he talks about what it's like to live under the constant threat of being shut down.", "\n\n“Every month or every two months every one of us got into a depression,” he says. “", "You know, having nightmares. ", "But, this is normal in these times. ", "What should I say?”", "\n\nSome people I spoke with said that Açık Radyo might still be open because closing them would be more trouble than it’s worth. ", "That there might be a lot of international pressure if anything happened to them.", "\n\nBut their listenership is on the smaller side: only 40,000 daily listeners in a city of 15 million.", "\n\nWhen I ask Omer Madra about the station getting shut down, or the possibility of getting arrested, he quotes a Turkish folk saying:\n\n“Fear won't help you with the Grim Reaper.”", "\n\nBut he doesn’t really want to talk about the possibility. “", "That’s a nightmare. ", "Let’s forget about it. ", "We'll do our best; 22 years has passed,\" he says. \"", "We have made our mistakes, but we never change our ways and we never will.”", "\n\nMadra changes the topic and opens up a book written by a nine-year-old fan. “", "So the main hero of the story,” he explains, “is a radio station and they're struggling against a corrupt king ... And they win! ", "This is fantastic!”", "\n\nHe tells story after story, talking about the community of thousands of guests, programmers and friends who have come through the station since 1995.", "\n\nStaying enthusiastic, and staying defiant.", "\n\nThis story was originally published in February 2018." ]

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[ "(CNN) The family of a Jordanian fighter pilot mercilessly killed by ISIS is calling for total revenge.", "\n\nIn response, Jordan executed two prisoners -- Sajida al-Rishawi , a would-be suicide bomber whose release ISIS had previously demanded as part of a prisoner exchange, and Ziad Karbouli, a former top aide to the deceased leader of al Qaeda in Iraq, Abu Musab al-Zarqawi.", "\n\nThe pilot's father is demanding his country do more.", "\n\n\"These were criminals and there is no comparison between them and Moath. ", "His blood is more valued than Sajida al-Rishawi and Ziad Karbouli,\" said al-Kasasbeh's father, Safi. \"", "I demand that revenge should be bigger than executing prisoners.\"", "\n\nHis son's horrific death was recorded and the video was posted online Tuesday.", "\n\nCNN is not showing the images, which drew global condemnation and prompted protests and vows of retaliation in Jordan.", "\n\nKing Abdullah has promised a strong response, saying that ISIS isn't just fighting his nation, but warring against \"noble Islam\" itself.", "\n\nJUST WATCHED Pilot's uncle: Want whatever it takes to destroy ISIS Replay More Videos ... MUST WATCH Pilot's uncle: Want whatever it takes to destroy ISIS 03:28\n\nThe country now wants to step up airstrikes against the terrorist organization, according to a source with direct knowledge of the situation.", "\n\nBut the pilot's uncle, Yassin Al Rawashdeh, told CNN that he also wants to see ground troops involved in the U.S.-led coalition against ISIS in Iraq and Syria.", "\n\nSaid the pilot's father: \"I demand that this criminal organization (ISIS) ... should be annihilated.\"", "\n\n'An earthshaking retaliation'\n\nDemonstrators took to the streets in Amman and the pilot's hometown immediately after the video was made public.", "\n\nOne protester held a poster that read: \"They burned our hearts, so let's burn their dens, and their prisoners in our prisons.\"", "\n\nJUST WATCHED Outraged Jordan vows 'relentless war' on ISIS Replay More Videos ... MUST WATCH Outraged Jordan vows 'relentless war' on ISIS 02:24\n\nJordanian government spokesman Mohammad al-Momani has vowed \"an earthshaking retaliation\" and \"a revenge that equals the tragedy that has befallen the Jordanians.\"", "\n\nExactly what that response will look like remains to be seen, although the outlines of it are starting to take shape.", "\n\nJordan's military is seeking to conduct more of the anti-ISIS airstrikes assigned by the coalition, a U.S. official told CNN. ", "According to that official, the number of strikes Jordan can carry out will depend on the location of the targets, weather and other factors.", "\n\nKilling on big screens?", "\n\nISIS apparently made a big show of the pilot's brutal execution in Raqqa, its stronghold in Syria.", "\n\nAn activist network, \"Raqqa Is Being Slaughtered Silently,\" reported that the killing was being shown, repeatedly, on large screens across the city.", "\n\nOne of ISIS' propaganda production outlets posted a video online that appears to show a crowd cheering as flames around the pilot grow.", "\n\nJUST WATCHED Expert: Video most gruesome, disturbing I've ever seen Replay More Videos ... MUST WATCH Expert: Video most gruesome, disturbing I've ever seen 03:59\n\nThe video features a tight shot of a boy, looking up as if in awe and saying that he would \"burn the pilot\" himself if he had a chance and that \"all Arab tyrants should also be burned.\" ", "The boy can also be heard saying \"Obama the dog.\"", "\n\nBecause the video is carefully orchestrated propaganda, CNN has no way to know if people in Raqqa really feel this way, if other children were present or whether the video participants' responses were authentic or a result of intimidation.", "\n\nThere are anti-ISIS activists inside Raqqa who operate very quietly. ", "One of them, with \"Raqqa Is Being Slaughtered Silently,\" told CNN on Tuesday that on January 8, he was standing in the street when several ISIS fighters approached, bragging that they had set the pilot on fire.", "\n\nPhotos: Jordanian pilot killed by ISIS Photos: Jordanian pilot killed by ISIS Jordanian Queen Rania, center, holds a placard during a demonstration in Amman, Jordan, on Friday, February 6, after the death of pilot Moath al-Kasasbeh by ISIS. ", "Al-Kasasbeh was burned alive in a video recently released by ISIS militants. ", "Hide Caption 1 of 14 Photos: Jordanian pilot killed by ISIS Jordan's King Abdullah II, center, greets a relative of al-Kasasbeh's while paying his condolences on Thursday, February 5. ", "Hide Caption 2 of 14 Photos: Jordanian pilot killed by ISIS People in Amman pray for al-Kasasbeh on Wednesday, February 4. ", "Hide Caption 3 of 14 Photos: Jordanian pilot killed by ISIS Muslims pray in the streets of Amman on February 4. ", "Hide Caption 4 of 14 Photos: Jordanian pilot killed by ISIS Jordanian Christians in Amman pray during a Mass held for al-Kasasbeh on February 4. ", "Hide Caption 5 of 14 Photos: Jordanian pilot killed by ISIS Jordanians gather in Amman on Tuesday, February 3, after reports that al-Kasasbeh had been killed. ", "Hide Caption 6 of 14 Photos: Jordanian pilot killed by ISIS Supporters and family members of al-Kasasbeh gather in Amman after reports of his death on February 3. ", "Hide Caption 7 of 14 Photos: Jordanian pilot killed by ISIS Supporters and family members say prayers on February 3. ", "Hide Caption 8 of 14 Photos: Jordanian pilot killed by ISIS U.S. Secretary of State John Kerry, left, meets with Jordan's King Abdullah II, center, and Crown Prince Hussein on February 3 in Washington. ", "Kerry described al-Kasasbeh as everything he says ISIS is not: \"He was brave, compassionate and principled. ", "That he was murdered after his father's plea for compassion reminds all the world that this foe has no agenda other than to kill and destroy and places no value on life, including that of fellow Muslims.\" ", "Hide Caption 9 of 14 Photos: Jordanian pilot killed by ISIS Japanese Vice Foreign Minister Yasuhide Nakayama, left, shakes hands with a Jordanian lawmaker visiting the Japanese Embassy in Amman on February 2. ", "Two Japanese hostages, Haruna Yukawa and Kenji Goto, were also recently killed by ISIS. ", "Hide Caption 10 of 14 Photos: Jordanian pilot killed by ISIS Jordanian youth gather for a candlelight vigil February 2 in Amman to condemn the killing of the two Japanese hostages. ", "Hide Caption 11 of 14 Photos: Jordanian pilot killed by ISIS A banner with a picture of al-Kasasbeh is raised by workers near a tent in Amman on Friday, January 30. ", "Hide Caption 12 of 14 Photos: Jordanian pilot killed by ISIS Angry relatives of al-Kasasbeh protest at the entrance to Jordan's royal palace in Amman on Wednesday, January 28. ", "Hide Caption 13 of 14 Photos: Jordanian pilot killed by ISIS A man comforts al-Kasasbeh's wife during the protest in front of the royal palace on January 28. ", "Hide Caption 14 of 14\n\nOther ISIS members acted impressed but dubious, and a disturbingly juvenile moment ensued in which the ISIS fighters making the claim said that it was true, they were there and saw it.", "\n\nJordan last week said it was willing to release al-Rishawi, the would-be suicide bomber, in exchange for al-Kasasbeh, but the swap never happened. ", "The Jordanian government repeatedly asked ISIS to show proof that the pilot was still alive.", "\n\nShortly after the video of al-Kasasbeh's killing became public, Jordanian military spokesman Mamdouh Al Amri said that authorities believe the pilot had been killed as far back as January 3, before ISIS began making its public demands for the release of al-Rishawi.", "\n\nPilot 'gave his life defending his faith'\n\nKing Abdullah arrived back in Jordan on Wednesday after cutting short a visit to the United States, where he met with President Barack Obama.", "\n\n\"The brave pilot gave his life defending his faith, country and nation and joined other Jordanian martyrs who gave their lives for Jordan,\" Abdullah said in a televised statement Tuesday, describing ISIS as a cowardly and deviant group that has nothing to do with Islam.", "\n\nAl-Kasasbeh was captured by ISIS in December after his fighter jet crashed near Raqqa.", "\n\nJUST WATCHED Is the U.S.-led coalition winning against ISIS? ", "Replay More Videos ... MUST WATCH Is the U.S.-led coalition winning against ISIS? ", "02:12\n\nThe pilot was one of eight children, according to the Jordan Times. ", "He was from Karak governorate and graduated from King Hussein Air College, the newspaper said.", "\n\nAt the time of his capture, his father told the paper that his son was \"a very modest and religious person\" who memorized the Quran and \"was never harmful to anyone.\"", "\n\nU.S. Secretary of State John Kerry described al-Kasasbeh as everything ISIS is not: \"He was brave, compassionate and principled.\"", "\n\n\"That he was murdered after his father's plea for compassion reminds all the world that this foe has no agenda other than to kill and destroy, and places no value on life, including that of fellow Muslims,\" Kerry said.", "\n\nISIS is known to be holding at least two Western hostages still: John Cantlie, a British journalist who has appeared in a number of ISIS-produced videos, and an American woman who is a 26-year-old aid worker." ]

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[ "Q:\n\nCasting/Mapping Delegates\n\nI have a method\n public List<DTO.User> GetUsers(Func<Domain.", "User, bool> expression)\n {\n var users = new List<DTO.User>();\n\n using(UserContext context = new UserContext())\n {\n // obviously an error\n users = context.", "Users.", "ToList();\n }\n\n return users;\n\n }\n\nNotice the DTO.User (a DTO) and Domain.", "User (a domain entity from EF)\nSo I use AutoMapper to map entities like this\n public List<DTO.User> GetUsers()\n {\n var users = new List<DTO.User>();\n\n using(UserContext context = new UserContext())\n {\n\n Mapper.", "CreateMap<Domain.", "User, DTO.User>();\n users = \n Mapper.", "Map<List<Domain.", "User>,List<DTO.User>>(context.", "Users.", "ToList());\n }\n\n return users;\n\n }\n\nAlright, this looks OK but.. I want the GetUser method to accept a delegate expression as a parameter. ", "I have a grid in the ui that displays the user list and it has many filtering options, so I want my UI to just call 1 method instead of creating method per filter.", "\n // filter by username\n List<DTO.User> users = userBL.GetUsers(u => u.UserName.", "Contains(txtUserName.", "Text));\n\n // filter by ID\n List<DTO.User> users = userBL.GetUsers(u => u.== txtUserID.Text);\n\n ...\n\nSo I came up with the Idea like this in my DAL layer\n public List<DTO.User> GetUsers(Func<DTO.User, bool> expression)\n {\n var users = new List<DTO.User>();\n\n using(UserContext context = new UserContext())\n {\n Mapper.", "CreateMap<Domain.", "User, DTO.User>();\n\n Func<Domain.", "User, bool> predicate;\n\n // this is an error on AutoMaper\n predicate = Mapper.", "Map<Func<DTO.User,bool>, Func<Domain.", "User, bool>>(expression)\n\n // I also tried direct casting which is an obvious fail\n //predicate = (Func<Domain.", "User,bool>)expression;\n\n users = \n Mapper.", "Map<Domain.", "User, DTO.User>(context.", "Users.", "Where(predicate).ToList());\n }\n\n return users;\n\n }\n\nSo basically, I'm trying to cast or map the DTO delegate to Domain delaget for it to be use in the .Where() method of the domain.", "User list. ", "Is it possible? ", "thanks in advance.", "\n\nA:\n\nI'm almost sure that you cannot map delegate to another delegate but your code has even more problems:\n\nIf you pass Func<User, bool> to your Linq-to-entities query you will do the same as you do now. ", "It will pull all data from the database and execute filter in your application server's memory. ", "You must pass Expression<Func<User, bool>> to execute it on DB server.", "\nI don't know whole your architecture and complexity of the application but I feel that placing conversion to DTOs directly in DAL is not good. ", "I can imagine doing this only in EFv1 when using EntityObjects.", "\n\n" ]

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[ "Nadine Dorries: Go Compare\n\nThis entry was posted on\n\nMonday, February 7th, 2011 at\n\n2:47 pm and is filed\n\nunder Tories! ", "Tories! ", "Tories!.", "\n\n[NOTE – Because I’m not a plagiarising prick like Paul Staines or Ian Hislop and I don’t take credit for other people’s work, I must begin with a BIG ‘thank you’ to Iain Marley for his excellent Excel work on the current expenses, and to Unity for digging out the Marketing Management (Midlands) Ltd data from archived expenses. ", "Both of them are proper gents.]", "\n\nYou’ve got to hand it to Chris Gill, editor of Bedfordshire on Sunday; he made a pretty good show of holding Nadine Dorries to account with this little article, but it’s an underarm throw at best, and easily batted away.", "\n\nThis article also declares that Dorries was “cleared of any wrongdoing” but does not mention that this was after a Parliamentary investigation in which Dorries could only explain herself by saying that she had lied to her constituents about where she lived most of the time. ", "The article also manages to completely avoid any mention of the subsequent police investigation or the fact that this matter has since been passed on to the CPS.", "\n\nDo you know what this reminds me of? ", "This reminds me of the Downing Street memos that revealed Murdoch’s flunkies and Blair’s flunkies had been coordinating objections from The Sun and the government response and the subsequent tabloid response ahead of time, so as to better maintain the illusion that this tabloid was acting in the interests of their readers, and not operating as The Downing Street Echo.", "\n\nYes, it is absurd to compare Dorries to the Prime Minister. ", "So I’m going to do what Chris Gill didn’t do, and look a little closer at the data, then compare Dorries to every MP, just to show him how it’s done. (", "Assuming, of course, he wants this job done right at all.)", "\n\nFirst of all, if you take the expenses for all MPs and apply a total to each MP, you are mere moments away from a league table of the most expensive MPs:\n\nMPs with greatest total expenses claims (May 2010 – October 2010): Simon Hart (Con.) – ", "£35,256.26\n\nNadhim Zahawi (Con.) – ", "£31,902\n\nNadine Dorries (Con.) – ", "£31,673.17\n\nKeith Simpson (Con.) – ", "£29,916.44\n\nJane Ellison (Con.) – ", "£28,752.82 (Source: Parliament’s searchable archive of MPs’ expenses from 2010 onwards.)", "\n\n[Psst! ", "Please do note that the five most expensive MPs are all Conservatives. ", "It is the Conservatives who are only in power because of a coalition agreement, but pretend to have a popular mandate as they impose their ideology on us under the guise of austerity measures. ", "This is yet another indication – as if you need one – that the whole thing is a Tory con.]", "\n\nNadine Dorries isn’t just more expensive than the Prime Minister or a couple of local MPs, she’s more expensive than almost every MP in the House. ", "Gosh, I wonder how Chris Gill and his staff at Bedfordshire on Sunday missed that one. ", "I assume simple addition isn’t beyond them, but just in case numbers do cause confusion in his office, here is a graph comparing the recently-published expenses claims of all MPs, with Dorries highlighted:\n\nMoving on to another matter that received no mention in Bedfordshire on Sunday; let’s look again at the very strong indications that Nadine Dorries has continued paying her close friend and neighbour Lynn Elson out of the public purse.", "\n\nThe following is a collation of all known payments since 2008* from Nadine Dorries to ‘Marketing Management’ (full name; Marketing Management Midlands Ltd), a company owned and operated by Nadine’s good friend, close neighbour and drinking buddy, Lynn Elson. ", "Under that data, you will see the claims that I recently contended were very likely to have been made to Marketing Management Midlands Ltd (the amounts in bold):\n\nNadine Dorries – Confirmed Payments to Marketing Management (Midlands) Ltd Pty Yr —- Date ———— Allowance Type ———- Expenditure Type —– Amount 08/09 ___ 30/09/08 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,290.00\n\n08/09 ___ 30/09/08 _____ Comms Expenditure _ ____ General Costs _______ £6,554.75\n\n08/09 ___ 01/11/08 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,525.00\n\n08/09 ___ 01/12/08 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00\n\n08/09 ___ 06/02/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00\n\n08/09 ___ 04/03/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00 09/10 ___ 06/11/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00\n\n09/10 ___ 11/06/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00\n\n09/10 ___ 21/07/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00\n\n09/10 ___ 06/10/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£4,025.00\n\n09/10 ___ 06/10/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00\n\n09/10 ___ 16/12/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00\n\n09/10 ___ 21/12/09 _____ Staffing non-payroll ______ Agencies etc. _______ ", "£3,450.00 Nadine Dorries – Suspected Payments to Marketing Management (Midlands) Ltd Pty Yr —- Date ——- Expense Category —– Expense Type —– Amount 10/11 ___ 11/05/10 ___ Staffing __________ Professional Services (Staff) ___ £3,525.00\n\n10/11 ___ 11/06/10 ___ Staffing __________ Professional Services (Staff) ___ £3,525.00\n\n10/11 ___ 31/08/10 ___ Staffing __________ Professional Services (Staff) ___ £3,525.00\n\n10/11 ___ 15/09/10 ___ Staffing __________ Professional Services (Staff) ___ £3,525.00\n\n10/11 ___ 14/10/10 ___ Staffing __________ Professional Services (Staff) ___ £3,525.00 (Source: Parliament’s searchable archive of MPs’ expenses from 2008-2010.) [", "NOTE – There was also a payment of £9987.50 (£8500 + VAT) in 2007 which prompted a complaint from a former researcher.]", "\n\n1. ", "Note the very similar amounts (one an exact match) with very similar classifications.", "\n\n2. ", "The pre-2010 payments to Marketing Management were labelled for ‘PR, media and research’, ‘public relations, media and research’, ‘media and research retainers fee’, ‘research and secretarial service’ and/or ‘media and research’. ", "Two out of the five payments from 2010 onwards (in bold) were labelled ‘media and research’.", "\n\n3. ", "The remaining three of these five recent (identical) amounts (in bold) were simply labelled ‘MM‘ under their Short Description, presumably by the submitter of the claim (Dorries or her staff) if not the IPSA team. ", "Dorries is the only MP with entries using this label as a part of any description. ", "I suspect MM is short for ‘Marketing Management’.", "\n\n4. ", "Dorries has yet to deny these payments were made to Marketing Management (Midlands) Ltd, and her past conduct has shown that she or one of her little gang of thugs will issue a shrill if not overly hostile denial if there is even the smallest opportunity to highlight and capitalise on the slightest inaccuracy or discrepancy. ", "However, the only objection raised so far (courtesy of Phil Hendren of ‘Dizzy Thinks’, another close friend and neighbour of Dorries’) has been this; “Why have you put a [Bloggerheads] imprint on an image that is a screenshot from Crown copyright content?”", "\n\nExcuse me while I gloss over that crime of the century and carry on looking at these expense claims…\n\nThere is good reason to suspect that all of these recently-revealed payments were made to Marketing Management (Midlands) Ltd., which is owned and operated by Lynn Elson. ", "Has Dorries simply continued paying her close friend out of the taxpayer’s pocket while quietly redefining/relabeling her role?", "\n\nLynn Elson has a background in media sales and marketing, NOT in research. ", "Though she may have some undeclared expertise in marketing research, this is not the same as political research, not by a long shot. ", "Political research is a role in which Lynn Elson has no little-to-no documented experience, never mind the kind of expertise that would justify monthly retainers of this scale.", "\n\nIf the money was spent with Lynn Elson and/or her company, what services were provided in exchange for this money? ", "This question is especially pertinent when you consider that Lynn Elson’s proclaimed area of expertise is PR (Public Relations), as Dorries has suffered a series of public relations disasters since the election, and Lynn Elson has been instrumental in dealing with the fallout in ways that cannot be denied.", "\n\nIf we are to give Nadine Dorries the benefit of the doubt and assume that near to all of this money went on research along with whatever definition she applies to ‘media’, it still doesn’t look too clever.", "\n\nTake a look at the five MPs who claimed the most for media-related expenses (e.g. ads in the local paper, websites, etc.) ", "and research combined:\n\nMPs with highest expenses claims relating to media and/or research (May 2010 – October 2010): Nadine Dorries (Con.) ", "£20,033.75\n\nNick de Bois (Con.) ", "£9,332.98\n\nRory Stewart (Con.) ", "£9,126.97\n\nKeith Simpson (Con.) ", "£8,488.10\n\nTherese Coffey (Con.) ", "£7,764.50 (Source: Parliament’s searchable archive of MPs’ expenses from 2010 onwards.)", "\n\n[Psst! ", "All Tories at the top of the table. ", "Again.]", "\n\nEven this is being far too generous to Dorries, as most of the MPs who came within shouting distance of her under this comparison did so because of payment of an annual subscription to ‘PRU’ (the grandly-titled Parliamentary Resources Unit) that really should be halved if we’re to provide a fair comparison.", "\n\nTake a look at that margin, even without this adjustment; Dorries is ahead by a remarkable amount, even when she is treated with great generosity in this selection/interpretation of the figures.", "\n\nAnd it’s actually quite likely to be far, far worse than this looks; this comparison was made in this way because Dorries classified part if not all of these expenses as relating to ‘Research and media services’, but I doubt very much if any of this money was spent on research, and if it was, I sincerely doubt the taxpayer got value for money.", "\n\nI would think the extraordinary level of expenditure alone warrants some added scrutiny by the media if not the authorities, even if the most likely recipient fails to set off alarm bells left, right and centre.", "\n\nWhat was this money spent on? ", "What does Dorries have to show for it? ", "Even if it was spent more on research than media/marketing/PR, how does Dorries justify this extraordinary level of expense that is double that of any colleague coming anywhere near this level of expenditure? ", "What was this ‘research’ for? ", "Hopefully not something to do with her ongoing religious mission to reduce access to abortion.", "\n\nOh, and why isn’t the editor of Bedfordshire on Sunday asking these questions and/or reporting the matter of her previous expenses claims that has not only been forwarded to the police for investigation, but subsequently passed on to the CPS?", "\n\nChris Gill, the editor of Bedfordshire on Sunday, is either soft in the head or soft on Dorries. ", "Bedfordshire is being let down by their MP, and the man who is supposed to keep her honest hold her to account.", "\n\nThank you for your kind attention, and for sitting quietly through all of this data. ", "Here is your reward:\n\nCheers all.", "\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n" ]

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[ "Q:\n\nHow do I ask a question outside of meta?", "\n\nI am new and I don't see the button, I can only ask meta questions.", "\n\nA:\n\nThat's because you are on the meta site.", "\nTo ask a question on any other site just go there and ask.", "\nHere is a list of all sites:\nhttp://stackexchange.com/sites#name\n\n" ]

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[ "Endoscopic sedation and monitoring practice in Germany: results from the first nationwide survey.", "\nThe use of sedation (e. g., of short-acting propofol) for gastrointestinal endoscopy has shown an upward trend in the United States and Europe over the last decade. ", "This survey aimed at providing nationwide data on the current practice of endoscopic sedation and monitoring in Germany. ", "A 21-item survey regarding current practices of endoscopy, sedation and monitoring in gastrointestinal endoscopy was sent to 3 802 members of the German Society of Digestive and Metabolic Diseases (DGVS). ", "A total of 1 061 / 3 802 (28%) questionnaires were returned. ", "The respondents performed an average of 28 esophagogastro-duodenoscopies (EGDs) and 25 colonoscopies per week. ", "Endoscopic procedures were staged in a hospital setting (60%) more often than in private practices (40%). ", "The majority of the EGDs (74%) and colonoscopies (87%) were carried out under sedation, however, this fact may be influenced by a recall bias. ", "The most frequently used agents for sedation were midazolam in 82% and propofol in 74% of the cases. ", "The most common sedation regimens applied were propofol plus benzodiazepines (38%) and benzodiazepines with an opioid (35%). ", "Patients were routinely monitored by pulse oximetry (97%), automated blood pressure readings (29%) and/or electrocardiography (13%). ", "Supplemental oxygen was routinely administered in 34% of them. ", "Endoscopists' satisfaction with sedation was greater among those using propofol than in the group applying benzodiazepines (visual analogue scale, 8.8 +/- 0.9 vs. 8.2 +/- 1.3, p < 0.0001). ", "Besides the common administration of short-acting benzodiazepines, sedation with propofol is also gaining ground in Germany; it is applied mainly in low doses (up to 150 mg). ", "German endoscopists are highly satisfied with these sedation regimens, with propofol significantly leading the score. ", "Patient monitoring predominantly follows currently prevailing guidelines." ]

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[ "based on Lowry methodologies.", "\npanicSELL = more than 90% total points losses for all stocks closing lower on the day & more than 90% total volume for all stocks closing lower on the day.", "\neod agst 21, panicSell GSPC\nAttached Thumbnails" ]

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[ "WLQB\n\nWLQB (93.5 FM, \"El Patron 93.5\") is a radio station broadcasting a Regional Mexican format. ", "Licensed to Ocean Isle Beach, North Carolina, United States, the station is owned by iHeartMedia, Inc., through licensee AMFM Radio Licenses, L.L.C. Its studios are located on the U.S. 17 Bypass in Myrtle Beach, and its transmitter is in Shallotte, North Carolina.", "\n\nHistory\nThe call letters WDZD were formerly used by WLTT (now WILT) when that station was at 93.5 FM.", "\n\nIn January 1999, \"hyperactive rock\" radio station \"93.5 Asylum\" signed on in Myrtle Beach, South Carolina. ", "Darren Taylor, assistant program director and afternoon DJ, said that in addition to Metallica, Black Sabbath, Judas Priest and Iron Maiden, the station would play bands that did not get a lot of radio airplay, such as Static X, Rage Against the Machine, Godsmack, and Kid Rock. ", "Other artists on WDZD included Rob Zombie, Collective Soul, Lenny Kravitz, Hole, The Black Crowes, silverchair, Korn, Marilyn Manson, Stone Temple Pilots, Soundgarden, Beastie Boys, Smashing Pumpkins, AC/DC, Nirvana, Pearl Jam, Creed, Faith No More, Placebo, The Offspring, and Jonny Lang. ", "DJs who joined the station on February 8 were Freaky Chick, Art, Monkey Boy from WWSK, and Pork Chop of KUFO in Portland, Oregon. ", "Booger of WWXM was music director. ", "Scrap Jackson, operations manager for Root Communications in Myrtle Beach, said the target audience was males in their 20s, and \"93-5 is truly an alternative station as Webster defined it.\"", "\n\nBecause the signal could not be heard throughout the Myrtle Beach market (though Wilmington listeners could hear it), this station did not perform well. ", "WDZD was changed to Memories from ABC Radio Networks, a soft oldies satellite format, in 2000, and the name became \"Lite 2000\".", "\n\nSeveral years later, WDZD began airing the country music heard on WGTR, but the stations went their separate ways in 2005. ", "WDZD became \"La Que Buena 93.5, La Estación De Las Estrellas\", with a Regional Mexican format and the call sign WLQB.", "\n\nIn 2013, WLQB became adult contemporary B93.5, with \"Ocean Isle and Calabash's Best of the '80s, '90s, and Today!\"", "\n\nOn May 15, 2014, Qantum Communications announced that it would sell its 29 stations, including WLQB, to Clear Channel Communications (now iHeartMedia), in a transaction connected to Clear Channel's sale of WALK AM-FM in Patchogue, New York to Connoisseur Media via Qantum. ", "The transaction was consummated on September 9, 2014.", "\n\nOn May 5, 2017, WLQB returned to Regional Mexican as \"El Patron\". ", "On February 28, 2019, the station changed the call sign to WLLZ. ", "One week later, the call letters were swapped with WDTW-FM in Detroit. ", "That station had changed formats on March 1st to one that used \"WLLZ\" in its branding (WLLZ was a set of heritage calls in the Detroit market which iHeartMedia was able to reserve and claim in order to facilitate the format switch). ", "On March 15, 2019, the call sign was changed back to WLQB.", "\n\nReferences\n\nExternal links\n\nLQB\nCategory:IHeartMedia radio stations\nCategory:Radio stations established in 1999\nCategory:1999 establishments in North Carolina\nCategory:Regional Mexican radio stations in the United States\nCategory:Spanish-language radio stations in North Carolina" ]

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[ "\"\"\"\nAuthors: Wouter Van Gansbeke, Simon Vandenhende\nLicensed under the CC BY-NC 4.0 license (https://creativecommons.org/licenses/by-nc/4.0/)\n\"\"\"\nimport torch\nimport numpy as np\nimport collections\nfrom torch._six import string_classes, int_classes\n\n\n\"\"\" Custom collate function \"\"\"\ndef collate_custom(batch):\n if isinstance(batch[0], np.int64):\n return np.stack(batch, 0)\n\n if isinstance(batch[0], torch.", "Tensor):\n return torch.stack(batch, 0)\n\n elif isinstance(batch[0], np.ndarray):\n return np.stack(batch, 0)\n\n elif isinstance(batch[0], int_classes):\n return torch.", "LongTensor(batch)\n\n elif isinstance(batch[0], float):\n return torch.", "FloatTensor(batch)\n\n elif isinstance(batch[0], string_classes):\n return batch\n\n elif isinstance(batch[0], collections.", "Mapping):\n batch_modified = {key: collate_custom([d[key] for d in batch]) for key in batch[0] if key.find('idx') < 0}\n return batch_modified\n\n elif isinstance(batch[0], collections.", "Sequence):\n transposed = zip(*batch)\n return [collate_custom(samples) for samples in transposed]\n\n raise TypeError(('Type is {}'.format(type(batch[0]))))\n" ]

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[ "[Image via Himasoku\n\nKotaku East East is your slice of Asian internet culture, bringing you the latest talking points from Japan, Korea, China and beyond. ", "Tune in every morning from 4am to 8am. ", "Prev Next View All\n\nNow, Hideaki Anno of Evangelion is rich and famous. ", "But he wasn’t always that way. ", "He’s paid his dues in full, even when he was barely getting paid at all.", "\n\n\n\n\nWay back in December 1984, Japanese manga Comic Box Jr. (via Himasoku) published a piece in which Anno went through, month by month, what he had experienced that year.", "\n\n1984 would prove a turning point for the young Anno. ", "Nausicaä, for which he animated a key scene, was released, and that December he established Gainax.", "\n\n\nIn this panel comic, Anno described what happened and also listed how much money he made each month. ", "It’s eye-opening if you are unfamiliar with how crap anime pay is. ", "But if you are already aware of that, then this will seem somewhat normal. ", "Sadly.", "\n\n(Note: The average total monthly salary of a full-time worker in Japan in the mid-1980s was around 317,000 yen. ", "Use that number to compare Anno’s monthly pay.)", "\n\nJanuary to March\n\n[Image via Himasoku\n\n\nJanuary (1月)\n\nBecause of NXXXXcaä*, sleeping at the studio with the cockroaches. ", "Didn’t have a place I could go home to anyway. ", "SALARY: 150,000 yen\n\n*Anno humorously censored the movie’s title.", "\n\nFebruary (2月)\n\nThe final spurt continues. ", "No socks, because washing them is a pain in the ass. ", "Snow continues for days, and I go get deep-fried tofu. ", "SALARY: 150,000 yen\n\nMarch (3月)\n\nThe prime of my life. ", "With my NXXsiXXX salary, got a three-piece suit. ", "Also got a girlfriend. ", "Yay! ", "SALARY: 200,000 yen\n\nApril to June\n\n[Image via Himasoku\n\n\nApril (4月)\n\nIllness got worse, and I recuperate at a friend’s house. ", "Broke up with my girlfriend, and since I’m not working, I fervently read Dazai. ", "I’m lonely... SALARY: None\n\nMay (5月)\n\nBecause of MaXXXss*, staying overnight at Anime FXXXnd**. ", "This period continues like before. ", "Gruelling. ", "SALARY: 300,000 yen\n\n*Here, apparently, Macross. **", "Seems to be the studio Anime Friend.", "\n\nJune (6月)\n\nMacXXXX keeps on going. ", "When it finishes, I’ll do part-time or whatnot. ", "It’s exceedingly hot. ", "SALARY: 150,000 yen\n\nJuly to August\n\n[Image via Himasoku\n\n\nJuly (7月)\n\nGot a color TV and been going to play pachinko. ", "But, getting that money back is impossible, and seeing the light, I give up. ", "It’s futile... SALARY: Minus\n\nAugust (8月)\n\nBack in home the first time in a while (my hometown, though, is Ube in Yamaguchi). ", "Partying, days fly by. ", "But then, when I get back to Tokyo, I’m behind in my schedule and unable to work. ", "SALARY: Nothing\n\nSeptember (9月)\n\nNow, I’m spending my days having fun. ", "For a friend’s wedding, I head back to Osaka by bike. ", "It should’ve cost only 4,000 yen, but I got nabbed by a motorcycle cop and it ended up being more expensive than going by train. (", "I got the bike from from Mr. M.)\n\n\nSALARY: 10,000 yen\n\nOctober to December\n\n[Image via Himasoku\n\n\nOctober (10月)\n\nGot paid for part-time gig I begged Mr. K for, and I think I’ll go get a part-time job painting Mr. M’s villa in Nagano. ", "I’m happy food money materialized! ", "SALARY: 80,000 yen\n\nNovember (11月)*\n\nNow, living with two friends in a six-tatami mat studio we’re making. ", "I want my own room asap!!", "\n\n\n*No salary listed.", "\n\nDecember (12月)*\n\nAmid this plight, I guess the new year will come... I’m anxious. ", "But without thinking, hohoo!", "\n\n\n*No salary listed.", "\n\nThat December, the studio Anno co-founded was Gainax, which would go on to create Evangelion. ", "The rest is anime history." ]

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[ "https://www.zippi.co.uk/watercolour-flamingo-print200009Watercolour Flamingo Printhttp://dh4pzatwjvlc6.cloudfront.net/resize-product/490/5ma/print_portrait/chewartwork/Watercolour-Flamingo-11723/portrait_web_0nly.jpg11.75GBPInStock/Portfolio/chewartwork/Watercolour Flamingo/Find Art/Prints'Watercolour Flamingo' is a fantastically vibraint design by our popular animal artist chewartwork. ", "This design has been taken from the artists original watercolour painting and finished off with a lick of pencil and coloured chalk markers. ", "This pink flamingo would look fantastic on any Zippi product and is very on trend! ", "Prints£9.99chewartworkprint_portrait\n\nJavaScript seems to be disabled in your browser. ", "You must have JavaScript enabled in your browser to utilize the functionality of this website.", "\n\nEuropean & Rest of the World Delivery(No signature required but fully trackable)\n\n5 - 7 working days\n\n£9.99\n\nAbout the Design & Artist\n\nI've been drawing all my life and I love it! ", "I specialise in animal art and pet portraits. ", "Fave materials are chalk markers and watercolours. ", "I sell my original works www.etsy.com/shop/chewARTWORK\n\n'Watercolour Flamingo' is a fantastically vibraint design by our popular animal artist chewartwork. ", "This design has been taken from the artists original watercolour painting and finished off with a lick of pencil and coloured chalk markers. ", "This pink flamingo would look fantastic on any Zippi product and is very on trend!", "\n\nArt designs look simply stunning on our premium quality prints. ", "We use high definition printing to capture the vivid colours and to ensure none of the detail is lost. ", "Our prints are available to buy in landscape or portrait, and you can choose between a gloss or matt finish too.", "\n\nNeed help with your order?", "\n\nEmail us\n\nOur website uses cookies to improve your user experience. ", "If you continue browsing, we assume that you consent to our use of cookies. ", "More information can be found in our Cookies Policy which is in our Privacy Policy" ]

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[ "The landscape of American film has changed considerably in the 30 years since Joel and Ethan Coen announced themselves with their blackly comic neo-noir debut Blood Simple.", "\n\nOnce dismissively bracketed as ‘arthouse’, the Coens are among a handful of gifted filmmakers to have transformed the cinematic panorama without compromising their unique sensibility; to the extent their bleakly violent 2007 masterpiece No Country For Old Men won Best Film and Best Director Oscars and made a ton of money at the box office to boot.", "\n\nWith this, their 16th film, the Coens almost out-Coen themselves with a Russian doll of a movie that’s as enigmatic as it is engrossing.", "\n\nThe roster of seemingly cursed characters with a leaning towards self-destruction is a growing one in the Coens’ filmography and Llewyn Davis’ tractionless folk musician is right up there with Barton Fink, The Man Who Wasn’t There‘s Ed Crane Larry Gopnik from A Serious Man.", "\n\nLlewyn (Oscar Isaac) is, like the songs he plays, “never new and never gets old” and spends his days drifting around New York’s early-60s Greenwich Village playing the odd gig and relying on the generosity of friends for a place to lay his head. ", "You get the sense things have been this way since his former musical partner Mike committed suicide a few years earlier, while his only solo album, Inside Llewyn Davis, has fallen through the critical and commercial cracks.", "\n\nHis inertia has left him bitter, despite (or because of) it being almost entirely his own fault. ", "Llewyn simply can’t fathom how or why the folk-by-numbers tunes of the innocuous Troy Nelson (Stark Sands) “connect with people” and can’t hide his derision when playing session guitar on the inane folk-pop pap Please Mr Kennedy (the film’s standout hilarious scene) written by his friend Jim (Justin Timberlake). ", "Meanwhile, Jim and Llewyn’s ex-flame, the perennially angry Jean (Carey Mulligan), are also starting to make waves on the folk scene as a duet – another sign that he’s being left behind.", "\n\nOpportunities present themselves, but Llewyn has a compulsion to snatch defeat from the jaws of something more prosperous. ", "An audition for respected Chicago producer Bud Grossman (F. Murray Abraham) comes to naught when, instead of playing something catchy, Llewyn instead chooses the sombre ballad The Death Of Queen Jane. ", "Grossman’s pithy summation “I don’t see a lot of money here” firstly reminds us why it’s called the music business, and secondly underscores the fact Llewyn’s always going to be a square box trying to fit in a round hole.", "\n\nThe Coens’ very best films open themselves up to multiple interpretations and Inside Llewyn Davis is no different. ", "For me, the oppressive sense of death hangs over the film like a shroud, to the extent that it could be argued the world we see Llewyn wandering around is some kind of purgatory.", "\n\nBruno Delbonnel’s chilly cinematography lends the film a ghostly pallor, while the eerie road trip Llewyn takes with beat poet Johnny Five (Garrett Hedlund) and obnoxious Dr John-alike jazz muso Roland Turner (the one and only John Goodman) from New York to Chicago is like something out of a supernatural nightmare, with ominous-sounding vehicles screeching past their car.", "\n\nFurthermore, the cat(s) that Llewyn cannot seem to escape from have long been regarded as a symbol of death, while the fact one of the cats is called Ulysses could be a reference to Tennyson’s celebrated poem of the same name (rather than James Joyce’s novel) about a man with the spectre of death hanging over him.", "\n\nThe songs Llewyn performs are also soaked in morbidity, from The Death Of Queen Jane, to Hang Me Oh Hang Me (“wouldn’t mind the hangin… but the layin in the grave so long”), while the film’s elliptical structure could be seen as purgatorial. ", "Mind you, it just as easily be about a poor schmuck living day-to-day and who gets saddled with a cat. ", "That’s the Coens for you.", "\n\nIsaac gives a superlative performance as the downtrodden Llewyn, a curious figure who’s his own worst enemy but somehow illicits our sympathy. ", "There’s something both maddening and admirable about his bloody-mindedness.", "\n\nThe Coens have been accused in the past of being unsympathetic towards their characters and it’s a charge that’s been levelled at Llewyn Davis. ", "This is to miss the point, however. ", "Llewyn is flawed, of that there is no doubt, but Isaac injects the character with real pathos.", "\n\nIt may be as difficult to pin down as its leading character, but Inside Llewyn Davis is achingly beautiful and melancholic and another masterpiece from the Coens." ]

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[ "Q:\n\nwhy django not found module psycopg2 in django2.2 and python 3.8\n\nI install django 2.2.10 and python 3.8 and psycopg2 2.8.4 but when i try migration with command (python manage.py migrate) confront this error:\nraise ImproperlyConfigured(\"Error loading psycopg2 module: %s\" % e)\ndjango.core.exceptions.", "ImproperlyConfigured: Error loading psycopg2 module: No module named 'psycopg2'\npsycopg2 in 32-bit. ", "i try any solution that available in stackoverflow but this error don't dissolve\ndatabases in settings.py:\nDATABASES = {\n 'default': {\n 'ENGINE': 'django.db.backends.postgresql_psycopg2',\n 'NAME': 'postgres',\n 'USER': 'seyyedh',\n 'PASSWORD' : '123456',\n 'HOST':'localhost',\n 'PORT' : '5432',\n }\n}\n\nA:\n\nI understand that psycopg2 installed on another virtual env while main virtual env running \nso I unistalled that virtual env and error solved\n\n" ]

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[ "<!", "DOCTYPE HTML>\n<html lang=\"en\">\n\n<head>\n <meta http-equiv=\"refresh\" content=\"0; url=index.htm#TooltipMouseMenu\">\n <meta http-equiv=\"Content-Type\" content=\"text/html; charset=utf-8\">\n <link rel=\"canonical\" href=\"index.htm#TooltipMouseMenu\">\n <title>Redirection</title>\n</head>\n\n<body>\n <p>Redirecting to <a href=\"index.htm#TooltipMouseMenu\">ToolTip Mouse Menu</a>.</p>\n</body>\n\n</html>\n" ]

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[ "Going on the name alone you’d have a hard time figuring out exactly what the functionality was and why you would want to preview your inbox? ", "But the feature is aimed at people who want to access their Gmail accounts through a slow connection. ", "Gmail can take quite a while to load fully, but that might not be something you have noticed if you only ever access it through a speedy connection.", "\n\nOn a slow connection you could be sitting there for several minutes only to find out you didn’t have any new e-mails you wanted to read anyway. ", "So Google have come up with a solution. ", "While Gmail loads properly it will display a static image showing the ten most recent messages added to your Inbox. ", "Based on that information you can decided whether to continue letting Gmail load or use the time elsewhere.", "\n\nA very simple feature, but an effective one if you are relying on a slow connection. ", "I tried enabling it while accessing Gmail through my fast home connection and you don’t even have time to look at the preview image. ", "But it is something to keep turned on if you don’t know how good some connections you will be surfing with are." ]

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[ "Nancy Tate\nNude\n\nNancy Tate was born in New York and grew up there, but moved to France in the 1990’s to work as a model. ", "She enjoyed living there so much (and she speaks French fluently) she decided to stay there permanently. ", "After working as a model for a number of years, she branched out and started acting. ", "In addition to TV and film work, she has also done work, including motion capture acting, in some video games. ", "When Ms. Tate breaks out the ta tas in 13 French Street (2007) you will be handling your joystick. ", "We first get a peek at the peepers when she hits the beach topless then later she walks into a room with her shirt open and her jugs out surprising a guy that is there and making us smile." ]

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[ "Q:\n\nHow do I remove dead links from the whisker search bar in xubuntu 16.04?", "\n\nI have searched through the entire menu editor, deleting everything I do not want. ", "However if I use the search feature in whisker the entries remain as dead links.", "\n\nA:\n\nI found it by removing the links from\ncd ~/.local/share/applications\nrm gog_com-Dragonsphere_1.desktop\nrm unity-editor*\n\nFor some reason, I was given a prompt to remove these, but for some reason they persisted under multiple deletes. ", "They were removed simply with sudo privileges. ", "\n\n" ]

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[ "Hey everyone welcome to Pai's Kitchen so\ntoday I am sharing with you my\nmother-in-law's famous turnip cake\nrecipe which is also known as \"Lo Bak Go\" in\nCantonese now my mother-in-law is so\nwell known for this dish she makes an\nawesome version of it and we all in the\nfamily look forward to it every Chinese\nNew Year so this year I thought I have\nto get this on camera so this recipe\nwill never get lost because it's too\ngood so I went over to her house watched\nher make it cuz of course she doesn't\nhave anything written down and I filmed\nher make it so that I could now make it\nand share it with you yay long live the\nLo Bak Go recipe! ", "And it's a bit of prep\nwork but it's actually really easy and\nit's so so so delicious and also for\nnext week\nI'm going to share with you how Thai\npeople eat these turnip cakes so we have\nour own little thing that we do with the\nturnip cake as well so if you love\nturnip cake, stay tuned for next week\nalright let's get started.", "\nSo even though this recipe is commonly\ntranslated in\nEnglish as turnip cake you don't\nactually use a turnip you use a daikon\nradish which I have here peeled and\nshredded into strings so what I use is\none of these Thai julienne peeler which\nmakes it really fast really convenient\nbut you don't have to use it you can\ngrate it with a grater but I prefer this\nbecause it gives a bigger strings and\nyou get more of a texture in the daikon\ncake at the end or you can also just\nhand chop it so I've got some that I\nhand slice over here and then you just\nget a little juliennes and you can make\nit a little bit bigger if you like\nthings a little chunkier my\nmother-in-law she makes a huge batch like\nshe'll make three times this amount, so what she'll use is a food processor with\nthe grater attachment and she just runs\nthe daikon through that we're gonna set\naside let's talk about the things we put\nin the Lo Bak Go, these wonderful dried\nproducts over here dried shrimp is\npretty classic you probably want to have\nthat I've got some dried shitake\nmushrooms\nsome Chinese sausage and some dried\nscallops so the dry scallops is\nexpensive so I'm making a bit of a\nluxury Lo Bak Go here because my\nmother-in-law always does it, if you\ndon't have it, can't find it do not worry\nabout it if you just have three you'll\nbe totally fine and what you want to do\nis you want to soak these three dry\nproducts in some hot water until they're\ncompletely hydrated give them at least a\nfew hours the scallops will take a\nlonger time and then what you do with\nthe dried shrimp is you just roughly\nchop them with the mushrooms you just\nfinely dice them with the Chinese\nsausage which you do not have to soak do\nnot soak your Chinese sauces just finely\ndice them like this and with the\nscallops I just want to show you because\na lot of people don't work with dry\nscallops very much, this is actually the\nfirst time I've worked with dried\nscallops, so once the scallops are\ncompletely hydrated so you see how much\nbigger they get\nThey'll shred really easily into\nstrings okay and that's what\nyou do, you just shred them into little\nfibers just like that\nand the dried scallops give such a lovely seafood\numami flavor I can't describe it like\nthese things smell so good like dry\nsquid type smell if you've ever had\ndried grilled squid before so good okay\nso there's my scallop and also I should\nnote that the water that you use to soak\nthese things you want to keep because\nthat is flavorful water that\nwill add into the cake itself adding\nextra flavor and that's pretty much all\nthe prep there really isn't that much\nlet's get cooking so the first thing I'm\ngonna do is render out the fat from my\nLaap Cheung or my Chinese sausage at this\npoint keep your heat quite low because\nthese sausages are quite sweet if the\nheats too high it'll burn quickly and it\nwon't have a chance to render out the\nfat so you see how much pork fat has\ncome out yes that is exactly what we\nwant now what I want to do is saute all\nmy other seafood ingredients my scallops\ngo in\nand my dried shrimp and mushrooms which\nI guess is not a seafood but you know\nwhat I mean\nand we're saute these until they start\nto toast and become really really\naromatic if you hear the word turnip\ncake and you've never had it before you\nmight think as I honestly thought that\nsounds terrible like a turnip cake the\ntwo words that you don't expect to be\nnext to each other, right? ", "but when you\nhave it it's like oh man, like, that is so\ngood! ", "And this is the reason why it\ndoesn't just tastes like you're eating a\nturnip when they start to pop that's how\nyou know they're starting to get to\nwhere you want it to be whoo all right\nI'm gonna turn this off now and get it\nout of the pan so in the same pan I'm\ngonna turn the heat back on I'm gonna\nadd the daikon now and now I'm just\ngonna toss this around until it's wilted\nslightly so you can imagine when my\nmother-in-law makes this she makes three\ntimes the amount of what I have now so\nwhenever she makes it it's like a big\nproduction so I took her recipe and\nscaled it down so that it's a little\nmore manageable okay so it's wilted a\nlittle, I'm gonna now add all that\nsoaking water that we save so the water\nfrom the mushrooms, the scallops, the dried\nshrimp at all that and just watch the\nbottom sometimes there's a little bit of\ngrit and dirt that comes out of those\ndry products so I\nnever pour all the way to the bottom\nbecause I don't want the little pieces\nof grits and now I'm gonna let the\ndaikon cook until it's completely done\nbasically until it's nice and soft takes\nabout seven minutes maybe ten if your\npieces are a little bigger I'm gonna cover\nit with a lid that's barely big enough\nand keep the heat on low and I'm gonna\ncome in and stir it every once in a while just\nto get it redistributed with all the\njuices we'll be right back\nOkay, whoo!", "\nlike daikon noodles! ", "I'm gonna drain the\ndaikon in my sieve here and the key and\nthis is why this recipe tastes so good\nis we are gonna save all of that cooking\nliquid because that has all the flavor\nfrom all the things that we soaked and\nthe flavor of the daikon as well, you see\nsome recipes where they cook the daikon\nand throw away the cooking water you're\nnot gonna get as good of a flavor that\nway get this in and I want to press\neverything out because I want to measure\nhow much liquid I have at the end of the\nday so you want to definitely press out\nas much water as you can but I mean it\ndoesn't have to be completely dry but\nyou want to get it to a point where you\nknow you lift it and there is no water\njust pouring out anymore I'm still\ngetting some drips so I want to press\nthat out okay the daikon goes back into\nthe wok and now with this liquid I want\nto measure out one cup of water and you\nshould have just about a cup if you use\none cup of water to soak your mushrooms, your scallops and your dried shrimp\nyou go through this whole process and\nyou're gonna end up around one cup if\nyou don't have enough add just a little\nmore water if you have too much just\npour out that extra a little bit you\nshouldn't have a ton of extra and my\ngosh it's like I planned for it I have\nexactly one cup of liquid I'm gonna let\nthis cool just a little bit just until\nit's warm meanwhile I am back in the wok\nI'm gonna throw in the seafood... I keep\nwanting to call it the seafood mix but\nit's not just seafood there's pork and\nmushrooms in there and I'm going to use\nthis time to get everything tossed\ntogether evenly distributed\nand my heat is off at this point I'm\njust mixing\nso my daikon juice, which sounds delicious,\nhas cooled down a bit and you just need\nit to be not hot so if it's still warm\nthat's okay okay let's talk the cake\npart so the flour that we need is going\nto be rice flour comes in a red bag like\nthis any Asian grocery store should have\nit and also I'm going to add a\nlittle bit of tapioca starch and that's\ngonna give the texture a little bit more\nof a bounce rice flour alone is totally\nfine if you don't have this you can do\nall rice flour but it will be softer\nshall we say...which you might prefer\nso try it out if you don't have this and\nso I'm just gonna mix this into my\ndaikon juice here and we mix the flour\ninto the water just so it then\ndistributes more easily once we mix it\nwith the daikon and with a mini whisk\nwe're gonna give this a stir until there\nare no more lumps and this is why you\ndidn't want the liquid hot because in\nyour flour would cook in that liquid if\nit was piping hot okay so now that goes\ninto the daikon my heat by the way is\nstill off so I can take my time doing\nthis if I keep my heat on right now\nit'll start to congeal and then I have\nto rush but now I'm just taking my time\nokay let's do seasoning before I forget\nI'm gonna do just a little bit of salt\nsome sugar, white pepper and I'm doing\nquite a bit of white pepper because I\nlike that flavor, and just a little bit\nof vegetable oil I'm using avocado oil\nactually for some extra lubrication when\nI give this a quick mix and I can turn\nthe heat back on now actually so I'm\njust gonna do a medium heat and I'm just\ngonna mix this until this becomes a\nthick paste now even though we're still\ngoing to cook.. we're gonna steam the\ndaikon cake I keep calling it daikon\ncake we're to steam the turnip cake but\nright now as you can see the liquid and\nthe daikon are not together it's pooling\naway from it and so if we steam it right\nnow you won't get an even texture so you\nwant to cook it just enough so that the\nflour is no longer running away from the\ndaikon which is a similar technique that\nI used in my garlic chive dumplings\nrecipe and if you haven't seen that you\ngotta check it out I'll link it right\nhere it's so delicious yeah as you can\nsee it doesn't take very long at all so\nyou want to be scraping the bottom\nand that is it I'm gonna turn the heat\noff now so now that we've got it nice\nand thick I need to put it in a pan so\nwe can steam it so you can steam this in\nwhatever container you like okay it can\nbe lots of little ones one big one a\nloaf pan I'm using a seven inch round\ncake pan which fits this nicely you can\ndo it in like an aluminum foil container\nas well now you want to smooth this out\nmake sure there aren't any gaps on the\nside and that's it now we've got to get\nthe steamer set up so I've got a new\nsteamer set up here you normally see me\nuse my big steamer just wanted to show\nyou another thing you can do is just put\na bamboo steamer on top of a pot that\nsort of the same diameter or you can\nalso use one of these thingies and just\nput it inside a big pot it's just with\nthis it's a little harder to get out\nbecause you're gonna I gotta like dig\nyour hand in through the pot but\nwhatever works for you\nso now this goes on top I cover it one\nhour that's it and then it's done so\nit's been an hour\njust want to show you\nwhat that looks like\nso to tell whether or not this is done I mean like\nI've never steamed this for an hour and\nit not be done so if you're making this\nsize you can be sure my mother-in-law\nmakes three at a time so she steams it\nfor an hour and a half cuz there's just\nmore stuff in there but a lot of people\nwhat they do is they just use a\ntoothpick they stick it in the middle\nthey pull it out and you'll get some\ncreamy wet stuff on it but it should\nlook translucent so as you can see\nbefore it went in it was white but now\nit's sort of clear ish so that's what\nyou're going for you're not looking for\nthe toothpick to be dry because when\nit's really hot it's not gonna come out\nsuper dry. ", "Sure-fire way though, my\nfavorite way of doing it is I use a\nthermometer I stick a thermometer in and\nif\nthat gets to 200F and above you are done\nand that's it now we can't do anything\nwith it until it's cool so I'm gonna go\nrelax for a second\nSo my Lo Bak Go has had\nsome time to cool you want it to be\ncompletely room temp it just makes it so\nmuch easier to cut if it's still warm\nit's just a little jiggly okay so I'm\ngonna run a flat something or other\nalong the sides\nso what I'm showing you\nnow is how to eat this thing\ndim sum style now let's hope it all\ncomes out.", "\nTa da! ", "See? ", "that's why you put\nparchment paper on the back and now I'm\ngonna have to slice this into really\nwhatever shape you want so what am I\ngonna do here\nlet's do inch thick slices\nso you can eat this however you want but\nI'll give you a suggestion for nice\nplating should you want to impress\nsomebody so I just find that shingling\nthem make them look a little bit better\nthan just sticking them straight on a\nplate and then if you want a little\ngreenery is always nice you know random\ngreen onions always saves the day I\nusually eat this with some soy sauce and\nalso some hot sauce like a sriracha or\nsomething so let's see\nI just do a quick dip here shake off\nand then a dip here\nif you're eating communally you may want\nto just like use a spoon rather than dip\nbut hey it's just me here\nPerfect. ", " Just perfect.", "\nand because I know I'm gonna eat\nthis with soy sauce I made the seasoning\nof the...I shouldn't say I my\nmother-in-law because this is her recipe\nlike word-for-word I didn't change\nanything she makes it so that on its own\nit's a little mild but with a light dip\nin the soy sauce you don't want to\noverdo it it just it just reaches\nperfection a little tartness and\nspiciness from the hot sauce the texture\nof this is perfect it's creamy but with\nthat little bit of tapioca starch it it\nhas a little bit of a bounce to it not\ntoo much but it's not mushy and you can\nyou know there's a lot of stuff going on\nbecause we put like the Laap Cheong and\nthe dried shrimp and the mushroom so\nthat gives it a lot of texture as well I\nmean when I to be really really honest\nwhen I first came across this dish and\nit was like turnip cake\ndaikon cake that does not sound good at\nall but when I tried it and I was like\noh my god like this stuff is good and\nit's hard to stop a lot of times they'll\nhave this with eggs for breakfast as\nwell so I hope you give this a\nthe recipe has always will be on HotThaiKitchen.com and if you want to\njoin us on Patreon and have access to\nsome extra bonus content you can check\nout all the details in the link below\nand if you haven't subscribed to the\nshow make sure you do so you don't miss\na recipe and click the bell icon as well\nso you get a notification when I post a\nnew video thank you as always for\nwatching and I will see you next time\nfor your next delicious adventure\n \n" ]

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[ "The second Twin Cities man in as many weeks to admit to his role in a plot to fight alongside Syrian terrorists said he was moved to do so by his Muslim faith, despite atrocities he knew were committed overseas.", "\n\nZacharia Abdurahman, 20, explained to U.S. District Judge Michael Davis that he felt it was his duty to join the Islamic State in Iraq and the Levant (ISIL) to help alleviate suffering among Syrian citizens, although he knew the group committed beheadings and had burned prisoners alive.", "\n\n“In Syria, I’ve seen videos of elderly parents and kids calling out, not to their fellow countrymen, but saying, ‘Where are the Muslims?’ ” ", "Abdurahman told Davis and a full courtroom that included his parents. “", "I took it upon myself as a responsibility that I had an obligation to go. ", "It is a worse sin to not listen to their cries.”", "\n\nIn exchange for pleading guilty to a single count of conspiring to provide material support for ISIL — a charge that could bring up to 30 years in prison — Abdurahman faces a maximum of 15 years. ", "A related conspiracy charge was dropped.", "\n\n“You understand that material support means more than taking a vacation in Syria?” ", "Davis asked.", "\n\n“Yes, your honor,” Abdurahman said.", "\n\nZacharia Yusuf Abdurahman\n\nAbdurahman, a onetime computer science student at Minneapolis Community and Technical College, spoke softly. ", "He was repeatedly nudged by his attorney, Jon Hopeman, to say “your honor” while addressing Davis. ", "Upon entering the courtroom, he glanced back at his family, who smiled and wiped their eyes.", "\n\nHe is the third defendant in the conspiracy to plead guilty. ", "Abdullahi Yusuf pleaded guilty in February.", "\n\nUnlike fellow defendant Hanad Musse, who pleaded guilty last week, Abdurahman did not hesitate to name his fellow co-conspirators — some who await trial in February, others who made it to Syria and are at large or believed dead.", "\n\nAmong them, Abdurahman also named the informant critical to the government’s case: Abdirahman Bashiir. ", "The FBI paid Bashiir $41,000 through August to secretly record his friends.", "\n\nStill, Abdurahman admitted that he wasn’t entrapped by the informant — an argument made by the seven defendants’ families since they were charged earlier this year.", "\n\n“The idea was there before,” Abdurahman told Davis. “", "Joining ISIS and going to Syria was there before even the [informant] came along.”", "\n\nThe hourlong hearing shed some light on the organization’s tactics to recruit American youth. ", "Despite being Somali, Abdurahman wasn’t interested in joining Al-Shabab, a terror organization that successfully recruited dozens of young Twin Cities Somali men from 2007 to 2012.", "\n\n“With Al-Shabab it was mostly targeted to Somali people, and ISIS is targeted to Western youth,” Abdurahman said. “", "They were in English and show things that Western youth do.”", "\n\nAbdurahman said that he learned of atrocities committed by ISIL after his friend Abdi Nur, also a part of the conspiracy, successfully made it to Syria. ", "He said he was aware of beheadings and burning prisoners alive, but not rapes. ", "He said he watched the television network Al-Jazeera, and through its coverage was convinced the victims were criminals who deserved it.", "\n\nDavis responded that he knew the news service, and that it wouldn’t report that the victims deserved to be beheaded. “", "Don’t try to fool with me on that one,” he said.", "\n\nDavis asked emphatically if Abdurahman ever saw footage of a beheading.", "\n\n“I didn’t see exactly, but I knew about them,” Abdurahman responded.", "\n\nAbdurahman also laid out for Davis his failed attempt to fly to Europe through JFK International Airport, then make his way to Syria. ", "He backed out of a second attempt to fly to Syria through Mexico.", "\n\nAsked by Assistant U.S. Attorney John Docherty whether it was because of a change of heart, Abdurahman responded, “No sir, I thought I was gonna get caught.”", "\n\nHis sentencing date has not been scheduled.", "\n\nAfterward, Abdurahman’s father, Yusuf, stood by while other family members embraced outside the courtroom, which once again bore a heavy security presence.", "\n\n“If someone does the crime, they should be held accountable.” ", "Sadik Warfa, deputy director for Global Somali Diaspora, above, speaking to the media after the hearing\n\n“I thought he did a good job,” his father said of his son’s confessions.", "\n\nSadik Warfa, a Somali community leader and liaison for the families of the defendants, was subdued after months of mounting a vigorous defense.", "\n\nWarfa said Abdurahman is appropriately taking responsibility.", "\n\n“If someone does the crime,” he said, “they should be held accountable.”", "\n\nStaff writer Paul McEnroe contributed to this report." ]

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[ "Identification of stair climbing ability levels in community-dwelling older adults based on the geometric mean of stair ascent and descent speed: The GeMSS classifier.", "\nThe aim was to develop a quantitative approach to identify three stair-climbing ability levels of older adults: no, somewhat and considerable difficulty. ", "Timed-up-and-go test, six-minute-walk test, and Berg balance scale were used for statistical comparison to a new stair climbing ability classifier based on the geometric mean of stair speeds (GeMSS) in ascent and descent on a flight of eight stairs with a 28° pitch in the housing unit where the participants, 28 (16 women) urban older adults (62-94 years), lived. ", "Ordinal logistic regression revealed the thresholds between the three ability levels for each functional test were more stringent than thresholds found in the literature to classify walking ability levels. ", "Though a small study, the intermediate classifier shows promise of early identification of difficulties with stairs, in order to make timely preventative interventions. ", "Further studies are necessary to obtain scaling factors for stairs with other pitches." ]

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[ "The present invention relates to a system for determining a soil characteristic, in particular, a system for analysis of the size of individual particles to determine characteristics of soil samples over a geographic area for agricultural applications.", "\nAn agricultural field generally includes a variety of soil characteristics. ", "It is particularly useful to evaluate the soil to determine the optimum crops for maximum yield potential and for treatment methods available.", "\nReference is made to U.S. Pat. ", "No. ", "4,630,773, entitled, Method and Apparatus for Spreading Fertilizer; U.S. Pat. ", "No. ", "5,355,815, entitled, Closed-Loop Variable Rate Applicator; and U.S. Pat. ", "No. ", "5,887,491, entitled, Soil Analysis Assembly and System.", "\nAll documents cited herein, including the foregoing, are incorporated herein by reference in their entireties for all purposes.", "\nThe present invention relates to a soil analysis system for determining: 1) a percentage of particles within certain size ranges in a region of interest in a soil sample, for example, size ranges comparable to sand, silt, and clay; and 2) a general soil characterization of the soil sample as a function of the percentage of the particles in each size range.", "\nAlthough soil type can include particular characteristics such as the physical nature of the soil, e.g., average particle size of sand, silt, clay, and the like, and their respective relationships, a general reference to the term soil type can include a variety of other characteristics and properties of a soil sample.", "\nThe soil analysis apparatus determines a particular soil characteristic of a soil sample, in particular, the general physical nature of particles and the percentage of particles having generally common physical features. ", "The soil analysis system is configured to determine a soil sample as one of generally sand, silt, clay, sandy clay, silty clay, sandy clay loam, clay loam, silty clay loam, loamy sand, sandy loam, loam, and the like.", "\nWith the soil analysis system, a series of soil samples can be analyzed to advantageously determine the relative soil makeup over a geographic area. ", "Sand, silt, and clay each have a generally distinct size range relative to one another and their respective percentage in a soil sample can determine a general soil character. ", "For example, sand is generally characterized by large particle size; silt by medium particle size; and clay by small particle size. ", "The relationship of each soil sample to another can be used to map soil characteristics over a geographic area.", "\nThe soil analysis system includes an image analysis assembly coupled to an image sensor to isolate particles and calculate individual particle size to advantageously determine characteristics of a plurality of soil samples throughout a geographic area. ", "The soil information may be further analyzed to determine a treatment plan as a function of the soil characteristics and the respective location of each soil sample in a geographical area.", "\nIn sum, the invention relates to a soil analysis system. ", "The soil analysis system includes a sensor device and an image analysis assembly. ", "The sensor device produces information corresponding to an image of at least a portion of one or more particles in one or more portions of a soil sample. ", "The image analysis assembly is operatively coupled to the sensor device and determines a category for each of the one or more particles. ", "The category is based on a function of size or surface area of each particle. ", "The soil analysis system may determine a category for the one or more portions of the soil sample. ", "The category may include clay, sandy clay, silty clay, sandy clay loam, clay loam, silty clay loam, sand, loamy sand, sandy loam, loam, and silt. ", "The image analysis assembly may further include a particle size calculation assembly for determining the size of the one or more particles and a soil determination assembly for determining at least one category of soil. ", "The soil analysis system may further include a first light source positioned at an angle relative to the soil sample on a first side of the sensor device and a second light source positioned at an angle relative to the soil sample on a second side of the sensor device. ", "The first light source may have a first wavelength and the second light source may have a second wavelength different from the first wavelength. ", "The sensor device may distinguish at least a portion of one or more edges of the one or more particles. ", "The particle size calculation assembly may determine an average radius of the one or more particles. ", "The image analysis assembly may determine if a particle has been substantially isolated. ", "The image analysis assembly may compare the size of the one or more particles in the soil sample to data relating to sand, silt, and clay and categorize the one or more particles as one of sand, silt, and clay. ", "The image analysis assembly may determine the percentage of sand, silt, and clay in the soil sample and categorize the soil sample. ", "The image analysis assembly may be operatively coupled to a controller for operation of an apparatus for treatment of a geographic area. ", "The image analysis assembly may be operatively coupled to a mapping system. ", "The image analysis assembly may be operatively coupled to a map analysis system for analyzing one or more data maps. ", "The mapping system may integrate one or more soil type maps with one or more data maps. ", "The controller may functionally cooperate with one or more maps relating to characteristics of a geographic area.", "\nThe invention also relates to a soil imaging assembly including a sensor device and a soil image assembly. ", "The sensor device produces at least one form of an image corresponding to one or more portions of a soil sample including a plurality of particles. ", "The sensor device has sufficient resolution to distinguish the plurality of particles. ", "The soil image assembly functionally cooperates with the image sensor. ", "The image sensor and the soil image assembly communicate with one another to determine at least one of: a) one or more categories of particles in the soil sample; b) a percentage of each category of particle in the soil sample; and c) a category of soil representative of the percentages of the one or more categories of particles in the soil sample. ", "The sensor device may include a photosensitive imaging device. ", "The photosensitive imaging device may include a charged coupled device. ", "The charged coupled device may includes color capability. ", "The soil imaging assembly may further include a first and second light source. ", "Each light source has one or more wavelengths corresponding to at least one of red, green, and blue.", "\nThe invention also relates to a method for analyzing soil including: positioning a photosensitive imaging device adapted to convert light intensity to an image in a functional relationship with one or more portions of a soil sample, the soil sample including one or more particles; producing information corresponding to an image of at least a portion of the one or more particles; isolating at least a portion of the one or more particles; calculating a size of the one or more particles; comparing the size of the one or more particles to data relating to at least one of sand, silt, and clay; classifying the one or more particles as one of sand, silt, and clay; determining the percentage of the sand, silt, and clay in the one or more portions of the soil sample; comparing the percentages of the sand, silt, and clay to data relating to at least one category of soil; and classifying the one or more portions of the soil sample as at least one of clay, sandy clay, silty clay, sandy clay loam, clay loam, silty clay loam, sand, loamy sand, sandy loam, loam, and silt." ]

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[ "Magnetic plasmon resonance.", "\nIt is demonstrated that metallic horseshoe-shaped (also referred to as u-shaped) nanostructures can exhibit a magnetic resonance in the optical spectral range. ", "This magnetic plasmon resonance is distinct from the purely geometric LC resonance occurring in perfectly conducting split rings because the plasmonic nature of the metal plays the dominant role. ", "Similarly to the electrical surface plasmon resonance, the magnetic plasmon resonance is determined primarily by the metal properties and nanostructure geometry rather than by the ratio of the wavelength and the structure's size. ", "Magnetic plasmon resonance occurs in nanostructures much smaller in size than the optical wavelength. ", "Electromagnetic properties of periodically assembled horseshoe-shaped nanostructures are investigated, and the close proximity of the electrical and magnetic plasmon resonances is exploited in designing a negative index metamaterial. ", "Close to the magnetic plasmon resonance frequency both magnetic permeability mu and electric permittivity epsilon can become negative, paving the way for the development of subwavelength negative index materials in the optical range." ]

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[ "How tight is the noose of death?", "\n\nEvery society in human history, has sought the obedience of each of its members to certain laws. ", "The most powerful tool each of them has had at its disposal to achieve that end has been fear. ", "And the greatest fear being the fear of the final end, each of them has used death a penalty to deter men from violation of the most sacred of these laws.", "\n\nBut there has always existed a struggle between those who fought for abolition of death penalty and those who fought to continue this practice believing it to be essential to maintaining law and order. ", "With just 58 states still retaining it as a legal punitive measure, it is clear who is winning.", "\n\nHowever, when it comes to India, there is little political and public support for the abolitionists. ", "Instead incoherent public outrage erupts every time the judiciary seems to show leniency towards perpetrators of heinous crimes. ", "Therefore the more prominent issue is, not whether the death sentence should be done away with, but how often and in what circumstances the punishment should be awarded. ", "And towards promoting awareness and the formation of a coherent public opinion capable of influencing policy on this issue, an attempt has been made to explain the principle of “rarest of rare” which is the basis of sentencing in matters of crime punishable with death.", "\n\nThe reasons for birth of “the rarest of rare” –\n\nIndia, like any other country has its share of crime, reported and covered by the media. ", "But not all cases of crime, even where the offence committed is essentially the same, are covered in the same manner and reacted to in the same way by the people. ", "For there exists a difference in the brutality and nature of a crime, the circumstance of its commission, the person(s) it was committed by and the certainty about the guilt of the accused. ", "The variations in these factors warrant different treatment of the various cases of the same offence.", "\n\nDue to this reason, impossibility of laying down standards is at the very core of the criminal law as administered in India(1). ", "The Indian Penal Code has been drafted in a way so as to invest the judges with a very wide discretion in the matter of fixing the degree of punishment. ", "For every offence the act provides not a fixed punishment but only an upper and/or a lower limit to the quantum of punishment.", "\n\nSimilarly death penalty is prescribed as an alternative to life imprisonment and discretion is given to the court to decide the cases in which it should be awarded. ", "So a matter of grave concern is how this discretion is exercised and what circumstances justify the use of it in favour of death penalty.", "\n\nThe Constitution of this country provides the fundamental right to equality before law, under Article 14. ", "This is an obligation on the state to treat, every person equally (subject to reasonable classifications). ", "In the matter of deciding sentence, this responsibility translates to ensuring that the judiciary exercises its discretion on the same standards and considerations in every case. ", "However, besides the recording of special reasons(2) there is no other legislative principle to guide the courts in the exercise of this discretion in cases of crimes punishable with death. ", "This lack of an objective standard meant that the subjective perception of crime of individual judges determined whether an accused got death sentence or life imprisonment in cases of murder. ", "Thus, the fate of an accused depended to a very large extent upon who judged him/her, for in the same case, where for one judge death penalty was deserved, for another life imprisonment was sufficient, a situation clearly unfair and in violation of Article 14.", "\n\nTo replace judge centric sentencing with a principled sentencing procedure in order to save death penalty from being challenged as unconstitutional, the Supreme Court of India gave birth to the principle of the “rarest of rare” in the case of Bachan Singh v. State of Punjab(3). ", "This principle not only sought to ensure that individuals are put on an equal pedestal to be judged but also brought death penalty in conformity with the Right to Life embodied in Article 21 of the Constitution as will be explained below.", "\n\nRationale behind the principle and its understanding –\n\nA layman’s understanding of “rarest of rare” being a class/category of exceptional cases in which the court pronounces death penalty for offence punishable with death, is not wrong. ", "But it is insufficient without an understanding of when a case is considered to fall in this category. ", "For that, it is important to realize the rationale behind this principle.", "\n\nArticle 21 of the Constitution of India provides the right to life to all people, embodying a real and abiding concern for the dignity of human life which postulates resistance to taking it through law’s instrumentality. ", "Depriving a person of his/her life according to procedure established by law is an exception to this right and it is a settled rule of interpretation of law, that exceptions must be construed narrowly. ", "Add to this the requirement under Section 354(3) of the CrPC of stating special reasons for awarding death, the legislative policy of making death an ‘exceptional’ penalty becomes clear.", "\n\nIn light of these beacons of legislative policy, the SC laid down that the extreme penalty of death can be inflicted only in “gravest cases of extreme culpability”. ", "Life imprisonment is the rule and death sentence is the exception. ", "The use of this exception will only be justified “when the alternative option is foreclosed“. ", "This oft quoted phrase is at the crux of the principle of the rarest of rare. ", "In the simplest terms, it means that only when the facts of the case make the alternative of life imprisonment completely meaningless, can death sentence be pronounced.", "\n\nTo understand when life imprisonment is rendered pointless, it is important to contrast the nature of death penalty and life imprisonment. ", "Incarceration from society serves not only the purpose of deterrence and retribution, but also of reformation. ", "The nature of the penalty is such that it can be revoked if it is felt that a convict has been reformed and is not a threat to society anymore. ", "Death penalty on the other hand is irrevocable and there is no scope for reformation/rehabilitation.", "\n\nThus, the alternative option of imprisonment can be said to be foreclosed only in those cases where there is absolutely no possibility of reformation. ", "Only when the court is satisfied the convict will always remain a threat to society and cannot be corrected, can it use this “exceptionally narrow opening” of death penalty, ensuring there is no harm in future. ", "Due to this reason the term “rarest of rare” has been used.", "\n\nHow and when can it be said whether a convict is beyond reformation?", "\n\nThe judicial precedents on this question are numerous and cannot be discussed in their entirety here. ", "The basic necessary requirement is to dispassionately weigh the circumstances aggravating the culpability of the convict against those mitigating it to judge the reformability of a convict. ", "It is here that the discretion of the court is to be exercised. ", "These circumstances not only include circumstances relating to the crime but also to the criminal. ", "The heinousness or brutality of a crime is not the only ground for consideration but only one of the many. ", "Never can the circumstances of the criminal that were a factor in his/her committing the crime, such as motivation of the convict, state of mind, social life, economic condition, etc, be discounted at any cost as this information is crucial in deciding whether the criminal will be a menace to the society in future and the probability of his reformation. ", "For example – If cold blooded murder was committed by a person with no criminal record due to some extraordinary mental pressure, or under the impression that he was morally correct in his act, it can be said there is scope for reformation.", "\n\nConclusion –\n\nWhen a state has the power to take away life, the responsibility of the state with respect to it cannot be understated. ", "As citizens who shape this country’s policies, this responsibility extends to us in the form of a duty to be conscious of this power and to debate how it is to be used. ", "The basis on which this power is exercised, as it exists today, has been explained through this post, to stimulate that debate. ", "No matter what school of thought you belong to, humanitarian supporting abolition or a conservative disciplinarian espousing a more liberal use of death penalty, armed with an understanding of this principle one can begin to intelligently analyze and criticize the approach of the judiciary.", "\n\n(1) Jagmohan Singh v. State of U.P., [(1973) 1 SCC 20]\n\n(2) Section 354(3) of the CrPC\n\n(3) Bachan Singh v. State of Punjab [(1980) 2 SCC 684]\n\nArticle by-\n\nAniket Jain\n\nAmity Law School (GGSIPU), New Delhi\n\n[Submitted as an entry for the MightyLaws.in Blog Post Writing Competition, 2011]\n\nMightyLaws is not responsible or liable for the views expressed by the authors. ", "The articles are general information and should not be treated as legal advice. ", "Please read the Disclaimer for further clarifications.", "\n\nOne Comment → “How tight is the noose of death?”", "\n\nprasanna kapoor\n\n7 years ago\n\nTo defend death sentence is to admit that there comes a stage in a human being when the person is believed to be beyond correction and learning, with no scope for transformation and reformation, beyond the hope of doing anything which will be of any use to any member of the society .However, its rare to come across a human condemned to death who is so derelict that his mother, children and friends do not come to meet him and feel nothing for him." ]

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[ "Strain dependent rate of Li+ elimination associated with toxic effects of lethal doses of lithium chloride in mice.", "\nStrain differences in response to the administration of two lethal doses (700 and 900; mg/kg) of lithium chloride were studied in eight week old males from six genetic strains of mice. ", "Two parameters were considered; (a) toxicity (time to death) and (b) hypothermia. ", "Lithium distribution in the body (blood, seven tissues, excreta and urine) were evaluated for each strain following IP injection of 200 mg/kg dose of LiCl. ", "The strain differences were significant for toxicity. ", "The order of susceptibility of the strains was 129/ReJ greater than S.W. greater than C3H/S greater than DBA/2 = Balb/c greater than C57/6J with a 15-fold difference between the most susceptible and the least susceptible strain at the 900 mg/kg dose. ", "Strain differences for hypothermic response at both doses were not significant. ", "Significant strain differences were also observed for lithium distribution in different parts of the body, excreta and urine. ", "The concentration of Li+ found in urine and excreta was positively correlated with resistance (time to death at 900 mg/kg LiCl) to the toxic effect of lithium. ", "The lithium concentration in blood, muscle and lung on the other hand reflected a negative correlation with toxicity. ", "The susceptibility of a strain could be characterized by its inherent lithium excretory ability, particularly through urine. ", "It may suggest an involvement of membrane transport mechanisms in determining toxicity to lithium compounds." ]

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[ "Wesley Hitt/Getty Images\n\nLouisiana Tech's Trent Taylor, the school's all-time leader in receptions, was running a deep route at practice earlier this season when he noticed a Ryan Higgins pass coming in low.", "\n\nAs it approached Taylor in the end zone, he turned his butt toward the ball, let it sail between his legs and caught it for a touchdown.", "\n\n\"Everyone kind of freaked out,\" Taylor said.", "\n\nTaylor regularly turns Louisiana Tech practices into his own little circus. ", "He catches punts behind his back and between his legs, and his pass-catching theatrics would play well with the Harlem Globetrotters.", "\n\nAnd on Saturdays, Taylor and the Bulldogs have made defenses look like the Washington Generals.", "\n\nLouisiana Tech averages 44 points per game, and its offense includes the nation's most dangerous trio: Taylor (second nationally in catches and third in receiving yards), Higgins (third in passing yards) and speedster Carlos Henderson (tied for second in touchdown catches with 17).", "\n\nTaylor will put a bow on a record-setting career Friday in the Armed Forces Bowl against Navy. ", "He's already sixth on the NCAA's all-time receptions list, and with eight more catches Friday—he averages 9.5 per game on the season—he'd move into third. ", "He's 17th all-time in receiving yards, and his yearly average (120.8) would move him into 14th.", "\n\nStacy Revere/Getty Images\n\nVideo Play Button Videos you might like\n\nAnd he had just one scholarship offer out of high school.", "\n\nThe explanation for that is simple: Trent Taylor is 5'8\".", "\n\nTaylor was a star at nearby Evangel Christian Academy. ", "He put up 1,650 receiving yards and 20 touchdowns as a senior, and he was the MVP in the state title game. ", "But his height kept recruiters away, and it even took convincing to get Louisiana Tech to take a shot.", "\n\nEvangel head coach Byron Dawson had a strong relationship with former Louisiana Tech head coach Sonny Dykes. ", "Dykes had recruited Dawson's brother, Keyunta Dawson, to Texas Tech. ", "Dawson told Dykes that Taylor reminded him of Wes Welker, whom Dykes had also coached at Texas Tech.", "\n\n\"I remember Coach Dykes telling me, 'Wes Welker played defense in high school and he was a tough kid,'\" Dawson said. \"", "I remember telling him that Trent Taylor not only plays defense for us, he's one of our hardest hitters, and at that time in the season, he was leading the state in picks. ", "He had five picks in the first three football games that year.\"", "\n\nDykes took a shot on Taylor, and Skip Holtz kept the commitment when he got the job after Dykes left in December 2012 to become the head coach at California.", "\n\nTaylor was an impact player as a true freshman, catching 28 passes for 260 yards and two touchdowns that year from the slot.", "\n\nTaylor's role has evolved through the years due to an effort to get him the ball more often.", "\n\n\"When you have that kind of production, you have to move him around,\" Holtz said. \"", "You don't always want people knowing where he's going to be, because then he's too easy to double cover. ", "We've had to get kind of inventive with some of the formations.\"", "\n\nParker Waters/Associated Press/Associated Press\n\nThat has been a sound strategy, as a pass in Taylor's direction rarely hits the ground no matter the trajectory. ", "Among wide receivers who have played at least 50 percent of their team's snaps, Taylor has the third-lowest drop rate in the nation at 3.15 percent, according to Pro Football Focus.", "\n\n\"I can't tell you how many balls he's laid out to get where you didn't think there was any chance he could go get it,\" Holtz said.", "\n\nThat's an attribute that could get Taylor a look in the NFL. ", "He's a long shot to get drafted, but he's in the mold of a Welker or Dallas Cowboys slot receiver Cole Beasley, both undrafted players.", "\n\n\"I know it's not going to be easy to make it into the NFL,\" Taylor said. \"", "That's the elite of the elite. ", "It's something that I've always wanted to do. ", "I just need one team to give me an opportunity, and that's all I can ask for.\"", "\n\nTaylor showed his full arsenal of abilities this year in part because of the chemistry he had with his quarterback. ", "Higgins started six games as a freshman, but Holtz brought in a graduate transfer in 2014 (Cody Sokol) and 2015 (Jeff Driskel) to be the starter. ", "This offseason Holtz turned over the offense to Higgins.", "\n\nWesley Hitt/Getty Images\n\n\"My relationship with the one-year guys, as the season went on we had to build that relationship and grow on the move with it—midseason-type stuff—but with Ryan, I've been around him the past four years and that was nothing we had to work on,\" Taylor said. \"", "That brotherhood and that connection was already there. ", "That was a step ahead for us.\"", "\n\nHiggins has found a way to get Taylor the ball despite the fact that he's seeing double and triple coverages. ", "That's where his height becomes an advantage. ", "It's difficult for opponents to get their hands on Taylor, and his quickness allows him to sneak free of multiple defenders.", "\n\n\"It's like chasing a cat,\" Dawson said.", "\n\n\"He's much shiftier because he's got a lower center of gravity, and he's quick as he can be,\" Holtz said. \"", "He's not going to run a 4.3. ", "He's not the guy that is just going to run by, but trying to stop him on a mid- or out-breaking route is very difficult to do.", "\n\n\"I'm sure a lot of people who are recruiting by height, weight and speed, he doesn't fit the bill. ", "If you recruit the intangibles, he's pretty special.\"", "\n\nThe proof has been in the numbers and one spectacular catch after another. ", "The one that sticks out in Holtz's mind is a grab Taylor made at Mississippi State last season. ", "The ball was floating toward the sideline, and Taylor had to leap to catch it.", "\n\n\"And while he's flying out of bounds, he's got the wherewithal to put his elbow on the ground first, because that's the only thing he could get inbounds,\" Holtz said.", "\n\nThe acrobatic catches have led to a regular occurrence during postgame handshakes. ", "Opposing coaches will approach Holtz and want to talk about the amazing catch Taylor had that day.", "\n\nIf only they could have seen what he did in practice...\n\n\"The special ones make you walk off the field every day and say, 'Did you see that catch? ", "Did you see that move? ", "Did you see that route?'\" ", "Holtz said. \"", "That's what the special ones make you do every day when you walk off the practice field—not just the game field but the practice field.", "\n\n\"It's like he woke up this morning just to come to practice. ", "This is what I've been waiting for all day is to play football.\"", "\n\nC.J. Moore covers college basketball and football for Bleacher Report. ", "You can follow him on Twitter @CJMooreBR." ]

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[ "Introduction {#Sec1}\n============\n\nMicroalgae, a large and heterogeneous group of microscopic algae, are an almost untapped pool of metabolic versatility. ", "As many of the species occurring in nature have not yet been identified and/or physiologically characterised, their potential awaits exploitation in the biotechnological manufacturing of high-value biomolecules or deliberately enriched biomass (Guedes et al. [", "@CR50]; Raja et al. [", "@CR91]; Rosenberg et al. [", "@CR96]; Wijffels [@CR122]). ", "The term 'microalgae' is typically used in its narrowest sense as a synonym for photoautotrophic, unicellular algae utilising CO~2~ and gaining energy from light. ", "Although certain species are obligate photoautotrophs, numerous microorganisms currently classified as microalgae are in fact obligate heterotrophs (Droop [@CR31]; Gladue and Maxey [@CR45]), and others are capable of both heterotrophic and photoautotrophic metabolism either sequentially or simultaneously (Chojnacka and Marquez-Rocha [@CR21]; Droop [@CR31]; Gladue and Maxey [@CR45]; Lee [@CR68]).", "\n\nHeterotrophic cultivation without light and with the controlled addition of an organic source of carbon and energy is similar to procedures established with bacteria or yeasts in multipurpose stirred closed tanks sterilised by heat. ", "To date, only a small number of microalgal species have been cultured heterotrophically in conventional bioreactors (Chen [@CR15]; Perez-Garcia et al. [", "@CR87]). ", "The few commercialised processes in which microalgae are grown under heterotrophic conditions are focussed on the manufacture of polyunsaturated fatty acids (PUFA) in 100-m^3^ scale (Behrens [@CR5]). ", "These biotechnological processes represent a sustainable alternative to the extraction of PUFA from fish oil (Apt and Behrens [@CR1]; Barclay et al. [", "@CR3]; Barclay [@CR2]; Kyle and Gladue [@CR65]; Kyle et al. [", "@CR66]; Mendes et al. [", "@CR79]; Wynn et al. [", "@CR126]). ", "Several other heterotrophic processes that utilise microalgae have been established at laboratory scale to deliberately enrich the biomass with compounds such as pigments and antioxidants (Pulz and Gross [@CR89]; Raja et al. [", "@CR91]; Spolaore et al. [", "@CR108]). [", "l]{.smallcaps}-Ascorbic acid (Running et al. [", "@CR97]) and polysaccharides (Ramus [@CR92]) are examples of commercially valuable extracellular products obtained from microalgae. ", "Classes of compounds that are found in microalgae and that exhibit desirable properties for treating inflammation, tumours and viral or microbial infections are attracting new interest (Guedes et al. [", "@CR50]). ", "Moreover, research in the rapidly expanding field of biofuels (Wijffels and Barbosa [@CR123]) provides a valuable source of fundamental information on the physiology and biochemistry of microalgae, producing high-value compounds (e.g. Brányiková et al. [", "@CR10]; Xiong et al. [", "@CR129]). ", "The growing interest in microalgae, either non-recombinant or with appropriate genetic modification (Potvin and Zhang [@CR88]; Specht et al. [", "@CR107]), suggests that heterotrophic microalgal processes offer significant commercial opportunities (Rosenberg et al. [", "@CR96]).", "\n\nIn contrast to plants or seaweeds, in which biomass is fairly compact, the harvesting of unicellular microalgae dispersed in natural habitats of microbial consortia is not as straightforward. ", "Low cell densities of several grams per litre are an important cost factor for established production processes with photoautotrophic microalgae in conventional open ponds or photobioreactors (Molina Grima et al. [", "@CR80]). ", "However, cell densities of more than 100 g l^−1^ cell dry weight, achieved with *Chlorella*, *Crypthecodinium* and *Galdieria* species, highlight the potential of heterotrophic microalgal processes (de Swaaf et al. [", "@CR26]; Doucha and Lívanský [@CR29]; Graverholt and Eriksen [@CR47]; Wu and Shi [@CR124]). ", "Moreover, systematic screening for new compounds is only feasible provided that sufficient quantities of concentrated biomass from axenic (pure) cultures are attainable (Olaizola [@CR85]; Wijffels [@CR122]).", "\n\nFrom taxonomic studies, it is acknowledged that microalgae exhibit considerable metabolic plasticity (Trainor [@CR112]). ", "In response to their surroundings, particular species can occur in alternative phenotypes, and these can result in the altered formation of metabolites and/or products. ", "Thus, the composition of biomass (or intracellular products) or the production of desired extracellular products is typically affected by culture conditions (Hu [@CR54]; Illman et al. [", "@CR55]; Jakobsen et al. [", "@CR59]; Lv et al. [", "@CR74]; Shi et al. [", "@CR105]; Xiong et al. [", "@CR129]; Yongmanitchai and Ward [@CR130]). ", "In turn, this large environmental adaptability provides opportunities to modify the production of targeted natural compounds and to control their formation at high titres, yields, productivities and the required quality (purity). ", "However, screening the various (natural) phenotypes under different conditions is a complex, time-consuming task involving a large number of culture variables. ", "The basic principles of systematic screening were established during studies of the species suitable for use in aquaculture hatcheries (Gladue and Maxey [@CR45]).", "\n\nAlthough the opportunities for heterotrophic processes with microalgae have been considered in several review papers (Apt and Behrens [@CR1]; Borowitzka [@CR7]; Lee [@CR68] as well as more recently by Eriksen [@CR38] and Perez-Garcia et al. [", "@CR87]), few cover aspects of cultivation technology in depth (e.g. Chen [@CR15]; Chen and Chen [@CR16]). ", "In an attempt to address the outstanding issues, this review paper outlines the current best practices in the heterotrophic high-cell-density cultivation of microalgae for the production of biomass or specific products for health and nutraceutical applications. ", "The main topics dealt with include (1) the characteristics of microalgae suitable for heterotrophic cultivation, (2) the appropriate chemical composition of mineral growth media, (3) strategies for high-cell-density cultivation and (4) the principles of customising biomass composition. ", "Thus, the potential and limitations of fedbatch technology are outlined. ", "The generic process strategies described are based on experimental data collected for non-recombinant microalgae and are, in principle, also applicable to emerging strains improved by genetic engineering.", "\n\nCultivation of microalgae in conventional stirred bioreactors {#Sec2}\n=============================================================\n\nThe microalgal species which are currently attracting commercial interest grow under heterotrophic conditions and perform efficiently in conventional bioreactors in a similar manner to bacteria or yeast (Riesenberg and Guthke [@CR94]). ", "Such sophisticated, safe and controllable bioreactor systems are used to produce novel high-value compounds with microalgae. ", "In contrast, established microalgal products are mostly manufactured by traditional outdoor photoautotrophic technologies (Lee [@CR67]). ", "If a product is unique or is not obtainable in the desired quality or quantity by other means (such as extraction from animal or plant material or chemical synthesis), the superior heterotrophic growth characteristics become less critical. ", "Performance losses may also be acceptable in cases where patent infringements need to be prevented. ", "Nevertheless, using microalgae instead of bacteria or yeasts provides the opportunity to establish a new intellectual property claim in the manufacture of competitive products (Borowitzka [@CR6]).", "\n\nGeneral prerequisites and constraints {#Sec3}\n-------------------------------------\n\nIn order to be optimally suited for cultivation in conventional stainless steel stirred bioreactors, a particular microalgal species should meet a number of desirable criteria (Table [1](#Tab1){ref-type=\"table\"}). ", "The primary prerequisite is the ability to grow heterotrophically in an inexpensive, well-defined mineral medium with a high degree of resistance to mechanical and chemical stress. ", "Table 1Prerequisites, benefits and constraints of heterotrophic cultivation in conventional stirred bioreactorsPrerequisites/benefitsConstraintsBioreactor cultivationPerformance independent of climateHigh oxygen demandReduced downstream costsSophisticated substrate feed controlEnhanced productivity and/or titreRheological limitations (at high viscosity)Control of substrate concentrationsCritical/toxic levels of metabolitesScalable process strategiesHigh costs for (new) equipmentUse of multi-purpose bioreactorsLow land requirementIndoor and cGMP operationCulture mediaEnergy of light not requiredEnhanced risk of contamination (organic carbon substrate, temperature, pH)Defined (mineral) and inexpensiveCorrosion (high salinity, critical pH)Easy to steriliseExpensive ingredients (vitamins, amino acids)Non-corrosive (low salinity, acidity)Non-defined composition (e.g. yeast extract)Contamination protection (due to high salinity, extreme pH levels, high temperature \\> 40 °C)SpeciesAvailable as axenic cultureSurface adhesionReasonable specific growth rateAggregate formationMechanical resistanceSecretion of viscous metabolitesTemperature achievable with conventional cooling (25--40 °C)Osmotic stress (at substrate over-dosing)Robust and resistant (to long periods of refrigeration, freezing, repeated cultivation, sudden condition changes)Intracellular product harvest (hampered by rigid cell walls)Compiled from: Borowitzka [@CR6]; Chen [@CR15]; Doucha and Lívanský [@CR28] and [@CR29]; Doucha et al. [", "@CR30]; Gladue and Maxey [@CR45]; Perez-Garcia et al. [", "@CR87]; Schmidt et al. [", "@CR100]; Wu and Shi [@CR125]\n\n### Need for axenic cultures {#Sec4}\n\nAn additional crucial prerequisite is the requirement for a monoculture in a long-term bioreactor operation. ", "To date, this is still hampered by the dearth of axenic (pure) cultures of species isolated from the environment. ", "In heterotrophic cultures, the advantage of preventing the growth of contaminants through selective photoautotrophic conditions is not a possibility. ", "Thus, any (minor) contamination introduced with the inoculum could easily outgrow the desired microalgal species.", "\n\nThe particular obstacle can largely be overcome by modern methods of flow cytometry. ", "For example, fluorescence-activated cell sorting permits the efficient differentiation and subsequent isolation of single cells based upon their morphology (size) and variation in autofluorescence (Cellamare et al. [", "@CR14]; Sensen et al. [", "@CR101]; Surek and Melkonian [@CR110]). ", "The rate of success for the isolation of axenic microalgal cultures collected from natural habitats was reported to be considerably higher than with a classical approach (Surek and Melkonian [@CR110]). ", "Furthermore, for selectivity reasons and the resulting ease of handling, microalgae such as *Galdieria sulpuraria*, which perform well at 42 °C and at a pH of 2, are desirable.", "\n\n### Restrictions due to high salinity {#Sec5}\n\nShould growth in the presence of sea salt (and thus at a very high salinity of about 35 g kg^−1^ of Na/KCl and high osmolarity) be essential for good performance of a particular species, additional investments in vessels coated with special materials like polyether ether ketone are necessary. ", "However, high salinity has not always been linked to increased corrosion of metallic materials (Schmidt et al. [", "@CR100]). ", "The requirement of marine species for high salt concentrations is sometimes unwittingly overestimated and the salt concentration may be significantly reduced without productivity loss (Kiy et al. [", "@CR62]). ", "On the other hand, high salt conditions have been found to significantly enhance lipid formation. ", "Upon changing the sodium chloride concentration from 10 to 20 g l^−1^ in a culture of *N. laevis*, the synthesis of total lipids, the production of eicosapentaenoic acid (EPA) and the accumulation of polar lipids increased while the synthesis of neutral lipids decreased (Chen et al. [", "@CR18]).", "\n\nSpecies used in heterotrophic processes {#Sec6}\n---------------------------------------\n\nThe ability of a number of microalgal species to grow with organic carbon substrates has been demonstrated previously (Droop [@CR31]; Gladue and Maxey [@CR45]). ", "However, the number of current commercially important microalgae that are capable of growth on organic carbon substrates in the dark, and where experience of fedbatch cultivation has been gained, is very limited.", "\n\n### Growth characteristics {#Sec7}\n\nBoth the (growth) kinetic and stoichiometric characteristics of these microalgae, along with values for other microalgal species obtained from batch cultures, are summarised in Table [2](#Tab2){ref-type=\"table\"}. ", "This table encompasses fast-growing species with a specific growth rate higher than 0.09 h^−1^ (e.g. *Chlorella*, C*rypthecodinium*, *Nitzia*, *Prototheca* spp.) ", "and species that grow at about half the rate, but where a lot of cultivation experience is available (e.g. *Galdieria*, *Haematococcus*, *Nannochloropsis* or *Schizochytrium* spp.). ", "These specific growth rates correspond to doubling times of between 7 and 15 h. Interestingly, the *Chlorella* genus exhibits a wide range of growth rates with glucose, which vary with species and growth conditions, such as temperature, pH or dissolved oxygen concentrations (Shi et al. [", "@CR105]). ", "The latter condition, in particular, can be controlled in high-cell-density (heterotrophic) cultures as the specific growth rate can be deliberately reduced to assure sufficient oxygen supply (Doucha and Lívanský [@CR29]). ", "Furthermore, heterotrophic growth of *Dunaliella* sp. ", "and *Nannochloropsis* sp. ", "is possible but is not practicable due to its very slow growth (Gladue and Maxey [@CR45]). ", "Table 2Growth characteristics of microalgae in heterotrophic batch culturesSpecies*μ* ~max~*Y* ~*x/s*~*T*pHCarbon sources^a^*s*~inhib~Products^b^References (for growth parameters only)h^−1^g~CDW~ g^−1^°C−log \\[H^+^\\]g l^−1^*Chlamydomonas reinhardtii*P/H0.0350.52356.9Acetate\\>0.4BiomassBoyle and Morgan ([@CR9])Chen and Johns (1996)*Chlorella protothecoides*P/H0.0900.47286.6Glucose (acetate, glycerol)\\>24Lutein, lipids, biodiesel violaxanthinO\\'Grady and Morgan ([@CR83])Xiong et al. ([", "@CR127])Shi et al. ([", "@CR103])*Chlorella pyrenoidosa*P/H0.2010.50356.9Glucose (acetate, glutamate, lactate)\\>10Ascorbic acid, luteinRunning et al. ([", "@CR97]), Wu et al. (", "2007)*Chlorella regularis*P/H0.2400.6366.5Glucose (acetate, ethanol)\\>10Biomass~,~ intracellular phytochemicalsEndo et al. ([", "@CR36]), Sansawa and Endo ([@CR99])*Chlorella vulgaris*P/H0.1800.55--0.69366.0 -- 7.5Glucose (acetate, glutamate, lactate)n.a.", "BiomassDoucha and Lívanský ([@CR29])*Chlorella zofingiensis*P/H0.0310.44305.5Glucose (fructose, galactose, mannose, lactose, sucrose)\\>20AstaxanthinIp and Chen ([@CR57])*Crypthecodinium cohnii*H0.0890.56257.2Glucose (acetate)\\>20DHAJiang and Chen ([@CR61])*Dunaliella* sp.", "P/H\\< 0.010n.a.267.5--8.3Acetate, lactate, glucose, glutamate, glyceroln.a.", "Biomass beta-caroteneGladue and Maxey ([@CR45])*Euglena gracilis*P/H0.0450.43252.8--3.5Glucose, (acetate, alanine, aspartate, asparagine, ethanol, glutamate)n.a.", "Alpha-tocopherolOgbonna et al. ([", "@CR82]), Fujita et al. ([", "@CR41])*Galdieria sulphuraria*P/H0.045--0.0480.48--0.50422Glucose\\>200PhycocyaninSchmidt et al. ([", "@CR100])Sugar beet molasses (fructose, sucrose)\\>350*Haematococcus pulvialis*P/H0.009n.a.258Acetate (glucose, asparagine)\\>1.6Astaxanthin, cantaxanthin, luteinHata et al. ([", "@CR51])*Nannochloropsis oculata*P/H\\< 0.007n.a.267.5--8.3Glucose (ethanol)n.a.", "Biomass, EPAGladue and Maxey ([@CR45])*Nitzschia alba*H0.106n.a.30n. ", "a.Lactate, succinaten.a.", "Biomass, EPALewin and Lewin ([@CR71])Glucose, glutamate*Nitzschia laevis*H0.0170.44208.2Acetate, glucosen.a.", "EPAWen et al. ([", "@CR120]),*Prototheca zopfii*H0.3300.81217.2Glucose (acetate)n.a.[l]{.smallcaps}-Ascorbic acidRunning et al. ([", "@CR98])*Scenedesmus actus*P/H0.040n.a.306Glucose\\>1BiomassOgawa and Aiba ([@CR81])*Schizochytrium sp.*H0.0710.42277Glucose\\>200PUFA, DHA, GLAGanuza et al. ([", "@CR43])*Tetraselmis sueica*P/H0.0280.41257.5Acetate (glucose, glutamine, lactate)n.a.", "Lipids, PUFA n-3 HUFADay and Tsavalos ([@CR23]), Gladue and Maxey ([@CR45])*μ* ~max~ maximum specific growth rate, *Y* ~*x/s*~ biomass yield determined in batch culture at given temperature (*T*), *s* ~inhib~ substrate concentration resulting in a decrease of the specific growth rate and/or biomass yield with the particular substrate, *H* heterotroph, *P* (facultatively) photoautotroph, *n.a.* ", "not available, *DHA* docosahexaenoic acid, *EPA* eicosapentaenoic acid, *GLA* gamma-linolenic acid, *HUFA* highly unsaturated fatty, *PUFA* polyunsaturated fatty acids^a^Substrates known to support heterotrophic growth (adapted from Lee [@CR68])^b^Mainly adapted from Guedes et al. ([", "@CR50]), Raja et al. ([", "@CR91]) and Spolaore et al. ([", "@CR108])\n\nThe specific microalgae's tolerance to certain extracellular substrate concentrations of several grams per litre, as outlined in Table [2](#Tab2){ref-type=\"table\"}, is a feature that also allows particular species to be readily grown to high cell densities in batch culture. *", "Galdieria sulphuraria* reached the highest specific growth rates at glucose concentrations of between 2 and 166 g l^−1^, while a glucose concentration of 200 g l^−1^ was regarded as inhibiting its growth (Schmidt et al. [", "@CR100]). ", "Other highly tolerant species are *Schizochytrium* and *Thraustochytrium*, both known to accumulate large quantities of lipids within their biomass (Jain et al. [", "@CR58]; Kiy et al. [", "@CR62]). ", "Although *Chlorella* sp. ", "principally grow at glucose concentrations of more than 60 g l^−1^ (Ip and Chen [@CR57]), residual concentrations as low as 10 g l^−1^ significantly inhibit their growth (Sansawa and Endo [@CR99]; Wu and Shi [@CR124]; Xiong et al. [", "@CR127]).", "\n\n### Instigating the photosynthetic apparatus in the dark {#Sec8}\n\nMost of the 'classic' microalgal species are recognised primarily as photoautotrophs. ", "Studies on the effect of repeated (and long-term) propagation in the absence of light and using an organic carbon/energy source for the production of substances involved in the photosynthetic apparatus of microalgae are not yet conclusive (Graverholt and Eriksen [@CR47]; Sansawa and Endo [@CR99]; Shen et al. [", "@CR102]; Xiong et al. [", "@CR128]). ", "Some of these substances continue to be synthesised in the dark, for example, the light-harvesting pigment phycocyanin from *G. sulphuraria* (Eriksen [@CR37]).", "\n\nNevertheless, the inability of obligate photoautotrophs to grow and divide without photosynthetically derived energy is often the main obstacle preventing the efficient heterotrophic production of microalgal metabolites. ", "This can be overcome through appropriate genetic engineering, for example, the introduction of a gene encoding a glucose transporter as demonstrated by Zaslavskaia et al. ([", "@CR131]). ", "Another technically driven means involves exploiting mixotrophic cultures, where microalgal cultures are simultaneously exposed to an organic carbon source and light (Liang et al. [", "@CR72]; Liu et al. [", "@CR73]; Chen et al. [", "@CR17]; Sloth et al. [", "@CR106]; Feng et al. [", "@CR40]; Garcia et al. [", "@CR44]; Ma and Chen [@CR76]). ", "These do, however, require specially constructed illuminated bioreactors. ", "It has also been suggested that light-dependent production can be deliberately induced by 'oxidative stress', triggered by substances other than light (e.g. H~2~O~2~ or Fe^2+^; Ip and Chen [@CR56]; Kobayashi et al. [", "@CR64]).", "\n\nComposition of culture media and microalgal biomass {#Sec9}\n---------------------------------------------------\n\nMost of the culture media for growing microalgae in vitro have been developed using, as a base, the stoichiometric composition of the microbial biomass grown under regular physiological conditions (Egli [@CR34]; Egli and Fiechter [@CR35]). ", "Information on the composition of microbial biomass in relation to the formation of a particular product is very limited and may vary depending on species and culture conditions. ", "For natural phytoplankton (representing a heterogeneous consortium of microalgae), the proportions of the elements are typically derived from the 'Redfield ratio' dating back to 1934, suggesting a molar ratio of C~106~N~16~P~1~ as described in Falkowski ([@CR39]). ", "This has recently been further extended to include other important elements (Ho et al. [", "@CR52]; Quigg et al. [", "@CR90]). ", "The stoichiometric composition of phytoplankton is comprehensively reviewed by Klausmeier et al. ([", "@CR63]). ", "For heterotrophic cultures of *Chlorella vulgaris*, a molar stoichiometry of C~3.96~H~7.9~O~1.875~N~0.685~P~0.0539~K~0.036~Mg~0.012~ was determined (Sansawa and Endo [@CR99]), and this has been reflected in optimised media compositions for biomass production in high-cell-density fedbatch processes (e.g. Doucha and Lívanský [@CR29]; Xiong et al. [", "@CR127]). ", "All of the major molecules in microalgae (i.e. proteins, carbohydrates, lipids) contain carbon as the principal element, with oxygen, hydrogen and nitrogen at lower, or even zero, concentrations (Fig.", " [1](#Fig1){ref-type=\"fig\"}). ", "Typically, in media for heterotrophic cultures that support optimal growth, all of the constituents are supplied in stoichiometric excess to the organic carbon source. ", "Applying stoichiometric principles to an established medium for photoautotrophic cultures of *Chlorella* spp. (", "Vonshak [@CR114]), the medium was shown to be deficient in iron, magnesium, sulphur and nitrogen. ", "When optimised, a fivefold increase in biomass concentration was achieved (Mandalam and Palsson [@CR77]). ", "Fig.", " 1Compositional variation in *Chlorella* sp. ", "biomass. *", "Left*, molecular composition, lower and upper limits determined at low and high nitrogen availability in heterotrophic cultures of *C. protothecoides* (adapted from Xiong et al. [", "@CR129]). *", "Right*, proportions of macro and micro elements (adapted from Oh-Hama and Miyachi [@CR84])\n\nFor most of the microalgal species capable of heterotrophic growth, glucose or acetate is an adequate source of energy and carbon (Table [2](#Tab2){ref-type=\"table\"}; Lee [@CR69]; Lee [@CR68]; Perez-Garcia et al. [", "@CR87]). ", "In addition, low-cost media formulations with molasses or carob pulp syrup, or the waste streams from sugar or milk processing industries, have been successfully used as alternatives to glucose (Mendes et al. [", "@CR78]; Schmidt et al. [", "@CR100]). ", "Although microalgae grow with various carbonaceous compounds, glucose is the preferred carbon source because of its ease of handling, accessibility and safety (Lee [@CR69]; Perez-Garcia et al. [", "@CR87]; Sun et al. [", "@CR109]). ", "In particular, glucose is used for the production of high-value compounds where the processes need to be reproducible for prospective regulatory approval for pharmaceutical manufacture. ", "Acetate and ethanol are possible alternatives but, because of their respective corrosive effects or high flammability, are only used when an exceptional productivity enhancement is achieved (de Swaaf et al. [", "@CR25]; de Swaaf et al. [", "@CR26]; Ogbonna et al. [", "@CR82]). ", "Although the cost of (pure) glucose for microalgal production of high-value compounds is less critical than in the biofuel field, opportunities for valorisation of the biomass after isolation of the target compound are desirable. ", "Examples of such valorisation include the subsequent production of animal and fish feed or its use as an energy-rich biomass for the production of biofuels (Brennan and Owende [@CR11]; Chisti [@CR20]).", "\n\nNitrate, ammonia and/or urea are the preferred nitrogen sources at a bioreactor scale (Grobbelaar [@CR49]). ", "Tryptone, glycine and yeast extract have also been evaluated for their potential to enhance growth or product formation (Shen et al. [", "@CR102]). ", "Moreover, growth data suggest that nitrogen source preference might vary between the species (Shen et al. [", "@CR102]; Xiong et al. [", "@CR127]). ", "Yeast extract, a complex component with a high carbon content, is not defined at the single-element level but is frequently used as a source of nitrogen, amino acids, vitamins and trace elements (Grant and Pramer [@CR46]). ", "As its composition varies from lot to lot, supplementation with yeast extract makes precise stoichiometric process control impossible. ", "Moreover, the depletion of some of the components of yeast extract has been shown to result in a linear growth pattern. ", "For example, in a heterotrophic culture with *C. cohnii*, a non-specific nutritional limitation was detected, which coincided with a change from exponential to linear growth while continuously feeding glucose to maintain a residual concentration of between 5 and 20 g l^−1^ (de Swaaf et al. [", "@CR26]). ", "It was concluded that nitrogen, solely derived from the yeast extract, was most probably depleted, resulting in the onset of the linear phase, a cessation of cell division and the diversion of added glucose into the accumulation of lipids within the cell.", "\n\nFurthermore, several microalgae that are grown in pure culture with mineral medium require supplementation with the vitamins cobalamin and/or thiamine (Carvalho et al. [", "@CR13]; Croft et al. [", "@CR22]; Droop [@CR32]). ", "In turn, species capable of endogenously synthesising cobalamin need traces of cobalt (Grobbelaar [@CR49]).", "\n\nHigh-productivity processes {#Sec10}\n===========================\n\nThe development of appropriate strategies for enhancing biomass and/or product formation is based on understanding (Carvalho et al. [", "@CR13]; Grobbelaar [@CR49]; Hu [@CR54]) and exploitation of the flexibility (adaptability) of biomass composition within its upper and lower limits as defined by different culture conditions and/or the altered supply of chemical elements in the culture medium. ", "Achieving the desired (optimum) process performance, however, is far from straightforward, as some objectives are by their very nature contradictory (e.g. the highest product titre vs. the shortest process duration, the highest product purity vs. the highest biomass or product formation rates and yields).", "\n\nHigh cell densities achieved {#Sec11}\n----------------------------\n\nIn the scientific literature concerning the mass cultivation of microalgae, the term 'high-cell-density culture' (HCD) is ill defined but is generally applied to those values of biomass concentration that fall within the range of the highest values published for photoautotrophic or heterotrophic processes. ", "For a photoautotrophic system, the highest biomass concentration achieved to date is 40 g l^−1^ of cell dry weight (CDW) with thin-layer cultures (Doucha and Lívanský [@CR27]). ", "However, in heterotrophic fedbatch cultures of *Chlorella* sp. ", "concentrations ranging from approximately 100 g l^−1^ to greater than 150 g l^−1^ CDW are currently achievable (Table [3](#Tab3){ref-type=\"table\"}; e.g. de Swaaf et al. [", "@CR25]; Doucha and Lívanský [@CR29]; Graverholt and Eriksen [@CR47]; Schmidt et al. [", "@CR100]; Hauser, unpublished data). ", "Typically, such high cell densities are attainable in fedbatch operation where the increasing biomass is retained and thus accumulates in the bioreactor. ", "A highly concentrated solution of the growth substrate is added in a controlled mode, which in turn determines the specific growth rate and limits the concentration of the residual substrate in the culture broth (e.g. glucose concentration in the feed solution ranging from 100 to 570 g l^−1^, where the highest concentration was used by de Swaaf et al. ([", "@CR26])). ", "As the actual data relating to the time courses of the effective (working) culture volume are generally not provided in the publications (Table [3](#Tab3){ref-type=\"table\"}), it is not possible to calculate the amount of biomass produced (in grams) and, thus, the specific growth rates. ", "Table 3Overview of fedbatch strategies for high-cell-density culture heterotrophic cultivations of microalgaeSpecies*x* ~end~*c* ~p,end~Substrate*s* ~0,batch~*s* ~in~*s* ~fb~*s* ~res~*V* ~0~*t (t* ~fb~*)*Control strategyReferences(g l^−1^)(g l^−1^)(g l^−1^)(g l^−1^)(g l^−1^)(g l^−1^)(l)(h)*Chlorella protothecoides*51.2Lipids25.8Glucose19.5100n.d.2--245^a^167 (133)PulsedXiong et al. ([", "@CR127])*Chlorella protothecoides*48.0Lipids0.22Glucose40240n.d.10--302.5240 (147)PulsedShi et al. ([", "@CR104])*Chlorella pyrenoidosa*116.2Biomass*x* ~end~Glucose104992241.2--9.410118.5 (95)StepwiseWu and Shi ([@CR124])*Chlorella regularis*84.0Biomass*x* ~end~Glucose10570n.d.0.5--103030 (24)PulsedSansawa and Endo ([@CR99])*Chlorella vulgaris*117.2Biomass*x* ~end~Glucose655001305--4535^b^32 (16)PulsedDoucha and Lívanský ([@CR29])*Chlorella vulgaris*165.8Biomass*x* ~end~Glucose205002530--17660.5 (11)ExponentialHauser, unpublished data*Chlorella zofingiensis*51.8Astaxanthin0.03Glucose20n.d.n.d.5--202360 (264)PulsedSun et al. ([", "@CR109])*Cryptecodinium cohnii*83.0DHA11.7Ethanol5.58002175--101220 (191)*p*O~2~de Swaaf et al. ([", "@CR25])*Cryptecodinium cohnii*109.0DHA19.0Acetic acid5.751049182∼ 01400 (380)pHde Swaaf et al. ([", "@CR26])*Cryptecodinium cohnii*26.0DHA1.7Glucose5570825--201^c^120 (120)Stepwisede Swaaf et al. ([", "@CR26])*Cryptecodinium cohnii*42.0DHA1.9Carob syrup8.8^d^n.d.n.d.5--10^d^1.25100.4*p*O~2~Mendes et al. ([", "@CR78])*Euglena gracilis*48.0α-Tocopherol0.01Glucose15696n.d.\\> 12.5^a^182 (151)PulsedOgbonna et al. ([", "@CR82])*Euglena gracilis*39.5α-Tocopherol0.04Ethanol15800n.d.\\> 12.5^a^455 (433)PulsedOgbonna et al. ([", "@CR82])*Galdieria sulphuraria*109.0Phycocyanin2.9Glucose50500157\\<0.51.2336 (144)StepwiseGraverholt and Eriksen ([@CR47])*Galdieria sulphuraria*72.0Phycocyanin0.28Glucose50500178\\<0.31.5250 (115)*p*O~2~Schmidt et al. ([", "@CR100])*Galdieria sulphuraria*116.0Phycocyanin0.35Molasses52.5^d^750356^d^2--5^d^1.5^d^338 (172)*p*O~2~Schmidt et al. ([", "@CR100])*Nitzschia laevis*22.1EPA0.70Glucose2040022\\<31.5336 (192)StepwiseWen et al. ([", "@CR120])*Nitzschia laevis*40.0EPA1.1Glucose205045\\<62.2336 (216)StepwiseWen and Chen ([@CR118])*x* ~end~ concentration of biomass (determined as cell dry weight, CDW) at the process end point, *c* ~p,end~ concentration of particular products (docosahexaenoic acid, eicosapentaenoic acid) at the process end point, *s* ~0,batch~ initial substrate concentration in batch phase, *s* ~in~ substrate concentration of the feed solution added, *s* ~fb~ accumulated amount of substrate added during the fedbatch phase per litre of the final volume, *s* ~res~ residual substrate concentration in bulk medium during the fedbatch phase, *V* ~*0*~ initial culture volume, i.e. working volume or reactor volume, where *V* ~0~ is not available, scale-up was reported to be 200 l or 120 m^3^ in Apt and Behrens ([@CR1]), *t* total process duration with *t* ~fb~ as duration of the fedbatch phase, *control strategy* being either a predefined stepwise or exponentially increasing rate of substrate feed, pulsed addition of substrate or substrate addition resulting from a feedback control within defined limits of dissolved oxygen concentration (*p*O~2~) or pH, *n.d.* ", "not determinable from the data provided in the paper, *DHA* docosahexaenoic acid, *EPA* eicosapentaenoic acid^a^Reactor volume^b^200 l^c^120 m^3d^Given in g glucose\n\nFurthermore, biomass concentrations of more than 40 g l^−1^ CDW have been achieved in batch cultures with the few microalgal genera that tolerate exceptionally high substrate concentrations (Table [2](#Tab2){ref-type=\"table\"}; e.g. *Galdieria*, *Schizochytrium* and *Thraustochytrium* in Schmidt et al. [", "@CR100]; Jain et al. [", "@CR58]; Kiy et al. [", "@CR62], respectively). ", "For instance, high-cell-density batch cultures with the obligate heterotrophic *Prototheca* sp. ", "and *Aurantiochytrium* sp. ", "were described by Running et al. ([", "@CR98]) and Jakobsen et al. ([", "@CR59]), respectively. ", "In the latter, the cell dry weight increased from 40 to 90 g l^−1^ during a post-exponential growth phase while the lipid content of the biomass increased between circa 10% and 60%. ", "In this context, the term 'biomass growth' needs to be differentiated as either the cells' proliferation due to cell division or an increase in cell mass not directly linked to an increase in cell number.", "\n\nDo high-cell-density culture and rapid growth imply high productivity? {#", "Sec12}\n----------------------------------------------------------------------\n\nAlthough microalgal biomass is the only target in some processes (Becker [@CR4]; Brown et al. [", "@CR12]; Doucha et al. [", "@CR30]; Duerr et al. [", "@CR33]; Tokusoglu and Unal [@CR111]), the apparent prime focus on HCD cultures often obscures the ultimate objective for any microalgal process, which is to achieve the highest product concentration of the desired quality in the shortest possible time. ", "From the basic data summarised in Table [3](#Tab3){ref-type=\"table\"}, the product to biomass yield (*Y* ~*p*/*x*~, in g g^−1^) and the volumetric productivities (*r* ~*x*~ or *r* ~*p*~, in g l^−1^ h^−1^) can be calculated. ", "In principle, however, interpreting productivities that have been computed on the basis of average values for the whole process duration can be misleading.", "\n\nMaintaining growth at the maximum specific growth rate (*μ*, in h^−1^) does not often correlate with the highest attainable rate of specific product formation (*q* ~p,~ in g g^−1^ h^−1^). ", "Generally, the kinetic models accepted of microbial growth association also apply for microalgae. ", "For instance, in continuous cultures, the maximum production of EPA by photoautotrophically grown *Nannochloropsis* sp. ", "was achieved at dilution rates in the range of 0.004--0.013 h^−1^ while maximum biomass productivity was obtained at higher dilution rates ranging between 0.011 and 0.017 h^−1^ (Zou et al. [", "@CR135]). ", "Similarly, the highest DHA content as well as the highest degree of fatty acid unsaturation of *Crypthecodinium cohnii* was measured at low glucose concentrations (5 g l^−1^) and thus at a slow growth rate (Jiang and Chen [@CR61]). ", "The formation of EPA by *Nitschia laevis* in continuous heterotrophic culture was, on the contrary, reported to occur at a higher dilution rate and higher glucose concentration than maximum growth (Wen and Chen [@CR119]). ", "A positive growth association was however reported to apply to the biosynthesis of astaxanthin in *Chlorella zofingiensis* (Wang and Peng [@CR117]). ", "The above information illustrates that product formation kinetics can fall into either positive or non-/negative growth-associated product formation or a combination of both. ", "Especially in those cases where product formation is not correlated with maximal growth, it is advantageous to have full control over the specific growth rate. ", "In general, such fine-tuning of growth is achieved by the controlled addition of medium constituents in fedbatch cultivation.", "\n\nDifferent carbon substrates lead to different biomass/substrate yields and also affect the formation of the targeted product. ", "As a consequence, maximum product formation does not always correlate with maximum biomass concentration. ", "For instance, in a culture of *C. cohnii* grown with acetic acid, 77 g l^−1^ of biomass and 9.5 g l^−1^ of docosahexaenoic acid (DHA) were harvested after 210 h (de Swaaf et al. [", "@CR26]). ", "In an alternative process strategy using ethanol as the carbon and energy source, less biomass (59 g l^−1^) generated more DHA (10.4 g l^−1^) in a shorter period of time (200 h; de Swaaf et al. [", "@CR25]). ", "In another example, *Euglena gracilis* grown with glucose reached 48 g l^−1^ of biomass and 150 μg g~CDW~^−1^ of α-tocopherol in 182 h (Ogbonna et al. [", "@CR82]). ", "When fed with ethanol, the growth slowed significantly; however, the product yield was enhanced by a factor of approximately 10, reaching 1,200 μg g~CDW~^−1^ and 39.5 g l^−1^ of biomass in 455 h.\n\nAs biomass growth slows, for instance, due to the effect of temperature or restricted substrate availability, cell division decelerates and the formation of storage products typically increases simultaneously. ", "PUFA synthesis in certain species, such as eicosapentaenoic acid in *Chlorella minutissima*, has been reported to occur preferentially at temperatures lower than those required for optimal growth (Yongmanitchai and Ward [@CR130]). ", "However, in the diatom *Phaeodactylum tricornutum*, maximum product yield and maximum biomass concentration were achieved at the same cultivation temperature between 21.5 and 23 °C. ", "In contrast, the lutein yield (*Y* ~*p/x*~) of heterotrophically grown *Chlorella protothecoides* was increased from 4.25 to 4.59 mg g^−1^ by raising the cultivation temperature from 24 to 35 °C (Shi et al. [", "@CR105]).", "\n\nStrategies to enhance productivity in fedbatch cultures {#Sec13}\n-------------------------------------------------------\n\nFedbatch cultivation is the most effective technique for reaching high biomass concentrations in a short time and controlled manner. ", "Typically, this is achieved in cultures grown heterotrophically through controlling the rate of addition of the organic carbon and energy source (i.e. the substrate feed). ", "Varying feed strategies can lead to different efficiencies of biomass and/or product formation.", "\n\nIn contrast to batch mode, osmotic or toxic effects due to high substrate concentrations can be avoided in a fedbatch culture. ", "Moreover, perfusion technology (with cell retention but exchange of culture medium) is appropriate when inhibitory metabolites, which would otherwise affect biomass growth or product formation, need to be removed (Wen and Chen [@CR118]). ", "Auto-inhibition effects have been described in the literature for the cultivation of different species or desired products, such as fatty acids (Bosma et al. [", "@CR8]; Javanmardian and Palsson [@CR60]; Zou et al. [", "@CR135]).", "\n\nThe microalgal high-cell-density processes described in the literature (Table [3](#Tab3){ref-type=\"table\"}) employ several different strategies for substrate addition, which are optimised with respect to both the physiological requirements of the particular species and the technical restrictions of the available equipment. ", "The majority of heterotrophic processes employing fedbatch mode, and using microalgae to produce high-value compounds that have been described systematically in recent publications, concentrate on some five to ten species and can be categorised by their target product as follows: Polyunsaturated fatty acids, like DHA (Chi et al. [", "@CR19]; de Swaaf et al. [", "@CR26]; Ganuza and Izquierdo [@CR42]) and EPA (Wen and Chen [@CR118]; Wen et al. [", "@CR120]), using *C. cohnii*, *Nitzschia laevis*, *Schizochytrium* sp. ", "or *Ulkenia* sp.", "Carotenoids, like astaxanthin (Sun et al. [", "@CR109]) and lutein (Shi et al. [", "@CR104]), using *Chlorella* sp., ", "and tocopherols with *E. gracilis* (Ogbonna et al. [", "@CR82])Phycobiliproteins like phycocyanin using *G. sulphuraria* (Graverholt and Eriksen [@CR47]; Schmidt et al. [", "@CR100])\n\nThe principal differences of the fedbatch processes listed in Table [2](#Tab2){ref-type=\"table\"} are (1) the cells' physiological state which is both affected by unrestricted or controlled substrate availability, (2) the limited (since controlled) availability of an element other than carbon and (3) the control strategy, which is either a predefined open-loop control or a feedback control (closed loop).", "\n\n### Pulsed addition of an organic carbon and energy source {#Sec14}\n\nThe pulsed addition of a carbon source is frequently employed in the high-cell-density cultivation of *Chlorella* sp. (", "Doucha and Lívanský [@CR29]; Sansawa and Endo [@CR99]; Shi et al. [", "@CR104]; Sun et al. [", "@CR109]; Xiong et al. [", "@CR127]) and has also been applied in processes with *E. gracilis* (Ogbonna et al. [", "@CR82]) and *G. sulphuraria* (Schmidt et al. [", "@CR100]). ", "Following the depletion of the substrate during an initial batch phase, the residual glucose concentration in the bioreactor is typically maintained within pre-determined upper and lower concentration limits. ", "With *C. zofingiensis* and *C. protothecoides*, the upper limits were set at concentrations of approximately 24 or 30 g l^−1^, respectively. ", "Higher levels would have inhibited biomass growth (Sansawa and Endo [@CR99]; Shi et al. [", "@CR104]; Sun et al. [", "@CR109]; Xiong et al. [", "@CR127]). ", "The pulsed addition of a highly concentrated substrate solution was repeatedly triggered (about five to seven times during the entire process) whenever the glucose concentration dropped below a defined concentration of several grams per litre (Fig.", " [2](#Fig2){ref-type=\"fig\"}). ", "As described in a later section on feedback control strategies, overdosing with substrate can be prevented by implementing an automated dosing strategy based on monitoring the dissolved oxygen concentration. ", "Fig.", " 2Principles of controlling growth and product formation through different modes of substrate addition. ", "The three pictograms in each row show (from *left* to *right*) the time dependence of the following variables within the fedbatch phase of a bioreactor cultivation of *C. vulgaris* and their maximum (*max*), minimum (*min*), optimum (*opt*) or residual (*res*) values as indicated by the *horizontal dashed lines*: specific growth rate (*μ*), specific substrate utilisation rate (*q* ~*s*~) and specific product formation rate (*q* ~*p*~); concentrations of biomass (*x*) and the growth-limiting substrate (*s*) in the bioreactor, where the substrate concentration in the bioreactor was either determined by pulsed addition at predefined limits (*s* \\> *s* ~1~ and *s* \\< *s* ~2~) or reached a residual concentration (*s* ~res~) below which the substrate cannot be utilised at the particular specific growth rate; mode of substrate addition. ", "In the *left-hand* pictograms, growth-associated kinetics of the product formation was applied accordingly to the formula: *q* ~p~ = *Y* ~*p/x*~ · *μ*, where *Y* ~*p/x*~ is a constant product yield per biomass coefficient. ", "A constant specific growth rate near to its maximum (*μ* ~max~) and correspondingly exponentially increasing biomass concentration is achieved with pulsed substrate addition (first row, derived from the data of Doucha and Lívanský [@CR29]). ", "With continuous substrate addition and an exponentially increasing feed rate (*second row*), a desired constant specific growth rate (*μ* ~opt~ \\< *μ* ~max~) is controlled at the optimum for product formation. ", "To reach near-optimum conditions, the exponential addition can also be approximated by a stepwise increasing feed rate (*dashed step-like line*)\n\nPulsed fedbatch strategies are therefore appropriate to species where growth is inhibited by very high substrate concentrations but where residual substrate concentrations of several grams per litre can be tolerated. ", "Biomass is developed at the highest specific growth rates when growth occurs in the continuous presence of an excess of substrate and in a balanced medium. ", "The values for a specific growth rate achieved in such fedbatch processes are comparable to those rates attained during unrestricted, exponential growth in a batch culture (e.g. *μ* ~max~ \\> 0.18 h^−1^ for *C. vulgaris*; Doucha and Lívanský [@CR29]). ", "The pulsed fedbatch strategy is applicable to systems required to produce compounds where formation is tightly associated with fast biomass growth. ", "In addition, the combined production strategies can be applied to systems where rapidly built biomass is essential during the first process phase, prior to a subsequent differently controlled phase that promotes product formation (e.g. Ganuza et al. [", "@CR43]; Hata et al. [", "@CR51]).", "\n\n### Continuous addition of an organic carbon and energy source {#Sec15}\n\nPotential strategies for continuous substrate addition are usually categorised using mathematical functions that describe the time dependence of the rate of substrate addition (i.e. the feed profile). ", "Such strategies encompass substrate addition at constant or predefined rates. ", "Predefined rates can increase or decrease following linear or exponential functions or by equivalent, stepwise approximations (Fig.", " [2](#Fig2){ref-type=\"fig\"}). ", "However, the only feed profiles that are currently used to grow microalgae are those with stepwise increasing or decreasing feed rates (for example, *Chlorella*, *Crypthecodinium*, *Galdieria* and *Nitzschia* by Wu and Shi ([@CR124]), de Swaaf et al. ([", "@CR25]), Graverholt and Eriksen ([@CR47]) and Wen and Chen ([@CR118]), respectively).", "\n\nThe optimum feed profile for product formation can be determined by using a rational approach provided that the effect of appropriate control variables (including *μ*) on the targeted productivity has been quantified and, preferably, captured in a model (Wu and Shi [@CR124]; Zhang et al. [", "@CR132]; Zhang et al. [", "@CR133]; Zhang et al. [", "@CR134]). ", "In addition, models based on hybrid neural networks can be used to predict optimum fedbatch strategies. ", "A feed profile that included an exponentially increasing glucose addition over several steps, each at a constant feed rate, was successfully applied to a *Chlorella pyrenoidosa* culture to attain a biomass concentration of 116 g l^−1^ at an average productivity of 1.02 g l^−1^ h^−1^ (Wu and Shi [@CR124]). ", "Similarly, with a culture of *G. sulphuraria*, the feed rate was increased up to 3.7 times in one step per day, achieving 27.8 g l^−1^ of biomass and an average productivity of approximately 0.33 g l^−1^ h^−1^ (Graverholt and Eriksen [@CR47]). ", "Following an initial batch culture, the substrate was continuously added at a specific rate, which was lower than the specific glucose utilisation rate required to support the biomass, i.e. a *μ* ~max~ of 0.053 h^−1^. Residual glucose concentrations were maintained below 0.5 g l^−1^ and the specific growth rate was controlled at 0.046 h^−1^ during the fedbatch phase.", "\n\nSpecific growth rate can be controlled at a particular defined rate, lower than its maximum, by continuous (preferably exponential) substrate addition. ", "This allows product formation to be enhanced when its optimum is not linked to the fastest biomass growth (as illustrated in the pictograms in Fig.", " [2](#Fig2){ref-type=\"fig\"}). ", "However, the strategy of controlling the *μ* at a certain (optimum) value as demonstrated with bacteria and yeast has not yet been described in the literature on microalgae.", "\n\n### Substrate addition determined by feedback control {#Sec16}\n\nA feedback control strategy allows a continuous adaptation of the rate of substrate addition based on physiological criteria, such as the production of acids or bases (de Swaaf et al. [", "@CR26]), or oxygen utilisation (de Swaaf et al. [", "@CR25]; Schmidt et al. [", "@CR100]). ", "The changes in pH and *p*O~2~ values resulting from biomass growth (or product formation) are countered up to a predefined value.", "\n\nIn an auxostat-fedbatch system with *Schizochyrium* sp., ", "the pH was continuously controlled at a value of 7 through the addition of ammonium hydroxide solution (Ganuza et al. [", "@CR43]). ", "In this manner, both pH and an excess of nitrogen were controlled while the growth of the biomass reflected the utilisation of the carbon substrate. ", "The substantial technical benefit of such a system is the potential to replace the ammonium hydroxide solution used for pH control with a potassium hydroxide solution. ", "In this way, the desired onset of the production of lipids (DHA) is readily triggered through nitrogen deprivation (i.e. the nitrogen level decreases to zero from the concentration accumulated during the ammonium hydroxide addition phase). ", "Effectively, this process strategy is fedbatch with respect to the nitrogen addition but is batch with respect to the (carbon) growth substrate. ", "In a fedbatch process producing DHA with *C. cohnii* (de Swaaf et al. [", "@CR25]), the acetic acid used as the carbon/energy substrate was added via a pH control system to maintain a pH of 6.5. ", "This resulted in the continuous addition of acetic acid at a rate which followed a time course determined by the metabolic requirements of the biomass.", "\n\nFeedback control based on the dissolved oxygen concentration (*p*O~2~ or DO) is another process strategy that is technically feasible to prevent overdosing of the substrate. ", "As determination of the residual concentration of the substrate typically involves a time delay, monitoring the decrease/increase in *p*O~2~ has the advantage such that the pulsed addition of substrate can be appropriately timed (Schmidt et al. [", "@CR100]).", "\n\nStrategies for customising biomass composition by adapting the culture medium {#Sec17}\n-----------------------------------------------------------------------------\n\nThe following strategies, potentially combined with fedbatch culture, allow product formation or biomass composition to be further controlled: Controlling the availability of components in the growth medium other than carbonReplacing a medium component with an alternative (e.g. using a different carbon or nitrogen source or exchanging sulphur with selenium)Adapting the culture conditions (for example, *T*, *p*O~2~, pH) to conditions that would typically be outside of the optimal range for biomass growth\n\n### Affecting the proportions of macromolecules within the biomass {#Sec18}\n\nBiomass composition can be customised and/or product formation can be enhanced through tailoring the composition of the culture medium. ", "The latter is achieved by controlling the consumption of a particular element through ensuring that its supply and, thus, availability are limited. ", "An example of this principle is seen in the range of biomass composition achievable with *C. protothecoides* (Fig.", " [1](#Fig1){ref-type=\"fig\"}).", "\n\nLipid content has been reported to increase under nutrient-deprived conditions such as low concentrations of nitrogen (Griffiths and Harrison [@CR48]; Hsieh and Wu [@CR53]; Illman et al. [", "@CR55]; Jakobsen et al. [", "@CR59]; Lv et al. [", "@CR74]; Lynn et al. [", "@CR75]; Rodolfi et al. [", "@CR95]; Widjaja et al. [", "@CR121]; Yongmanitchai and Ward [@CR130]), phosphorus (Lynn et al. [", "@CR75]; Reitan et al. [", "@CR93]; Rodolfi et al. [", "@CR95]) and silicon (Griffiths and Harrison [@CR48]; Lynn et al. [", "@CR75]). ", "Low nitrogen concentrations were also reported to increase the cellular contents of lutein in *C. protothecoides* (Shi et al. [", "@CR104]) and astaxanthin in *C. zofingiensis* (Ip and Chen [@CR57]).", "\n\nN-deprivation regimes are most frequently expressed as the molar carbon-to-nitrogen (C-to-N) ratio (Ip and Chen [@CR57]; Shi et al. [", "@CR104]; Sloth et al. [", "@CR106]; Wen et al. [", "@CR120]). ", "Grown at a high C-to-N ratio, the cell dry mass of *C. protothecoides* contained up to 53.8% lipids compared to 25.2% obtained in low C-to-N medium. ", "This lipid increase was accompanied by a drop in protein content from 25.8% at low C-to-N to 10.5% at a high C-to-N ratio (Xiong et al. [", "@CR129]).", "\n\n### Biomass enrichment by replacing its constituents {#Sec19}\n\nThe enrichment of the microalgal biomass with (readily bio-available) selenium at extraordinarily high volumetric productivities and final concentrations (\\> 0.4 mg Se per gram of biomass) is governed by a different mechanism than the enrichment by lipids. ", "Microalgae, which are grown in medium containing a lower-than-stoichiometrically-required concentration of sulphur, are exposed to inorganic selenium in the form of selenite. ", "Depending on the algae species, the cells are capable of incorporating the element at different levels, preferentially into intracellular protein, e.g. *C. vulgaris* or *Scenedesmus quadricauda* in Doucha et al. ([", "@CR30]) and Umysová et al. ([", "@CR113]), respectively.", "\n\nConclusions and future trends {#Sec20}\n=============================\n\nRecent advances in microalgal biotechnology have created opportunities for the efficient production of high-value (natural) compounds with the properties of plant-derived products that provide unique benefits (e.g. plant-like glycosylation) compared to their analogues resulting from chemical synthesis or recombinant microorganisms. ", "The laboratory-scale bioreactor cultivations included within this review provide a first insight into the feasibility of carrying out heterotrophic processes with microalgae at an industrial scale. ", "These processes have, in part, already been commercialised with the biotechnological production of PUFA. (", "To date, the authors are not aware of any literature on the heterotrophic large-scale fedbatch cultivation of microalgae, in contrast to literature on batch cultivation referred to by Apt and Behrens [@CR1]; Behrens [@CR5]; Wynn et al. [", "@CR126]). ", "This review confirms that the development of efficient, economically feasible large-scale bioprocesses remains an obstacle to the commercialisation of the promising microalgae technology.", "\n\nThe generic cultivation strategies outlined are based on the experimental data of natural microalgae but, in principle, could also be applied to emerging strains improved by genetic engineering. ", "Fundamental knowledge enabling strain design may be derived from advanced metabolic flux analyses (Xiong et al. [", "@CR129]). ", "A promising new avenue for transgenic microalgae is developing based on the knowledge gained over the past two decades, which includes the complete sequencing of the first microalgal genomes (Leon-Banares et al. [", "@CR70]; Parker et al. [", "@CR86]; Rosenberg et al. [", "@CR96]; Walker et al. [", "@CR115]; Walker et al. [", "@CR116]).", "\n\nThe authors wish to thank Christian Meier and Katerina Bisova for their generous help in collecting and evaluating the wealth of information available. ", "In particular, Petr Hyka, Dominik Lüthy and Ganna Aleshcheva are acknowledged for spending considerable time on designing and finalising the drawings and Michael Cook for critical proofreading.", "\n\nOpen Access {#d30e4054}\n===========\n\nThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Texting and Driving Leads to Collision Repair Salt Lake City\n\nThe Best Auto Resources readership should be well aware that texting and driving in Salt Lake City leads to requiring the services of a collision repair Salt Lake City and worse. ", "Distracted driving is on the upswing in the United States and we think it is fair to lay the blame squarely in the lap of the smartphone. ", "Distracted driving leads to car accidents and car accidents lead the car straight to the collision repair shop. ", "With any luck the passengers in the cars will emerge from the accident with only minor scrapes and bruises but all too often they will emerge with major injuries or (heaven forbid) not emerge at all.", "\n\nThe way to avoid heading to the collision repair shop is to stop texting while driving. ", "Of course there are other ways to wind up in a collision repair shop but the simple act of refraining from texting while driving will go a long way towards avoiding ending up in a collision repair shop. ", "Accordingly, once one makes the decision to stop texting while driving once and for all he or she must then take steps to minimize the other factors that could potentially lead to a car accident.", "\n\nEven if every step that could potentially be taken to avoid a car accident it is still impossible to eliminate car accidents entirely. ", "This is true because one can never account for the actions of others. ", "In other words, no matter how safe you are as a driver, another driver could be acting irresponsible and cause an accident through no fault of your own. ", "Perhaps the only way to avoid an accident is entirely is to not drive at all. ", "Even then a car could run you over unless you happen to be standing in a location inaccessible to cars." ]

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[ "You can help to support this show and the rest of the Suicide Squadcast Network through Patreon at this link! ", "Thank you for your support!", "\n\nIn this episode, Tim and Scott talk about:\n\nThe petition for the Zack Snyder cut was hacked.", "\n\nPotential artwork for the Justice League Steelbook was revealed.", "\n\nFilming is reported to begin in early 2018 for Shazam at the Pinewood studios in Toronto!", "\n\nDirector David Sandberg gives his recommended reading for Shazam!", "\n\nCooper Andrews has joined the cast of Shazam!", "\n\nThe first set photo has been revealed for Shazam!", "\n\nDirector David Ayer says that Gotham City Sirens is still in development!", "\n\nThe Question is slated to appear soon on either the big or small screens!", "\n\nDeathstroke is reportedly unavailable again for the Arrowverse.", "\n\nAnd we take a bunch of listener questions!", "\n\nWe discuss all of this, and much, much more!", "\n\nWhere to find us:\n\nFollow The Suicide Squadcast on Twitter at @SuicideSquadcst\n\nFollow Tim on Twitter at @Allenfire\n\nFollow Scott on Twitter at @ScottDC27\n\nEmail us at [email protected]\n\nSubscribe to The Suicide Squadcast Network:\n\nThe show's intro music was composed by Tim Yoko. ", "The show's outro music was composed by Jordan Funk.", "\n\nWe are a proud member of the Batman Podcast Network! ", "Please go check out the other great shows that can be found there!" ]

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[ "'A true partner around the table?' ", "Perceptions of how to strengthen public health's contributions to the alcohol licensing process.", "\nThere are increased opportunities for public health practitioners (PHPs) in England to shape alcohol availability and reduce harms through a statutory role in licensing processes in local government. ", "However, how public health can effectively influence alcohol licence decision-making is little understood. ", "A mixed methods study was conducted to identify challenges faced by PHPs and mechanisms to strengthen their role. ", "This involved a survey of practitioners across London local authorities (n = 18) and four focus group discussions with a range of licensing stakeholders (n = 36). ", "Survey results indicated a varied picture of workload, capacity to respond to licence applications and levels of influence over decision-making among PHPs in London. ", "Practitioners described a felt lack of status within the licence process, and difficulties using and communicating public health evidence effectively, without a health licensing objective. ", "Strategies considered supportive included engaging with other responsible authorities and developing understanding and relationships over time. ", "Against political and resource constraints at local and national government levels, pragmatic approaches for strengthening public health influence over alcohol licensing are required, including promoting relationships between stakeholders and offering opportunities for PHPs to share best practice about making effective contributions to licensing." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nRegular Expression of patterns.", "EMAIL_ADDRESS\n\nDoes anyone know what the exact regular expression of androids patterns.", "EMAIL_ADDRESS uses?", "\nI need to use the same pattern for PHP. ", "Thank you.", "\n\nA:\n\nthis is how PHP filter email\n$Email = \"[email protected]\";\n\nif (filter_var($Email, FILTER_VALIDATE_EMAIL))\n echo \"Email Is Valid\";\nelse\n echo \"Email Isn't Valid\";\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Life stress and clinically elevated MMPI scales: gender differences in the moderating influence of coping.", "\nCoping styles were evaluated as moderators of life stress-psychopathology relationships. ", "Five hundred twenty-one undergraduates (271 females and 250 males) completed the Life Experiences Survey, the Coping Strategies Inventory, and the MMPI. ", "To assess maladaptive coping styles, groups were constructed for each of 8 clinical scales (Hs, D, Hy, Pd, Pa, Pt, Sc, and Ma) composed of all subjects with a clinically significant elevation on that scale. ", "The coping styles of these \"clinical\" groups were compared to the coping styles of \"normal\" groups, made up of subjects whose life stress scores were approximately the same but whose corresponding MMPI scale scores were within normal limits. ", "To assess adaptive coping styles, a group of effective copers (with high life stress but normal MMPI profiles) was compared to a group of less effective copers (with high life stress but with at least one scale outside of normal limits). ", "All groups were constructed separately for gender. ", "The predicted gender differences and specific coping style-psychopathology relationships were, by and large, found. ", "Coping style differences between the effective and less effective copers were also found. ", "These findings suggest that several coping styles are important moderators of life event stress-psychopathology relationships." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Phylogenetic relatedness limits co-occurrence at fine spatial scales: evidence from the schoenoid sedges (Cyperaceae: Schoeneae) of the Cape Floristic Region, South Africa.", "\nSpecies co-occurrence at fine spatial scales is expected to be nonrandom with respect to phylogeny because of the joint effects of evolutionary (trait convergence and conservatism) and ecological (competitive exclusion and habitat filtering) processes. ", "We use data from 11 existing vegetation surveys to test whether co-occurrence in schoenoid sedge assemblages in the Cape Floristic Region shows significant phylogenetic structuring and to examine whether this changes with the phylogenetic scale of the analysis. ", "We provide evidence for phylogenetic overdispersion in an alliance of closely related species (the reticulate-sheathed Tetraria clade) using both quantile regression analysis and a comparison between the mean observed and expected phylogenetic distances between co-occurring species. ", "Similar patterns are not evident when the analyses are performed at a broader phylogenetic scale. ", "Examination of six functional traits suggests a general pattern of trait conservatism within the reticulate-sheathed Tetraria clade, suggesting a potential role for interspecific competition in structuring co-occurrence within this group. ", "We suggest that phylogenetic overdispersion of communities may be common throughout many of the Cape lineages, since interspecific interactions are likely intensified in lineages with large numbers of species restricted to a small geographic area, and we discuss the potential implications for patterns of diversity in the Cape." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "25 year anniversary of the link between the North and the Black Sea\n\n25 year anniversary of the link between the North and the Black Sea\n\nTo celebrate the 25th anniversary of the Main-Danube Canal, the Bavarian State Chancellery invited to a trip in the Altmühltal valley on 8 September 2017 together with Federal Minister of Transport Alexander Dobrindt and Joachim Herrmann, Bavarian Minister of Internal Affairs, Construction and Transport. ", "Martin Staats (MSG eG), President of the Federal Association of German Inland Navigation(BDB), and BDB Vice President Friedrich Weigert (Kuehne + Nagel Euroshipping GmbH), BDB Board Member Andreas Dicke (Bavaria Schiffahrts- und Speditions-AG) participated in the event.", "\n\nOn the occasion of this anniversary, BDB President Martin Staats emphasized: “The Main Danube Canal has finally closed the gap between the North Sea and the Black Sea and facilitated transporting goods on the waterway across Europe. ", "It is not only a great achievement in water engineering, but is also particularly important for securing prosperity in Bavaria,” he stressed.", "\n\nAn appreciation of the 171 kilometers waterway, connecting the Main at Bamberg with the Danube in Kelheim, which was approved for transport on 25 September 1992, is more than appropriate. ", "With a construction period of 32 years the canal was a “mammoth project”. ", "This is also reflected by the fact that no more waterway project of this magnitude has been implemented in Germany since then.", "\n\nOn average, 6.7 million tonnes of goods have been transported on the canal annually since 1992, with a peak of just under 9 million tonnes – thus surpassing the expectations previous to the construction. ", "The canalplays a major role in the German and European waterway network, particularly for the transport of bulk goods such as food and feed (28% of the total transport volume in 2016), fertilizers (16%), agricultural and forestry products (15%) as well as iron, steel and others Metals (12%)." ]

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[ "Q:\n\nif size == 4,7,10,13, .... so on... in jQuery\n\nI know i can do like this...\nif (Size == 4 | Size == 7 | Size == 10 | Size == 13 | Size == 16 | Size == 19)\n{alert(\"Yes!\")}", "\n\nBut any better coding ?", "\n\nA:\n\nif(Size%3==1&&Size<20&&Size>3 )\n{alert(\"yes\");}\n\nA:\n\nYou can use jQuery.inArray :\nif (jQuery.inArray(Size, [4, 7, 10, 13, 16, 19])>=0) {\n\nNote that the goal can only be readability, not performances.", "\nIf you have only those 6 values and if they never change, the ugly if you made (with || instead of |) is a perfectly correct solution.", "\n\nA:\n\nswitch (Size) {\n case 4:\n case 7:\n case 10:\n case 13:\n case 16:\n case 19:\n alert(\"Yes!\");", "\n}\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Oxford University Scientific Society\n\nThe Oxford University Scientific Society (OUSS) is a student scientific society at the University of Oxford. ", "It was founded in 1882 as the Oxford University Junior Scientific Club. ", "It is one of the oldest undergraduate science societies in the world. ", "It organizes talks on scientific subjects on a weekly basis.", "\n\nFormer speakers include Nobel prize laureates (John E. Walker, Peter Mansfield, Peter J. Ratcliffe) and other well-known scientists (Roger Penrose, Richard Dawkins).", "\n\nOUSS also organizes visits to places of scientific interest, which have included tours of the Bodleian Library, Museum of the History of Science, TOAD distillery in Oxford, the Joint European Torus project, and the National Space Centre in Leicester. ", "In April 2012 they held a large-scale debate on gerontology at the Sheldonian Theatre between Aubrey de Grey and Colin Blakemore, chaired by Sir Richard Peto.", "\n\nHistory \n\nOxford University increased its provision for science in the second half of 19th century, with the first scientific degree awarded in 1850. ", "A number of scientific ventures were undertaken, including the building of the Pitt Rivers Museum and the Clarendon Lab, and the proportion of undergraduates doing a scientific degree increased every year.", "\n\nOxford University Junior Scientific Club was founded in November 1882. ", "At that time there were around 25 students admitted to a scientific course every year (they accounted for 7% of the student body) and most of them soon joined the newly formed society. ", "Edward Poulton and Halford Mackinder were among its founders.<ref>Oxford University Junior Scientific Club. ", "Nature, Volume 137, Issue 3475, pp. ", "941 (1936). ", "</ref> The Club aimed to \"bring together undergraduate and bachelor of arts members of the University for the discussion of scientific matters\". ", "After one year four fifths of students doing studying science were members of the club, and it also attracted members studying non-scientific disciplines. ", "Graduates often stayed connected with the club after leaving the university. ", "In 1889 it had 102 members, and in 1894, around 200, and this number stayed approximately the same until the First World War.", "\n\nDuring first 30 years of its existence the club served as a platform to integrate science undergraduates as well as recent graduates and allowed them to present their original research. ", "Although the society invited senior university members and distinguished academics to speak during so-called \"special meetings\", its main events were the fortnightly \"ordinary meetings\", in which papers about recent developments in science or about original research were read. ", "Originally around half of those papers were read by current undergraduates, although it changed with time in favour of the graduate speakers. ", "With no research degrees in Oxford, the ordinary meetings were one of the few opportunities for graduates to arouse interest about their scientific work. ", "Famous students involved in those early years of the Junior Scientific Club include Nevil Sidgwick, Frederick Soddy, Henry Moseley and Julian Huxley.", "\n\nSpecial meetings with distinguished academics developed into an annual series of \"Boyle Lectures\", endowed and published from the society's subscription. ", "Among the people who delivered those lectures were William Ramsay, Lord Kelvin and Henry Acland. ", "Some of those lectures have been subsequently made into books. ", "Once every two years the Club organized science festivals, called \"conversaziones\", in the Pitt Rivers Museum. ", "Conversaziones comprised popular-level lectures and exhibitions in Pitt Rivers. ", "They attracted around 1000 people from around Oxford. ", "One of such conversaziones was described in the journal Nature from 6 July 1936.", "\n\nThe club published its own journal, the Journal of the Oxford University Junior Scientific Club. ", "It was edited every term from 1887 to 1912 and also after the First World War. ", "Its style and composition were similar to other contemporary science periodicals, with some numbers containing as many as 100 pages. ", "The articles were devoted to the papers read at the society's meetings or to general scientific developments. ", "The journal also contained notes about current and former members of the club. ", "In 1897 it was renamed Transactions of the Oxford University Junior Scientific Club''.", "\n\nBy the beginning of the 20th century some specialized scientific societies were set up in Oxford and they were better suited for presenting undergraduate's research work. ", "The quality of postgraduate teaching also improved. ", "Those changes brought forth a shift in the activities of the Junior Scientific Club in 1920s. ", "It concentrated mainly on inviting high-profile scientific speakers. ", "This has remained the society's activity up to the present day.", "\n\nThe society's archives are largely available in the Bodleian Library.", "\n\nPeople \n\nThe Senior Member is Professor Kay Davies, FRS (Genetics).", "\nThe following are patrons:\n\n Peter Atkins (Chemistry)\n Colin Blakemore (Physiology)\n Marcus du Sautoy (Mathematics)\n Sir Roger Penrose (Mathematics)\n\nReferences \nThe 'History' section is largely based on the article:\n\nExternal links \n Oxford University Scientific Society website\n\nCategory:Student organizations established in 1882\nScientific Society\nCategory:Scientific societies based in the United Kingdom" ]

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

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[ "Catherine Tuttle\n\nYears of admissions experience\n\n8\n\nCredentials Highlight\n\nFormer Associate Director of Duke University’s Fuqua School of Business\n\n\"I am glad to have had Catherine's advice, encouragement and support during this journey and could not recommend her and Fortuna highly enough.\"", "\n\nA skilled admissions coach, marketer and career counselor, Catherine is an expert at crafting messages that are specifically tailored to an admissions committee. ", "She brings deep MBA experience as a former Associate Director of Duke University’s Fuqua School of Business.", "\n\nAt Duke, Catherine worked in the Career Management Center, serving as the liaison with Admissions and leading the career counseling team to create, implement, and evaluate full-time and executive career programs. ", "She has extensive experience coaching MBA students to prepare for the recruiting process and is one of Fortuna’s resume experts.", "\n\nCatherine holds a BA and an MEd from North Carolina State University.", "\n\nQ & A\n\nWhy are you passionate about coaching?", "\n\nI am passionate about coaching because I’m passionate about people. ", "I absolutely love getting to know my clients. ", "There’s a lot of self-reflection in this process and we go way past surface level when it comes to crafting the perfect application. ", "What I find is that people are often blind to their own strengths and in getting to know them personally and professionally, I am able to help them identify and embrace their true potential.", "\n\nWhat’s your coaching superpower?", "\n\nI am told that I put clients at ease. ", "I don’t rattle easily and I’ve seen a lot over the past 10 years, so when clients are feeling overwhelmed or stressed, I help them clear the noise and chatter in their head. ", "Whether it’s clarifying their career goals or trying to decide where to invest their time when they’re busy with a full-time job, volunteer activities and multiple applications, I listen, I repeat and I clarify their goals. ", "From there we’re able to determine next steps and continue to move forward.", "\n\nwhat you should be doing now to plan for your mba career goals\n\nINTERESTED IN WORKING WITH Catherine?", "\n\nAlthough we cannot guarantee your preferred coach selection because of workload capacity, we will always do our best to match you up with the coach of your choice if you have a specific request. ", "You may indicate your preference when you sign up for a free consultation." ]

{ "pile_set_name": "Pile-CC" }

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[ "-11)*p*p*p)/p)*p*p*p**(19/4)*p*(p**10)**(-18) assuming p is positive.", "\np**(-649/4)\nSimplify (o**(3/5)/(o**(-7/5)*o))/(o/(o**(-1/8)*o*o*o)*o)**26 assuming o is positive.", "\no**(95/4)\nSimplify ((r/(r/r**(-3)))**39/(r*r**(-12)*r*r**(-5)))**(-34) assuming r is positive.", "\nr**3468\nSimplify (r**3)**(3/4)/(r/r**(-12)*r*r**2) assuming r is positive.", "\nr**(-55/4)\nSimplify c**5*c/(((c*c*c*c*(c/(c**(1/6)/c))/c*c)/c)/c*c)*(c/(c**(-2/9)/c*c*c)*c)**47 assuming c is positive.", "\nc**(1055/18)\nSimplify (i*i**16*i**(-12/7))/(i**0/i)**21 assuming i is positive.", "\ni**(254/7)\nSimplify (n*n/(n**14*n*n))/n**(1/16)*((n/(n/n**4))/n*n)**(9/5) assuming n is positive.", "\nn**(-549/80)\nSimplify (c/c**(-1/2))**8*(c/(c/(c/(c/(c/c**2))))*c*c)**(1/10) assuming c is positive.", "\nc**(121/10)\nSimplify d**(2/17)*d*(d**4/d)/d*d*(d**(-4)/d)**(-14) assuming d is positive.", "\nd**(1260/17)\nSimplify (((b*b**(4/3))/b)/b**(-5/7))/((b**(-13)*b)/(b/(((b/(b**(-2)*b)*b)/b)/b))) assuming b is positive.", "\nb**(295/21)\nSimplify ((o*(o**12/o)/o)/o**33)**(-2/59) assuming o is positive.", "\no**(44/59)\nSimplify (i**(-10)/(i**(-8/3)*i))/(i**(-2/5)*((i/(i/((i**(-2/11)*i)/i)*i))/i)/i) assuming i is positive.", "\ni**(-784/165)\nSimplify ((a*a/a**(-3/5))**(-2/3)*(a**(-2/7))**(-9))**(-4/23) assuming a is positive.", "\na**(-352/2415)\nSimplify ((n*n**8*n/(n/(n/n**(-1)*n*n*n)))/((n**(1/4)*n)/n*n**(-8)))**(6/13) assuming n is positive.", "\nn**(261/26)\nSimplify ((f*f*f**(2/25)*f)/(f*f**11*f))/(f**(4/17)*f**(-28)*f) assuming f is positive.", "\nf**(7159/425)\nSimplify (b/(b/(b*b**(-28)))*((b/(b*b**(1/2)))/b)/b)/(b**(1/5)*b/b**31*b) assuming b is positive.", "\nb**(-7/10)\nSimplify ((s/(s*s/(s/(((s*s**(-10))/s)/s))*s))/s*s**2)**(-33) assuming s is positive.", "\ns**(-363)\nSimplify (j**(-9)/j)**(-18)/((j/(j*j**(19/5)))/(j/j**(6/11))) assuming j is positive.", "\nj**(10134/55)\nSimplify (k**2)**(-48)/(k*k**(-4))**(-1/21) assuming k is positive.", "\nk**(-673/7)\nSimplify (y**(-36)*y*y*(y*y*y**(-10/13)*y)/y)**(2/39) assuming y is positive.", "\ny**(-284/169)\nSimplify (l**15/l*l*l/l**(5/7))/((l*l/(l*l**9*l))/(l*l**0/l*l)) assuming l is positive.", "\nl**(177/7)\nSimplify (x/(x**(-1)/x))**1/((x/(x/(x**(-2/7)*x)))/x**(-4/5)) assuming x is positive.", "\nx**(52/35)\nSimplify (v**(2/13)*v*v/(v**(-3/5)*v))/(v**(-1/7)*v**(1/12)/v) assuming v is positive.", "\nv**(15361/5460)\nSimplify (((u*u*(u**9/u)/u*u*u)/(u**(-8)*u*u))/((u*u/((u/((u**(2/7)/u)/u)*u)/u)*u)/(u*u*u**(-2/11)*u)))**(-3/25) assuming u is positive.", "\nu**(-4512/1925)\nSimplify (s/(s**(-9/4)/s))**(18/5)*(s**(-1/6))**(6/5) assuming s is positive.", "\ns**(151/10)\nSimplify ((o*o**(-12))/(o*o*o**(-3)))/(o**(-5))**(-11) assuming o is positive.", "\no**(-65)\nSimplify (o/(o*o**(-2/21))*(o/o**14)/o)/(o**4*o/o**(2/23)) assuming o is positive.", "\no**(-9089/483)\nSimplify (((p/((p**6*p)/p*p)*p*p)/(p/(p*p/p**(-16)*p)))**(-32))**(1/19) assuming p is positive.", "\np**(-448/19)\nSimplify (c/(c**(-2/13)*c))**(-31)/((((c*(c/c**17*c)/c*c)/c)/c)/(c/c**(-2/3))) assuming c is positive.", "\nc**(503/39)\nSimplify (a**(-3/8)/(((((a**(-2)*a)/a)/a)/a)/a)*((a*a/(a*a*a**(3/8)/a))/a)/(a*a**2/a))**(-1/7) assuming a is positive.", "\na**(-9/28)\nSimplify a**(-12)*a**(-16/5)*(a**(4/15))**(-37) assuming a is positive.", "\na**(-376/15)\nSimplify (j**(-2/33))**2*(j**(-6/11))**46 assuming j is positive.", "\nj**(-832/33)\nSimplify ((g**10/g*g)/(g*g/((g/(g*g/(g*g**21)))/g)))/(g*g/(g/(g*g*g**7/g))*g)**(-32) assuming g is positive.", "\ng**348\nSimplify w**(-28)/((w*w**17)/w)*(w**(-2/45))**(-23) assuming w is positive.", "\nw**(-1979/45)\nSimplify (a/a**(8/3))/(a/a**(-1))*a**5*a**17/a assuming a is positive.", "\na**(52/3)\nSimplify ((q/((q*q**(-1/15))/q)*q)/q**7)/(q*q**(-1/2)*q/(q/(q/(q/(q**(-5)*q)*q)))) assuming q is positive.", "\nq**(-13/30)\nSimplify (l/(l*l/(l/l**13))*l/(l**(1/9)/l)*l)**(-21/4) assuming l is positive.", "\nl**(637/12)\nSimplify ((w/w**(-8))**(-2/27))**(1/16) assuming w is positive.", "\nw**(-1/24)\nSimplify (a/((a**(2/9)*a)/a))**45/((a**(-2/15)/a)/a*a**(-2)/a) assuming a is positive.", "\na**(602/15)\nSimplify (q**1*(q*q**(-7)/q)/q)/((q/((q/((q*q**(-10)*q*q*q)/q*q)*q)/q))/q**(-3/11)) assuming q is positive.", "\nq**(-14/11)\nSimplify p**(3/2)*p*p*p/(p*p**(-1/24))*(p**21)**(-11) assuming p is positive.", "\np**(-5459/24)\nSimplify q**(1/4)/q**13*q**(-1/21)*q*q**(-16) assuming q is positive.", "\nq**(-2335/84)\nSimplify (j*j**(-4))**(-4/11)*(j/(((j*j**2)/j)/j*j)*j*j*j)**39 assuming j is positive.", "\nj**(870/11)\nSimplify w/(w*w**9)*w**(-11)*w**14/(w*w**(-7)/w) assuming w is positive.", "\nw\nSimplify r**(-12)*r**(-13)*r**(-2)*r**(-5/4) assuming r is positive.", "\nr**(-113/4)\nSimplify (l/(l*l/l**(-1/8)*l*l)*l**2*l*l)/(l*l**(-1/4))**(-7) assuming l is positive.", "\nl**(49/8)\nSimplify (m/((((m/(m/(m/(m*m*m**(-2/5))))*m)/m)/m)/m)*m**(3/13))/((m/m**2)/m*m)**(-18) assuming m is positive.", "\nm**(-921/65)\nSimplify (l*l**(-5))/l*l**22*(l**(-4/7)*l)/l*l*l**21 assuming l is positive.", "\nl**(269/7)\nSimplify (i**(-2)*i*i)**(14/11)/(i*i/i**(2/25))**(-34) assuming i is positive.", "\ni**(1632/25)\nSimplify (o**(-13)/((o*o**(-2/83)*o)/o))/((((o*o/(o*o*o**(-21)*o))/o)/o)/(o*o**(1/8))) assuming o is positive.", "\no**(-20485/664)\nSimplify (z**(3/10)/(z*z*((z*z*z/(z*z*z*z**(-25)*z*z)*z)/z)/z*z))/((z*z/(z*z**(-18)*z)*z)/z**(5/2)) assuming z is positive.", "\nz**(-206/5)\nSimplify ((b**(-1/3))**(-14/3)*(b*b**(-1/4)*b)/b**(-1/6))**(16/9) assuming b is positive.", "\nb**(500/81)\nSimplify (a**(-4/5)*a*a**1*(a**1)**40)**(-21) assuming a is positive.", "\na**(-4326/5)\nSimplify (o**3/(o/(o*o/(o/(o*o**(13/3)/o*o)*o))))/(o**21*(o**(-4/3)/o*o)/o) assuming o is positive.", "\no**(-34/3)\nSimplify m*m/m**(2/11)*m*m*m*m**12/m*m**(3/10)*m**(-2)*m assuming m is positive.", "\nm**(1663/110)\nSimplify ((u**7*u*(u*u*u*u*u/(u**(1/3)/u))/u*u)**21)**(-22) assuming u is positive.", "\nu**(-6314)\nSimplify (t**5*t**(-1/26)/t)/(t*t/t**(-7/4))**(-2) assuming t is positive.", "\nt**(149/13)\nSimplify (v*v/v**(19/5)*v)/v**(-11/5)*(v**(-15))**(-4/5) assuming v is positive.", "\nv**(67/5)\nSimplify (((r**(1/18)*r)/r*r**(14/5))**(1/5))**(-30) assuming r is positive.", "\nr**(-257/15)\nSimplify ((q*q*q**(-1/13)*q**(2/17))**(-4))**(-3) assuming q is positive.", "\nq**(5412/221)\nSimplify k**(-4/7)/k*k*k*k*k/k**(-2/13)*k*k**(2/15)*k**(4/9)/k assuming k is positive.", "\nk**(12941/4095)\nSimplify (f**(-10/11)*(f*f**5/f)/f)/((f**19*f)/f**10) assuming f is positive.", "\nf**(-76/11)\nSimplify p**3*p**8*(p/p**(-3))**23 assuming p is positive.", "\np**103\nSimplify ((((g/g**(-5))/g)/g)/g**(-4/9)*g**0/(g*g**(-4)*g))**(-16/5) assuming g is positive.", "\ng**(-928/45)\nSimplify ((l**(2/5)*l**(3/7))**(-15/2))**(-12) assuming l is positive.", "\nl**(522/7)\nSimplify (y**(-2/65)*y**(-40)*y*y)**(-9) assuming y is positive.", "\ny**(22248/65)\nSimplify ((j*j**7*j*j**(-1)*j)**25)**33 assuming j is positive.", "\nj**7425\nSimplify c/(c**(-4)*c)*c*c*c**(-5/9)*c*c*c/c**(2/33)*c*c*c*c**(1/32)*c assuming c is positive.", "\nc**(39331/3168)\nSimplify (((c/((c/(c*c**12))/c))/(c**(-13)*c*c))**19)**19 assuming c is positive.", "\nc**9025\nSimplify (n*n*n/(n**(3/10)*n)*n*n/((n/(n*n**11))/n*n)*n**(-3/8)/(n*n*n**(8/3)))**(-5/6) assuming n is positive.", "\nn**(-1159/144)\nSimplify (z**5/(z/((z*z**(-1/4)/z*z)/z*z)))/((z**(10/9)*z)/z**(2/19)) assuming z is positive.", "\nz**(1877/684)\nSimplify (s**2)**(-1/93)*(s*s*s/s**(2/7))**(-16) assuming s is positive.", "\ns**(-28286/651)\nSimplify (t**4)**3/(t*t/(t**4*t))**(-5/2) assuming t is positive.", "\nt**(9/2)\nSimplify (((s*(s**1/s)/s)/s)**28*(s*s**(-1/3)*s*s)/(s**(-9)*s*s))**(-39) assuming s is positive.", "\ns**715\nSimplify (s**16/(s*s/(s*s/(s**10/s))*s))/((s*s**(3/4))/(s*s**(1/2)*s*s)) assuming s is positive.", "\ns**(31/4)\nSimplify (n*n**(-5/6)*n*n**(-2/33)/n*n)/(n/(n/(n/(n/n**6)))*n**(2/21)*n) assuming n is positive.", "\nn**(-2767/462)\nSimplify (n**5)**26/((n**4/n)/n)**28 assuming n is positive.", "\nn**74\nSimplify (y**(-2/17)*y)/y*y**(6/23)*y**(-35)/y**(-18) assuming y is positive.", "\ny**(-6591/391)\nSimplify (l**(6/5)/(l*l**(1/10))*(l/(l*l**(-2/7)*l)*l)**(-4/19))**(-19/6) assuming l is positive.", "\nl**(-53/420)\nSimplify s/(s/((s/s**(-2/21))/s))*s**8*(s**(-1/2)*s)/s*s/(s*s/s**(2/7))*s assuming s is positive.", "\ns**(331/42)\nSimplify (t/(t/t**(1/14))*t)/((t*t**(-10))/t)*(t**1*t)/(t*(t*(t/(t/(t*(t**30*t)/t)))/t)/t) assuming t is positive.", "\nt**(-251/14)\nSimplify t/((t/t**(5/3))/t)*t**(3/2)*(t*t**(-4))/t**(1/16) assuming t is positive.", "\nt**(53/48)\nSimplify ((f/f**(-2/19)*f*f*f*f*f/(f/f**(-5/3)))**2)**(1/2) assuming f is positive.", "\nf**(196/57)\nSimplify r**(-1/27)/r*((((r*((r*r*r*r*r*(r*(r/(r**7/r*r" ]

{ "pile_set_name": "DM Mathematics" }

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[ "The Aurora World Closed Beta Set for March\n\nIt’s time to get ready for yet another Asian MMO import. ", "The MMORPG in question this time is The Aurora World (try to say Aurora 5 times fast), a tri-faction MMO with notable feature highlights such as 300-player PvP battles, a pet system that evolves as you level while doubling as a mount and…yeah that’s all I’ve got. ", "That isn’t to say that is all there is to do in the game. ", "There are PvE quests and inevitable bosses to slay all in an effort to restore balance to a war torn land destroyed at one point in time by angry gods (what MMO land hasn’t been). ", "In the end though, I had a hard time finding more available info on the game.", "\n\nA quick glance at the site reveals all the aforementioned features along with 4 professions to choose from, each having two sub-classes you can spec into. ", "Curiously 3 of the professions are magic based in some way with only one profession, -the typical Warrior- utilizing physical attacks. ", "Regardless, if you want to try out The Aurora World you will need to wait till March 7th which is when the official closed beta is set to launch. ", "Beta keys will be made available soon and you can bet we will have some here for you to snag in order to try the game out for yourself. ", "Check out the trailer above for some random gameplay and a cute panda wearing a backpack.", "\n\nYou May like:\n\n33 Readers Commented\n\nIt’s not about game developer. ", "It’s more about game players. ", "I like Age of Wushu which combines PVP and MMO, no class and career. ", "It has thousands of Kung Fu skills, internal skills, and fighting styles. ", "It’s totally different from other fight games.", "\n\nThe game was fun but after 30 got HARD and at the time we had 0 Healers in are nation and 4 warriors lvl 31+ try to do the 1st dungeon and we fail so hard mobs hit you for 400-600 a time and your hp is only 3000 (we were good geared xD) but apart from that the game is fun and the pet is mount idea is BRILL flying swords/discs and also Epic looking Dragon how can you go rong the Item mall in game can make it P2W but not so much in this game from what i seen in Alpha test\n\nGraphics really aren’t that bad but I am from the nes and snes era so I’m not as spoiled as most modern gamers when it comes to that. ", "The pets look interesting and I don’t mind tab target as long as the controls aren’t completely horrible. ", "Animations seem to make up for the dated visuals but we’ll just have to wait and see if it was worth translating it or not. ", "I usually prefer games that take a unique artistic approach if visuals are sacrificed for gameplay though so i am not going to hold my breath in anticipation for this.", "\n\nThere is still a market for these old school,tab target MMORPGS. ", "The graphics are not really that bad. ", "My computer isn’t high end,though,so I do tend to go for games with lower graphical settings.", "That being said,I’ll probably pass. ", "Doesn’t really seem like my type of game. ", "There may still be a market for this type of game,I’m just not part of that market.", "\n\nas “shocking” as this may be for most of you guys i liek tab target games i dont “prefer” them over games like tera or raiderz in which u move “freely” by a way and u got full control of your char but idk i like em i will give this game a try for sure even though its outdated although i dont like the “4 classes 3 sorcerers and 1 warrior class” idea if what the article say is true ofc but we will see\n\nI agree. ", "Companies should look what is going on with the market and stop from early stages to invest money in sure to fail games. ", "Players nowadays are firstly attracted by the graphics, gameplay mechanic, content and story in this orders. ", "If you think you develop games for 10 year old PCs you better think again. ", "Those people if they were 10 now they are 20 so they will buy a new PC for sure.", "\n\nthe order you gave is not necceserly right and i dont think u in a position to say what u said and represent all games of the world of so graphics isnt the 1st thing gamers look i personally first check gameplay even if graphics are 10 years old or so also some new games(planetside 2,tera and so on)need high spec pcs and people arent in a position to change a graphci card or a video card or a sound card or anything at all computer wise every month anymore there is an economy crisis and idk where u live and if u fell the economy ripping u apart but personally it does that to me.i am also not sure if u talkin about ages here(the 10,20 numbers you refered to)but there will be always new and old gamers througout the world its not like people will suddenly stop getting interested on mmos so thats my answer if u were refering to ages and 1 last thing i thing companies(old ones especially or companies who have many games under their names)are too busy tryin to get a new game out and get money to pay attention to whats going on with other companies games i am personally glad this game will be out cause tera,vindictus.raiderz(these 3 are just examples)and games like that seem overall the same thing to me maybe its not your cup of tea?idk just dont speak as u represent every game in the world please.", "Thanks for your opinion and have a nice day\n\nI would agree with you, but those asian games, especially the new 2.5d browsers, are the most expensive.", "\nAnd sadly there are players spending lots of money on these games, just to be on the top rank.", "\nwhy? ", "because some are noobs, and others have few time to play , so they can only win by money. ", "and that kind of games give them that opportunity.", "\nAnd we all know it, so do not come with bullshit talk, couse these companies only care one thing, our money!" ]

{ "pile_set_name": "Pile-CC" }

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[ "Piotr Firlej\n\nPiotr Firlej (died 1553) was a Polish nobleman (szlachcic).", "\n\nFirlej married Katarzyna Teczynska and together they had three children: Jan Firlej, Mikołaj Firlej and Andrzej Firlej.", "\n\nPiotr became voivode of Lublin Voivodship in 1537 and voivode of Ruthenian Voivodship in 1545. ", "In 1514 he participated in the Battle of Orsza and was a trusted adviser of Queen Bona Sforza and King Zygmunt II August. ", "He founded the cities of Janowiec and Lubartów and built castles there.", "\n\nCategory:15th-century births\nCategory:1553 deaths\nCategory:Polish nobility\nPiotr\nCategory:Lublin Voivodes" ]

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

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[ "Shooting at the 2010 Asian Games – Women's skeet\n\nThe women's skeet competition at the 2010 Asian Games in Guangzhou, China was held on 23 November at the Guangzhou Shotgun Centre.", "\n\nSchedule\nAll times are China Standard Time (UTC+08:00)\n\nRecords\n\nResults\n\nQualification\n\nFinal\n\nReferences\n\nISSF Results Overview\n\nExternal links\nOfficial website\n\nWomen Shotgun S" ]

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

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[ "B-Complex, Full Spectrum\n\nBiotin\n\nBiotin is an essential coenzyme for a variety of carboxylation reactions, and is involved in the metabolism of fats, sugars and amino acids. ", "Biotin is crucial for the utilization of glucose for energy, the breakdown and utilization of fatty acids in energy production, and the removal of the amine group in amino acid metabolism, thereby assisting amino acid synthesis into protein and the formation of DNA and RNA. ", "Also is effectiveness in promoting healthy hair and nails.", "\n\nBiotin is an essential coenzyme for a variety of carboxylation reactions, and is involved in the metabolism of fats, sugars and amino acids. ", "Biotin is crucial for the utilization of glucose for energy, the breakdown and utilization of fatty acids in energy production, and the removal of the amine group in amino acid metabolism, thereby assisting amino acid synthesis into protein and the formation of DNA and RNA. ", "Also is effectiveness in promoting healthy hair and nails. **", "\n\nSupplement Facts\n\nServing Size: 1 VCaps\n\nServing per Container: 90\n\nAmount Per Serving\n\n% DV\n\nBiotin\n\n5mg\n\n1667%\n\nCholine Bitartrate\n\n100mg\n\n*\n\nOrganic Lecithin\n\n400mg\n\n*\n\nOrganic Citrus Bioflavanoids\n\n200mg\n\n*\n\n*Daily Value not established\n\nOther Ingredients: plant-derived capsule\n\nSuggested Use: As a dietary supplement take 1 VCaps daily or as directed by a physician.", "\n\nPrice: $17.98\n\nQuality & Purity\n\nOur Products are carefully crafted by hand.", "\n\nWe manufacture in the United States, by us in our facility.", "\n\nWe ship our products direct to you to guaranty the freshness.", "\n\nFreshly manufactured - never expired or closeout products.", "\n\nNo excipients or fillersOur goal is to manufacture our supplements as pure as possible, so we don't use fillers, binders, or chemical excipients. ", "Other manufacturers, in an effort to keep costs down, dilute their products with cheap fillers and excipients, which cheats you out of the active ingredient and contaminates your product with unneeded chemicals. ", "Purity, Quality, and Results is our #1 goal.", "\n\nPurchase manufacturer direct at wholesale priceBuy directly from the manufacturer and save. ", "We cut out the middlemen and pass the savings on to you. ", "With Green Organic Supplements, you pay the same low wholesale price that the chain stores pay. ", "Did you know that most companies do not manufacture their products but use 3rd party manufacturers. ", "Since we manufacture all of our own products we can control the quality and purity through the entire manufacturing process.", "\n\nBiotin is a vitamin that is found in small amounts in numerous foods.", "\nBiotin is used for preventing and treating biotin deficiency associated with pregnancy, long-term tube feeding, malnutrition, and rapid weight loss. ", "It is also used orally for hair loss, brittle nails, skin rash in infants (seborrheic dermatitis), diabetes, and mild depression.", "\nHow does it work?", "\nBiotin is an important component of enzymes in the body that break down certain substances like fats, carbohydrates, and others.", "\nThere isn’t a good laboratory test for detecting biotin deficiency, so this condition is usually identified by its symptoms, which include thinning of the hair (frequently with loss of hair color) and red scaly rash around the eyes, nose, and mouth. ", "Nervous system symptoms include depression, exhaustion, hallucinations, and tingling of the arms and legs. ", "There is some evidence that diabetes could result in biotin deficiency.", "\nFrom Web MD\n\n**The statements and claims about specific products throughout the site have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease. ", "All product information is for general informational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. ", "All product information is for general informational purposes only and is not intended to substitute for medical advice from your physician or other health care professional. ", "You should consult with a health-care professional before starting any diet, exercise or supplementation program especially if you suspect you may have a health problem." ]

{ "pile_set_name": "Pile-CC" }

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[ "// Copyright 2018 Frank Schroeder. ", "All rights reserved.", "\n// Use of this source code is governed by a BSD-style\n// license that can be found in the LICENSE file.", "\n\n// Package assert provides helper functions for testing.", "\npackage assert\n\nimport (\n\t\"fmt\"\n\t\"path/filepath\"\n\t\"reflect\"\n\t\"regexp\"\n\t\"runtime\"\n\t\"strings\"\n\t\"testing\"\n)\n\n// skip defines the default call depth\nconst skip = 2\n\n// Equal asserts that got and want are equal as defined by\n// reflect.", "DeepEqual. ", "The test fails with msg if they are not equal.", "\nfunc Equal(t *testing.", "T, got, want interface{}, msg ...string) {\n\tif x := equal(2, got, want, msg...); x !", "= \"\" {\n\t\tfmt.", "Println(x)\n\t\tt.Fail()\n\t}\n}\n\nfunc equal(skip int, got, want interface{}, msg ...string) string {\n\tif !", "reflect.", "DeepEqual(got, want) {\n\t\treturn fail(skip, \"got %v want %v %s\", got, want, strings.", "Join(msg, \" \"))\n\t}\n\treturn \"\"\n}\n\n// Panic asserts that function fn() panics.", "\n// It assumes that recover() either returns a string or\n// an error and fails if the message does not match\n// the regular expression in 'matches'.", "\nfunc Panic(t *testing.", "T, fn func(), matches string) {\n\tif x := doesPanic(2, fn, matches); x !", "= \"\" {\n\t\tfmt.", "Println(x)\n\t\tt.Fail()\n\t}\n}\n\nfunc doesPanic(skip int, fn func(), expr string) (err string) {\n\tdefer func() {\n\t\tr := recover()\n\t\tif r == nil {\n\t\t\terr = fail(skip, \"did not panic\")\n\t\t\treturn\n\t\t}\n\t\tvar v string\n\t\tswitch r.(type) {\n\t\tcase error:\n\t\t\tv = r.(error).Error()\n\t\tcase string:\n\t\t\tv = r.(string)\n\t\t}\n\t\terr = matches(skip, v, expr)\n\t}()\n\tfn()\n\treturn \"\"\n}\n\n// Matches asserts that a value matches a given regular expression.", "\nfunc Matches(t *testing.", "T, value, expr string) {\n\tif x := matches(2, value, expr); x !", "= \"\" {\n\t\tfmt.", "Println(x)\n\t\tt.Fail()\n\t}\n}\n\nfunc matches(skip int, value, expr string) string {\n\tok, err := regexp.", "MatchString(expr, value)\n\tif err !", "= nil {\n\t\treturn fail(skip, \"invalid pattern %q. %s\", expr, err)\n\t}\n\tif !", "ok {\n\t\treturn fail(skip, \"got %s which does not match %s\", value, expr)\n\t}\n\treturn \"\"\n}\n\nfunc fail(skip int, format string, args ...interface{}) string {\n\t_, file, line, _ := runtime.", "Caller(skip)\n\treturn fmt.", "Sprintf(\"\\t%s:%d: %s\\n\", filepath.", "Base(file), line, fmt.", "Sprintf(format, args...))\n}\n" ]

{ "pile_set_name": "Github" }

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[ "Jason Segel Joining '80s-Era Comedy, 'Undercover Cop' For DreamWorks\n\nBy\nEdward Davis\n|\nThe PlaylistFebruary 3, 2011 at 11:54AM\n\nSteve Zaillian's Film Rites company is on a major roll (as is the Academy Award-winning writer himself). ", "The production banner has \"The Cold Light of Day,\" starring \"Superman\"-to-be Henry Cavill, and \"Red Riding Hood\" coming out later this year (the former with Summit, the latter with Warner Bros.), they inked a first-look, two-year producing deal with DreamWorks last spring and most recently they're working on the English-language adaptation of the Spanish sci-fi time-travel pic, \"Time Crimes,\" at the studio as well.", "\n\nSteve Zaillian's Film Rites company is on a major roll (as is the Academy Award-winning writer himself). ", "The production banner has \"The Cold Light of Day,\" starring \"Superman\"-to-be Henry Cavill, and \"Red Riding Hood\" coming out later this year (the former with Summit, the latter with Warner Bros.), they inked a first-look, two-year producing deal with DreamWorks last spring and most recently they're working on the English-language adaptation of the Spanish sci-fi time-travel pic, \"Time Crimes,\" at the studio as well.", "\n\nDreamWorks and Film Rites now have another project in the works: a comedy called, \"Undercover Cop\" that has Jason Segel attached to star. ", "Even better, it's being written by a recent on-the-rise Black List scribe.", "\n\nWhile no official logline has been given, the film will be nostalgic for the 1980s and is inspired by the \"true story of a former cop that infiltrated the New Jersey criminal underworld in the era of feathered hair, zipper jackets and Bruce Springsteen's 'Born in the U.S.A.,' \" says The Hollywood Reporter.", "\n\nThe script will be penned by Jason Micallef, who wrote \"Butter,\" the screenplay that came in at #3 on the 2008 Black List and hits theaters later this year starring Jennifer Garner, Hugh Jackman and Olivia Wilde, just to name a few." ]

{ "pile_set_name": "Pile-CC" }

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[ "14 Words by Email\n\nSunday, 5 February 2012\n\nOn this day February 5th:\n1428-King Alfonso V, ordered Sicily's Jews to attend conversion sermons.", "\n1788-Sir Robert Peel, founder of the Metropolitan Police was born in Bury, Lancashire.", "\n1917-The Congress of the United States passed the Immigration Act of\n1917 over President Woodrow Wilson's veto. ", "Also known as the Asiatic\nBarred Zone Act, it forbade immigration from nearly all of south and\nsoutheast-Asia.", "\n1918-The steamship Tuscania, travelling as part of a British convoy and\ntransporting over 2,000 American soldiers to Europe, was torpedoed and\nsunk off the coast of Ireland by German submarine U-77.", "\n1922-Christiaan Rudolf De Wet, Boer General, and politician died aged 67 in Dewetsdorp, Orange Free State.", "\n1923-Mass arrests of socialists and communists in Italy.", "\n1943-Benito Mussolini removed Count Galeazzo Ciano, his son-in-law, from\nhis position as head of Italy's Foreign Ministry and took over the\nposition himself.", "\n1958-A 7,600-pound Mark 15 hydrogen bomb was lost by the US Air Force\noff the coast of Savannah, Georgia, never to be recovered.", "\n1962-French President Charles De Gaulle called for Algeria to be granted independence, enraging millions of French Patriots.", "\n1971-Apollo 14 Mission - Alan Shepard and Edgar Mitchell aboard Lunar Module Antares landed on the Moon at Fra Mauro formation.", "\n1994-Byron De La Beckwith was convicted of the 1963 murder of the\ncommunist, so called civil rights leader, Medgar Evers in a Zionist\nkangaroo court. ", "He was sentenced to life imprisonment without the\npossibility of parole. ", "He died in January 2001 aged 80." ]

{ "pile_set_name": "Pile-CC" }

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[ "01-474 Opinion\n\n No. ", "01-474\n\n IN THE SUPREME COURT OF THE STATE OF MONTANA\n\n 2002 MT 53N\n\n\n\n ROBERT J. BLACKWELL, Liquidating Trustee of\n Popkin & Stern Liquidating Trust,\n\n Plaintiff and Respondent,\n\n v.\n\n RONALD U. LURIE,\n\n Defendant and Appellant,\n\n NANCY LURIE, RYAN LURIE and MICHAEL LURIE,\n as parties whose property interests are affected by the\n Orders being appealed from,\n\n Appellants.", "\n\n\n\n\n APPEAL FROM: District Court of the Eighteenth Judicial District,\n In and for the County of Gallatin,\n The Honorable Mike Salvagni, Judge presiding.", "\n\n\n COUNSEL OF RECORD:\n\n For Appellants:\n\n Bryan P. Fay and Christopher R. Angel; Angel Law Firm,\n Bozeman, Montana\n\n For Respondent:\n\n Philip Walsh; Walsh & McKenna, Bozeman, Montana\n\n\n\n Submitted on Briefs: December 6, 2001\n\nhttp://www.lawlibrary.mt.gov/dscgi/ds.py/Get/File-14267/01-474_Opinion.html (1 of 4)6/19/2006 3:14:33 AM\n\f 01-474 Opinion\n\n Decided: March 26, 2002\n Filed:\n\n __________________________________________\n Clerk\n\n\n\n\nChief Justice Karla M. Gray delivered the Opinion of the Court.", "\n\n\n¶1 Pursuant to Section I, Paragraph 3(c), Montana Supreme Court 1996 Internal Operating Rules, the\nfollowing decision shall not be cited as precedent. ", "It shall be filed as a public document with the Clerk\nof the Supreme Court and shall be reported by case title, Supreme Court cause number and result to the\nState Reporter Publishing Company and to West Group in the quarterly table of noncitable cases issued\nby this Court.", "\n\n¶2 Ronald U. Lurie, Nancy Lurie, Ryan Lurie, and Michael Lurie appeal from two orders entered by\nthe Eighteenth Judicial District Court, Gallatin County, relating to Robert J. Blackwell's efforts to\nenforce a foreign judgment against Ronald U. Lurie. ", "We affirm.", "\n\n¶3 Blackwell's efforts to collect on a $1.1 million Missouri bankruptcy court judgment against Ronald\nU. Lurie have brought the parties before this Court on several occasions. ", "See State ex rel. ", "Blackwell v.\nDistrict Court (1997), 282 Mont. 530, 934 P.2d 1041; Lurie v. Sheriff of Gallatin County (1997), 284\nMont. 207, 949 P.2d 1163 (Lurie I); Blackwell v. Lurie (1997), 284 Mont. 351, 943 P.2d 1318; Lurie v.\nBlackwell (1997), 285 Mont. 404, 948 P.2d 1161 (Lurie II); Lurie v. Sheriff of Gallatin County, 2000\nMT 103, 299 Mont. 283, 999 P.2d 342 (Lurie III). ", "Here, the District Court granted a preliminary\ninjunction prohibiting Ronald U. Lurie and Nancy Lurie from transferring two parcels of real property\nlocated in Gallatin County, Montana, pending trial of Blackwell's fraudulent transfer action against\nthem. ", "The court also extended until November 9, 2004, the period in which Blackwell is entitled to have\nwrits of execution issued on the foreign judgment which has been filed in Gallatin County. ", "The Luries\ncontend the District Court erred in issuing both of the above orders. ", "They also argue the court erred in\nordering that all the personal property previously seized by the Gallatin County Sheriff may be sold at a\nsheriff's sale to satisfy the judgment against Ronald U. Lurie, with half of the proceeds to be returned to\nNancy Lurie.", "\n\n¶4 Our standard of review of an order granting or denying a preliminary injunction is whether the\ndistrict court abused its discretion. ", "Sweet Grass Farms, Ltd. v. Board of County Com'rs of Sweet Grass\nCounty, 2000 MT 147, ¶ 20, 300 Mont. 66,\n ¶ 20, 2 P.3d 825, ¶ 20 (citation omitted). ", "The remaining issues on appeal represent questions of law.", "\nConsequently, our standard of review is whether the district court's conclusions are correct. ", "See Steer,\nInc. v. Department of Revenue (1990), 245 Mont. 470, 474-75, 803 P.2d 601, 603.", "\n\n¶5 A preliminary injunction may be granted in any of the five situations described in § 27-19-201,\n\n http://www.lawlibrary.mt.gov/dscgi/ds.py/Get/File-14267/01-474_Opinion.html (2 of 4)6/19/2006 3:14:33 AM\n\f 01-474 Opinion\n\nMCA. ", "The District Court granted Blackwell's application for a preliminary injunction under subsection\n(2), finding that it appeared Blackwell will suffer irreparable injury if the injunction is not granted, and\nalso under subsection (1), finding that it appeared Blackwell was entitled to relief consisting of\nrestraining the commission of the act complained of. ", "The Luries challenge the preliminary injunction by\ncontending Blackwell is unable to show he will suffer irreparable harm or injury if a preliminary\ninjunction is not granted under § 27-19-201(2), MCA, because the lis pendens which he has filed against\ntheir Gallatin County real property will fully protect him from subsequent purchasers or encumbrancers.", "\nThey do not challenge the District Court's finding under, and application of, § 27-19-201(1), MCA, in\nissuing the preliminary injunction.", "\n\n¶6 We need not address the Luries' challenge to the preliminary injunction on the grounds set forth in\n§ 27-19-201(2), MCA. ", "Even if they prevailed on the contention they advance, the District Court's\nissuance of the preliminary injunction under § 27-19-201(1), MCA, remains a separate, independent and\nunchallenged basis on which to uphold the preliminary injunction. ", "We conclude, therefore, that the\nDistrict Court did not abuse its discretion in granting the preliminary injunction.", "\n\n¶7 The Luries' challenge to the District Court's order extending the period in which Blackwell may\nhave writs of execution issued is indirect. ", "They point out that the bankruptcy court judgment, filed in\nGallatin County as a foreign judgment, is for a deficiency calculated at $1,121,743, but that the\nbankruptcy court ordered the amount is to be reduced if the amount of the deficiency is ultimately\ndetermined to be less. ", "As a result, the Luries claim the exact amount of the deficiency has not been\nestablished and, therefore, no judgment currently exists which satisfies the § 25-13-301, MCA,\nrequirement that a writ of execution state the amount actually due on the judgment. ", "We disagree. ", "The\nbankruptcy court judgment is for a sum certain and the Luries have not established the occurrence of any\ncondition subsequent obligating Blackwell to seek modification of the judgment. ", "We hold the District\nCourt did not err in extending the period in which Blackwell may have writs of execution issued.", "\n¶8 In extending the time for obtaining writs of execution, the District Court also specifically gave\nBlackwell authority to sell, at sheriff's sale, personal property which has been seized by the Gallatin\nCounty Sheriff. ", "The Luries raise two issues regarding this grant of authority.", "\n\n¶9 First, the Luries contend there must be a judicial determination as to the respective interests of\nRonald U., Nancy, Ryan, and Michael Lurie in the seized property before the sheriff sells that property.", "\nIn Lurie III, ¶ 15, however, this Court determined property seized in Gallatin County that was held by\nboth Ronald U. and Nancy Lurie is owned either in joint tenancy or tenancy in common and is subject to\nexecution. ", "There, Nancy Lurie also claimed that some of the personal property seized in Gallatin\nCounty was acquired by her with her own separate funds. ", "See Lurie III, ¶ 4. ", "We affirmed the District\nCourt's dismissal of Nancy Lurie's claim for conversion and granted the Gallatin County Sheriff \"full\nsummary judgment\" on Nancy Lurie's complaint for claim and delivery. ", "Lurie III, ¶ 24. ", "Lurie III is res\njudicata as to Nancy Lurie and all such personal property. ", "Michael and Ryan Lurie–the adult sons of\nRonald U. and Nancy Lurie–first raised their claims of interest in the property by affidavit dated October\n23, 2000. ", "As a result, their claims are barred by the two-year statute of limitations set forth in § 27-2-\n207, MCA, which began to run in November of 1994 when the Gallatin County Sheriff seized the\npersonal property.", "\n\n\n http://www.lawlibrary.mt.gov/dscgi/ds.py/Get/File-14267/01-474_Opinion.html (3 of 4)6/19/2006 3:14:33 AM\n\f 01-474 Opinion\n\n¶10 The Luries also contend the District Court erred in authorizing the sale of personal property in\nwhich Nancy Lurie has a joint interest with Ronald U. Lurie, with half of the proceeds to be returned to\nNancy. ", "They rely on our statement in Letz v. Letz (1950), 123 Mont. 494, 502, 215 P.2d 534, 538, in\nwhich this Court stated that while the undivided interest of a cotenant may be attached, the attaching\nofficer may sell on execution only the debtor's interest.", "\n\n¶11 Unlike the present case, Letz involved a pre-judgment writ of attachment by the sheriff, not a writ\nof execution based on a district court judgment. ", "The Luries cite to no statute or opinion from this Court\nprohibiting the District Court from ordering the sale of the personal property in the Gallatin County\nSheriff's possession and the return of one-half of the gross proceeds to Nancy Lurie. ", "A court has the\npower to enforce its judgment through any order or writ necessary to carry the judgment into effect. ", "See\nLittle Horn State Bank v. Stops (1976), 170 Mont. 510, 512, 555 P.2d 211, 212. ", "We hold the District\nCourt did not err in ordering the sale of the personal property in the Gallatin County Sheriff's possession\nand the return of half the proceeds to Nancy Lurie.", "\n\n¶12 Affirmed.", "\n\n /S/ KARLA M. GRAY\n\n We concur:\n\n /S/ PATRICIA COTTER\n /S/ JIM REGNIER\n /S/ TERRY N. TRIEWEILER\n /S/ JIM RICE\n\n\n\n\n http://www.lawlibrary.mt.gov/dscgi/ds.py/Get/File-14267/01-474_Opinion.html (4 of 4)6/19/2006 3:14:33 AM\n\f" ]

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[ "Background {#Sec1}\n==========\n\nLiver steatosis is the buildup of triglycerides in the form of lipid droplets in liver which can be a result of several causes such as alcohol consumption, viral hepatitis or metabolic dysfunction \\[[@CR1], [@CR2]\\]. ", "When the fat proportion of liver is larger than 5--10%, it is considered as fatty liver disease that with further progress associated with inflammation may irreversibly result in severe conditions such as hepatocellular carcinoma, diabetes mellitus or other metabolic complications \\[[@CR1], [@CR3]\\]. ", "The prevalence of fatty liver disease is estimated as high as around 30% of the population \\[[@CR4]\\]. ", "An accurate and efficient method to diagnose liver fat extent is important for the clinical practice.", "\n\nTo quantitatively evaluate liver fat fraction nowadays, liver biopsy can be used which is essential for the diagnosis of non-alcoholic steatohepatitis (NASH) and is the only reliable procedure that differentiates non-alcoholic fatty liver (NAFL) from NASH, despite limitations due to sampling variability \\[[@CR5]\\]. ", "However, such invasive approach may encounter the problem of limited tissue sampling, serious complications and the low acceptance for patients \\[[@CR6]\\]. ", "Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) quantification is a procedure to non-invasively quantify liver fat extent by providing high-quality fat fraction maps of the entire liver. ", "It is considered to be even more accurate than liver biopsy for the liver fat quantification \\[[@CR5]\\]. ", "MR mDIXON quantification is one of such technique specifically for Philips MRI system \\[[@CR7]\\]. ", "But the lack of accessibility due to the expensive cost of MRI systems significantly restricts the use of this technique in clinical practice. ", "Medical ultrasound imaging is widely used and experienced doctors may qualitatively diagnose fatty liver disease based on ultrasound images. ", "However, such diagnosis is subjective, operator-dependent and not quantitative \\[[@CR8]\\].", "\n\nQuantitative ultrasound demonstrates the capability to some extent for the diagnosis of fatty liver disease. ", "The estimation of fundamental acoustic parameters such as echo attenuation and backscatter coefficient (BSC) were developed for liver fat quantification to characterize the tissue microstructure \\[[@CR9]\\]. ", "Some study has been published with a good result with a correlation between them and the result of MRI-PDFF as 0.79 \\[[@CR10]\\]. ", "Many previous studies also have evaluated the parameters such as echo attenuation, elasticity, viscosity (dispersion slope) and shear wave attenuation, respectively, for liver fat quantification \\[[@CR11]--[@CR14]\\]. ", "However, to simultaneously evaluate different parameters and make the comparison for liver fat quantification, it is required to design a specific ultrasound transmitting and receiving sequence to realize the multiple parameter estimation simultaneously. ", "One aim of our study is for this purpose. ", "Meanwhile, we theoretically derive and further introduce the parameter estimation of shear wave absorption by the use of the designed ultrasound shear wave sequence. ", "For all the estimated parameters, the performance of each one is evaluated on liver fat quantification with the results from MR mDIXON quantification as the ground truth. ", "We further explores the use of the combination of all quantitative parameters on liver fat quantification by introducing a learning-based model, which achieves a significant improvement on performance and might provide a new direction for ultrasound tissue characterization in clinical application.", "\n\nResults {#Sec2}\n=======\n\nSubjects {#Sec3}\n--------\n\nThe study included the patients who underwent routine ultrasound examination for the evaluation of the degree of hepatic steatosis from the physical examination center of Shanghai Public Health Clinical Center. ", "Meanwhile, anthropometric measurement was performed and fasting venous blood samples were obtained for the determination of blood routine, liver function and hepatitis virus indication. ", "Subjects were eligible for our study if they had no other known liver disease and did not have contraindications to MRI examination. ", "Table [1](#Tab1){ref-type=\"table\"} shows the complete inclusion and exclusion criteria \\[[@CR15]\\] for which the assessment is mainly based on blood test and medical history of the patients. ", "Based on these criteria, totally 60 participants who completed the ultrasound scanning for the data acquisition of multiple parameter estimation with the use of Philips EPIQ ultrasound system and the Philips MR mDIXON quantification examinations on the same day were selected for the study. ", "An example is demonstrated for the acquired ultrasound and MR imaging data as in Fig.", " [1](#Fig1){ref-type=\"fig\"}. ", "The appropriate ultrasound imaging plane should mainly contain the liver parenchyma region at the depth from 3 to 5 cm by avoiding vessel or any other structural objective and the acquired ultrasound data for one patient should cover the patient's liver parenchyma region as much as possible. ", "The corresponding estimation results may thus represent the situation of the patient's liver parenchyma region.", "Table 1Inclusion and exclusion criteria of patients for the studyInclusion criteria Age \\> 18 years With a negative hepatitis B virus surface antigen and hepatitis C virus antibody Willingness to undergo ultrasound and magnetic resonance examinations Signed informed consent formExclusion criteria With a history of other liver disease or diabetes Excess alcoholic drinking \\[[@CR15]\\] (≥ 20 g/day for men and ≥ 10 g/day for women) Taking hypolipidemic drug, liver protectant, or drugs that could cause steatosis With clinical symptoms or signs of other liver disease MR examination contraindications (such as claustrophobia, cardiac pacemakers or metal implants) Pregnant patients Fig.", " 1Demonstration of the acquired data in the study. **", "a** denotes the interface of the ultrasound data acquisition based on the designed ultrasound sequence. **", "b**, **d** The direct logarithmic results of the envelope of the corresponding raw radiofrequency ultrasound data. **", "c**, **e** The MRI fat quantification results. **", "b**, **c** are from the patient with liver fat fraction as 2.56%. **", "d**, **e** are from the patient with liver fat fraction as 29.45%. ", "The scale bar in ultrasound images denotes the intensity and the one in MRI images denotes the percentage of fat fraction\n\nThe population of our study consisted of 22 women and 38 men for which the age ranged from 19 to 69 years old and the body mass index (BMI) ranged from 18.3 to 34.9 kg/m^2^. Hepatic fat proportion quantified by MR mDIXON quantification ranged from 2.0 to 47.2% with the average value as 9.1%. ", "Table [2](#Tab2){ref-type=\"table\"} shows the details of the related information. ", "All patient data are available from the Department of Radiology in Shanghai Public Health Clinical Center affiliated Fudan University.", "Table 2Characteristics of the study patientsMR mDIXON quantification hepatic fat content (%)\\< 55--1010--20\\> 20TotalCharacteristic Number of participants261811560 Age (year)36 (23--67)43 (19--69)49 (27--68)32 (26--42)41 (19--69) Sex (male/female)20/69/95/64/138/22Anthropometric measures Weight (kg)64.9 ± 11.168.3 ± 8.173.7 ± 13.278.8 ± 11.968.8 ± 11.5 Height (cm)168.5 ± 6.2165.5 ± 5.4164.3 ± 6.2169.8 ± 5.2167.0 ± 6.1 BMI (kg/m^2^)22.9 ± 3.125.0 ± 2.427.2 ± 3.227.4 ± 2.824.7 ± 3.4Ultrasound parameter estimated results Echo attenuation (dB/MHz/cm)0.654 ± 0.1320.713 ± 0.0590.791 ± 0.1170.832 ± 0.0460.706 ± 0.121 Elasticity (kPa)9.45 ± 3.909.75 ± 5.338.62 ± 2.4110.3 ± 4.509.46 ± 4.15 Dispersion slope (m/s/Hz)3.27 ± 10.25.54 ± 4.172.62 ± 10.12.97 ± 6.553.82 ± 8.48 Shear wave attenuation (Neper/m)183.1 ± 57.9178.7 ± 24.7161.6 ± 41.3138.7 ± 19.6175.2 ± 46.3 Shear wave absorption (Neper/m)61.1 ± 16.859.6 ± 11.355.3 ± 14.549.3 ± 9.5558.9 ± 14.6 Model by using the combination of all parameters (%)4.5 ± 4.37.8 ± 2.413.1 ± 4.325.9 ± 2.48.3 ± 6.7\n\nPhantom results {#Sec4}\n---------------\n\nThe sampling rate for the acquired ultrasound radiofrequency data is 40 MHz. ", "The three push focus depths of the designed specific ultrasound shear wave sequence are 0.03 m, 0.04 m and 0.05 m, respectively. ", "After engineer optimization, the spacing values used for the shear wave measurement points are correspondingly 0.0012 m, 0.0013 m and 0.0015 m.\n\nExperiments on the 040GSE phantom (CIRS Inc., USA) were first performed to validate the parameter estimation methods. ", "Table [3](#Tab3){ref-type=\"table\"} shows the related results. ", "The ground truth of echo attenuation was known for the phantom and it can be seen that the corresponding estimation results are well consistent with the ground truth. ", "Meanwhile, the standard deviation of the results is small, which denotes the robustness of the echo attenuation estimation method and the signal stability of tracking echo. ", "For the elasticity results, it can be seen that they are in the acceptable range of the designed 24 kPa for the Zerdine material of the CIRS phantom. ", "Since there is no ground truth for the estimated parameters except echo attenuation, a house-made oil phantom was constructed to further evaluate the 040GSE phantom results. ", "Compared with the 040GSE phantom, the house-made oil phantom was made with 20% gelatin and 20% animal oil (bovine) to simulate the situation with a relatively large extent of fat fraction. ", "It can be seen that the dispersion is much larger than the one from the 040GSE phantom, which is as expected for a larger viscosity and validates the estimation algorithm to some extent. ", "For the results of shear wave attenuation and shear wave absorption, their values change and manifest as negative correlation with the increase of fat fraction, which indicate their connection between the parameters and fat fraction and could be referred for the following experiments on patient data.", "Table 3Experimental results on phantomsEstimated parameterPhantom040GSE\\\n0.5 dB region040GSE\\\n0.7 dB regionHouse-made oil phantomEcho attenuation (dB/MHz/cm)0.5132 ± 0.03670.7018 ± 0.03730.7563 ± 0.1605Elasticity (kPa)22.1111 ± 8.597117.8650 ± 5.106851.6250 ± 5.8750Dispersion slope (m/s/Hz)0.4821 ± 0.26120.4518 ± 0.37923.5391 ± 2.2279Shear wave attenuation (Neper/m)65.9084 ± 4.072274.8187 ± 18.337151.9126 ± 17.4872Shear wave absorption (Neper/m)53.6819 ± 1.488061.9683 ± 3.833838.4690 ± 5.1999\n\nPatient results {#Sec5}\n---------------\n\nThe result distributions of the estimated parameters and the learning-based model's output for different fat proportion segments were demonstrated in the second part of Table [2](#Tab2){ref-type=\"table\"}. ", "Figure [2](#Fig2){ref-type=\"fig\"} further demonstrates the correlation distributions of the results for all 60 patient data with the MR mDIXON quantification results. ", "To quantitatively evaluate the different methods, the correlation coefficient (CC) values are applied between the estimation results and the liver fat proportion from MR mDIXON quantification \\[[@CR16]\\]. ", "The details of the related CC values are shown in Table [4](#Tab4){ref-type=\"table\"}. ", "Among the individual parameter estimation, echo attenuation achieves the best performance. ", "Compared with echo attenuation, shear wave absorption and shear wave attenuation are less effective. ", "They demonstrate as negative correlation with liver fat fraction, which is consistent with the observation from the phantom results. ", "Low-correlation coefficients with liver fat proportion are manifested for elasticity and viscosity, which denotes their limited capability on quantifying liver fat proportion individually. ", "However, the performance significantly improves for the learning-based model by combining all the parameters together and the CC value achieves as high as 0.83. ", "The detailed regression results of the model are further analyzed by comparing it with the MR mDIXON quantification results. ", "The root mean square error is only 4.47% for liver fat proportion estimation, which achieves state-of-the-art for ultrasound liver fat quantification \\[[@CR3]\\].Fig.", " 2The experimental results of all 60 patient data denoting the relationship between the estimated parameters and the liver fat proportion from MR mDIXON quantification, which are **a** echo attenuation, **b** elasticity, **c** dispersion slope, **d** shear wave attenuation, **e** shear wave absorption and **f** model using the combination of all parameters Table 4The correlation coefficients between the estimation results and the liver fat proportion from MR mDIXON quantificationMethodsCorrelation coefficients*P* valueEcho attenuation0.4594 (95% CI 0.2327 to 0.6388)0.00022Elasticity0.0283 (95% CI -0.2273 to 0.2802)0.83Dispersion slope0.0447 (95% CI -0.2116 to 0.2953)0.73Shear wave attenuation− 0.2542 (95% CI − 0.4773 to − 0.0003)0.050Shear wave absorption− 0.2599 (95% CI − 0.4820 to − 0.0064)0.044Model using the combination of all parameters0.8305 (95% CI 0.7306 to 0.8956)\\< 0.00001\n\nWe further perform the statistical analysis to investigate the experimental results. ", "Since the percentage values of liver fat proportion is the liver fat quantification results of MR mDIXON quantification, it is needed to apply a thresholding value as a certain percentage to identify the patient label for the discrimination of fatty liver disease to evaluate different methods. ", "In our study, the thresholding value was chosen as 5% for the detailed evaluation, which is based on the previous clinical studies \\[[@CR1], [@CR3]\\]. ", "Sensitivity (SEN), specificity (SPC), positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC) and the area under the receiver operating characteristic (AUC) are the detailed evaluation criteria. ", "The receiver operating characteristic (ROC) curves of different methods are demonstrated in Fig.", " [3](#Fig3){ref-type=\"fig\"}. ", "It can be observed that the result of the established model using all the estimated parameters outperforms the ones of individual parameters obviously. ", "The optimal cut-off values from the ROC curves are determined based on Youden's index \\[[@CR17]\\] and based on them, the detailed statistical results are shown in Table [5](#Tab5){ref-type=\"table\"}. ", "From the quantitative evaluation results, echo attenuation achieves the best performance among the individual parameters. ", "This is consistent with the information from the structure of the established regression tree model in which echo attenuation plays a significant role as the fundamental node shown as in Fig.", " [4](#Fig4){ref-type=\"fig\"}. ", "For echo attenuation to discriminate fatty liver disease, the optimal cut-off value is 0.69 dB/MHz/cm in our study and it is consistent with the previously reported work \\[[@CR18]\\]. ", "Furthermore, Table [5](#Tab5){ref-type=\"table\"} clearly manifests the significant improvement from the model by combining all the parameters. ", "The accuracy as 76% for echo attenuation increased to 90% as for the established model. ", "Since echo attenuation is comparable with the B-mode assessment by experienced doctors \\[[@CR18]\\], the proposed learning-based model can help significantly increase the accuracy of the diagnosis of fatty liver disease for clinical practice. ", "For the outputs of the established model, the optimal cut-off value is 6.6%. ", "It is close to the selected 5% for the discrimination of fatty liver disease.", "Fig.", " 3The receiver operating characteristic (ROC) curves of different methods for the discrimination of fatty liver disease Table 5The statistical analysis of the experimental results of different methods regarding the discrimination of fatty liver diseaseMethodStatistical results with the corresponding optimal cut-off values from ROC curves for different methodsSEN (%)SPC (%)PPV (%)NPV (%)ACC (%)AUCEcho attenuation84.3867.8675.0079.1776.670.73Elasticity78.1332.1456.8256.2556.670.51Dispersion slope90.6339.2963.0478.5766.670.60Shear wave attenuation84.3832.1458.7064.2960.000.54Shear wave absorption78.1346.4362.5065.0063.330.60Model by using the combination of all parameters87.5092.8693.3386.6790.000.93 Fig.", " 4The details of the established regression tree model by combining all the parameters where ×1, ×2, ×3, ×4 and ×5 denote the parameter values of shear wave absorption, echo attenuation, elasticity, dispersion slope and shear wave attenuation, respectively\n\nTo further validate the effectiveness of the proposed method, we randomly use a small proportion of the entire patient data as the independent testing data and the rest of the data is correspondingly used for the establishment of the machine-learning model. ", "To observe the performances of the established models under various conditions of clinical data availability, the proportion for the independent testing data varies as 5%, 10% and 15%, respectively. ", "The repeated cross-validation number for each value of the proportion is 10 to statistically guarantee the precise evaluation of the established model. ", "The results of the validation are demonstrated in Table [6](#Tab6){ref-type=\"table\"}. ", "It can be seen that the performance of the proposed method is stable as maintaining CC value around 0.8 with the liver fat quantification results of MR mDIXON quantification. ", "Meanwhile, when the proportion of the independent testing data increases, the model's performance manifests a slight decrease, which denotes the data size does impact the performance of the model since it is a data-based machine-learning model.", "Table 6The validation results of the proposed method by randomly using a proportion of the patient data as the independent testing data and using the rest of the patient data to establish the corresponding machine-learning modelProportion of the independent testing data in the entire patient data (%)Correlation coefficients between the model's estimation results and the liver fat proportion from MR mDIXON quantificationP value50.8249 (95% CI 0.7223 to 0.8920)\\< 0.00001100.8049 (95% CI 0.6925 to 0.8791)\\< 0.00001150.7816 (95% CI 0.7173 to 0.8326)\\< 0.00001\n\nDiscussion {#Sec6}\n==========\n\nUltrasound imaging is widely utilized in clinical practice. ", "However, the conventional way highly depends on the operation of physician even just for diagnosing the existence of fatty liver disease. ", "It is subjective, qualitative and often leads to the problem of non-reproducibility and inaccuracy. ", "A previous study \\[[@CR3]\\] attempted to realize the liver fat quantification. ", "However, its quantification approach still mainly depended on the appropriate acquisition of the hepatic-renal imaging plane, which remains operator-dependent. ", "To solve such problem, our study explored the potential method to only use the objective, robust and quantitative parameters for liver fat quantification. ", "It should be noted that by intention, any operator-dependent process is excluded in the quantification of fatty liver.", "\n\nFrom the results of individual estimated parameters, it can be observed that the attenuation in the axis-beam direction is positively correlated with the results of MR mDIXON quantification and conversely, the parameters of shear wave energy dissipation are negatively correlated. ", "This interesting phenomenon demonstrates the difference between longitudinal ultrasound signal and shear ultrasound signal even based on the same characteristic change for the material. ", "It provides the physical evidence regarding the characteristics of shear wave signals for the future study.", "\n\nIt can be seen that from our study, the combination of all parameters establishes the foundation of the excellent performance of the learning-based model for liver fat quantification. ", "First, these parameters should be able to be robustly estimated, which guarantees the accuracy of the following established model. ", "Furthermore, these parameters are preferable to be supplemented for each other on signal information. ", "For a generated ultrasound propagation phenomenon, the obtained longitudinal and shear signals include all the generated signals. ", "When the estimated parameters represent the entire signal information for these two directions, the ultrasound representation of the target tissue can be thus considered as well defined. ", "Meanwhile, to use a mechanical model to define a target tissue, elasticity and viscosity can well define the mechanical model. ", "Based on all the considerations, the five parameters in our study are chosen and applied for the related processing of tissue characterization. ", "Such set of parameters is considered as a \"complete\" signal set. ", "Here, the \"complete\" means that once the parameter values in such parameter set for a target tissue is determined, the target tissue can be well characterized and in the high-dimensional space defined by the parameter set, the target tissue can be thus well discriminated with other objectives even if the performance of individual parameters is limited. ", "Such idea has been preliminarily verified by our study. ", "It provides an approach for the research not just for liver fat quantification, but furthermore for the goal of tissue characterization.", "\n\nBased on the characteristics of relatively simple operation, low examination cost and high penetration rate of medical ultrasound imaging, the proposed model by combining all the estimated parameters demonstrates its high clinical value for liver fat quantification. ", "Compared with MR mDIXON quantification and liver biopsy, it provides a relatively better method for liver fat quantification in clinical work. ", "Limitations of the present study also need to be mentioned. ", "Subjects in our study were enrolled in a single clinical center and the sample size was relatively small, which should be improved in the future multi-center study.", "\n\nConclusions {#Sec7}\n===========\n\nIndividual ultrasound and shear wave parameters demonstrate limited capability for liver fat quantification. ", "However, by combining them together, the established learning-based model may achieve a good performance. ", "It verifies the idea that in the high-dimensional space defined by the proposed ultrasound parameter set, the target tissue can be well defined and discriminated with other objectives. ", "It provides an approach not just for liver fat quantification, but furthermore for the goal of ultrasound tissue characterization.", "\n\nMethods {#Sec8}\n=======\n\nUltrasound multiple parameter estimation {#Sec9}\n----------------------------------------\n\nWhen transmitting an ultrasound push at a focus in the longitudinal direction (through the beam axis), the shear wave signal resulting from the generated acoustic radiation force can be observed through the shear direction at the focus using tracking-echo beams adjacent to this push beam. ", "For one measurement of all the ultrasound parameters in our study, the designed specific ultrasound shear wave sequence consists of three ultrasound pushes and each push focuses at a different depth. ", "The tracking-echo signals with the format as raw radiofrequency (RF) data are correspondingly obtained after each push. ", "Based on the received signals from such single ultrasound sequence, the methods for simultaneously estimating all the ultrasound parameters in our study are correspondingly proposed to be performed, for which the main consideration is the robustness of estimation.", "\n\nConventional echo attenuation is directly estimated from the tracking-echo RF signals. ", "A least-squares method is applied with the learning-based optimization for its parameters \\[[@CR18]\\]. ", "The power spectrum of the backscattered echo signals can be described as$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{Sp}}\\left( {f,z} \\right) = G\\left( {f,z} \\right) \\cdot A\\left( {f,z} \\right) \\cdot B\\left( f \\right)$$\\end{document}$$where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{Sp}}$$\\end{document}$ is the power spectrum of the backscattered echo signal with $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$f$$\\end{document}$ as frequency and $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$z$$\\end{document}$ as the depth. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$G$$\\end{document}$ represents the combined effects from the settings of system and beamforming. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$A$$\\end{document}$ represents the total attenuation through the path from the transducer surface to the depth of interest, which is defined as $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$A\\left( {f,z} \\right) = \\exp ( - 4\\beta fz)$$\\end{document}$ where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\beta$$\\end{document}$ is the effective attenuation coefficient of the conventional echo. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$B$$\\end{document}$ denotes the backscatter coefficient in the region of interest that is defined as $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$B\\left( f \\right) = bf^{n}$$\\end{document}$ where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$b$$\\end{document}$ is a constant coefficient and $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$n$$\\end{document}$ represents the dependence with frequency. ", "By obtaining the echo signal with the same setting for system and beamforming from a reference phantom, the ratio of the echo signal's power spectrums from the target to that from the reference phantom at the same depth can be expressed as$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{RS}}\\left( {f,z} \\right) = \\frac{{B_{\\text{tar}} \\left( f \\right)}}{{B_{\\text{ref}} \\left( f \\right)}} \\cdot \\frac{{A_{\\text{tar}} \\left( {f,z} \\right)}}{{A_{\\text{ref}} \\left( {f,z} \\right)}} = \\frac{{b_{\\text{tar}} f^{{n_{\\text{tar}} }} }}{{b_{\\text{ref}} f^{{n_{\\text{ref}} }} }}\\exp \\left( { - 4\\left( {\\beta_{\\text{tar}} - \\beta_{\\text{ref}} } \\right)fz} \\right)$$\\end{document}$$where the subscripts of $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{tar}}$$\\end{document}$ and $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{ref}}$$\\end{document}$ represent the target tissue and the reference phantom, respectively. ", "The natural logarithm of both sides of Eq.", " [2](#Equ2){ref-type=\"\"} is performed and the equation can be further expressed as$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\ln \\left\\{ {RS\\left( {f,z} \\right)} \\right\\} = \\ln \\frac{{b_{\\text{tar}} }}{{b_{\\text{ref}} }} + \\left( {n_{\\text{tar}} - n_{\\text{ref}} } \\right)\\ln f - 4\\left( {\\beta_{\\text{tar}} - \\beta_{\\text{ref}} } \\right)fz$$\\end{document}$$\n\nA least-squares fitting process can be thus applied over the band of frequencies that are contained in the echo signals by Eq.", " [3](#Equ3){ref-type=\"\"} based on the known acoustic properties of the reference phantom. ", "The conventional echo attenuation can be thus obtained for the target tissue.", "\n\nFor the shear wave signals at certain depths, elasticity can be robustly estimated with the method by measuring the shear time-to-peak displacement \\[[@CR19], [@CR20]\\]. ", "For shear wave signals, it can be proven that in nearly incompressible soft tissues such as liver parenchyma in our study,$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$E = 3\\rho \\cdot c_{\\text{shearwave}}^{2}$$\\end{document}$$where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$E$$\\end{document}$ is the elasticity also known as Young's modulus. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\rho$$\\end{document}$ is the liver density that is assumed as 1.0 g/cm^3^ \\[[@CR19]\\] here. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$c_{\\text{shearwave}}^{{}}$$\\end{document}$ is the shear wave propagation speed. ", "With tracking-echo RF signals, the tissue displacement caused by shear wave propagation can be estimated and manifest the location change of the peaks of shear wave displacements from different tracking beams. ", "Therefore, the shear wave propagation speed can be obtained by equivalently measuring the peak propagation speed. ", "The elasticity can be thus estimated based on Eq.", " [4](#Equ4){ref-type=\"\"}.", "\n\nSince the shear wave dispersion slope is positively correlated with the viscosity, the shear wave dispersion slope is practically and robustly estimated with the obtained shear wave signals to represent the related tissue characteristics of viscosity in our study \\[[@CR12], [@CR13], [@CR20], [@CR21]\\]. ", "The shear wave velocity $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$v_{\\text{shearwave}}$$\\end{document}$ can be defined as$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$v_{\\text{shearwave}} \\left( f \\right) = \\frac{2\\pi f \\cdot \\Delta d}{\\Delta \\varphi }$$\\end{document}$$where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$f$$\\end{document}$ is the frequency component. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\Delta d$$\\end{document}$ is the distance between two adjacent tracking beams for which $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\Delta \\varphi$$\\end{document}$ denotes the corresponding phase shift due to the stimulated shear wave propagation. ", "It is noted that no rheological model is assumed in our study and only a linear model is applied for the shear wave dispersion estimation. ", "Based on Eq.", " [5](#Equ5){ref-type=\"\"}, the shear wave dispersion slope $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{SDS}}$$\\end{document}$ can be thus defined as$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{SDS}} = \\frac{{\\partial v_{\\text{shearwave}} \\left( f \\right)}}{\\partial f}$$\\end{document}$$for which the practical estimation from Eq.", " [6](#Equ6){ref-type=\"\"} is to calculate the slope of a linear fitting of shear wave velocities versus different frequency components with the range from 50 to 300 Hz.", "\n\nBased on the shear wave signals from all the locations of tracking-echo beams, shear wave attenuation can be robustly estimated with a model-free method \\[[@CR14]\\]. ", "The maximum values of shear wave displacements are estimated for each tracking-echo beam. ", "The ratios between these maxima and the one from the first tracking-echo beam are further calculated. ", "These ratios are assumed as exponentially depending on the propagation distance of tracking-echo beams that can be written as$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{MDR}}_{i} = e^{{ - \\alpha \\cdot d_{i} }}$$\\end{document}$$where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$${\\text{MDR}}_{i}$$\\end{document}$ denotes the ratio of maximum shear wave displacements between the *i*th and the first tracking-echo beams. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$d_{i}$$\\end{document}$ denotes the distance between the *i*th and the first tracking-echo beams. ", "The estimation of shear wave attenuation is realized by calculating the slope α from the fitting of the Eq.", " [7](#Equ7){ref-type=\"\"}. ", "It is noted that the estimation of shear wave attenuation was performed only in the near region of every push focus in our study. ", "The diffraction related to the acoustic radiation force \\[[@CR22], [@CR23]\\] could be thus negligible to some extent for the estimation.", "\n\nIt is hypothesized in our study that the energy dissipation in tissue could be an important bio-marker for liver lipid content. ", "Therefore, the estimation of shear wave absorption is further introduced for liver fat quantification and it emphasizes the energy that is absorbed and transferred for the generation of shear wave phenomenon. ", "Theoretically, for shear wave signals, it can be proven \\[[@CR24]--[@CR26]\\] that$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\frac{{\\partial^{2} S_{x} }}{{\\partial t^{2} }} - \\left( {c_{\\text{shearwave}}^{2} + \\gamma \\frac{\\partial }{\\partial t}} \\right)\\Delta_{lp} S_{x} = F_{x}$$\\end{document}$$where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$x$$\\end{document}$ represents the beam axis. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$t$$\\end{document}$ is time. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$S_{x}$$\\end{document}$ denotes the shear wave displacement along the $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$x$$\\end{document}$ direction. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$c_{\\text{shearwave}}^{{}}$$\\end{document}$ is the shear wave propagation speed. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\gamma$$\\end{document}$ denotes the shear viscosity. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\Delta_{\\text{lp}}$$\\end{document}$ denotes the Laplacian operator. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$F_{x}$$\\end{document}$ represents the radiation force that stimulates the shear wave phenomenon. ", "Based on Eq.", " [8](#Equ8){ref-type=\"\"} and with the further assumption of pulsing modulation, it can be theoretically derived \\[[@CR24]--[@CR26]\\] that$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$S_{{x_{\\text{focus}} ,\\text{max} }} = \\frac{{\\sqrt \\pi \\sigma a^{2} t_{0} I_{0} }}{8c\\rho \\gamma } \\cdot e^{{ - 2\\sigma \\cdot x_{\\text{focus}} }} \\propto I_{0} \\cdot e^{{ - 2\\sigma \\cdot x_{\\text{focus}} }}$$\\end{document}$$where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$S_{{x_{\\text{focus}} ,\\text{max} }}$$\\end{document}$ denotes the maximum displacement of the generated shear wave at the focus depth $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$x_{\\text{focus}}$$\\end{document}$. $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$a$$\\end{document}$ is the aperture size. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$t_{0}$$\\end{document}$ denotes the initial time. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$c$$\\end{document}$ is the ultrasound speed that could be assumed as 1540 m/s. $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\rho$$\\end{document}$ is the liver density assumed as 1.0 g/cm^3^ here \\[[@CR19]\\]. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\sigma$$\\end{document}$ denotes the shear wave absorption coefficient. ", "$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$I_{0}$$\\end{document}$ is the acoustic intensity of the initial ultrasound wave on the beam axis that is defined as$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$I_{0} = \\frac{{P_{0}^{2} }}{2c\\rho }$$\\end{document}$$where $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$P_{0}^{{}}$$\\end{document}$ represents the initial acoustic pressure.", "\n\nFor the details about the related theory of shear wave absorption coefficient, the work by Rudenko et al. ", "\\[[@CR24]\\] was well performed for the related theoretical derivations. ", "Based on them, we propose an approach to practically realize the estimation of shear wave absorption coefficient. ", "It can be seen that according to Eq.", " [9](#Equ9){ref-type=\"\"}, $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$S_{{x_{\\text{focus}} ,\\text{max} }}$$\\end{document}$, $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$I_{0}$$\\end{document}$ and $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$x_{\\text{focus}}$$\\end{document}$ are the only parameters that require to know their values for the practical estimation of shear wave absorption coefficient $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\sigma$$\\end{document}$. Therefore, the approach for shear wave absorption estimation was to first obtain the maximum displacements of the generated shear waves focused at the three focus depths in our designed specific ultrasound shear wave sequence. ", "Then, for every acoustic push, the applied voltage $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$V_{0}^{{}}$$\\end{document}$ on the transducer elements was recorded since $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$P_{0}^{{}}$$\\end{document}$ could be considered as proportional to the applied voltage $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$V_{0}^{{}}$$\\end{document}$ of the transducer elements. ", "Thus $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$I_{0}$$\\end{document}$ based on Eq.", " [10](#Equ10){ref-type=\"\"} could be considered as proportional to the value of $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\frac{{V_{0}^{2} }}{2c\\rho }$$\\end{document}$, which is utilized as the practical value to compensate the difference for the initial intensities $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$I_{0}$$\\end{document}$ of the three different acoustic pushes. ", "Since the ultrasound system is exactly the same one for different acoustic pushes, this approximation would not affect the shear wave absorption coefficient estimation at all. ", "After compensating the initial intensities $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$I_{0}$$\\end{document}$ and obtaining the values as $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\frac{{S_{{x_{\\text{focus}} ,\\text{max} }} }}{{I_{0} }}$$\\end{document}$, a curve fitting was simply performed with an exponential form in which the focus depth was the variable. ", "The shear wave absorption coefficient $\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$\\sigma$$\\end{document}$ can be directly and conveniently calculated from this fitting.", "\n\nModel by using the combination of all parameters {#Sec10}\n------------------------------------------------\n\nEach of the above estimated parameters may represent some aspect of the physical characteristics of target tissue (as liver fat in our study). ", "Therefore in our study, it was hypothesized that by simultaneously considering the entire set of these robustly estimated parameters, the target tissue should be able to be better represented and identified compared with using one individual parameter. ", "In other words, the target tissue could be well characterized in the high-dimensional space defined by all the estimated parameters. ", "To verify this hypothesis, a machine-learning method was applied in our study to establish the model in such high-dimensional space. ", "However, to avoid the over-fitting for the learning-based model since the sample number in our study was as small as 60, we should select the model that is relatively simple compared with the state-of-the-art ones. ", "Based on such consideration, the regression tree was applied as the learning-based model in our study \\[[@CR27]\\]. ", "Figure [4](#Fig4){ref-type=\"fig\"} demonstrated the details of the established regression tree in which ×1, ×2, ×3, ×4 and ×5 denote the parameter values of shear wave absorption, echo attenuation, elasticity, dispersion slope and shear wave attenuation, respectively. ", "This model is for the purpose to investigate the potential connections for the physical characteristics represented by the different estimated parameters. ", "The hierarchical structure of the model approximates the non-linearity in the parameter space while maintaining the low-computational complexity that is specifically appropriate for clinical practice.", "\n\nCC\n\n: correlation coefficient\n\nAUC\n\n: area under the receiver operating characteristic\n\nNASH\n\n: non-alcoholic steatohepatitis\n\nNAFL\n\n: non-alcoholic fatty liver\n\nMRI-PDFF\n\n: magnetic resonance imaging based proton density fat fraction\n\nBSC\n\n: backscatter coefficient\n\nBMI\n\n: body mass index\n\nRF\n\n: radiofrequency\n\nSEN\n\n: sensitivity\n\nSPC\n\n: specificity\n\nPPV\n\n: positive predictive value\n\nNPV\n\n: negative predictive value\n\nACC\n\n: accuracy\n\nROC\n\n: receiver operating characteristic\n\n**Publisher\\'s Note**\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.", "\n\nXiudong Shi and Wen Ye contributed equally to this work\n\nThe technique support of Yinhui Deng and He Wang from Philips Research China were highly appreciated.", "\n\nXS and WY designed the method and drafted the original manuscript; FL, RZ, QH, and CS carried out the experiments and analyzed the data; JY and YS provided supports for the research, designed the method, and revised the manuscript. ", "All authors read and approved the final manuscript.", "\n\nThis work is supported by the Shanghai Science and Technology Innovation Plan (19441903100), the Shanghai Municipal Science and Technology Commission Program (1541196900) and the National Natural Science Foundation of China (61471125).", "\n\nThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.", "\n\nThis prospective study was approved by our institutional review board of Shanghai Public Health Clinical Center Affiliated to Fudan University. ", "All patients gave their full informed consent before liver examination. ", "The procedure followed was in accordance with the Declaration of Helsinki.", "\n\nAll authors give their consent for publication.", "\n\nThe authors declare that they have no competing interests.", "\n" ]

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[ "Rice University professor Dan Wallach wrote a blog post in February that discussed the threat that network eavesdropping poses to Android users. ", "Several applications, including the platform's native Google Calendar software, don't use SSL encryption to protect their network traffic. ", "Wallach speculated that the calendar software could be susceptible to an impersonation attack.", "\n\nResearchers at the University of Ulm followed up on Wallach's findings and devised a proof-of-concept attack to demonstrate the vulnerability. ", "Several of Google's applications use the ClientLogin authentication system but fail to use SSL to encrypt their communication with Google's servers, making them susceptible to eavesdropping attacks.", "\n\nClientLogin is designed to allow applications to trade a user's credentials for an authentication token that identifies the user to the service. ", "If the token is passed to the server in an unencrypted request, it could potentially be intercepted and used by the attacker.", "\n\nThe authentication tokens remain valid for two weeks, during which time the attacker has relatively broad access to the user's account in a specific Google service. ", "The researchers found that Android's calendar sync, contact sync, and Picasa sync are all susceptible.", "\n\nAlthough the bug has already been fixed (for calendar and contact sync, but not Picasa) in Android 2.3.4—the latest version of the operating system—the vast majority of mobile carriers and handset manufacturers haven't issued the update yet. ", "According to Google's own statistics, this means that 99.7 percent of the Android user population is still susceptible to the vulnerability.", "\n\nThis reflects the need for better update practices among Android hardware vendors. ", "During a keynote presentation at the recent Google I/O event, product manager Hugo Barra acknowledged the problematic nature of the Android update process and told developers that an effort to address the issue is in the works. ", "At a press briefing following the keynote, Google's Andy Rubin offered some additional details.", "\n\nThere is no actual plan in place at this time, but a number of Google's largest handset and carrier partners have formed a working group to begin setting the guidelines for a new update initiative. ", "The participants intend to guarantee the availability of regular updates for a period of 18 months on new handsets. ", "They could also potentially define some boundaries to reduce the gap between when a new version of Android is released and when it is deployed over the air.", "\n\nAlthough the initiative is still at a very early stage and the policies it formulates will be entirely voluntary, it already has preliminary buy-in from enough prominent Android stakeholders to make it credible. ", "The leading Android handset manufacturers and all four of the major US carriers are currently involved.", "\n\nIf the group can build consensus around a reasonable set of update policies, it would be a big win for Android adopters. ", "It would ensure that security issues like the ClientLogin bug can be remedied in a timely manner. ", "Another positive side effect is that it would help diminish the uncertainty about product lifespan that frustrates many Android end users. ", "The fact that so many Android users are still at risk from a vulnerability that has already been fixed is a telling sign of the need for faster updates.", "\n\nUpdate: following widespread reports of this issue, Google has come up with a way to mitigate the issue on the server side. ", "The fix will reportedly be rolling out soon." ]

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[ "Turbochargers are widely used on internal combustion engines and, in the past, have been particularly used with large diesel engines, especially for highway trucks and marine applications.", "\nMore recently, in addition to use in connection with large diesel engines, turbochargers have become popular for use in connection with smaller, passenger car power plants. ", "The use of a turbocharger in passenger car applications permits selection of a power plant that develops the same amount of horsepower from a smaller, lower mass engine. ", "Using a lower mass engine has the desired effect of decreasing the overall weight of the car, increasing sporty performance, and enhancing fuel economy. ", "Moreover, use of a turbocharger permits more complete combustion of the fuel delivered to the engine, thereby reducing the overall emissions of the engine, which contributes to the highly desirable goal of a cleaner environment.", "\nThe design and function of turbochargers are described in detail in the prior art, for example, U.S. Pat. ", "Nos. ", "4,705,463, 5,399,064, and 6,164,931, the disclosures of which are incorporated herein by reference.", "\nTurbocharger units typically include a turbine operatively connected to the engine exhaust manifold, a compressor operatively connected to the engine air intake manifold, and a shaft connecting the turbine and compressor so that rotation of the turbine wheel causes rotation of the compressor impeller. ", "The turbine is driven to rotate by the exhaust gas flowing in the exhaust manifold. ", "The compressor impeller is driven to rotate by the turbine, and, as it rotates, it increases the air mass flow rate, airflow density and air pressure delivered to the engine cylinders.", "\nAs the use of turbochargers finds greater acceptance in passenger car applications, three design criteria have moved to the forefront. ", "First, the market demands that all components of the power plant of either a passenger car or truck, including the turbocharger, must provide reliable operation for a much longer period than was demanded in the past. ", "That is, while it may have been acceptable in the past to require a major engine overhaul after 80,000-100,000 miles for passenger cars, it is now necessary to design engine components for reliable operation in excess of 200,000 miles of operation. ", "It is now necessary to design engine components in trucks for reliable operation in excess of 1,000,000 miles of operation. ", "This means that extra care must be taken to ensure proper fabrication and cooperation of all supporting devices.", "\nThe second design criterion that has moved to the forefront is that the power plant must meet or exceed very strict requirements in the area of minimized NOx and particulate matter emissions. ", "Third, with the mass production of turbochargers, it is highly desirable to design a turbocharger that meets the above criteria and is comprised of a minimum number of parts. ", "Further, those parts should be easy to manufacture and easy to assemble, in order to provide a cost effective and reliable turbocharger.", "\nTurbocharger efficiency over a broad range of operating conditions is enhanced if the flow of motive gas to the turbine wheel can be controlled, such as by making the vanes pivotable so as to alter the geometry of the passages therebetween. ", "The design of the mechanism used to effect pivoting of the vanes is critical to prevent binding of the vanes. ", "Other considerations include the cost of manufacture of parts and the labor involved in assembly of such systems.", "\nAdditionally, the design of the vane is critical to both the efficiency of the gas delivery to the turbine, as well as the reliability of the variable geometry assembly. ", "While movement of the vanes allows for control of the gas delivery, it also adds the problem of leakage past the moveable vanes. ", "Additionally, due to the extreme environment that the moveable vanes are placed in, the structure of the vanes, especially where pivotally connected via vane posts and the like, must be sound to avoid failure.", "\nIn U.S. Pat. ", "No. ", "6,679,052 to Arnold, the Applicant attempted to improve efficiency of the air delivery to the turbine wheel by providing a vane having a convex portion adjacent the leading edge and a concave portion adjacent the vane trailing edge. ", "As shown in FIG. ", "1, the Arnold vane 106 has an outer surface 108, an inner surface 110, a leading edge 112, a trailing edge 114, an actuation tab 116, and a post hole 118. ", "The leading edge 112 is characterized by having a larger radius of curvature such that an adjacent portion of its outer surface 108 is located a greater distance from the actuation tab 116, thereby increasing the airfoil thickness of the vane adjacent the leading edge. ", "The inner surface 110 has a shape that is defined by two differently shaped sections. ", "Moving from the leading edge 112, the inner surface has a convex-shaped portion 120 that is defined by a radius of curvature that is greater than that of the leading edge to contour or blend the leading edge into the inner surface. ", "The convex-shaped portion 120 extends from the leading edge 116 to just past the tab 116. ", "Moving from the convex-shaped portion 102, the inner surface has a concave-shaped portion 122 that extends to the vane trailing edge 122.", "\nThe Applicant in Arnold felt that the enlarged and upwardly oriented leading edge and the shape of the inner surface of this vane would operate to provide improved aerodynamic effect. ", "However, the Arnold vane still suffered from the drawback of leakage between the vane and the adjacent components (the upstream and downstream nozzle rings which are not shown.) ", "While the Arnold vane 106 had a curved surface in a longitudinal direction of the vane inner surface 110, it had a flat surface in a traverse direction. ", "Such a flat surface along the inner surface 110 in a traverse direction can provide a substantially uniform pressure profile along the traverse direction and promotes leakage along the side edges of the vane between the vane and the adjacent components such as the nozzle rings between which the vane is sandwiched.", "\nThe Applicant in Arnold provided yet another embodiment of a vane that was again intended to provide improved aerodynamic effects and improve efficiency. ", "This other embodiment is shown in FIG. ", "2 and is a vane 124 having an outer surface 126, an inner surface 128, a leading edge 130, a trailing edge 132, an actuation tab 134, and a post hole 136. ", "The leading edge 130 is characterized by having a somewhat smaller radius of curvature, and the inner surface 128 comprises three differently shaped sections. ", "Moving from the leading edge 130, the inner surface 128 has a downwardly canted generally planar section 138 that extends away from the vane leading edge adjacent the tab 134 at an angle of approximately 45 degrees. ", "The canted section 138 extends for less than about ¼ the total distance along the inner surface and is transitioned to a convex section 140. ", "The convex section is defined by a radius of curvature that is generally less than that used to define the arc of the outer surface 126. ", "The convex section 140 extends along the inner surface to about the mid point of the vane and defines a point of maximum airfoil thickness for the vane.", "\nSimilar to the other Arnold embodiment, vane 124 still suffered from the drawback of leakage between the vane and the adjacent components (the upstream and downstream nozzle rings which are not shown). ", "While the Arnold vane 124 had multiple curved surfaces in a longitudinal direction of the vane inner surface 128, it had a flat surface in a traverse direction. ", "Such a flat surface along the inner surface 128 in a traverse direction can provide a uniform pressure profile in the traverse direction and promotes leakage along the side edges of the vane between the vane and the adjacent components such as the nozzle rings between which the vane is sandwiched.", "\nFIG. ", "17 shows a perspective view of a vane S, which corresponds to the vane illustrated in FIG. ", "1 of EP-A-1 422 385. ", "As can be seen from FIG. ", "17, the prior art vane S fastened on the shaft W has a sealing flange F on the vane mounting ring side, said flange being designed to be substantially circular and concentric with the axis of the vane shaft, in order to reduce the leakage flow between the vane shaft and hole in the vane mounting ring and to protect the hole from the ingress of particles.", "\nIn order to ensure the mechanical adjustment function of the vane S, an axial gap between the vane S and the vane mounting ring and also the second wall, such as, for example, the disk, is required. ", "However, the leakage flow occurring through this axial gap has a negative impact on the efficiency of the turbocharger, in particular when there are small quantities of exhaust gas. ", "In order to keep the leakage flow losses as small as possible, on the one hand the axial gap has to be designed to be as small as possible and, on the other hand, the highest possible throttling action has to be achieved in the gap.", "\nAs can be seen from the cross-sectional view of FIG. ", "18 of the appended drawing, the only contribution made by the prior art turbocharger to reducing the leakage flow is provided only by an axial length section of the vane, based on its total length, which corresponds substantially to the diameter of the sealing flange F.\nThus, there is a need for a vane that improves sealing in a turbocharger, such as a variable geometry turbocharger. ", "There is a further need for such a vane that is reliable and cost-effective. ", "There is yet a further need for such a vane that facilitates assembly of the turbocharger." ]

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[ "Q:\n\nPHP - converting hexdec value to version string\n\nI'm working with an undocumented API that serves a version number as hexdec value. ", "I wish to convert this to the versioning string.", "\nExample\nThe API serves the following value: 117473280 (hexdec('7008000'))\nThis should be converted to the string: 7.00\nI've made the following function to do this:\nfunction getFirmwareFromDechex($dechex) {\n if(!empty($dechex) || $dechex !", "== '0') {\n $dechex = dechex($dechex);\n $dechex = substr($dechex, 0, 3);\n $dechex = number_format($dechex / 100, 2);\n \n return $dechex;\n }\n \n return false;\n}\n\necho getFirmwareFromDechex('117473280');\n\nAnd this works. ", "However, when it has to convert version 10.00, it converts it to 1.00.", "\nHow can I make the function compatible with higher version numbers such as 10.00?", "\nUpdate\nAfter looking how the third party displays these versions on their website, it does seem I need to pad the number to the left with a 0.", "\n\nA:\n\nI think the hex string should be 8 bytes long, so pad the start with 0's (str_pad() with STR_PAD_LEFT) and then take the first 4 characters...\nfunction getFirmwareFromDechex($dechex) {\n if(!empty($dechex) || $dechex !", "== '0') {\n $dechex = str_pad(dechex($dechex), 8, 0, STR_PAD_LEFT);\n $dechex = substr($dechex, 0, 4);\n $dechex = number_format($dechex / 100, 2);\n\n return $dechex;\n }\n\n return false;\n}\n\n" ]

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[ "A high-ranking Yemeni security official has told McClatchy that the\nObama administration’s recently announced terror threat which supposedly\ntargeted US embassies had “no basis in fact” and was manufactured\nmerely to dampen opposition to drone strikes." ]

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[ "1. ", "Field of the Invention\nThe field of the invention is that of the flow of aircraft traffic over the airport areas before they takeoff or after they have landed and of the electronic and data processing means allowing the route to be followed over these areas to be indicated to the crews.", "\n2. ", "Description of the Prior Art\nConventionally, during taxiing phases over an airport area, the pilots receive taxiing instructions from the air traffic control or ATC. ", "FIG. ", "1 shows a partial plan view of an airport area Z. In this area, the aircraft A situated on the taxiway B must get to the takeoff runway “27L” appearing in black in FIG. ", "1. ", "The pilot will receive a taxiing instruction indicating to him for example to go via the taxiways “BD20” and “Y11”. ", "An ATC instruction authorizing the taxiing is also called taxiing clearance. ", "These instructions give pilots the authorization to taxi up to a certain point without fear of any conflict with another aircraft or another vehicle. ", "The ATC communicates this information by voice and the pilots remember it and may write it down on paper or in a text input area, such as a “scratchpad”, of an electronic control unit. ", "This unit can be an MCDU, acronym for “Multi Control Display Unit”. ", "The pilots then use paper maps to locate themselves within the airport area and follow the route indicated.", "\nCurrently, some onboard systems can calculate the route to be followed based on these instructions and display this route on electronic airport maps in order to simplify the navigation task of the pilots. ", "The system must therefore recognize the clearances perfectly in order to be able to process them and display them.", "\nSeveral solutions are possible for inputting the clearances. ", "Indeed, the clearance can be entered into the system: Either automatically, by receiving the information needed for the display of the clearance via a digital link or by voice recognition; Or through manual intervention by the pilot. ", "In the latter case, he inputs the ATC instruction as a text which is then interpreted by the system and then displayed on the map. ", "The input operation can be carried out on a touch screen and read by a writing recognition system or more simply, the input can be done on an alphanumeric keyboard. ", " \nIn the case of a manual intervention by the pilot, inputting on an alphanumeric keyboard offers the advantage of being able to use editing means such as the MCDU units already present on many aircraft.", "\nIn general, the taxiing instructions indicate the destination which, by way of example, might be “holding position”, “stand”, “runway” then the route to be followed composed of names of taxiways. ", "Thus, an instruction generally takes the following form:\nTAXI TO [Halt Position] VIA [Specific Route to be Followed]\nIn order to input an instruction without ambiguities, this instruction must be input by introducing a separator between each airport element so as to allow the system to easily find it and without errors in a database. ", "For example, the instruction ATC: “TAXI TO stand E10 VIA taxiways T40, T41 and M2” corresponds to the pilot inputting the following: “E10-T40-T41-M2”. ", "However, the addition of a separator between each element adds a workload for the pilot who runs the risk of not having the time to input the complete instruction dictated to him by the ATC." ]

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[ "Why Could Bill and Hillary Clinton be Very Unhappy Today?", "\n\nSomething happened last night that took the Clinton's all the way back to 1992 -- but with a very different outcome.", "\n\nBill Clinton became President of the United States in 1992, beating Pres. ", "Bush, in large part because of two very simple words -- Ross Perot.", "\n\nIn 1992, President George H. W. Bush was running for re-election. ", "He was relatively popular because of the recent victory in the First Gulf War, but had run into problems with a sluggish economy. ", "Running against him was a young, relatively untested Democratic governor from Arkansas named Bill Clinton.", "\n\nWhat changed everything was the entrance of Ross Perot, the Texas billionaire. ", "Perot ended up getting 18% of the vote, which in all probability came largely from Republicans. ", "So Bill Clinton ended up winning the Presidency -- with only 43% of the popular vote!", "\n\nOne of Bill and Hillary's great hopes for victory in 2016 has now been dashed. ", "They undoubtedly hoped that Donald Trump in 2016 would do what Ross Perot did in 1992 -- and run as an independent billionaire third party candidate. ", "That would pull millions of votes away from the Republicans and help assure another Clinton victory.", "\n\nNow that Trump has firmly ruled out a third party candidacy, that option is gone for the Clintons. ", "an Hillary still win? ", "It is certainly a possibility -- but now she will be running against a united, and not a divided, Republican party. ", "So the history of 1992 looks unlikely to repeat itself in 2016. ", "And Republicans breathed a great sigh of relief!" ]

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[ "Samad (crater)\n\nSamad is a crater in the northern hemisphere of Saturn's geologically active moon Enceladus. ", "Samad was first discovered in Voyager 2 images. ", "It is located at 60.3° North Latitude, 4.5° West Longitude and is across. ", "Currently available images are too low in resolution to determine if this crater has been tectonically deformed, but the lack of a prominent central dome suggests Samad has not undergone the level of viscous relaxation of other craters in its size range, like Dalilah or Ahmad. ", "Samad is located near the larger craters Aladdin and Ali Baba.", "\n\nSamad is named after a Sheikh who guides Musa and Talib to the mountains in the tale \"The City of Brass\" from One Thousand and One Nights.", "\n\nReferences \n\nCategory:Impact craters on Enceladus" ]

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