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[ "Characterization of PfDYN2, a dynamin-like protein of Plasmodium falciparum expressed in schizonts.", "\nDynamin superfamily members are large GTPases conserved through evolution mainly described as mechanochemical enzymes involved in membrane scission events. ", "The Plasmodium falciparum dynamin-2 (Pfdyn2) gene was cloned from the FcB1 strain. ", "PfDYN2 belongs to the dynamin-like protein subgroup of the dynamin superfamily since it possesses a large GTPase domain together with the conserved dynamin_M and GED domains. ", "Recombinant PfDYN2 was able to bind GTP, to hydrolyze GTP into GDP and to self-associate in low-salt conditions. ", "PfDYN2 expression was restricted to schizonts where it localized in punctuate structures within the parasite cytoplasm. ", "PfDYN2 partly co-localized with markers of the parasite endoplasmic reticulum, Golgi apparatus and apicoplast, suggesting it could be implicated in vesicular trafficking and/or organelle fission events known to occur during the last hours of the parasite development in erythrocytes. ", "PfDYN2 and the previously described PfDYN1 are the only two dynamin superfamily members identified in the P. falciparum genome and the available data suggest that this situation is conserved in the Apicomplexa phylum." ]

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[ "A : \"a\" B ;\n : \"b\" A ;\nB : \"a\" B ;\n : \"b\" C ;\nC : \"a\" B ;\n : \"a\" ;\n" ]

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[ "Q:\n\nJavaFX FXML, для чего Controller?", "\n\nВ уроках об FXML говорится об пользе и преимуществах разделения интерфейса и логики в программах, но есть ещё непонятный мне класс \"Controller\" (помимо классов логики и интерфейса) . ", "В чём его идея, какую функцию он выполняет? ", "В чём преимущество такого подхода? ", "\n\nA:\n\nВозможно, Вам будет интересно мое мнение:\nЛично я считаю, что термин \"controller\" в документации FXML следует воспринимать\nне более, чем то, что в других технологиях называется \"code behind\".", "\nТо есть это просто дополнительный код для выполнения задач связанных с отображением\n\"вида\" (view). (", "Под \"видом\" я здесь имею в виду конкретный участок пользовательского интерфейса).", "\nFXMLLoader с помощью инъекций связывает объект контроллера с деревом объектов,\nкоторое он нагенерил по fxml-разметке. ", "А также предоставляет некоторые другие \nвозможности, например, одностороннюю привязку (\"${expression}\") атрибутов-свойств и прочее.", "\nНо вот, к примеру, двусторонняя привязка (\"#{...}\") FXMLLoader'ом так до сих пор не реализована,\nи класс контроллера — это как раз подходящее место для ее описания.", "\nБез сомнения, то, что будет в этом \"code behind\" полностью зависит от вашего подхода и самодисциплины.", "\nКак со стороны размещения бизнес-логики, так и со стороны разделения зон ответственности программиста и дизайнера.", "\nИменно Вам решать, будет ли этот класс толстым носителем логики, или лишь тонкой прослойкой между моделью и видом.", "\nПри этом, даже, если вы будуте использовать какой-то определенный фреймворк (например, mvvmFx),\nто это не спасет вас от возможности ошибочно разместить часть бизнес-логики модели в \"code behind\"\nопределенного вида (эта ошибка может и обнаружится, когда такая функциональность потребуется в другом месте).", "\nС другой стороны, помня о том, что css-стили (кроме USER_AGENT) имеют определенное преимущество над JavaFx-свойствами узлов, \nв контроллере имеет смысл описывать настройки интерфейса с помощью JavaFx-свойств, а не заданием css-стилей —\nдля того, чтобы дизайнер впоследствии смог исправить интерфейс указанием css-стилей.", "\nИ даже в этом случае программист может сказать свое \"последнее слово\", восстанавливая значение свойства в обработчике изменения этого свойства ;)\n\nПод словами \"определенное преимущество\" я имею ввиду то, что \ncss-стиль перекрывает соответствующее ему свойство. ", "Но только в момент\nперепроверки стилей. ", "А до этой перепроверки будет действовать свойство.", "\nНапример, можно установить какое-либо свойство узлу (в обработчике нажатия другой кнопки) и это будет отражено на экране, но при наведении на узел курсора мыши, узлу устанавливается\nпсевдокласс hover и выполняется переустановка его стилей в соответствии\nс псевдоклассом, тем самым свойство будет заменено стилем. ", "После того, \nкак курсор мыши будет убран с узла, у него будет также убран псевдокласс hover. ", "Это изменение псевдоклассов опять повлечет переустановку стилей узла, но в этих стилях не указано то изменение, которое делалось для свойства в обработчике. ", "Поэтому свойство на экране отражено не будет, хотя оно и работало вначале некоторое время.", "\n\n" ]

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[ "× Thanks for reading! ", "Log in to continue. ", "Enjoy more articles by logging in or creating a free account. ", "No credit card required. ", "Log in Sign up {{featured_button_text}}\n\nFormer Nebraska center Brady Heiman is transferring to South Dakota.", "\n\n“I have a good relationship with the coaches and know a lot of the players,” Heiman said. “", "They see me as not a traditional 5 and being able to pick and pop along with being able to move off the block.”", "\n\nThe Platteview graduate left the Husker program after one season. ", "He was one of several players told not to return by new coach Fred Hoiberg.", "\n\nHeiman appeared in 30 games his freshman season, averaging 8.5 minutes and 1.8 points per game. ", "The 6-foot-11, 215-pound center shot 59.5% from the floor and 29.4% from the foul line.", "\n\nHeiman heard from several Division I programs after his name was entered in the transfer portal. ", "He settled on three schools — UNO, South Dakota and Colorado State — because they were close to home.", "\n\nHe ultimately chose the Coyotes.", "\n\nOut of high school, Heiman picked NU over scholarship offers from 10 D-I programs, including South Dakota and UNO." ]

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[ "Surfactant-histidine-heme ternary complex as a simple artificial heme enzyme in organic media\nA surfactant-heme complex which shows peroxidase activity in organic media has been prepared by a method utilizing water-in-oil (W/O) emulsions. ", "Both the aqueous phase pH and the type of surfactant appeared to have prominent effect on the catalytic activity of the heme complex in benzene. ", "The catalytic efficiency of the heme complex was enhanced more than ten times by adding histidine to the aqueous phase of W/O emulsions in the preparation process. ", "The enhancement of peroxidase activity was observed only in a nonaqueous medium due to the increase of the effective concentration of histidine as an activator. ", "In the present study, we propose a simple preparation method for an artificial heme enzyme which works in nonaqueous media. ", "Copyright 1999 John Wiley & Sons, Inc." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Introduction\n============\n\nPost-translational modifications are critical mechanisms through which protein activity is regulated. ", "Conjugation of ubiquitin can control the function of target proteins in multiple ways, including degradation, subcellular localization, and activity ([@B1], [@B2]). ", "The consequences of ubiquitylation vary depending on the type and length of the ubiquitin chain, and many proteins are controlled through ubiquitylation ([@B1][@B2][@B4]). ", "The process itself is highly regulated with a cascade involving ubiquitin-activating, ubiquitin-conjugating, and ubiquitin-ligating enzymes promoting the conjugation of ubiquitin to selected target proteins. ", "This process can be reversed by the activity of deubiquitylating enzymes (DUBs)[^4^](#FN4){ref-type=\"fn\"} that remove ubiquitin ([@B5], [@B6]).", "\n\np53 is a potent tumor suppressor protein that is primarily regulated at the level of protein stability ([@B7]). ", "A number of ubiquitin ligases that target p53 for polyubiquitylation and degradation have been described, including MDM2 ([@B8], [@B9]), Chip ([@B10]), Pirh2 ([@B11]), and ARF-BP1 ([@B12]). ", "MDM2 itself is also regulated by ubiquitylation and degradation, and several DUBs, including USP7 ([@B13]), USP2a ([@B14]), and USP15 ([@B15]), have been shown to promote p53 degradation by deubiquitylating and stabilizing MDM2. ", "p53 is also the direct target of a number of DUBs, including USP10 ([@B16]), USP29 ([@B17]), USP42 ([@B18]), and Otubain1 ([@B19]). ", "After DNA damage and its phosphorylation by ATM, USP10 localizes to the nucleus to stabilize p53. ", "USP42 was shown to play a role in accelerating the stabilization of p53 in response to genotoxic stress. ", "However, it was clear from these studies that lack of USP42 delayed but did not prevent the full stabilization of p53 protein ([@B18]).", "\n\nAs with other protein modification systems, the potential number of target proteins exceeds the number of DUBs (around 100 in humans ([@B20])), indicating that each DUB is likely to target many different proteins. ", "In our continued analysis of USP42 function, we have identified monoubiquitylated histone H2B as a target for deubiquitylation by USP42. ", "The dynamic interchange and balance between ubiquitylation and deubiquitylation of histones is critical for the regulation of transcription ([@B21][@B22][@B26]), and our data suggest that USP42 may be an important component of this fundamental level of control of transcriptional activity.", "\n\nEXPERIMENTAL PROCEDURES\n=======================\n\n### \n\n#### Tissue Culture\n\nCells were cultured in DMEM supplemented with glutamine and 10% FCS.", "\n\n#### Plasmids\n\nGFP-FLAG-USP42 and USP42 C120A have been described before ([@B18]). ", "All deletion constructs were derived by PCR-based deletion using KOD Hot Start polymerase (Merck Millipore, 71842).", "\n\n#### Transfection\n\nCells were transfected with the indicated plasmids (Genejuice, Merck Millipore, 70967) or siRNA (Hiperfect, Qiagen, 301705) as described before ([@B18]).", "\n\n#### Western Blotting\n\nGels were transferred to a nitrocellulose membrane using a Mighty Small chamber from Hoefer. ", "Blots were blocked in 5% milk TBS-Tween for at least 20 min and incubated with the appropriate antibodies overnight at 4 °C on a shaker. ", "After three 5-min washes with TBS-Tween, the blots were incubated with the appropriate LI-COR Biosciences secondary antibody (in 5% milk TBS-Tween in a 1:10,000--20,000 dilution) followed by LI-COR Biosciences Odyssey detection (*K* set to 1). ", "Antibodies used were: USP42 (Atlas, HPA006752), GFP (Abcam, ab6556; Roche Applied Science, 11814460001), H2B (Cell Signaling Technology, 2934), RNA Pol II (Santa Cruz, SC-65884), actin (Santa Cruz, SC-1616), tubulin (Santa Cruz, SC-8035), Ubi-H2B (Cell Signaling Technology, 5546), H2A (Cell Signaling Technology, 3636), and Ubi-H2A (Millipore, 05-678; Cell Signaling Technology, 8240). ", "Western blots were quantified using the LI-COR Biosciences Image Studio software V 2.1.10 and plotted using PRISM software from GraphPad.", "\n\n#### Immunoprecipitation\n\nCells were washed once with PBS, scraped in 1 ml of PBS into a 1.5-ml Eppendorf tube, and centrifuged for 5 min at 3000 rpm at 4 °C in a refrigerated Eppendorf microcentrifuge. ", "Cells were subsequently lysed in lysis buffer (50 m[m]{.smallcaps} Tris-HCl, pH 7.4, 150 m[m]{.smallcaps} NaCl, 0.25% deoxycholic acid, 1% Nonidet P-40, protease inhibitor mixture (Roche Applied Science, 04693159001)) and sonicated in a Bioruptor (20 s at lowest setting) to lyse the chromatin. ", "Magnetic protein G beads (Invitrogen, 10004D) or Dynabeads Rat anti-Mouse IgM (Invitrogen, 11039D) were washed three times in lysis buffer and blocked in lysis buffer plus 5% BSA for 1 h. Beads, antibody, and lysates were mixed; the volume was topped up to 700 μl with lysis buffer and samples were rotated overnight at 4 °C, washed three times in lysis buffer and boiled in 1× SDS reducing loading buffer for elution.", "\n\n#### Immunofluorescence\n\nConfocal immunofluorescence was performed as described previously ([@B27]). ", "In brief, cells were cultured on coverslips at approximately 70% confluence. ", "At harvesting, cells were washed three times in PBS, fixed in 4% paraformaldehyde for 15 min, and stained with DAPI solution. ", "For colocalization of USP42 and DNA-bound RNA Pol II, cells were washed in CSK buffer (0.3 [m]{.smallcaps} sucrose, 10 m[m]{.smallcaps} PIPES, 3 m[m]{.smallcaps} MgCl~2~, 1 m[m]{.smallcaps} EGTA, 0.5% Triton X-100) prior to fixation to remove unbound soluble proteins.", "\n\n#### FACS Analysis\n\nA U2OS clone stably expressing CMV Cherry and doxycycline-inducible GFP was established by puromycin selection over 3 months followed by colony picking and characterization. ", "After transfection with plasmids or siRNA, cells were induced with doxycycline or solvent control as described in the text. ", "Cells were then harvested by trypsinization and resuspended in 1% FCS in PBS-Tween followed by immediate FACS analysis (BD FACSAria). ", "FlowJo was used to determine the median fluorescence.", "\n\n#### Chromatin Immunoprecipitation\n\nChromatin immunoprecipitation was performed as described before ([@B18]).", "\n\n#### In Vitro Deubiquitylation Assays\n\nUSP42 constructs were expressed in HEK293T cells, lysed in radioimmune precipitation assay buffer, and purified by precipitation using GFP-trap_M matrix (CromoTek, gtm-20). ", "Histones were purified from HeLa cells using an acid extraction protocol (Abcam). ", "In brief, nuclear extracts were incubated with 0.2 [n]{.smallcaps} HCl overnight followed by centrifugation, aliquoting, freezing in liquid N~2~, and storage at −80 °C. ", "Assays: HeLa histones were thawed, rebuffered with NaOH, and diluted in 50 m[m]{.smallcaps} Tris, pH 8 to a volume of 80 μl. ", "Aliquots were added to purified USP42 on GFP-trap_M matrix and incubated at room temperature, and 10-μl samples were taken at the indicated time points, mixed 1:1 in 2× SDS loading buffer, and boiled for 5 min to stop the deubiquitylation reaction.", "\n\n#### Fractionation\n\nCells were treated as described previously ([@B31]). ", "In brief, after fractionation into nuclear and cytoplasmic fractions, the nuclear fraction was further separated by incubation in lysis buffer (described above) and centrifuged into DNA bound (pellet) and nuclear soluble fractions.", "\n\nRESULTS AND DISCUSSION\n======================\n\nOur previous work showed that USP42 can target p53 for deubiquitylation, with depletion of USP42 resulting in delays in stabilization of p53 and recruitment of p53 to target gene promoters ([@B18]). ", "However, these studies also showed that USP42 loss did not impact the fully activated levels of p53, which were stabilized to a similar extent irrespective of USP42 expression within 16 h of genotoxic or ribosomal stress. ", "In these studies, the low dose of actinomycin D used has been shown to induce ribosomal stress and specifically activate p53 rather than more generally interfere with transcription ([@B28]). ", "In agreement with these published data, we have found that depletion of USP42 does not impact recruitment of p53 to the *p21(CDKN1A)* promoter when examined at a 16-h time point after induction of a p53 response with low dose actinomycin D ([Fig. ", "1](#F1){ref-type=\"fig\"}*A*). ", "Interestingly, USP42 was also recruited to the *p21* locus after actinomycin D treatment, but importantly the binding of USP42 was at sites distinct from those bound by p53. ", "Although ChIP assays detected p53 on its well characterized binding site in the *p21* distal promoter ([@B29]), USP42 was detected further downstream at the transcription start site of the *p21* gene ([Fig. ", "1](#F1){ref-type=\"fig\"}*B*). ", "To determine whether USP42 recruitment depends on the activation of *p21* transcription by p53, we repeated the experiment in control and p53 knockdown cells ([Fig. ", "1](#F1){ref-type=\"fig\"}*C*). ", "Although USP42 recruitment to the start site and the first intron was clearly increased following low dose actinomycin D treatment, this was at least partially dependent on p53 because a knockdown of p53 caused a reduction of USP42 recruitment. ", "Taken together these data suggest that USP42 participates in transcription regulation through a mechanism that is dependent on p53 but likely to be independent of direct binding to p53. ", "An overview of the ChIP primers is shown in [Fig. ", "1](#F1){ref-type=\"fig\"}*G*.", "\n\n{#F1}\n\nTo further understand this role of USP42, we examined its localization in the cell. ", "Fractionation studies indicated that USP42 was associated with the insoluble chromatin fraction, and this localization was independent of DUB activity because it was also seen with the catalytically inactive USP42 mutant C120A ([Fig. ", "1](#F1){ref-type=\"fig\"}*D*). ", "Immunofluorescence analysis of endogenous proteins showed that USP42 was present in nuclear foci that co-localized with DNA-bound RNA Pol II using antibodies to detect both total and activated (phosphorylated) RNA Pol II ([Fig. ", "1](#F1){ref-type=\"fig\"}*E*), and endogenous USP42 and RNA Pol II were shown to co-immunoprecipitate ([Fig. ", "1](#F1){ref-type=\"fig\"}*F*). ", "This was of particular interest because a proteomic analysis of USP42-binding proteins had shown association of USP42 with histone H2B and other components of the transcriptional machinery (not shown).", "\n\nTo confirm this interaction, we immunoprecipitated endogenous USP42 from cells and were able to detect a specific interaction with histone H2B ([Fig. ", "2](#F2){ref-type=\"fig\"}*A*). ", "Expression of USP42 mutants targeting the linker domain and the C-terminal lysine-rich domain ([Fig. ", "2](#F2){ref-type=\"fig\"}*B*) showed that although the DUB-inactive USP42 C120A mutant retained the ability to bind histone H2B, this interaction was reduced with the ΔKK mutant and lost with the Δlinker mutant ([Fig. ", "2](#F2){ref-type=\"fig\"}*C*). ", "Immunofluorescence studies confirmed that both wild type and C120A USP42 proteins retained localization within nuclear foci previously associated with DNA-bound RNA Pol II, whereas the ΔKK mutant showed a diffuse nuclear localization, and the Δlinker mutant was relocalized to subnuclear structures likely to be nucleoli ([Fig. ", "2](#F2){ref-type=\"fig\"}*D*).", "\n\n{#F2}\n\nThe binding of USP42 to histone H2B suggested that USP42 may target histones for deubiquitylation. ", "Indeed, *in vitro* analysis showed that USP42 is able to efficiently deubiquitylate histone H2B ([Fig. ", "2](#F2){ref-type=\"fig\"}, *E* and *F*). ", "This activity was dependent on the DUB activity of USP42 because the C120A mutant was unable to deubiquitylate histone H2B in this assay ([Fig. ", "2](#F2){ref-type=\"fig\"}, *E* and *F*). ", "Interestingly, the ΔKK mutant and Δlinker mutants retained the ability to deubiquitylate histone H2B in this *in vitro* assay, suggesting that the failure of these mutants to effectively target histone H2B in cells is a reflection of their inappropriate localization rather than a loss of DUB activity. ", "In the *in vitro* assay, USP42 showed a similar ability to deubiquitylate histones H2A and H2B ([Fig. ", "2](#F2){ref-type=\"fig\"}*G*). ", "However, in cells, the ubiquitination of histone H2A was not affected by USP42 depletion, whereas the overall level of ubiquitylated H2B was modestly but consistently increased ([Fig. ", "2](#F2){ref-type=\"fig\"}*H*). ", "These results indicate that the ability of USP42 to target proteins is regulated by factors in addition to DUB activity such as the control of appropriate cellular localization.", "\n\nBecause histone H2B ubiquitylation and deubiquitylation are important for transcriptional regulation ([@B22]), we postulated that USP42 may be able to influence transcription efficiency from promoters beyond those regulated by p53. ", "To analyze an effect of USP42 on more general transcription, we turned to a model system in which fluorescent reporter proteins (Cherry and GFP) are stably integrated in the genome and expressed from constitutive (CMV, Cherry) or inducible (doxycycline, GFP) promoters. ", "This system makes it possible to directly manipulate the induction of GFP without having to take other regulatory processes into account. ", "In addition, this system allows us to normalize expression of the reporter protein on a per cell basis rather than to a housekeeping factor that itself may be regulated by USP42. ", "siRNA depletion of USP42 resulted in an overall reduction of CMV-driven Cherry expression detected directly by FACS ([Fig. ", "3](#F3){ref-type=\"fig\"}, *A* and *B*). ", "Interestingly, depletion of USP42 also slightly reduced the basal expression of doxycycline-driven GFP and substantially decreased the induced levels of GFP expression following doxycycline treatment of the cells ([Fig. ", "3](#F3){ref-type=\"fig\"}, *C* and *D*). ", "The inhibition of GFP expression on a basal level and postinduction with doxycycline could be observed at both mRNA ([Fig. ", "3](#F3){ref-type=\"fig\"}*E*) and protein levels ([Fig. ", "3](#F3){ref-type=\"fig\"}*F*), confirming that modulation of USP42 expression regulates the transcription of both constitutive and inducible promoters.", "\n\n{#F3}\n\nTo determine whether the knockdown of USP42 also affects the transcription of endogenous loci, we analyzed the effect of USP42 knockdown on the transcription of p53 target genes upon its induction with actinomycin D and Nutlin. *", "p21* was chosen because we have demonstrated that USP42 is recruited to the *p21* transcription start site after p53 induction ([Fig. ", "1](#F1){ref-type=\"fig\"}*B*), and induction of p53 itself relies mainly on stabilization of protein levels rather than induction of p53 transcription. ", "To extend the study, we also examined a further 19 p53-inducible genes ([Fig. ", "3](#F3){ref-type=\"fig\"}*G*). ", "As expected, p53 target genes were induced upon both Nutlin and actinomycin D treatment, resulting in increased mRNA expression ([Fig. ", "3](#F3){ref-type=\"fig\"}*G*). ", "USP42 depletion decreased the transcription of most of these target genes, although some (*CASP1*, *PUMA*, *BAX*, *PIDD*, and *WIP1*) were not affected ([Fig. ", "3](#F3){ref-type=\"fig\"}*G*). ", "We have shown previously that USP42 depletion retards the stabilization of p53. ", "Importantly, therefore, at this time point (16 h), p53 protein was fully stabilized regardless of USP42 status ([Fig. ", "3](#F3){ref-type=\"fig\"}*H*). ", "Nevertheless, expression of target proteins p21 and MDM2 remained at lower levels, correlating with the lower mRNA expression ([Fig. ", "3](#F3){ref-type=\"fig\"}*G*).", "\n\nTo assess how the knockdown of USP42 induces a change in transcription from an endogenous promoter, we investigated the influence of USP42 reduction on the *p21* promoter. ", "Although p53 was recruited to the p53 response element following actinomycin D treatment ([Fig. ", "1](#F1){ref-type=\"fig\"}*A*), there was no change in the level of H2B ubiquitylation around this site, and the knockdown of USP42 did not lead to an increase of H2B ubiquitylation here ([Fig. ", "4](#F4){ref-type=\"fig\"}*A*). ", "By contrast, increased H2B ubiquitylation was detected at the transcriptional start site and first intron of the *p21* gene following actinomycin D treatment (where USP42 was bound; [Fig. ", "1](#F1){ref-type=\"fig\"}*B*). ", "Reduction of USP42 expression by siRNA led to a further increase of H2B ubiquitylation ([Fig. ", "4](#F4){ref-type=\"fig\"}*A*) but did not alter overall deposition of histone H2B ([Fig. ", "4](#F4){ref-type=\"fig\"}*C*). ", "Interestingly, USP42 did not affect H2A ubiquitylation ([Fig. ", "4](#F4){ref-type=\"fig\"}*B*) or deposition ([Fig. ", "4](#F4){ref-type=\"fig\"}*D*). ", "These results suggest that USP42 can specifically modulate the levels of H2B ubiquitylation in the first nucleosomes of the *p21* coding sequences in response to p53 activation. ", "To determine the outcome of USP42 knockdown on *p21* transcription, we analyzed p21 mRNA levels at several time points after induction with and without USP42 depletion ([Fig. ", "4](#F4){ref-type=\"fig\"}*E*). ", "As we had demonstrated before, USP42 knockdown lowers p21 transcription at the early time points of p53 induction as a reflection of the reduced levels of p53 ([@B18]). ", "However, at time points where p53 levels ([Fig. ", "3](#F3){ref-type=\"fig\"}*H*) and p53 recruitment to the *p21* promoter ([Fig. ", "1](#F1){ref-type=\"fig\"}*A*) have become equal, the levels of *p21* mRNA expression remain lower in USP42-depleted cells ([Fig. ", "4](#F4){ref-type=\"fig\"}*E*). ", "To determine whether the increased levels of Ubi-H2B observed at the *p21* locus after USP42 depletion affected RNA Pol II migration, we analyzed RNA Pol II distribution in a ChIP experiment. ", "Interestingly, we could observe increased levels of RNA Pol II association at the proximal region of the *p21* transcriptional start site upon USP42 knockdown, whereas USP42-depleted cells showed a reduction in RNA Pol II levels in the more distal part of the *p21* gene ([Fig. ", "4](#F4){ref-type=\"fig\"}*F*). ", "Taken together these results are consistent with a model where stalling of RNA Pol II at the transcriptional start site and inhibition of transcriptional progression are caused by an inability to deubiquitinate H2B.\n\n{#F4}\n\nTo extend our studies beyond p53, we investigated how USP42 reduction alters the induction of E2F1 target genes in an inducible system. ", "As observed with the induction of GFP ([Fig. ", "3](#F3){ref-type=\"fig\"}) and p53 ([Figs. ", "3](#F3){ref-type=\"fig\"} and [4](#F4){ref-type=\"fig\"}), depletion of USP42 reduced the mRNA expression of most of the E2F1-induced target genes examined ([Fig. ", "5](#F5){ref-type=\"fig\"}*A*). ", "Again, we found three examples of genes that were not significantly affected by USP42 depletion (*TAp73*, *FOXM1*, and *CCNE1*), indicating that the requirement for USP42 to promote transcription is not universal.", "\n\n{#F5}\n\nTaken together the results support a model whereby USP42 directly influences transcription by deubiquitylating histone H2B at transcriptional start sites ([Fig. ", "5](#F5){ref-type=\"fig\"}*B*). ", "As demonstrated in [Fig. ", "4](#F4){ref-type=\"fig\"}, the effect of USP42 is specific to H2B at the transcriptional start site (correlating with the site of USP42 binding to the promoter) rather than more globally affecting histone ubiquitylation. ", "This correlates with our observation that USP42 depletion has only a modest but reproducible impact on overall ubiquitylated H2B levels ([Fig. ", "2](#F2){ref-type=\"fig\"}*H*). ", "We suggest that this may reflect the selectivity of USP42 function in only controlling ubiquitylation, and thereby transcription, of a subset of promoters and the fact that promoters only constitute a very small part of the genome. ", "How USP42 gets recruited to the promoters is not yet understood, although our data suggest that efficient recruitment of USP42 depends on the binding of the transcription factors such as p53 ([Fig. ", "1](#F1){ref-type=\"fig\"}*C*).", "\n\nOur study identifies a role for USP42 in the regulation of transcription and provides evidence that this may be mediated through the control of histone ubiquitylation. ", "A previous proteomic analysis of the DUB interactome described an association of USP42 with histones, but also with a large number of other proteins, including other DUBs ([@B30]). ", "Although we can identify an effect of USP42 on histone H2B ubiquitylation, it is clear that the biological outcome of USP42 activity may also reflect the interaction with many other proteins. ", "Although ubiquitylation of histones is an important mechanism to regulate transcription, the exact outcome of the regulation or misregulation of histone ubiquitylation is complex, making the effect of USP42 activity difficult to predict. ", "This activity of USP42 acts in concert with our previously described function in the transient regulation of p53 stability, and we believe these to be independent functions of USP42. ", "How USP42 is recruited to the transcriptional start site of *p21* will require further investigation, although our work suggests that this does not depend on DUB activity. ", "Possibly USP42 is a component of the transcriptional machinery that is recruited in response to p53 binding to the promoter. ", "Our preliminary studies suggest that USP42 modulation will have disparate effects on transcription depending on the promoter and activating signal, and future studies will be required to define in more detail the physiological function of USP42. ", "However, our work reveals another component of this critical pathway for the regulation of gene expression in mammalian cells.", "\n\nThis work was supported by Cancer Research UK Grant C596/A10419.", "\n\nThe abbreviations used are: DUBdeubiquitylating enzymeActDactinomycin DChIPchromatin immunoprecipitationUSPubiquitin-specific peptidaseUbiubiquitinPolpolymerase.", "\n\nWe thank Peter Adams and Steve Jackson for helpful discussions and Biological Services at the Cancer Research UK Beatson Institute for technical assistance.", "\n\n[^1]: Both authors contributed equally to this work.", "\n\n[^2]: Present address: Centre de recherche en cancérologie de Lyon, Inserm UMR1052, CNRS UMR5286 Centre Léon Bérard, Bâtiment Cheney D Université Claude Bernard Lyon 1, 28 rue Laennec, F-69008 Lyon, France.", "\n" ]

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[ "The response of paroxysmal supraventricular tachycardia to overdrive atrial and ventricular pacing: can it help determine the tachycardia mechanism?", "\nStandard electrophysiologic techniques generally allow discrimination among mechanisms of paroxysmal supraventricular tachycardia. ", "The purpose of this study was to determine whether the response of paroxysmal supraventricular tachycardia to atrial and ventricular overdrive pacing can help determine the tachycardia mechanism. ", "Fifty-three patients with paroxysmal supraventricular tachycardia were studied. ", "Twenty-two patients had the typical form of atrioventricular (AV) junctional (nodal) reentry, 18 patients had orthodromic AV reentrant tachycardia, 10 patients had atrial tachycardia, and 3 patients had the atypical form of AV nodal reentrant tachycardia. ", "After paroxysmal supraventricular tachycardia was induced, 15-beat trains were introduced in the high right atrium and right ventricular apex sequentially with cycle lengths beginning 10 msec shorter than the spontaneous tachycardia cycle length. ", "The pacing cycle length was shortened in successive trains until a cycle of 200 msec was reached or until tachycardia was terminated. ", "Several responses of paroxysmal supraventricular tachycardia to overdrive pacing were useful in distinguishing atrial tachycardia from other mechanisms of paroxysmal supraventricular tachycardia. ", "During decremental atrial overdrive pacing, the curve relating the pacing cycle length to the VA interval on the first beat following the cessation of atrial pacing was flat or upsloping in patients with AV junctional reentry or AV reentrant tachycardia, but variable in patients with atrial tachycardia. ", "AV reentry and AV junctional reentry could always be terminated by overdrive ventricular pacing whereas atrial tachycardia was terminated in only one of ten patients (P < 0.001). ", "The curve relating the ventricular pacing cycle length to the VA interval on the first postpacing beat was flat or upsloping in patients with AV junctional reentry and AV reentry, but variable in patients with atrial tachycardia. ", "The typical form of AV junctional reentry could occasionally be distinguished from other forms of paroxysmal supraventricular tachycardia by the shortening of the AH interval following tachycardia termination during constant rate atrial pacing. ", "Atrial and ventricular overdrive pacing can rapidly and reliably distinguish atrial tachycardia from other mechanisms of paroxysmal supraventricular tachycardia and occasionally assist in the diagnosis of other tachycardia mechanisms. ", "In particular, the ability to exclude atrial tachycardia as a potential mechanism for paroxysmal supraventricular tachycardia has important implications for the use of catheter ablation techniques to cure paroxysmal supraventricular tachycardia." ]

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[ "If this is your first visit, be sure to\ncheck out the FAQ by clicking the\nlink above. ", "You may have to register\nbefore you can post: click the register link above to proceed. ", "To start viewing messages,\nselect the forum that you want to visit from the selection below.", "\n\nWhat a fun little read! ", "I got it yesterday and read it after cartoons (it was a grand day for toons yesterday!). ", "This ish was a fantastic capper to it all!", "\n\nAnyone else kinda want an Or-Man figure now?", "\n\nOh, and an adventure like this gives us an in-Universe excuse for the Mini-Masters we've been coveting...!", "\n\nNot to sound like a creepy cheerleader for Uki, but it's nice to know there is at least one person on this forum who is extremely positive & friendly all the time. ", "I don't think I could be that nice even if you paid me. ", "If we ever give out awards for \"forum member of the month\", Uki gets my vote. ", "-Mr. ", "Shokoti\n\nI just read it right now...and wow, what a strange issue, I LOVED it. ", "It was a fun read, it reminded me of the Tiny Titans and Super Hero Squad issues I bought for my niece a while back but with more zaniness to it, Motu style! ", "I do hope we'll get more one-shots in the future, I really like them all (#1 not so much). ", "The 8 bit scene and the one that reminded me of Calvin and Hobbes were pretty cool! ", "All in all, a good issue!", "\n\nIf this is the best they can do for the future of Masters of the Universe in media then they should leave it alone,they obviously had no creativity going into writing and producing this comic,the constant refrences to Batman,Pac-man,Spongebob all show how they had no ideas for Orko.", "\n\nI know comics are supposed to be fun but that was a disaster,imo,the other comics have been great and some good new twists on the He-man story but this for me was a huge let down.", "\n\nI thought it was a lot of fun.", "\nBit filmation, bit of fun poked at other properties.", "\nI think it's great they are trying different things with these digital comics - serious/horror/noir/comedy - they are cheap enough an if nothing else hopefully it helps gauge what aspects of MOTU the majority if fans prefer.", "\n\nlol....luckily he didn't ask. ", "Instead he wants to know when the new cartoon is coming out. ", "I told him I don't know but if it did it would be pretty cool. ", "I'm all for a little bit darker story, but I love the family friendly aspect He-man always had. ", "I don't really want adult only R-Rated He-man (ie. ", "Sin City Evil Lyn) Orko was fun and I'm looking forward to a few more like it. (", "How bout a Gwildor issue!)", "\n\nI can see how everyone enjoyed it, and I found a few fun surprises in there like Batman as well. ", "But I was still disappointed with this issue. ", "It feels like DC is just trying to fill a quota for Mattel and don't really care about MOTU. ", "Scott's 3 mini-comics did a better job at telling a story and pushing Eternia and the characters forward. ", "I think my disappointment stems from my hopes that these one shots would do the same, kind of like Man-At Arms and Randor, simple storys that really pushed or opened up the characters in a new needed light. ", "Evil-Lyn and Orko did not do that for me. ", "And what happened to the main comic book, how often are they releasing it? ", "Feels like it's been months.", "\n\nThe delay in the comic (the next issue isn't even a regular issue, it's the Skeletor origin issue) isn't helping perception of these, I suppose. ", "But I think it's best to think of these as featurettes on a DVD rather than a main story.", "\n\nI cant make up my mind if i absolutly love it or really really hate it - there's no inbetween. ", "On the neg side the artwork before and after Orko's magic is really poor, but on the other, the middlle stuff really did look like Orko's mind which was good and there were some funny moments. ", "And as for Jessica Sorceress...\n\nConsidering it only cost $1. ", "You cant really complain about price\n\nIf there's something strange in the neighbourhood, who you gonna' call? ", "HE-MAN!!!!" ]

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[ "Making Marines at boot camp is a sacred mission that the Corps rarely changes.", "\n\nBut the commandant is revising the schedule for the 12-week regiment to make sure that new Marines can succeed in follow-on training.", "\n\nStarting in February, Marines will have an extra week following the Crucible to learn from drill instructors, Marine-to-Marine, Gen. Robert Neller told Marine Corps Times in an exclusive interview. ", "The number of training days will remain the same.", "\n\nThe move comes after Neller and Sergeant Major of the Marine Corps Ronald Green noticed that Marines were struggling both physically and mentally at training after boot camp, Neller said. ", "Some Marines had not adjusted to the fact that they were Marines, not recruits.", "\n\n“We ask these young men and women to grow up really fast,” Neller said. “", "They’ve made the transformation from recruit to Marine and then we shoot them out the door. ", "What we’re trying to do is give them a little bit of time to get used to that and understand that OK, you’ve got your eagle, globe and anchor, you’ve earned the title ‘Marine,’ that’s just the beginning.", "\n\n“Now it’s actually going to become more difficult because more and more of the responsibility to live up to being a Marine, to live a life of honor, courage and commitment, is more and more going to be on your shoulders.”", "\n\nCurrently, Marines earn their eagle, globe and anchor after completing the Crucible during the 11th week of recruit training.", "\n\nThe Crucible is 54 hours of combat drills, during which recruits get little sleep as they are put through simulated attacks day and night. ", "Recruits learn they need to scream to be heard over the simulated gunfire, and that any illumination can give away their positions.", "\n\n× Fear of missing out? ", "Sign up for the Marine Corps Times Daily News Roundup to receive the top Marine Corps stories every afternoon. ", "Thanks for signing up. ", "By giving us your email, you are opting in to the Marine Corps Times Daily News Roundup.", "\n\nFor recruits, the grueling ordeal is the last hurdle to overcome before they are officially Marines. ", "The final week of boot camp is called “Marine Week,” during which the new Marines are no longer treated as recruits.", "\n\nWhen recruits arrive at Parris Island and San Diego in November, they will face the Crucible during the 10th week of boot camp so that they will have two weeks to adjust to being Marines before leaving the recruit depots, officials said. ", "Instead of being called “Marine Week,” the time after boot camp will be called “Phase 4” of recruit training.", "\n\n“It doesn’t change any of the graduation requirements,” Neller said. “", "The standards are the standards. ", "Nothing has changed. ", "We’re just trying to facilitate the maturity of these young men and women in a more rapid process.”", "\n\nDrill instructors will still be charge of training during Phase 4, but Marines will have more responsibility and they will be able to ask instructors questions, he said.", "\n\nThe change is a long time coming. ", "Over the past couple of years, Corps officials have talked to drill instructors and recruit training depot commanders as part of a review of boot camp, Neller said.", "\n\n“The consensus was: As part of the transformation from a civilian to a Marine, we were not giving newly made Marines enough time to get used to being a Marine before we sent them off on their way to begin the rest of the transformation, when they went to Marine Combat Training and on to the MOS School,” Neller said.", "\n\nDrill instructors felt that having more time with the new Marines would provide a “huge opportunity” to better prepare them for success, Neller said. ", "The training environment changes completely when Marines complete the Crucible and drill instructors can talk to them as fellow Marines, not recruits.", "\n\nDuring Phase 4 of boot camp, drill instructors will have more time to convey to the new Marines that they have made the first step, but defending the nation is a serious business and now they will have to assume the responsibilities that come with being a Marine, he said.", "\n\n“Now you’ve got somebody who’s been a drill instructor, who’s been intimately involved in this transformation, and now they have another few days to talk to their new Marines as a fellow Marine about what it’s going to be like as they get ready to go out and begin the rest of their journey as a Marine,” Neller said.", "\n\nInitially, the Marine Corps had concerns that moving the Crucible earlier in recruit training could make boot camp less physically strenuous, Neller said. ", "However, Marines will continue to train physically during the last two weeks of boot camp. ", "The difference will be that the Marines will PT because they know it’s their responsibility, not because they are being told to by drill instructors.", "\n\n“Any time you change something, people are going to say, ‘Well, what’s wrong with the way we did it?’” ", "Neller said. “", "There’s nothing wrong with the way we did it. ", "We’re trying to keep the very, very best of what we do now and add something to make it even better. ", "They’re going to PT every day.”", "\n\nStill, Neller acknowledges that any change to boot camp is bound to draw criticism, but he noted that boot camp has transformed over time, such as when then-Commandant Gen. Charles Krulak added the Crucible to recruit training in the 1990s.", "\n\n“This is a normal evolution of the recruit training experience,” Neller said. “", "Of course, everybody thinks, proudly, ‘Hey, it was never as hard as when I went through.’ ", "OK. ", "I got that. ", "The proof will be in the performance of these soon-to-be recruits.”" ]

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[ "Q:\n\nSumming values after every third position in data frame in R\n\nI am new to R. I have a data frame like following\n>df=data.frame(Id=c(\"Entry_1\",\"Entry_1\",\"Entry_1\",\"Entry_2\",\"Entry_2\",\"Entry_2\",\"Entry_3\",\"Entry_4\",\"Entry_4\",\"Entry_4\",\"Entry_4\"),Start=c(20,20,20,37,37,37,68,10,10,10,10),End=c(50,50,50,78,78,78,200,94,94,94,94),Pos=c(14,34,21,50,18,70,101,35,2,56,67),Hits=c(12,34,17,89,45,87,1,5,6,3,26))\n\nId Start End Pos Hits\nEntry_1 20 50 14 12\nEntry_1 20 50 34 34\nEntry_1 20 50 21 17\nEntry_2 37 78 50 89\nEntry_2 37 78 18 45\nEntry_2 37 78 70 87\nEntry_3 68 200 101 1\nEntry_4 10 94 35 5\nEntry_4 10 94 2 6\nEntry_4 10 94 56 3\nEntry_4 10 94 67 26\n\nFor each entry I would like to iterate the data.frame in 3 different modes. ", "For an example, for Entry_1 mode_1 =seq(20,50,3)and mode_2=seq(21,50,3) and mode_3=seq(22,50,3). ", "I would like sum all the Values in Column \"Hits\" whose corresponding values in Column \"Pos\" that falls in mode_1 or_mode_2 or mode_3 and generate a data.frame like follow:\nId Mode_1 Mode_2 Mode_3\nEntry_1 0 17 34\nEntry_2 87 89 0\nEntry_3 1 0 0\nEntry_4 26 8 0 \n\nI tried the following code:\n mode_1=0\n mode_2=0\n mode_3=0\n mode_1_sum=0\n mode_2_sum=0\n mode_3_sum=0\n for(i in dim(df)[1])\n {\n if(df$Pos[i] %in% seq(df$Start[i],df$End[i],3))\n {\n mode_1_sum=mode_1_sum+df$Hits[i]\n print(mode_1_sum)\n }\n mode_1=mode_1_sum+counts\n print(mode_1)\n\n ifelse(df$Pos[i] %in% seq(df$Start[i]+1,df$End[i],3))\n {\n mode_2_sum=mode_2_sum+df$Hits[i]\n print(mode_2_sum)\n }\n mode_2_sum=mode_2_sum+counts\n print(mode_2)\n\n ifelse(df$Pos[i] %in% seq(df$Start[i]+2,df$End[i],3))\n {\n mode_3_sum=mode_3_sum+df$Hits[i]\n print(mode_3_sum)\n }\n mode_3_sum=mode_3_sum+counts\n print(mode_3_sum)\n}\n\nBut the above code only prints 26. ", "Can any one guide me how to generate my desired output, please. ", "I can provide much more details if needed. ", "Thanks in advance.", "\n\nA:\n\nIt's not an elegant solution, but it works.", "\nm <- 3 # Number of modes you want\n\nfoo <- ((df$Pos - df$Start)%%m + 1) * (df$Start < df$Pos) * (df$End > df$Pos)\ntab <- matrix(0,nrow(df),m)\nfor(i in 1:m) tab[foo==i,i] <- df$Hits[foo==i]\n\naggregate(tab,list(df$Id),FUN=sum)\n# Group.1 V1 V2 V3\n# 1 Entry_1 0 17 34\n# 2 Entry_2 87 89 0\n# 3 Entry_3 1 0 0\n# 4 Entry_4 26 8 0\n\n-- EXPLANATION --\nFirst, we find the indices of df$Pos That are both bigger than df$Start and smaller than df$End. ", "These should return 1 if TRUE and 0 if FALSE. ", "Next, we take the difference between df$Pos and df$Start, we take mod 3 (which will give a vector of 0s, 1s and 2s), and then we add 1 to get the right mode. ", "We multiply these two things together, so that the values that fall within the interval retain the right mode, and the values that fall outside the interval become 0.", "\nNext, we create an empty matrix that will contain the values. ", "Then, we use a for-loop to fill in the matrix. ", "Finally, we aggregate the matrix.", "\nI tried looking for a quicker solution, but the main problem I cannot work around is the varying intervals for each row. ", "\n\n" ]

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[ "Share this article\n\nGreen Bay Packers President and CEO Mark Murphy, a 1973 Clarence High School graduate, addresses student athletes and community members in the Clarence High School gymnasium, Monday, Feb. 29, 2016. (", "Derek Gee/Buffalo News)\n\nPackers' president shares life lessons from 'Big Murph'\n\nThe greatest athlete ever to emerge from Clarence High School told a gym filled with young dreamers that he once was a shy, skinny 15-year-old who walked the same hallways they do.", "\n\nMark Murphy stood behind a lectern Monday, in a jacket and tie, and shared the story of a 45-year journey that took him from starring in football, basketball, and baseball for the Red Devils to running one of the most iconic teams in NFL history, the Green Bay Packers. ", "On a table to his right, flanked by Clarence High and Packer helmets, were the two Super Bowl rings he won as a safety for the Washington Redskins and as president and CEO of the Packers, and an NFC Championship ring he also won with the Redskins.", "\n\nBehind the rings was the reason for Murphy’s visit: a golden NFL football that he was presenting to his alma mater as part of a league initiative to have former Super Bowl players throughout the country give a ball commemorating the game’s 50th anniversary to their high schools.", "\n\nGreen Bay Packers President and CEO Mark Murphy, a 1973 Clarence High School graduate, signs the jersey of 11-year-old Ben Gregor to the delight of his teammates in the Clarence High School gymnasium. (", "Derek Gee/Buffalo News)\n\nThe ceremony provided an opportunity for the audience comprised mainly of jersey-wearing varsity, junior varsity and youth football players to see and hear what the game can do for someone who literally had walked in their shoes. ", "Murphy readily acknowledged that it’s a “difficult time for the sport,” with safety concerns on the rise and participation at the youth level declining, even as television ratings spike and attendance remains strong for the NFL.", "\n\nBut he made no bones about the fact he was there to deliver the message on the other side of the coin – to emphasize the “values and benefits” of football.", "\n\n“It’s a tremendous game,” Murphy said. “", "In terms of the lessons learned, there’s not another game like football.”", "\n\nWhen Murphy was a youngster, his family moved around a lot. ", "His father, Hugh, was a labor negotiator in the steel industry, and wound up taking a job as director of labor relations for Roblin Steel in Western New York when Murphy was in tenth grade. ", "Murphy was a rabid fan of the Buffalo Bills, now his “second-favorite team,” and even worked security at Rich Stadium. ", "His favorite player growing up? “", "It’s embarrassing,” Murphy said. “", "O.J. Simpson.” ", "As the crowd laughed, he added, “He was a good player.”", "\n\nFor most of his life, Murphy was known as “Little Murph” to his father’s “Big Murph.” ", "But after arriving in Clarence from Houston, Murphy gained another nickname befitting his long, slender frame: “Tex.”", "\n\n“Big Murph” would always share what he called “pearls of wisdom” with his son. ", "Through his teenage years, “Tex” usually responded with an eye roll when he heard his father say things like: “No pain, no gain … You’re going to meet the same people on the way up that you meet on the way down … If you find a job you love, you’ll never work a day in your life.”", "\n\n“I thought, ‘My father’s so corny. ", "Why does he keep saying those things?’” ", "Murphy recalled. “", "But as I got older, and I started to experience things, I found that those pearls of wisdom really make some sense.”", "\n\nIn fact, he credits them with helping him to forge a successful career on the business side of the game after his playing days came to a bitter end. ", "Among the biggest that continue to be part of the roadmap for his life: “Build bridges, don’t burn them.”", "\n\nDavid Trophy, 8, tries on one of the three Super Bowl rings belonging to Green Bay Packers President and CEO Mark Murphy, a 1973 Clarence High School graduate, after an appearance by Murphy in the Clarence High School gymnasium. (", "Derek Gee/Buffalo News)\n\nMurphy learned the eternal value of this during his time as the NFL Players Association representative of the Redskins during one of the most difficult labor periods in league history. ", "As vice president of the NFLPA and a member of its bargaining committee, he was part of the union’s decision to call a strike that wiped out seven games of the 1982 season.", "\n\nTo say Murphy was unpopular with NFL management would be a gross understatement. ", "Jack Kent Cooke, who owned the Redskins at the time, called him a “communist.” ", "Quoting Cook, Murphy said, “Mark Murphy is fine young man, but I wouldn’t want him as a bargainer.” ", "Murphy also said he believed his role with the NFLPA “shortened his career,” accusing the Redskins of using an injury he suffered early in the 1983 season as an excuse to release him after the year and effectively have him blackballed by the rest of the league.", "\n\n“I was bitter for many years,” he said, the hard feeling lingering as he pursued a law degree at Georgetown.", "\n\nHowever, it was during those highly contentious meetings in ’82 that Murphy formed a friendship with a “young attorney” actually sitting on the opposite side of the negotiating table: Paul Tagliabue, who seven years later would become commissioner of the NFL. ", "In 1992, after Murphy became athletic director at Colgate University – from where the Redskins signed him as an undrafted free agent in 1977 – Tagliabue asked him to join the league’s player-advisory and youth football committees. ", "Murphy accepted.", "\n\n“And I am convinced that I would not be in the position I am in now were it not for my relationship with Paul Tagliabue,” Murphy said.", "\n\nHe offered another example involving a current Packer player, wide receiver James Jones. ", "After seven seasons in Green Bay (2007-2013), Jones signed with the Oakland Raiders as a free agent. ", "But after being released by the Raiders and New York Giants, the Packers, desperate for a replacement for injured Jordy Nelson, welcomed Jones back in 2015, because, as Murphy told him, “You did not burn any bridges here.” ", "Jones finished as Green Bay’s leader in receiving yards (890) and touchdowns (eight).", "\n\nYet another “Big Murph” pearl that has served him well is: “Don’t sweat the small stuff. ", "Keep things in perspective.”", "\n\nMurphy cited two examples, as a player and an executive, of how that advice came in handy.", "\n\nHe remembered performing his best in the Redskins’ victory against the Miami Dolphins in Super Bowl XVII because he didn’t forget that the keys for success “on a large stage” were no different than those for a smaller one: hard work and preparation.", "\n\nMurphy also didn’t allow himself to be overwhelmed when, not long after leaving his post as athletic director at Northwestern to join the Packers in 2007, he was faced with Brett Favre, the franchise’s all-time best player, deciding to retire … then choosing to unretire. ", "By then, however, the organization had committed to going with Aaron Rodgers as its quarterback, resulting in a trade that sent Favre to the New York Jets.", "\n\n“The Packers are a very unique organization. ", "We don’t have a single owner; we’re owned by the community and have 370,000 shareholders, and I hear from these shareholders quite a bit,” Murphy said. “", "So after we traded Brett Favre, I get a letter from James from Milwaukee. ", "And he says, ‘Dear, Mark Murphy, you, sir, are a complete and total idiot. ", "Only an idiot would trade the greatest player in the history of the Green Bay Packers. ", "I will never again support the Green Bay Packers.’”", "\n\nIt was around the same time that Murphy received some devastating news. “", "Big Murph” was dying of cancer.", "\n\n“So,” Murphy said, “I kept thinking to myself, ‘Keep it in perspective. ", "This is what happens when players’ careers end. ", "You’re going to move past this, you’re going to get through it.’ ", "And eventually we did make it through (winning a Super Bowl with Rodgers, who would become a top-flight quarterback himself).", "\n\n“It was a difficult time,” Murphy added. ", "But he didn’t allow it to get the better of him “because of my father’s sayings and (recognizing that) the things that he was dealing with were much more important than the end of a career of a player.”", "\n\nOn Monday, a bunch of young dreamers at Clarence High School got a first-hand look at where their hallways can lead.", "\n\nVic Carucci – Vic Carucci covers the Bills and NFL for The News. ", "With four decades of experience as a pro football writer and broadcaster, he is a co-host on SiriusXM NFL Radio and a Pro Football Hall of Fame selector. ", "Vic has authored 10 books about football (including multiple New York Times best-sellers) and is a past president of the Professional Football Writers of America." ]

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[ "Wildlife plot set for tract by reservoir\n\n12:20 AM,\nSep. 22, 2013\n\nA wildlife refuge is planned for the Ross Barnett Reservoir area.", "\n\nWritten by\n\nBrian Albert Broom\nbbroom@clarionledger.com\n\nExperiencing the outdoors may soon be much more convenient for those living in the greater Jackson area. ", "The U.S. Fish and Wildlife Service recently announced a proposal to establish a National Wildlife Refuge in Jackson's backyard.", "\n\nThe proposed refuge will include up to 5,000 acres of undeveloped land bounded by the Ross Barnett Reservoir to the north and Lakeland Drive to the south. ", "Within the project area, 2,712 acres are currently owned by Mississippi Department of Transportation and will be turned over to the USFWS upon approval of the refuge." ]

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[ "/***********************************************************************************************************************\n* DISCLAIMER\n* This software is supplied by Renesas Electronics Corporation and is only intended for use with Renesas products. ", "No \n* other uses are authorized. ", "This software is owned by Renesas Electronics Corporation and is protected under all \n* applicable laws, including copyright laws. ", "\n* THIS SOFTWARE IS PROVIDED \"AS IS\" AND RENESAS MAKES NO WARRANTIES REGARDING\n* THIS SOFTWARE, WHETHER EXPRESS, IMPLIED OR STATUTORY, INCLUDING BUT NOT LIMITED TO WARRANTIES OF MERCHANTABILITY, \n* FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT. ", "ALL SUCH WARRANTIES ARE EXPRESSLY DISCLAIMED. ", "TO THE MAXIMUM \n* EXTENT PERMITTED NOT PROHIBITED BY LAW, NEITHER RENESAS ELECTRONICS CORPORATION NOR ANY OF ITS AFFILIATED COMPANIES \n* SHALL BE LIABLE FOR ANY DIRECT, INDIRECT, SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES FOR ANY REASON RELATED TO THIS \n* SOFTWARE, EVEN IF RENESAS OR ITS AFFILIATES HAVE BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES.", "\n* Renesas reserves the right, without notice, to make changes to this software and to discontinue the availability of \n* this software. ", "By using this software, you agree to the additional terms and conditions found by accessing the \n* following link:\n* http://www.renesas.com/disclaimer\n*\n* Copyright (C) 2018 Renesas Electronics Corporation. ", "All rights reserved.", "\n***********************************************************************************************************************/\n/***********************************************************************************************************************\n* File Name : vecttbl.h\n* Description : Has function prototypes for exception callback functions.", "\n***********************************************************************************************************************/\n/***********************************************************************************************************************\n* History : DD.MM.YYYY Version Description\n* : 31.10.2018 1.00 First Release\n* : 28.02.2019 1.01 Fixed coding style.", "\n* : 31.07.2019 1.02 Added typedef for option-setting memory.", "\n***********************************************************************************************************************/\n\n/***********************************************************************************************************************\nIncludes <System Includes> , \"Project Includes\"\n***********************************************************************************************************************/\n\n/***********************************************************************************************************************\nMacro definitions\n***********************************************************************************************************************/\n/* Multiple inclusion prevention macro */\n#ifndef VECTTBL_HEADER_INC\n#define VECTTBL_HEADER_INC\n\n/***********************************************************************************************************************\nTypedef definitions\n***********************************************************************************************************************/\n#if defined(__GNUC__)\ntypedef struct st_ofsm_sec_ofs3\n{\n uint32_t __OSIS1reg;\n uint32_t __OSIS2reg;\n uint32_t __OSIS3reg;\n uint32_t __OSIS4reg;\n} st_ofsm_sec_ofs3_t;\n\ntypedef struct st_ofsm_sec_ofs4\n{\n uint32_t __TMINFreg;\n uint32_t __MDEreg;\n uint32_t __OFS0reg;\n uint32_t __OFS1reg;\n} st_ofsm_sec_ofs4_t;\n#endif /* defined(__GNUC__) */\n\n/***********************************************************************************************************************\nExported global functions (to be accessed by other files)\n***********************************************************************************************************************/\n\n#endif /* VECTTBL_HEADER_INC */\n\n" ]

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[ "Celebrity Gossip Blog!", "\n\nJack Osbourne Diagnosed With MS\n\nJack Osbourne has been diagnosed with a condition called multiple sclerosis. ", "The sad news comes just 2 weeks after the arrival of baby Pearl Clementine with his fiancée Lisa Stelly. ", "He told ‘People’ magazine: “I was just angry and frustrated and kept thinking, ‘Why now?’ ", "I’ve got a family and that’s what’s supposed to be the most important thing.”", "\n\nIt could potentially affect his vision and balance going forward, as it affects the nervous system and impairs muscle control. ", "It is not currently known what stage his illness has reached yet. ", "Meanwhile, supportive sister Kelly has written on Twitter: “Please support my brother in not only his bravery but honesty! ", "I love you so much Jack & I’m so proud of you!”" ]

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[ "PUBLIC MARKS from mbertier with tags blog & tags\n\n05 April 2006 14:30\n\nSWiK is a community driven resource for open source software. ", "Try starting a page about your favorite project, syndicating a blog for a topic, or browsing through tags people have added to projects or pages." ]

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[ "to prove itself right even if it has made\na mistake, it misuses the law’s nitty gritty to keep maligning the ‘victim’,\njust to maintain a point. ", "Any withdrawal or back tracking of the actions taken\nby an organisation will be construed as a mistake. ", "Rear Admiral (Retd) BR Menon\nwho was the Chairman of Managing Director of Goa Shipyard Ltd (GSL) between\n1995-2000 reminiscences that, “My only mistake was that I was trying to clense\nthe GSL,” and yes, he has written it candidly in his book ‘Honesty Victimised,\nCBI Politicised’.", "\n\nIn his book, he explains that the\ntravails, mudslinging and tardy functioning of the Central Bureau of\nInvestigations (CBI) as we see today are not new. ", "Describing his personal\nexperience while dealing with the CBI, in his book, Admiral Menon speaks of the\nrot that had afflicted the system decades ago. ", "The book mentions his saga of\ntrials and tribulations of an honest and a high calibre Indian Naval officer\nwho was prosecuted by the CBI as a result of deliberate political victimization\nand how he fought for thirteen long years to get himself exonerated and\nacquitted after his retirement.", "\n\nHe explains in his book that as a CMD of GSL he did what was\nmost essentially required to transform the decaying Shipyard by influx of\nillegal unions backed by political forces. ", "He derecognised all the political\nunion leaders and officer bearers and asked them to contest elections within\nthe campus of the GSL. ", "He also ensured that he did not heed to many requests\nfrom the then Defense Minister to give jobs to his cronies. “", "I am here to\nimprove the assets of GSL and not to increase its liabilities,” Admiral Menon\nmentions it in his book.", "\n\nThe\nbook exposes on how a bold defence officer had the moral courage with\nconviction to take on the CBI and the state machinery upfront." ]

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[ "Where do Bush and Graham fit in the ranks of the biggest Trump haters of this election? ", "Below we've ranked the top 10 Trump detractors, based on the length of their anti-Trump sentiments, their willingness to vocalize it and their relative prominence in the Republican political world.", "\n\nAD\n\nAD\n\n10. ", "The entire early 2015 Republican Party: The fact that Trump is the GOP nominee is all the more surprising because even GOPers hated him just a little more than a year ago. ", "HATED him. ", "As of February 2015, an early poll of potential Iowa GOP caucus-goers found 68 percent disliked Trump. ", "Again, this was Republicans. ", "Similarly, 69 percent of potential New Hampshire GOP primary voters disliked him, according to another poll. ", "This is the kind of thing that made us and others declare that Trump could never win the GOP nomination. ", "We were wrong, but we had our reasons.", "\n\n9. ", "Tim Miller: Miller was the communications director for Bush's presidential campaign. ", "When that ended, he took on a similar role for Our Principles PAC, the leading anti-Trump super PAC. ", "Through it all, Miller took it as his mission to needle Trump -- on social media and in real life. ", "This exchange -- in the spin room following a March debate -- was particularly awkward.", "\n\nMiller is still at it despite it all. ", "Here's what he said when Trump blasted Graham on Friday.", "\n\n8. ", "David Brooks: The cerebral New York Times conservative columnist spews less vitriol than many on this list, but he has been one of the longest and most steadfast of the Trump critics within the intellectual wing of the party. ", "Here's Brooks from a mid-March column headlined \"No, Not Trump, Not Ever\":\n\nAD\n\nAD\n\nDonald Trump is epically unprepared to be president. ", "He has no realistic policies, no advisers, no capacity to learn. ", "His vast narcissism makes him a closed fortress. ", "He doesn’t know what he doesn’t know and he’s uninterested in finding out. ", "He insults the office Abraham Lincoln once occupied by running for it with less preparation than most of us would undertake to buy a sofa.", "\n\nThat's pretty stinging.", "\n\n7. ", "Rick Wilson: The ever-quotable GOP media strategist was calling for the party to fight back against Donald Trump long ago -- when everyone was still playing nice and hoping eventually just he'd go away. ", "We'll let Wilson's September Politico magazine piece speak for him: \"With the scenery-chewing, oxygen-sucking political black hole that is Donald Trump, I have one question for the 'don’t attack' camp; how’s that working out for you?\" ", "And: \"You could be living on a diet of lead paint, cheap vodka and Real Housewives and still know more than Trump does about, well, everything.\"", "\n\n6. ", "Rep. Justin Amash (R-Mich.): Amash has been a prominent Ted Cruz supporter, but his criticisms of Trump have gone further than most anyone. ", "In early March, he said, \"Trump is not a noninterventionist in foreign affairs; he's a national populist who will adopt any position that advances his political ends.\" ", "He also said Trump might pose a \"bigger threat\" to limited government than either Hillary Clinton or Bernie Sanders. ", "He was one of the first to label Trump \"dangerous.\"", "\n\n\n\n5. ", "The Bush family: It's not just that Trump destroyed Jeb's chances of being president by labeling him as \"low energy.\" ", "It's that everything Trump represents -- brashness, ego, a disregard for the rules -- runs counter to the famous Bush gentility. ", "The day before the news broke that Jeb wouldn't vote for Trump, his father and brother made clear they wouldn't be endorsing the real estate mogul. ", "Barbara Bush, the family matriarch, admitted she was \"sick\" of Trump in February, adding: \"He's said terrible things about women, terrible things about the military. ", "I don't understand why people are for him, for that reason.\"", "\n\nAD\n\nAD\n\n4. ", "Bill Kristol: The Weekly Standard editor and prominent GOP thinker has wavered a bit on Trump, but seems to have landed in a very anti-Trump space. ", "He has often mused about running a third option, even recently floating Sen. Ben Sasse (R-Neb.), who we'll get to below. “", "I just don't think he has the character to be president of the United States,” Kristol said Wednesday. “", "It's beyond any particular issue I disagree with him on, or who he picks as VP or something.” ", "Kristol added that Trump “likes rapists” – a reference to Mike Tyson’s endorsement.", "\n\n3. ", "Mitt Romney: The 2012 GOP presidential nominee accepted Trump’s endorsement four years ago, but he’s got no time for him this time around. ", "Romney delivered a lengthy rebuke of Trumpism after Super Tuesday two months ago, saying “Donald Trump is a phony, a fraud. ", "His promises are as worthless as a degree from Trump University. ", "He's playing the American public for suckers: He gets a free ride to the White House and all we get is a lousy hat.” (", "But how do you really feel?) ", "Romney now says he won’t attend the GOP convention this year.", "\n\n2. ", "Sen. Ben Sasse (R-Neb.): Sasse is second on this list only because he’s used less severe language than No. ", "1. ", "But he’s been no less strident. ", "In fact, he’s the only senator who has long said he will never vote for Trump. ", "And on Wednesday night, he launched a lengthy tweetstorm reinforcing his call for a third option. ", "Sasse is a rising star who has led the #NeverTrump movement from the start. ", "And he's not backing down." ]

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[ "iPhone 11 Release Date, Features, Price, And a Short Review\n\nWe all know that there was a lukewarm response for the LCD screen of the iPhone XR. ", "We may see a total shift to the OLED screen on iPhone X11. ", "No need to say that the new-generation iPhone will come up with 5G. Apart from that, we can expect some cool things based on Al. ", "There is a great possibility that Apple comes with a good camera which is always has been outstanding. ", "And it is more likely to say that it will run the future based on a powerful Artificial intelligence program. ", "So, we may see different modes and also a personalize camera app that studies the aesthetic preferences of the users. ", "And Apple working on the new series of the chip which they call that bionic chip. ", "Now let’s talk about iPhone 11 Release Date, Features, Price, And a Short Review.", "\n\nIn this post, we will talk about the iPhone 11 release date, features, price, and some kind of reviews. ", "So, if you want to know about iPhone 11 more stay with us and read this article carefully. ", "The iPhone 11 is something of a surprise – I mean that it brings more advanced technology and the capability of camera and etc. ", "The iPhone 11 is designed, developed, and marketed by Apple Inc. It is the thirteenth generation lower-priced iPhone succeeding the iPhone XR. ", "So, it was invalid on September 10, 2019, alongside the higher-end iPhone 11 pro flagship at the Steve Jobs Theater in Apple Park. ", "However, Apple would likely pay attention to clamors of customers requesting for iPhone 11. ", "So, let’s talk about it one by one.", "\n\niPhone 11 Release Date\n\nSo, due to all the differences now its time to know about the iPhone 11 release date. ", "Most of the people were taught that the iPhone 11 will release in 2020. ", "On the other hand, Apple release it’s iPhone 11 on September 20th, 2019. ", "And at its fall 2019 event, Apple announced that the iPhone 11, 11 Pro, and 11 Pro Max was released on September 20th. ", "This was about its release date now let’s talk about its price and how much will it cost?", "\n\niPhone 11 Price, How Much Will it Cost?", "\n\niPhone 11 price\n\nSo, int the previous paragraph we talked about iPhone 11 release date. ", "Now in this part, we will talk about its price and how much money do we need to buy it? ", "Apple on September 20 invalid the iPhone 11, it’s the new flagship $699 smartphone that offers a range of powerful features at an affordable price tag. ", "Moreover, the more expensive iPhone 11 pro, and the iPhone 11 pro max, the iPhone 11 is going to be an iPhone perfect for most of the people. ", "So, as I mentioned iPhone 11 will cost $699, the iPhone 11 pro will cost $999, and the iPhone 11 pro max will retail $1,099. ", "Apple is promoting the trade-ins of previous models to lower the cost.", "\n\niPhone 11 Features – iPhone 11 Release Date\n\nCamera\n\niPhone 11 Camera\n\nApple has doubled the number of lenses on offer here. ", "Where the iPhone XR had one, on the rare things are much more grains for 2019, with a hole window containing two 12MP sensors. ", "The iPhone 11 includes a dual-lens 12MP rare camera arrey. ", "here is one f/2.4 ultra-wide-angle lens with a 120-degree field of view and 2x optical zoom out and one f/1.8 wide-angle lens. ", "The iPhone 11 supports 4K video at up to 60 fps and 1080p slow motion at up to 240 fps. ", "The phone also features an audio zoom feature that focuses audio on the area that is zooming in on, similar to the Pro model.", "\n\nDisplay\n\nSo, iPhone 11 has a 6.1-inch display that uses LCD technology rather OLED. ", "That means that you won’t get the richness of colors, nor the deep black and bright whites. ", "You will find on the handset with more advanced screen tech. ", "So, its resolution is 1792×828 pixels ( 216 PPI ) with a maximum brightness of 625 nits and 1400: 1 contrast ratio. ", "What’s less attractive is the thicker border around the outside of the display – these days we’re seeing a lot of phones, including ones with a lower price tag than the iPhone 11, come with edge-to-edge displays, and with no notch at the top.", "\n\nFinal Words for iPhone 11 Release Date\n\nSo, this was all about the iPhone 11 release date, features, and price. ", "I hope that this article was helpful for you and you take some advantages from this article. ", "So, if you have got any sort of question you can ask me by commenting below on the comment box. ", "We tried to give your answer as soon as possible. ", "However, if you want to support us just subscribe to our blog with your email address. ", "Thanks for visiting." ]

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[ "/* AUTO-GENERATED FILE. ", " DO NOT MODIFY.", "\n *\n * This class was automatically generated by the\n * aapt tool from the resource data it found. ", " It\n * should not be modified by hand.", "\n */\n\npackage com.example.appfileproviderclientdemo1;\n\npublic final class R {\n public static final class attr {\n }\n public static final class dimen {\n /** Default screen margins, per the Android Design guidelines. ", "\n\n Example customization of dimensions originally defined in res/values/dimens.xml\n (such as screen margins) for screens with more than 820dp of available width. ", "This\n would include 7\" and 10\" devices in landscape (~960dp and ~1280dp respectively).", "\n \n */\n public static final int activity_horizontal_margin=0x7f040000;\n public static final int activity_vertical_margin=0x7f040001;\n }\n public static final class drawable {\n public static final int ic_launcher=0x7f020000;\n }\n public static final class id {\n public static final int action_settings=0x7f080000;\n }\n public static final class layout {\n public static final int activity_app=0x7f030000;\n }\n public static final class menu {\n public static final int app=0x7f070000;\n }\n public static final class string {\n public static final int action_settings=0x7f050002;\n public static final int app_name=0x7f050000;\n public static final int hello_world=0x7f050001;\n }\n public static final class style {\n /** \n Base application theme, dependent on API level. ", "This theme is replaced\n by AppBaseTheme from res/values-vXX/styles.xml on newer devices.", "\n \n\n Theme customizations available in newer API levels can go in\n res/values-vXX/styles.xml, while customizations related to\n backward-compatibility can go here.", "\n \n\n Base application theme for API 11+. ", "This theme completely replaces\n AppBaseTheme from res/values/styles.xml on API 11+ devices.", "\n \n API 11 theme customizations can go here. ", "\n\n Base application theme for API 14+. ", "This theme completely replaces\n AppBaseTheme from BOTH res/values/styles.xml and\n res/values-v11/styles.xml on API 14+ devices.", "\n \n API 14 theme customizations can go here. ", "\n */\n public static final int AppBaseTheme=0x7f060000;\n /** Application theme. ", "\n All customizations that are NOT specific to a particular API-level can go here. ", "\n */\n public static final int AppTheme=0x7f060001;\n }\n}\n" ]

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[ "Green Man is one of the few absolute, cast-iron festival bankers. ", "Year after year, you know the lineup’s going to be up there with the best of them (despite it being independent, with only a fraction of the budget that bigger festivals have at their disposal); you also know that even if it wasn’t, you’d still have a lovely time - without wanting to sound like an old crusty, It’s the vibes, maaaaan. ", "OK, that wasn’t entirely successful…\n\nGreen Man’s formula, on the other hand, most certainly is. ", "An intimate, picturesque setting (the Brecon Beacons in Wales) combined with reasonable prices, decent, healthy food (if you’re that way inclined, if not there’s yer classic burger ‘n’ chips) and a lot of entertainment on offer – musical and otherwise.", "\n\nAvi Buffalo (Saturday, Far Out Stage)\n\nThe buzz around 19-year-old Avigdor Zahner-Isenberg's music this year has been nothing short of deafening, but if you've still not acquainted yourself with the self-titled debut LP yet then fear not – these folk-pop melodies are firmly from The Shins' school of immediacy, and will prove the perfect tonic for any sore heads after the first night whatever your level of familiarity. ", "Trying to keep a straight face during the woefully titled 'Summer Cum' will be rather amusing, too. ", "RW\n\nThe Big Eyes Family Players (Friday, Film Tent)\n\nA Sheffield based, Domino-affiliated rolling folk troupe, the Big Eyes Family Players bring their delicate instrumentation to Green Man for a special one-off performance in the Film Tent, providing a live soundtrack to three clips from Czech filmmaker Jan Svankmajer. ", "If they're in anything like the sort of form they were earlier this month supporting A Hawk and a Hacksaw for DiS in Sheffield, this promises to be a wonderful introduction to the festival - and, for those new to the band, the craft of Big Eyes. ", "RW\n\nGold Panda (Sunday, Far Out Stage)\n\nPlaying on Greco-Roman Soundsystem's late-night lineup, Gold Panda's leftfield, cut-and-paste electronica is a more downbeat affair than elsewhere on the bill, his glitchy sampling creating a dreamy, blissed-out brand of psychedelic house. ", "Previously responsible for acclaimed remixes for the likes of HEALTH, the Field and Telepathe, his You EP was released this year, and in turn featured re-workings from Dam Mantle and Minotaur Shock. ", "Obvious reference points are Four Tet and 'Swim'-era Caribou, with both artists' previous Green Man live form suggesting that this could just be the perfect closer to your 2010 experience. ", "KH\n\nFew would contest the breaks and electronica duo's suitability for the job, their pedigree in the A/V field having seen them work alongside Pioneer to create the now industry-standard DVJ-X1 professional DVD player. ", "Here, they stick mainly to Ninja Tune label-mates, with sets by DJ Food & DK and DJ Cheeba, but also rope in the King of Mainstream A/V, DJ Yoda. ", "We're expecting each act at their most dancefloor-filling, so expect a comprehensive A–Z of cult and radio-friendly breaks and hip-hop, cut with spacey live visuals. ", "KH\n\nIslet (Saturday, Far Out Stage)\n\nIslet's policy of shunning online self-promotion in favour of building a word-of-mouth following effectively leaves them traceable only via their live appearances. ", "It's a bold approach for any band, being one which appeals mainly to live music purists and incorrigible Luddites. ", "Happily, though, it's in their live performance that their strengths really lie; their shape-shifting, nonsensical take on art-pop at its most comfortable when you witness the boundlessly energetic instrument-swapping which creates it. ", "KH\n\nLone Wolf (Sunday, Far Out Stage)\n\nLone Wolf (aka Paul Marshall) is a Leodensian wonder whose live show has been described as a Leeds-by-London Supergroup (it contains members of Grammatics [RIP], Metronomy, and Duels). ", "It's a spectacle we await eagerly after many plays of excellent debut album The Devil and I (out now on Bella Union ), and repeated viewings of his incredible video for 'Keep Your Eyes on the Road' (a homage to Peter Gabriel's 'Sledgehammer' clip). ", "Here's hoping the intricacies that permeate the record translate to a live setting – if they do, we're in for a treat. ", "FW\n\nMountain Man (Friday, Main Stage)\n\nThese Vermot Sirens bring their bewitching harmonies to Wales, and we reckon they're a dead cert to provide one of the weekend's genuine 'mouths open' moments. ", "Their debut offering Made The Harbour (Bella Union, again) has all the charm and swing of the corn fields of the Deep South, the sparseness of the Mid-Western prairies and the sparkle of the snow-covered mountain tops of their own State. ", "After hearing about their impromptu, a capella Glasto set in June, we started getting really excited. ", "FW\n\nRace Horses (Saturday, Main Stage)\n\nHaving changed their name in 2009 after the threat of legal action from the actual radio station, The Artists Formerly Known As Radio Luxembourg possess more or less exactly the kind of sound you'd expect to hear on a Green Man bill. ", "For a festival so closely aligned with all things SFA, their off-kilter psychedelic-pop sounds right at home. ", "KH\n\nSilver Columns (Sunday, Green Man Pub)\n\nYou've probably heard of Adem, but you won't have heard him like this. ", "His electro-pop side project with Johnny Lynch (aka Scots folky The Pictish Trail) might not be pushing many envelopes – except maybe for the one marked 'FAO: Hot Chip's lawyer' – but it's a radical and really very enjoyable departure from both their dayjobs. ", "Debut album Yes, And Dance does exactly what it says on the tin. ", "RW\n\nSmoke Fairies (Friday, Green Man Pub)\n\nChichester-spawned duo Smoke Fairies sound as rare and ethereal as their name suggests, and this should be the perfect setting for them – at the Green Man Pub, as the sun goes down on the opening night. ", "Debut album Through Low Light And Trees isn't out until September, but their luscious harmonies should prove immediately arresting for newcomers. ", "RW\n\nWho are you most looking forward to? ", "If you’ve not plotted your weekend yet, here’s a handy clashfinder - although we haven't been able to verify the times listed here, so didn't include them above. ", "See you in the ‘Beacons!" ]

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[ "Tags\n\nStoystownOntario.", "Balsam-Lake A woman provides testimonyHondo as to the illness she experiencedafterliving for two months underneath an array of cell phone antennasCooper-City that Tynan were placed. ", "PronunciationGuide You Say it How in Michigan? ", "for. ", "Get the namesright with onlineguide developed by the Bureau of Services for BlindPersonsBraille and Talking Book Library This pronunciation guide was initially." ]

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[ "A lawsuit aimed at stopping crossover voting in Mississippi was dismissed by a judge in the state on Tuesday.", "\n\nThe race has been caught up in controversies about the practice of \"crossover voting,\" in which some outside groups are accusing Sen. Thad Cochran's (R-MS) campaign of encouraging Democrats and African-American voters to support him in the runoff.", "\n\nThe lawsuit, by Ronald W. Swindall, a supporter of Mississippi state Sen. Chris McDaniel (R) was filed on Monday. ", "McDaniel is facing Cochran in the runoff for the GOP nomination for U.S. Senate.", "\n\nIn Mississippi, voters don't register by party in primaries. ", "Mississippi state law prohibits people from voting in the Republican runoff if they voted in the Democracy primary on June 3.", "\n\nSwindall filed the new lawsuit in chancery court in Jones County on Monday. ", "It was dismissed by Chancery Judge Deborah Grambell on Tuesday according to the Associated Press.", "\n\nTea partiers who support McDaniel have been citing a Mississippi law that stipulates a voter can only vote in a party primary if the voter plans to back that primary's nominee in the general election. ", "In 2008 a federal appeals court ruled that law as unenforceable." ]

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[ "Q:\n\nsum of marked Poisson variables\n\nI would like to calculate the expected value of the sum of $N+1$ (assume $N$ is large) marked Poisson variables $X$ with intensity $\\lambda$ over subset $I$:\n$$\nS=\\left\\langle\\sum_{i \\in I} X_i\\right\\rangle\n$$\nwhere in subset $I$ we count only variables larger than some threshold $\\alpha$: $X >\\alpha$ and don't count $k$ numbers following after occurrence of any \"event\": $X >\\alpha$.\nFor example in order to illustrate the subset $I$ selection rule, let's take an array of 7 Poisson variables with intensity $\\lambda=5$: $Y= [5\\ 11\\ 7\\ 5\\ 2\\ 3\\ 2]$ and $\\alpha=4$ and $k=2$.\nIn this case, the sum S is $S=X_0+X_3=5+5=10$. We don't count elements $X_1$, $X_2$ and $X_4$, $X_5$ because they occur after \"the events\" $X_0>\\alpha$ and $X_3>\\alpha$, and $X_6$ because $X_6<\\alpha$.\nMany thanks in advance. ", "\n\nA:\n\nLet $S_n$ denote the expected value based on an array of size $n\\geqslant1$ and $S_n=0$ for every $n\\leqslant0$. Let $m=E[X\\mid X\\gt\\alpha]$. Let $T$ the time of the first success in an i.i.d. ", "sequence with probability of success $p=P[X\\gt\\alpha]$ hence $P[T=i]=pq^{i-1}$ for every $i\\geqslant1$, where $q=1-p$. Then, for every $n$,\n$$\nS_n=mP[T\\leqslant n]+\\sum_{i\\geqslant1}P[T=i]\\,S_{n-i-k}.", "\n$$\nThus, $S_n=mP[T\\leqslant n]=m(1-q^n)$ for every $n\\leqslant k+1$. Consider the series\n$$\ns(x)=\\sum_{n\\geqslant1}S_nx^n,\\qquad t(x)=\\sum_{n\\geqslant1}P[T=n]x^n,\\qquad t_1(x)=\\sum_{n\\geqslant1}P[T\\leqslant n]x^n.", "\n$$\nThe recursion above translates into\n$$\ns(x)=mt_1(x)+x^ks(x)t(x).", "\n$$\nSince $t_1(x)=t(x)/(1-x)$, this yields\n$$\ns(x)=\\frac{mt(x)}{(1-x)(1-x^kt(x))}.", "\n$$\nSince $t(x)=px/(1-qx)$, one gets\n$$\ns(x)=\\frac{mpx}{(1-x)(1-qx-px^{k+1})}=\\frac{mpx}{(1-x)^2D(x)},\n$$\nwith $D(x)=1+px+px^2+\\cdots+px^k$.\nWhen $|x|\\lt1$, $|qx+px^{k+1}|\\lt q+p=1$ hence $1-qx-px^{k+1}\\ne0$. Thus, $D(x)$ has no root $x$ such that $|x|\\leqslant1$. Finally, when $n\\to\\infty$,\n$$\n\\frac{S_n}n\\to\\frac{mp}{D(1)}=\\frac{m}{k+p^{-1}}.", "\n$$\n\n" ]

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[ "First Nation Screaming Eagles\n\nThe First Nation Screaming Eagles were a Canadian Junior ice hockey team based in Thunder Bay, Ontario. ", " They played in the Thunder Bay Junior B Hockey League and were eligible to compete for the Keystone Cup, Junior B Championship of Western Canada.", "\n\nHistory\nThe First Nation Screaming Eagles joined the Thunder Bay Junior B Hockey League in 2010.", "\n\nIn their first season, they finished fourth out of four teams in the Thunder Bay League and lost their semi-final against the eventual champion Thunder Bay Northern Hawks in 3-games-straight.", "\n\nOn word that the league was expanding, the Eagles elected to fold after only one season instead of incurring more travel costs.", "\n\nSeason-by-season standings\n\nExternal links\nScreaming Eagles Site\n\nCategory:2010 establishments in Ontario\nCategory:2011 disestablishments in Ontario\nCategory:Defunct Lakehead Junior Hockey League teams\nCategory:Sport in Thunder Bay" ]

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[ "Stryjki, Masovian Voivodeship\n\nStryjki is a village in the administrative district of Gmina Tłuszcz, within Wołomin County, Masovian Voivodeship, in east-central Poland.", "\n\nReferences\n\nStryjki" ]

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[ "Stevan Majiedt\n\nSteven Arnold Majiedt (born 18 December 1960 in Kenhardt) is a judge of the Constitutional Court of South Africa and formerly served on the country's Supreme Court of Appeal and as an acting judge on the Constitutional Court. ", "He is best known for his judgment in National Commissioner of the SAPS v Southern Africa Litigation Centre, which pioneered universal jurisdiction and was a focal precedent in the scandal over the South African government's failure, in violation of an ICC arrest warrant and domestic court order, to arrest Omar al-Bashir.", "\n\nReferences\n\nCategory:1960 births\nCategory:Living people\nCategory:Judges of the Constitutional Court of South Africa" ]

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[ "Statistics of U.S. Businesses: 2002:\nFinance & Insurance\nNew York\n\nNew York - Finance & Insurance\n- by Employment Size of Enterprise\nIntroductory text includes scope and methodology.", "\nTable includes only establishments with payroll.", "\nNonemployers are shown separately.", "\nFor descriptions of column headings and rows (industries), click on the appropriate underlined element in the table.", "\n\nNew York - Finance and insurance\n- by Year\nIntroductory text includes scope and methodology.", "\nTable includes only establishments with payroll.", "\nNonemployers are shown separately.", "\nFor descriptions of column headings and rows (industries), click on the appropriate underlined element in the table.", "\n\nNew York - Finance & Insurance\n- by Subsector\nIntroductory text includes scope and methodology.", "\nTable includes only establishments with payroll.", "\nNonemployers are shown separately.", "\nFor descriptions of column headings and rows (industries), click on the appropriate underlined element in the table." ]

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[ "---\nabstract: 'The ability to filter quantum states is a key capability in quantum information science and technology, where one-qubit filters, or polarizers, have found wide application. ", "Filtering on the basis of entanglement requires extension to multi-qubit filters with qubit-qubit interactions. ", "We demonstrate an optical entanglement filter that passes a pair of photons if they have the desired correlations of their polarization. ", "Such devices have many important applications to quantum technologies.'", "\nauthor:\n- Ryo Okamoto\n- 'Jeremy L. O’Brien'\n- 'Holger F. Hofmann'\n- Tomohisa Nagata\n- Keiji Sasaki\n- Shigeki Takeuchi\ntitle: An Entanglement Filter\n---\n\nFilters, that pass the desired and reject the unwanted (material, signal, frequency, polarization, etc) are one of the most important scientific and technological tools available to us. ", "Quantum information science and technology is concerned with harnessing quantum mechanical effects to gain exponential improvement and new functionality for particular tasks in communication [@gi-rmp-74-145], computation [@nielsen], measurement [@gi-sci-306-1330], and lithography [@bo-prl-85-2733]. ", "Perhaps the most unique of these quantum mechanical features is entanglement. ", "Filters which act on the quantum correlations associated with entanglement must operate non-locally on multiple quantum systems, typically two-level qubits. ", "Such a device has been proposed for photonic qubits [@ho-prl-88-147901], however, the technical requirements to build such a device, an optical circuit with two ancillary photons and multiple quantum gates, requiring both quantum interference and classical interference in several nested interferomters, have been lacking.", "\n\nWe demonstrate an entanglement filter by combining two key recent technological approaches—a displaced-Sagnac architecture [@na-sci-316-726] and partially polarizing beam splitters [@la-prl-95-210504; @ki-prl-95-210505; @ok-prl-95-210506]. ", "The entangling capability of the filter was verified, distinguishing it from classical ones. ", "As our entanglement filter acts on photonic qubits, it is promising for quantum technologies, as photons are the logical choice for communication [@gi-rmp-74-145; @gi-nphot-1-165], metrology [@na-sci-316-726; @hi-nat-450-393] and lithography [@da-prl-87-013602], and are a leading approach to information processing [@ob-sci-318-1567]. ", "The filter can be used for the creation as well as the purification of entanglement [@pa-nat-410-1067; @ya-nat-421-343], which will be important in realizing quantum relays and repeaters for long distance quantum communication.", "\n\nThe most common examples of a filter for photonic qubits is a polarizer that transmits only the horizontal component of the incident photons (Fig. ", "1A). ", "Polarization filters are crucial for the initialization and read out of photonic qubits as well as for the measurement related effects such as the quantum Zeno effect [@mi-jmp-18-756; @kw-prl-83-4725]. ", "More sophisticated photonic filters that transmit only single photon states while rejecting higher photon number states have also been realized by using ancillary photons and photon detection to induce the required optical non-linearity [@sa-pra-71-021801; @sa-prl-96-083601; @re-prl-98-203602]. ", "The concept of a polarization filter can be extended to a higher dimensional Hilbert space of multi-qubits and one may anticipate that the necessary qubit-qubit interactions required will also require the use of ancillary photons.", "\n\nThe two-photon polarization filter proposed in [@ho-prl-88-147901] is a device that transmits photon pairs only if they share the same horizontal or vertical polarization without decreasing the quantum coherence between these two possibilities (Fig. ", "1B). ", "As this filter is not sensitive to the individual polarization of the photons, it can preserve and even create entanglement between the photons passed through it (Fig. ", "1C). ", "The filter achieves this two qubit filtering effect by using two ancilla photons as probes that detect whether the two input photons are in the desired states or not. ", "Detection of the ancilla photons indicates a successful filter operation, requiring no post-selection in the output. ", "Note that this is a significant difference between this filter and the function realized by output post-selection on a polarizing beam splitter [@pa-nat-410-1067; @pi-pra-64-062311], where it is necessary to eliminate the cases where both photons exit on the same side. ", "Because our filter should reliably produce the correct two photon output in separate ports of the device, it can be integrated into larger quantum information networks, just like a one-qubit polarization filter. ", "It is therefore possible to apply it to a wide range of problems, such as encoding quantum information in multiple-qubits and entanglement purification from mixed entangled states.", "\n\nThe operation of this filter can be summarized by a single operator $\\hat{S}$ describing the effect on an arbitrary two photon input state [@ho-prl-88-147901]: $$\\hat{S}=\\frac{1}{4}({|HH\\rangle \\langle HH|-|VV\\rangle \\langle VV|}),$$ where $|HH\\rangle$ and $|VV\\rangle$ denotes the state where both incident photons are horizontally ($H$) and vertically ($V$) polarized, respectively. ", "This operator filters out the $|HV\\rangle$ and $|VH\\rangle$ components of the two photon state without reducing the coherence between the remaining $|HH\\rangle$ and$|VV\\rangle$ components. ", "The negative sign between the terms is a consequence of the phase difference between two photon reflection and two photon transmission at the beam splitters. ", "The factor of 1/4 is an expression of the transmission probability of 1/16 for $|HH\\rangle$ and $|VV\\rangle$. It should be noted however that the detection of the ancilla photons indicates a successful transmission of the two input photons, so that it is not necessary to detect the output photons in order to know that they were successfully transmitted.", "\n\nTo understand the unique quantum properties of this filter, it is useful to consider the effects of the filtering process on two diagonally polarized photons. ", "As diagonal polarizations are coherent superpositions of horizontal and vertical polarizations ($|P\\rangle\\equiv\\frac{1}{\\sqrt{2}}(|H\\rangle+|V\\rangle)$; $|M\\rangle\\equiv\\frac{1}{\\sqrt{2}}(|H\\rangle-|V\\rangle)$), two diagonally polarized photons have a well defined coherence between their $|HH\\rangle$ and $|VV\\rangle$ components that determines whether their diagonal polarizations are parallel ($+$) \\[*eg*: $|PP\\rangle ~/~ |MM\\rangle = \\frac{1}{2}(|HH\\rangle+|VV\\rangle\\pm ...)$\\] or orthogonal ($-$) \\[*eg*: $|PM\\rangle ~/~ |MP\\rangle = \\frac{1}{2}(|HH\\rangle-|VV\\rangle \\pm ...)$\\]. ", "The operator $\\hat{S}$ preserves the magnitude of this coherence, but flips the sign: Eq. ", "1. ", "Therefore, the correlation between the diagonal polarizations is inverted; parallel inputs resulting in the superpositions of the orthogonal outputs and vice versa. ", "Moreover, the coherence between $|HH\\rangle$ and $|VV\\rangle$ indicates a correlation between the circular polarizations—opposite directions ($+$) or same direction ($-$). ", "Thus, filtering out the $|HV\\rangle$ and $|VH\\rangle$ components of two diagonally polarized input photons also generates correlations between the circular polarizations of the photons, indicating the generation of entanglement.", "\n\nA schematic of the optical quantum circuit for the entanglement filter Fig. ", "2A shows that multi photon interferences occur at each of the four beam splitters BS1 to BS4. ", "The crucial ones are BS2 and BS3. ", "The working principle of the quantum circuit is as follows: whenever one of the ancilla photons meets a single input photon at BS2 or BS3, two photon quantum interference between the reflection of both photons and the exchange of ancilla and input photon reduces the probability of finding a single photon at D1 or D2 to zero (Fig. ", "2A, inset) [@ho-prl-59-2044]. ", "Thus, a single horizontally polarized photon cannot pass the circuit, resulting in the elimination of the $|HV\\rangle$ and $|VH\\rangle$ components. ", "However, the $|HH\\rangle$ component can pass because the two input photons will both arrive at BS2 or BS3 together (the two H photons undergo quantum interference at BS1). ", "In that case, the negative probability amplitude corresponding to the exchange of the ancilla photon and one of the input photons is higher than the positive probability amplitude for three photon reflection, and the $|HH\\rangle$ component is transmitted with a flipped phase.", "\n\nTo realize the quantum optical circuit of Fig. ", "2A, we have combined two recent technological approaches in order to simplify and stabilize quantum optical circuits: the displaced-Sagnac architecture [@na-sci-316-726] and partially polarizing beam splitters (PPBSs) [@la-prl-95-210504; @ki-prl-95-210505; @ok-prl-95-210506]. ", "The PPBSs reflect vertically polarized photons perfectly while transmitting/reflecting horizontally polarized photons with 50% probability. ", "Replacing all the beam splitters (BS1 to BS4) with such PPBSs, we can remove the four polarizing beamsplitters used to separate the two polarizations (Fig. ", "2B). ", "The remaining optical path interferometer is realized as a displaced Sagnac interferometer (Fig. ", "2C). ", "In this setup, all the four polarization modes of two input photons pass through all the optical components inside the interferometer so that the path-differences between those four polarization modes are robust against drifts or vibrations of optical components.", "\n\nWe used photons generated via type-I spontaneous parametric down-conversion [@bu-prl-25-84]. ", "The pump laser pulses (82 MHz, @ 390 nm) pass through a beta-barium borate (BBO) crystal twice to generate two pairs of photons. ", "Two photons in one of the pairs are used as the signal photons, and the two photons in the other pair are used as the ancillary photons. ", "The visibility of the Hong-Ou-Mandel dip [@ho-prl-59-2044] was $96\\pm1 \\%$ for two photons in the same pair, and $85\\pm5 \\%$ for photons from different pairs. ", "To test the performance of our quantum filter circuit, we used coincidence measurements between the four threshold detectors at D1, D2 and the two outputs, rather than using photon number discriminating detectors [@ta-apl-74-1063; @ki-apl-74-902; @ga-nphot-1-585; @ka-nphot-2-425] for D1 and D2, as we needed to analyze the polarization state of the output to confirm correct operation. ", "This polarization analysis was performed using pairs of half wave plates and quarter wave plates together with polarizing beam splitters.", "\n\nFirst, we checked the essential operation of the filter circuit: we prepared input signal photons in the four combinations of horizontal (H) and vertical (V) polarizations (which we call the Z-basis states) and observed how those input states are filtered by the circuit (Fig. ", "3). ", "It is clear from the experimental data that the photon pairs are transmitted through the filter when the two input photons share the same polarization (HH or VV), and most of the pairs are filtered out when the two input photons have different polarization (HV or VH). ", "The fidelity of this process can be defined as the ratio of correctly transmitted photon pairs to the total number of transmitted photon pairs. ", "For the filter’s operation on horizontal and vertical polarizations, the fidelity is $F_{Z\\rightarrow Z}=0.80$.\n\nNext, it is necessary to test the preservation of quantum coherence between the $|HH\\rangle$ and the $|VV\\rangle$ components transmitted by the filter. ", "As explained above, this can be done by using diagonally polarized photons in the input. ", "We prepared pairs of photons in all combinations of diagonal linear polarizations $|P\\rangle$ and $|M\\rangle$ (the X-basis states) as signal inputs. ", "The input photons are then in an equal superposition of the four different horizontal/vertical polarization states $|HH\\rangle$, $|HV\\rangle$, $|VH\\rangle$, and $|VV\\rangle$ (with different signs of the coherences for each of the four different inputs). ", "The filter should transmit only the HH and the VV components while preserving the quantum coherence between them. ", "As a result, the ideal output states are entangled states with maximal correlations in both the circular and the diagonal polarizations. ", "To test this entanglement generation, we first detected the output photons in the right-circular $|R\\rangle\\equiv (|H\\rangle+i|V\\rangle)/\\sqrt{2}$ and left-circular $|L\\rangle\\equiv (|H\\rangle-i|V\\rangle)/\\sqrt{2}$ polarizations (Y-basis). ", "The predicted correlations between the circular polarizations of the output are observed with a fidelity of $F_{X\\rightarrow Y}=0.68$. To complete the test of entanglement generation, we also detected the diagonal polarizations of the output to test whether the polarization correlation is correctly flipped by the filter. ", "The fidelity of this filter operation is $F_{X\\rightarrow X} =0.60$. Taken together, the three experimental tests are sufficient for the evaluation of the quantum filter operation. ", "Because almost all the errors conserve horizontal/vertical polarization (see Appendix 1), the probability of the correct operation $\\hat{S}$ is given by the process fidelity $$F_p = (F_{z->z}+F_{x->y}+F_{x->x}-1)/2 = 0.54.$$ The entanglement capability of the filter can be evaluated as $C=2 F_p-1 = 0.08$, and so our experimental results provide clear evidence of the entangling capability of the quantum filter operation.", "\n\nThe entanglement filter will be a key element in the control of multi-photon quantum states, with a wide range of applications in entanglement based quantum communication and quantum information processing. ", "For the present tests of the performance of the quantum filter circuit, we used threshold detectors to monitor the output state. ", "For applications where the output state cannot be monitored, high-efficiency number-resolving photon detectors [@ta-apl-74-1063; @ki-apl-74-902; @ga-nphot-1-585; @ka-nphot-2-425] could be used at D1 and D2 to generate the heralding signals. ", "Such a circuit could be used for on-demand generation of entangled photons, non-destructive entanglement purification, and could be implemented using an integrated waveguide architecture [@po-sci-320-646]. ", "This work was supported by the Japan Science and Technology Agency (JST), Ministry of Internal Affairs and Communication (MIC), Japan Society for the Promotion of Science (JSPS), 21st Century COE Program, Special Coordination Funds for Promoting Science and Technology.\\\n\n[10]{}\n\nN. Gisin, G. Ribordy, W. Tittel, H. Zbinden, [*Rev. Mod. ", "Phys.*]{} [**", "74**]{}, 145 (2002).", "\n\nM. A. Nielsen, I. L. 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Ou, L. Mandel, [*Phys. ", "Rev. Lett.*]{} [**", "59**]{}, 2044 (1987).", "\n\nD. C. Burnham, D. L. Weinberg, [*Phys. ", "Rev. Lett.*]{} [**", "25**]{}, 84 (1970).", "\n\nS. Takeuchi, J. Kim, Y. Yamamoto, H. H. Hogue, [*Appl. ", "Phys. ", "Lett.*]{} [ **", "74**]{}, 1063 (1999).", "\n\nJ. Kim, S. Takeuchi, Y. Yamamoto, H. H. Hogue, [*Appl. ", "Phys. ", "Lett.*]{} [ **", "74**]{}, 902 (1999).", "\n\nE. J. Gansen, [*et al.*]{}, [*", "Nature Photon.*]{} [**", "1**]{}, 585 (2007).", "\n\nB. E. Kardynal, Z. L. Yuan, A. J. Shields, [*Nature Photon.*]{} [**", "2**]{}, 425 (2008).", "\n\nA. Politi, M. J. Cryan, J. G. Rarity, S. Yu, J. L. O’Brien, [*Science*]{} [**320**]{}, 646 (2008).", "\n\nAppendix 1 {#appendix-1 .unnumbered}\n==========\n\n*Derivation of the process fidelity.* ", "The errors due to the change of input horizontal/vertical polarization (i.e. $|HH\\rangle \\to |HV\\rangle$) are negligibly small in our experiment shown in Fig. ", "3B ( $Z \\to Z$ measurement ). ", "Based on this fact, we can assume that the input horizontal/vertical polarization is preserved in our filter, and thus our filter operation can be well described in terms of superpositions of $|HH \\rangle \\langle HH|$, $|HV \\rangle \\langle HV|$, $|VH \\rangle \\langle VH|$ and $|VV \\rangle \\langle VV|$. Under this assumption, we can estimate the process fidelity of our entanglement filter as follows.", "\n\nIt is convenient to express the errors in terms of the superpositions $$\\begin{aligned}\n\\hat{S}_{0}=\\sqrt{2}(|HH \\rangle \\langle HH|-|VV \\rangle \\langle VV|),\n\\nonumber \\\\\n\\hat{S}_{zz} =\\sqrt{2}(|HH \\rangle \\langle HH|+|VV \\rangle \\langle VV|),\n\\nonumber \\\\\n\\hat{S}_{xy} =\\sqrt{2}(|HV \\rangle \\langle HV|+|VH \\rangle \\langle VH|),\n\\nonumber \\\\\n\\hat{S}_{xx} =\\sqrt{2}(|HV \\rangle \\langle HV|-|VH \\rangle \\langle VH|).\\end{aligned}$$ Here, $\\hat{S}_{0}$ represents the intended operation of the entanglement filter, $\\hat{S}_{zz}$ represents the operation with a phase flip error between $|HH \\rangle$ and $|VV \\rangle$, and $\\hat{S}_{xy}$, $\\hat{S}_{xx}$ represent the leakage (or transmission error) of the $|HV \\rangle$ and $|VH \\rangle$ components, either with or without a phase flip between these components. ", "The operation of our filter can then be written as $$\\label{eq:pm}\n%\\rho_{out}= \\sum_{n,m} \\chi_{nm} \\hat{S}_n \\rho_{in} \\hat{S}_m\nE(\\rho_{in})= \\sum_{n,m} \\chi_{nm} \\hat{S}_n \\rho_{in} \\hat{S}_m$$ where $n,m \\in \\{0, zz, xy, xx\\}$ and $\\chi_{nm}$ are the process matrix elements of the noisy quantum process.", "\n\nEach of our experimentally observed truth table operations $i\\to j$ is correctly performed by $\\hat{S}_{0}$ and one other operation $\\hat{S}_n$, as indicated by the index $n=ij$ for $i,j \\in \\{x,y,z\\}$. For example, in case of the $z\\to z$ truth table, operation $\\hat{S}_{0}$ and $\\hat{S}_{zz}$ result in the correct operation and $\\hat{S}_{xy}$ and $\\hat{S}_{xx}$ give false results. ", "Therefore, the fidelities $F_{i\\to j}$ can be given by the sums of the probability $F_p=\\chi_{0,0}$ for the correct operation $\\hat{S}_{0}$ and the probabilities $\\eta_{ij} = \\chi_{nn}$ for the errors $\\hat{S}_n$ as follows. ", "$$\\begin{aligned}\nF_{z \\to z}=F_p+\\eta_{zz}\n\\nonumber\n\\\\\nF_{x \\to y}=F_p+\\eta_{xy}\n\\nonumber\n\\\\\nF_{x \\to x}=F_p+\\eta_{xx}\n\\label{eq:fid}\\end{aligned}$$ Note that these relations between the diagonal elements of the process matrix and the experimentally observed fidelities can also be derived from eq. (", "\\[eq:pm\\]) using the formal definition of the experimental fidelities. ", "In this case the fidelities are determined by the sums over the correct outcomes $|(j)_l \\rangle$ in $E(|(i)_k\\rangle \\langle(i)_k|)$, averaged over all inputs $|(i)_k \\rangle$, $$\\begin{aligned}\nF_{i\\to j} &=& \\sum_{l,k} \\langle(j)_l| E( |(i)_k\\rangle \\langle(i)_k| ) |(j)_l \\rangle/4) \\\\\n&=& \\sum_{n,m} \\chi_{nm} (\\sum_{l,k} \\langle(j)_l|\\hat{S}_n|(i)_k \\rangle \\langle(i)_k|\\hat{S}_m|(j)_l \\rangle/4).\\end{aligned}$$ Here $k,l \\in \\{1,2,3,4\\}$, and $(i)_k$ denotes the $k$ th state of the $i$ basis states. ", "For example, $|(i)_1 \\rangle=|HH \\rangle, |(i)_2 \\rangle=|HV \\rangle, |(i)_3 \\rangle=|VH \\rangle, |(i)_4 \\rangle=|VV \\rangle$ for $i=z$. The sums over initial states $k$ and final states $l$ are one for $n=m=0$ and for $n=m=ij$ and zero in all other cases, confirming the results in eq.(\\[eq:fid\\]).", "\n\nSince the diagonal elements of the process matrix correspond to the probabilities of the orthogonal basis operations, their sum is normalized to one, so that $\\sum_n \\chi_{nn}=F_p+\\eta_{zz}+\\eta_{xy}+\\eta_{xx}=1$. It follows that the sum of all three experimentally determined fidelities is $F_{z \\to z}+F_{z \\to y} + F_{x \\to x} = 2 F_p+1$. Therefore, the process fidelity of our circuit is given by $$F_p=(F_{z \\to z}+F_{x \\to y}+F_{x \\to x}-1)/2 = 0.54.$$\n" ]

{ "pile_set_name": "ArXiv" }

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[ ".. _illuminants:\n\n.. include:: global.txt\n\nObservers and Illuminants\n=========================\n\nIlluminants and observer angles are used in all color spaces that use\nreflective (instead of transmissive) light. ", "Here are a few brief overviews\nof what these are and what they do:\n\n* `Understanding Standard Illuminants in Color Measurement`_ - Konica Minolta\n* `What is Meant by the Term \"Observer Angle\"?", "`_ - XRite\n\nTo adjust the illuminants and/or observer angles on a color::\n\n lab = LabColor(0.1, 0.2, 0.3, observer='10', illuminant='d65')\n\nTwo-degree observer angle\n-------------------------\n\nThese illuminants can be used with ``observer='2'``, for the color spaces\nthat require illuminant/observer:\n\n* ``'a'``\n* ``'b'``\n* ``'c'``\n* ``'d50'``\n* ``'d55'``\n* ``'d65'``\n* ``'d75'``\n* ``'e'``\n* ``'f2'``\n* ``'f7'``\n* ``'f11'``\n\nTen-degree observer angle\n-------------------------\n\nThese illuminants can be used with ``observer='10'``, for the color spaces\nthat require illuminant/observer:\n\n* ``'d50'``\n* ``'d55'``\n* ``'d65'``\n* ``'d75'``\n\n.. _Understanding Standard Illuminants in Color Measurement: http://sensing.konicaminolta.us/2013/11/Understanding-Standard-Illuminants-in-Color-Measurement/\n.. _What is Meant by the Term \"Observer Angle\"?: ", "http://www.xrite.com/product_overview.aspx?ID=773&Action=support&SupportID=3544\n" ]

{ "pile_set_name": "Github" }

[ 0.000866600894369185, 0.0005835787742398679, 0.0013862948399037123, 0.000796827080193907 ]

[ "---\nabstract: |\n For a complex simple Lie algebra of type $A$, given a family of elements $f_\\la\\in \\mathbb Z[\\Lambda],\\la\\in \\Lambda^+,$ we show that $f_\\la$ is just the formal character of the Weyl module $V(\\la) $ if $f_\\la$ satisfy two natural conditions.\\\n **Keywords:** formal characters, tensor product, Weyl modules\n\n [**2000 MR Subject Classification:**]{} 17B10 20G05\nauthor:\n- Zhongguo Zhou\ndate:\n- \n- |\n *College of Science, Hohai University\\\n Nanjing, 210098, P.R.China.\\\n [ [e-mail: zhgzhou@hhu.edu.cn]{}\\\n ]{}* \ntitle: |\n Rigidity of formal characters of\\\n Lie algebras of type $A$ \n---\n\nIntroduction\n============\n\nLet $\\g_l$ be a complex simple Lie algebra of type $A_l$, and let $V(\\la)$ be the Weyl module. ", "The formal character $\\ch_\\lambda$ of $V(\\la)$ is determined by the Weyl character formula or by other methods, such as the Freudenthal formula. ", "The Littlewood-Richardson coefficient, $c_{\\mu,\\,\\nu}^\\la$ defined the multiplicity of $V(\\la)$ in $V(\\mu)\\bigotimes V(\\nu)$, can be determined according to the formal character $\\ch_\\lambda.$ In this paper we shall consider the following problem:\n\n*Given a family of elements $f_\\la\\in \\mathbb\nZ[\\Lambda],\\la\\in \\Lambda^+,$ when are they equal to $\\ch_\\la?$*\n\nWe prove that two natural conditions are enough to do so. ", "The one says it should contain right information about the Weyl module for proper subalgebras of $\\g_l,$ that is to say, for all $\\beta =\\lambda-\\mu, $ $m_\\lambda(\\mu)=n_\\lambda(\\mu), $ if $|\\mbox{Supp}(\\beta)|<l.$ The other says the number $n_{\\mu,\\,\\nu}^\\la $, defined similarly to $c_{\\mu,\\,\\nu}^\\la$, should satisfy $n_{\\mu,\\,\\nu}^\\lambda=n_{\\lambda,\\,-w_0\\nu}^\\mu.$\n\nThe motivation for this problem comes from the modular representation theory of linear algebraic groups in positive characteristic, especially the Lusztig conjecture. ", "In Lusztig’s theory, the $\\ch L(\\lambda)$ is given by the Kanzhdan-Lusztig polynomials and $\\ch V(\\mu)'s.$ The first condition on $\\ch L(\\lambda)$ can be proved by an induction on rank. ", "So we want to find out some natural condition to ensure the conjecture. ", "Hence we consider the problem in complex field at first, the most simple case.", "\n\nnotations\n=========\n\nLet $\\g_l$ be a complex simple Lie algebra of type $A_l$, and let $\\Delta=\\{\\al_1, \\al_2,\\cd, \\al_l\\}$ be the set of simple roots. ", "Let $\\Lambda$ be the set of weights, and $\\omega_1, \\omega_2,\n\\cdots, \\omega_l$ the set of fundamental dominant weights. ", "Then the set of dominant weights is denoted by $\\Lambda^+.$ Let $\\ch_\\lambda$, $\\lambda\\in \\Lambda^+$, be the formal character of the Weyl module $V(\\lambda)$, they form a free $\\mathbb Z$-module of the commutative ring $\\mathbb Z[\\Lambda]$, with base $\\{e(\\lambda),\\lambda\\in\\Lambda\\},$ and multiplication $e(\\lambda)*e(\\mu)=e(\\lambda+\\mu).$ Let $W$ be the Weyl group, action on $\\mathbb Z[\\Lambda]$ naturally as $\\sigma e(\\lambda)\n=e(\\sigma\\lambda).$ Set $$\\mathbb Z[\\Lambda]^W=\\{f\\in \\mathbb Z[\\Lambda]\\,|\\, wf=f, \\;\\;w\\in W\\}.$$ Let $W_\\lambda $ be the $W$-orbit of $\\lambda$ and $h(\\lambda )=\\sum_{x\\in\nW_\\lambda} e(x).$ Let $\\Pi(\\lambda)$ be the set of saturated weights of weight $\\lambda$ and $\\Pi^+(\\lambda)=\\Pi(\\lambda)\\cap \\Lambda^+.$ It is well known that $$\\ch_\\lambda=\\sum_{x\\in\\Pi^(\\lambda)}m_\\lambda(x)e(x)=\\sum_{\\mu\\in\n\\Pi^+(\\lambda)}m_\\lambda(\\mu)h(\\mu), \\;\\;\\lambda\\in \\Lambda^+,$$ forms a basis of $\\mathbb Z[\\Lambda]^W.$\n\nRecall that $w_0$ is the longest element of $W$ with the action $w_0\\omega_i=-\\omega_{l-i}.$ Let $c_{\\mu,\\,\\nu}^\\la$ be the Littlewood-Richardson coefficient. ", "According to the complete reducibility of $\\g_l$-modules and $$\\dim\\hom(U\\otimes V, W)=\\dim\\hom(U ,W\\otimes V^*),$$ we have $$[V(\\mu)\\otimes V(\\la): V(\\nu)]=[V(\\nu)\\otimes V(\\la)^*: V(\\mu)]=[V(\\nu)\\otimes V(-w_0\\la): V(\\mu)].$$ Hence $$c_{\\mu,\\,\\la}^\\nu=c_{\\nu,\\,-w_0\\la}^\\mu.$$\n\nmain results\n============\n\n[**3.1.**]{} ", "Let $\\beta=\\sum_{i=1}^{l}k_i\\alpha_i,$ define $$\\mbox{Supp}(\\beta)=\\{\\alpha_i\\,| \\,k_i\\neq 0\\}.$$ For $\\lambda \\in \\Lambda^+,$ set $f_{\\lambda}\n=\\sum_{\\mu\\in \\Pi^+(\\lambda)}n_\\lambda(\\mu)h(\\mu)\n=\\sum_{x\\in \\Pi(\\lambda)}n_\\lambda(x)e(x)\n\\in \\mathbb Z[\\Lambda]^W$ satisfied $n_\\lambda(\\lambda)=1, n_\\lambda(x)=0,$ if $x\\notin \\Pi(\\lambda).$ Then $f_{\\lambda}$ is also a basis of $\\mathbb Z[\\Lambda]^W.$ Hence there exists unique $n_{\\mu,\\,\\nu,}^\\lambda $ such that $$f_{\\mu}* f_{\\nu}=\\sum_{\\lambda\\in\\Pi^+(\\mu+\\nu)}n_{\\mu,\\,\\nu}^\\lambda f_{\\lambda}.$$ By the definition of $f_{\\lambda}'s,$ we have $$n_{\\mu,\\,\\nu}^{\\mu+\\nu}=1; n_{\\mu,\\,\\nu}^\\lambda=n_{\\nu,\\,\\mu}^\\lambda.$$\n\n\\[th1\\] If these $f_{\\lambda}$ satisfy the following two conditions:\n\n\\(1) for all $\\beta =\\lambda-\\mu, m_\\lambda(\\mu)=n_\\lambda(\\mu)$, if $|{\\rm{Supp}}(\\beta)|<l.$\n\n\\(2) $n_{\\mu,\\,\\nu}^\\lambda=n_{\\lambda,\\,-w_0\\nu}^\\mu.$\n\nThen $f_{\\lambda}=ch_\\lambda, n_{\\mu,\\,\\nu}^\\lambda=c_{\\mu,\\,\\nu}^\\lambda.$\n\nThe two conditions in theorem \\[th1\\] are very natural. ", "The first one comes from restricting $V(\\lambda)$ to subalgebra with smaller rank and the second one is because the tensor-hom adjunction. ", "So it is surprised that $ch_\\lambda, n_{\\mu,\\,\\nu}^\\lambda$ can be determined completely only by two conditions. ", "Hence we call this property as the rigidity of formal characters or representation ring of Lie algebra.", "\n\nFirstly, we need a lemma.", "\n\nFor $f_{\\lambda},$ the numbers $n_{\\mu,\\,\\nu}^\\lambda$ are uniquely determined by $n_\\lambda(\\mu),$ and vice versa.", "\n\n[[**Proof:** ]{}]{}Because $f_{\\mu}* f_{\\nu}\\in \\mathbb Z[\\Lambda]^W$ and $f_\\lambda,\n\\lambda\\in \\Lambda^+$, form the basis of $\\mathbb Z[\\Lambda]^W,$ so $f_{\\mu}* f_{\\nu}$ can be written in terms of a linear combination of base elements $f_{\\lambda}, \\lambda\\in \\Lambda^+$, i.e. $$f_{\\mu}* f_{\\nu}=\\sum_{\\lambda\\in\\Pi^+(\\mu+\\nu)}n_{\\mu,\\,\\nu}^\\lambda f_{\\lambda}.$$ Therefore all these $n_{\\mu,\\,\\nu}^\\lambda$ are uniquely determined.", "\n\nNow suppose that we know $n_{\\mu,\\,\\nu}^\\lambda$ already, and will determine $n_\\lambda(\\mu)$ recursively according to a suitable partial order in $\\Lambda^+$ as follow.", "\n\nLet $\\lambda,\\mu\\in \\Lambda^+,$ define $\\mu< \\lambda$ if $\\mu\\prec \\lambda $ or $ \\lambda-\\mu\\in \\Lambda^+.$\n\nFor the fundamental weights $\\omega_i$ and $0,$ their saturated weight set $\\Pi(\\omega_i)$ only contains one dominate weight. ", "So $$f_{\\omega_i}=h(\\omega_i), \\;\\; f_{0}=h(0)=e(0).$$ Suppose that $\\lambda\\in \\Lambda^+$ does not be a fundamental dominate weight or 0, then there exist $\\mu,\\nu\\in\\Lambda^+,$ such that $$\\lambda=\\mu+\\nu, \\; \\mu< \\lambda,\\; \\nu< \\lambda.$$ Then $$f_{\\mu}* f_{\\nu}=f_{\\lambda}+\\sum_{s\\in \\Pi^+(\\lambda),\\, s\\neq \\lambda}n_{\\mu,\\,\\nu}^s f_{s},$$ i.e. $$f_{\\lambda}=f_{\\mu}* f_{\\nu}-\\sum_{x\\in \\Pi^+(\\lambda),\\, s\\neq \\lambda}n_{\\mu,\\,\\nu}^s f_{s}.$$ Therefore we can get a precise expression for $f_{\\lambda}$ because all $f_{\\mu}, f_{\\nu}, f_{s}, n_{\\mu,\\,\\nu}^s$ can be determined recusively as $\\mu< \\lambda, \\nu< \\lambda ,s< \\lambda$. The lemma is proved.", "\n\n[**Remark**]{}: This lemma doesn’t work for type $B_l.$ For example, for $B_2,$ we can’t determine $(1,0)_{(0,0)}$ by using the above method because there is no way to decompose $(1,0)$ into a sum of two non-trivial dominate weights.", "\n\n[**3.2.**]{} ", "From the equation $f_{\\lambda}=f_{\\mu}* f_{\\nu}-\\sum_{x\\in \\Pi^+(\\lambda),\n\\, s\\neq \\lambda}n_{\\mu,\\,\\nu}^s f_{s}$, we have more precise expression. ", "$$\\begin{aligned}\nf_{\\lambda}\\!\\!\\!\\!\\!\\!&&=\\sum_{t\\in \\Pi(\\lambda)}n_\\lambda(t)e(t)\\\\\n&&=\n\\sum_{y\\in \\Pi(\\mu)}n_\\mu(y)e(y)*\n\\sum_{z\\in \\Pi(\\nu)}n_\\nu(z)e(z)\n-\\sum_{s\\in \\Pi^+(\\lambda),s\\neq \\lambda}n_{\\mu,\\,\\nu}^s\n\\sum_{x\\in \\Pi(s)}n_s(x)e(x)\\\\\n&&=\n\\sum_{y\\in \\Pi(\\mu),z\\in \\Pi(\\nu)}n_\\mu(y)n_\\nu(z)e(y+z)\n-\\sum_{s,x\\in \\Pi(\\lambda),s\\neq \\lambda,}n_{\\mu,\\,\\nu}^s n_s(x)e(x)\\\\\n&&=\n\\sum_{t\\in\\Pi(\\lambda)}\\left(\n\\sum_{y\\in \\Pi(\\mu),z\\in \\Pi(\\nu),y+z=t}n_\\mu(y)n_\\nu(z)\\right)e(t)-\\\\\n&&-\\sum_{t\\in \\Pi(\\lambda)}\\left(\\sum_{s\\in \\Pi(\\lambda),s\\neq \\lambda,}n_{\\mu,\\,\\nu}^s n_s(t)\\right)e(t).\\end{aligned}$$ Hence $$\\begin{aligned}\n{\\label{gsi}}\nn_\\lambda(t)=\n\\sum_{y\\in \\Pi(\\mu),z\\in \\Pi(\\nu),y+z=t}n_\\mu(y)n_\\nu(z)\n-\\sum_{s\\in \\Pi(\\lambda),s\\neq \\lambda}n_{\\mu,\\,\\nu}^s n_s(t),\\end{aligned}$$ and then $$\\begin{aligned}\nn_{\\mu,\\,\\nu}^t\n=\n\\sum_{y\\in \\Pi(\\mu),z\\in \\Pi(\\nu),y+z=t}n_\\mu(y)n_\\nu(z)\n-\\sum_{s\\in \\Pi(\\lambda),s\\neq t,}n_{\\mu,\\,\\nu}^s n_s(t).\\end{aligned}$$\n\nNote from the two formulas that $n_\\lambda(t)$ is only depended on those numbers $$\\begin{aligned}\n& n_\\mu(y), \\quad & \\mu-y\\preceq \\lambda-t, \\mu<\\lambda;\\\\\n & n_\\nu(z) ,\\quad & \\nu-z\\preceq\\lambda-t,\\nu< \\lambda; \\\\\n & n_s(t), n_{\\mu,\\,\\nu}^s, \\quad & t\\preceq s\\prec \\lambda\\end{aligned}$$ and $n_{\\mu,\\,\\nu}^t$ is only depended on those numbers $$\\begin{aligned}\n& n_\\mu(y), \\quad & \\mu-y\\preceq \\lambda-t, \\mu<\\lambda;\\\\\n & n_\\nu(z) ,\\quad & \\nu-z\\preceq\\lambda-t,\\nu< \\lambda; \\\\\n & n_s(t), n_{\\mu,\\,\\nu}^s, \\quad & t\\prec s\\preceq \\lambda.\\end{aligned}$$ We can substitute $n_{\\mu,\\,\\nu}^s,s\\succ t$, in (2) for those in (1), and obtain $$\\begin{aligned}\n\\label{eqn3}\nn_\\lambda(t)=n_{\\mu,\\,\\nu}^t +g(n_\\mu(y),n_\\nu(z),n_s(x)),\\end{aligned}$$ where $g(n_\\mu(y),n_\\nu(z),n_s(x)) $ is determined by $ n_\\mu(y), n_\\nu(z), n_s(x),t\\preceq x,s\\preceq \\lambda$ and $ s-x\\prec\\lambda-t.$\n\nWe now prove the theorem by induction on $\\Lambda^+$ with the partial order $\\lq\\lq<\"$ and on $\\Pi(\\lambda)$ with the partial order $\\lq\\lq\\prec\".$\n\nIt is only need to prove $n_\\lambda(\\mu)=m_\\lambda(\\mu), \\lambda\\in \\Lambda^+,\\mu\\in\\Pi^+(\\lambda).$\n\nFirstly, if $\\lambda=\\omega_i$ or $0,$ their saturated weight set $\\Pi(\\lambda)$ only contains one dominate weight. ", "So the theorem holds by the definition of $f_\\lambda.$\n\nSuppose that $\\lambda\\in \\Lambda^+, $ not be fundamental weights $\\omega_i$ or 0. ", "Then $n_\\lambda(\\lambda)=1=m_\\lambda(\\lambda).$ Let $\\mu\\in \\Pi^+(\\lambda),\\beta=\\lambda-\\mu.$ Consider the three cases as follows:\n\n\\(1) when $|\\rm{Supp}(\\beta)|<l,$ we have $n_\\lambda(\\mu)=m_\\lambda(\\mu)$ by the first condition in theorem.", "\n\n\\(2) when $|\\rm{Supp}(\\beta)|=l $ and $\\beta=\\alpha_1+\\alpha_2+\\cdots+\\alpha_l=\\omega_1+\\omega_l,$ we have $\\mu=\\lambda-\\beta=\\lambda-\\omega_1-\\omega_l,$ thus $\\lambda_1\\geq 1,\\lambda_l\\geq 1.$ Moreover, $\\lambda=(\\lambda-\\omega_1)+\\omega_1, \\lambda-\\omega_1\\in \\Pi^+(\\lambda)$.\n\nBy the second condition of theorem, we have $$n_{\\omega_1,\\,\\lambda-\\omega_1}^\\mu=n_{\\omega_1,\\,\\lambda-\\omega_1}^{\\lambda-\\omega_1-\\omega_l}\n=n_{\\lambda-\\omega_1-\\omega_l,\\,-w_0\\omega_1}^{\\lambda-\\omega_1}\n=n_{\\lambda-\\omega_1-\\omega_l,\\,\\omega_l}^{\\lambda-\\omega_1}=1.$$ The last equation holds because $${\\lambda-\\omega_1-\\omega_l+\\omega_l}-({\\lambda-\\omega_1})=0.$$ We also have $$c_{\\omega_1,\\,\\lambda-\\omega_1}^\\mu\n =c_{\\omega_1,\\,\\lambda-\\omega_1}^{\\lambda-\\omega_1-\\omega_l}\n =c_{\\lambda-\\omega_1-\\omega_l,\\,-w_0\\omega_1}^{\\lambda-\\omega_1}\n =c_{\\lambda-\\omega_1-\\omega_l,\\,\\omega_l}^{\\lambda-\\omega_1}\n =1.$$ Therefore, $$n_{\\omega_1,\\,\\lambda-\\omega_1}^\\mu\n=c_{\\omega_1,\\,\\lambda-\\omega_1}^\\mu.$$ For $\\omega_1<\\lambda, \\,\\lambda-\\omega_1<\\lambda,$ according to equation (\\[eqn3\\]) and induction hypothesis, we have $$\\begin{aligned}\n&&n_\\lambda(\\mu)=n_{\\omega_1,\\,\\lambda-\\omega_1}^\\mu +g(n_{\\omega_1}(y),n_{\\lambda-\\omega_1}(z),n_s(x))\\\\\n&&=c_{\\omega_1,\\,\\lambda-\\omega_1}^\\mu +g(c_{\\omega_1}(y),c_{\\lambda-\\omega_1}(z),c_s(x))=c_\\lambda(\\mu).\\end{aligned}$$ (3) When $|\\rm{Supp}(\\beta)|=l $ and $\\beta=\\alpha_1+\\alpha_2+\\cdots+\\alpha_l+\\beta_1,\\beta_1\\succ 0,$ we have $\\mu=\\lambda-\\omega_1-\\omega_l-\\beta_1.$ If $\\lambda_i> 0, \\lambda_j=0 $ and $j<i,\\,$ let $\\nu=\\lambda-\\omega_i, $ then $\\lambda=\\nu+\\omega_i,$ and $$n_{\\omega_i,\\,\\nu}^\\mu\n=n_{\\omega_i,\\,\\lambda-\\omega_i}^{\\lambda-\\omega_1-\\omega_l-\\beta_1}\n=n_{\\lambda-\\omega_1-\\omega_l-\\beta_1,\\, -w_0\\omega_i}^{\\lambda-\\omega_i}\n=n_{\\lambda-\\omega_1-\\omega_l-\\beta_1,\\, \\omega_{l-i}}^{\\lambda-\\omega_i}\n=n_{\\mu,\\, \\omega_{l-i}}^{\\nu}.$$ For $$\\begin{aligned}\n&&\\mu+\\omega_{l-i}-{\\nu}\\\\\n&&={\\lambda-\\omega_1-\\omega_l-\\beta_1+ \\omega_{l-i}}-{\\lambda+\\omega_i}\\\\\n&&=-(\\omega_1+\\omega_l)-(\\omega_{l-i}+\\omega_i)-\\beta_1\\\\\n&&=-\\sum_{k=1}^l\\alpha_k+\\sum_{k=1}^{min(l-i,\\,i)}\\sum_{j=k}^{l-k}k\\alpha_k-\\beta_1,\\end{aligned}$$ let $\\mu+\\omega_{l-i}-{\\nu}=\\sum_{j=1}^lk_j\\alpha_j,$ then $k_1\\leq 0.$\n\n\\(i) if $k_1< 0,$ then $\\nu\\notin \\Pi(\\mu+\\omega_{l-i}),$ we have $n_{\\mu,\\, \\omega_{l-i}}^{\\nu}=0\n=c_{\\mu,\\, \\omega_{l-i}}^{\\nu}.$\n\n\\(ii) if $k_1= 0,$ then $|\\rm{Supp}(\\mu+\\omega_{l-i}-{\\nu})|<l,$ we have by the first condition $$n_{\\mu,\\, \\omega_{l-i}}^{\\nu}\n=c_{\\mu,\\, \\omega_{l-i}}^{\\nu}.$$ Moreover, $$c_{\\omega_i,\\,\\nu}^\\mu\n=c_{\\omega_i,\\,\\lambda-\\omega_i}^{\\lambda-\\omega_1-\\omega_l-\\beta_1}\n=c_{\\lambda-\\omega_1-\\omega_l-\\beta_1,\\, -w_0\\omega_i}^{\\lambda-\\omega_i}\n=c_{\\lambda-\\omega_1-\\omega_l-\\beta_1,\\, \\omega_{l-i}}^{\\lambda-\\omega_i}\n=c_{\\mu,\\, \\omega_{l-i}}^{\\nu}.$$ Therefore, we have also $$n_{\\omega_i,\\,\\nu}^\\mu\n=c_{\\omega_i,\\,\\nu}^\\mu.$$ Similarly, by the induction hypothesis and equation (\\[eqn3\\]) we have $$n_\\lambda(\\mu)=c_\\lambda(\\mu).$$ The theorem is proved.", "\n\n[**3.4.**]{} ", "One of the conditions in theorem is about $m_\\lambda(\\mu),$ and the other is about $n_{\\mu,\\,\\nu}^\\lambda.$ There exists difficulty to generalize the theorem to Lie algebras of other type. ", "Only the two conditions in theorem are not enough to determined $m_\\lambda(\\mu).$ We need to find out a suitable condition. ", "As said before, the motivation for this problem in this paper comes from the modular representation theory of linear algebraic groups in positive characteristic. ", "It is more difficulty to find out natural conditions in this case, for the second condition does not hold in general. ", "We will consider these problems in the future.", "\n\n[**Acknowledgement:**]{} This work was supported by the Fundamental Research Funds for the Central Universities 2009B26914 and 2010B09714. ", "biblabel\\#1[\\#1.]{}", "\n\n[9]{}\n\nGasharov, Vesselin ,A short proof of the Littlewood-Richardson rule, European Journal of Combinatorics (1998)19 (4): 451-453,\n\n, [Springer-Verlag]{}, [New York/Heidelberg/Berlin]{}, [1972]{}.", "\n\nJ. C. Jantzen, Representations of algebraic groups, Academic Press, Orlando, 1987; 2nded., ", "Amer. ", "Math. ", "Soc., ", "Providence, RI, 2003.", "\n" ]

{ "pile_set_name": "ArXiv" }

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[ "Q:\n\nNeo4j Server vs. Embedded\n\nI'am a little bit confused about what is the best solution for my application. ", "As I've seen so far, I have to choose between neo4j standalone (RestGraphDatabase) and an EmbeddedGraphDatabase (the RemoteGraphDatabase is not for production use yet). ", "\nPros REST:\n-> Different services can access the neo4j DB (sample: i have one service that is responsible for Nodes of kind A,B and C. The second service is responsible for nodes D and H and can connect D-nodes to A-nodes). ", "In that way i have clean domain structures. ", "Every service is only responsible for its own domain nodes. ", "I can update each service and don't have to shutdown my whole application.", "\n-> I can access the neo4j DB from different languages (PHP)\nCons:\n- Performance is not that good as an EmbeddedGraphDatabase (since the neo4j server and the services are on the same machine the latency is not that big).", "\n- No transactions\nMy questions:\nIs this a good decision to go with the standalone server? ", "Or should I use the embedded one and mix up the services into a big one? ", "Is it possible to run a big (complex) application without transaction support?", "\n\nA:\n\nYou're correct that performance with the REST server will be less. ", "However, you can have something like transactions with the REST server using batch operations; see http://docs.neo4j.org/chunked/milestone/rest-api-batch-ops.html. ", "You can also build domain specific server plugins that perform your transactional logic on the server side: http://docs.neo4j.org/chunked/milestone/server-extending.html.", "\nIf your architecture requires that you be able to access the database from multiple client machines, your only options are the REST server or Neo4j HA (High Availability). ", "HA is only available with a Neo4j Enterprise license.", "\nLet application architecture inform which tools are used, not the other way around. ", "If you've already decided that your application is best as separate services, don't combine them into one just to support the underlying persistence model. ", " I don't know anything about your application, but from your description, I would choose the REST server and utilize batches or server plugins.", "\n\nA:\n\nIt all depends on your use-case. ", "You already listed some of the pro's and con's.", "\nOne other pro for the server is the web-admin / visualization.", "\nYou have some more options. ", "You can have an embedded graphdb for high performance and have only some services run embedded, and use a custom, domain centric remote (REST or otherwise) API to expose the graph database for other services.", "\nThe same can be achieved by using the Neo4j Server and add some of the more performance critical services as Server-Plugins or Extensions which are also able to expose a custom remote API that suits your use-cases probably better.", "\nI would start using the embedded graph db for developing your services, if you want to expose certain endpoints to other services later, it is quite easy to switch to the Neo4j server.", "\nIn the REST-API there is one transaction per request, for larger operations there is a batch operation in the API.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Prostaglandins in osteoid osteoma.", "\nOsteoid osteoma is a tumour of bone characterised by pain which is relieved by aspirin and nonsteroidal anti-inflammatory drugs. ", "Very high levels of prostaglandins have been found in the lesion. ", "In five patients with osteoid osteoma, prostaglandin E2 (PGE2) and prostacyclin (PGI2) synthesis in the nidus yielded 1155.6 +/- 496.5 (mean +/- SD) and 245.2 +/- 89.8 pg/mg respectively, values which are 33 and 26 times higher than in fragments of normal bone. ", "The sclerotic bone around the nidus produced both prostaglandins at the same rate as normal bone. ", "In three patients the excretion rate of the major urinary metabolite of systemic PGI1 was reduced to 50% one month after removal of the tumour. ", "The urinary excretion rate of 6-keto-PGF1 alpha, reflecting intrarenal PGI2 synthesis, was not changed after operation. ", "These results offer new insight into the pain mechanism in osteoid osteoma." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Attached is report mentioned above.", "\n\nThanks,\nJosie Call\nRates & Certificates\n402-398-7258\nFax: 402-398-7006" ]

{ "pile_set_name": "Enron Emails" }

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[ "Q:\n\nSwipe effect like inshorts news app\n\nlink check this news app, i want to develop like this.", "\ni want swipe up/down side effect..\ni tried this code,but not correctly swiping as i want.", "\nin this code when i swipe up/down,only the text is changing not a layout. ", " \n public class ArticlesActivity extends Activity implements GestureDetector.", "OnGestureListener{\n\n ImageView image,imageArticle;\n TextView tv1,tv2,tv3;\n private GestureDetector gd;\n LinearLayout layout;\n\n @Override\n protected void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n setContentView(R.layout.activity_articles);\n\n //Creating GestureDetector Object\n gd = new GestureDetector(this, this);\n }\n\n @Override\n public boolean onTouchEvent(MotionEvent event) {\n // TODO Auto-generated method stub\n //Registering TouchEvent with GestureDetector\n return gd.onTouchEvent(event);\n }\n\n @Override\n public void onBackPressed() {\n // TODO Auto-generated method stub\n //Destroying Activity\n finish();\n }\n\n @Override\n public boolean onDown(MotionEvent arg0) {\n // TODO Auto-generated method stub\n return false;\n }\n\n @Override\n public boolean onFling(MotionEvent e1, MotionEvent e2, float velocityX, float velocityY) {\n\n // TODO Auto-generated method stub\n //Defining Sensitivity\n float sensitivity = 50;\n //Swipe Up Check\n if(e1.getY() - e2.getY() > sensitivity){\n //Setting Image Resource to Up_Arrow on Swipe Up\n tv1.setText(\"Some Text\");\n tv2.setText(\"Some Text\");\n tv3.setText(\"Some Text\");\n image.setImageResource(R.drawable.logo);\n imageArticle.setImageResource(R.drawable.ic_launcher);\n return true;\n }\n //Swipe Down Check\n else if(e2.getY() - e1.getY() > sensitivity){\n //Setting Image Resource to Down_Arrow on Swipe Down\n\n tv1.setText(\"Some Text\");\n tv2.setText(\"Some Text\");\n tv3.setText(\"Some Text\");\n image.setImageResource(R.drawable.ic_launcher);\n imageArticle.setImageResource(R.drawable.logo);\n return true;\n }\n else{\n //If some error occurrs, setting again to Default_Image (Actually it will never happen in this case)\n image.setImageResource(R.drawable.logo);\n return true;\n }\n }\n\n @Override\n public void onLongPress(MotionEvent arg0) {\n // TODO Auto-generated method stub\n\n }\n\n @Override\n public boolean onScroll(MotionEvent arg0, MotionEvent arg1, float arg2,\n float arg3) {\n // TODO Auto-generated method stub\n return false;\n }\n\n @Override\n public void onShowPress(MotionEvent arg0) {\n // TODO Auto-generated method stub\n\n }\n\n @Override\n public boolean onSingleTapUp(MotionEvent arg0) {\n // TODO Auto-generated method stub\n return false;\n }\n}\n\nA:\n\nThis will work like inshorts app\n\nmain.xml\n<com.cardviewanimation.", "VerticalViewPager\n android:id=\"@+id/verticleViewPager\"\n android:layout_width=\"match_parent\"\n android:layout_height=\"match_parent\"/>\n\ncontent_main.xml\n<?", "xml version=\"1.0\" encoding=\"utf-8\"?", ">\n<LinearLayout xmlns:android=\"http://schemas.android.com/apk/res/android\"\nxmlns:card_view=\"http://schemas.android.com/apk/res-auto\"\nandroid:orientation=\"vertical\"\nandroid:layout_width=\"match_parent\"\nandroid:layout_height=\"match_parent\">\n\n<android.support.v7.widget.", "CardView\n android:id=\"@+id/card_view\"\n android:layout_gravity=\"center\"\n android:layout_width=\"fill_parent\"\n android:layout_height=\"wrap_content\"\n android:layout_margin=\"5dp\"\n card_view:cardCornerRadius=\"2dp\"\n card_view:contentPadding=\"10dp\">\n\n <LinearLayout\n android:layout_width=\"match_parent\"\n android:layout_height=\"wrap_content\"\n android:orientation=\"vertical\">\n\n <ImageView\n android:id=\"@+id/imageView\"\n android:layout_width=\"match_parent\"\n android:layout_height=\"300dp\"\n android:src=\"@drawable/background\"\n android:scaleType=\"fitXY\"/>\n\n <TextView\n android:id=\"@+id/textView\"\n android:layout_width=\"wrap_content\"\n android:layout_height=\"wrap_content\"\n android:layout_marginTop=\"10dp\"/>\n </LinearLayout>\n</android.support.v7.widget.", "CardView>\n</LinearLayout>\n\nVerticleViewPagerActivity.java\npublic class VerticleViewPagerActivity extends AppCompatActivity {\n\nVerticalViewPager verticalViewPager;\n\n@Override\nprotected void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n setContentView(R.layout.main);\n Toolbar toolbar = (Toolbar) findViewById(R.id.toolbar);\n setSupportActionBar(toolbar);\n\n verticalViewPager = (VerticalViewPager) findViewById(R.id.verticleViewPager);\n verticalViewPager.setAdapter(new VerticlePagerAdapter(this));\n }\n}\n\nVerticlePagerAdapter.java\npublic class VerticlePagerAdapter extends PagerAdapter {\n\nString mResources[] = {\"To start off lets understand what exactly Android CardView is? ", "Its a new widget for Android, which can be used to display a card sort of a layout in android. ", "As you may know Android material design is inspired from paper and ink concept. ", "Mostly it displays views on top of each other, with shadows. ", "In simple terms, Android CardView is such a view which has all material design properties, most importantly showing shadows according the elevation. ", "The best part about this view is that it extends FrameLayout and it can be displayed on all the platforms of android since it’s available through the Support v7 library. ", "Lets have a look at some of its properties:\",\"To start off lets understand what exactly Android CardView is? ", "Its a new widget for Android, which can be used to display a card sort of a layout in android. ", "As you may know Android material design is inspired from paper and ink concept. ", "Mostly it displays views on top of each other, with shadows. ", "In simple terms, Android CardView is such a view which has all material design properties, most importantly showing shadows according the elevation. ", "The best part about this view is that it extends FrameLayout and it can be displayed on all the platforms of android since it’s available through the Support v7 library. ", "Lets have a look at some of its properties:\"};\n\nContext mContext;\nLayoutInflater mLayoutInflater;\n\npublic VerticlePagerAdapter(Context context) {\n mContext = context;\n mLayoutInflater = (LayoutInflater) mContext.getSystemService(Context.", "LAYOUT_INFLATER_SERVICE);\n}\n\n@Override\npublic int getCount() {\n return mResources.length;\n}\n\n@Override\npublic boolean isViewFromObject(View view, Object object) {\n return view == ((LinearLayout) object);\n}\n\n@Override\npublic Object instantiateItem(ViewGroup container, int position) {\n View itemView = mLayoutInflater.inflate(R.layout.content_main, container, false);\n\n TextView label = (TextView) itemView.findViewById(R.id.textView);\n label.setText(mResources[position]);\n container.addView(itemView);\n\n return itemView;\n}\n\n@Override\npublic void destroyItem(ViewGroup container, int position, Object object) {\n container.removeView((LinearLayout) object);\n}\n}\n\nVerticalViewPager.java\n public class VerticalViewPager extends ViewPager {\n\npublic VerticalViewPager(Context context) {\n super(context);\n init();\n}\n\npublic VerticalViewPager(Context context, AttributeSet attrs) {\n super(context, attrs);\n init();\n}\n\nprivate void init() {\n // The majority of the magic happens here\n setPageTransformer(true, new VerticalPageTransformer());\n // The easiest way to get rid of the overscroll drawing that happens on the left and right\n setOverScrollMode(OVER_SCROLL_NEVER);\n}\n\nprivate class VerticalPageTransformer implements ViewPager.", "PageTransformer {\n private static final float MIN_SCALE = 0.75f;\n @Override\n public void transformPage(View view, float position) {\n\n if (position < -1) { // [-Infinity,-1)\n // This page is way off-screen to the left.", "\n view.setAlpha(0);\n\n } else if (position <= 0) { // [-1,0]\n // Use the default slide transition when moving to the left page\n view.setAlpha(1);\n // Counteract the default slide transition\n view.setTranslationX(view.getWidth() * -position);\n\n //set Y position to swipe in from top\n float yPosition = position * view.getHeight();\n view.setTranslationY(yPosition);\n view.setScaleX(1);\n view.setScaleY(1);\n\n } else if (position <= 1) { // [0,1]\n view.setAlpha(1);\n\n // Counteract the default slide transition\n view.setTranslationX(view.getWidth() * -position);\n\n // Scale the page down (between MIN_SCALE and 1)\n float scaleFactor = MIN_SCALE\n + (1 - MIN_SCALE) * (1 - Math.abs(position));\n view.setScaleX(scaleFactor);\n view.setScaleY(scaleFactor);\n\n } else { // (1,+Infinity]\n // This page is way off-screen to the right.", "\n view.setAlpha(0);\n }\n }\n}\n\n/**\n * Swaps the X and Y coordinates of your touch event.", "\n */\nprivate MotionEvent swapXY(MotionEvent ev) {\n float width = getWidth();\n float height = getHeight();\n\n float newX = (ev.getY() / height) * width;\n float newY = (ev.getX() / width) * height;\n\n ev.setLocation(newX, newY);\n\n return ev;\n}\n\n@Override\npublic boolean onInterceptTouchEvent(MotionEvent ev){\n boolean intercepted = super.onInterceptTouchEvent(swapXY(ev));\n swapXY(ev); // return touch coordinates to original reference frame for any child views\n return intercepted;\n}\n\n@Override\npublic boolean onTouchEvent(MotionEvent ev) {\n return super.onTouchEvent(swapXY(ev));\n}\n}\n\nA:\n\nI got the solution for your problem as inshorts app using vertical view pager. ", "I am sharing some code that can serve your purpose.", "\npublic class VerticalViewPager extends ViewPager {\n\npublic VerticalViewPager(Context context) {\n this(context, null);\n}\n\npublic VerticalViewPager(Context context, AttributeSet attrs) {\n super(context, attrs);\n setPageTransformer(false, new DefaultTransformer());\n}\n\nprivate MotionEvent swapTouchEvent(MotionEvent event) {\n float width = getWidth();\n float height = getHeight();\n\n float swappedX = (event.getY() / height) * width;\n float swappedY = (event.getX() / width) * height;\n\n event.setLocation(swappedX, swappedY);\n\n return event;\n}\n\n@Override\npublic boolean onInterceptTouchEvent(MotionEvent event) {\n boolean intercept = super.onInterceptTouchEvent(swapTouchEvent(event));\n //If not intercept, touch event should not be swapped.", "\n swapTouchEvent(event);\n return intercept;\n}\n\n@Override\npublic boolean onTouchEvent(MotionEvent ev) {\n return super.onTouchEvent(swapTouchEvent(ev));\n}\n}\n\nAs you can see the class above uses the DefaultTransformer class for transformation which implement ViewPager.", "PageTransformer for custom animation this class code is given below\npublic class DefaultTransformer implements ViewPager.", "PageTransformer {\n\n@Override\npublic void transformPage(View view, float position) {\n float alpha = 0;\n if (0 <= position && position <= 1) {\n alpha = 1 - position;\n } else if (-1 < position && position < 0) {\n alpha = position + 1;\n }\n System.out.println(\"alpha--\" + alpha);\n view.setAlpha(alpha);\n System.out.println(\"position--\" + position);\n System.out.println(\"view.getWidth()--\" + view.getWidth());\n view.setTranslationX(view.getWidth() * -position);\n float yPosition = position * view.getHeight();\n System.out.println(\"yPosition---\"+yPosition);\n view.setTranslationY(yPosition);\n}\n}\n\nand my activity code is like this \npublic class SwipeUpActivity extends AppCompatActivity {\n\n@Override\nprotected void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n setContentView(R.layout.activity_swipe_layout);\n setTitle(\"\");\n initViewPager();\n}\nprivate void initViewPager() {\n VerticalViewPager viewPager = (VerticalViewPager) findViewById(R.id.vertical_viewpager);\n //viewPager.setPageTransformer(false, new ZoomOutTransformer());\n //viewPager.setPageTransformer(true, new StackTransformer());\n String title = \"ContentFragment\";\n viewPager.setAdapter(new ContentFragmentAdapter.", "Holder(getSupportFragmentManager())\n .add(ContentFragment.newInstance(title, 1))\n .add(ContentFragment.newInstance(title, 2))\n .add(ContentFragment.newInstance(title, 3))\n .add(ContentFragment.newInstance(title, 4))\n .add(ContentFragment.newInstance(title, 5))\n .set());\n //If you setting other scroll mode, the scrolled fade is shown from either side of display.", "\n viewPager.setOverScrollMode(View.", "OVER_SCROLL_NEVER);\n}\n\nThe layout named activity_swipe_layout is like this\n<?", "xml version=\"1.0\" encoding=\"utf-8\"?", ">\n<RelativeLayout xmlns:android=\"http://schemas.android.com/apk/res/android\"\nandroid:layout_width=\"match_parent\"\nandroid:background=\"#A6000000\"\nandroid:layout_height=\"match_parent\">\n\n<gmaillogindemo.com.irk.transforms.", "VerticalViewPager\n android:id=\"@+id/vertical_viewpager\"\n android:layout_width=\"match_parent\"\n android:layout_height=\"match_parent\" />\n\nand the result is looking like this:\n\nafter swipe up \n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "a + 15651 = 0, -39*a + 62538 = 4*f - 41*a. ", "What are the prime factors of f?", "\n2, 3, 1303\nLet c be ((-14)/10 - -2) + (-486)/(-15). ", "Let l = 37 - c. What are the prime factors of l/(-2) - 2 - (4 + -53)?", "\n3, 5\nSuppose -5*m + 5*b = -2720, -4*b = 6*m - 8*m + 1084. ", "Let o = -250 + m. What are the prime factors of o?", "\n2, 37\nLet v = 30655 - 14758. ", "List the prime factors of v.\n3, 7, 757\nLet a be 198*(-6)/9*(-161)/14. ", "Suppose -13*l = 283 - a. List the prime factors of l.\n5, 19\nLet y = -3339 - -6225. ", "List the prime factors of y.\n2, 3, 13, 37\nLet k(t) = -3*t**2 - 34*t + 4. ", "Let w be k(-11). ", "Suppose 2*y + y - w = 0. ", "Suppose 0 = -2*d - i + 37, i = -y*d - 3*i + 100. ", "What are the prime factors of d?", "\n2\nSuppose 7*n + 46684 - 238852 = -11*n. ", "What are the prime factors of n?", "\n2, 17, 157\nLet y(o) = 9*o**2 + 819*o + 19. ", "List the prime factors of y(-100).", "\n23, 353\nLet t(s) = 6*s**3 + 5*s**2 + s. Let f(g) = -7*g**3 - 6*g**2 - 1. ", "Let d(c) = 5*f(c) + 6*t(c). ", "Let o be d(2). ", "List the prime factors of 133 - o - (-1 + -2).", "\n11\nLet a = -21 - -26. ", "Suppose 3*w - 18 = -0*r - 4*r, 34 = 4*r - a*w. ", "Suppose 0 = -13*v + r*v + 840. ", "List the prime factors of v.\n2, 3, 5\nSuppose 0 = 67*m - 62*m - u - 265712, -4*m - 5*u + 212616 = 0. ", "List the prime factors of m.\n2, 7, 13, 73\nSuppose q - 5 = 0, 0*h - 3*h + 23469 = 3*q. ", "What are the prime factors of h?", "\n2, 3, 1303\nSuppose -108*c + 1437525 + 814973 = 89*c. ", "What are the prime factors of c?", "\n2, 5717\nLet x(f) = f**3 - 4*f**2 + 9. ", "Let a be x(3). ", "Suppose 2*p + y - 1365 - 394 = a, -3*p + 2671 = -5*y. ", "List the prime factors of p.\n2, 3, 7\nSuppose i - 2*l - 5029 = 0, 4*l + 25157 = 6*i - i. List the prime factors of i.\n7, 719\nLet z(f) = -2*f + 13. ", "Let i be z(7). ", "Let y be -5*(2/6)/(i/3). ", "Suppose 278 = 7*j - y*j. ", "What are the prime factors of j?", "\n139\nLet r = -19 + 21. ", "Suppose 2*p + r*j - 28 + 0 = 0, 4 = -j. ", "Suppose p*q - 23*q = -500. ", "What are the prime factors of q?", "\n2, 5\nSuppose -29*c + 28*c = 32. ", "Let h be ((-285)/38)/(3/c). ", "Let t = h - 30. ", "What are the prime factors of t?", "\n2, 5\nList the prime factors of 15 + (-467495)/(-42) + 3/18.", "\n2, 5573\nSuppose 1339*z + 65340 + 59743 = 1346*z. ", "List the prime factors of z.\n107, 167\nSuppose 0 = -i - 6*i. ", "Suppose 3*h + 7 - 16 = i. Suppose -5*w - h*y + 301 = -140, -y - 273 = -3*w. ", "List the prime factors of w.\n2, 3, 5\nLet h(c) = -c**2 - 16*c + 2. ", "Let i be h(-16). ", "Let f be ((1 - 4) + 0)/(i + -3). ", "Suppose -f*t - 72 = -o, -t + 5*t = -5*o + 455. ", "List the prime factors of o.\n3, 29\nSuppose 3*b - l - 48352 = 0, -4*b - 23*l + 27*l = -64456. ", "List the prime factors of b.\n3, 199\nLet t(b) = 8*b**2 - 18*b - 13. ", "Let v be t(-12). ", "Suppose -7*m = -2*m - v. What are the prime factors of m?", "\n271\nList the prime factors of 14214/4 + (-4)/(-8).", "\n2, 1777\nLet x(q) = q**3 + 8*q**2 - 10*q + 1. ", "Let k be x(-9). ", "Suppose -850 = -3*y + 5*w - k*w, 3*y = 2*w + 857. ", "What are the prime factors of y?", "\n3, 5, 19\nLet g(p) = 2*p**2 + 63*p + 871. ", "List the prime factors of g(-114).", "\n19681\nSuppose h + 41793 = 5*s, 235*h = 237*h - 4. ", "What are the prime factors of s?", "\n13, 643\nLet k be (-1)/(-2)*(5 - -1) - 2. ", "Suppose 4*z = a + 3 + k, 4*z = 4. ", "Suppose a = -4*o + 10 + 6, 154 = 2*b + o. What are the prime factors of b?", "\n3, 5\nLet l be (1 - 15) + -11 + 10. ", "Let t be (10/l)/(0 + (-4)/18). ", "Suppose -231 = -6*j + t*j. ", "What are the prime factors of j?", "\n7, 11\nLet l(x) be the first derivative of 11*x**2 + 15*x + 7. ", "Let i be l(4). ", "Suppose 0 = -6*h + 443 + i. What are the prime factors of h?", "\n7, 13\nLet u = 15 - 29. ", "Let x be (-378)/(-22) - 22/121. ", "Let q = x + u. What are the prime factors of q?", "\n3\nLet n(d) = 3*d**3 + 212*d**2 - 201*d + 107. ", "What are the prime factors of n(-70)?", "\n23977\nLet o(k) = 246*k**3 - 14*k**2 + 10*k - 42. ", "Let j(m) = 49*m**3 - 3*m**2 + 2*m - 8. ", "Let d(b) = 11*j(b) - 2*o(b). ", "List the prime factors of d(2).", "\n2, 89\nSuppose -161 = -18*g + 11*g. ", "Suppose 0 = g*l - 37*l + 2240. ", "What are the prime factors of l?", "\n2, 5\nLet h = 707 - 208. ", "Let s = 343 + h. List the prime factors of s.\n2, 421\nLet z(b) = b**3 - 46*b**2 - 70*b - 196. ", "List the prime factors of z(50).", "\n2, 197\nLet f(y) = -2*y**3 + 15*y**2 - 27*y - 74. ", "List the prime factors of f(-6).", "\n2, 5, 53\nSuppose -3*q + 3120 + 12299 = 4*a, -2*q = 4*a - 15426. ", "List the prime factors of a.\n2, 5, 193\nLet o(r) = 2846*r + 38. ", "What are the prime factors of o(3)?", "\n2, 67\nLet c(p) be the first derivative of 4*p**3/3 - 30*p**2 - 12*p - 37. ", "What are the prime factors of c(21)?", "\n2, 3, 41\nSuppose -3*x - 70 = -5*i, -2*i - 5*x = -6*i + 56. ", "Let j be (-25652)/i - 26/(-91). ", "What are the prime factors of 2 - j/(-12)*(-3)/2?", "\n3, 7, 11\nLet p = -7428 - -8047. ", "List the prime factors of p.\n619\nLet x(h) = -19 + 11*h**2 - h**3 - 2*h**2 + 4*h**2 - 18*h. ", "Suppose 3*z = w + 36, 0 = -3*z - 2*z + 2*w + 61. ", "What are the prime factors of x(z)?", "\n5\nLet v(m) = 2*m**3 - 49*m**2 + 23*m + 32. ", "Let o be v(24). ", "Suppose 5*b = -5*u + o*u + 1499, b + 3*u - 289 = 0. ", "List the prime factors of b.\n2, 149\nLet h(k) = k**3 - 3*k**2 - 3*k - 1. ", "Let u be h(4). ", "Suppose -5*p + 35 = 5*z, -u*z = 2*z - 2*p - 21. ", "Suppose z*t + 5*t = 780. ", "List the prime factors of t.\n2, 3, 13\nSuppose -5*r + 39 + 76 = 0. ", "Suppose 25*c - 654 = r*c - 4*d, -2*d + 989 = 3*c. ", "List the prime factors of c.\n331\nLet u(m) = m**2 - 8*m - 24. ", "Let g be u(10). ", "Let s be -32 - 0/((-2)/8*g). ", "Let l = 85 - s. What are the prime factors of l?", "\n3, 13\nLet f = -35719 - -108744. ", "List the prime factors of f.\n5, 23, 127\nSuppose 4*l = -3*z + 159895, 100 = -5*l + 75. ", "What are the prime factors of z?", "\n5, 7, 1523\nLet g(q) = -16*q + 4. ", "Let s be g(1). ", "Let m = -127 - s. Let f = m + 193. ", "List the prime factors of f.\n2, 3, 13\nLet z(u) = 31*u**3 + u**2 - 4*u - 3. ", "Let v be z(-2). ", "Let l = v + 357. ", "Let g = l + -21. ", "List the prime factors of g.\n97\nLet d = -61 - -65. ", "Let p(y) = 21*y + 21*y - d + y + 17*y. ", "What are the prime factors of p(3)?", "\n2, 11\nSuppose -l + 124 + 18 = 0. ", "What are the prime factors of l/12 + 15/90?", "\n2, 3\nLet p = 0 + -51. ", "Let q = 23 + p. List the prime factors of q/49 - (-204)/14.", "\n2, 7\nLet a be -9*1*69/(-9). ", "Suppose 55*r = 51*r - 4. ", "What are the prime factors of 34/(-17) + a + r?", "\n2, 3, 11\nSuppose j + 41 = -8. ", "Let i = -48 - j. List the prime factors of 0 + i - 480/(-5).", "\n97\nLet t(f) = -f**3 - 6*f**2 - f - 3. ", "Let h be t(-6). ", "Suppose -h*s - s = 72. ", "What are the prime factors of (-6)/s + (-226)/(-6)?", "\n2, 19\nSuppose 0 = 75618*w - 75615*w - 118287. ", "What are the prime factors of w?", "\n3, 13, 337\nLet s(k) = -k**3 - 2*k**2 + 81*k + 15. ", "Let d = 305 + -318. ", "List the prime factors of s(d).", "\n821\nSuppose 25*k = 15*k + 80. ", "List the prime factors of ((-26)/k)/((-1350)/192 + 7).", "\n2, 13\nSuppose -103802 = -168*q + 151*q. ", "List the prime factors of q.\n2, 43, 71\nLet q(h) = h**3 - 9*h**2 - 27*h + 64. ", "What are the prime factors of q(22)?", "\n2, 43, 67\nLet y = -18736 - -46568. ", "List the prime factors of y.\n2, 7, 71\nLet b(t) = 2*t**2 + 7*t - 15. ", "Let q be b(-12). ", "Let m be 1/(-4) - q/(-36). ", "List the prime factors of 9/(-24)*-86 - m/20.", "\n2\nLet w(r) = r**2 + 20. ", "Let f = 72 + -59. ", "Suppose -f*s - 30 = -10*s. ", "What are the prime factors of w(s)?", "\n2, 3, 5\nLet n = -263 + -112. ", "Let q = 1482 + -809. ", "Let g = q + n. What are the prime factors of g?", "\n2, 149\nLet u = 314 - 302. ", "Suppose u*w - 727 = 3761. ", "List the prime factors of w.\n2, 11, 17\nWhat are the prime factors of (-106017)/(-8) + ((-21)/(-8))/(-21)?", "\n2, 3313\nSuppose 2*i + 3*m = 792, -m + 1634 = 5*i - 333. ", "Suppose 2*j + 3*d = 847, j - 5*d = i + 24. ", "What are the prime factors of j?", "\n2, 211\nLet l(h) = -10*h + 22. ", "Suppose m = 3*m + 18. ", "Let s be l(m). ", "Suppose -2*b + 3*i + 61 = 0, 2*i = -4*b - 2*i + s. What are the prime factors of b?", "\n29\nLet v = 3144 + -2507. ", "What are the prime factors of v?", "\n7, 13\nLet v(z) = 6*z**2 - 65*z - 820. ", "List the prime factors of v(-41).", "\n3, 41, 97\nSuppose -286 = 3*a + 2*h, 3*a + 0*h - 2*h = -302. ", "Let t = a + 119. ", "What are the prime factors of t?", "\n3, 7\nList the prime factors of (25/225 + (-215670)/(-54))/((-1)/(-3)).", "\n2, 3, 1997\nLet k be (96/(-9))/(-8)*3. ", "Suppose 0 = -k*a + m + 41, 5*a - 4*m = -8*m + 67. ", "What are the prime factors of 3/6 - a/(-2)?", "\n2, 3\nLet i = 69987 + -41849. ", "List the prime factors of i.\n2, 11, 1279\nLet q be (-245)/((-8)/6 - -1). ", "Let h be (6/9)/(-2 + 1480/q). ", "Suppose h + 93 = x. List the prime factors of x.\n2, 71\nSuppose g = -4*f - 10, 0 = 5*g + f + 12 - 0. ", "Let d be g/1*(-10)/4. ", "Suppose d*y + 285 - 885 = 0. ", "What are the prim" ]

{ "pile_set_name": "DM Mathematics" }

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[ "Nicolis G and Nicolis C, indicate in the book Foundations of Complex Systems (2012)[1]; that the question whether deterministic dynamical systems may generate behaviors similar to the Hurst phenomenon remains at this stage completely open. ", "However, it seems important to mention that some preliminaries calculations of the Hurst exponent have been done for a Lorenz deterministic dynamical system[2] (Mata, 1991[3], 1993[4]); particularly for the study of a time series of the intensity of convective motion, in order to visualize the potential existence of persistence with (0.64 < Hurts exponent <0.78) or low-frequency variability for this Lorenz system’s[5].", "\n\nFigure 1: Rydzyna Castle. ", "Originally, it was built at the beginning of 15th century. ", "It was one of the most splendid palaces in Great Poland (1704-1709) residences of Polish king Stanislaw Leszczynski. ", "His daughter Maria became queen of France and mother of king Louis XVI. ", "Later the castle was taken over by Prussian authorities. ", "In 1919 the Versailles Treaty gave it back to Poland. ", "In 1970 was taken over by the Association of Polish Mechanical Engineers (S.I.M.P). ", "In 1994 was awarded by EUROPA NOSTRA recognition of an excellent restoration work. ", "Source: Internet.", "\n\nRecently, some articles appear in the literature (Suyal et al, 2009, Ghil et al, 2011, Tarnopolski, 2015) in relation to study sunspot, extremes events and low dimension discrete conservative system respectively and how they are related to the Hurst phenomenon.", "\n\nSuyal et al (2009)[6] explain the presence of multiple Hurst exponents[7] by their resemblances (similarities, similitude) to the deterministic chaotic attractors having one or more (multiple) center of rotation in phase space. ", "They conclude that estimating a single Hurst exponent form the data where different linear regimes exist may be improper. ", "It is convenient to mention that time series of precipitation under climate change may have different Hurst exponents due to the non-stationary condition of the process. ", "The authors analyzed a deterministic dynamical system represented by the Rössler system (Rössler, 1979)[8] and also the Lorenz system. ", "It is concluded that Hurst exponent for the Lorenz system, for the value “x” (for the intensity of convection), reach value of 0.93 (first part of the linear scaling) and 0.64 for the second part of the linear scaling. ", "The first one corresponds to the trajectory rotating about individuals fixed points while the second one is for all three fixed points.", "\n\nGhill et al (2011)[9] did a review work on extreme events, their causes and consequences. ", "The review covers theoretical aspect of time series analysis and extreme value theory, as well as deterministic modeling of extreme events, via continuous and discrete dynamics models. ", "Extreme events as defined by Kantz et al (2005)[10]: (1) they are rare, (2) they occur irregularly, (3) they exhibit an observable that take on an extreme value, (4) they are inherently to the system under study, rather than being due to external shocks.", "\n\nThe linear part of a temporal structure in the noisy part of a time series is given by the auto-correlation function (AFC); this structure is also freely referred to a persistence or memory. ", "The so called long memory is suspected to occur in many natural processes such as river runoff (Kallache et al, 2005[11], Muldesse et al, 2007[12]) which is characterized by slow decay of the ACF. ", "This slow decay is often referred as the Hurst phenomenon (Hurst, 1951[13]). ", "One of the earliest schemes for estimating long range dependence (LRD) parameter is the rescaled-range statistic (R/S). ", "It was originally proposed by Hurst (1951) when studying the Nile River low minima (Hurst 1952[14], Kondrashov et al, 2005[15]). ", "The ACF describes the linear interdependence of two instance of a time series separated by the lag τ. ", "A diverging sum (or infinite memory) given by\n\n∑ ρ (τk) = ∞\n\nIt characterizes a long range dependent (LRD) process, also called long memory process or long range correlated. ", "The example for an ACF with such a diverging sum shows an algebraic decay for a large time lags τ\n\nNow, the spectral density [S(f)] and the ACF ρ (τ) are Fourier transform of each other. ", "Then S(f) can also be used to describe long term memory. ", "In this representation the LRD property reveals itself as a spectral density that diverges at zero frequency. ", "Then, S(f) ~ |f|-βfor |f|—–> 0, withan exponent0<β = 1-ϒ<1that is the conjugate of the behavior of ρ (τ) at infinity (Rudin, 1987)[17].", "\n\nThe parameters β and ϒ are only two of several parameters to quantify LRD properties. ", "A uncomplicated way is to estimate the auto correlation function from the time series and fit a power law according to ρ (τ) = τ-ϒ for τ —-> ∞ (to the largest time lags). ", "This is done very often by least-square fitting a straight line to the autocorrelation function values plotted in a log-log coordinates. ", "Then, the exponent found is an estimate of ϒ.\n\nOne of the initial methods to estimate long range dependence parameters is the rescaled range statistic (R/S). ", "It was originally proposed by Hurst, 1951 when studying the Nile River flow minimum water level. ", "The estimate parameter is now called the Hurst exponent. ", "The R/S technique and estimation of the Hurst exponent have been extensively discussed in the long range dependence literature (Mandelbrot and Wallis, 1969[18], Salas et al, 1979[19], Salas, 1993[20], Mesa and Poveda, 1993[21], Katsev and L’Heureux, 2003[22], Koutsoyianis, 2003[23], Sakalauskiené, 2003[24], Baranik and Kristoufek, 2012[25], Fernandez-Martinez et al, 2014[26]).", "\n\nIn particular, Klemes (1974)[27] established in the abstract of his paper “the Hurst phenomenon is not necessarily [only] an indicator of infinite memory of a process. ", "It can also be caused by non-stationarity in the mean and by random walks with one absorbing barrier, which often arise in natural storage systems. ", "Attention is drawn to the fact that inferences about physical features of a process, based on operational models, can be not only inaccurate but grossly misleading”. ", "The author concluded that the Hurst phenomenon cannot be attributed to one specific physical cause. ", "The reasons can be because the existence of infinite memory or it can be brought about specific storage systems (an issue that is more a hydrological perspective rather that a mathematical one) or it can be a result of non-stationarity, in the process central tendency. ", "This last attribution has been analyzed by Boes and Salas, 1978[28] in terms of the non-stationarity of the mean and the Hurst phenomenon. ", "Four models were selected for comparison via simulation. ", "The four models are (1) ARMA (1, 1) with standard normally distributed noise, (2) a Klemes-Potter model[29] with geometrical distributed time spans of common means, (3) Klemes-Potter model with geometrical distributed time spans of common means, exponentially distributed means with parameter λ, and standard normally distributed noise and (4) a simple case of a mixture model with geometrical distributed time span and a Bernoulli-distributed mixing distribution. ", "The rescaled range (R/S) of partial sums was used to compare the long-term persistence of the four models. ", "The results suggest that it is the autocorrelation function that influences the behavior of the expected rescaled range. ", "As the authors mentioned “the similarity was expected since the rescaled range is a function of partial sums, and the central limit theorem indicates that such sums are approximately normally distributed and normal distribution are determined by their autocorrelation structure”.", "\n\nAs an illustration a pox diagram which is self-explanatory is presented in the following figure.", "\n\nAnother method is the detrended fluctuation analysis (Kantelhardt et al, 2001[30], Király and Janosi, 2004[31] ). ", "As well as the rescaled range (R/S), it produces a heuristic estimator; hence confident intervals are not readily available, thus making statistical inference rather difficult.", "\n\nConclusions\n\nPerhaps, the following question needs a reaction (response): What are the mechanisms that could generate persistencies and the associated Hurst phenomena? [", "32]\n\nNote: Perhaps, this will be the question at the beginning and later to mention that the topic is open like it was mention at first lines.", "\n\nPerhaps, one has to be clear that there are common classes of methods for identifying “persistence” characteristics in time series, those which measure autocorrelation and those which perform a Fourier, wavelet or other transformation. ", "One common example of the former approach is the Hurst exponent (Hurst 1951). ", "This technique breaks a time series into a number of subseries samples of increasing length and calculates the rescaled range (R/S)[33] of each subseries. ", "The Hurst exponent is then given by the slope of the logarithm of R/S over the logarithm of the number of element in each subseries. ", "It is based on the idea that S increases with increasing time series length, at a greater rate if the time series contain persistence. ", "It has been an issue that long time series are required to produce a valid Hurst exponent (Wallis and O’ Connell 1973, page 363, Vogel et al, 1998). ", "However, values obtained for many authors (e.g, Mesa, Gupta and O’Connell, 2012)) have indicated Hurst exponent values greater than 0.5. ", "An analysis of the Hurst exponent does seem suitable from data provided from GCMs. ", "Rocheta et al, 2014 showed a comparison of the Hurst exponent with a modified aggregated persistence score (APS) for observed record and showed that there were reasonable correlation between this two metrics. ", "They also used to compare the Hurst exponent calculated from GCMs data with the APS. ", "The results show that there is more scatter between the two metrics when they both identify an undersimulation of persistence in the GCMs.", "\n\nDeterministic dynamical system (The Lorenz model) and Hurst Phenomenon\n\nIn 1963 Edward Lorenz was working on models to describe the convection in the earth’s atmosphere. ", "The basic laws that govern this event are formulated as non linear differential equations which contain derivatives with respect to both space and time. ", "Lorenz expanded the equations into a set of trigonometric functions in space and truncated the resulting infinitely many ordinary differential equation for the amplitudes of these modes to a three-dimension system. ", "Perhaps, this is the first set of nonlinear equations known to exhibit chaotic behavior.", "\n\nThis now notorious system which derived as a simplified model of Rayleigh Bénard convection in the atmospheres is known as Lorenz equations and is given by the following equations\n\ndx/dt = Pr (y-x),\n\ndy/dt = Ra x – y – xz with Pr, Ra, b ≥ 0, (1.1)\n\ndz/dt = xy – bz.", "\n\nWhere Pr is the Prandtl number, the ability to conduct heat, the parameter b is related to the aspect ratio, the ratio between the vertical and horizontal dimension of the layer describing the geometrical properties of the system. ", "The Rayleigh number (Ra) is the varied control parameter which depend basically or most importantly, the vertical temperature gradient in the fluid or gas layer.", "\n\nFigure 3: A physical interpretation of the Lorenz system can be elaborated as follow, x, y, z represent: (x) the intensity of convection motion, (y) is proportional to the temperature difference between the ascending and descending currents (same sign of x and y mean that warmer fluid is raising) and (z) is proportional to the distortion of the average vertical profile of temperature from linearity, positive values of z means strong gradient near boundaries. ", "Two cases are represented for (x, z) Ra= 28 (above) and for (x, z) Ra=56 (below). ", "Source: Internet Presentation.", "\n\nOne fixed point of the Lorenz model (1.1) is obviously the origin X1 = (0, 0, 0). ", "In addition, we have\n\nThe Hurst phenomenon is a measure of autocorrelation (persistence and long memory).", "\n\nEstimation of the Hurst exponent (H) has been determined for the “x” value with Pr=10, b=8/3 and Ra=24.74. ", "The results indicated average Hurst exponent greater (H) than 0.5 (Mata 1991) and with Pr=16, b=4 and Ra=50 (Suyal et al 2009) which indicated on both cases a long-term dependence.", "\n\nTurbulence Flow and Hurst exponent\n\nFor turbulence flow Helland and Van Atta, 1978[34], estimation of the statistical property called the ‘rescaled range’ (R/S) in grid-generated turbulence has been determined and exhibit a Hurst coefficient H = 0·5 for 43 < UT/M < 1850, where M is the grid size M and U is the mean velocity. ", "As known, theoretically H = 0·5 for independence of two observations separated by a time interval T, and the deviation from H = 0·5 is referred to as the ‘Hurst phenomenon’. ", "The rescaled range (R/S) obtained for grid turbulence contains an initial region UT/M < 43 of large H, approaching 1·0, corresponding approximately to the usual region of a finite non-zero autocorrelation of turbulent velocity fluctuations. ", "For UT/M > 1850 the rescaled range breaks from H = 0·5 and rises at a significantly faster rate, H = 0·7-0·8, implying a long-term dependence or possibly non-stationarity at long times. ", "The measured autocorrelations remain indistinguishable from zero for UT/M > 20. ", "The break in the trend H = 0·5 is probably caused by motions on scales comparable to characteristic time scales of the wind-tunnel circulation. ", "Rescaled-range analysis is a powerful statistical tool for determining the time scale separating the grid turbulence from the background wind-tunnel motions.", "\n\nAlso turbulence flow, longitudinal velocity fluctuations, for stratified flow generated in a wind tunnel has been analyzed by Salas and Mata, 1980[35] in terms of the Hurst phenomenon. ", "An ARIMA process was found to fit the shape of the autocorrelation function.", "\n\nGeneral Circulation Models and Hurst Phenomenon\n\nHow adequately general circulation model reflect the low frequency behavior of precipitation? ", "This issue is extremely important. ", "It is a proper question and therefore need an appropriate response. ", "Droughts (Pellertier and Turcotte, 1997)[36] effectively are manifestation of low frequency climate behavior. ", "Therefore, general circulation models should be able to replicate droughts with severity and lengths consistent with historic observations and also should have the ability to predict future drought statistic (Lettenmaier and Wood, 2009)[37]; also the reliability of water supply reservoirs is closely related to persistence of below average inflow (Hurst et al, 1965[38], Douglas et al, 2002[39], Whiting, 2006[40])\n\nJain and Eischeid, 2008[41] and Fraedrich et al, 2009[42] report that the Hurst exponent (H) in a 1000 year simulation of the present day climate with a coupled general circulation model in a present day constant greenhouse environment agree closely with H estimated from the observations. ", "However a paper by Rutten et al, 2009[43] analyzed global gridded observed precipitation observations (records) from the 20th century, and 20th century runs from four global circulation models and for different climate scenarios[44]. ", "The results show that the observations had Hurst exponent values that are (considerably) larger than the values computed for precipitation from global circulation models (GCMs). ", "This implies that climate model simulation may not adequately reflect the low frequency behavior of precipitation observed in historical records. ", "Koutsoyiannis et al, 2008[45] concluded that GCMS do not reproduce natural inter-annual fluctuations and generally underestimated the variance and the Hurst exponent of the observed time series.", "\n\nRocheta et al, 2014[46], indicate that general circulation models (GCMs) provide reliable simulations of global and continental scale atmospheric variables, nonetheless have limited ability in simulating variables important for water resource management at regional to catchment scales. ", "An important GCM unfairness (bias) in managing water resources infrastructure is the underrepresentation of low-frequency variability a typical characteristic to the simulation of droughts and floods. ", "Aggregate persistence score (APS) is used to indentifies regions where GCMs weakly represent the amount of variability seen in the observed precipitation. ", "The results show that there were (1) large spatial variations in the ability (skill)of GCMs to capture observed precipitation, (2) extensive (widespread) under simulation of rainfall persistence characteristics in GCMs, and (3) substantial improvement in rainfall persistence after applying bias correction.", "\n\nAs an illustration the results for Global Hurst exponent from observed precipitation is presented in figure 4, and" ]

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[ "Pterolophia ochreosticticollis\n\nPterolophia ochreosticticollis is a species of beetle in the family Cerambycidae. ", "It was described by Stephan von Breuning in 1968.", "\n\nReferences\n\nCategory:Pterolophia\nCategory:Beetles described in 1968" ]

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[ "Miter guide devices, sometimes called fixtures or guages are well known for cutting complementary angled surfaces on workpieces. ", "U.S. Pat. ", "No. ", "4,165,668 describes a modern miter guage assembly for use with a table saw and it refers to a number of representative earlier patents on similar devices. ", "In none of these prior art patents, however, is there a disclosure of right and lefthand guide assemblies which have every possible degree of freedom so that workpieces can be held in any one of an infinite number of overlapped positions on the saw table. ", "See U.S. Pat. ", "No. ", "3,344,819 for a disclosure of an illustrative miter guage having certain limited degrees of freedom.", "\nIt is the principal objection of the present invention to provide matched right and lefthand guide assemblies each having a number of articulated parts which can be locked together in an infinite variety of rigid positions. ", "This permits the choice of one optimum miter position, depending upon the size and number of overlapped workpieces which are to be advanced together into the saw." ]

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[ "Q:\n\nvim: alias yank and copy to xclip\n\nI've got a cntrl c and cntrl v mapped to xclip, however its a hassle to have to remember to use instead of regular y and p. Is there a way to alias the two or send contents of y and p to xclip, so I can just use y and p for all copy and pasting?", "\nvmap <C-c> y:call system(\"xclip -i -selection clipboard\", getreg(\"\\\"\"))<CR>:call system(\"xclip -i\", getreg(\"\\\"\"))<CR>\nnmap <C-v> :call setreg(\"\\\"\",system(\"xclip -o -selection clipboard\"))<CR>p\")\")\")\"))\n\nA:\n\nAre you trying to use the X clipboard for all copy and pastes? ", " If so, a good alternative to xclip is to make sure you're using a vim with X support (it's really easy to compile Vim if your version doesn't have it) and then add the following to your vimrc:\nset clipboard=unnamed\n\nAll yanks and deletes will then automatically go to the * register (which is the X selection register).", "\nInstead of setting clipboard=unnamed, you can also use the X selection register for a single operation by using (e.g.)\n\"*yw\n\"*yy\n\"*ya(\n\nor whatever.", "\nObviously, this doesn't answer your question as to how to use xclip, but hopefully it offers an alternative approach.", "\n\n" ]

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[ "\nAsk HN: Any health tips? - ", "seymores\nWhat works for you and what don't. ", "Lets hear it.<p>I don't know about you guys but vitamin b complex really helps in my ability to focus and mental acuity.", "\n======\nkeefe\nIn my view, we are physical/emotional/intellectual creatures and harmonious\nfunctioning of all three centers leads to exponentially increasing\nproductivity.", "\n\nPhysically, I treat the body as a machine that runs on macronutrients (fiber,\nprotein,carbs) and micronutrients. ", "I looked up daily requirements of each\nmacro and I make sure I get them. ", "Micronutrients come from a vitamin. ", "A\ncornerstone of my diet is the protein smoothie - orange juice, brown rice\nprotein, probiotic yogurt. ", "Muscles are made of protein and they grow by\nstressing them until they breakdown then letting them regrow bigger. ", "So, I do\ncardio every day and weights alternating upper/lower 5/7 days.", "\n\nEmotionally, the key for me is minimizing lying and living according to my\nprinciples. ", "I also make sure to take time to take pleasure and relaxation.", "\nThis does wonders for my motivation. ", "I also try not to express or fixate on\nnegative emotions, rather to take them as a signal that change is required and\nthen let them go by as unnecessary wastes of energy.", "\n\nIntellectually, I am merciless with myself. ", "I use lists and lots, really a\nlot, totally excessive numbers of tests to make sure that I'm not seeing what\nI want to see.", "\n\nThat's about my philosophy of living a healthy life.", "\n\n~~~\nmixmax\nI'm curios about the tests. ", "Can you expand?", "\n\n~~~\nkeefe\nnothing particularly interesting really. ", "most of them are in junit. ", "otherwise,\nit's simple stuff like marking off when I stick to schedule or violate it,\nestimating times and then checking those estimates.", "\n\n------\nlotharbot\nDrink enough water. ", "Even _slight_ dehydration causes fatigue, emotional\ndiscomfort, and loss of focus. (", "There's an easy way to tell if you're\nhydrated: your urine will be nearly clear.)", "\n\nGet enough sleep.", "\n\nEat a balanced diet: lots of veggies and fruit, some lean meat and dairy, and\nthe right amount of carbs to keep your blood sugar consistent without adding\ntoo many empty calories.", "\n\nKeep your body moving. ", "Sitting in your chair staring at a screen for 8\nstraight hours is stressful. ", "Get up and take a short walk while you're\nthinking through a problem. ", "Pick up a hobby like biking, swimming, or martial\narts.", "\n\n~~~\nseymores\nBut taking vitamin B complex make my urine bright pretty yellow :-)\n\n------\njavanix\nStay away from ALL fast food. ", "Even their \"healthy\" choices are designed to\nmaximize profit margins, and there's just something unsavory about decades of\nprocessed food.", "\n\nI stopped eating fast food about 3 years ago, and I have felt healthier ever\nsince - I didn't change any other significant part of my diet/living situation\n- and I've only gotten sick once or twice, my migraines have decreased despite\nthe added stress of college, plus I've become a better cook.", "\n\n------\nmetamemetics\n-Fruit is healthy\\quick\\convenient\\delicious and is always a great standby. ", "Try to eat a little fat with them though (walnuts, almonds, hazelnuts are great) to stabilize the blood sugar impact and absorb any Vitamin A.\n\n-Cook with coconut oil or olive oil\n\n-If you don't like eating your veggies, try them with more garlic. ", "Or add spinach in with whatever you're cooking, it gets a good flavor once heated and even works with pasta.", "\n\n-Vitamin D supplement is extremely important if you are moderately nocturnal, you also can't absorb any calcium without it (look into this late-night coders)\n\n------\nm0nty\nI went low-carb three weeks ago and have lost c. 6lbs (edited!) ", "since. ", "I gave\nup alcohol a week later (still have the occasional one though). ", "Feeling much\nbetter, sleeping better, more energy, etc. ", "I have always been skeptical of\n\"fad\" diets but this one is working fine for me. \"", "Good Calories, Bad Calories\"\nby Gary Taubes was the starting point for all this.", "\n\n~~~\novi256\nThat much weight loss (6 Kg) sounds great! ", "Good job. ", "Be careful with loosing\ntoo much too fast, that could leave you with skin folds (excess skin hanging\nloose). ", "I seem to remember 1 kg per week is the safe amount. ", "Ask a physician.", "\n\n~~~\nm0nty\nAck! ", "I meant 6lbs, 3Kg!!", "\n\nMy understanding is it tails off after a few weeks, but thank you for the\nadvice. ", "I think it has something to do with fluid loss in the early stages or\nsomething like that.", "\n\n~~~\ncarbocation\nYes. ", "Glycogen is branched, polymerized glucose, and has a strong affinity for\nwater. ", "When you go low-carb, you reduce your glycogen stores, and thus your\nwater stores. ", "This type of weight loss is rapid but temporary (insofar as it's\nnot a reduction in what most people want to lose: fat).", "\n\n------\ntokenadult\nAvoid fads. ", "Overdoses of this or that trendy food or supplement are surely a\nbad idea. ", "Support healthy eating by daily outdoor exercise. ", "Get more sleep\nthan you have been getting recently.", "\n\n~~~\nseymores\nI think almost everyone I know in the IT industry underestimate how important\nit is to get enough sleep.", "\n\n~~~\nwazoox\nUntil you get older. ", "I recently came to the realisation that I need three days\nto overcome the fatigue of a 3 hours night sleep. ", "That means I can't afford a\nshort night every week, else my productivity will drop dramatically.", "\n\n------\nchipsy\nI believe strongly in the power of supplements to structure the rest of diet.", "\nHere is my current supplement structure:\n\nMultivitamin + 6000 IU Vitamin D + Calcium\n\nOmega-3\n\nWhey protein(at approximately the bodybuilder-style \"one gram per pound\nbodyweight\" level)\n\nFor meals I mostly eat in a low-carb/paleo fashion - because I find the fatty\nfoods easier to digest, overall. ", "Protein, fat, fiber, are what I look for(and\nquality fats too, a lot of the cheap vegetable oils seem shady and give me bad\nreactions). ", "Adding the whey protein really helped because it nullified a lot\nof the cravings that would make me break the meal plan. ", "Discovery: if you eat\nlike a bodybuilder, even without training you're going to start looking sort\nof like one.", "\n\nThe other supplements are general health measures to help my mood, alertness\nand immune system. ", "My GF, who has not yet bought into clean eating, recently\ngot the same bug as I did at about the same time. ", "I barely realized it was\nthere and was over it in three days. ", "She was taken down for about a week with\nsome vicious \"can't-do-a-thing\" days in the middle. ", "I've only been with her a\nshort while, so I hope I can encourage her.", "\n\n------\nCytokineStorm\nWhy rely on HN's anecdotal advice when you can use scientific evidence?", "\n\n[http://www.informationisbeautiful.net/play/snake-oil-\nsupplem...](http://www.informationisbeautiful.net/play/snake-oil-supplements/)\n\n------\njohnswamps\nA cup of tea and 5-15 minutes of meditation always helps to start my day.", "\n\n------\nawolf\nDaily exercise (biking, running, or swimming) has greatly increased my overall\ncoding productivity. ", "I'm able to work longer hours with a higher level of\nfocus.", "\n\n------\nscorpioxy\nJust one, exercise.", "\n\nI try to exercise at least 3 times a week, I do some cardio and then exercise\nwith weights. ", "After a month or so, your food intake will likely change and\nyou'll start to realize what you need in terms of nutrition. ", "Your body will\nalso become stronger and you will sleep much better and the exercise itself is\ngreat for stress relief.", "\n\nAs far as supplements, I don't like them. ", "Even the case of taking multi-\nvitamins is getting mixed reviews from physicians.(I take a vitamin D\nsupplement on Dr's orders)\n\n------\nDougWebb\nI had a bad cholesterol profile: low HDL and high LDL and triglycerides. ", "I\nreally didn't want to take any statins because of the dangerous side-effects,\nso my doctor prescribed niacin instead: Niaspan. ", "I had taken over-the-counter\nniacin before with no results, but the Niaspan gave me the niacin flush that\nfirst night, and after a few months my LDL, triglycerides, and total\ncholesterol were all in well inside the healthy range, and my HDL was just\nbelow the healthy range. ", "I just had my six-month followup blood tests, but I\nhaven't gotten the results yet. ", "I'm expecting to be in pretty good shape.", "\n\nI've taken between 1000mg and 3000mg per night, adjusting based on my body's\nresponse. ", "At first the flush happened within an hour of taking the pills, then\nit either stopped or it was happening while I slept. ", "I ramped up the dosage as\nthe flush effect weakened and I stayed at 3000mg for a while, but now that's\ntoo much. ", "It seems like my body only needs 2000mg now for the full effect, but\nI don't flush until about six hours after I take the pills. ", "Based on my blood\ntest results, I may ramp up again to get the flush faster or back off to\nreduce it.", "\n\nThe flush itself lasts about an hour. ", "It's not comfortable, but it's not bad\neither. ", "You get hot, red, and kind of itchy. ", "I understand that it's part of\nthe healthy effect of the niacin: expanding your blood vessels and washing out\ntoxins through your skin (which causes the itching).", "\n\nIf you want to try this, you need to get the prescription stuff. ", "The OTC\nniacin is definitely not the same, at least not here in the US where vitamins\nare unregulated food products that generally don't contain what they claim to\ncontain.", "\n\n~~~\ncarbocation\nNiacin has toxicities, just like statins. ", "Except for niacin's flush (which is\nnot indicative of any harm, but can be quite uncomfortable), I think the\nabsolute risk of dangerous toxicity for both statins and niacin is very low.", "\nTaking both, in supervised fashion, is reasonable.", "\n\nAs an aside, I agree with you re: getting prescription niacin. ", "If you do go\nwith the over-the-counter stuff, make sure it is _not_ \"no-flush\". ", "The\nevidence is not consistent with the notion that no-flush niacin has any lipid-\nmodifying effect.", "\n\n~~~\nDougWebb\nAny drug can cause problems, and you should always inform yourself before you\ntake them. ", "The niaspan information is here:\n<http://www.rxabbott.com/pdf/niaspan.pdf>\n\nFrom what I've read, it's tough to overdose on niacin, especially the\nsustained-release forms. ", "There are also apparently no deaths or long-term\nharmful results from overdoses either. ", "However, they warn against using\nniaspan if you've already got liver or kidney problems or if you're taking\nstatins too. ", "I also read a warning that ER doctors can misinterpret the\nsymptoms of a niacin overdose as an allergic reaction and give a treatment\nwhich does a lot more harm than the niacin would on its own.", "\n\nI don't have any handy references about statins, but I've read that the side-\neffects are both more common and more dangerous; so much so that it's\nquestionable whether or not they should be allowed on the market at all.", "\nThey're also less effective than niaspan, I believe. ", "The anecdotal evidence I\nhave is that my mom was taking a statin for a while. ", "It improved her\ncholesterol, but she also developed the bad heel pains that supposedly\nindicate a dangerous side-effect from the statin is occuring. ", "When she stopped\nthe statin, her heel pain went away. ", "Since then her cholesterol hasn't been\nbad (though it did get somewhat worse after stopping the statin) but if it\ngets bad again I'm going to insist she try the niaspan instead.", "\n\nFor what it's worth, I don't work for the company that makes Niaspan. ", "I'm just\na very satisfied customer.", "\n\n~~~\ncarbocation\nSustained-release niacin is well known to cause hepatic toxicity. ", "This is\nreported both in the label that you reference, and in the primary literature.", "\nThese problems do not occur with immediate-release preparations - only with\nsustained release (such as Niaspan). ", "So that is worth being aware of.", "\n\nStatins are among the safest drugs ever used - so much so that most medical\npeople talk about trying to give them to more, not fewer, people. ", "Like niacin,\nstatins can lead to insulin resistance. ", "Statins don't appear to increase\ncancer risk, which was in question for awhile. ", "There is some literature\nsupporting the notion that reduced LDL may lead to increased cancer, but this\nis not dependent on the mechanism of cancer, and this conclusion is not yet\nsupported by enough data to make it a concern for anyone. ", "Heart disease is\nwhat will kill most Americans, so this is still the primary concern.", "\n\n------\nfizx\nQuit drinking soda.", "\n\n------\ntheycallmemorty\nGo to bed and get up at the same time every day.", "\n\nDon't do anything in your bedroom except sleep and sex.", "\n\n------\nwatmough\nTake a fish oil supplement and a multivitamin.", "\n\nEat as little as you can get away with allowing you to control your weight (up\nor down!), ", "and do everything you can to reduce your stress levels.", "\n\n------\nchett\nOver the last 6 months I've lost a little over 20 lbs by eating healthier and\nexercising.", "\n\nI tracked what I ate with an iPhone app and joined the gym. ", "Tracking food\nintake was tedious but helped me unlearn bad eating habits. ", "I've gone from\npanting after 5 minutes on the treadmill to running 4 miles in about 35\nminutes. ", "I feel like I've found a sustainable, enjoyable pastime that will\nkeep me in good health for years to come. ", "Support from my wife was crucial\ntoo.", "\n\n------\nbpourriahi\nI have read no books on Vitamin D and only a couple asthma-related articles on\nits benefits. ", "My lungs were in severe pain and I had been looking for anything\nthat could help, so I tried it. ", "WOW. ", "HUGE difference. ", "Turns out D is extremely\nimportant and being deficient can impair and damage many things. ", "It has helped\nwith focus, agility, and I feel MUCH better. ", "It has really help with my\ndepression and lack of focus, which were very serious issues (I was unable to\nwork.. seriously).", "\n\nTry it for yourself and judge. ", "Not the puny 400IU a day. ", "Take 10,000IU a day\nfor a week (it's not toxic) and see if you feel better.", "\n\nI have hypothyroid and this perpetuates D deficiency.. I desperately needed\nit. ", "But most people need more Vitamin D, and its effects are widespread and\nlargely unknown. ", "You can do your own research, but please don't tell me its\ntoxic because of the FDA. ", "Try for yourself and pay attention to your body.", "\nJust know 400IU is worthless.", "\n\n------\njuliend2\n(organic) vitamin D helped me this winter because there is less sun during\nthese months (in Canada).", "\n\nI also sit a lot less in front of my computer since i've read\n[http://www.businessweek.com/print/magazine/content/10_19/b41...](http://www.businessweek.com/print/magazine/content/10_19/b4177071221162.htm)\n(thanks HN for this) .", "\n\n------\nmsluyter\nAdopt a program of RSI prevention, whether you have it or not.", "\n\n------\nlena\nDon't forget your teeth. ", "Dental health is correlated with general health, and\nsome dental problems are not reversible (I have severe erosion because I used\nto drink soft drinks all day).", "\n\nApart from diligent tooth brushing (give the inside of your teeth as much time\nas the outside, and brush at least 2 minutes) eating habits are very important\nfor dental health as well.", "\n\n\\- Limit the amount of times you eat (it is better to eat 6 candies in one\nsitting than it is to eat 4 pieces of candy during the day) \\- Don't drink\nsoda, but realise that for your teeth apple and other fruit juices are just as\nbad, so severely limit them as well. \\- ", "Don't brush your teeth immidiately\nafter eating. \\- ", "Eat xylitol mints or chew xylitol gum after meals\n\n------\nArtifex\nAvoid all wheat, oats and soy products for a week. ", "See how you feel.", "\n\nTurned out I had a gluten sensitivity for the longest time, and I felt loads\nbetter going off all gluten.", "\n\nSoy also acts as a phytoestrogen in the male body - could potentially be\ncounteracting testosterone production.", "\n\n------\nkrmmalik\nSomeone taught me a philosophy \"Eat Well, Move Well, Think Well\", which i am\ntrying to implement in my life right now.", "\n\nEat Well - Other than the obvious, this also related to your environment, in\nterms of the quality of the water you drink, the detergents you use and their\nharmful effects etc\n\nMove Well - Its not just about plenty of exercise, but more about the right\nkind of exercise. ", "Anything that stimulates the correct response from your\nspine which feeds back to the brain\n\nThink Well - Having a positive, can do attitude as well as performing\nvisualization exercises of yourself in a healthy state, since the mind cannot\ndifferentiate between reality and imagery in the brain.", "\n\n------\ngcv\nPlenty of exercise. ", "Try hundredpushups.com for a nice, easy-to-start program.", "\n\n~~~\nwazoox\nBe careful that pushups can get hard. ", "I had shoulder pains after doing more\nthan 50 pushups a day for a few weeks (down to 30 now).", "\n\nVary exercise, and particularly do aerobic exercise, walking, biking, running,\nswimming, skipping rope... The best is to do some exercise every day.", "\n\n~~~\nfreshfey\nYour shoulder pain is not the result of the pushup program, but more the\nresult of bad form, disbalances in your body (one muscle group is stronger and\nhas to support the other one -> more tension on the weak) or other health\nissues.", "\n\n~~~\nwazoox\nOh yes it is. ", "I had ankle and knee pain running more than 40 km a week, too.", "\nI'm simply getting too old for more than 2 hours of intense sport a day, I had\nto get back to 60 to 90 minutes.", "\n\n------\ntjstankus\nPay attention to macronutrients (carbohydrates/protein/fat) and eat them in\nproportion to each other. ", "You'll need to do some reading and a bit of\nexperimentation to find what fits your needs best. ", "Getting the right balance\nof macronutrients will postively affect your mental acuity. ", "That and exercise.", "\nIf you're getting enough exercise, it's much easier to get good sleep. ", "Once\nthese big picture things are in place, _then_ worry about micronutrients\n(vitamins).", "\n\n------\njohnmw\nMy uncle lived to 106 and until he was about 102 he had more energy than me.", "\nApart from his good genes (alas, he was an uncle in law), I think his two main\nsecrets were:\n\n1\\. He loved life. ", "Really loved it. ", "He kept active, doing the things he loved\nuntil he died. ", "2\\. He seemed to live pretty much stress free.", "\n\n------\nsev\n* Stay far away from microwaves\n\n* Don't drink soda\n\n* No fast food\n\n* Have fruits and veggies daily\n\n* Lots of water\n\n* Exercise daily\n\n* Stretch daily\n\n* Meditate/Yoga\n\n~~~\nwesley\nIs the microwave myth still going strong here?", "\n\n------\nhga\nIf you have problems with insomnia or even a tiny bit of seasonal depression:\n[http://www.amazon.com/Philips-goLITE-BLU-Therapy-\nDevice/dp/B...](http://www.amazon.com/Philips-goLITE-BLU-Therapy-\nDevice/dp/B001I45XL8/)\n\n------\nwhimsy\nWasn't there a blog post by someone within the last few weeks re: some sort of\n\"hacker workout schedule\" involving x pushups, y crunches and z something\nelse?", "\n\nThat looked intriguing to me, but I forget where it was.", "\n\n------\nmichael_dorfman\nFollowing health tips you found on internet discussion sites (even ones as\ninteresting as HN) is a bit like chewing gum you found on the sidewalk.", "\n\nSeriously: \"What works for you and what doesn't\"? ", "Science.", "\n\n------\nwallflower\nA foam roller. ", "Awesome for relaxation.", "\n\n[http://www.livestrong.com/article/24888-using-foam-roller-\nba...](http://www.livestrong.com/article/24888-using-foam-roller-back-pain/)\n\n------\nscorxn\nDespite the ad-peppering, <http://www.simplefit.org/> has some good info and a\nvery manageable workout/nutrition schedule.", "\n\n------\nprotomyth\nI was told to take vitamin b complex by a doctor because my finger tips were\ngoing numb (I thought it was something worse). ", "I don't think it helped my\nfocus.", "\n\n------\npraptak\nAs a medicine doctor and a former president of USA I advice you not to seek\nhealth advice from anonymous guys on the internet. ", "Btw, yerba mate kicks ass.", "\n\n------\nmbenjaminsmith\nGet enough sleep; eat fresh / organic meats, veggies, fruits; exercise\n(training for amateur competition is good); try to stay as positive as\npossible.", "\n\n------\njacoblyles\nDon't eat such large portions, and cut back on the caffeine. ", "Both of these\nthings help me stay mentally sharp.", "\n\n------\nspython\nGive up smoking. ", "Really.", "\n\n------\nzackola\ndon't drink soda. ", "eat more vegetables, eat less meat.", "\n\n------\nwendroid\nGet to bed by midnight & get up when you wake (no alarm clock).", "\n\nOnly eat wholemeal wheat.", "\n\nEat plenty of greens - broccoli, kale, savoy cabbage (high iron stuff)\n\nEat an apple on your way to the office.", "\n\nCoffee only before mid-day\n\n------\nedkennedy\nWelcome to BODYBREAK, with Hal Johnson and Joanne McCloud.", "\n\nGreens+ extra energy eliminates the need for mid afternoon naps, and as a side\nbenefit you may not need to drink coffee anymore! ", "Piracetam/Aniracetam has\npersonally proven effective for focus, memory and mental acuity. ", "ZMA can\nincrease the quality of sleep as well as assist muscle growth and testosterone\nproduction. ", "Exercise improves mood and many other health factors. ", "We recommend\ntrying this workout: <http://www.bodybuilding.com/fun/timothyf.htm> Tim Ferris\nalso has a diet designed for losing weight:\n[http://www.fourhourworkweek.com/blog/2007/04/06/how-to-\nlose-...](http://www.fourhourworkweek.com/blog/2007/04/06/how-to-lose-20-lbs-\nof-fat-in-30-days-without-doing-any-exercise/)\n\nSEX. ", "Lots of it. ", "reduce your stress and practice good fitness emotionally and\nphysically. ", "I read something interesting this morning that stress can cause\nincreases in abdominal fat, which is the worst type of fat in terms of it's\nlong term health detriment.", "\n<http://stress.about.com/od/stresshealth/a/cortisol.htm>\n\nHave a healthy attitude, stay positive, and remember KEEP FIT AND HAVE FUN!!!", "\n\n~~~\nedkennedy\nI guess this message would of been better conveyed in video format.", "\n\n~~~\nwhimsy\nIt would have been better if it didn't read like an infomercial.", "\n\n~~~\nedkennedy\nSometimes I forget everyone is not Canadian. ", "Bodybreak was a series of\neducational ads on Canadian TV in the 80's. ", "For ex: Here's an exercise you can\ndo sitting down.", "\n[http://www.youtube.com/watch?v=t1p6K0xGKd0&feature=relat...](http://www.youtube.com/watch?v=t1p6K0xGKd0&feature=related)\n\n" ]

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[ "Guided wave modes in porous cylinders: Theory.", "\nThe classical theory of wave propagation in elastic cylinders is extended to poro-elastic mandrel modes. ", "The classical theory predicts the existence of undamped L modes and damped C, I, and Z modes. ", "These waves also appear in poro-elastic mandrels, but all of them become damped because of viscous effects. ", "The presence of the Biot slow bulk wave in the poro-elastic material is responsible for the generation of additional mandrel modes. ", "One of them was already discussed by Feng and Johnson, and the others can be grouped together as so-called D modes. ", "The damping of these D modes is at least as high as the damping of the free-field slow wave." ]

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[ "She is told she was abandoned. ", "Only much later would she learn that her family had been a casualty of anti-Asian immigration policy in the United States. ", "Her American father got Congress to pass a special bill that would have allowed her to enter the U.S., yet she went most of her 67 years without knowing that.", "\n\n\"So many coincidences happened in my life,\" she said in an interview at her house outside Tokyo. \"", "But altogether, you know, I managed to put the whole story, that now I'm settled, and I have peace of mind. ", "Thank goodness that I don't have to live with two people anymore.\"", "\n\nThose two people are Mary Ann Vaughn, the girl she was born as, and Marianne Wilson, the girl that fate made her.", "\n\nHer father, Texas-born James Vaughn, arrived in Japan in early 1946. ", "The 20-year-old civilian was assigned to a U.S. military base in Yokohama. ", "He met 16-year-old Vivienne Wilson working in the PX to help support her family. ", "Their daughter, Mary Ann Vaughn, was born in a Yokohama hospital on April 17, 1949.", "\n\nIt was an ill-fated romance. ", "The military denied Vaughn permission to marry Wilson, based on U.S. immigration law, because she was half-Japanese. ", "Back in the U.S., he wrote to Congress, which passed a law allowing Wilson and her daughter to enter the U.S. It was dated Aug. 5, 1950.", "\n\nThat very day Vivienne Wilson died of tuberculosis. ", "Mary Ann was 16 months old.", "\n\nWilson's family asked her nanny to take care of Mary Ann until her father returned. ", "He never did.", "\n\nShe didn't know she was American. ", "In fact, she was taught to be terrified of Americans. ", "But ultimately, an organization set up to help orphans left behind by American soldiers found her.", "\n\nIn letters to the Swedish consul in Tokyo in 1955, the group reported that Mary Ann's nanny wanted to adopt her, but questioned whether that was advisable, given her impoverished circumstances.", "\n\nSweden decided it should find a home for her, and a custody battle ensued. ", "The court ruled in Sweden's favor in 1958.", "\n\nUnder a compromise with the Swedish Embassy, the child would go to an international school, live with a foreign host family during the week and stay with her nanny Fumi Yamaguchi on weekends.", "\n\nThat wasn't the only change the deal required. ", "Until then, the girl had been known as Mary Ann Yamaguchi. \"", "From now on,\" Yamaguchi told her, \"your name is going to be Marianne Wilson.\"", "\n\nIt was a name she hated. ", "Marianne is the Swedish version of Mary Ann, and in her 9-year-old mind, it was the source of all her troubles. ", "She struggled to learn English, and while she met other mixed-race children, it didn't help her understand her own family.", "\n\nOn her deathbed in 1975, Yamaguchi told Marianne everything. ", "James Vaughn was her father, and he hadn't abandoned her, but had tried to find her. ", "She gave her old photos, and said, these are your parents.", "\n\nMarianne did not investigate further until after she had a family of her own and had become Marianne Wilson Kuroda. ", "Even then it took years to get answers. ", "In 2004, the Japanese Red Cross told her: We found James Vaughn, but unfortunately he died 11 months ago. ", "And you have a younger brother in America.", "\n\nThree months later, she was flying to Albuquerque, New Mexico.", "\n\nShe and her 56-year-old half-brother, Steve Vaughn, compared photos. ", "They found they had similar ones of their father. ", "They visited the grave of their father, who had died on Feb. 3, 2003, at the age of 77.", "\n\n\"I had to give him respect, you know. ", "But, um, hmm, it was like, you know, 'Why did you die 11 months ago?'\" ", "Marianne said. \"", "You could have lived a little bit longer after all these years.\"", "\n\nShe decided to claim her U.S. citizenship, in his honor. ", "It would take 12 years. ", "U.S. officials had questions about the law, and about why someone who did not intend to move to America wanted citizenship.", "\n\n\"Her case is a consequence of this history of discrimination from immigration law and citizenship law that I thought really needed to be corrected,\" said Rose Cuison Villazor, a professor at the Immigration Law Clinic at the University of California, Davis, who helped Marianne. \"", "There was ... this awful history that I felt needed to be addressed as a matter of justice.\"", "\n\nThe U.S. ultimately granted Marianne citizenship. ", "A photo posted this June on Facebook shows a smiling Marianne standing outside the U.S. Embassy in Tokyo, holding up the oath of allegiance she had just signed.", "\n\nShe says she has one more task. ", "She wants to visit the cemetery in the west Texas city of Spur where her paternal grandparents are buried.", "\n\n\"I want to show them my American passport and say, 'Grandpa, Grandma. ", "I'm home.'\"" ]

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[ "Re: Game: Are you?", "\n\nRe: Game: Are you?", "\n\nNot any more. ", "I used to be but (true story) I went there one time and the pool was closed, with signs reading \"closed due to biohazard.\" ", "Upon further inquiry, the \"biohazard\" turned out to be a piece of poo. ", "They had to empty the entire pool and clean it and refill it. ", "Now I don't go to the Y any more.", "\n\nAre you the kind of person that would still swim in a pool even if you thought kids had peed in it?", "\n\n\"The day will come when, after harnessing space, the winds, the tides, gravitation, we shall harness for God the energies of love. ", "And, on that day, for the second time in the history of the world, we will have discovered fire.\"" ]

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[ "The Left Lurches Left\n\nHot on the heels of actress Cynthia Nixon’s from-the-left primary challenge of incumbent Andrew Cuomo in the upcoming New York governor’s race comes a bold plan from Senator Bernie Sanders to guarantee every American a job. ", "Bernie’s plan amounts to the same feel-good hand-waving that was a major plot point in the endearing but frighteningly naive 1993 political movie Dave – a plan long on sentiment and “this is how things should be” but wholly divorced from reality. ", "Even Bernie’s own people have no idea how much his plan (which, on first glance, seems to be about giving the unemployed government jobs at $15 an hour) would cost, but estimates put it at a trillion a year. ", "As far as I’m concerned, this “jobs” program is nothing more than putting a false veneer of respectability on a gigantic money handout. ", "Jobs that don’t have a reason for existing (i.e. most government jobs and any make-work program) don’t contribute value to the economy or create wealth of any sort, meaning that the wages for those jobs has to be sucked out of the productive economy. ", "This is obvious to anyone who doesn’t put blind partisanship ahead of reality, and even attempting it would be enormously destructive to the nation. ", "Yes, some of Bernie’s economists support the plan, but these people are either partisan liars or idiots.", "\n\nThese two chestnuts stand out in a broader “progressivizing” of the already-too-far-Left. ", "Since Clinton’s shocking loss to the Untethered Orange Id, itself the culmination of a thousand previous electoral losses during the left-march of the Obama years, the Left has decided, against the obvious message of those losses, that it should continue with its progressive agenda, and indeed expand upon it, rather than recalibrate and offer up something different to the public.", "\n\nYes, I speak of the Left as a single entity. ", "Given that diversity of opinion therein, even a tightly constrained “diversity” within the orthodoxy, is met with rabid attacks and infliction of personal destruction, it makes more sense for outsiders to look at the Left as a Monolith than to sort out competing ideas among its players. ", "This is reinforced by the lock-step conformity that’s demanded of its politicians, and the war that the liberal establishment wages on those who stray.", "\n\nWhile the Right deserves pillory for those among its ranks who’ve embraced the nationalist/protectionist agenda and abandoned small government principles and free market ideals, at least therein we can say that there’s a battle of ideas going on there. ", "Not so on the Left, where hare-brained schemes like Bernie’s jobs giveaway get written about in glowing sophistry by people whose pedigrees strongly suggest should know better. ", "Worse, reliable liberals like Cuomo who, as the New York Post’s Michael Goodwin noted, delivered the “Holy Trinity of the left’s agenda — passing gay marriage, gun control and banning fracking,” are being pushed even further leftward by the monolith. ", "Cuomo and others who are suddenly not liberal enough comply meekly lest they suffer the Monolith’s wrath.", "\n\nConservative commentators point out, correctly, that the Left is bereft of new ideas. ", "It’s hard to advance new ideas, however, when the Monolith has already decided what’s correct, and demands absolute compliance.", "\n\nTrump’s unpopularity has put a lot of fresh wind in the Left’s sails, and that what’s increasingly looking like a mid-term rebuke at the ballot box is seen as an opportunity to press forward with the Monolith’s agenda, despite the rejection of that agenda by Obama-era voters. ", "So, instead of an offering of new or centrist proposals that might draw those outside the core constituency, the Left appears to be banking on the same sort of “I’m voting against Hillary” mindset that helped Trump win to put them back in power, policy ideas notwithstanding. ", "Strike that – policy ideas to the contrary. ", "It’s rather evident that a number of policies the Left loathes: fracking, deregulation, drillbabydrill, etc, have had a good effect on jobs and prosperity. ", "It’s also rather evident that a number of policies the Left embraces: bigger government, more regulation, alternative energy subsidies, expanded welfare, have done harm to the nation AND have worked against them at the ballot box. ", "Yet despite the evidence, the Monolith would rather exploit the current political wind to reinstate itself and revisit harmful policies than to reinvent itself (see: Bill Clinton, 1995-2000) and reap success.", "\n\nThis leftward lurch in terms of policy is born of the Left’s continued embrace of take-no-prisoners political correctness and social justice lunacy. ", "It’s also egged on by a vicious cycle of one-upmanship with the Right’s pro-Trump hard-liners. ", "Compromise and common ground are alien concepts today, and giving even an inch of concession is simultaneously treated as a surrender by one’s own and an opening for triumphant attack by one’s opponents.", "\n\nIn Edgar Allan Poe’s gothic horror classic, The Pit And the Pendulum, an unnamed protagonist is strapped to a table, and a sharp blade on the end of a swinging pendulum goes back and forth above his chest. ", "With each swing, the blade gets lower and lower. ", "Our politics today feels just like this story. ", "The power in Washington swings cyclically between the Republicans and the Democrats, and each sees as its primary (and perhaps only) goal, when it is out of power, as the recapturing of power. ", "Often, without regard to consequences or the best interests of the nation (despite rhetoric to the contrary). ", "And, as with Poe’s killing machine, each swing of power seems to move the nation closer and closer to ruin. ", "The debt goes up, government spending grows with no regard for effectiveness or efficiency, and power continues to accrete to the “ins.”", "\n\nThe Republicans, when wholly out of power during Obama’s first year plus in office, promised all sorts of small government reforms, and were swept into the House by the Tea Party movement that embraced those promises. ", "Once there, they immediately sought to defenestrate those small government promises, but were briefly checked by the principled Tea Party freshmen who, despite being told to shut up and do as instructed, held firm on tax cuts and some other issues. ", "No matter – in time the party’s bigs won out, and when given the Senate and then the White House, defaulted back to their big government, big spending ways.", "\n\nOne of the great fears of a Trump victory was the damage it would do to the GOP and its (stated but rarely heeded) small government principles. ", "While Trump has actually done some small-government things with regard to taxation, regulation and the Court, he and the GOP leadership don’t seem to give a flying [redacted] about spending, and the worry that this would allow the Left to move even further left by shifting the “middle” in that direction seems to be materializing.", "\n\nI am twice-retired, a former rocket engineer and a former small business owner. ", "At the very least, it makes for interesting party conversation. ", "I'm also a life-long libertarian, I engage in an expanse of entertainments, and I squabble for sport.", "\n\nNowadays, I spend a good bit of my time arguing politics and editing this website." ]

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[ "Ligand migration and protein fluctuations in myoglobin mutant L29W.\nWe have determined eight X-ray structures of myoglobin mutant L29W at various experimental conditions. ", "In addition, infrared spectroscopic experiments are presented, which are discussed in the light of the X-ray structures. ", "Two distinct conformations of the CO-ligated protein were identified, giving rise to two stretching bands of heme-bound CO. ", "If L29W MbCO crystals are illuminated around 180 K, a deoxy species is formed. ", "The CO molecules migrate to the proximal side of the heme and remain trapped in the so-called Xe1 cavity upon temperature decrease to 105 K. The structure of this photoproduct is almost identical to the equilibrium high-temperature deoxy Mb structure. ", "If the temperature is cycled to increasingly higher values, CO recombination is observed. ", "Three intermediate structures have been determined during the rebinding process. ", "Efficient recombination occurs only above 180 K, the characteristic temperature for the onset of protein dynamics. ", "Rebinding is remarkably slow because bulky residues His64 and Trp29 block important migration pathways of the CO molecule." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Phase identification and structure solution by three-dimensional electron diffraction tomography: Gd-phosphate nanorods.", "\nHydrothermal synthesis of GdPO4 in the presence of poly(methacrylic acid) yields nanorods with a diameter of 15 nm and an aspect ratio of 20. ", "Powder X-ray diffraction patterns showed that the GdPO4 nanorods display peaks characteristics for both monoclinic and hexagonal structures. ", "Three-dimensional electron diffraction tomography (3D EDT) was used to determine the structures ab initio on the basis of reciprocal volume reconstruction of electron diffraction data sets collected from single nanorods. ", "The crystal structure of the monoclinic form was shown to be P21/n, corroborating previous work. ", "We were able to solve the 3D structure of the hexagonal P6222 form, which has not been reported previously. ", "Our work shows that 3D EDT is a powerful method that can be used for solving structures of single nanocrystals." ]

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[ "About\n\n$10,822\n\npledged of $10,000 goal\n\n66\n\nbackers\n\n\"WE ARE: A Nation of Immigrants\" is a large-scale public art installation, designed to uplift the voices of immigrants\n\nThis extraordinary public art exhibit features larger-than-life portraits of local immigrants, which will be hung on the churches of the historic New Haven Green and surrounding areas. ", "These 25-foot photographic portraits underscore our common humanity, bringing immigrants of diverse backgrounds into the public square to be seen, contemplated and appreciated. ", "Whether recent citizens or longtime residents, documented or undocumented, eager travelers or fleeing refugees, these courageous men and women continue to form the heart of our sanctuary city and to define our country.", "\n\n\"WE ARE\" celebrates immigrants from all corners of the world\n\nFrom the beginning immigrants founded, forged, and fostered our settlements. ", "Over the centuries they broke ground for new technologies, industries and processes to enlighten our existence, and build a better tomorrow. ", "The public arts installation, \"WE ARE: A Nation of Immigrants\" acknowledges and celebrates refugees and immigrants. ", "It seeks to build stronger and more tolerant communities by building familiarity and awareness, and revealing what is already there, the common and inherent dignity we all possess. ", "Through his bold yet intimate portraits, photographer Joe Standart invites us to be more aware and compassionate.", "\n\nThe \"WE ARE\" team is extremely grateful for the help and support of IRIS (Integrated Refugee and Immigrant Services), Junta, ULA and others. ", "This project has been initiated in part to support their efforts.", "\n\nHelp us raise $10,000 to print and hang these dignified portraits\n\nWe are turning to the Kickstarter community for help in funding the installation of this exhibit. ", "It includes the printing and installation of 14 large photographic murals, measuring 9' x 25,' many of which will be presented on the walls of the historic churches on the New Haven Green - thus linking today's immigrants with our heritage as a country founded and nurtured by immigrants.", "\n\nThis Kickstarter is a small but important part of this project. ", "We are hoping to far surpass the stated goal, which will allow us to exceed expectations for this installation and community outreach. ", "Have fun and think generous!", "\n\n\"WE ARE\" is proud and grateful for the support of Trinity Church (pictured here) along with that of Center Church and United Church for presenting many of the portraits.", "\n\nThe murals will be installed in various parts of the city, including on the historic Pirelli building at IKEA New Haven...\n\nThanks to the generosity and desire to support our immigrants, IKEA New Havenhas granted permission to present our portrait on the iconic Pirelli building immediately off of I-95, which 200,000 people pass by every day. ", "The portrait will measure 48' x 68'. ", "IKEA New Haven will also sponsor the installation of this image.", "\n\n1-½” stainless steel frames, standing 8' tall (see below), are being constructed to continue presenting the story and to visually link the murals on the churches. ", "Clustered in one of Connecticut's most historic and beautiful community greens, the installation is designed to offer a more intimate, face-to-face, contemplative encounter with the portraits. ", "The frames placement on the highly trafficked Green demands that they be extremely sturdy and safe.", "\n\nMonoliths and Images on Center Church.", "\n\nThis exhibit invites the local community, visitors to New Haven, all immigrants, the International Festival of Arts & Ideas, and graduates of multiple colleges/universities and their visiting families to consider the role and place of the American immigrant at a critical time, when national immigration policy is being crafted. ", "The exhibit will run from May – September, with the portraits and DACA histories used in creative ways to bring attention to our nation of immigrants. ", "The project may travel to other cities.", "\n\nMark your calendars for these dates. ", "Join us at our Opening Celebration:\n\nApril 21, 2018: Naturalization Ceremony\n\nApril 24, 2018: City of New Haven 380th Anniversary\n\nJune 8, 2018: Opening Celebration\n\nAugust 15, 2018: Exhibit Closing\n\nThe core installation consists of approximately 8 large-scale (25 foot high), dignified portraits of refugees and immigrants attached to the exterior walls of the three Churches on the Green and to other venues. ", "The 20 monolithic structures link the churches. ", "Additionally, Portrait banners will be on display in various parts of the city including on the Library, on City Hall, and other structures.", "The exhibit will be installed over a period of time allowing us to celebrate several city events in the process: A Naturalization ceremony on April 21, The 380th Anniversary of the founding of the City on April 24th, and the graduation of several universities and colleges during the week of May 21st. ", "The official opening will take place on Friday, June 8 at 6 PM at the west end of Center Church - the day before the opening of the International Festival of Arts and Ideas. ", "All are invited – We expect an audience of well over 220,000. ", "The Exhibit will close on August 15.", "\n\nOur Team: Our team is made of of individuals passionate about building a stronger New Haven and country, and includes Andy Wolf, Director of the City's Division of Culture and Tourism, Jennifer Aniskovich, not for-profit advisor, Duo Dickinson, architect and conservator for Trinity Church on the Green, Lucy McClure, organizing director on Nasty Women New Haven, Randi McCray, director of UrbanCollective, Reverend Kevin Ewing, pastor of Center Church on the Green, and others.", "\n\nExhibition Poster\n\nA special limited edition, 18\" x 24\" version of our exhibition poster will be available as a reward for contributions at the $60+ level. ", "Edition will be 30 prints, hand numbered and signed by Joe Standart.", "\n\nKickstarter is not a store.", "\n\nPledge $2,000 or more\nAbout $2,000\n\nTake your portrait!", "\n\nYour portrait taken by Joe Standart in his studio in Lyme CT. ", "You will receive one 11x14\" print on glossy paper. ", "Portrait to be taken at a mutually agreed upon time before September 30, 2018. ", "This can be a tax deductible reward by making it at http://www.portraitofamerica.org/newhaven/support-opportunities/ and notifying Joe@JoeStandart.com." ]

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[ "// Copyright (c) Jupyter Development Team.", "\n// Distributed under the terms of the Modified BSD License.", "\n\nimport { Signal } from '@lumino/signaling';\n\nimport { ActivityMonitor } from '@jupyterlab/coreutils';\n\nimport { sleep } from '@jupyterlab/testutils';\n\nclass TestObject {\n one = new Signal<TestObject, number>(this);\n\n two = new Signal<TestObject, string[]>(this);\n}\n\ndescribe('@jupyterlab/coreutils', () => {\n describe('ActivityMonitor()', () => {\n let testObj: TestObject;\n let signal: Signal<TestObject, number>;\n\n beforeEach(() => {\n testObj = new TestObject();\n signal = testObj.one;\n });\n\n describe('#constructor()', () => {\n it('should accept a signal', () => {\n const monitor = new ActivityMonitor<TestObject, number>({ signal });\n expect(monitor).toBeInstanceOf(ActivityMonitor);\n });\n\n it('should accept a timeout', () => {\n const monitor = new ActivityMonitor<TestObject, string[]>({\n signal: testObj.two,\n timeout: 100\n });\n expect(monitor).toBeInstanceOf(ActivityMonitor);\n });\n });\n\n describe('#activityStopped', () => {\n it('should be emitted after the signal has fired and a timeout', async () => {\n let called = false;\n const monitor = new ActivityMonitor({ signal, timeout: 100 });\n monitor.activityStopped.connect((sender, args) => {\n expect(sender).toBe(monitor);\n expect(args.sender).toBe(testObj);\n expect(args.args).toBe(10);\n called = true;\n });\n signal.emit(10);\n expect(called).toBe(false);\n await sleep(100);\n expect(called).toBe(true);\n });\n });\n\n describe('#timeout', () => {\n it('should default to `1000`', () => {\n const monitor = new ActivityMonitor<TestObject, number>({ signal });\n expect(monitor.timeout).toBe(1000);\n });\n\n it('should be set-able', () => {\n const monitor = new ActivityMonitor<TestObject, number>({ signal });\n monitor.timeout = 200;\n expect(monitor.timeout).toBe(200);\n });\n });\n\n describe('#isDisposed', () => {\n it('should test whether the monitor is disposed', () => {\n const monitor = new ActivityMonitor<TestObject, number>({ signal });\n expect(monitor.isDisposed).toBe(false);\n monitor.dispose();\n expect(monitor.isDisposed).toBe(true);\n });\n });\n\n describe('#dispose()', () => {\n it('should dispose of the resources used by the monitor', () => {\n const monitor = new ActivityMonitor<TestObject, number>({ signal });\n monitor.dispose();\n expect(monitor.isDisposed).toBe(true);\n });\n\n it('should be a no-op if called more than once', () => {\n const monitor = new ActivityMonitor<TestObject, number>({ signal });\n monitor.dispose();\n monitor.dispose();\n expect(monitor.isDisposed).toBe(true);\n });\n });\n });\n});\n" ]

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[ "Death to CAPTCHA! ", "Google wants to make them invisible using AI\n\nEnhance your handset with five free professional add-ons\n\nThis article was taken from the July 2014 issue of Wired magazine. ", "Be the first to read Wired's articles in print before they're posted online, and get your hands on loads of additional content by <span class=\"s1\">subscribing online.", "\n\nADVERTISEMENT\n\nToday's smartphones are powerful pocket computers packed with sensors. ", "Yet they could be more useful still, which is why a number of companies are developing add-ons to plug in, clip on or wirelessly connect to further augment your smartphone's capabilities. ", "Our favourites promise to put professional tools in the hands of the smartphone-toting masses. ", "Here are five of the best.", "\n\nRead more\n\nYour next personal shopper will be a couture-crazy chatbot\n\nByAdam Born\n\nWith AliveCor's monitor you can press the metal plate to your chest or fingertips to get an instant ECG readout. ", "Analyse the data with the accompanying AliveECG app or upload it to your doctor to detect irregular heart rhythms. ", "£169\n\nSmartphone cameras have improved, but they can't take DSLR-quality images. ", "The QX100 aims to bridge the gap by packing a Carl Zeiss lens into a small cylinder fitting on to the back of a smartphone, and takes pictures that get close to professional calibre.£399\n\nADVERTISEMENT\n\nRead more\n\nThe world's largest telescope just got bigger (thanks to Ireland)\n\nThe FLIR ONE transforms your smartphone into a thermal-imaging camera, providing Predator-style stealth vision. ", "The device could be a boon for contractors and DIYers seeking heat-loss spots or water damage. ", "Not quite X-ray vision, but close. ", "$350\n\nADVERTISEMENT\n\nThis offers laser-accurate measurements and instant 3D models of structures from up to 180 metres away. ", "Manufacturer ikeGPS claims the device - which combines a rangefinder, GPS and 3D compass - is useful for surveyors of all kinds. ", "£370" ]

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[ "Musikantinnen in der S-Bahn : Besinnungslose Netzklatschaffen\n\nWenn zwei flotte Musikantinnen die Frankfurter S-Bahn beschwingt beschallen – darf man da auch schlechtgelaunte Einwände erheben?", "\n\nDer Hype schlechthin auf Facebook und Co. ist zurzeit ein Video von zwei Musikantinnen, die in der Frankfurter S-Bahn den Song „Kiss“ von Prince performen. ", "Pose hoch zehn als extrovertierte Gutelaunebärinnen. ", "Thumbs up.", "\n\nIm weiteren Verlauf mischt sich auch noch ein betrunkener Fahrgast aka berühmter Musiker ein und lallt ein paar Reime dazwischen. ", "Also eigentlich nur das übliche Trauerspiel in unseren öffentlichen Verkehrsmitteln. ", "Dennoch wurde das Klickmonster fünfhunderttausend mal geteilt und 25 Millionen mal aufgerufen.", "\n\nUnd keiner weiß, warum, während der brave Jongleur an der Straßenkreuzung und der Old-School-Schnorrer vor dem Supermarkt völlig unbeachtet bleiben. ", "Dabei machen die wenigstens keinen Krach.", "\n\nDenn die Fahrgäste in der S-Bahn sind vielleicht müde. ", "Sie haben den ganzen Tag gearbeitet, während die Mädchen vor dem Spiegel fröhliche Gesichter einstudierten, die am Ende doch nur wirken wie von einem Begeisterungsgenerator ausgeworfen, der wegen eines Kurzschlusses aus dem Fundus der Clownsschule aussortiert wurde.", "\n\nOft wollen die Leute auch einfach nur in Ruhe aus dem Fenster starren oder Zeitung lesen. ", "Und da kommen diese beiden Schreihühner in den Wagen und lärmen ohne jede Rücksicht los. ", "Warum kann man das nicht verbieten, genauso wie Satire und Reklame?", "\n\nFrohe Weisen\n\nWie viel edler wirkt da im Vergleich ein alter rumänischer Harmonikaspieler. ", "Schüchtern wird eine frohe Weise gespielt, schön kurz und nicht zu laut, und ganz ohne diese sich selbst lawinenhaft reproduzierende Hysterie der hippen Ruhestörerinnen. ", "Freundlich blitzen die Goldzähne, der Dank für jede kleine Spende kommt vom Herzen. ", "Er musiziert für sein karges Auskommen und nicht für Klicks.", "\n\nDie beiden Damen brauchen kein Geld. ", "Sie wollen nur spielen. ", "Und posen. ", "Und nerven. ", "Sie leben nur von Luft und Likes. ", "Ihr Nektar ist ihre geil authentische Selbstbesoffenheit, ihr Manna die Bewunderung einer gleichgeschalteten Masse besinnungsloser Netzklatschaffen, die die Kommentarspalten zum Video mit postanalphabetischem Kack vollspammen: Das ist alles so super, so wahnsinnig super, supi geradezu, supersüß, lolwhat.", "\n\nBegeisterungstaliban\n\nWer die Mädels und ihre Musik weniger super findet oder gar Mitleid mit den zwangsbeglückten Opfern der brutalen Charme-Attacke äußert, ist ein kleingeistiger Lahmarsch. ", "Sie gießen gesammelten Spott über diejenigen S-Bahn-Fahrgäste aus, die vornehm und still dasitzen – mit einem „Stock im Arsch“ hier, und einem „typisch deutsch“ dort, zieht die Begeisterungstaliban ausgerechnet über die einzig wahren Helden des Filmchens her.", "\n\nHelden nämlich, weil es ihnen gelingt, als Einzige so etwas wie Haltung und Würde zu bewahren und zugleich angesichts der massiven Belästigung nicht auszuflippen. ", "Sie lassen sich nicht provozieren, glauben weiter an ein Grundrecht auf schlechte Laune und die konstruktive Kraft des Negativen.", "\n\nDie hohlen Fun-Typen können vielleicht ihre Ohren, Nerven und schließlich ihre Körper töten, doch niemals ihre unsterblichen Misanthropenseelen." ]

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[ "Introduction {#Sec1}\n============\n\nAlzheimer's disease (AD) is the most common form of dementia. ", "The prevalence of AD is strongly correlated with increasing age, and is a consequence of progressive neurodegeneration occurring over a period of several years, or even decades. ", "This neurodegeneration leads to a gradual decline in cognitive, functional and behavioural processes, producing characteristic symptoms such as memory loss, confusion, agitation, and difficulties performing the activities of daily living. ", "The symptoms become more severe over time, creating a decline in independence and an increasing reliance on caregiver support. ", "By the end stages of AD, the patient is frequently bedridden, with substantial impairments (if not complete loss) of continence, swallowing, eating, speech, and motor abilities.", "\n\nExtensive research into the underlying disease processes of AD has identified common pathological changes, with a leading hypothesis centring on neurotoxic protein deposits in the brain (amyloid plaques, neurofibrillary tangles). ", "These are accompanied by disruptions in neurotransmitter levels, neuronal cell death, and brain (cortical) atrophy. ", "Amyloid plaques consisting mainly of insoluble amyloid-beta peptide, and are a key histopathological feature of the AD brain. ", "However, it has been proposed that the soluble oligomers of amyloid-beta, rather than the insoluble deposits, are primarily responsible for neurodegeneration and the impairment of synaptic function---including an effect on glutamatergic signalling pathways (see below) (De Felice et al. [", "@CR21]; Lacor et al. [", "@CR54]). ", "Subsequently, pathological changes in neurotransmission can be associated with the characteristic clinical symptoms observed in AD. ", "For example, in AD, there are impairments in glutamatergic and cholinergic signalling, which are involved in learning and memory processes in healthy individuals. ", "Dysfunction in the glutamatergic system may lead to direct impairment of cognition and, in the long term, neuronal loss. ", "Glutamate is responsible for approximately 70 % of the excitatory neurotransmission in the central nervous system (CNS), particularly in the cortical and hippocampal regions (Danysz et al. [", "@CR19]). ", "When the *N*-methyl-[d]{.smallcaps}-aspartate (NMDA) receptor is activated by glutamate, calcium (Ca^2+^) ions flow into the post-synaptic neurone (Dingledine et al. [", "@CR24]). ", "In a normal physiological situation, this triggers a signalling cascade that produces synaptic plasticity such as long-term potentiation (LTP) (Cacabelos et al. [", "@CR12]), and thereby facilitates the higher order processes of learning and memory. ", "According to some hypotheses, in AD, NMDA receptors are constantly over-activated, leading to sustained Ca^2+^ influx (Cacabelos et al. [", "@CR12]; Danysz and Parsons [@CR18]; Parsons et al. [", "@CR71]). ", "This creates a pathological 'background noise' against which normal physiological glutamate signalling cannot be detected (Danysz and Parsons [@CR18]). ", "Furthermore, prolonged Ca^2+^ overload in the post-synaptic neurones generates a form of 'slow excitotoxicity', producing a gradual neurodegenerative effect (Cacabelos et al. [", "@CR12]; Danysz and Parsons [@CR18]; Kornhuber and Weller [@CR52]; Lancelot and Beal [@CR55]; Parsons et al. [", "@CR72]). ", "It is probable that this pathological over-activity is due to increased resting glutamate concentrations, as well as increased receptor sensitivity to resting glutamate levels (Albin and Greenamyre [@CR1]; Danysz and Parsons [@CR18]). ", "Certainly, some evidence suggests that various toxins, acting through NMDA receptors, e.g. amyloid-beta oligomers, can produce increased sensitivity and/or tonic activity of glutamate receptors, leading to neuronal death (De Felice et al. [", "@CR21]; Lacor et al. [", "@CR54]; Nyakas et al. [", "@CR69]; Szegedi et al. [", "@CR88]; Wenk et al. [", "@CR101]; Wu et al. [", "@CR108]) and decreasing synaptic plasticity (Nakagami and Oda [@CR65]). ", "In addition to this glutamatergic pathology, amyloid-beta peptides have also been shown to depress the release, synthesis, and axonal transport of acetylcholine (ACh) (Auld et al. [", "@CR7]; Nyakas et al. [", "@CR69]).", "\n\nCholinergic dysfunction in the basal and rostral forebrain is associated with even early cognitive impairments observed in AD, correlates with cognitive decline, and forms the basis of the 'cholinergic hypothesis' of AD (Perry et al. [", "@CR79]; Terry and Buccafusco [@CR91]). ", "The involvement of the cholinergic system in AD was further strengthened by preclinical studies in which cholinergic antagonists were shown to impair memory in animals, and studies in which damage/lesions that interfered with cholinergic input from the basal forebrain (to the neocortex and hippocampus) led to memory deficits in both animals and humans (reviewed in Terry and Buccafusco [@CR91]). ", "In humans, several studies of scopolamine (a pan-muscarinic receptor antagonist) have indicated that cholinergic neurotransmission is pivotal to normal memory acquisition, facilitating immediate recall (Drachman [@CR25]; Mewaldt and Ghoneim [@CR61]; Petersen [@CR80])---possibly by preventing proactive interference between stored information and new memory (Atri et al. [", "@CR4]). ", "Furthermore, analyses of biopsy samples from the neocortex found that choline uptake, choline acetyltransferase activity and resulting ACh synthesis were all markedly reduced in patients with AD---indicating a loss of presynaptic cholinergic nerve endings (Sims et al. [", "@CR87]). ", "Overall, it is hypothesised that the degeneration of cholinergic neurones leads to a decline in the level of ACh, and the resulting weakened signalling contributes to cognitive decline and memory impairment in AD (Francis et al. [", "@CR32]; Sims et al. [", "@CR87]; Terry and Buccafusco [@CR91]; Turrini et al. [", "@CR93]). ", "In addition, AD brains have a reduced number of cholinergic neuronal nicotinic receptor ion channels (α7 and α4β2) (Nordberg [@CR68]) and functional uncoupling of cholinergic muscarinic M1 (G-protein coupled) receptors (Joseph et al. [", "@CR47]; Thathiah and De Strooper [@CR92]).", "\n\nReflecting these pathological patterns, the two drug classes currently available for the treatment of AD are the uncompetitive NMDA receptor antagonist, memantine (which normalises dysfunctional glutamatergic neurotransmission), and acetylcholinesterase inhibitors (AChEIs: donepezil, galanthamine and rivastigmine, which all raise ACh levels). ", "As monotherapies, these drug types have demonstrated significant symptomatic efficacy in AD, and existing clinical data suggest that their combined use may bring additional benefit. ", "For example, in a randomised, controlled clinical study of patients with moderate to severe AD, treatment with memantine and donepezil produced significant symptomatic (cognitive, functional, behavioural and global) advantages over donepezil monotherapy (Tariot et al. [", "@CR90]). ", "There are also indications that combined treatment could produce long-term benefits, and favourably influence time to nursing home admission (Atri et al. [", "@CR5]; Lopez et al. [", "@CR56]).", "\n\nHere, we discuss the potential mechanisms that may underlie these clinical observations, including the scientific rationale for targeting two different neurotransmitter systems to achieve additive clinical effects.", "\n\nMechanism of Action: Memantine {#Sec2}\n------------------------------\n\nMemantine is indicated for the treatment of patients with moderate to severe AD, and has shown significant symptomatic efficacy in several large-scale, controlled clinical studies (Reisberg et al. [", "@CR83]; Tariot et al. [", "@CR90]; Winblad et al. [", "@CR107]). ", "There is also evidence that memantine may be effective in delaying clinical worsening, and decreasing the emergence of behavioural symptoms including agitation and aggression (Wilcock et al. [", "@CR103]; Wilkinson and Andersen [@CR104]).", "\n\nMemantine has been characterised as an uncompetitive, voltage-dependent NMDA receptor antagonist, with moderate binding affinity, and rapid blocking--unblocking receptor kinetics (Danysz et al. [", "@CR19]; Parsons et al. [", "@CR71]). ", "This unique binding profile enables memantine to integrate in the glutamatergic signalling system, and influence dysfunctional NMDA receptor activation in AD. ", "Under normal, resting, physiological conditions, NMDA receptor channels are blocked by magnesium (Mg^2+^) ions. ", "Upon the arrival of a strong transient glutamate synaptic signal, the post-synaptic membrane becomes depolarised, relieving the voltage-dependent Mg^2+^ channel block, and the NMDA channel opens to allow Ca^2+^ ion flow into the post-synaptic neurone. ", "However, it has been suggested that in AD, due to glutamate and amyloid-beta driven constant low-level stimulation there is a decrease in membrane potential, removing the NMDA receptor channel blockade by Mg^2+^ ions, increasing the continuous flow of Ca^2+^ ions into the post-synaptic neurone, and thereby creating a 'background noise' of stimulation at rest. ", "Electrophysiological studies have indicated that memantine binds within the ion channel of the NMDA receptor (Chen et al. [", "@CR15]; Parsons et al. [", "@CR71]). ", "Importantly, memantine binds with moderate affinity and voltage dependency, which means that at moderate levels of prolonged stimulation (i.e. under pathological conditions) memantine continues to block the NMDA receptor channel---unlike the weaker binding Mg^2+^ ion (Albrecht et al. [", "@CR2]; Parsons et al. [", "@CR71], [@CR73], [@CR75]). ", "However, when high concentrations of glutamate are transiently present (i.e. when a physiological signal arrives), memantine dissociates from the receptor, and normal neurotransmission proceeds (Albrecht et al. [", "@CR2]; Frankiewicz and Parsons [@CR34]; Parsons et al. [", "@CR73], [@CR75]). ", "Thus, in AD, memantine may reduce the pathological 'background noise' of dysfunctional glutamate signalling, allowing physiological signals to be better distinguished (Danysz et al. [", "@CR19]). ", "Furthermore, in vivo and in vitro testing has shown that this effect translates into a reversal of learning impairments induced by over-activation of NMDA receptors (e.g. Zajaczkowski et al. [", "@CR111]).", "\n\nIn addition to this facilitation of signalling processes, preclinical investigations indicate that memantine's mechanism may also serve to protect neurones from the excitotoxicity of excessive glutamate stimulation. ", "This has been demonstrated in vitro (Parsons et al. [", "@CR73], [@CR74]), and in vivo where memantine protected against excitotoxicity induced by direct or indirect over-activation of NMDA receptors (Keilhoff and Wolf [@CR48]; Misztal et al. [", "@CR63]; Wenk et al. [", "@CR98], [@CR99]; Willard et al. [", "@CR106]).", "\n\nAs mentioned earlier, the presence of amyloid-beta has been linked with pathological effects on the glutamatergic system, indirectly triggering excess tonic levels of glutamate in and around the synaptic cleft by inhibiting the astroglial glutamate transporter (Nyakas et al. [", "@CR69]) and reducing glutamate reuptake (Harris et al. [", "@CR43]; Noda et al. [", "@CR67]). ", "According to some authors, amyloid-beta peptides may also stimulate NMDA receptors either as a direct agonist, or secondary to interactions with, e.g. post-synaptic anchoring proteins (De Felice et al. [", "@CR21]; Mattson et al. [", "@CR59]; Szegedi et al. [", "@CR88]; Wu et al. [", "@CR108]).", "\n\nLinking in with the 'amyloid-beta hypothesis', memantine has been shown to protect against pathological changes and learning deterioration induced by intra-hippocampal injection of amyloid-beta (Miguel-Hidalgo et al. [", "@CR62]). ", "Moreover, memantine restored deficits in cognition, and reduced levels of insoluble and soluble amyloid-beta peptide in triple-transgenic mice with AD-like pathology (Martinez-Coria et al. [", "@CR58]). ", "Memantine has also specifically demonstrated protection against amyloid-beta-induced synaptic deterioration (Lacor et al. [", "@CR54]) and generation of reactive oxygen species (De Felice et al. [", "@CR21]; Klein et al. [", "@CR50]). ", "Despite these findings the way in which memantine's mechanisms link to its clinical efficacy in AD has still not been fully characterised.", "\n\nMechanism of Action: Acetylcholinesterase Inhibitors {#Sec3}\n----------------------------------------------------\n\nThe AChEIs (donepezil, galanthamine and rivastigmine) are indicated for the treatment of AD from the mild stages onwards (Birks [@CR11]; Wilkinson et al. [", "@CR105]). ", "By inhibiting the action of the ACh-hydrolyzing enzyme acetylcholinesterase (AChE---the predominant cholinesterase in the brain), the AChEIs aim to boost ACh levels and thus alleviate disease symptoms associated with the progressive loss of cholinergic function in AD. ", "Studies have shown that lowered synthesis of ACh (including reduced choline acetyltransferase activity, required for ACh synthesis) is associated with greater cognitive impairment in dementia, including AD (Francis et al. [", "@CR32]; Perry et al. [", "@CR78]). ", "In contrast, raised ACh concentrations in the brain have been shown to increase the expression of nicotinic ACh receptors on cholinoceptive neurones (Barnes et al. [", "@CR8]), and are also linked to improved function of other neurotransmitter systems associated with cognitive function, e.g. glutamate (Dijk et al. [", "@CR23]; Francis et al. [", "@CR33]). ", "Therefore, AChE inhibition was identified as a useful therapeutic strategy to enhance cholinergic neurotransmission, even though patients with advanced AD show reductions in AChE levels of up to 90 % (Giacobini [@CR36]). ", "Clinical support for this treatment approach comes from multiple clinical studies in which AChEIs have benefited patients' cognitive, functional and global status (Birks [@CR11]). ", "However, despite clear evidence of efficacy in the clinical setting, the exact mechanisms and pathways that link AChE inhibition and ACh activity with symptomatic improvements in AD are not fully understood.", "\n\nAlthough the three AChEIs display no notable differences in their clinical efficacy (Birks [@CR11]), their underlying mechanisms can be distinguished in terms of target protein specificity. ", "Donepezil is a specific and reversible inhibitor of AChE (Davidsson et al. [", "@CR20]; Wilkinson et al. [", "@CR105]), and also independently interacts with neuronal nicotinic ACh receptors (Di Angelantonio et al. [", "@CR22]). ", "In contrast, rivastigmine is a pseudo-irreversible inhibitor of AChE (Davidsson et al. [", "@CR20]; Weinstock [@CR97]) (i.e. via a temporary covalent bond), and has a similar level of affinity for butyrylcholinesterase (BuChE) (Weinstock [@CR97]; Wilkinson et al. [", "@CR105]). ", "BuChE is a non-specific enzyme that can hydrolyse ACh and other choline esters, and which is most predominant outside the CNS, with brain levels increasing in severe AD (Giacobini et al. [", "@CR37]; Weinstock [@CR97]; Wilkinson et al. [", "@CR105]). ", "Galanthamine is a selective, reversible inhibitor of AChE and is claimed to enhance the intrinsic action of ACh on nicotinic receptors, with a potential link to amyloid-beta clearance (Popa et al. [", "@CR81]; Takata et al. [", "@CR89]; Wilkinson et al. [", "@CR105])---although this latter effect is controversial. ", "It does not seem that these different specificities contribute substantially to any differentiation in the therapeutic effects of the AChEIs (Wattmo et al. [", "@CR96]).", "\n\nCombining the Action of Memantine and the AChEIs {#Sec4}\n------------------------------------------------\n\nAs described above, memantine and the AChEIs target two different pathological aspects of AD---the dysfunctional glutamatergic and cholinergic transmitter systems, respectively. ", "The combined use of memantine and an AChEI in the treatment of AD is therefore a logical, rational approach, although the underlying mechanisms and interactions are likely to be complex and partially reciprocal as their signalling pathways are interconnected and multiplexed.", "\n\n### Connections in the Glutamatergic and Cholinergic Pathways {#Sec5}\n\nThere is considerable evidence supporting the link between the cholinergic and glutamatergic pathways, including their relationship in the pathology of AD. ", "Glutamatergic neurones in the amygdala, reticular formation, hippocampus and cerebral cortex make synaptic connections with cholinergic neurones located in the medial septum, diagonal band of Broca and the nucleus basalis of Meynert (NbM). ", "These cholinergic neurones, in turn, innervate the neocortex and hippocampus (Fig.", " [1](#Fig1){ref-type=\"fig\"}a) (Bigl et al. [", "@CR10]; Carnes et al. [", "@CR14]; Fadel et al. [", "@CR28]; Fournier et al. [", "@CR31]; Francis et al. [", "@CR32], [@CR33]; Mesulam and Mufson [@CR60]; Moor et al. [", "@CR64]; Wu et al. [", "@CR109]). ", "There is also evidence that synaptic activation of NMDA receptors stimulates synaptic ACh release from basal forebrain neurones (Fournier et al. [", "@CR31]; Moor et al. [", "@CR64]), although these findings are somewhat controversial (Fadel et al. [", "@CR28]; Giovannini et al. [", "@CR39]). ", "In addition, some 'cholinergic' neurones of the basal forebrain appear to release both ACh and glutamate (Allen et al. [", "@CR3]).Fig.", " 1Links between the glutamatergic and cholinergic pathways\n\nEnhancement of ACh transmission and/or activation of nicotinic/muscarinic acetylcholine receptors increases LTP in most regions of the hippocampus, where glutamatergic pyramidal neurones provide the major intrinsic projection pathways (Drever et al. [", "@CR26]; Kenney and Gould [@CR49]). ", "NMDA, amyloid-beta, and a decrease in Mg^2+^ ions, all impair LTP in the hippocampus; an effect that is prevented by the action of memantine (Frankiewicz and Parsons [@CR34]; Klyubin et al. [", "@CR51]; Martinez-Coria et al. [", "@CR58]; Parsons et al. [", "@CR73]).", "\n\nIn terms of neurodegeneration, excessive activation of glutamate receptors (particularly NMDA-type receptors) has been implicated in processes underlying the degeneration of cholinergic cells in AD (Greenamyre and Young [@CR40]). ", "For example, neuronal degeneration caused by direct injection of NMDA into the rat basal forebrain leads to reduced levels of choline acetyltransferase activity in the cortex, and this effect is prevented by memantine (Wenk et al. [", "@CR98], [@CR99]). ", "Furthermore, memantine rescues basal forebrain cholinergic neurones from the toxic effects of amyloid-beta peptides, and attenuates amyloid-beta-induced cholinergic fibre loss in the parietal neocortex (Fig.", " [1](#Fig1){ref-type=\"fig\"}b) (Nyakas et al. [", "@CR69]).", "\n\nTherefore, it seems that cholinergic neurones are vulnerable to the hyperactivity of the glutamate/NMDA receptor system, while glutamatergic neurones may be both the cause and the subsequent target of neuronal degeneration.", "\n\n### Preclinical Data on the Combined Action of Memantine and the AChEIs {#Sec6}\n\nIn light of the interplay between the glutamatergic and cholinergic pathways, the combined use of memantine and the AChEIs has been examined in several preclinical studies. ", "Importantly, investigations in vitro, in vivo and ex vivo have shown that memantine does not attenuate the AChE blockade produced by therapeutically relevant concentrations of clinically used AChEIs (Enz and Gentsch [@CR27]; Gupta and Dekundy [@CR42]; Wenk et al. [", "@CR100]).", "\n\nWith regard to combined efficacy, the effect of memantine plus donepezil on cognitive deficits was examined in triple-transgenic mice exhibiting cognitive impairment and high brain levels of amyloid-beta plaques and neurofibrillary tangles (Martinez-Coria et al. [", "@CR57]). ", "In 6- and 15-month-old transgenic mice, memantine, and the combination of donepezil and memantine, significantly improved spatial memory (acquisition and retention) (Martinez-Coria et al. [", "@CR57]). ", "Donepezil treatment alone significantly improved the retention (but not the acquisition) of spatial memory in younger mice, but no significant effects were seen in older mice (Martinez-Coria et al. [", "@CR57]). ", "In both age groups, the memantine--donepezil combination was the only treatment that significantly improved latency to reaching the platform location (Martinez-Coria et al. [", "@CR57]).", "\n\nThe combined effects of memantine and donepezil on spatial memory were also specifically examined in the APP23 mouse model using a complex dry-land maze test (Neumeister and Riepe [@CR66]). ", "In 4.5-month-old APP23 mice with cognitive deficits, treatment with memantine plus donepezil produced significant improvements in both resting time and moving time, which were greater than those observed with either treatment alone (Neumeister and Riepe [@CR66]). ", "Notably, treatment with memantine alone produced a significant improvement in resting time, but not moving time, and donepezil treatment improved moving time, but not resting time (Neumeister and Riepe [@CR66]). ", "These findings led the authors to suggest that combination treatment with memantine and donepezil was exerting a synergistic effect on spatial learning ability in these animals, with the individual drugs acting differentially: memantine addressing resting time (possibly reflecting memory retrieval), and donepezil influencing moving time (possibly reflecting memory acquisition) (Neumeister and Riepe [@CR66]).", "\n\n### 3-Neurone Model {#Sec7}\n\nBased on available preclinical evidence of the actions of memantine and the AChEIs, the 3-neurone model is proposed to explain the better efficacy of combination treatment.", "\n\nIt is established that memantine and the AChEIs intervene at separate points of the disrupted signalling cascades in AD. ", "Acting at the NMDA receptor, memantine lowers the pathologically increased tonic level of excitation of the glutamatergic synapse at rest (neurone 2---see Fig.", " [2](#Fig2){ref-type=\"fig\"}). ", "This is likely to have a twofold impact: firstly, it reduces the background noise, so that incoming physiological signals can be better distinguished; secondly, it reduces the constant pathological influx of Ca^2+^, and thereby helps to prevent the neurone being stimulated in a way that would cause both dysfunction, synaptotoxicity and ultimately cell death (neurone 2) (Parsons et al. [", "@CR73], [@CR75]). ", "Overall, tonic NMDA receptor activation is reduced, which delays the neurodegeneration of cholinergic neurones bearing NMDA receptors, and synaptic NMDA receptor activation is facilitated (Fig.", " [3](#Fig3){ref-type=\"fig\"}). ", "Supplementing this effect, the AChEIs may serve to amplify (i.e. bring towards normal) the pathologically weakened signal from cholinergic neurones by delaying ACh breakdown at cholinergic nerve endings (reviewed in Palmer and Gershon [@CR70]). ", "In this way, neurotransmission (to neurone 3) is preserved, with the improved signal detected against the lowered background noise (Fig.", " [2](#Fig2){ref-type=\"fig\"}). ", "Together, such effects would help to maintain the glutamatergic/cholinergic signalling cascades, and consequently facilitate LTP and memory processes.", "Fig.", " 2The '3-neurone model' for the action of memantine and the AChEIs in ADFig.", " 3Schematic showing the proposed effect of memantine on the activity of NMDA\n\nClearly, this model is an integrated and simplified view of what is known to be a highly complex system. ", "In particular, the 3-neurone model does not take into account that neurotransmission is unlikely to be a simple one-directional process. ", "In practice, glutamatergic neurones not only make synaptic connections with cholinergic neurones, but cholinergic neurones also influence glutamatergic transmission in areas such as the cortex and hippocampus. ", "Therefore, applied together, memantine and AChEIs have the potential to act at different places in interconnected pathways, with complementary mechanisms potentially producing additive effects opposing disease pathology. ", "In addition to this restoration of function, memantine also appears to protect against excitotoxicity and therefore consequent neurodegeneration.", "\n\nClinical Implications {#Sec8}\n---------------------\n\nIt is well documented that the glutamatergic and cholinergic neuronal systems influence each other, and that their joint dysfunction is central to the effects produced by AD pathology. ", "Consequently, the combined use of memantine and an AChEI to address these two pathological aspects of AD would appear to be a highly rational approach to treatment. ", "From a pharmacodynamic perspective, combining two different drug mechanisms is a recognised means of increasing overall effect size, via a synergistic or additive interaction. ", "This is schematically illustrated in Fig.", " [4](#Fig4){ref-type=\"fig\"}, which shows how combining memantine and the AChEIs could produce a greater clinical effect size without exceeding the individual dose-limiting boundaries for either drug. ", "Beyond this, preclinical studies also indicate that memantine may confer a neuroprotective benefit.", "Fig.", " 4Schematic illustration of the hypothesised clinical effect size with combined memantine and AChEI treatment\n\nIt is interesting to note that in monotherapy, memantine and the AChEIs appear to have additional positive effects on some differing behavioural domains---memantine producing improvements in agitation/aggression and delusions (Gauthier et al. [", "@CR35]), and AChEIs (donepezil) affecting the domains of depression, anxiety and apathy (Feldman et al. [", "@CR29]). ", "This would seem to be further evidence (albeit indirect) that the two drugs do not act via the same mechanisms, or exclusively within the same pathways/brain regions.", "\n\nIn practice, the application of combination treatment in AD obviously relies upon proven safety and efficacy in the clinical setting. ", "Drug interaction studies in healthy adults (Periclou et al. [", "@CR77]; Yao et al. [", "@CR110]) and in patients with AD (Shua-Haim et al. [", "@CR86]) have shown a lack of pharmacokinetic interactions between memantine and each of the AChEIs. ", "Combination treatment has also proven to be well tolerated in randomised, controlled studies of patients at all stages of AD (Porsteinsson et al. [", "@CR82]; Tariot et al. [", "@CR90]; Grossberg et al. [", "@CR41]; Howard et al. [", "@CR46]), as well as in post-marketing surveillance of dementia patients in German clinical practice (Hartmann and Möbius [@CR44]). ", "Indeed, some gastrointestinal side effects of the AChEIs (diarrhoea, faecal incontinence, nausea) have been reported less frequently with combination treatment (Tariot et al. [", "@CR90]) and discontinuation rates after 24 weeks are also decreased compared with AChEI monotherapy (Porsteinsson et al. [", "@CR82]; Tariot et al. [", "@CR90]). ", "The pooled analysis of two randomised, controlled 24-week studies has shown a similar incidence of adverse events in patients treated with the combination of memantine and donepezil and in patients treated with placebo and donepezil (Atri et al. [", "@CR6]). ", "Interestingly, this pooled analysis, performed in patients with moderate to severe AD, has also shown that the frequency of agitation was approximately two times less in the memantine/donepezil combination treatment group compared to placebo/donepezil group.", "\n\nIn terms of efficacy, several large-scale clinical studies have included patients receiving combination treatment, and shown favourable outcomes (Tariot et al. [", "@CR90]; Atri et al. [", "@CR5]; Lopez et al. [", "@CR56]; Grossberg et al. [", "@CR41]). ", "In one randomised, double-blind controlled study in 404 patients with moderate to severe AD, treatment with memantine and donepezil produced significant benefits across cognitive, functional, behavioural and global domains, when compared with donepezil monotherapy (Tariot et al. [", "@CR90]). ", "Post hoc analyses of this study revealed the superiority of combination treatment over AChEI monotherapy in specific areas such as language and memory (Schmitt et al. [", "@CR85]), toileting and higher-level functions (Feldman et al. [", "@CR30]), and agitation/aggression and irritability (including decreased symptom emergence) (Cummings et al. [", "@CR16]; Gauthier et al. [", "@CR35]). ", "In addition, more patients responded with symptom improvement or stabilisation in the combination treatment group than in the group receiving monotherapy with donepezil (van Dyck et al. [", "@CR94]).", "\n\nDifferent results were reported when memantine/AChEI treatment was investigated in a randomised, double-blind controlled study in 433 patients with mild to moderate AD, in which the combination was not found to be statistically superior to AChEI monotherapy (Porsteinsson et al. [", "@CR82]). ", "The apparently contradictory results from these two studies (Tariot et al. [", "@CR90]; Porsteinsson et al. [", "@CR82]) have led to some uncertainties in recommendation of the combination treatment as reflected in the EFNS guidelines for the diagnosis and management of AD (Hort et al. [", "@CR45]). ", "However, patients included in the study published by Porsteinsson et al. ([", "@CR82]) had a mild to moderate degree of AD compared to moderate to severe disease severity in the study published by Tariot et al. ([", "@CR90]). ", "It should be noted that memantine is not approved for the treatment of mild AD, neither in the European Union nor in the USA or Japan. ", "In order to address the differences in study populations of these two studies (Tariot et al. [", "@CR90]; Porsteinsson et al. [", "@CR82]), a post hoc meta-analysis was performed. ", "In this analysis, in which patients with mild AD were excluded, significant benefits of the combination treatment compared to donepezil monotherapy were seen for patients with moderate to severe AD (Atri et al. [", "@CR6]). ", "This analysis provides further support that the combination treatment is the most effective in moderate to severe AD patients.", "\n\nA randomised, double-blind controlled clinical study with 677 moderate to severe AD patients which investigated an extended release formulation of memantine 28 mg in combination with an AChEI compared to AChEI alone has, again, shown statistically significant treatment effects favouring combination treatment (Grossberg et al. [", "@CR41]; Bassil et al. [", "@CR9]).", "\n\nThe most recent randomised, controlled clinical study investigated what happens to the patients with moderate to severe AD treated with donepezil when: (a) memantine was added to the existing donepezil therapy (combination treatment group); (b) existing donepezil monotherapy was continued (donepezil monotherapy treatment group); (c) memantine was introduced to the patients and donepezil was discontinued (memantine monotherapy treatment group) and (d) donepezil was discontinued without introduction of memantine (placebo treatment group) (Howard et al. [", "@CR46]). ", "Due to recruitment difficulties, the initially calculated sample size of 800 patients had to be reduced to 295 recruited patients. ", "In addition, there was a high and disproportionate treatment discontinuation rate (approximately 60 %), leaving only 20 patients in the placebo arm and 38 patients in the combination arm at end of study (week 52). ", "Yet, despite these limitations, the best treatment effects, seen in both primary efficacy parameters (cognition and activities of daily living), were achieved in the combination treatment group at week 30 and were still present at week 52 (although no longer statistically significant for the given small sample size).", "\n\nRegarding disease progression, pooling clinical data from two randomised controlled studies showed that combination therapy could significantly reduce the occurrence of marked clinical worsening in patients with moderate to severe AD, as compared with AChEI monotherapy (Wilkinson and Andersen [@CR104]; Atri et al. [", "@CR6]). ", "Consistent with this, observational studies found that combination treatment appeared to slow cognitive and functional decline in the long term (modelled progression over 4 years vs AChEI treatment alone) (Atri et al. [", "@CR5]), and may delay time to nursing home admission (Lopez et al. [", "@CR56]). ", "Interestingly, an open-label study also showed that the majority of patients with moderately severe AD, who had continued cognitive decline with AChEI monotherapy, responded positively (stable/improved Mini-Mental State Examination (MMSE) score) upon addition of memantine (Dantoine et al. [", "@CR17]).", "\n\nBased on the results from the available clinical studies, the authors of a recent clinical review concluded that the combination therapy for AD seems to be safe, well tolerated and may represent the current gold standard for moderate to severe AD (Patel and Grossberg [@CR76]). ", "In another recent clinical review Schmidtke et al*. (*[", "@CR84]) state that combination therapy with memantine and an AChEI should be implemented when the patient progresses from *mild* to *moderate* AD. ", "This has been shown in a recent cohort study, in which 686 patients with mild to moderate AD from 16 specialised clinics in France were followed for 4 years (Gillette-Guyonnet et al. [", "@CR38]). ", "Whereas 89 % of patients were treated with AChEI monotherapy at baseline, 26 % used memantine/AChEI combination therapy by year 4. ", "This is also in accordance with the approved labels, since in Europe AChEIs are approved for the treatment of patients with *mild* AD, whereas both drug groups (AChEIs and memantine) are approved for moderate AD.", "\n\nCombination therapy is already considered in the current clinical practice of AD treatment, but the frequency of its use differ between countries (Calabrese et al. [", "@CR13]; Vidal et al. [", "@CR95]). ", "Variations in the prescription rates of combination therapy between different countries reflect real-life routine clinical practice as well as differences in the reimbursement status in each country. ", "Combination treatment was found to be cost-effective compared with the use of an AChEI alone (Lachaine et al. [", "@CR53]; Weycker et al. [", "@CR102]) and clinical studies clearly provide evidence for its usefulness. ", "However, the major stumbling blocks hindering the recommendation of combination therapy for even more AD patients seem to be cost and the therapeutically nihilistic attitude among many practitioners that current AD therapies are not worth prescribing (Patel and Grossberg [@CR76]). ", "As a consequence, a large number of AD patients might be deprived of the currently best possible treatment. ", "This is of special concern for a devastating condition like AD, for which no cure exists and for which combining existing treatments with different modes of action is a valid approach towards treatment optimisation.", "\n\nIn summary, preclinical data confirm that the combination of two existing treatment mechanisms---memantine and an AChEI---may be a useful approach for the management of AD. ", "The two drugs target different (although interconnected) pathological pathways, and it has been proposed that their complementary activity may produce greater effects than either drug alone. ", "This theory has been borne out by results from the currently available clinical studies of combination therapy, which have demonstrated significant efficacy (beyond that of AChEI monotherapy) and good tolerability in patients with moderate to severe AD.", "\n\nEditorial assistance for this article was provided by Cambridge Medical Communication Ltd.\n\nConflict of interest {#d30e1086}\n====================\n\nThe authors are employees of Merz Pharmaceuticals GmbH, Germany. ", "Editorial assistance was funded by Merz Pharmaceuticals GmbH, Germany.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "All relevant data are within the paper and its Supporting Information files.", "\n\nIntroduction {#sec001}\n============\n\nThe ability to focus on task-relevant events is critical for goal-directed behavior. ", "However, this focus on task-relevant events increases the risk of missing events that may not be task-relevant but are still important. ", "For example, while somebody is in a grocery store looking for apples, the person will respond to the ringing of his or her own mobile phone \\[[@pone.0146567.ref001]\\] and also to that of somebody else's, despite the fact that responding is not relevant for purchasing apples. ", "While responding to task-irrelevant environmental cues may not be useful in the context of ones' goals, it is often unknown whether and when important information may be presented. ", "Therefore, it seems beneficial to have a general system that continuously monitors the environment. ", "Hearing seems particularly useful for this task, because unlike vision, is not restricted to a location in space.", "\n\nTo study this monitoring system in auditory perception, previous research has presented series of tones to examine whether the brain detects deviations in these tone series \\[[@pone.0146567.ref002]\\]. ", "Most studies have employed oddballs: One tone is presented repeatedly (the standard) and is replaced occasionally (e.g., on 20% of trials) by another tone (the deviant). ", "This deviation results in an auditory mismatch negativity (MMN) in the event-related potential (ERP). ", "That is, in the difference ERP (computed as the ERP to deviants minus the ERP to standards), the auditory MMN represents a frontal-central negativity between 100 and 250 ms after tone onset. ", "Two mechanisms for the MMN have been proposed: sensory memory and neural adaptation \\[[@pone.0146567.ref003]\\]. ", "In the traditional view as sensory memory (or similar models such as regularity violation and predictive coding) (for review, see \\[[@pone.0146567.ref003]\\]), the MMN reflects the detection of the mismatch between the auditory sensory memory and the incoming deviant \\[[@pone.0146567.ref002], [@pone.0146567.ref004], [@pone.0146567.ref005]\\]. ", "In terms of neural adaptation, the MMN reflects a less attenuated N1-response to the (infrequent) deviant than the (frequent) standard \\[[@pone.0146567.ref006]\\].", "\n\nThe degree to which the MMN is independent of attention has been debated for several decades \\[[@pone.0146567.ref007], [@pone.0146567.ref008]\\]. ", "In most previous studies, subjects showed an auditory MMN even when they read a book or watched a silent movie \\[[@pone.0146567.ref009]--[@pone.0146567.ref020]\\]. ", "In fact, current guidelines recommend recording the auditory MMN while subjects perform an interesting visual task (e.g., watch a silent movie) and are told to ignore task-irrelevant auditory stimuli \\[[@pone.0146567.ref004]\\]. ", "However, because subjects may not strongly direct their attention on these tasks, the findings cannot be taken as strong evidence that the processing of task-irrelevant tones is independent of attention. ", "Further, because in many studies, the visual stimuli for the main tasks and the tones were presented asynchronously \\[[@pone.0146567.ref009]--[@pone.0146567.ref021]\\], subjects may have shifted their attention between the visual stimuli of the main task and the tones.", "\n\nIn contrast, when subjects performed visual tasks that required them to attend closely to the visual stimuli, the auditory MMN to simultaneously presented task-irrelevant, auditory oddballs decreased (i.e., the MMN amplitude became less negative) in most studies \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\], although one study reported no effect \\[[@pone.0146567.ref027]\\] and another study reported an increase of the MMN \\[[@pone.0146567.ref028]\\]. ", "In all of these studies, participants performed demanding visual tasks that required continuous vigilance. ", "Simultaneously, an oddball task was presented in which the task-irrelevant tones were either a standard tone (on most trials) or a deviant tone. ", "Also, high and low visual demands were tested as different levels of the same task. ", "Further, the trials were presented simultaneously with the visual stimuli to maximize competition between the task-relevant visual stimuli and the task-irrelevant tones. ", "Thus, these studies had a stronger manipulation of attention than other tasks that permitted subjects to simply alternate their attention between the visual task and the tones \\[[@pone.0146567.ref022]\\]. ", "Results for most studies suggest that when the demands of the visual task increased, the amplitude of the auditory MMN decreased \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]. ", "These findings suggest that the processes that elicit the MMN require attentional resources. ", "That is, processes of standard formation and/or deviance detection \\[[@pone.0146567.ref003], [@pone.0146567.ref005], [@pone.0146567.ref029], [@pone.0146567.ref030]\\] or neural adaptation \\[[@pone.0146567.ref003], [@pone.0146567.ref006]\\] are impaired by demanding visual tasks.", "\n\nDespite the apparent decrease of the MMN by visual task demands, an MMN remains even under high visual demands \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]. ", "For example, in a rapid serial visual presentation (RSVP) task, participants had to monitor rapid sequences (at 11.1 Hz) of letters for the occasional numeral \\[[@pone.0146567.ref022]\\]. ", "During low visual demands, target numerals were shown at 100% contrast and distracter letters at 5% contrast (for 90 ms each). ", "During high visual demands, all stimuli were shown at 5% contrast (for 20 ms each). ", "The task-irrelevant tones (standard and deviant) were presented every fourth visual stimulus. ", "Data were analyzed only for tones that preceded the first target numeral, while participants attended the letter stream. ", "Results showed that during the visual task with high demands, the MMN decreased but was not eliminated. ", "This attests to the robustness of the auditory MMN despite increases in visual task demands.", "\n\nHowever, it may be that even stronger manipulations of visual attention might further reduce, if not eliminate the MMN. ", "An extensive line of research has shown that perceptual load decreases processing of distracters \\[[@pone.0146567.ref031]\\]. ", "According to load theory \\[[@pone.0146567.ref032], [@pone.0146567.ref033]\\], attentional resources are limited, and targets and distracters compete for attentional resources. ", "If a main task consumes all of the available attentional resources (i.e., high perceptual load), then attention is not drawn to distracters and they are processed less.", "\n\nIn support of strong effects of perceptual load, high perceptual load decreased sensitivity (as indexed by *d′*) in detecting concurrent tones \\[[@pone.0146567.ref034]\\]. ", "Participants performed a letter identification task (X or N) within a ring of six letters. ", "During low perceptual load, the target letter was shown together with smaller Os, whereas during high perceptual load, the target letter was shown together with other letters (randomly drawn from the set of H, K, M, V, W, and Z). ", "Simultaneous with the onset of the letter ring, a short tone was presented on some trials. ", "Participants were instructed both to detect the tone and to identify the letter. ", "In three experiments (conducted to rule out potential confounds), the sensitivity to detect tones decreased during high load. ", "The authors concluded that these findings suggest that high perceptual load produces inattentional deafness.", "\n\nBecause previous behavioral research suggests that perceptual load decreases distracter processing \\[[@pone.0146567.ref034]\\], the current study used a similar task to study effects of perceptual load on the auditory MMN. ", "As in the original study, participants performed a letter detection task with different levels of visual perceptual load while irrelevant tones were presented simultaneously with the onset of the letter ring. ", "Although we tried to follow the design of the original study as much as possible, several modifications were implemented in order to optimize the task for MMN analysis. ", "First, a tone (either standard or deviant) was presented on each trial. ", "Second, the inter-trial interval (ITI) was reduced to 1 s (from 4.9 s) to increase the number of tone trials and thus, the signal-to-noise ratio for obtaining an MMN. ", "Third, because of the short ITI (1 s), a simpler letter detection task (X) rather than the letter identification task (X or N) was used to ensure reaction times below 1 s (as revealed by pilot testing). ", "Perceptual load was manipulated such that during low load, six identical letters were shown, and during high load, six different letters were shown. ", "Fourth, tone intensity was increased to match intensities used in previous MMN studies in order to maximize sensitivity in obtaining an MMN and to permit comparison of the present MMN results with those in previous studies \\[[@pone.0146567.ref022]--[@pone.0146567.ref028]\\]. ", "Fifth, participants were instructed to ignore the tones (rather than to detect the tones as in the original study). ", "Taken together, our task was not identical to that of Raveh and Lavie but was adapted to optimize it for the measurement of the auditory MMN and to make its parameters comparable (i.e., tone on every trial, rather high tone intensity, and instructions to ignore the tones) to those used in previous MMN studies that manipulated visual task demands \\[[@pone.0146567.ref022]--[@pone.0146567.ref028]\\].", "\n\nIn sum, the present study examined the effects of visual perceptual load on the auditory MMN to task-irrelevant tones. ", "Because perceptual load tasks decrease detection sensitivity to concurrent tones \\[[@pone.0146567.ref034]\\], we predicted that high perceptual load will reduce---if not eliminate---the auditory MMN. ", "Although previous studies \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\] suggested that demanding visual tasks decrease the MMN, we predicted that effects of perceptual load on the auditory MMN may be stronger than those of other manipulations.", "\n\nMaterials and Methods {#sec002}\n=====================\n\nParticipants {#sec003}\n------------\n\nParticipants (*N* = 28; mean age = 25.0, *SD* = 3.3; 9 women) were students from local universities in Stockholm, Sweden. ", "The study was approved by the Stockholm section of the Central Ethical Review Board in Sweden and was conducted in accordance with the guidelines in the Helsinki Declaration. ", "All participants gave written informed consent, were debriefed after the experiment, and were compensated with one movie voucher.", "\n\nMaterials and Procedure {#sec004}\n-----------------------\n\nParticipants performed a speeded letter detection task (detect X) and were instructed to push the space bar whenever an X was shown (20% of trials) (see [Fig 1](#pone.0146567.g001){ref-type=\"fig\"}). ", "On each 1-s trial, a 6-letter ring was shown for 100 ms. ", "The 6 letters were shown at positions 2, 4, 6, 8, 10, and 12 o' clock. ", "A small dot was shown at the center of the letter ring throughout the experiment. ", "Participants were instructed to keep their gaze on this dot while covertly attending to the 6 letters in the ring. ", "The size of each letter was 0.53 x 0.53 degrees (visual angle), the distance between the centers of the letters was 0.98 degrees, and the diameter of the ring (for the centers of the letters) was 3.38 degrees. ", "During low load, the 6 letters were identical, whereas during high load, the 6 letters were different. ", "On each trial, letters were drawn randomly without replacement from the set of H, K, M, N, V, W, and Z. On 20% of the trials (response trials), the letter X was shown (six Xs during low load and one X together with 5 other letters during high load). ", "For each set of five consecutive trials, a response trial occurred only during one of the first three trials (randomly determined). ", "Thus, there were at least 2 nonresponse trials before the next response trial.", "\n\n{#pone.0146567.g001}\n\nParticipants performed 10 blocks of 250 trials each (i.e., 200 nonresponse trials and 50 response trials) with short breaks in between blocks. ", "Between consecutive blocks, low and high load alternated. ", "Each participant started with either low or high load (counterbalanced across participants). ", "In total, participants performed 1000 nonresponse trials and 250 response trials for each load.", "\n\nWhile participants performed the letter detection task, tones were presented simultaneously with the onset of the letter rings. ", "Tones were presented with over-ear headphones (Sennheiser HD 280 Pro). ", "Participants were instructed to ignore the tones. ", "The standard tone (75 ms) and the deviant tone (30 ms) were complex tones with f0 = 500 Hz (higher harmonics at 1000 Hz and 1500 Hz with a drop of 3 dB/harmonic) at 76 dB SPL and with a 5 ms fade in and a 5 ms fade out. ", "Over trials, 20% of tones were deviants during both response trials and nonresponse trials. ", "The number of standard trials in between successive deviants ranged from 2 to 6 (mean = 4 trials). ", "For the 1250 trials in each load, 800 trials were standards and 200 were deviants during nonresponse trials, and 200 were standards and 50 were deviants during response trials. ", "The experiment was programmed in Presentation 14.8 (Neurobehavioral Systems, Albany, CA).", "\n\nBefore the first block, participants practiced the relevant task (low or high load) until they felt that instructions were clear and they were ready to start the main task. ", "At the beginning of each block, between 5 to 8 nonresponse trials with standard tones were presented but were not analyzed.", "\n\nElectroencephalography {#sec005}\n----------------------\n\n### EEG recording {#sec006}\n\nEEG data were recorded only from six electrodes at standard 10/20 positions (Fpz, Fz, Cz, M1, M2, and tip of nose) with an Active Two BioSemi system (BioSemi, Amsterdam, Netherlands). ", "Fpz, Fz, and Cz were recorded with pin electrodes in a 64-electrode EEG cap; and M1, M2, and the tip of the nose were recorded with flat electrodes attached with adhesive disks. ", "Two additional, system-specific electrodes were recorded with pin electrodes in the EEG cap. ", "The CMS (between PO3 and POz) served as the internal reference electrode, and DRL (between POz and PO4) as the ground electrode. ", "Data were sampled at 512 Hz and filtered with a hardware low-pass filter at 104 Hz. ", "No high-pass filter was used. ", "All physiological data was processed offline using the FieldTrip toolbox in MATLAB \\[[@pone.0146567.ref035]\\]. ", "Continuous data were re-referenced to the tip of the nose.", "\n\n### ERP analysis {#sec007}\n\nTo minimize movement artifacts, ERPs were computed only for correct rejections (i.e., nonresponse trials without any button presses) (e.g., \\[[@pone.0146567.ref036], [@pone.0146567.ref037]\\]). ", "Also, standard tones were excluded if they followed immediately after a deviant \\[[@pone.0146567.ref038], [@pone.0146567.ref039]\\]. ", "Epochs were extracted from 100 ms before tone onset to 800 ms after. ", "Each epoch was baseline corrected with the 100-ms interval before tone onset. ", "For each participant, amplitude ranges within individual epochs were extracted, and the distribution of these amplitude ranges across epochs was inspected to exclude apparent outliers. ", "This inspection was blind to the condition (i.e., tone deviance by load) of individual trials. ", "To identify the MMN, a difference wave was computed as the ERP to deviants minus the ERP to standards; in this analysis, low and high load were collapsed. ", "On the basis of visual inspection (see [Results](#sec009){ref-type=\"sec\"} for more information), the MMN was defined between 160 and 220 ms after tone onset. ", "For this interval, mean amplitudes were extracted for Fz and Cz for each condition. ", "Before artifact rejection, at least 637 trials with standard tones and 190 trials with deviant tones were available for each load condition. ", "After artifact rejection, at least 539 trials (i.e., more than 82.5%) with standard tones and 173 trials (i.e., more than 86.5%) with deviant tones were available. ", "For completeness, we also analyzed the data on all trials (i.e., before artifact rejection, there were 1000 standard trials and 250 deviant trials for each load condition). ", "Importantly, the results for the MMN matched those reported below. ", "For example, for the mean MMN amplitudes (i.e., deviant minus standard) at Fz (with nose as reference) between 160 and 220 ms, the mean difference (low load minus high load) was 0.12 μV, 95% CI \\[-0.64, 0.89\\]. ", "These findings suggest that our concern about movement artifacts was unnecessary. ", "Nonetheless, we report results from our (a priori) data processing strategy.", "\n\nData Analysis {#sec008}\n-------------\n\nIn the behavioral analysis, responses faster than 200 ms were excluded. ", "Because the task had a rapid pace (ITI of 1 s), we were concerned that responses faster than 200 ms may be late responses to the previous trial. ", "A 200-ms interval rather than a shorter interval was chosen to ensure that all potentially late responses were excluded. ", "If these late responses were included, then these responses would have artificially decreased performance, as a late response to a target trial would count as a false alarm (on the subsequent trial) as well as a miss (on the current trial). ", "However, when we counted the number of such fast false alarms across all conditions for each subject, the maximum number was 7 (mean = 2.2 trials). ", "Because the maximum number of potential false alarms was 1000, this number seems negligible. ", "Although additional analyses showed that it did not matter for the results whether we included or excluded the fast responses, we report results after excluding responses below 200 ms. ", "Hit rates and false alarm rates were computed for each condition (i.e., tone deviance by load). ", "Signal detection analyses were performed to compute *d′* and *c* \\[[@pone.0146567.ref040]\\]. ", "To avoid floor and ceiling effects on hit and false alarm rates, we added 0.5 trial in the numerator and 1 trial in the denominator \\[[@pone.0146567.ref041]\\].", "\n\nStatistical analyses of our data followed recent guidelines \\[[@pone.0146567.ref042], [@pone.0146567.ref043]\\]. ", "These guidelines advocate against null hypothesis significance testing in favor of estimation. ", "In estimation, the data are used to obtain a point estimate (e.g., observed mean) and an interval estimate (i.e., 95% CI) of the best estimate of the true (population) effect size. ", "Accordingly, the size of the 95% CI provides information about the precision of the estimation \\[[@pone.0146567.ref042], [@pone.0146567.ref043]\\]. ", "Notably, the 95% CI must not be interpreted as the 95% probability that the obtained CI captures the actual effect size \\[[@pone.0146567.ref044]\\]. ", "In practice, the 95% CI should be viewed as our best estimate of the true effect size, given the present data \\[[@pone.0146567.ref043]\\]. ", "This estimate may then be evaluated in relation to previous findings by integrating all studies in a meta-analysis \\[[@pone.0146567.ref042]\\]. ", "Strictly speaking however, this interpretation of CI in terms of precision and likelihood is formally incorrect \\[[@pone.0146567.ref045]\\]. ", "But, when *t* tests are used to evaluate mean differences (as used here), the formally correct *likelihood interval* (size 1/8) is identical to a 96% CI \\[[@pone.0146567.ref046]\\]. ", "For simplicity and to follow current guidelines, we report the 95% CIs but discuss them in terms of likelihood intervals (i.e., the range of values that fit best in predicting the data).", "\n\nResults {#sec009}\n=======\n\n[Table 1](#pone.0146567.t001){ref-type=\"table\"} shows means (and *SD*s) for behavioral performance and mean amplitudes for the four conditions formed by combining the independent variables tone deviance (standard vs. deviant) and perceptual load (low vs. high). [", "Table 2](#pone.0146567.t002){ref-type=\"table\"} shows the results of the repeated-measures ANOVAs for the main effects (i.e., deviance and load) and their interaction. ", "The table also shows each effect size expressed as a mean difference (*M*~diff~) together with the two-tailed 95% CIs \\[[@pone.0146567.ref047]\\]. ", "The interaction between load and tone deviance was captured by the difference score between difference scores \\[[@pone.0146567.ref048]\\]. ", "That is, within each load, a difference score was computed as responses to deviants minus responses to standards. ", "Then, another difference score was computed as the difference score for low load minus the difference score for high load.", "\n\n10.1371/journal.pone.0146567.t001\n\n###### Means (and *SD*s) for behavioral performance and mean amplitudes for the four conditions (deviance by load).", "\n\n![](", "pone.0146567.t001){#pone.0146567.t001g}\n\n Variable Low loadstandard Low load deviant High loadstandard High loaddeviant \n ------------------- ------------------ ------------------ ------------------- ------------------ -------- ------- -------- -------\n *d′* 4.89 0.49 4.70 0.40 3.41 0.87 3.32 0.86\n *c* 0.25 0.20 0.28 0.22 0.87 0.39 0.74 0.42\n RT hits (ms) 447.80 37.79 443.06 36.28 558.62 60.75 552.67 67.23\n Mean amps (μV) \n   Fz (nose) 1.89 2.25 -0.04 2.36 0.62 2.14 -1.27 2.22\n   Cz (nose) 1.74 2.36 0.17 2.43 -0.11 2.02 -1.34 2.20\n   Mastoids (nose) -1.55 1.88 -0.49 1.99 -1.99 1.47 -1.07 1.29\n   Fz (mastoids) 3.44 2.71 0.45 2.21 2.62 2.71 -0.21 2.38\n   Cz (mastoids) 3.29 2.76 0.66 2.29 1.88 2.55 -0.28 2.21\n\n10.1371/journal.pone.0146567.t002\n\n###### Results of repeated-measures ANOVAs with the independent variables Deviance (deviant minus standard), Load (low load minus high load), and their interaction on behavioral performance and mean amplitudes.", "\n\n![](", "pone.0146567.t002){#pone.0146567.t002g}\n\n Variable *F* *p* *M*~diff~ 95% CI \n ----------------- --------- --------- ----------- --------- --------\n *d′* \n   Deviance 8.23 .008 -0.14 -0.24 -0.04\n   Load 107.66 \\< .001 1.44 1.15 1.72\n   Dev x Load 0.96 .335 -0.10 -0.29 0.10\n *c* \n   Deviance 3.61 .068 -0.05 -0.11 0.01\n   Load 48.33 \\< .001 -0.53 -0.69 -0.38\n   Dev x Load 4.54 .042 0.16 0.01 0.31\n RT hits (ms) \n   Deviance 6.78 .015 -5.34 -9.55 -1.13\n   Load 213.38 \\< .001 -110.22 -125.70 -94.74\n   Dev x Load 0.07 .788 1.22 -8.00 10.43\n Fz (nose) \n   Deviance 57.39 \\< .001 -1.91 -2.43 -1.39\n   Load 19.38 \\< .001 1.25 0.67 1.83\n   Dev x Load \\< 0.01 .952 -0.03 -0.91 0.85\n Cz (nose) \n   Deviance 24.33 \\< .001 -1.40 -1.98 -0.82\n   Load 36.99 \\< .001 1.68 1.12 2.25\n   Dev x Load 0.69 .412 -0.33 -1.16 0.49\n Mastoids (nose) \n   Deviance 35.81 \\< .001 1.00 0.65 1.34\n   Load 4.40 .045 0.51 0.01 1.01\n   Dev x Load 0.18 .676 0.14 -0.55 0.84\n Fz (mastoids) \n   Deviance 126.63 \\< .001 -2.91 -3.44 -2.38\n   Load 10.48 .003 0.74 0.27 1.21\n   Dev x Load 0.51 .481 -0.17 -0.66 0.32\n Cz (mastoids) \n   Deviance 71.29 \\< .001 -2.40 -2.98 -1.81\n   Load 25.84 \\< .001 1.17 0.70 1.65\n   Dev x Load 4.47 .044 -0.48 -0.94 -0.01\n\nFor all ANOVAs, *F*(1, 27). ", "Deviance refers to the main effect of deviant minus standard, Load refers to the main effect of low load minus high load, and Dev x Load refers to their interaction (i.e., \\[deviant--standard for low load\\]--\\[deviant--standard for high load\\]). *", "M*~diff~ is the mean difference score of the comparison. ", "It expresses the comparison in its original units (μV) and thus, is an unstandardized effect size measure of the comparison of interest.", "\n\nBehavior {#sec010}\n--------\n\nAs shown in [Table 1](#pone.0146567.t001){ref-type=\"table\"} and confirmed by the repeated-measures ANOVAs ([Table 2](#pone.0146567.t002){ref-type=\"table\"}), compared to high load, low load showed better letter detection performance (i.e., larger *d′* and shorter RTs to hits). ", "Also, compared to standard tones, deviant tones lowered performance slightly (i.e., lower *d′*). ", "Participants were generally more conservative (i.e., *c* was more positive) during high load than low load.", "\n\nEvent-related potentials (MMN) {#sec011}\n------------------------------\n\n[Fig 2](#pone.0146567.g002){ref-type=\"fig\"} shows mean ERP waves for the relevant electrodes, separately for the four conditions (i.e., Deviance x Load). ", "In the comparison of deviants versus standards at around 200 ms after tone onset, the ERPs are relatively negative for deviants versus standards at Fz and Cz (top row) and relatively positive at the mastoids (bottom row). ", "This relative negativity at Fz and Cz with a polarity reversal at the mastoids is a central feature of the MMN (for review, see \\[[@pone.0146567.ref004]\\]). ", "To isolate the MMN for each load condition, the difference waves were computed as deviants minus standards at each level of load.", "\n\n{#pone.0146567.g002}\n\n[Fig 3](#pone.0146567.g003){ref-type=\"fig\"} shows the ERP difference waves (deviants minus standards, referenced to the tip of the nose, with 95% CI) at Fz (top), Cz (middle), and mastoids (bottom) for low and high load (left), the subsequent difference waves between load conditions (middle), and a scatterplot of mean amplitudes (160--220 ms) for low and high load across individuals (right). ", "As shown in the left panel, the MMN was apparent around 200 ms in the negative wave for Fz and Cz (top and middle) and in the positive wave for the mastoids (bottom). ", "In the present analyses, the MMN was defined in terms of the first peak (160 to 220 ms).", "\n\n{#pone.0146567.g003}\n\nNote that Fz and Cz also tended to show a second negative peak at around 240 ms (see [Fig 3](#pone.0146567.g003){ref-type=\"fig\"}). ", "Because the mastoids did not show such a second peak, this second peak is probably an N2b \\[[@pone.0146567.ref049]\\]. ", "The N2b peaks about 250--300 ms after tone onset is often observed when participants attend overtly to the stimuli, but it can also be observed for covert attention \\[[@pone.0146567.ref050]\\]. ", "Thus, the observation that visual task performance was lower when deviants were presented (see Tables [1](#pone.0146567.t001){ref-type=\"table\"} and [2](#pone.0146567.t002){ref-type=\"table\"}) is consistent with the idea that the deviants captured covert attention. ", "Critically, only the first peak showed a polarity reversal over the mastoids; this is typically considered to be an indicator for the genuine MMN \\[[@pone.0146567.ref049]\\]. ", "Further note that no P3a was apparent; that is, there was no relative positivity for deviants versus standards at either Fz or Cz about 250 ms after tone onset (e.g., Zhang et al., ", "2006).", "\n\nAs shown in the left panel and also in the middle panel (i.e., the difference wave between the two load conditions), the MMN was comparable for the two load conditions. ", "That is, the ERP difference wave between high and low load was centered on zero (middle panel), and individual mean MMN amplitudes for low and high load were distributed symmetrically around the central diagonal (right panel).", "\n\n[Fig 4](#pone.0146567.g004){ref-type=\"fig\"} shows mean amplitudes (referenced to the tip of the nose, with 95% CI) between 160--220 ms after tone onset for the four conditions (tone deviance by load) at Fz (left) and Cz (right). ", "As shown in the bottom row, although there was clear evidence for an overall MMN (i.e., deviant minus standard was negative), there was no evidence for an interaction between load and deviance, suggesting that the MMN was comparable during low and high load. ", "As shown in Tables [1](#pone.0146567.t001){ref-type=\"table\"} and [2](#pone.0146567.t002){ref-type=\"table\"}, mean amplitudes for Fz and Cz and the mastoids (when referenced to the tip of the nose) provided no evidence for an interaction between tone deviance and load. ", "For completeness, we also analyzed effects on Fz and Cz when referenced to the mastoids \\[[@pone.0146567.ref023], [@pone.0146567.ref024]\\]. ", "Because of the polarity reversal of the MMN over the mastoids or ears, the mastoids or ears may be used as a reference to maximize sensitivity (for review, see \\[[@pone.0146567.ref004]\\]). ", "Although no interaction was observed for Fz, results provided some evidence for an interaction at Cz. ", "That is, the MMN was relatively more negative during low load (-2.64 μV) than during high load (-2.16 μV), and this difference (-0.48 μV) had a 95% CI of -0.94 and -0.01 (this CI did not include zero, and the effect was thus, significant at *p* \\< .05).", "\n\n![", "Mean amplitudes (referenced to tip of nose) for the four conditions (Deviance x Load) across 160--220 ms after tone onset at Fz (left) and Cz (right).\\\nThe top row shows condition means (95% CI for each variable), and the bottom row shows mean difference scores (95% CI for the differences) between conditions for effects of load (low minus high), tone deviance (deviant minus standard), and the interaction (i.e., \\[deviant--standard at low load\\]--\\[deviant--standard at high load\\]).](pone.0146567.g004){#pone.0146567.g004}\n\nDiscussion {#sec012}\n==========\n\nThe present study used a perceptual load task with visual stimuli that substantially decreased behavioral detection sensitivity to simultaneous, task-irrelevant tones \\[[@pone.0146567.ref034]\\]. ", "Therefore, we predicted that this perceptual load would reduce the auditory MMN to simultaneous, task-irrelevant tones. ", "Results showed that although high perceptual load decreased task performance (lower *d′* and longer RTs to hits), a robust MMN was observed during both low and high perceptual load with no convincing evidence for differences between low and high load.", "\n\nThe present study found an MMN at Fz and Cz (with a polarity reversal at the mastoids) during both low and high perceptual load. ", "However, there was no clear evidence that perceptual load decreased the MMN. ", "These results were obtained when the MMN was measured with the tip of the nose as a reference, as recommended \\[[@pone.0146567.ref004]\\]. ", "We also measured the MMN at Fz and Cz referenced to the mastoids to maximize the size of the MMN (for review, see \\[[@pone.0146567.ref004]\\]). ", "When referenced to the mastoids, the MMN at Cz (but not at Fz) showed a significant effect of load (*p* \\< .05) in that the 95% CI did not include zero (-0.94 to -0.01 μV). ", "However, if visual demands actually changed the MMN by as little as -0.01 μV, then this effect would seem to be as meaningful as no change. ", "Because these findings are tentative at best and were not obtained at the main electrode (i.e., Fz), these findings do not provide convincing evidence that the MMN decreases during high perceptual load.", "\n\nWhereas perceptual load did not seem to affect the MMN, it had large effects on behavioral performance. ", "High perceptual load decreased detection sensitivity (by about 1.5 *SD*) and increased reaction times to hits (by about 110 ms). ", "Notably, [Table 1](#pone.0146567.t001){ref-type=\"table\"} suggests that across loads, detection performance decreased slightly when the concurrent tone was a deviant rather than a standard. ", "This observation matches results for an MMN at both levels of load in that the tones were apparently processed irrespective of load.", "\n\nOne possible argument for the apparent absence of effects of perceptual load on the MMN is that the present level of high perceptual load was not high enough to observe effects on the MMN. ", "Indeed, it is possible that a stronger manipulation of perceptual load might result in clearer effects of perceptual load on the MMN. ", "Unfortunately, a general criticism of load theory \\[[@pone.0146567.ref032], [@pone.0146567.ref033]\\] is that there is no independent criterion for a high level of perceptual load \\[[@pone.0146567.ref051]\\]. ", "As such, the reasoning for effects of load risks becoming circular: If there is an effect of load, then the level of load was high enough. ", "If there is no effect of load, then it was not high enough \\[[@pone.0146567.ref052]\\]. ", "In this study, we used a task that clearly decreased sensitivity (as indexed by *d′*) in detecting concurrent tones \\[[@pone.0146567.ref034]\\], and participants in our study were instructed to ignore the tones. ", "Thus, it seemed reasonable to expect similar (or at least any) effects of perceptual load on the MMN. ", "Also, although we used louder tones than Raveh and Lavie, the present tone intensity was comparable to that used in previous studies on effects of demanding visual tasks on the MMN \\[[@pone.0146567.ref022]--[@pone.0146567.ref028]\\]. ", "Thus, the present findings for perceptual load can be readily compared with findings obtained with other manipulations in this previous MMN research.", "\n\nAnother possible argument for the present findings may be that our main electrodes were positioned only at midline (Fz, Cz) and were thus, insensitive to potential laterality effects. ", "However, laterality effects seem to be most apparent for changes in speech stimuli (phoneme changes) \\[[@pone.0146567.ref002]\\] and for laterally presented stimuli \\[[@pone.0146567.ref053]\\]. ", "Because we used bilateral tones that differed only in duration, laterality effects seem unlikely. ", "In support, similar studies in this field included lateral electrodes but apparently found effects only at midline electrodes \\[[@pone.0146567.ref022], [@pone.0146567.ref024]--[@pone.0146567.ref028]\\]. ", "So, we chose only Fz and Cz and the mastoids because the MMN is captured well by these electrodes (for review, see \\[[@pone.0146567.ref004]\\]). ", "Also, because of limited resources, we decided to use fewer electrodes but run more subjects (our study included 28 subjects whereas previous studies had a mean of 13 subjects, range = 10 to 20).", "\n\nIn terms of null-hypothesis significance testing, the present findings represent so-called null findings in the main analyses (because *p* \\> .05). ", "However, our study design was appropriate, the study was carefully conducted, and our results showed clear evidence for an overall MMN. ", "Therefore, the present results are valid findings. ", "As such, these results should increase our understanding of the effects of visual demands on the MMN by prompting two questions. ", "First, do the present findings show that the effect of perceptual load on the MMN is smaller than that of other, similar visual task demands? ", "According to null-hypothesis significance testing, it may be argued that our study did not find significant effects whereas most previous research apparently did \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]. ", "Thus, we should examine why our study apparently did not find any effect. ", "For example, is it possible that we did not observe an effect because we used duration deviance rather than frequency deviance \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]? ", "Although this reasoning has a long tradition in Psychology, it is problematic because even exact replications of studies that sample from the same population can be expected to vary because of sampling error \\[[@pone.0146567.ref043]\\]. ", "If so, the present findings may not be surprising or noteworthy because they might simply reflect chance variability between studies. ", "Simply put, because of chance, the observed effect sizes in different studies will be bigger or smaller than the true effect size. ", "Thus, it may well be that our study just happened to sample at the lower end of this range. ", "As described below, a heterogeneity analysis within a meta-analysis can address quantitatively if the variability in effect sizes between studies is likely due to chance (i.e., all studies sample from a single effect size population) or if there is reason to believe that there is systematic variability (heterogeneity) between studies (i.e., different effect size populations are sampled). ", "Notably, we originally proposed that the auditory MMN would be reduced more by perceptual load than by other visual task demands. ", "A meta-analysis would also be useful to address this question. ", "Specifically, the meta-analysis should show evidence for systematic variability (heterogeneity) between studies with a stronger decrease of the MMN from perceptual load than other visual tasks. ", "However, the present null findings seem to suggest that if anything, perceptual load had either a weaker or similar effect on the MMN compared to other tasks. ", "The heterogeneity analysis within the meta-analysis will be helpful in distinguishing between these two possibilities.", "\n\nSecond, do the present null findings challenge the idea of effects of visual task demands on the MMN? ", "Because Psychology as a discipline has traditionally published only significant findings, this publication bias produces effect sizes that are overestimated \\[[@pone.0146567.ref054]--[@pone.0146567.ref056]\\]. ", "Accordingly, does the combined evidence across the present findings and previous studies with other visual demanding tasks support the conclusion that the MMN decreases during increased visual task demands?", "\n\nIn sum, a meta-analysis would be useful to quantitatively determine whether or not the present findings differ systematically from previous results, and whether or not the evidence for an effect is changed when present and previous findings are combined \\[[@pone.0146567.ref043], [@pone.0146567.ref057], [@pone.0146567.ref058]\\]. ", "To address these questions, we performed a meta-analysis of the present results together with previous studies that used a similar set-up \\[[@pone.0146567.ref022]--[@pone.0146567.ref028]\\].", "\n\nMeta-analysis {#sec013}\n-------------\n\nWe conducted a meta-analysis (with the ESCI software in \\[[@pone.0146567.ref043]\\]) of the effects of visual task demands on the MMN in the EEG. ", "Inspired by an estimation approach \\[[@pone.0146567.ref042], [@pone.0146567.ref043]\\], we attempted to quantitatively integrate our findings with those of previous studies with meta-analytic tools. ", "Meta-analysis is often viewed as a comprehensive quantitative integration of numerous studies on a rather wide topic. ", "However, meta-analytic tools are already useful to combine results of at least two studies \\[[@pone.0146567.ref043]\\]. ", "Thus, our selective meta-analysis should not be seen as an attempt to review all available evidence on effects on the MMN, but instead an attempt to quantitatively integrate only previous, published studies that closely resembled the present study design. ", "Thus, this meta-analysis was highly selective in that published studies were included only if they used EEG, the visual task demands were continuous and varied between high and low load within the same task, and the task-irrelevant tones were typical standards and deviants (i.e., oddballs) that were presented simultaneously with the visual stimuli. ", "Accordingly, studies were excluded for the following reasons (but are mentioned only once even if they fulfilled several criteria). ", "Studies with other measures such as steady-state evoked potentials, MEG, or fMRI \\[[@pone.0146567.ref059]--[@pone.0146567.ref062]\\], studies in which visual and auditory stimuli were presented asynchronously \\[[@pone.0146567.ref009]--[@pone.0146567.ref021], [@pone.0146567.ref063], [@pone.0146567.ref064]\\], studies in which subjects had to read (see also \\[[@pone.0146567.ref022]\\]) or perform a working memory task \\[[@pone.0146567.ref015], [@pone.0146567.ref018], [@pone.0146567.ref064]--[@pone.0146567.ref066]\\], studies in which different tasks rather than task levels were compared \\[[@pone.0146567.ref017], [@pone.0146567.ref067]--[@pone.0146567.ref069]\\], studies with patterned auditory sequences rather than typical oddballs \\[[@pone.0146567.ref070]\\], and studies of clinical populations \\[[@pone.0146567.ref069], [@pone.0146567.ref071]\\] or altered states of consciousness \\[[@pone.0146567.ref072], [@pone.0146567.ref073]\\].", "\n\nBecause results for electrode Fz were reported in all articles, this meta-analysis focused on mean amplitudes at Fz, consistent with current guidelines \\[[@pone.0146567.ref004]\\]. ", "The MMN amplitude at Fz was recorded between about 100 to 250 ms after stimulus onset and with a reference on the mastoid or ear \\[[@pone.0146567.ref023], [@pone.0146567.ref024]\\], tip of the nose \\[[@pone.0146567.ref022], [@pone.0146567.ref026]--[@pone.0146567.ref028]\\], or the chin \\[[@pone.0146567.ref025]\\]. ", "Thus, this meta-analysis quantifies the published evidence for effects of visual task demands on the auditory MMN in studies that closely resembled the present study design.", "\n\nThe first meta-analysis combined five studies \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]. ", "Although two more studies fit our selection criteria \\[[@pone.0146567.ref027], [@pone.0146567.ref028]\\], they were excluded in this first meta-analysis because the predictions were unclear, as described further below. [", "Table 3](#pone.0146567.t003){ref-type=\"table\"} shows the main statistics that were used for the meta-analysis, and [Fig 5](#pone.0146567.g005){ref-type=\"fig\"} shows a forest plot. ", "In regards to the first five studies, one study \\[[@pone.0146567.ref023]\\] reported only the inferential statistics of the overall ANOVA with three conditions (i.e., for baseline, low load, and high load; with *F* = 4.6 and *p* \\< .05) and did not report inferential statistics for the specific comparison between low and high load. ", "Although the study reported means and standard deviations (see Table 4 in \\[[@pone.0146567.ref023]\\]), the standard deviations refer to the variability within each condition and not to the variability of the difference scores between conditions. ", "However, this variability of difference scores between conditions is critical in order to conduct inferential tests in repeated-measures designs \\[[@pone.0146567.ref043], [@pone.0146567.ref074], [@pone.0146567.ref075]\\]. ", "In an attempt to estimate these data, we generated random data that matched the reported descriptives for the three conditions (see Table 4 in \\[[@pone.0146567.ref023]\\]). ", "This approach worked well to match results for another study \\[[@pone.0146567.ref028]\\], as described below. ", "In contrast, for 20,000 randomly generated data sets that matched the descriptives for the three conditions in the study \\[[@pone.0146567.ref023]\\], the minimum *F* value was 9.5 and the maximum *p* value was .003 (after Greenhouse-Geisser correction). ", "Because we could not simulate matching data, we simply assumed that the specific contrast between low and high load was significant at *p* = .05.", "\n\n{#pone.0146567.g005}\n\n10.1371/journal.pone.0146567.t003\n\n###### Statistics for amplitudes at Fz used in the meta-analysis.", "\n\n![](", "pone.0146567.t003){#pone.0146567.t003g}\n\n Study *N* Low load (μV) High load (μV) Mean Diff (low-high) *SD* Diff *t* 95% CI \n ----------------------------------------------------------------- ----- --------------- ---------------- ---------------------- -------------------------------------------- --------------------------------------------- --------------------------------------------- ---------------------------------------------\n Kramer et al. (", "1995) 10 -1.05 0.19 -1.24 1.73[^a^](#t003fn001){ref-type=\"table-fn\"} -2.26[^a^](#t003fn001){ref-type=\"table-fn\"} -2.48[^a^](#t003fn001){ref-type=\"table-fn\"} -0.01[^a^](#t003fn001){ref-type=\"table-fn\"}\n Singhal et al.(2002) 20 -2.80 -2.40 -0.40 0.81 -2.20 -0.78 -0.02\n Haroush et al. (", "2010) 13 -2.20 -1.87 -0.33 0.61 -1.96 -0.70 0.04\n Yucel et al. (", "2005, JoCN) 13 -2.67 -1.06 -1.61 2.69 -2.16 -3.23 0.01\n Yucel et al. (", "2005 NR) 13 -2.75 -2.14 -0.61 1.13 -1.94 -1.30 0.07\n Muller-Gass et al. (", "2007)[^a^](#t003fn001){ref-type=\"table-fn\"} 9 \\- \\- 0.00 1.51 0.00 -1.16 1.16\n Zhang et al. (", "2006) 11 -1.18 -2.10 0.92 0.79[^a^](#t003fn001){ref-type=\"table-fn\"} 3.84[^a^](#t003fn001){ref-type=\"table-fn\"} 0.39[^a^](#t003fn001){ref-type=\"table-fn\"} 1.45[^a^](#t003fn001){ref-type=\"table-fn\"}\n Present study 28 -1.93 -1.90 -0.03 2.27 -0.06 -0.91 0.85\n\n^a^Values were estimated.", "\n\nIn the meta-analysis with five studies \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\] (see [Fig 5](#pone.0146567.g005){ref-type=\"fig\"}), a random effects analysis (*k* = 5, *N* = 69) showed that the MMN amplitude (i.e., deviant minus standard) was larger (i.e., more negative) during low than high visual demands. ", "That is, for the comparison of MMN during low load minus MMN during high load, the mean amplitude difference = -0.50 μV, 95% CI \\[-0.79, -0.22\\]. ", "Notably, there was no evidence for heterogeneity among the effect sizes, *Q*(4) = 5.34, *p* = .25. ", "The proportion of total variance that reflects variation in true effect size was estimated to be 25% (*I*^2^ = 25.06%). ", "Therefore, evidence from previous studies suggests that visual task demands decrease the auditory MMN.", "\n\nNext, we included our results in the meta-analysis ([Fig 5](#pone.0146567.g005){ref-type=\"fig\"}). ", "Overall results of a random effects analysis (*k* = 6, *N* = 97) confirmed that the MMN was more negative during low than high visual demands, mean difference = -0.46 μV, \\[-0.72, -0.20\\]. ", "There was still no evidence for heterogeneity among the effect sizes, *Q*(5) = 6.28, *p* = .28. ", "The proportion of total variance that reflects variation in true effect size was estimated to be 20% (*I*^2^ = 20.42%). ", "Thus, the present findings fit in well with those of previous research \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\].", "\n\nIn the meta-analyses above, we excluded two studies with visual tracking tasks that involved moving circles \\[[@pone.0146567.ref027], [@pone.0146567.ref028]\\]. ", "In these studies, several moving circles were shown and subjects had to track a subset of these circles while remembering which circles to track. ", "This task differs from that of the other studies \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]. ", "In these previous studies, subjects monitored a radar screen to detect and identify aircrafts during either low or high target density \\[[@pone.0146567.ref023]\\], landed an aircraft while ignoring tones during either low or high turbulence levels \\[[@pone.0146567.ref024]\\], used a joystick to center a moving cursor that changed in velocity (low demand) or acceleration (high demand) \\[[@pone.0146567.ref025], [@pone.0146567.ref026]\\], or monitored a rapid visual stream of letters for two numerals with the stimuli at either low demands (high contrast, long duration) or high demands (low contrast, short duration) \\[[@pone.0146567.ref022]\\]. ", "In contrast to these tasks, the visual tracking task with moving circles required subjects to remember which circles to track and to track several circles at the same time during high visual demands.", "\n\nIn one study \\[[@pone.0146567.ref028]\\], participants had to track continuously one, three, or five moving circles (out of ten) while irrelevant tones were presented. ", "In contrast to previous research, findings suggested that high task demands increased (rather than decreased) the MMN. ", "That is, the mean MMN amplitudes at Fz were -1.18 μV while tracking one circle, -1.43 μV while tracking three circles, and -2.10 μV while tracking five circles. ", "Thus, the MMN amplitudes increased (i.e., became more negative) with the number of tracked circles. ", "The authors reasoned that in contrast to previous studies, their visual tracking task loaded visual spatial working memory and that this increase in the MMN fits with predictions for cognitive load rather than perceptual load. ", "Specifically, whereas perceptual load should decrease distracter processing, cognitive load should increase distracter processing \\[[@pone.0146567.ref033]\\]. ", "However, recent evidence suggests that visual spatial working memory has the same effects as perceptual load \\[[@pone.0146567.ref076]--[@pone.0146567.ref079]\\]. ", "Accordingly, load theory would seem to predict that the visual tracking task (similar to perceptual load) should decrease the MMN rather than increase the MMN, opposite to the actual findings with the visual tracking task. ", "Because predictions for the visual tracking task are mixed, we excluded this study in the above meta-analyses. ", "Similarly, the other study \\[[@pone.0146567.ref027]\\] was excluded in the above meta-analyses because it used a similar visual tracking task. ", "Participants tracked either one (of two) moving circles or two (of four) moving circles.", "\n\nFor completeness, however, these two studies were added in the next meta-analysis \\[[@pone.0146567.ref027], [@pone.0146567.ref028]\\]. ", "Because one study \\[[@pone.0146567.ref027]\\] did not report enough data to compute the relevant statistics, the mean effect of load on the MMN was estimated as zero and the *SD* of the difference scores was estimated as 1.51 (i.e., the pooled *SD* of the difference scores for the five published studies in the first meta-analysis). ", "For the other study \\[[@pone.0146567.ref028]\\], the effect of load was defined in terms of the difference between tracking one versus five circles. ", "Thus, the mean difference of the MMN was 0.92. ", "However, as for another study discussed above \\[[@pone.0146567.ref023]\\], the authors reported inferential statistics only for the overall ANOVA with three conditions (i.e., tracking 1, 3, or 5 circles, *F* = 5.02, *p* \\< .03 after Greenhouse-Geisser correction) and not the specific comparison between one and five circles. ", "To estimate inferential statistics of this specific comparison, we simulated data for the three conditions with matching descriptives (see Table 4 in \\[[@pone.0146567.ref028]\\]). ", "From 20,000 simulations, we selected the data set that had the closest match with an overall *F* value of 5.02 and *p* = 0.029 after Greenhouse-Geisser correction. ", "Then, results of a paired *t* test between the conditions with one and five circles were used in the meta-analysis (see [Table 3](#pone.0146567.t003){ref-type=\"table\"}). ", "The estimated *SD* of the difference scores was 0.79. ", "After including these additional studies \\[[@pone.0146567.ref027], [@pone.0146567.ref028]\\], results of a random effects analysis suggested heterogeneity among the effect sizes (*k* = 8, *N* = 117), *Q*(7) = 32.85, *p* \\< .001. ", "The proportion of total variance that reflects variation in true effect size was estimated to be 79% (*I*^2^ = 78.69%). ", "Importantly, it appeared that only the study that found an increase in MMN contributed to this heterogeneity \\[[@pone.0146567.ref028]\\]. ", "When this study was excluded (*k* = 7, *N* = 106), the heterogeneity was small, *Q*(6) = 6.98, *p* = .32, *I*^2^ = 14.05%. ", "For these remaining seven studies, the MMN was more negative during low than high visual demands, mean difference = -0.43 μV, \\[-0.67, -0.18\\]. ", "These findings confirm the usefulness of the meta-analysis because it provides quantitative evidence that a different population effect was sampled in one study \\[[@pone.0146567.ref028]\\] than in the remaining studies.", "\n\nGeneral Discussion {#sec014}\n==================\n\nThe present study found a MMN at Fz and Cz (with a polarity reversal at the mastoids) during both low and high load, but the MMN did not differ between low and high load. ", "We performed a meta-analysis to assess how the present results fit in with the overall evidence for an effect of demanding visual tasks on the MMN. ", "This meta-analysis did not provide any evidence that the effect of perceptual load on the MMN in the present study differed systematically from that observed in previous tasks \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]. ", "Such systematic variability would have been expected if the present perceptual load task was less (or more) effective than other tasks in decreasing the MMN. ", "Accordingly, the present findings do not suggest that perceptual load differed systematically from (i.e., was less effective than) other demanding visual tasks in its effect on the MMN. ", "Further, this lack of variability among effect sizes suggests that the choice of reference electrode may be irrelevant, as well as the choice of using a duration deviant (in the present study) rather than a frequency deviant (as in previous studies).", "\n\nThe meta-analysis further allowed us to assess the combined evidence for effects of visual task demands on the MMN. ", "As shown in [Fig 5](#pone.0146567.g005){ref-type=\"fig\"}, the meta-analysis of all available evidence (*k* = 6, *N* = 97) suggested that demanding visual tasks decrease the MMN. ", "So, the combined evidence that includes our findings supports the idea that demanding visual tasks decrease the auditory MMN to simultaneous distracters. ", "Therefore, visual task demands disrupt the process of sensory memory by either impairing standard formation and/or deviance detection \\[[@pone.0146567.ref005], [@pone.0146567.ref030], [@pone.0146567.ref080]\\], or the process of neural adaptation \\[[@pone.0146567.ref006]\\].", "\n\nHowever, the present meta-analysis may overestimate the true effect size. ", "Because of publication bias, studies have traditionally been published in Psychology only if they reported significant findings \\[[@pone.0146567.ref054]--[@pone.0146567.ref056]\\]. ", "Because significant findings tend to have larger effect sizes than non-significant findings \\[[@pone.0146567.ref081]--[@pone.0146567.ref083]\\], the present meta-analysis may overestimate the true effect. ", "Although tentative, the funnel plot in [Fig 5](#pone.0146567.g005){ref-type=\"fig\"} suggests that there may be a publication bias because the funnel lacks studies in the lower right corner of the funnel. ", "This corner would show studies that typically would not be statistically significant because they have smaller (or even positive) effect sizes and larger sampling error. ", "This observation could not be tested formally because recommendations for common tests of funnel asymmetry require at least 10 studies \\[[@pone.0146567.ref084]\\]. ", "However, to reduce the possible effects of publication bias, one approach is to reduce the asymmetry by excluding studies that contribute most to the asymmetry \\[[@pone.0146567.ref085]\\]. ", "When the two studies on the lower left-hand side of the funnel plot were excluded \\[[@pone.0146567.ref023], [@pone.0146567.ref025]\\], there remained an overall effect on the MMN. ", "Before excluding these two studies (*k* = 6, *N* = 97), mean difference = -0.46 μV, \\[-0.72, -0.20\\], and after excluding these two studies (*k* = 4, *N* = 74), mean difference = -0.37 μV, \\[-0.59, -0.15\\]. ", "Indeed, this limited influence of these two studies is already apparent in the forest plot of the meta-analysis ([Fig 5](#pone.0146567.g005){ref-type=\"fig\"}), as the small size of the dots shows that their relative contribution to the overall effect is small. ", "Thus, even if publication biases are considered by excluding two studies, the remaining evidence suggests that demanding visual tasks decrease the MMN to simultaneous auditory distracters. ", "However, the credibility of this conclusion is discussed further below under limitations.", "\n\nIn the meta-analysis, we excluded two studies with a visual tracking task \\[[@pone.0146567.ref027], [@pone.0146567.ref028]\\] because the predictions were not entirely clear. ", "The authors in one study \\[[@pone.0146567.ref028]\\] reasoned that because their visual tracking task loaded visual spatial working memory, this cognitive load should increase distracter processing \\[[@pone.0146567.ref033]\\]. ", "However, in recent modifications of load theory, visual spatial working memory is argued to have similar effects as perceptual load \\[[@pone.0146567.ref076]--[@pone.0146567.ref079]\\]. ", "Accordingly, load theory would seem to predict that the visual tracking task should decrease MMN rather than increase MMN, which is the opposite of the actual findings from the visual tracking task. ", "Importantly, when we included the results of the visual tracking tasks \\[[@pone.0146567.ref027], [@pone.0146567.ref028]\\], there was evidence for heterogeneity among effect sizes (79% of total variance reflects variation in true effect size). ", "However, this heterogeneity was mainly due to one study \\[[@pone.0146567.ref028]\\]. ", "When this study was excluded, heterogeneity among effect sizes was small (\\<14%). ", "These findings suggest two possibilities: First, visual tracking tasks may actually differ in their effects from that of other visual demands. ", "Second, it is not visual tracking tasks per se but something specific in this study \\[[@pone.0146567.ref028]\\] that resulted in a different effect. ", "Unfortunately, the (null) findings of the other study \\[[@pone.0146567.ref027]\\] are consistent with both possibilities. ", "Similarly, another visual tracking study \\[[@pone.0146567.ref070]\\] did not find an effect of task load (i.e., tracking 1 of 2 compared to 3 of 6 circles) on the MMN. ", "This study did not use the typical oddball task but used a regular pattern of tones as the standard and the violation of this pattern of tones as the deviant. ", "Furthermore, close inspection of load theory \\[[@pone.0146567.ref032], [@pone.0146567.ref033]\\] suggests that theoretically, there is no clear reason why cognitive load in the present task design should increase attention to tones. ", "According to load theory, attention is required to focus on the task-relevant stimuli in the context of task-irrelevant distracters. ", "Cognitive load (in terms of working memory) reduces this attentional focus and thus, increases distraction \\[[@pone.0146567.ref086]\\]. ", "This question has been most commonly tested with dual tasks in that a primary task that requires focused attention (e.g., Stroop) is combined with a secondary task that increases cognitive load (e.g., working memory) \\[[@pone.0146567.ref087]\\]. ", "Because the task design in the visual tracking tasks does not fit this typical task design (e.g., \\[[@pone.0146567.ref088]\\]), it is unclear why visual tracking tasks should increase the MMN. ", "Nonetheless, because the heterogeneity of effect sizes in the meta-analysis (which includes study \\[[@pone.0146567.ref028]\\]) provides some evidence that visual tracking tasks may increase the MMN, future studies are needed to determine whether or not the effects of visual tracking tasks on the MMN match those of other visual task demands.", "\n\nThe main limitation of the present study is that we conducted the meta-analysis only after conducting this study. ", "Prior to designing this study, we approached the literature from a null hypothesis significance perspective, which suggested clear effects of visual task demands on the auditory MMN, as well as clear behavioral effects of perceptual load. ", "We were therefore surprised when our results did not suggest any effects of perceptual load on the MMN, despite the fact that our sample size was at least twice as the average sample size in previous studies. ", "However, in hindsight, our null findings are not entirely surprising if the results of our meta-analysis are used to estimate the power of our study. ", "To estimate power, we assumed that the true effect size was captured in the meta-analysis of the five previous studies \\[[@pone.0146567.ref022]--[@pone.0146567.ref026]\\]. ", "The mean difference was -0.50 μV (*k* = 5, *N* = 69). ", "Because *t*(68) = -3.51, the corresponding effect size in terms of Cohen's *d*~z~ was -0.42 (see equation 7 in \\[[@pone.0146567.ref075]\\]). ", "With this effect size, a two-tailed alpha of .05, and a sample size of 28, power = .57 (estimated with G\\*Power, \\[[@pone.0146567.ref089]\\]). ", "To obtain a power of .90, at least 62 subjects would have been required. ", "Because of limited power, the present null findings do not provide convincing evidence for or against an effect of perceptual load on the MMN. ", "From an estimation perspective \\[[@pone.0146567.ref043]\\], the limits of the 95% CI for the present results (between -0.91 and 0.85 μV) are quite wide and thus, provide only an imprecise estimate of the true effect size.", "\n\nCritically, this apparent limitation in knowledge gain was apparent only after conducting the meta-analysis and was not obvious from the traditional narrative review. ", "Because a narrative review has these limitations, a meta-analysis provides an excellent tool to integrate previous findings quantitatively \\[[@pone.0146567.ref043]\\]. ", "As Gene V. Glass, a pioneer of meta-analysis in Psychology, wrote: \"the proper integration of research requires the same statistical methods that are applied in primary data analysis\" (p. 6, \\[[@pone.0146567.ref090]\\]). ", "Indeed, it is surprising that researchers (like us) are extremely diligent to use statistical methods when analyzing their own data (i.e., primary data analysis) but use a narrative review when summarizing the previous literature. ", "Because of the advantages of meta-analytic tools, several journals (e.g., Lancet) now require that researchers put their study in context by combining previous studies meta-analytically and providing a pooled estimate of the effect size \\[[@pone.0146567.ref091], [@pone.0146567.ref092]\\]. ", "Although this places substantial demands on researchers, it provides a context in which to quantitatively evaluate the knowledge gained from the new study.", "\n\nThe results of the present meta-analysis are highly informative for future research in this area. ", "If the true effect size is assumed to be captured by the present results together with previous studies that showed homogenous effect sizes \\[[@pone.0146567.ref022]--[@pone.0146567.ref027]\\], the mean difference was -0.43 μV (*k* = 7, *N* = 106). ", "Because *t*(105) = -3.46, the corresponding effect size in terms of Cohen's *d*~z~ was -0.34 (see equation 7 in \\[[@pone.0146567.ref075]\\]). ", "With this effect size, a two-tailed alpha of .05, and a desired power of .90 \\[[@pone.0146567.ref089]\\], at least 93 subjects would be required.", "\n\nWhereas power is used in significance testing, *precision* is used in estimation \\[[@pone.0146567.ref042], [@pone.0146567.ref043]\\]. ", "Precision may be more informative than power because it can be used to estimate the expected size of the confidence intervals in meaningful units. ", "Given *t*(105) = -3.46 and a mean difference of -0.43 μV, the *SD* of the difference scores was 1.28 (p. 200 in \\[[@pone.0146567.ref093]\\]). ", "Using the *Precision one* page in ESCI \\[[@pone.0146567.ref043]\\], we determined that if 1.28 is assumed as the population *SD* and *n* = 93, then the expected average size of the margin of error would be 0.31 μV with 99% assurance. ", "This means that in 99% of all replications, the 95% CI would extend no more than 0.31 μV above and below the observed mean effect.", "\n\nThe meta-analysis suggests that to obtain sufficient power, any future study probably needs to include at least 93 subjects. ", "This study would need to run as many subjects as were run in all seven studies that were included in the meta-analysis (*k* = 7, *n* = 106) \\[[@pone.0146567.ref022]--[@pone.0146567.ref027]\\]. ", "Unfortunately, there are three reasons to suggest an even larger sample size than *n* = 100. ", "One reason is that the above precision analysis suggests that with 99% assurance (i.e., in 99% of replications), a reasonable estimate for the margin of error will be +/- 0.31 μV. Notably, the present meta-analysis (*k* = 7, *n* = 106) obtained a margin of error of 0.24 μV. Thus, the 95% CI is consistent with a true effect size of -0.18 μV (i.e., -0.43 +0.24). ", "If this is the true effect size, then the 95% CI in a future study with *n* = 100 might well cross zero (i.e., -0.18 + 0.31 = +0.13). ", "Therefore, a precision of 0.10 μV seems more desirable, but improving precision to 0.10 μV with 99% assurance would require more than 700 subjects. ", "Such a task seems too demanding for an individual research lab, but may be tackled in a collaborative project \\[[@pone.0146567.ref058]\\].", "\n\nAnother reason to recommend a very large sample size is that in general, a meta-analysis of many small, published studies tends to overestimate the true effect size (for review, see \\[[@pone.0146567.ref083]\\]). ", "In previous studies, sample sizes varied between 9 and 28 \\[[@pone.0146567.ref022]--[@pone.0146567.ref027]\\]. ", "If the results of the meta-analysis (*k* = 7, *N* = 106) with Cohen's *d*~z~ = -0.34 are assumed as the true effect size, then power for these studies ranged from .15 to .41. ", "As reviewed in several recent papers \\[[@pone.0146567.ref081]--[@pone.0146567.ref083]\\], low power has several undesirable consequences. ", "One of these consequences is that if significance is obtained in a low-powered study, then the true effect size is overestimated. ", "This phenomenon is called the *winner's curse* (for review, see \\[[@pone.0146567.ref083]\\]). ", "The reason is that if a study has low power, then an observed effect needs to be much larger than the true effect to yield significance. ", "Thus, in a meta-analysis of only small published studies, the individual studies may have inflated effect sizes, and this will inflate the estimated effect when these studies are combined in the meta-analysis. ", "In contrast, large studies should be less biased when it comes to overestimating the true effect size \\[[@pone.0146567.ref082], [@pone.0146567.ref083]\\]. ", "Simulations suggest that at a power of .30, effect size inflation may be 20% of the actual effect size (for review, see \\[[@pone.0146567.ref083]\\]). ", "To adjust for any bias from inflated effect sizes, we conducted a power analysis in which we simply reduced the observed effect size (*d*~z~) by 20% from -0.34 to -0.27. ", "For this effect size, 150 subjects would be required to obtain a power of .90 at two-tailed α = .05. ", "In terms of precision, the estimated precision (at 99% assurance) would be 0.23 μV, similar to the observed precision in the present meta-analysis.", "\n\nA third reason to recommend a large sample size is that small changes in data analytic strategies affect results more strongly in small than large studies. ", "This is referred to as *vibration of effects* \\[[@pone.0146567.ref055]\\]. ", "If researchers tend to select the most favorable results in their analyses, then the combined results from many small studies will suggest a stronger effect than the result from a single large study. ", "Such vibration of effects is a potential problem in EEG research because electrodes and intervals are often not selected a priori but only after looking at the data. ", "Because details of the data analyses are partly determined by the actual data, this circularity inflates effect sizes and has been referred to as double dipping \\[[@pone.0146567.ref094]\\], nonindependence error \\[[@pone.0146567.ref095], [@pone.0146567.ref096]\\], or baloney \\[[@pone.0146567.ref097]\\]. ", "To eliminate this error, guidelines recommend selecting electrodes and intervals only on the basis of previous research \\[[@pone.0146567.ref098]\\]. ", "In practice however, researchers often define electrodes and intervals from their own data as well as the previous literature. ", "One reasonable explanation may be that because the physical parameters differ slightly between studies, the effects on the EEG might also differ slightly between studies. ", "Nonetheless, this procedure is circular. ", "Therefore, future studies would provide strong evidence if data processing and selection of electrodes and intervals are defined a priori and preregistered \\[[@pone.0146567.ref099]\\].", "\n\nTaken together, the present meta-analyses suggest that future studies need to include a large sample size to improve knowledge gain. ", "One approach would be to conduct this research collaboratively \\[[@pone.0146567.ref058]\\]. ", "If this is not feasible, all individual studies should be published and made available for meta-analysis. ", "However, as discussed recently \\[[@pone.0146567.ref083]\\], some areas in neuroscience may have conducted many small studies in the same field that, when taken together, used more subjects than would have seemed necessary to address the research question. ", "This raises ethical considerations as to efficient use of resources.", "\n\nThe present research has at least five other limitations. ", "First, although the meta-analysis supports the conclusion that demanding visual tasks decrease the MMN, the mechanism for this decrease is unresolved. ", "The MMN has been proposed to reflect either sensory memory or neural adaptation (for review, see \\[[@pone.0146567.ref003]\\]). ", "Because the traditional oddball task (as used in all studies in the meta-analysis) potentially confounds both processes, a *many standards* task (or more formally called *equiprobable sequence*) reduces effects of neural adaptation on the MMN \\[[@pone.0146567.ref003], [@pone.0146567.ref100], [@pone.0146567.ref101]\\]. ", "The many standards task is run separately from an oddball task. ", "As in the oddball task with a single deviant and single standard, the *control* stimulus is the same stimulus as the deviant and is presented with the same probability as in the oddball task. ", "To illustrate with an example \\[[@pone.0146567.ref102]\\], in the oddball task, 500 Hz was the deviant (10%) and 550 Hz was the standard; and in the many standards task, 500 Hz was the control (10%). ", "Thus, the deviant in the oddball task and the control in the many standards task were presented with equal probability. ", "Different from the oddball task, however, the standard is replaced by several other stimuli so that across all stimuli (including the control), the probability for each stimulus is the same. ", "Because all stimuli in the many standards task are shown with the same probability, there should be no sensory memory effect (in contrast to the oddball task). ", "In the example study, the control (500 Hz) was presented together with nine other stimuli (between 550 and 1179 Hz) so that each stimulus had a probability of 10%. ", "Furthermore, on average, these stimuli should physically differ more strongly from the control (in the many standards task) than the standard differs from the deviant (in the oddball task). ", "In the example, the other nine stimuli (between 550 and 1179 Hz) differed more (on average) from the control than the standard (550 Hz). ", "The reason is that if neural adaptation to these stimuli also leads to neural adaptation to the control (because the stimuli somewhat resemble the control), then this neural adaptation effect should be smaller in the many standards task than in the oddball task, as the physical difference between control and the other stimuli is larger than that between deviant and standard. ", "Therefore, neural adaptation cannot account for the finding that the response is larger to the deviant than to the control. ", "So, by computing the response to the deviant in the oddball task minus the physically identical control in the many-standards task, the resulting difference ERP should be mainly affected by sensory memory rather than neural adaption \\[[@pone.0146567.ref101]\\]. ", "Future research may want to include this many-standards task, although confounding effects from neural adaptation and lateral inhibition may not be eliminated completely \\[[@pone.0146567.ref003], [@pone.0146567.ref006]\\]. ", "Further, even if the many-standards task may be successful in isolating sensory memory effects on the MMN, it would be unresolved if these changes are caused specifically by changes in standard formation or deviance detection \\[[@pone.0146567.ref003], [@pone.0146567.ref005], [@pone.0146567.ref029]\\]. ", "Last, although the mechanism for effects of attention on the MMN apparently involve corticofugal pathways, the exact neural mechanism has yet to be determined \\[[@pone.0146567.ref029]\\].", "\n\nSecond, our meta-analysis was highly selective in that we focused on studies that resembled the current study design as much as possible. ", "That is, we included studies only if they were published, used EEG, the visual task demands were continuous and varied between high and low load within the same task, and the task-irrelevant tones were presented in a typical oddball task simultaneously with the visual stimuli. ", "Because we included only published studies, our meta-analysis is mainly an attempt to quantitatively integrate previous research rather than to rely solely on a narrative review with a focus on significance. ", "Thus, meta-analytic tools with estimation permit more accurate representations of the combined evidence in a field than a narrative review \\[[@pone.0146567.ref043]\\]. ", "This is supported by successful meta-analyses of MMN-relevant studies \\[[@pone.0146567.ref103]--[@pone.0146567.ref107]\\], although this task may be impossible if methods vary too much \\[[@pone.0146567.ref108]\\]. ", "Further, the focus on studies that resembled the current study design as much as possible has the advantage that our meta-analysis addresses a specific question. ", "However, our selection criteria may not be shared by other researchers. ", "For example, it may well be that effects of studies that manipulated visual demands with different tasks (rather than within levels of the same task) or that presented patterned auditory sequences (rather than a typical oddball task) do not differ from those in the present meta-analysis. ", "These questions are beyond the scope of the present study, because a much more comprehensive meta-analysis would be needed to address these questions. ", "Because the MMN has been studied extensively, there is an abundance of studies that could be used to evaluate effects of different paradigms and the role of potential moderators of the MMN. ", "Such a future meta-analysis should also code for many study features (e.g., study quality, choice of deviance, task performance, EEG interval and electrodes) to test for moderating effects of these variables. ", "Because the present meta-analysis was limited to a few studies, the analysis of moderators was not feasible.", "\n\nThird, although the present study found strong behavioral effects of perceptual load, it could be argued that with stronger manipulations of perceptual load, even an effect on the MMN would be apparent. ", "However, unless there is a criterion for a high level of perceptual load that is independent from its effects on the MMN, this reasoning is circular (as addressed above). ", "However, a recent study \\[[@pone.0146567.ref051]\\] used the same visual stimuli in a visual search task and in a flanker task (i.e., perceptual load) and examined the correspondence of the behavioral effects between visual search task and flanker task. ", "Results showed that inefficient visual search (as indicated by large search slopes) corresponded with high perceptual load. ", "Because these results suggest that perceptual load may be defined independently (with reference to visual search), future studies may employ a similar set up to strengthen the claim for high perceptual load.", "\n\nFourth, the present results do not address gender differences. ", "When we designed the present study, we reviewed previous studies and found no evidence that gender differences were a matter of concern \\[[@pone.0146567.ref022]--[@pone.0146567.ref028]\\]. ", "For example, two studies used either only men \\[[@pone.0146567.ref023]\\] or mostly men (9 out of 11)\\[[@pone.0146567.ref028]\\]. ", "Because at our university, both genders are not represented equally, we tried to run as many subjects as possible in the available time rather than to try to counterbalance gender. ", "However, because gender differences on the MMN have been found in related areas \\[[@pone.0146567.ref109]--[@pone.0146567.ref111]\\], the present effects may be moderated by gender. ", "At face value, however, there is no apparent pattern because the two studies with mostly men reported effects in opposite directions \\[[@pone.0146567.ref023], [@pone.0146567.ref028]\\]. ", "Because large sample sizes are recommended for future studies, gender differences may need to be addressed in a meta-analysis. ", "To facilitate such a meta-analysis, the raw data should be made available (provided for our study in the [S1 File](#pone.0146567.s001){ref-type=\"supplementary-material\"}).", "\n\nFifth, the present study as well as the meta-analysis focused on a single electrode (Fz) and thus, did not consider laterality effects. ", "Again, previous studies did not suggest laterality effects \\[[@pone.0146567.ref022]--[@pone.0146567.ref028]\\]. ", "However, studies in other areas reported laterality effects for the MMN \\[[@pone.0146567.ref002], [@pone.0146567.ref053], [@pone.0146567.ref112]--[@pone.0146567.ref114]\\]. ", "Thus, future studies will need to address potential laterality effects.", "\n\nConclusions {#sec015}\n===========\n\nWe studied the effects of visual perceptual load on the MMN to simultaneous, auditory distracters in a typical oddball task. ", "The results of the empirical study did not provide evidence for an effect of perceptual load on the MMN. ", "A subsequent meta-analysis, however, suggested that the present (null) findings did not systematically differ from previous, similar studies that varied visual task demands. ", "When the available evidence was combined, the meta-analysis confirmed that demanding visual tasks reduce the MMN to auditory distracters. ", "However, because the meta-analysis was based on small studies and because of potential publication biases, future studies should have large samples (*n* \\> 150) to provide confirmatory evidence for the results of the present meta-analysis. ", "Future studies should also use control conditions that reduce confounding effects of neural adaptation, use load manipulations that are defined independently and also address gender differences and laterality effects. ", "Last, because the scope of the present meta-analysis was narrow, a more comprehensive meta-analysis is needed to determine whether or not the present results can be generalized to different task configurations (e.g., frequency vs. duration deviants, choice of electrodes, working memory tasks, intra- vs. intermodal). ", "Because the MMN has been studied extensively, there is an abundance of studies that may be used to evaluate effects of different paradigms and the role of potential moderators of the MMN.", "\n\nSupporting Information {#sec016}\n======================\n\n###### Data file in tab-delimited format.", "\n\n(TXT)\n\n###### \n\nClick here for additional data file.", "\n\nWe thank Professor Kimmo Alho and Professor Geoff Cumming for helpful comments on an early draft of our manuscript. ", "We also thank Dani Cosme for copyediting. ", "Any remaining errors are ours.", "\n\n[^1]: **Competing Interests:**The authors have declared that no competing interests exist.", "\n\n[^2]: Conceived and designed the experiments: SW MS MEN. ", "Performed the experiments: MS. ", "Analyzed the data: SW MS. ", "Contributed reagents/materials/analysis tools: SW MS MEN. ", "Wrote the paper: SW MS MEN.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "I’m so mad! ", "I need to read the rest of the “book” soon because I really want to know what is going to happen. ", "😉\n\nThis book reads like it was originally one long story that was broken up because YA don’t want long books (a publisher-type decision). ", "However, this does not work as well for this book because there are lots of open plot threads at the end of the book (hence my frustration).", "\n\nI enjoyed the characters and plots that wound through this book, although I thought the main character was a little dense to not think that the magicians would come looking for the magic item.", "\n\nI recommend reading this book when you have all (or at least most) of the series ready to read back-to-back.", "\n\nRelated\n\nThis entry was posted\non Thursday, May 3rd, 2012 at 4:28 pm and is filed under Path.", "\nYou can follow any responses to this entry through the RSS 2.0 feed.", "\nYou can leave a response, or trackback from your own site." ]

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[ "/**\n * Pivot Field List Default Sample\n */\nimport { pivot_dataset } from '../../../spec/base/datasource.spec';\nimport { PivotView } from '../../../src/pivotview/base/pivotview';\nimport { FieldList } from '../../../src/common/actions/field-list';\nimport { DataManager, ODataAdaptor, JsonAdaptor, ODataV4Adaptor, UrlAdaptor, WebApiAdaptor } from '@syncfusion/ej2-data';\nimport { DataSourceSettingsModel } from '../../../src/pivotview/model/datasourcesettings-model';\n\n//335 or 315\nPivotView.", "Inject(FieldList);\n\nlet oData: DataManager = new DataManager({\n url: 'https://js.syncfusion.com/demos/ejServices/Wcf/Northwind.svc/Orders/?$top=7',\n adaptor: new ODataAdaptor\n});\nlet jsonData: DataManager = new DataManager({\n json: pivot_dataset,\n adaptor: new JsonAdaptor\n});\nlet apiData: DataManager = new DataManager({\n url: 'http://controller.com/api',\n adaptor: new WebApiAdaptor\n});\nlet v4Data: DataManager = new DataManager({\n url: 'http://services.odata.org/V4/Northwind/Northwind.svc/Orders/',\n adaptor: new ODataV4Adaptor\n});\n\nlet oDataReport: DataSourceSettingsModel = {\n dataSource: oData as DataManager,\n expandAll: true,\n rows: [{ name: 'OrderID' }, { name: 'CustomerID' }],\n columns: [{ name: 'OrderDate' }, { name: 'ShipCity' }],\n values: [{ name: 'Freight' }],\n filters: [],\n};\nlet jsonReport: DataSourceSettingsModel = {\n dataSource: jsonData as DataManager,\n expandAll: true,\n rows: [{ name: 'product', caption: 'Items' }, { name: 'eyeColor' }],\n columns: [{ name: 'gender', caption: 'Population' }, { name: 'isActive' }],\n values: [{ name: 'balance' }, { name: 'quantity' }],\n filters: [],\n};\nlet apiReport: DataSourceSettingsModel = {\n dataSource: apiData as DataManager,\n expandAll: true,\n rows: [{ name: 'OrderID' }, { name: 'CustomerID' }],\n columns: [{ name: 'OrderDate' }],\n values: [{ name: 'Freight' }],\n filters: [],\n};\nlet v4Report: DataSourceSettingsModel = {\n dataSource: v4Data as DataManager,\n expandAll: false,\n rows: [{ name: 'OrderID' }, { name: 'CustomerID' }],\n columns: [{ name: 'ShipCity' }],\n values: [{ name: 'Freight' }],\n filters: [],\n};\n\n\nlet pivotGridObj: PivotView = new PivotView({\n dataSourceSettings: oDataReport,\n showFieldList: true,\n height: 350,\n width: 1200\n});\npivotGridObj.appendTo('#PivotView');\ndocument.getElementById('json').onclick = function () {\n pivotGridObj.dataSourceSettings = jsonReport;\n};\ndocument.getElementById('webapi').onclick = function () {\n pivotGridObj.dataSourceSettings = apiReport;\n};\ndocument.getElementById('odata').onclick = function () {\n pivotGridObj.dataSourceSettings = oDataReport;\n};\ndocument.getElementById('v4').onclick = function () {\n pivotGridObj.dataSourceSettings = v4Report;\n};" ]

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[ "Managing Livestock Mortalities\n\nA recent FDA rule is likely to impact the cost and/or availability of rendering services for cattle producers. ", "What is this rule and how will it impact service? ", "Are there other environmentally-responsible methods of carcass disposal? ", "This presentation was originally broadcast on June 19, 2009. ", "More…\n\nCategories\n\nAbout eXtension\n\nThis is a national Cooperative Extension resource\n\nThis work is supported by New Technologies for Agriculture Extension grant no. ", "2015-41595-24254 from the USDA National Institute of Food and Agriculture. ", "Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture." ]

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[ "module.exports = require('./build/webpack.statis.conf')\n\n// webpack-dev-server --hot --host localhost --port 8080 --public --content-base ./src" ]

{ "pile_set_name": "Github" }

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[ "A 25-year-old man was stabbed then lynched by a group of Muslim men who became angry after his elbow accidentally brushed against one of them at a crowded bar in West Delhi.", "\n\nSaijan Singh was stabbed more than six times, local media reported.", "\n\nSix Muslims dancing at the bar at West Gate Mall in the Rajouri Garden area were arrested.", "\n\nThe Hindu Post has more of the story:\n\nAccording to police, 25-year-old Sajjan Singh was stabbed more than six times by the accused. ", "With the help of CCTV cameras inside the mall, the accused were arrested, police said on Monday.", "\n\nSajjan worked as a driver in the Vigyan Bhavan and is survived by his mother and a brother.", "\n\nVijay Kumar, Deputy Commissioner of Police (West) said, “Six accused people identified as Saleem, main accused, Imran, Aleem, Abid, Samar and a juvenile were arrested on Monday evening. ", "They all are residents of Khyala area.”", "\n\nOn Sunday night, at around 8 pm, Sajjan Singh, a resident of Moti Bagh area along with his group of ten friends had gone for clubbing at the Toast Bar and Grill in West Gate Mall. ", "While dancing, Sajjan’s elbow accidentally brushed against Imran.", "\n\nThis infuriated Imran so much that he pushed Sajjan on the dance floor. ", "This led to a heated verbal altercation. ", "Enraged Imran called in his brother Saleem. ", "He along with Imran, Aleem and Abid called in their friends and they stabbed Sajjan in full public view.", "\n\nA senior investigator said, “One of the friends of the victim told us that the time of the incident when verbal altercation spiraled out of control, Sajjan allegedly started begging Saleem and his friends to resolve the matter amicably. ", "However, Saleem did not pay heed and kept on stabbing Sajjan till he lost consciousness.", "\n\nAfter killing, Saleem and his friends fled from the spot. ", "Whether the accused were drunk or not is yet to ascertained, said the DCP. ", "Meanwhile, body of the victim Sajjan has been sent for post-mortem and was handed over to his family.", "\n\nTalking to The Pioneer, Babul, Sajjan’s brother said, “Three men killed my brother. ", "All this happened right in front of Sajjan’s friends. ", "It was only at 9.30 pm that one of Sajjan’s friends called in to inform that my brother has been stabbed.”", "\n\nThis incident is similar in some respects to the stabbing of Junaid Khan by main accused Naresh onboard a passenger train after an argument over seat sharing spiraled out of control. ", "The key difference being that Naresh appears to have acted in self-defense, going by this report. ", "In this case, the victim Sajjan tried to pacify his attackers, but to no avail.", "\n\nSome will ask why this crime, shocking as it is, is being given a ‘communal angle’ by HinduPost because of our clear identification of victim as Hindu and attackers as Muslim. ", "It is a valid question. ", "We do not know if there was any communal motivation for this crime – for eg., ", "we are not privy to what was said by the attackers, whether they threw any communal slurs while attacking Sajjan, whether Sajjan’s Hindu identity inflamed his attackers primed as they are to regard the ‘kafir’ and ‘idolator’ as accursed, even sub-human.", "\n\nWe do not know any of this yet, still we believe that this is bigger than ordinary crime news and deserves to reach the common man – that a Hindu youth was killed in a crowded mall in broad daylight by a group of Muslims. ", "Given the way mainstream national media has created a climate that Muslims and Christians are cowering in fear as they are under attack from the majority Hindus of this country, it is important that such a poisonous & blatantly false narrative be countered by reporting the other side of the coin. ", "Given that a high Constitutional authority like the Vice President has recently claimed that fear and unease are growing among Muslims in Bharat, setting the narrative right becomes even more important.", "\n\nLets see how many of the #NotInMyName campaigners add Sajjan’s name to their hate tracker list, or whether the CM of Kerala offers any financial assistance to Sajjan’s family like he did for Junaid. ", "We are not holding our breath though….in all likelihood, Sajjan’s death will be quickly forgotten and Bharat will move on – the vicious secular politics in vogue since Independence has taught Hindus this harsh lesson again and again." ]

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[ "Optical sensors are known, consisting of a plurality of photo-sensitive elements, or pixels, able to detect light signals and to transmit them, in the form of electric signals, to a calculator which processes them and obtains images from them which it transmits to display devices; the latter are then able to allow a user to see such images or information deriving therefrom.", "\nPreviously, such optical sensors were made using CCD technology (Charge-Coupled Device), which guarantees a very satisfactory image quality in the presence of a well-controlled illumination, but are not able to operate optimally in the presence of a light which is greatly differentiated inside the same scene, that is, with an input signal having high dynamics, up to 150 dB.\nCCDs are also not very versatile from various points of view: they cannot easily be integrated with complex pilot circuits in a single silicon support (called microchip), and it is not possible to arbitrarily select a sub-window inside the matrix sensor.", "\nTo overcome some of these shortcomings of CCDs, optical sensors have been developed based on the CMOS type silicon technology (Seger, Graf, Landgraf—“Vision Assistance in Scene with extreme Contrast”—IEEE Micro, vol. ", "13 page 50, February 1993), which offer a good result in very differentiated lighting conditions inside the same scene. ", "This result is obtained by means of a conversion on logarithmic scale of the signal inside the photo-sensitive element or pixel.", "\nSuch logarithmic conversion, obtained for example by connecting an MOS type transistor in diode configuration to the photo-sensitive joint, as described in U.S. Pat. ", "No. ", "5,608,204, suffers in any case from the fundamental disadvantage that it supplies a low definition of the image in the event of low illumination. ", "High resolution images are obtained by means of a linear reading of the photo-sensitive element; this technique, however, has the disadvantage that it does not give the possibility of obtaining good quality images in very differentiated lighting conditions inside the same scene.", "\nThe Applicant has devised and embodied the present invention to overcome these shortcomings of the state of the art and to obtain further advantages." ]

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[ "Previously on Pretty Little Liars, Aria almost stabbed Ezra’s other fiancée to death because she broke out of the hospital after they broke all her bones after she was resurrected from a jungle kidnapping. ", "Spencer went on a date with the guy investigating her shooting and also investigating the whereabouts of her birth mother (who didn’t shoot Spencer, okay, but did kill her twin sister who was Spencer’s dad’s longtime mistress and the mother of Spencer’s half-brother who made out with Spencer’s sister and half-cousin who Spencer waltzed with as a ghost). ", "Emily and Paige and Ali scrambled together to form a last second love triangle. ", "Hanna did an operation on a lifesize doll with her own personal face stitched onto its head, and then missed an important business meeting due to that doll trying to murder her boyfriend. ", "And wherever Mona was, it was paradise by virtue of her presence.", "\n\nThere are about fifty million reasons why you shouldn’t make the big bad of your perpetual murder mystery a trans woman, and one of those fifty million reasons is you’re going to end up misnaming and misgendering her repeatedly as you try to explain her involvement and connections to the other bad guys on the show. ", "And as you misname and misgender her repeatedly, you’re going to reinforce the lies that trans women are just men in disguise and trans women are unhinged and it’s fine to call them dudes and etc. ", "and so on. ", "Your argument is, I guess, “We have to call her by her birth name and give her the pronouns she was assigned at birth to explain this twisty tangled mystery in a way that satisfies the audience.” ", "To which I say, “Hey, guess what, you’ve had years to figure this out and you should have thought through all the ways to sidestep contributing to a culture that relies on pervasive stereotypes to dehumanize and persecute trans women before you decided to make a trans woman your main villain.”", "\n\nTo wit: This this week Hanna and Spencer go on a deep dive to the suburbs looking for Mary Drake and what they find is Pastor Ted. ", "He’s harboring Mary Drake on his couch. ", "Why? ", "Well, because he’s Charlotte’s birth father, of course. ", "One time he was in love with Mary and then Mary got carted away to Radley and she never told him about Charlotte but then Charlotte showed up at church camp with her best friend Lucas Gottesman and Pastor Ted was like, “Hey, she looks like me and Mary Drake smashed together and, like her mother, seems to favor poison as a murder weapon” and that’s when he knew. ", "Peter also knew, years before the Liars found out Charlotte existed. ", "It’s some really good reveals. ", "I think I would have enjoyed them quite a lot, a gasping amount even, if I hadn’t needed to keep pausing the TV to glower at it due to everyone misnaming and misgendering Charlotte the whole time they were talking about her.", "\n\nSpencer also spends a fair amount of time glowering at her father, who insists that he and Veronica love her and are her real parents and, you know, maybe over the course of her teenage years they made a couple of mistakes in not revealing that Peter sired all of her friends and neighbors and she has a genetic predisposition for Radley-style machinations and so did Peter’s other kids who kept traipsing back and forth across the yard walloping everyone with shovels and burying them in Veronica’s hydrangea patch. ", "And, yes, that was one small series of perpetual mistakes that did, in fact, lead to Spencer and her friends getting held hostage in an underground lair. ", "But Peter is determined not to make that same mistake twice. ", "He’s been out there looking for Mary Darke. ", "He’s gonna find her and make sure she never messes with Spencer again. ", "It didn’t work out last time he tried it, when Mary sneaked into their house to stare at Spencer from the shadows in the middle of the night, but this time it’ll stick, he’s sure of it.", "\n\nADVERTISEMENT\n\nDetective Furey is also looking for Mary Drake, and also the murderer(s) of Archer Dunhill. ", "After Spencer takes him as her lover, he awakens to a call that the severed finger he got in the mail the other day is Archer’s, so he skedaddles out of Spencer’s sun-dapped bed and over to Rosewood High School to menace Alison about her dead husband who pretended to be a psychiatrist, drugged her, strapped her to a bed, and impregnated her. ", "She’s like, “Yes, motherfucker, a lot of people probably wanted him dead. ", "He was a fake psychiatrist who tortured his patients.” ", "Furey is mostly interested in how much Alison, specifically, wanted him dead, but his accusations are not her main concern today. ", "For today is her day to play The Game!", "\n\nAli has decided to go ahead and have an abortion and the show handles that decision and explanation with so much candor and elegance it makes the dumb stuff even dumber. ", "You can do it when you want to, writers. ", "You can write a good fun story and also be responsible. ", "Ali tells Emily that she’s decided to terminate her pregnancy and then explains the procedure, which includes taking one pill at the clinic and one pill at home. ", "None of this “ripping babies from the womb in the ninth month” nonsense the President of the United States of America terrorized everyone with in during his campaign. ", "Emily understands and supports Ali fully and offers to drive her to the clinic. ", "Ali graciously and immediately accepts her offer.", "\n\nAli’s abortion pamphlet peeps its way out of her bag in the teacher’s lounge and catches Paige’s eyes, which she is lucky to be possession of, to be honest with you; she nearly rolled them right out of her head when she told Emily she was leaving for a job in Iowa and Emily started to beg her to stay but turned her attention to Alison as soon as she walked into the room. ", "Ali catches Paige with the abortion leaflet and yells at her and then takes ten hilarious minutes to gather all her things from the table and storm out.", "\n\nWhat A.D. wants Ali to do is go shopping for baby clothes. ", "Easy enough. ", "Register for ten items and then back to babysitting Aria. ", "Ali points the beepy-clicker at any old thing in the baby store, remembering the whole time about being drugged and wheeled through the hospital to get inseminated. ", "When she turns the beepy-clicker in at the register, the lady gives her a little wrapped package for “the donor.” ", "You know, the donor. ", "The donor of the egg now fertilized inside Ali’s womb. ", "Ali opens up the bag and inside is a brilliant callback: It’s a necklace with some beads that spell out EMILY because Ali’s baby is Emily’s baby. ", "Ali rips herself out of the frame over this news, hollers at the baby store lady to give her the puzzle piece, and ransacks the shop until she finds it attached to a hanging mural.", "\n\nWhile Ali is coming to grips with this information, Emily is out and about dragging Paige’s heart over broken glass again. ", "First of all she tells Paige it’s a bummer she’s gonna take that job in Iowa because she thought they’d have a chance again when Paige showed back up in Rosewood. ", "Paige is like, “Yeah me too, obviously; it’s literally the only reason I’m here.” ", "They go out for pizza and exposit all the things they said and did, all the adventures and had and all donuts they ate, all their big decisions about their majors and first apartments, this romance they shared and life they lived together, with each other, OFF-SCREEN DURING THE TIME JUMP.", "\n\nWhat a waste. ", "What an infuriating, maddening waste.", "\n\nPaige McCullers has always been Pretty Little Liars‘ favorite rorschach. ", "Your Patronus or your Boggart depending on what was going on in your brain and heart and all the personal experiences you brought with you into her story. ", "A three-episode guest star who grew into redemption personified.", "\n\nYou get the feeling in all these Pretty Little Liars exit interviews and memoirs from the cast that the network and the studio had their hands all over every scene in every script of this TV show. ", "It was about the tweets and the Tumblr gif sets and the Teen Choice surfboards and the NOISE NOISE NOISE NOISE. ", "It’s why Ezra’s not dead or in jail, why he’ll end up riding off into the sunset with Aria. ", "And it’s also why the other Liars got cardboard cut out replacement love interests during the time jump, so they could inevitably dump them and be reunited with their most significant love interests on-screen. ", "And why for Emily, it was the opposite.", "\n\nThe criticism of Paige McCullers, even from professional TV critics, to this day, drips with barely masked disdain for the ways she’s not feminine enough, not gentle enough, not apologetic enough. ", "The way she doesn’t fit the mold of culturally acceptable womanhood. ", "Her hair, her button-downs, her muscle t’s. ", "The way she walks and the way she talks. ", "And the only reason those same people have loosened up on Ali is because she was punished, and thoroughly. ", "She didn’t apologize for who she was, for what she knew, and so suffered to atone.", "\n\nThis whole time, these whole seven years, I always come back to T.S. Eliot when I think of Paige and Emily and Ali. ", "Always and always in my head:\n\nAnd would it have been worth it, after all,\n\nAfter the cups, the marmalade, the tea,\n\nAmong the porcelain, among some talk of you and me,\n\nWould it have been worth while,\n\nTo have bitten off the matter with a smile,\n\nTo have squeezed the universe into a ball\n\nTo roll it toward some overwhelming question,\n\nTo say: “I am Lazarus, come from the dead,\n\nCome back to tell you all, I shall tell you all”\n\nIf one, settling a pillow by her head,\n\nShould say: “That is not what I meant at all;\n\nThat is not it, at all.”", "\n\nWhat a story it could have been if Paige had been given the same care and attention as the male love interests on this show, if she’d grown organically on-screen, and if Alison had been written with consistency and courage. ", "What a story to see Emily choose between her first love and her most significant relationship here in these final episodes, to know that either one would be a radical decision. ", "The queer Dead Blonde Girl, resurrected. ", "Or the self-harming kid in the closet who came out on TV during an epidemic of gay teen suicides in real life, and who lived and lived and lived and loved and got the girl. ", "My heart should have been broken by the beauty of this mess, the glorious breathtaking jumble of impossibility; one of the longest running lesbian characters on television choosing between two complicated, polarizing, unapologetic women. ", "Women who devastated and undid her and helped her and healed her, each in their way, hating themselves and each other and, in loving her, finding themselves made whole.", "\n\nWhat if Paige and Ali had been given the same mandate as Ezra? ", "What if any ferocious woman anywhere was ever given the same mandate as her dime-a-dozen white male counterpart? ", "It haunts me. (", "It haunts all of us now, whether we acknowledge it or not.)", "\n\nAnyway, Paige and Emily decide to race bikes to see if Paige will stay in Rosewood. ", "But Paige is just joking. ", "She’s already made up her mind not to go. ", "She pedals and pedals and hops off and smooches Emily on the lips and Emily smooches her back. ", "The camera spins around them and the music tries to feed you a bite of chocolate and call it a meal for your soul.", "\n\nEmily goes goes home to find out Ali’s pregnant with her fertilized egg. ", "This is obviously the first step in the landslide toward Emily and Ali’s #ENDGAME but in the meantime Spencer points out that they both have been violated, which is good, because they absolutely have been. ", "Three out of five happily ever afters as a result of a sexual violation isn’t really where I was hoping this show would end. ", "Wouldn’t it have been something else if this seven-year story about all the ways men take away women’s agency and violate their bodies and their boundaries had given Emily and Alison or Emily and Paige the latitude to really choose each other?", "\n\nAria meets up with Sydney in the back of some limo. ", "They take the “scenic route” around Rosewood while Sydney makes the case for Aria joining “the winning team.” ", "Somebody’s feeding her lines in an earpiece, which Aria realizes, but she stays in the car and listens to the pitch anyway. ", "It’s better than going back home to find Nicole shuffling around the house in Aria’s wedding dress reading Ezra’s true crime novels about both of their miserable lives. ", "When Aria finally shows up at Ali’s, the Liars yell at her and fill her in on Ali’s pregnancy. ", "The Game winds itself up and lands again on Hanna." ]

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[ "A device for blocking spectacle lenses is generally known from document U.S. Publication No. ", "2005/0139309. ", "The device comprises an imaging/aligning station, a measuring station and a blocking station generally in an arrangement alongside one another or in succession, between which stations the spectacle lenses can be automatically transported by a transport system with a spectacle lens mounting head. ", "The imaging/aligning station has a geometrically defined spectacle lens support on which a supported spectacle lens to be blocked can be manually aligned by rotation and/or displacement as desired or as required per prescription. ", "The aligned spectacle lens to be blocked can be mechanically measured in the measuring station at its face at which it is to be blocked. ", "On the other hand, the blocking station has a block piece mount in which a block piece or blocking ring is mounted in centered manner before the aligned spectacle lens is blocked on the block piece by the mentioned face by using a temporarily deformable blocking material, here an optically hardenable adhesive.", "\nThe transport system is in that case in a position of gripping and holding the spectacle lens, which is aligned in the imaging/aligning station, at its other face by the spectacle lens mounting head, then bringing it into a defined position above the measuring station and later the blocking station (horizontal CNC linear axis) and lowering the aligned spectacle lens in a defined manner at the respective station (vertical CNC linear axis) for it to be measured or blocked on the block piece. ", "In that regard, a feature is that the spectacle lens is positioned by the transport system in defined manner, i.e. at any preselectable height above the block piece, and during the blocking can be held in the defined relative position with respect to the block piece while leaving a blocking material receiving gap between spectacle lens and block piece (also termed “spatial blocking”).", "\nA significant advantage of this procedure is that the spectacle lens can be freely positioned in three dimensions in relation to the block piece, thus during blocking never experiences constrained orientation by the block piece, as a result of which also accuracy during blocking of the spectacle lens is increased. ", "The latter concerns, in particular, progressive lenses often referred to as PALs, in which it can be very difficult to correctly set these if they are supported on conventional circular blocking rings, because the progressive curve is not spherical and the spectacle lens is thus not seated fully or is seated loosely on the blocking ring. ", "On the other hand, in the case of “spatial blocking” it is possible to realize in problem-free manner, for example, a desired angular orientation, tilting and/or displacement of the spectacle lens relative to the block piece for, for example, prismatic blocking. ", "In addition, the thickness of the layer of blocking material or adhesive between spectacle lens and block piece is basically freely selectable in the case of “spatial blocking” so that, for example, there is avoidance of the risk of no blocking material being present at specific locations between spectacle lens and block piece because the blocking material could not reach there. ", "In this way, a whole-area support and adhesion/glueing of the spectacle lens can be guaranteed for processing of the blocked spectacle lens at the surface and/or edge. ", "Equally, it is possible to avoid undesired free gaps between spectacle lens and block piece in which liquid, in a given case as the consequence of capillary effects, could collect, which can lead to problems during coating (outgassing under vacuum) if the spectacle lens in the production process is to remain throughout on the block piece, such as described in, for example, document U.S. Pat. ", "No. ", "8,905,388.", "\nIn addition, it was proposed in document U.S. Pat. ", "No. ", "8,616,150 to develop the relevant category of prior art—also in the sense of widest possible automation of the blocking process for production of spectacle lenses on an industrial scale—in such a way that the transport system is in a position of positioning the spectacle lens, which is to be blocked, not only in two directions, but fully in three dimensions, before it is blocked on the block piece. ", "However, this requires six CNC movement axes, namely three CNC linear axes substantially perpendicular to one another and three CNC rotational or tilt axes about these linear axes.", "\nHowever, such CNC blockers—even with only two CNC movement axes—represent a substantial capital cost, need a relatively large installation area and as such are over-dimensioned for smaller prescription workshops as determined by reference to the spectacle lens throughput thereof.", "\nObviously, smaller blockers have already been proposed—see, for example, document U.S. Publication No. ", "2014/0315472—which are accordingly more advantageous and also require only a comparatively small installation area. ", "However, in this prior art the spectacle lenses to be blocked are aligned at the block piece, which significantly restricts the possible relative settings of the spectacle lens with respect to the block piece. ", "Shape-adapted block pieces were created here as a remedy, but this is with considerable outlay with respect to production and stocking of the different block pieces. ", "Genuine “spatial blocking” in the above sense is not possible with these prior art blockers.", "\nAccordingly, it is desired to create a simplest and most economic and compact device possible for the blocking of workpieces, particularly spectacle lenses, for processing and/or coating thereof even in smaller workshops, in which the workpiece is not subject to any significant restrictions with respect to its position relative to the block piece." ]

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[ "This story appears in the March 6, 2017, issue of SPORTS ILLUSTRATED. ", "To subscribe, click here.", "\n\nJames Harden stepped gingerly off the bus at the Kimpton Epic Hotel in downtown Miami, punchy after a two-hour flight from Houston following a 20-point loss to Golden State, and was greeted by a phalanx of photographers along Biscayne Bay. ", "They were not interested in Dwight Howard or Patrick Beverley, Clint Capela or Trevor Ariza. ", "Every camera was fixed on the Beard, and as he strode toward the sleek lobby, he lost himself in their lenses. ", "Why, he wondered naively, were they here? ", "How did they find him? ", "And what were his teammates thinking as they watched the whole high-pitched scene unfold? ", "He felt their eyes trained on him also. ", "Harden was used to fans lining up outside hotels for autographs and selfies, standard road procedure. ", "But not even LeBron James attracts paparazzi while shuffling between mid-market outposts on the regular-season docket. ", "There still exists a yawning gap between sports celebrity and Hollywood celebrity, though not as wide as it used to be.", "\n\n“What’s happening?” ", "Harden asked himself. “", "Who am I?”", "\n\nOn that warm afternoon, in the fall of 2015, it was a difficult question to answer. ", "Over three dizzying years he had metamorphosed from sixth man in Oklahoma City to leading man in Houston, culminating with a white-hot spring/summer when he carried the Rockets to the ’15 Western Conference finals, finished second in the MVP voting, inked a $200 million shoe contract and squired a ubiquitous reality star who makes a habit of transporting professional basketball players across the fame divide. “", "It was a lot,” Harden says, “and it was fast.”", "\n\nNear the end of his summer spree he sprained his ankle during a workout in Los Angeles and was forced to skip his usual beach runs. ", "He reported to training camp out of shape. ", "The Rockets started 0–3. ", "They fired head coach Kevin McHale at 4–7. ", "Tensions between Harden and Howard, simmering for years, boiled over. ", "Howard wanted early post feeds from Harden; Harden wanted high ball screens from Howard. ", "In the final seconds of a two-point loss at New Orleans in December, Harden waited for a screen from Howard that never came, and his subsequent drive was swallowed up. ", "Then, in Dallas in April, it happened again. ", "A player who joined the Rockets midseason eyed Harden and Howard, taking opposite routes out of the locker room. “", "When you come here,” a veteran counseled, “you have to pick your side.” ", "It was up to a 36-year-old interim coach, J.B. Bickerstaff, to manage the mess. ", "Interventions backfired.", "\n\nScott Halleran/Getty Images\n\n​\n\nIt might have been easier if Harden and Howard just threw punches—or at least posted subtweets. ", "But they are both non-confrontational by nature, so Harden stewed in silence, often ducking out of Toyota Center before he had time to stretch or ice. ", "He even drifted apart from Beverley, his closest friend on the team. “", "He was just ... distant,” Beverley says. “", "The losing was really hard on him.” ", "At Artesia High and Arizona State, in OKC and Houston, Harden did nothing but win. ", "After shootarounds last season, he routinely parked his Bentley across from the arena on Clay Street and vented to Scott Pera, his high school coach who is now an assistant at Rice.", "\n\nHarden never criticized Howard, and he still doesn’t. ", "He never complained about a combustible roster—Ty Lawson, Michael Beasley and Josh Smith under the same roof—or moaned about an inexperienced coach, at least not publicly. “", "He just ate it,” says a Rockets official. “", "He ate all of it.” ", "He was tending to Howard on the court and KhloéKardashian off, a double whammy of diva, made even more complex because Khloé was caring for estranged husband Lamar Odom after his overdose at a Nevada brothel. ", "At one point, Khloé took to a live video chat and denied that her sexuality was to blame for the Rockets’ struggles, though she chose a far spicier turn of phrase.", "\n\n​\n\nRemarkably, Harden still authored his most prolific season in 2015–16, setting career highs in points (29.0), assists (7.5) and rebounds (6.1) while dragging the Rockets to a short-lived playoff berth. ", "Howard put up his best field goal percentage ever (62.0). ", "Beverley eclipsed 40% from three-point range for the first time. ", "Ariza improved and Capela cracked the rotation. ", "Harden shrugs. ", "The defense, where dysfunction always reveals itself, was dismal. ", "He didn’t make any of the three All-NBA teams, a reminder that the highest class of superstar is not allowed to lose his locker room, no matter the extenuating circumstances.", "\n\nAt the end of the worst year of his life—the term he uses, and not lightly, having grown up in a mobile home on the outskirts of Compton—Harden gathered his four best friends, high school teammates who now live in Houston, to review summer plans. ", "Entourage carries a negative connotation in sports, as if it’s all Turtle and Johnny Drama, but the inner circle often provides the reality check. ", "Its members are sometimes the only ones who go back far enough to share unvarnished truth.", "\n\n“We just sat down in his house and let him know, ‘Something has to change,’” says Camilo (Juny) Valencia, a former Artesia guard. “‘", "You have to simplify.’”", "\n\nIt is a stormy Valentine’s Day in downtown Houston and Harden lounges on a red sofa at Toyota Center, as appropriate a time and place as any to discuss the power of relationships. “", "I might watch a movie tonight,” he says. “", "My mom is my valentine.” ", "Khloé has moved on to the Cavaliers and their relentless power forward, Tristan Thompson, while Harden has rekindled his partnership with the Rockets and his courtship of the MVP trophy. ", "A newly minted point guard, Harden is still averaging 28.9 points but now he is also leading the league with 11.3 assists, and if you combine his buckets and dimes, he is generating just less than half of Houston’s entire offense. ", "In a season of virtuoso performances, when the 50-point barrier has become porous, Harden is stretching the boundaries of what was considered possible for an individual player. ", "Twice he’s delivered 50-point triple doubles—which before this season hadn’t happened since 1973—including a 53/17/16 against the Knicks on New Year’s Eve, when he was directly responsible for 95 points.", "\n\n“I’m not worried about anything but hooping,” says Harden, 27, “and that may be why I’m having this kind of success.” ", "The process of untangling a crowded life began a year ago, when he and Khloé broke up after an eight-month romance, which began with a meeting at Kanye West’s basketball-themed birthday party at Staples Center in June. ", "Harden does not reference Khloé but reflects on the tabloid apparatus that accompanies her. “", "I didn’t like all the attention,” he says. “", "I feel like it was for no reason. ", "I wasn’t getting anything out of it except my name out there and my face out there, and I don’t need that. ", "It wasn’t uncomfortable, but it wasn’t me. ", "I don’t need pictures of myself when I’m driving my car. ", "Who cares? ", "What shoes am I wearing? ", "Who cares? ", "Where am I eating? ", "Who cares? ", "It was unnecessary stuff that I think trickled down to my teammates. ", "I had to eliminate that.”", "\n\nGreg Nelson/SI\n\n​\n\nHarden, as fame seeker, was never a fit. ", "Yes, he has the illustrious beard and the outrageous wardrobe, and his nightlife is a lot more fun than Netflix. ", "But his personality is muted, as anyone who interviews him can attest. “", "I think he wanted to take his fame out for a spin,” says a Rockets source, “and I think he decided he liked it better in the garage.” ", "Harden, who typically summers in L.A., chose Phoenix so he could avoid the tabloid big top and breathe the college air. “", "I wanted to be around the people who knew me before all this...\" he says, flicking the tuft on his chin. ", "It flows like an amoeba.", "\n\nHarden trained at Arizona State with longtime sports performance director Rich Wenner, who had introduced him to the Stairmaster as a smooth-faced freshman at Arizona State, and he did skills work with development coach Irving Roland, whom he met at the LeBron James Skills Academy a year later. “", "I need to get back to what I used to do,” Harden told the men, and they understood. ", "On the days he dragged, Roland threw YG or Meek Mill on the Pill, and he drew a second wind. “", "It was James Harden, 18-year-old, working out,” Wenner says. “", "No flamboyance, no drama, just James.”", "\n\nIn early June, Harden called Rockets CEO Tad Brown and said he intended to withdraw from the Olympics, an excruciating announcement for someone who treasures his Team USA memories. “", "I have to get my mind right, my body right and commit to this organization,” Harden said. ", "He sat in the Rockets’ war room on draft night even though they didn’t pick until the second round. ", "He accompanied executives to Atlanta for free-agent pitch sessions with Al Horford and Kent Bazemore, both of which were ultimately unsuccessful. ", "He hung out for a few days in Scottsdale with Kevin Durant, the prize of the market, which yielded some sumptuous dinners but no formal meetings.", "\n\nGone were Howard, Lawson, Beasley and Smith. ", "In their place were adults such as stretch forward Ryan Anderson, whom Harden started eyeing as a pick-and-roll partner in 2013, and sniper Eric Gordon. ", "Harden summoned the team to summer league in Las Vegas, where they watched the young Rockets, and then to a Drake and Future concert in Miami. “", "Guys sometimes go their own way in this league and do their own thing,” Harden says. “", "It’s way too easy to lose touch. ", "But it’s my job to control this locker room and make sure that what happened last year never happens again.”", "\n\nGreg Nelson/SI\n\nLeadership, at least the vocal variety, does not come easily to Harden, which is why he watches videos of Atlanta-based motivational speaker Tim Elmore for cues. “", "I have to open up,” Harden says. “", "I can’t be up here. ", "I have to be one of them.” ", "He stops plays at practice to review the angle of a screen with Capela. ", "He invites second-year center Montrezl Harrell to dinner on the road. ", "And after an overdue summit last summer, he touches base with Beverley daily. “", "You know what makes San Antonio so good?” ", "Beverley asks. “", "They have the talent, but everybody has talent. ", "What makes them different is they have their life in order. ", "Guys like me and James, we didn’t have a lot growing up, and this was a chance to go all out and get it. ", "But he’s got the money, the cars, the fame. ", "He’s seen all that and done all that. ", "It can just be about winning now.”", "\n\nHarden signed a four-year, $118 million extension with the Rockets in July 2016, sidestepping the specter of free agency. (", "Harden’s original deal would have been up in ’18.) ", "His obligations to Adidas were curtailed after the release of his first signature shoe in November. ", "The last of his high school pals moved out of his home. ", "Life is simple, by celebrity standards, and Houston is 42–18, the rare place where fewer stars produce more W’s. ", "Harden insists he’s changed, but more clearly, the environment around him has changed.", "\n\n“Ninety percent of teams in this league don’t have any alignment at all between the front office, the coaching staff and the players,” says one NBA head coach. “", "You looked at this team last year and they were all f----- up. ", "You look at them now and they are completely aligned. ", "James Harden has become Steve Nash—if Steve Nash were on steroids.”", "\n\nNash spent four landmark seasons in Phoenix with head coach Mike D’Antoni, capturing the MVP award twice, leading the league in assists three times, averaging 58 wins. ", "The Suns were small-ball revolutionaries with their spread pick-and-rolls, but they weren’t champions, and when they fell yet again to the Spurs in the 2007 playoffs D’Antoni started doubting the breakneck system he birthed. “", "When you don’t get over the hump, you question everything,” D’Antoni says. “", "Players questioned it, I questioned it, and I think I blinked.” ", "Maybe you’re wrong, D’Antoni told himself, and Phoenix acquired center Shaquille O’Neal in ’08, forming a traditional frontcourt with power forward Amar’e Stoudemire.", "\n\nOf course, bully ball didn’t work either, and D’Antoni left for the rebuilding Knicks a few months later, believing he had it right the first time. ", "He peddled his rollicking vision to Carmelo Anthony, which required a move from small forward to power forward, but Melo resisted. ", "After four years it was on to the Lakers, with Howard and Pau Gasol, either of whom could have been the five man in his offense. ", "But L.A. kept both of them—Shaq and Amar’e all over again. “", "It was doomed,” D’Antoni admits. ", "In ’14 he and his wife moved to his home state of West Virginia and bought a place at The Greenbrier. ", "He embarked on a happy retirement playing golf with fellow resident Jerry West.", "\n\nHe’d be teeing off right now, he believes, if not for the Warriors. ", "In the fall of ’14, D’Antoni was like basketball junkies everywhere, firing up League Pass and marveling at Steph Curry moonbeams. “", "I’m watching this,” D’Antoni recalls, “and I’m going, ‘Yeah, baby.’” ", "The Warriors’ head coach, Steve Kerr, was his general manager in Phoenix. ", "Their lead assistant, Alvin Gentry, was his lead assistant. ", "Several staffers and players used to be on his bench. ", "The Dubs were not an exact replica of the Suns—they ran fewer pick-and-rolls, for instance—but the lineups were small, the floor was spaced, and the tempo was Nash fast. ", "D’Antoni called Gentry regularly, and a couple times touched base with Kerr. ", "He took mental notes for potential jobs, brainstorming ways to replicate Draymond Green. ", "D’Antoni rejoiced when Golden State became the first so-called jump shooting team to win the title. “", "O.K., this does work,” he told himself. “", "I wasn’t stupid. ", "I wasn’t crazy. ", "You need the right players, the right mentality. ", "But it can be done.”", "\n\nBill Baptist/Getty Images\n\nIn the winter of 2015, D’Antoni finished a panel at the MIT Sloan Sports Analytics Conference and was trailed out the door by a pack of devotees. ", "The hoop nerds, who espoused the benefits of layups, open threes and little else, loved D’Antoni. “", "And I loved them,” D’Antoni says, “because they put on paper what I was trying to put on the floor.” ", "One of those endearing eggheads was Daryl Morey, the Rockets’ general manager and Sloan cofounder, who already applied D’Antoni’s rationale to almost every roster he built. ", "A year after D’Antoni played rock star at MIT—Morey’s term—the Rockets were in tatters. “", "I spent a lot of time being angry,” Morey says. ", "Last spring he interviewed several prospective head coaches who could overhaul Houston’s abysmal defense. ", "So it goes in coaching searches. ", "Organizations look to minimize their weakness rather than maximize their strength.", "\n\nHarden, like Curry and Nash, is never going to be a stopper. ", "But at 6' 5\" and 220 pounds, he is both wizard and giant, creating those cherished layups and corner threes through head fakes and step backs, sleight of hand and force of will. ", "If Mike D’Antoni and Daryl Morey had a baby, it would be James Harden, running high-efficiency pick-and-rolls at the top of the crib. ", "They formed a holy analytical trinity. ", "Owner Leslie Alexander, whose teams deployed stretch fours as far back as Matt Bullard and Robert Horry in the early 1990s, interviewed D’Antoni and endorsed him. ", "The Rockets knew they’d be panned for supposedly neglecting their D, but they were lining up behind their Beard. “", "Let’s not put a boat anchor on Secretariat,” Morey concluded, during a staff meeting at the end of the search. “", "Let’s double down.”", "\n\nThe first time D’Antoni and Harden met at Toyota Center as colleagues, they watched video of Nash. “", "James,” the coach cooed, “you can do all this.” ", "D’Antoni, who spent so many empty seasons trying to sell superstars on his system, wanted to coax Harden from the wing to the point. ", "Finally, he found a headliner he didn’t have to sway. “", "I can actually coach,” D’Antoni thought, “instead of convince.” ", "Another year, it might have been a harder conversation, but the NBA has caught up to D’Antoni, accepting his theories as truths. ", "Harden needed D’Antoni as much as D’Antoni needed him. ", "While the coach was trying to rebuild his career, the Beard was trying to streamline his life, and point guard was a place where he could do it. ", "His team, his ball, his decision. ", "Every possession, every game. ", "There is no nuance to the Rockets. ", "They are the James Harden Experience, unfiltered and unleashed.", "\n\n“This,” Harden says, “is probably what I should have been doing all along.”", "\n\nWhen he deconstructs his pet play, he frames his face with his hands, as if peering into an imaginary TV. “", "Clint sets the high screen, so I know the guy guarding me is gone,” Harden begins. “", "I’ve got a big in front of me, one-on-one, and I’ve got my head up trying to figure out who is going to come open. ", "My first read is Clint for the lob. ", "My second read, if one of their defenders sucks in, is the corner man for three. ", "My third read, if no one leaves a shooter, is to go all the way for the layup. ", "But if somebody rotates over, I’ll swing it, and try to get the three that way. ", "It’s all decided in a split second, but it’s never predetermined. ", "It seems fast, but when it’s happening, it’s so slow in my head.”", "\n\nThe Rockets play with pace, but they’re not seven seconds or less. ", "Even when Harden was a boy, he liked to cradle the ball before he determined his course, infuriating coaches who feared he’d let the shot clock run dry. ", "But the buzzer rarely sounded, and eventually, they recognized his gift for gauging time. ", "Ever deliberate, Harden ponders all sorts of matters as he pauses atop the key, Spalding in his hands. ", "Where is the help defender? ", "When was Ariza’s last shot? ", "When was Beverley’s last basket? ", "How do they feel about that?", "\n\n“It’s incredible how his mind works,” D’Antoni says. “", "He’s very aware of who’s happy, who’s unhappy, and why.” ", "Harden will never unify a locker room with impassioned oratory. ", "But at point guard, he can control his teammates’ emotions in a more pragmatic way, through their touches. ", "One reason Harden leads the NBA in turnovers, D’Antoni believes, is that he forces passes to players he’s worried about. ", "Another reason, of course, is that he handles the ball almost every second. ", "D’Antoni tried to hire Nash, whose turnover totals were also high, as a rabbi for Harden. ", "But Nash, like so many in D’Antoni’s orbit, was already committed to Golden State, where he is a player development consultant.", "\n\nGreg Nelson/SI\n\n​\n\nThis is the year of two transcendent teams (Warriors, Cavaliers) and two spectacular players (Harden, Russell Westbrook). ", "The Rockets would love to employ four superstars, but they’ve discovered some fringe benefits to one. ", "Hierarchy is understood. ", "Roles are fixed. ", "Starters are satisfied chipping in 12 points per game. ", "Anderson and Gordon, expats from New Orleans, came up with the idea to set up several feet behind the three-point line. ", "The extra distance imperils their accuracy, but provides even more space for Harden’s headlong drives. ", "Morey, who long trumpeted talent over harmony, has taken a slightly different approach. ", "The Rockets don’t have an elite player alongside Harden. ", "They have an elite fit.", "\n\nHouston has split a pair of meetings with the Warriors this season, but to outlast them in May, the Rockets might have to hit every three-pointer for two weeks. ", "They currently lead the league in threes, made and attempted, and D’Antoni bets those numbers will rise across the board with time. “", "The other night Denver made 24 threes,” D’Antoni says. “", "That’s where basketball is going. ", "Five years from now, that won’t be unbelievable. ", "Teams will be 25 for 50, 25 for 40. ", "Guys will start practicing from an earlier age and the percentage will keep going up.”", "\n\nWhether or not the Rockets are real contenders—“We’re convinced we can do it,” D’Antoni says. “", "We might be delusional”—Harden is something to behold, a puppet master with a ball instead of a string, requiring only that familiar high screen. ", "The pick-and-roll is the most common set in the NBA, and according to Houston’s data, no one has used it more efficiently than Harden since the stat was first tracked more than 15 years ago. “", "The smartest player in our league is LeBron James,” a rival head coach says. “", "James Harden is second.” ", "Before a game against Miami in February, Heat coaches examined ways to stifle the Beard, from trapping him out of the pick-and-roll to sagging under the screen and letting him fire. ", "When the Heat faced the Thunder in the 2012 Finals, they prioritized Harden over Westbrook and Durant, believing he was the superior playmaker even though he was the sixth man. “", "Whatever we do,” one Heat coach laughed, “he’ll still probably get 40 points and a triple double.” ", "He finished with 38 and a triple double.", "\n\nIn popular culture, performance is often inversely proportional to fame, a concept Harden has come to embrace. ", "On the court, he has never looked more potent, and off, he has never felt more anonymous, at least since the Beard. “", "I’m under the radar,” he says, stunning given his appearance and his play. ", "But it’s true, relative to past experience. ", "When Harden stands in the checkout aisle at Target, he lets his eyes wander to the tabloid racks and all the splashy covers.", "\n\n“I like knowing I’m not going to see myself,” he says. “", "It feels good.”" ]

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[ "On Decem­ber 14, the polit­i­cal advo­ca­cy group Our Rev­o­lu­tion host­ed a livestream event with Sen. Bernie Sanders (I‑Vt.) ", "and Rep. Kei­th Elli­son (D‑Minn.) ", "dis­cussing the need to reform the Demo­c­ra­t­ic Par­ty. ", "Both Sanders and Our Rev­o­lu­tion have endorsed Elli­son in his cam­paign to be the next chair of the Demo­c­ra­t­ic Nation­al Com­mit­tee (DNC). ", "What fol­lows is an abridged tran­script of their remarks, edit­ed for length and clarity.", "\n\nWe don't need to decide between social justice and economic justice—we got to have all of that justice together. ", "Do we not?", "\n\nBernie: What we are doing tonight is not sexy, and it’s not going to make the head­lines in the news­pa­pers all over the coun­try, but it is unprece­dent­ed for the Demo­c­ra­t­ic Par­ty and for the long-term future of our coun­try, and it is of enor­mous con­se­quence. ", "At a time of low vot­er turnout, at a time when mil­lions of Amer­i­cans are demor­al­ized polit­i­cal­ly and are sick and tired of estab­lish­ment pol­i­tics and estab­lish­ment eco­nom­ics, we are gath­ered here tonight not only in this build­ing but all over Amer­i­ca to begin the process of trans­form­ing Amer­i­can pol­i­tics and of cre­at­ing a gov­ern­ment which works for all of the peo­ple — not just the 1%.", "\n\nThat is what we are here to do, and in order to make that hap­pen our first step is to trans­form the Demo­c­ra­t­ic Par­ty from a top-down par­ty to a bot­tom-up body, to cre­ate a grass­roots orga­ni­za­tion of the work­ing fam­i­lies of this coun­try, the young peo­ple of this coun­try. ", "I will tell you, hav­ing been all over this great nation of ours, there is an incred­i­ble ide­al­ism of mil­lions of young peo­ple who believe in this coun­try and who love this coun­try and are pre­pared to fight to make this coun­try all that we can become. ", "I want to also urge all Amer­i­cans regard­less of income, regard­less of their race, their nation­al­i­ty, their sex­u­al ori­en­ta­tion, to jump into the polit­i­cal process and make the Demo­c­ra­t­ic Par­ty a demo­c­ra­t­ic par­ty with a small ​“d,” not just a cap­i­tal ​“d.”", "\n\nThis elec­tion for chair of the DNC is not a per­son­al­i­ty con­test — the media may think it is, but it’s not. ", "From what I can gath­er, Keith’s oppo­nents are decent peo­ple who want to improve the Demo­c­ra­t­ic Par­ty and want to see us become vic­to­ri­ous. ", "The key dif­fer­ence here is whether we con­tin­ue the sta­tus quo or whether we bring forth a very dif­fer­ent vision for the future of the Demo­c­ra­t­ic Par­ty. ", "That is what this elec­tion is about, and here is why we need to go for­ward in a very dif­fer­ent direc­tion than cur­rent­ly exists.", "\n\nThe painful truth is that despite Pres­i­dent Obama’s strong vic­to­ries in 2008 and 2012, the Demo­c­ra­t­ic Par­ty has lost enor­mous polit­i­cal ground over the last eight years. ", "The Repub­li­cans have just won the White House. ", "The Repub­li­cans now con­trol the Sen­ate. ", "The Repub­li­cans now con­trol the House. ", "Repub­li­can gov­er­nors now con­trol almost two-thirds of the state­hous­es in this coun­try, and over the last eight years Democ­rats have lost some 900 leg­isla­tive seats from one end of Amer­i­ca to the oth­er. ", "That is the sim­ple, indis­putable truth. ", "Clear­ly, what­ev­er the lead­er­ship of the Demo­c­ra­t­ic Par­ty has been doing over the last few years has failed, and we need fun­da­men­tal change.", "\n\nThe Repub­li­can Par­ty advo­cates cut­ting the Social Secu­ri­ty that the Amer­i­can peo­ple want to expand. ", "Repub­li­cans want to throw mil­lion Amer­i­cans off of their health insur­ance. ", "They now want to cut Medicare. ", "They want to cut Med­ic­aid. ", "They want to cut fed­er­al aid to edu­ca­tion. ", "Despite com­pet­ing against a Repub­li­can Par­ty that not only does not want to do any­thing sub­stan­tive about cli­mate change, to a large degree they do not even rec­og­nize the sci­en­tif­ic real­i­ty of cli­mate change — despite all of that, and much more — the Demo­c­ra­t­ic Par­ty has lost sig­nif­i­cant polit­i­cal ground. ", "We have got to ask why that has occurred.", "\n\nBroth­ers and sis­ters, the sta­tus quo is not work­ing, and we will not suc­ceed if we con­tin­ue along the same old path. ", "Now is the time for real change in the Demo­c­ra­t­ic Par­ty, now is the time to revi­tal­ize the Demo­c­ra­t­ic Par­ty and bring in peo­ple who have not been wel­comed in the past. ", "We should not be afraid of new ener­gy and new faces; we should wel­come and embrace new ener­gy and new faces. ", "Now is the time for a chair of the Demo­c­ra­t­ic Par­ty who has a very dif­fer­ent vision of the par­ty then those who are in con­trol today. ", "Now is the time for Kei­th Elli­son to become chair of the Demo­c­ra­t­ic Party.", "\n\nAs I know many of you are aware, Kei­th is cur­rent­ly the co-chair of the Con­gres­sion­al Pro­gres­sive Cau­cus, and has been one of the lead­ing pro­gres­sive voic­es on all of the major issues fac­ing the mid­dle class and work­ing fam­i­lies of our coun­try. ", "He has been there on pick­et lines. ", "He’s been up front and out front in terms of work­ers’ rights, in terms of the envi­ron­ment and cli­mate change, in terms of the need to cre­ate a health­care sys­tem that guar­an­tees health­care to all peo­ple as a right. ", "He has been out in front on women’s rights, on the rights of the LGBT com­mu­ni­ty, on the need for real crim­i­nal jus­tice reform, on the need for immi­gra­tion reform and on the need for real tax reform, so that Don­ald Trump and the oth­er bil­lion­aires start pay­ing their fair share of tax­es. ", "For many, many years Kei­th has been there not as a fol­low­er, but as a leader. ", "Unlike some of the oth­er can­di­dates run­ning for chair, Kei­th knew from day one that the TPP was a dis­as­ter for work­ing fam­i­lies and helped us defeat the TPP. ", "Kei­th is by nature a grass­roots orga­niz­er — that is what he does and that is who he is. ", "He is not a crea­ture of the inside-the-belt­way world; he is a per­son who lives in the real world, feels com­fort­able in the real world, and is going to bring the real world into the Demo­c­ra­t­ic Party.", "\n\nKei­th already has the sup­port of some of the strongest grass­roots orga­ni­za­tions and trade unions in this coun­try, and we have the sup­port of many, many pro­gres­sive elect­ed offi­cials. ", "But we have some­thing even more impor­tant than all of that right now: We have the sup­port of more than 600,000 men and women in every state in this coun­try, who have signed peti­tions to demand and urge that Kei­th Elli­son become the next chair of the Demo­c­ra­t­ic Par­ty. ", "600,000 peo­ple. ", "Our goal, and I urge all peo­ple to get involved in this process, is to take that 600,000 num­ber and make it a mil­lion. ", "Please get your friends and co-work­ers involved, please go to Our​Rev​o​lu​tion​.com and get your friends to sign up.", "\n\nBroth­ers and sis­ters, we are in a per­ilous and momen­tous moment in Amer­i­can his­to­ry. ", "You all know that, and we are going to need a polit­i­cal par­ty that has the guts to stand with work­ing fam­i­lies, has the guts to take on the big mon­ey inter­ests that con­trol to a large degree our eco­nom­ic and polit­i­cal life.", "\n\nIt is my great priv­i­lege to intro­duce to you some­one who I believe is going to be the next chair of the Demo­c­ra­t­ic Nation­al Com­mit­tee. ", "Please wel­come con­gress­man Kei­th Ellison.", "\n\nKei­th: If there was ever a moment when peo­ple who love this coun­try and the peo­ple in it need to step up and do every­thing they can to improve the lives of their fel­low Amer­i­cans, that moment is right now.", "\n\nIf I told you that you had an oppor­tu­ni­ty to fight for peo­ple who felt vul­ner­a­ble and scared in this Trump Amer­i­ca, would you do it? ", "If I told you that you had a chance to stand up and fight for work­ing peo­ple, would you do it? ", "If I told you that you could be the hero of folks who pour the cement, who teach the class­es, who take care of the folks in the hos­pi­tal, who take care of the chil­dren, who cook the food — I mean the hard-work­ing peo­ple of Amer­i­ca — would you step up and do some­thing for them?", "\n\nWell that’s good, because we need you to do all of that right now. ", "Because let me tell you, it’s hard to imag­ine some­body like Don­ald Trump being elect­ed pres­i­dent, but in a few days he will be the pres­i­dent. ", "I don’t know what stage in the whole spec­trum of grief you may be at, but I think we need to arrive at accep­tance that he’s about to be the pres­i­dent. ", "And that means that each of us and all of us have to do every sin­gle thing that we can to pro­tect our fel­low Amer­i­cans and to advance the cause of eco­nom­ic and social jus­tice. ", "This is a his­toric moment, this is a move­ment moment and this moment may well be the moment when the Amer­i­can peo­ple thought to reclaim their democ­ra­cy of, by and for the people.", "\n\nNow Trump ran say­ing stuff like, ​“more jobs, new trade mod­el.” ", "As soon as he got in there he said he was going to drain the swamp. ", "You remem­ber that one. ", "Well, he’s fill­ing up with lob­by­ists, bil­lion­aires, cor­po­rate exec­u­tives, hedge fund man­agers, all these folks. ", "We’re going to have the rich­est cab­i­net ever: If you just had a few mil­lion dol­lars, you’d be like the poor guy in that bunch.", "\n\nTrump said he said he’s going to fight for lit­tle peo­ple, yet he nom­i­nates as Sec­re­tary of Edu­ca­tion anoth­er bil­lion­aire who’s against pub­lic schools, when 90 per­cent of Amer­i­can school chil­dren will go to a pub­lic school. ", "Bet­sy DeVos wants to pri­va­tize them. ", "Trump said he was going to help work­ing peo­ple. ", "His nom­i­nee for labor sec­re­tary is anoth­er bil­lion­aire who makes bil­lions on the backs of low-wage fast-food work­ers. ", "He is actu­al­ly against the min­i­mum wage and would low­er it if he could. ", "This is the cab­i­net he’s picked so far. ", "He said he was going to appoint the best and most qual­i­fied, and yet Dr. Ben Car­son admits he knows noth­ing at all about housing.", "\n\nSo I guess it’s no sur­prise that Trump also nom­i­nat­ed a guy who says that there’s no such thing as cli­mate change to be the head of the Envi­ron­men­tal Pro­tec­tion Agency. ", "At a time when peo­ple are liv­ing in tox­ic areas all over this coun­try, he picks an EPA leader who is not in favor of pro­tect­ing peo­ple from envi­ron­men­tal haz­ards. ", "So peo­ple, we got our work cut out for us.", "\n\nWe can always count on the right wing to say that rich peo­ple don’t have enough mon­ey, and the poor folks have too much mon­ey. ", "We can always count on them to say the rich folks need one more tax cut, one more reg­u­la­tion that they don’t have to fol­low, and reg­u­lar work­ing peo­ple need one less thing that’s going to help them make it through the week. ", "Okay, so that’s them, what about us? ", "Are we going to hit the streets? ", "Are we going to organize?", "\n\nThis is what we got to do: Right now we got to reset the future of the Demo­c­ra­t­ic Par­ty. ", "We got to reset the Demo­c­ra­t­ic par­ty on the basis of grass­roots activism. ", "We got to reset the Demo­c­ra­t­ic Par­ty on the basis of work­ing peo­ple who are striv­ing every sin­gle day to make a bet­ter life for them­selves and their fam­i­lies right here in Amer­i­ca. ", "I’m talk­ing about African Amer­i­cans, white Amer­i­cans, Lati­no Amer­i­cans, Native Amer­i­cans. ", "I’m talk­ing about Asian Amer­i­cans, about peo­ple who are Jew­ish and Mus­lim and Chris­t­ian and Bud­dhist and Hin­du and those who have no faith at all. ", "I’m talk­ing about folks like you and me, folks like us that need to say that the Demo­c­ra­t­ic Par­ty has got to be demo­c­ra­t­ic, and it starts with get­ting some lead­er­ship in there that’s going to fight for that democ­ra­cy. ", "I’m telling you right now, this is the moment we have been wait­ing for: The time for us to stand up and fight back and reclaim our nation. ", "Y’all ready?", "\n\nNow I want to tell you that I am very proud to have your sup­port, and I’m so amazed at the tremen­dous turnout we have here tonight. ", "Big shoutout to the folks on the livestream. ", "If the Demo­c­ra­t­ic par­ty’s going to make any reforms, one of them has got to be that we use moments like this one — mass meet­ings of hun­dreds of thou­sands of peo­ple — to get togeth­er to talk about what we’re going to do to make our coun­try bet­ter for every­one. ", "We got to include every­body, and if tech­nol­o­gy can help us get more folks on the table, well then let’s do it.", "\n\nThe Demo­c­ra­t­ic Par­ty should be the par­ty of the peo­ple. ", "The Demo­c­ra­t­ic Par­ty should be the par­ty for those who want a bet­ter future for their chil­dren and grand­chil­dren. ", "It should be a par­ty that invests in work­ers and pro­tects their abil­i­ty to orga­nize and fight for a fair wage in good work­ing con­di­tions. ", "The Demo­c­ra­t­ic Par­ty should be a par­ty that believes every­one should have equal access to the Amer­i­can Dream and equal rights before the law. ", "The Demo­c­ra­t­ic Par­ty should say it does­n’t mat­ter what your col­or is, we’re going to treat you with fair­ness and equal­i­ty and respect. ", "It does­n’t mat­ter who you love and go to bed with at night; it does­n’t mat­ter who your clos­est of kin is, they are your choice and we respect and hon­or that choice. ", "That’s what the Demo­c­ra­t­ic Par­ty should be. ", "The Demo­c­ra­t­ic Par­ty should say whether you were born in Amer­i­ca or whether you came here, we respect you. ", "We believe that the Demo­c­ra­t­ic Par­ty should be the par­ty of, by and for the people.", "\n\nAnd yet, we know that even a good car some­times needs a tune-up. ", "You know what I mean. ", "It needs new wheels, new brake pads, new belts, new hoses, new oil; it needs new spark plugs, maybe needs a paint job, needs to get that win­dow that’s been cracked fixed. ", "You got to main­tain and update and invig­o­rate every­thing. ", "If you just let it slide, it tends not to work so well.", "\n\nWell now, I know some folks don’t want to hear it, but Democ­rats have lost 935 leg­isla­tive seats and Repub­li­cans now con­trol two-thirds of gov­er­nors’ offices — and let me tell you, the state leg­is­la­ture is very, very impor­tant, because that is where our vot­ing rights are made. ", "If you have a life­time ban on vot­ing if you have a felony, like they have in Flori­da, it’s because the state says so. ", "If you nev­er lose your right to vote, like they have in Ver­mont and Maine, that’s because the state says so.", "\n\nHow is it impact­ing the Amer­i­can peo­ple’s right to ful­ly par­tic­i­pate in democ­ra­cy when 935 leg­isla­tive seats and state leg­is­la­tures have been lost by Democ­rats? ", "How has it affect­ed redis­trict­ing? ", "It has dev­as­tat­ed us. ", "How has that affect­ed a wom­an’s right to choose in Ohio? ", "Gov­er­nor John Kasich said he has a 20-week ban on the right for a woman to choose abor­tion. ", "Let me tell you some­thing: This is none of his busi­ness. ", "It’s uncon­sti­tu­tion­al, but he did it because he wants a con­sti­tu­tion­al chal­lenge, because he wants the case to go up there, because he wants to see the Supreme Court strip away a wom­an’s right to make deci­sions for her fam­i­ly and her­self and her body. ", "That’s some­thing we have got to take very seri­ous­ly, but it’s going on at the state level.", "\n\nYou know what? ", "Rais­ing the min­i­mum wage is win­ning on bal­lot ini­tia­tives, but Democ­rats aren’t win­ning. ", "They like our ideas, but some­how our can­di­dates aren’t get­ting through. ", "We need a retool. ", "I don’t rec­om­mend folks smoke mar­i­jua­na, but I tell you it is crazy to throw peo­ple in jail for it, and when you see that all over the coun­try these bal­lot ini­tia­tives are pass­ing the right for med­ical and even recre­ation­al use. ", "Why fill up the jails for some­thing like that? ", "That does­n’t make no sense at all.", "\n\nI’m run­ning for DNC chair because it’s time to turn all of this stuff around. ", "It is time, and all of us have to step up. ", "Each of us know no DNC chair, no elect­ed offi­cial, can make the changes that have to be made. ", "They’re going to have to be made by the mil­lions of Amer­i­cans all across this coun­try who believe in equal­i­ty for all peo­ple, who believe in a fair econ­o­my, who believe that peo­ple have the right to choose and make their own per­son­al deci­sions, who believe that cli­mate change is going to destroy this world and our abil­i­ty to live on it unless we do some­thing right now. ", "This is what we’ve got to do. ", "We can remake this par­ty right now.", "\n\nI am a per­son who believes in uni­ty, and I do absolute­ly thank the folks who have been around for a long time and hon­or their insti­tu­tion­al mem­o­ry and thank them for their ser­vice. ", "But I also believe that it is absolute­ly time for a very seri­ous injec­tion of ener­gy and rein­vig­o­ra­tion. ", "These two things don’t need to be at odds; these things actu­al­ly, if they work togeth­er, can serve us all very, very well. ", "We all have our ideas about how things should go, so we need lead­er­ship that is going to say we’re going to stick togeth­er and stay togeth­er. ", "Maybe cuss each oth­er out a lit­tle bit, but at the end of the day we’re going to come out hold­ing hands and be a team.", "\n\nI also believe that we got to stand up tall for small. ", "Now, what do I mean by that? ", "You know, Howard Dean was right to say we need a 50-state strat­e­gy, but we got to go beyond that now. ", "We need a 3,141-county strat­e­gy. ", "We need strat­e­gy that gets gran­u­lar. ", "We need a block-by-block, a precinct strat­e­gy; we need a strat­e­gy that gets right down to the nit­ty-grit­ty, because the resources of the Demo­c­ra­t­ic Par­ty need to be moved right down clos­est to the vot­er. ", "That’s where they need to be. ", "I’m talk­ing about the mon­ey, the train­ing, the data, the resources. ", "But I can tell you that city offi­cials and state leg­isla­tive folks, and local coun­ty peo­ple, and just grass­roots rank-and-file do not feel like they are being heard or lis­tened to or included.", "\n\nThis a fact. ", "I’m just telling the truth. ", "If we want to win, we will lis­ten to our local offi­cials and our grass­roots rank-and-file. ", "We got to get small. ", "I already men­tioned to you that we have got to com­mu­ni­cate, we got to use live-stream­ing like we are right now and this has got to be our reg­u­lar prac­tice. ", "All of us togeth­er are smarter than any one of us, but if we don’t share infor­ma­tion and access, we can­not make max­i­mum use of all of the intel­li­gence and cre­ativ­i­ty that peo­ple are com­ing up with every day. ", "We will do these things, we will make use of the tal­ents that we have avail­able to us, so abun­dant if only we would let go of our need to con­trol every­thing and hand over the pow­er to the peo­ple clos­est to the voter.", "\n\nThe Demo­c­ra­t­ic Par­ty must always be a par­ty that stands for the respect and dig­ni­ty of all peo­ple. ", "Wal­ter Reuther was the farmer who spoke at the March On Wash­ing­ton, which was not only for civ­il rights but for jobs as well. ", "When Wal­ter Reuther of the Unit­ed Auto Work­ers got up there, he said that there’s a direct line between the bread box and bal­lot box.", "\n\nHe was right, was­n’t he? ", "We got to fight for eco­nom­ic jus­tice; we got to make sure that pros­per­i­ty for work­ing peo­ple is avail­able to them and that they have it. ", "We don’t need to decide between social jus­tice and eco­nom­ic jus­tice — we got to have all of that jus­tice togeth­er. ", "Do we not? ", "You know I’ve heard peo­ple talk about the white work­ing-class ver­sus the ris­ing new Amer­i­can elec­torate. ", "Well let me tell you some­thing, we got to stand for both. ", "We got to stand for all; we can nev­er sac­ri­fice between the two. ", "If we don’t stand up for both, we’re not going to have nei­ther one. ", "Because they would use trib­al­ism and racial manip­u­la­tion to low­er our wages. ", "Once they get us fight­ing with each oth­er on the basis of these things, they’re always going to come take the mon­ey. ", "We’ve got to stay together.", "\n\nWe have also got to turn out the vote. ", "In 2014, we saw a 70-year low in vot­er turnout. ", "In 2016, over 90 mil­lion eli­gi­ble vot­ers did not vote. ", "We say we’re only going to cam­paign in the swing states, and we’re only going to go to the like­ly vot­ers, and we leave lit­er­al­ly mil­lions of peo­ple not par­tic­i­pat­ing. ", "When we do that we leave our­selves to lose Wis­con­sin, which is a blue state. ", "We leave our­selves to lose Michi­gan, which is the home of the UAW. ", "We lose these states that we should win because we have this strat­e­gy that we’re only going to talk to cer­tain peo­ple. ", "What if we start­ed talk­ing to everybody?", "\n\nWe need to stop look­ing at each oth­er and seg­ment­ing each oth­er; and see each oth­er as true allies to rebuild this par­ty. ", "We’ve got to ener­gize activists at the grass­roots and unite all through­out this coun­try. ", "We’ve got to give Black Lives Mat­ter peo­ple a place where they can express them­selves elec­toral­ly. ", "We’ve got to give the Fight for 15 a par­ty where they feel good about express­ing them­selves elec­toral­ly. ", "The immi­gra­tion activists have got to have a place where they feel that there’s a par­ty that’s lis­ten­ing to them. ", "We’ve got to have a place for the folks who fight for cli­mate jus­tice, a par­ty that they can support.", "\n\nWe are off to a good start, because Sen­a­tor Sanders and Sec­re­tary Clin­ton com­bined to cre­ate the best plat­form the Demo­c­ra­t­ic Par­ty has ever seen. ", "I was priv­i­leged and hon­ored to have Bernie appoint me to the plat­form draft­ing com­mit­tee, and let me tell you, good things came out of it. ", "Because of that col­lab­o­ra­tion and that uni­ty, we got the best plat­form we’ve ever had. ", "We’ve got to use it to move for­ward. ", "We can orga­nize with this very impor­tant tool, and if you will take up this bat­tle and you will pledge to your­self and each oth­er that your love for this coun­try out­weighs any beef you may have with any­one, if you will promise to your­self that you will work hard every sin­gle day to make this Demo­c­ra­t­ic Par­ty real­ly work for the peo­ple, then we are not only look­ing at vic­to­ry in 2018 and redis­trict­ing in 2020. ", "We are look­ing at a gen­er­a­tion full of suc­cess for work­ing people.", "\n\nRepub­li­cans in 1964 thought that they were at the bot­tom, that they were down and out. ", "Peo­ple said con­ser­vatism was dead as a phi­los­o­phy because Gold­wa­ter lost to John­son in his­toric num­bers, and yet those guys are so com­mit­ted to mak­ing them­selves more mon­ey and exclud­ing peo­ple that they climb back up. ", "They won, and then they won some more. ", "And in 1980, this cul­mi­nat­ed in the elec­tion of Ronald Rea­gan, I’m telling you I don’t want to be like them, I don’t believe what they believe, but I will say that I appre­ci­ate deter­mi­na­tion when I see it. ", "And you and I bet­ter have the same lev­el, if not more, deter­mi­na­tion for work­ing people.", "\n\nDemoc­rats, lib­er­als, pro­gres­sives, the Left — we stand for the right val­ues. ", "I think that because we stand for the right val­ues, we think that’s all we have to do. ", "The peo­ple on the Right, they know that the pro­gram they’re push­ing is only going to ben­e­fit about 1% of the peo­ple, but they still live in a democ­ra­cy, so they have to fig­ure out a way to win. ", "We also have got to under­stand that just being right is not enough. ", "We’ve got to be uni­fied. ", "We got to be active. ", "We got to be fight­ing togeth­er. ", "We’ve got to be push­ing the right pro­gram; we’ve got to strength­en and uni­fy at the grass­roots lev­el, and we need a Demo­c­ra­t­ic Par­ty that’s going to help us do that.", "\n\nIf you’re ready to do those things, we are ready to win. ", "I need to ask you to do just a few things. ", "Bernie said that we need to sign those peti­tions. ", "We absolute­ly got to get a mil­lion sig­na­tures, okay? ", "If there are DNC mem­bers in your state, gen­tly and polite­ly tell them that you would like them to sup­port Elli­son for DNC chair. ", "Also, we need to be doing meet-ups all over this coun­try. ", "I’m talk­ing about meet-ups where peo­ple can meet like once a month, get some cook­ies, tea, cof­fee, what­ev­er you like, and just say you know what? ", "What if we did this, or what if we did that? ", "And then maybe you could have a lis­ten­ing ses­sion to real­ly feel how peo­ple are doing.", "\n\nHere’s the oth­er thing, there’s a lot of folks who vot­ed for Trump. ", "Don’t reject them; ask them what are you think­ing about? ", "How do you feel now? ", "Are you will­ing to work with us? ", "Now did he dis­ap­point you or do you still feel sat­is­fied? ", "Because there’s a whole lot of folks after they lose their health­care, they are going to be a lit­tle bit annoyed. ", "Don’t push them away, bring them in.", "\n\nAnd the last thing I want to ask you to do is just under­stand that there’s a lot of folks who might have their fam­i­ly roots south of the bor­der, and a guy who just got elect­ed said, ​“Build a wall.” ", "These peo­ple need our sup­port. ", "These are our broth­ers and sis­ters, and we can’t let them feel vul­ner­a­ble and afraid. ", "A dear friend of mine said to me recent­ly that she was called to a meet­ing with her friend. ", "She brought her lit­tle five-year-old daugh­ter with her. ", "And she said to my friend, if me and my hus­band are picked up and deport­ed, you know Juani­ta is born in Amer­i­ca, she’s a cit­i­zen: Would you take care of her? ", "You under­stand? ", "Think about hav­ing that con­ver­sa­tion. ", "That’s real for a lot of peo­ple. ", "There are oth­er peo­ple who were told that they were going to be banned from immi­grat­ing here based on their reli­gion. ", "Peo­ple who are Mus­lim, be a friend. ", "Peo­ple who are gay and les­bian, peo­ple who are Jew­ish — a lot of anti-Semi­tism has real­ly popped up. ", "You got to stand with every­body who is feel­ing vul­ner­a­ble right now. ", "Because one of the things Trump has uncorked is that hate machine, and we have got to resist it and stand up against it. ", "Our best weapon against it is our own sol­i­dar­i­ty. ", "Let’s remake the Demo­c­ra­t­ic Par­ty, everybody." ]

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[ "Glen Quaich\n\nGlen Quaich is a Scottish glen near Aberfeldy, Perthshire, which gets its name from the River Quaich which runs through it into Loch Freuchie.", "\n\nExternal links\nThe Quaich Aberfeldy\nVisit Dunkeld\nSporting Lets\n\nCategory:Glens of Scotland\nCategory:Valleys of Perth and Kinross" ]

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

[ 0.0031184041872620583, 0.0008471939363516867 ]

[ "---\nabstract: |\n Quantum theory imposes a strict limit on the strength of non-local correlations. ", "It only allows for a violation of the CHSH inequality up to the value $2\\sqrt{2}$, known as Tsirelson’s bound. ", "In this [paper]{}, we consider generalized CHSH inequalities based on many measurement settings with two possible measurement outcomes each. ", "We demonstrate how to prove Tsirelson bounds for any such generalized CHSH inequality using semidefinite programming. ", "As an example, we show that for any shared entangled state and observables $X_1,\\ldots,X_n$ and $Y_1,\\ldots,Y_n$ with eigenvalues $\\pm 1$ we have $\n |\\langle X_1Y_1 \\rangle + \\langle X_2Y_1 \\rangle + \\langle X_2Y_2\\rangle + \\langle X_3Y_2 \\rangle + \n \\ldots + \\langle X_nY_n \\rangle - \\langle X_1Y_n \\rangle| \\leq 2 n\\cos\\left(\\pi/(2n)\\right).", "\n $ It is well known that there exist observables such that equality can be achieved. ", "However, we show that these are indeed optimal. ", "Our approach can easily be generalized to other inequalities for such observables.", "\nauthor:\n- |\n Stephanie Wehner\\\n CWI, Kruislaan 413, 1098 SJ Amsterdam, The Netherlands\\\n wehner@cwi.nl\ntitle: 'Tsirelson bounds for generalized Clauser-Horne-Shimony-Holt inequalities'\n---\n\nNon-local correlations arise as the result of measurements performed on a quantum system shared between two spatially separated parties. ", "Imagine two parties, Alice and Bob, who are given access to a shared quantum state ${|\\Psi\\rangle}$, but cannot communicate. ", "In the simplest case, each of them is able to perform one of two possible measurements. ", "Every measurement has two possible outcomes labeled $\\pm 1$. Alice and Bob now measure ${|\\Psi\\rangle}$ using an independently chosen measurement setting and record their outcomes. ", "In order to obtain an accurate estimate for the correlation between their measurement settings and the measurement outcomes, they perform this experiment many times using an identically prepared state ${|\\Psi\\rangle}$ in each round. ", "Both classical and quantum theories impose limits on the strength of such non-local correlations. ", "In particular, both do not violate the non-signaling condition of special relativity. ", "That is, the local choice of measurement setting does not allow Alice and Bob to transmit information. ", "Limits on the strength of correlations which are possible in the framework of any classical theory, i.e. a framework based on local hidden variables, are known as *Bell inequalities* [@bell:epr]. ", "The best known Bell inequality is the Clauser, Horne, Shimony and Holt (CHSH) inequality [@chsh:nonlocal] [$$]{}|[X\\_1Y\\_1 ]{} + [X\\_1Y\\_2 ]{} + [X\\_2Y\\_1 ]{} - [X\\_2Y\\_2 ]{}| 2, [$$]{}where $\\{X_1,X_2\\}$ and $\\{Y_1,Y_2\\}$ are the observables representing the measurement settings of Alice and Bob respectively. ", "${\\langle X_iY_j \\rangle} = {\\langle\\Psi|}X_i \\otimes Y_j{|\\Psi\\rangle}$ denotes the mean value of $X_i$ and $Y_j$. Quantum mechanics allows for a violation of the CHSH inequality, but curiously still limits the strength of nonlocal correlations. ", "Tsirelson’s bound [@tsirel:original] says that for quantum mechanics [$$]{}|[X\\_1Y\\_1 ]{} + [X\\_1Y\\_2 ]{} + [X\\_2Y\\_1 ]{} - [X\\_2Y\\_2 ]{}| 2. [", "$$]{}\n\nPeres demonstrated how to derive Bell inequalities [@peres:allBell] even for more than two settings. ", "As Froissart and Tsirelson [@tsirel:hadron] have shown, these inequalities correspond to the faces of a polytope. ", "Computing the boundary of the space of correlations that can be attained using a classical theory therefore corresponds to determining the faces of this polytope. ", "However, determining bounds on the correlations that *quantum* theory allows remains an even more difficult problem [@massar:tsirel]. ", "All Tsirelson’s bounds are known for CHSH-type inequalities (also known as correlation inequalities) with two measurement settings and two outcomes for both Alice and Bob [@tsirel:hadron]. ", "Filipp and Svozil [@filipp:bell] have considered the case of three measurement settings analytically and conducted numerical studies for a larger number of settings. ", "Finally, Buhrman and Massar have shown a bound for a generalized CHSH inequality using three measurement settings with three outcomes each [@massar:tsirel].", "\n\nIn this [paper]{}, we investigate the case where Alice and Bob can choose from $n$ measurement settings with two outcomes each. ", "We use a completely different approach based on semidefinite programming in combination with Tsirelson’s seminal results [@tsirel:original; @tsirel:separated; @tsirel:hadron]. ", "This method is similar to methods used in computer science for the two-way partitioning problem [@boyd:book] and the approximation algorithm for MAXCUT by Goemans and Williamson [@goemans:maxcut]. ", "Cleve et al.", " [@cleve:nonlocal] have also remarked that Tsirelson’s constructions leads to an approach by semidefinite programming in the context of multiple interactive proof systems with entanglement. ", "Semidefinite programming allows for an efficient way to approximate Tsirelson’s bounds for any CHSH-type inequalities numerically. ", "However, it can also be used to prove Tsirelson type bounds analytically. ", "As an illustration, we first give an alternative proof of Tsirelson’s original bound using semidefinite programming. ", "We then prove a new Tsirelson’s bound for the following generalized CHSH inequality [@peres:book; @braunstein:inequ]. ", "Classically, it can be shown that [$$]{}|\\_[i = 1]{}\\^n [X\\_iY\\_i ]{} + \\_[i = 1]{}\\^[n-1]{} [X\\_[i+1]{}Y\\_i ]{} - [X\\_1Y\\_n ]{}| 2n - 2. [", "$$]{} Here, we show that for quantum mechanics [$$]{}|\\_[i = 1]{}\\^n [X\\_iY\\_i ]{} + \\_[i = 1]{}\\^[n-1]{} [X\\_[i+1]{}Y\\_i ]{} - [X\\_1Y\\_n ]{}| 2 n(), [$$]{}where $\\{X_1,\\ldots,X_n\\}$ and $\\{Y_1,\\ldots,Y_n\\}$ are observables with eigenvalues $\\pm 1$ employed by Alice and Bob respectively, corresponding to their $n$ possible measurement settings. ", "It is well known that this bound can be achieved [@peres:book; @braunstein:inequ] for a specific set of measurement settings if Alice and Bob share a singlet state. ", "Here, we show that this bound is indeed optimal for *any* state ${|\\Psi\\rangle}$ and choice of measurement settings. ", "This method generalizes to other CHSH inequalities, for example, the inequality considered by Gisin [@gisin:chsh]. ", "As outlined below, Tsirelson’s results also imply that any bound proved using this method can indeed be achieved using quantum mechanics. ", "As Braunstein and Caves [@braunstein:inequ] have shown, it is interesting to consider inequalities based on many measurement settings, in particular, the chained CHSH inequality above. ", "The gap between the classical and the quantum bound for this inequality is larger than for the original CHSH inequality with only two measurement settings. ", "They show that even for real experiments that inevitably include noise, this inequality leads to a stronger violation of local realism, and may thus lead to a better test.", "\n\nPreliminaries\n=============\n\nThroughout this [paper]{}, we write $u = (u_1,\\ldots,u_n)$ for an $n$-element vector. ", "$u \\cdot v$ denotes the inner product between vectors $u$ and $v$. Furthermore, ${\\mbox{\\rm diag}}(\\lambda)$ denotes the matrix with the components of the vector $\\lambda$ on its diagonal. ", "We write $A = [a_{ij}]$ to indicate that the entry in the $i$-th row and $j$-th column of $A$ is $a_{ij}$. We also use the shorthand $[n] = \\{1,\\ldots,n\\}$. $A^{\\dagger}$ is the conjugate transpose of matrix $A$. ", "A positive semidefinite $n \\times n$ matrix $A$ is a nonsingular Hermitian matrix such that $x^*Ax \\geq 0$ for all $x \\in \\Complex^n$ . ", "We use $A \\succeq 0$ to indicate that $A$ is positive semidefinite. ", "It will be important that a Hermitian matrix $A$ is positive semidefinite if and only if all of its eigenvalues are nonnegative .", "\n\nWe will need two ingredients for our proof. ", "First, the following result by Tsirelson [@tsirel:original Theorem 1] and [@tsirel:separated; @tsirel:hadron] plays an essential role.", "\n\n\\[tsirel\\] Let $X_1,\\ldots,X_n$ and $Y_1,\\ldots,Y_n$ be observables with eigenvalues in the interval $[-1;1]$. Then for any state ${|\\Psi\\rangle} \\in {\\mathcal{A}}\\otimes {\\mathcal{B}}$ and for all $s,t \\in [n]$ there exist real unit vectors $x_1,\\ldots,x_n$,$y_1,\\ldots,y_n \\in \\Real^{2n}$ such that [$$]{}[|]{}X\\_s Y\\_t[|]{} = x\\_s y\\_t. [", "$$]{}Conversely, let $x_s,y_t \\in \\Real^{N}$ be real unit vectors. ", "Let ${|\\Psi\\rangle} \\in {\\mathcal{A}}\\otimes {\\mathcal{B}}$ be any maximally entangled state where $\\dim({\\mathcal{A}}) = \\dim({\\mathcal{B}}) = 2^{{\\lceil{N/2}\\rceil}}$. Then for all $s,t \\in [n]$ there exist observables $X_s$ on ${\\mathcal{A}}$ and $Y_t$ on ${\\mathcal{B}}$ with eigenvalues $\\pm 1$ such that [$$]{}x\\_s y\\_t = [|]{}X\\_s Y\\_t[|]{}. [", "$$]{}\n\nIn particular, this means that we can rewrite CHSH inequalities in terms of vectors. ", "The second part of Tsirelson’s result implies that any strategy based on vectors can indeed be implemented using quantum measurements. ", "See [@tsirel:hadron] for a detailed construction.", "\n\nSecondly, we will make use of semidefinite programming. ", "This is a special case of convex optimization. ", "We refer to [@boyd:book] for an in-depth introduction. ", "The goal of semidefinite programming is to solve he following semidefinite program (SDP) in terms of the variable $X \\in S^n$\n\n[maximize]{}[${\\mbox{\\rm Tr}}(CX)$]{} &${\\mbox{\\rm Tr}}(A_iX) = b_i, i = 1,\\ldots,p$, and $X \\succeq 0$\n\nfor given matrices $C,A_1,\\ldots,A_p \\in S^n$ where $S^n$ is the space of symmetric $n \\times n$ matrices. ", "$X$ is called *feasible*, if it satisfies all constraints. ", "An important aspect of semidefinite programming is duality. ", "Intuitively, the idea behind Lagrangian duality is to extend the objective function (here ${\\mbox{\\rm Tr}}(CX)$) with a weighted sum of the constraints in such a way, that we will be penalized if the constraints are not fulfilled. ", "The weights then correspond to the dual variables. ", "Optimizing over these weights then gives rise to the *dual problem*. ", "The original problem is called the *primal problem*. ", "An example of this approach is given in the next section. ", "Let $d'$ denote the optimal value of the dual problem, and $p'$ the optimal value of the primal problem from above. ", "Weak duality says that $d' \\geq p'$. In particular, if we have $d' = p'$ for a feasible dual and primal solution respectively, we can conclude that both solutions are optimal.", "\n\nTsirelson’s bound {#tsirelBoundSection}\n=================\n\nTo illustrate our approach we first give a detailed proof of Tsirelson’s bound using semidefinite programming. ", "This proof is more complicated than Tsirelson’s original proof, however, it serves as a good introduction to the following section. ", "Let $X_1,X_2$ and $Y_1,Y_2$ denote the observables with eigenvalues $\\pm 1$ used by Alice and Bob respectively. ", "Our goal is now to show an upper bound for [$$]{}|[X\\_1Y\\_1 ]{} + [X\\_1Y\\_2 ]{} + [X\\_2Y\\_1 ]{} - [X\\_2Y\\_2 ]{}|. [", "$$]{}From Theorem \\[tsirel\\] we know that there exist real unit vectors $x_s,y_t \\in \\Real^4$ such that for all $s,t \\in \\01$ ${\\langle X_sY_t \\rangle} = x_s \\cdot y_t$. In order to find Tsirelson’s bound, we thus want to solve the following problem: maximize $x_1 \\cdot y_1 + x_1 \\cdot y_2 + x_2 \\cdot y_1 - x_2 \\cdot y_2$, subject to ${\\mbox{$\\parallel{x_1}\\parallel$}} = {\\mbox{$\\parallel{x_2}\\parallel$}} = {\\mbox{$\\parallel{y_1}\\parallel$}} = {\\mbox{$\\parallel{y_2}\\parallel$}} = 1$. Note that we can drop the absolute value since any set of vectors maximizing the above equation, simultaneously leads to a set of vectors minimizing it by taking $-y_1,-y_2$ instead. ", "We will now phrase this as a semidefinite program. ", "Let $G = [g_{ij}]$ be the Gram matrix of the vectors $\\{x_1,x_2,y_1,y_2\\} \\subseteq \\Real^4$ with respect to the inner product: $$G = \n\\left(\\begin{array}{cccc}\nx_1 \\cdot x_1 & x_1 \\cdot x_2 & x_1 \\cdot y_1 & x_1 \\cdot y_2 \\\\\nx_2 \\cdot x_1 & x_2 \\cdot x_2 & x_2 \\cdot y_1 & x_2 \\cdot y_2\\\\\ny_1 \\cdot x_1 & y_1 \\cdot x_2 & y_1 \\cdot y_2 & y_1 \\cdot y_2\\\\\ny_2 \\cdot x_1 & y_2 \\cdot x_2 & y_2 \\cdot y_1 & y_2 \\cdot y_2\n\\end{array}\\right).$$ $G$ can thus be written as $G = B^TB$ where the columns of $B$ are the vectors $\\{x_1,x_2,y_1,y_2\\}$. By  we can write $G = B^TB$ if and only if $G$ is positive semidefinite. ", "We thus impose the constraint that $G \\succeq 0$. To make sure that we obtain unit vectors, we add the constraint that all diagonal entries of $G$ must be equal to $1$. Define $$W = \\left(\\begin{array}{cccc} 0 &0& 1& 1\\\\\n0 & 0 & 1 & -1\\\\\n1 & 1 & 0 & 0\\\\\n1 & -1 & 0 & 0\n\\end{array}\\right).$$ Note that the choice of order of the vectors in $B$ is not unique, however, a different order only leads to a different $W$ and does not change our argument. ", "We can now rephrase our optimization problem as the following SDP:\n\n[maximize]{}[$\\frac{1}{2}{\\mbox{\\rm Tr}}(GW)$]{} &$G \\succeq 0$ and $\\forall i, g_{ii} = 1$\n\nWe can then write for the Lagrangian [$$]{}L(G,) = (GW) - (()(G - I)), [$$]{}where $\\lambda = (\\lambda_1, \\lambda_2, \\lambda_3,\\lambda_4)$. The dual function is then $$\\begin{aligned}\ng(\\lambda) &=& \\sup_G {\\mbox{\\rm Tr}}\\left(G\\left(\\frac{1}{2}W - {\\mbox{\\rm diag}}(\\lambda)\\right)\\right) + {\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda))\\\\\n &=& \\left\\{\\begin{array}{ll}\n {\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda)) & \\mbox{if } \\frac{1}{2}W - {\\mbox{\\rm diag}}(\\lambda) \\preceq 0\\\\[0.5mm]\n \\infty & \\mbox{otherwise}\n \\end{array} \\right.\\end{aligned}$$ We then obtain the following dual formulation of the SDP\n\n[minimize]{}[${\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda))$]{} &$-\\frac{1}{2}W + {\\mbox{\\rm diag}}(\\lambda) \\succeq 0$\n\nLet $p'$ and $d'$ denote optimal values for the primal and Lagrange dual problem respectively. ", "From weak duality it follows that $d' \\geq p'$. For our example, it is not difficult to see that this is indeed true. ", "Let $G'$ and $\\lambda'$ be optimal solutions of the primal and dual problem, i.e. $p' = \\frac{1}{2}{\\mbox{\\rm Tr}}(G'W)$ and $d' = {\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda'))$. Recall that all entries on the diagonal of $G'$ are 1 and thus ${\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda')) = {\\mbox{\\rm Tr}}(G'{\\mbox{\\rm diag}}(\\lambda'))$. Then $d' - p' = {\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda')) - \\frac{1}{2}{\\mbox{\\rm Tr}}(G'W) = {\\mbox{\\rm Tr}}(G'{\\mbox{\\rm diag}}(\\lambda') - \\frac{1}{2}G'W) = {\\mbox{\\rm Tr}}(G'({\\mbox{\\rm diag}}(\\lambda') - \\frac{1}{2}W)) \\geq 0$, where the last inequality follows from the constraints $G' \\succeq 0$, ${\\mbox{\\rm diag}}(\\lambda') - \\frac{1}{2}W \\succeq 0$ and [@boyd:book Example 2.24].", "\n\nIn order to prove Tsirelson’s bound, we will now exhibit an optimal solution for both the primal and dual problem and then show that the value of the primal problem equals the value of the dual problem. ", "The optimal solution is well known [@tsirel:original; @tsirel:separated; @peres:book]. ", "Alternatively, we could easily guess the optimal solution based on numerical optimization by a small program for Matlab [^1] and the package SeDuMi [@sedumi] for semidefinite programming. ", "Consider the following solution for the primal problem $$G' = \\left( \\begin{array}{cccc}\n 1 & 0 & \\frac{1}{\\sqrt{2}} & \\frac{1}{\\sqrt{2}}\\\\\n 0 & 1 & \\frac{1}{\\sqrt{2}} & -\\frac{1}{\\sqrt{2}}\\\\\n \\frac{1}{\\sqrt{2}} & \\frac{1}{\\sqrt{2}} & 1 & 0\\\\\n \\frac{1}{\\sqrt{2}} & - \\frac{1}{\\sqrt{2}} & 0 & 1\\\\\n \\end{array}\n \\right),$$ which gives rise to the primal value $p' = \\frac{1}{2}{\\mbox{\\rm Tr}}(G'W) = 2\\sqrt{2}$. Note that $G' \\succeq 0$ since all its eigenvalues are nonnegative  and all its diagonal entries are 1. ", "Thus all constraints are satisfied. ", "The lower left quadrant of $G'$ is in fact the same as the well known correlation matrix for 2 observables [@tsirel:hadron Equation 3.16]. ", "Next, consider the following solution for the dual problem [$$]{}’ = (1,1,1,1). [", "$$]{}The dual value is then $d' = {\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda')) = 2\\sqrt{2}$. Because $-W + {\\mbox{\\rm diag}}(\\lambda') \\succeq 0$, $\\lambda'$ satisfies the constraint. ", "Since $p' = d'$, $G'$ and $\\lambda'$ are in fact optimal solutions for the primal and dual respectively. ", "We can thus conclude that [$$]{}|[X\\_1Y\\_1 ]{} + [X\\_1Y\\_2 ]{} + [X\\_2Y\\_1 ]{} - [X\\_2Y\\_2 ]{}| 2, [$$]{}which is Tsirelson’s bound [@tsirel:original]. ", "By Theorem \\[tsirel\\], this bound is achievable.", "\n\nTsirelson’s bounds for more than 2 observables {#generalSemiDef}\n==============================================\n\nWe now show how to obtain bounds for inequalities based on more than 2 observables for both Alice and Bob. ", "In particular, we will prove a bound for the chained CHSH inequality for the quantum case. ", "It is well known [@peres:book] that it is possible to choose observables $X_1,\\ldots,X_n$ and $Y_1,\\ldots,Y_n$ such that [$$]{}|\\_[i = 1]{}\\^n [X\\_iY\\_i ]{} + \\_[i = 1]{}\\^[n-1]{} [X\\_[i+1]{}Y\\_i ]{} - [X\\_1Y\\_n ]{}| = 2 n (). [", "$$]{}We now show that this is optimal. ", "Our proof is similar to the last section. ", "However, it is more difficult to show feasibility for all $n$.\n\nLet $\\rho \\in {\\mathcal{A}}\\otimes {\\mathcal{B}}$ be an arbitrary state, where ${\\mathcal{A}}$ and ${\\mathcal{B}}$ denote the Hilbert spaces of Alice and Bob. ", "Let $X_1,\\ldots,X_n$ and $Y_1,\\ldots,Y_n$ be observables with eigenvalues $\\pm 1$ on ${\\mathcal{A}}$ and ${\\mathcal{B}}$ respectively. ", "Then $$|\\sum_{i = 1}^n {\\langle X_iY_i \\rangle} + \\sum_{i = 1}^{n-1} {\\langle X_{i+1}Y_i \\rangle} - {\\langle X_1Y_n \\rangle}| \n\\leq 2 n\\cos\\left(\\frac{\\pi}{2n}\\right),$$\n\nBy Theorem \\[tsirel\\], our goal is to find the maximum value for $\nx_1 \\cdot y_1 + x_2 \\cdot y_1 + x_2 \\cdot y_2 + x_3 \\cdot y_2 + \\ldots\n+ x_n \\cdot y_n - x_1 \\cdot y_n,\n$ for real unit vectors $x_1,\\ldots,x_n,y_1,\\ldots,y_n \\in \\Real^{2n}$. As above we can drop the absolute value. ", "Let $G = [g_{ij}]$ be the Gram matrix of the vectors $\\{x_1,\\ldots,x_n,y_1,\\ldots,y_n\\} \\subseteq \\Real^{2n}$. As before, we can thus write $G = B^TB$, where the columns of $B$ are the vectors $\\{x_1,\\ldots,x_n,y_1,\\ldots,y_n\\}$, if and only if $G\\succeq 0$. To ensure we obtain unit vectors, we again demand that all diagonal entries of $G$ equal $1$. Define $n \\times n$ matrix $A$ and $2n \\times 2n$ matrix $W$ by\n\n$$\\begin{aligned}\nA = \\left(\\begin{array}{ccccc}\n 1 & 1 & 0 & \\ldots & 0\\\\\n 0 & 1 & 1 & & \\vdots \\\\\n \\vdots & & \\ddots & \\ddots & 0\\\\\n 0 & & & 1 & 1\\\\ \n -1 & 0 & \\ldots & 0 & 1\\\\\n \\end{array}\n \\right),\\mbox{~}\nW = \\left(\\begin{array}{cc} \n 0 & A^{\\dagger}\\\\\n A & 0 \n \\end{array}\n \\right).\\end{aligned}$$\n\nWe can now phrase our maximization problem as the following SDP:\n\n[maximize]{}[$\\frac{1}{2}{\\mbox{\\rm Tr}}(GW)$]{} &$G \\succeq 0$ and $\\forall i, g_{ii} = 1$\n\nAnalog to the previous section, the dual SDP is then:\n\n[minimize]{}[${\\mbox{\\rm Tr}}({\\mbox{\\rm diag}}(\\lambda))$]{} &$-\\frac{1}{2}W + {\\mbox{\\rm diag}}(\\lambda) \\succeq 0$\n\nLet $p'$ and $d'$ denote optimal values for the primal and dual problem respectively. ", "As before, $d' \\geq p'$.\n\n#### Primal\n\nWe will now show that the vectors suggested in [@peres:book] are optimal. ", "For $k \\in [n]$, choose unit vectors $x_k,y_k \\in \\Real^{2n}$ to be of the form $$\\begin{aligned}\nx_k &=& (\\cos(\\phi_k), \\sin(\\phi_k),0,\\ldots,0),\\\\\ny_k &=& (\\cos(\\psi_k), \\sin(\\psi_k),0,\\ldots,0),\\end{aligned}$$ where $\\phi_k = \\frac{\\pi}{2n}(2k - 2)$ and $\\psi_k = \\frac{\\pi}{2n}(2k - 1)$. The angle between $x_k$ and $y_k$ is given by $\\psi_k - \\phi_k = \\frac{\\pi}{2n}$ and thus $x_k \\cdot y_k = \\cos\\left(\\frac{\\pi}{2n}\\right)$. The angle between $x_{k+1}$ and $y_k$ is $\\phi_{k+1} - \\psi_k = \\frac{\\pi}{2n}$ and thus $x_{k+1} \\cdot y_k = \\cos\\left(\\frac{\\pi}{2n}\\right)$. Finally, the angle between $-x_1$ and $y_n$ is $\\pi - \\psi_n = \\frac{\\pi}{2n}$ and so $-x_1 \\cdot y_n = \\cos\\left(\\frac{\\pi}{2n}\\right)$. The value of our primal problem is thus given by [$$]{}p’ = \\_[k=1]{}\\^n x\\_k y\\_k + \\_[k=1]{}\\^[n-1]{} x\\_[k+1]{} y\\_k - x\\_1 y\\_[n]{} = 2n (). [", "$$]{} Let $G'$ be the Gram matrix constructed from all vectors $x_k,y_k$ as described earlier. ", "Note that our constraints are satisfied: $\\forall i: g_{ii} = 1$ and $G' \\succeq 0$, because $G'$ is symmetric and of the form $G' = B^TB$.\n\n#### Dual\n\nNow consider the $n$-dimensional vector [$$]{}’ = () (1,…,1). [", "$$]{}In order to show that this is a feasible solution to the dual problem, we have to prove that $-\\frac{1}{2}W + {\\mbox{\\rm diag}}(\\lambda') \\succeq 0$ and thus the constraint is satisfied. ", "To this end, we first show that\n\n\\[aClaim\\] The eigenvalues of $A$ are given by $\\gamma_s = 1 + e^{i\\pi(2s+1)/n}$ with $s = 0,\\ldots,n-1$.\n\nNote that if the lower left corner of $A$ were $1$, $A$ would be a circulant matrix [@circulant], i.e. each row of $A$ is constructed by taking the previous row and shifting it one place to the right. ", "We can use ideas from circulant matrices to guess eigenvalues $\\gamma_s$ with eigenvectors [$$]{}u\\_s = (\\_s\\^[n-1]{},\\_s\\^[n-2]{},\\_s\\^[n-3]{},…,\\_s\\^1,\\_s\\^0), [$$]{} where $\\rho_s = e^{-i\\pi(2s+1)/n}$ and $s = 0,\\ldots,n-1$. By definition, $u = (u_1,u_2,\\ldots,u_n)$ is an eigenvector of $A$ with eigenvalue $\\gamma$ if and only if $Au = \\gamma u$. Here, $Au = \\gamma u$ if and only if $$\\begin{aligned}\n(i)&& \n\\forall j \\in \\{1,\\ldots,n-1\\}:\nu_j + u_{j+1} = \\gamma u_j,\\\\\n(ii)&& -u_1 + u_n = \\gamma u_n.\\end{aligned}$$ Since for any $j \\in \\{1,\\ldots,n-1\\}$ $$\\begin{aligned}\nu_j + u_{j+1} \n&=&\n\\rho_s^{n-j} + \\rho_s^{n-j-1} = \n\\\\\n&=&\ne^{-i(n-j)\\pi(2s+1)/n}(1+e^{i\\pi(2s+1)/n}) = \\\\\n&=&\n\\rho_s^{n-j} \\gamma_s = \\gamma_s u_j,\\end{aligned}$$ (i) is satisfied. ", "Furthermore (ii) is satisfied, since $$\\begin{aligned}\n-u_1 + u_n &=& - \\rho_s^{n-1} + \\rho_s^0 = \\\\\n&=& \n- e^{-i \\pi(2s+1)} e^{i\\pi(2s+1)/n} + 1 = \\\\\n&=&\n1 + e^{i\\pi(2s+1)/n} = \\\\\n&=&\n\\gamma_s \\rho_s^0 = \\gamma_s u_n.\\end{aligned}$$\n\n\\[biggestVal\\] The largest eigenvalue of $W$ is given by $\\gamma = 2\\cos\\left(\\frac{\\pi}{2n}\\right)$.\n\nBy , the eigenvalues of $W$ are given by the singular values of $A$ and their negatives. ", "It follows from Claim \\[aClaim\\] that the singular values of $A$ are [$$]{}\\_s = = 2 + 2(). [", "$$]{} Considering the shape of the cosine function, it is easy to see that the largest singular value of $A$ is given by $2 + 2\\cos(\\pi/n)\n= 4 \\cos^2(\\pi/(2n))$, the largest eigenvalue of $W$ is $\\sqrt{2 + 2\\cos(\\pi/n)} = 2 \\cos(\\pi/(2n))$.\n\nSince $-\\frac{1}{2}W$ and ${\\mbox{\\rm diag}}(\\lambda')$ are both Hermitian, Weyl’s theorem  implies that $$\\begin{aligned}\n&&\\gamma_{min}\\left(-\\frac{1}{2}W + {\\mbox{\\rm diag}}(\\lambda')\\right)\\\\\n&\\geq&\n\\gamma_{min}\\left(-\\frac{1}{2}W\\right) + \\gamma_{min}\\left({\\mbox{\\rm diag}}(\\lambda')\\right),\\end{aligned}$$ where $\\gamma_{min}(M)$ is the smallest eigenvalue of a matrix $M$. It then follows from the fact that ${\\mbox{\\rm diag}}(\\lambda')$ is diagonal and Claim \\[biggestVal\\] that $$\\begin{aligned}\n&&\\gamma_{min}\\left(-\\frac{1}{2}W + {\\mbox{\\rm diag}}(\\lambda')\\right)\\\\\n &\\geq& \n-\\frac{1}{2}\\left(2\\cos\\left(\\frac{\\pi}{2n}\\right)\\right) + \\cos\\left(\\frac{\\pi}{2n}\\right)\n= \n0.\\end{aligned}$$ Thus $-\\frac{1}{2}W + {\\mbox{\\rm diag}}(\\lambda') \\succeq 0$ and $\\lambda'$ is a feasible solution to the dual problem. ", "The value of the dual problem is then [$$]{}d’ = ((’)) = 2 n (). [", "$$]{} Because $p' = d'$, $G'$ and $\\lambda'$ are optimal solutions for the primal and dual respectively, which completes our proof.", "\n\nNote that for the primal problem we are effectively dealing with $2$-dimensional vectors, $x_k,y_k$. It therefore follows from Tsirelson’s construction [@tsirel:hadron] that given an EPR pair we can find observables such that the bound is tight. ", "In fact, these vectors just determine the measurement directions as given in [@peres:book].", "\n\nDiscussion\n==========\n\nOur approach can be generalized to other CHSH-type inequalities. ", "For another inequality, we merely use a different matrix $A$ in $W$. For example, for Gisin’s CHSH inequality [@gisin:chsh], $A$ is the matrix with 1’s in the upper left half and on the diagonal, and -1’s in the lower right part. ", "Otherwise our approach stays exactly the same, and thus we do not consider this case here. ", "Numerical results provided by our Matlab example code suggest that Gisin’s observables are optimal. ", "Given the framework of semidefinite programming, the only difficulty in proving bounds for other inequalities is to determine the eigenvalues of the corresponding $A$, a simple matrix. ", "Since our approach is based on Tsirelson’s vector construction, it is limited to CHSH-type inequalities for two parties.", "\n\nAcknowledgments\n===============\n\nMany thanks to Boris Tsirelson for sending me a copy of [@tsirel:original] and [@tsirel:separated], to Oded Regev for pointing me to [@boyd:book] and for introducing me to the concept of approximation algorithms such as [@goemans:maxcut], to Serge Massar for pointers, to Ronald de Wolf for the pointer to [@circulant] and proofreading, and to Manuel Ballester for alerting me to correct the journal reference of [@braunstein:inequ]. ", "Supported by EU project RESQ IST-2001-37559 and NWO vici project 2004-2009.", "\n\n[10]{}\n\nJ. S. Bell. ", "On the [E]{}instein-[P]{}odolsky-[R]{}osen paradox. , ", "1:195–200, 1965.", "\n\nS. Boyd and L. Vandenberghe. . ", "Cambridge University Press, 2004.", "\n\nS.L. Braunstein and C.M. Caves. ", "Wringing out better [B]{}ell inequalities. , ", "202:22–56, 1990.", "\n\nH. Buhrman and S. Massar. ", "Causality and [C]{}irel’son bounds. ", "quant-ph/0409066, 2004.", "\n\nJ. Clauser, M. Horne, A. Shimony, and R. Holt. ", "Proposed experiment to test local hidden-variable theories. , ", "23:880–884, 1969.", "\n\nR. Cleve, P. H[ø]{}yer, B. Toner, and J. Watrous. ", "Consequences and limits of nonlocal strategies. ", "In [*Proceedings of 19th IEEE Conference on Computational Complexity*]{}, pages 236–249, 2004. ", "quant-ph/0404076.", "\n\nS. Filipp and K. Svozil. ", "Tracing the bounds on [B]{}ell-type inequalities. ", "In [*Proceedings of Foundations of Probability and Physics-3*]{}, pages 87–94, 2004.", "\n\nN. Gisin. ", "ell inequality for arbitrary many settings of the analyzers. , ", "260:1–3, 1999.", "\n\nM.X. Goemans and D.P. Williamson. ", "Improved approximation algorithms for maximum cut and satisfiability problems using semidefinite programming. , ", "42:1115–1145, 1995.", "\n\nR. A. Horn and C. R. Johnson. . ", "Cambridge University Press, 1985.", "\n\nA. Peres. . ", "Kluwer Academic Publishers, 1993.", "\n\nA. Peres. ", "All the [B]{}ell inequalities. , ", "29:589–614, 1999.", "\n\nR.M.Gray. . ", "1971.", "\n\nJ. Sturm and AdvOL. ", "e[D]{}u[M]{}i. ", "http://sedumi.mcmaster.ca/.\n\nB. Tsirelson. ", "Quantum analogues of [B]{}ell inequalities: The case of two spatially separated domains. , ", "36:557–570, 1987.", "\n\nB. Tsirelson. ", "Some results and problems on quantum [B]{}ell-type inequalities. , ", "8(4):329–345, 1993.", "\n\nB. Cirel’son (Tsirelson). ", "Quantum generalizations of [B]{}ell’s inequality. , ", "4:93–100, 1980.", "\n\n[^1]: See [http://www.cwi.nl/\\~wehner/tsirel/]{} for the Matlab example code.", "\n" ]

{ "pile_set_name": "ArXiv" }

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", "You may picture traditional white diamonds when you think of a fabulous diamond ring, tennis bracelet or pair of stud earrings, but black diamonds are also luxurious in a variety of fashionable jewelry. ", "Black diamonds are unofficially a part of the colored diamonds category. ", "Colored diamonds, also known as fancy diamonds, are natural diamonds in a range of bright hues. ", "To select the very best diamond jewelry for your collection, consider this comparison of black diamonds and white diamonds.", "\n\nTop 5 Colors in Fancy Diamond Engagement Rings\n\nFancy diamond engagement rings are trendy, but still unique. ", "These rings feature colored diamonds, and they come in a spectrum of hues. ", "Engagement rings with bright, colorful stones add a splash of color to your daily wardrobe. ", "Fancy diamond engagement rings may feature a stunning, highly-saturated center solitaire or colorful accent diamonds and a white center stone. ", "These diamond engagement rings really speak to a bride's individuality with an important dash of personalization.", "\n\nBlack Diamond Buying Guide\n\nBlack diamonds have become an increasingly popular design element in diamond jewelry. ", "For a long time, fashion preferred the monochromatic look of white diamonds set in white gold. ", "While all that bright silvery sparkle was pretty, fashionistas were happy to embrace new options when fancy color and black diamonds made jewelry more colorful and interesting. ", "Yet many people had questions about these dark stones. ", "Are they really diamonds? ", "How do I wear black diamond jewelry? ", "Here are the answers to your questions about black diamonds.", "\n\nCoated Topaz Jewelry Fact Sheet\n\nTopaz is a popular gemstone because it is beautiful, versatile and available in a wide range of prices. ", "Common colors of topaz include blue, white, pink and gold. ", "Topaz can also be coated with a layer of film to change the color and enhance the appearance. ", "Some of the more popular coated topaz gem varieties include mystic topaz, ecstasy topaz, mercury mist topaz, Neptune garden topaz and twilight fire topaz. ", "These brilliant, beautiful topaz gems are unique and are often set into beautiful pieces of jewelry. ", "Coated topaz jewelry, like rings, necklaces, bracelets and earrings can bring a splash of color to any ensemble.", "\n\nFAQs about Colored Diamonds\n\nWhen you are shopping for beautiful jewelry, you will see many pieces featuring colored diamonds. ", "Colored diamonds, also called fancy diamonds, are available in yellow, pink, purple, black, grey, green, blue and orange. ", "Rings, pendants, earrings and tennis bracelets decorated with colored diamonds are very trendy and valuable. ", "If shopping for colored diamond jewelry is new territory for you, then you might be wondering how to select the very best diamond jewelry featuring these bright gems. ", "Use these frequently asked questions to gather information about colored diamond jewelry.", "\n\nHow to Choose Diamond Wedding Rings\n\nIf you're ready to pop the big question, choose diamond wedding rings for you and your beloved. ", "A simple gold ring has been the standard in wedding bands for centuries, but many modern brides and grooms are choosing wedding rings with more sparkle. ", "Diamond wedding rings allow you to add gems to your wedding jewelry ensemble. ", "These rings draw attention to your prized wedding jewelry. ", "Diamond wedding bands can be matched to your diamond engagement ring, creating a stylish combination. ", "If you feel overwhelmed by the many choices in diamond wedding bands, allow us to help you narrow down the options and select the wedding bands that will delight you and your beloved.", "\n\nWhat to Wear with a Cubic Zirconia Cocktail Ring\n\nRight now one of the trendiest pieces of jewelry is the cocktail ring. ", "Cubic zirconia cocktail rings allow women to indulge in extravagant rings without emptying their bank accounts. ", "Cubic zirconia rings are available in a range of styles and each is very durable. ", "High-quality cubic zirconia cocktail rings can be found in every price range. ", "You can choose from cubic zirconia rings with sparkling clear stones or colorful gems set in sterling silver, white gold, yellow gold or gold-plated silver. ", "Now that you are aware of the many stylish options available in cubic zirconia jewelry, use these tips to fashionably pair cocktail rings with the clothing and jewelry you already own.", "\n\nTop 5 Occasions for Giving a Diamond Heart Pendant\n\nJewelry is often the best gift for every occasion. ", "If the girl or woman in your life deserves a special diamond jewelry gift, consider diamond heart necklaces. ", "Diamond heart necklaces and heart pendants are luxurious and romantic. ", "Surprise your girlfriend with a white gold diamond necklace heart pendant that she can wear with her favorite cocktail dress. ", "Show your daughter how proud you are with a diamond heart pendant at her college graduation. ", "The special lady in your life can wear her diamond heart pendant anytime and think of your love and support. ", "Consider our top five occasions for giving diamond heart necklaces when you are shopping for diamond jewelry and luxury heart necklaces.", "\n\nTop 5 Styles of Cubic Zirconia Engagement Rings\n\nWhen you are shopping for engagement rings, you will find many featuring stunning cubic zirconias. ", "Choosing a cubic zirconia engagement ring can give you the style you really want, even if you can't afford the same style in the diamond ring category. ", "Cubic zirconia rings are built to last, especially if you select one with a platinum or gold setting. ", "Whether as a temporary, affordable engagement ring or as an eco-friendly investment ring, cubic zirconia rings make stylish choices.", "\n\nWedding Bands History Fact Sheet\n\nWedding bands and engagement rings have a rich history. ", "Though the rings themselves have changed and cultural meanings have evolved, a ring on the fourth finger of the left hand has long been a way to show the world that you are in love. ", "Wedding rings today can be found in traditional gold, platinum and diamond styles as well as unique gemstone, titanium and stainless steel varieties. ", "Learning a bit about wedding band and engagement ring history can help you decide what type of wedding jewelry is right for you.", "\n\nGemstone Jewelry Buying Guide\n\nGemstone jewelry both accessorizes our fashion choices and lets us show off a little. ", "Although the accessories can be casual, like a birthstone ring worn every day, or extravagant, like a ruby and diamond necklace saved for special occasions, sterling silver and gold are still the preferred metals for gemstone jewelry, making each piece a small luxury.", "\n\nBest Citrine Fashion Rings\n\nCitrine brings a range of yellow and gold hues to the jewelry world. ", "This fabulous gemstone looks great when paired with neutrals or warm hues. ", "To bring this light and bright stone to your wardrobe, choose a few citrine fashion rings in various trendy styles. ", "You can wear citrine rings with grey jeans, crisp white tops, black trousers, or vintage pastel dresses. ", "Citrine is a yellow type of quartz, and though it can hold its own against the most beautiful gemstones, it is not prohibitively overpriced like some jewelry can be. ", "Citrine is the perfect gemstone for fashion rings that you wear casually; it will glow in any light and stylishly accessorize both modern and retro outfits.", "\n\nTips on Different Types of Men's Bands\n\nA wedding band is often the most important piece of men's jewelry, as many men keep their accessories to a minimum. ", "It is important, therefore, to choose men's wedding bands that will be comfortable and that will showcase your personal style and go with everything in your closet. ", "You have many options when shopping for men's bands, including wedding ring bands made of gold, silver, platinum, titanium, stainless steel and tungsten. ", "You can also choose from men's wedding bands featuring diamonds, gemstones, engraving, inlaid designs and intricate details. ", "It is important to select men's bands that will go well with your other men's jewelry pieces or watch collection. ", "If the task of choosing men's wedding rings leaves you a bit confused, consider our tips for selecting men's rings before you start shopping.", "\n\nTips on Storing Pendants\n\nA collection of pendants is at the heart of most women's jewelry collections. ", "A diamond-covered kitten pendant, a heart-shaped gold locket and a birthstone solitaire necklace shouldn't be strewn across your dresser with your sterling silver rings and beaded earrings. ", "Storing your pendants properly is the best way to make sure that you'll wear them, getting the most out of your jewelry investment. ", "Use these jewelry storage tips to keep your pendants and necklaces organized.", "\n\nJewelry Box Buying Guide\n\nStunning diamond earrings, an armful of gold bangles, your first pearls and your beautiful wedding rings: Jewelry has emotional value as well as monetary value, and you want to keep your treasures safe by storing them in a jewelry box. ", "Good jewelry cases are available in many shapes, sizes and materials, and buying jewelry organizers can be frustrating if you are not sure of what you need. ", "Jewelry storage options are an important part of any wardrobe. ", "Jewelry cases protect your jewelry and watches just like dressers and closets protect your clothes and other fashion accessories. ", "Of course, a well-organized closet makes it easier to take care of a clothing wardrobe, and well-organized jewelry storage will do the same for your gold, diamonds and pearls. ", "To choose a good jewelry case, wooden box, jewelry stand or keepsake box, consider the construction, materials and design of the case or box. ", "This jewelry box buying guide is designed to help you sort through the options and make a more informed buying decision.", "\n\nBest Jewelry Ideas for Men\n\nJewelry can really add to the style of a man, depending on how he chooses to wear it. ", "The type and quantity you choose to wear really says a lot about you. ", "Wearing the right jewelry and watches can catch the eye and give you a look that is quite professional and classy, while wearing the wrong jewelry can appear tacky. ", "Whether you are buying men's jewelry for yourself or shopping for men's watches, rings, necklaces and bracelets to give as gifts, the best men's jewelry ideas are those that reflect your personal style and contribute to a sophisticated look. ", "Rings are one of the most common men's jewelry items and can require a lot of thought during the shopping process. ", "Whether you are shopping for a men's wedding band, a special ring for an anniversary or Valentine gift or just want to add a nice ring to your jewelry collection, masculine rings come in a variety of styles to suit nearly every man's taste. ", "Classic materials such as silver and gold are a great choice in men's rings because they are timeless and come in nearly every shape and size to fit you just right. ", "On the other hand, materials such as tungsten, titanium and stainless steel are becoming popular choices for men's rings because of their durability and sleek, modern look. ", "Men's rings are also available with diamonds and gemstones if you are interested in a ring with a little more flair. ", "The right watch will add a lot to your daily look, and should also be a highly functional piece. ", "You have a wide range of options when shopping for a men's watch. ", "If you feel overwhelmed by the process, then you might try narrowing it down by price, material and functions. ", "Men's watches are available in a wide range of prices, so establishing a budget is a great first step in the shopping process. ", "Additionally, with so many styles available, it is important to have a general idea of the look and type of material that you want in a watch. ", "Sporty watches with high quality plastic and leather straps are perfect additions to casual looks, while fancier watches made of gold, silver, titanium, stainless steel, tungsten and platinum can add a lot to a classy and dressy wardrobe. ", "When it comes to functions, shopping for the perfect watch becomes very personal. ", "Every man needs something different in a watch and you can find the perfect one for you, whether you want something very simple and basic or you desire a highly technical timepiece. ", "Shopping for men's bracelets, necklaces and earrings can be a little tricky and requires some careful thought. ", "Many men find that watches and rings are simply not enough for their jewelry wardrobe. ", "There are many different kinds of men's bracelets, necklaces, earrings and other unique pieces that you can add to create the right look for you. ", "These pieces come in many different varieties to suit your style preferences. ", "Necklaces and bracelets made of gold, silver, titanium and platinum add a bit of polish to an outfit, while natural materials such as hemp and leather provide a more understated look. ", "When shopping for men's earrings, personal style is a main factor and you can choose between studs with diamonds and gemstones, ear plugs, surgical steel hoops and many others. ", "Don't be afraid to let your personal style shine through, use men's jewelry pieces to accentuate every outfit in your closet. ", "View All Men's Jewelry Back to Guides Directory View All Men's Jewelry\n\nAnniversary Gemstones At-A-Glance\n\nGemstones have long been thought to bring a person luck. ", "On your anniversary, they're also a great way to show the special person in your life how much you care. ", "In addition to gems, precious metals and specific pieces are associated with some anniversary years. ", "Use this guide to choose an anniversary gift or a piece of gemstone jewelry for this milestone occasion. ", "Once you have determined which gemstone will be perfect for your anniversary, you might be wondering which type of jewelry to select. ", "Gemstone jewelry is available in a wide range of styles. ", "For a romantic reminder of your relationship that can be worn every day, look for anniversary rings. ", "Gemstone necklaces, bracelets, and earrings can be extravagant for special occasions or casual enough for regular wear. ", "Consider your loved one's wardrobe and style whenever you're shopping for jewelry gifts. ", "Some anniversaries are associated with a gemstone or precious metal and a coordinating celebration, called a \"jubilee.\" ", "Celebrate your 25th wedding anniversary with a silver jubilee, your 30th with a pearl jubilee, your 50th with a gold jubilee, your 60th with a diamond jubilee, your 70th with a sapphire jubilee, and your 80th with a ruby jubilee.", "\n\nDiamond Buying Guide\n\nFine jewelry is an investment that can last for generations, so it's important to know how to buy diamonds before you start shopping. ", "When purchasing diamond jewelry, pay attention to the four C's: color, clarity, cut, and carat weight. ", "These are the four characteristics by which a diamond's quality is measured. ", "If all four are ranked high, the diamond jewelry will cost more, but it will be that much more beautiful and valuable.", "\n\n* For your protection, all orders are screened for security purposes. ", "If your order is selected for review, our Loss Prevention Team may contact you by phone or email. ", "There may be a two business day delay to process your order.", "\n\n** Most Oversize orders are delivered within 1-4 weeks. ", "Some orders may take 6 weeks to be\ndelivered.", "\n\nFeatured\n\nShop Overstock™ and find the best online deals on everything for your home and your family. ", "We work every day to bring you discounts on new products across our entire store. ", "Whether you're looking for memorable gifts or everyday essentials, you can buy them here for less." ]

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[ "Introduction {#s0005}\n============\n\nAccording to the GLOBOCAN 2012 database, the most recent year for which statistics are available, lung cancer is the most common cancer (1.8 million cases) and the leading cause of cancer-related death (1.59 million deaths) worldwide [@bb0005]. ", "Tobacco smoking remains the dominant cause of all non--small cell lung cancers (NSCLCs) except in the case of adenocarcinomas with fusions or mutations of the kinase genes such as epidermal growth factor receptor (EGFR), which occur specifically in light or never-smokers [@bb0010]. ", "These mutations, which have been identified in exons 18 to 21 of the TK domain and appear most commonly in exon 19 (*del19*) and in exon 21 (*L858R*), activate the receptor tyrosine kinase pathway (hence the term \"activating mutations\"), leading to overstimulation of downstream signaling prosurvival pathways including Ras-Raf-MAP-kinase and PI3K-Akt-mTOR that confer oncogenicity. ", "Activating EGFR mutations, to which tumors are \"addicted\" for survival, are primarily associated with adenocarcinoma histology; frequently mutually exclusive with other activating tumor mutations; and only rarely found in large cell carcinomas, small cell carcinomas, and squamous carcinomas [@bb0015]. ", "While deletions in exon 19 and L8585R point mutation in exon 21 are considered activating, other EGFR mutations such as exon 20 insertions are not activating and, therefore, do not tend to respond to EGFR tyrosine kinase inhibitor (TKI) treatment.", "\n\nThe frequency of EGFR driver mutations in lung adenocarcinomas differs according to ethnicity and sex, appearing at a rate of approximately 10% to 15% in North Americans and Europeans [@bb0020] and as high as 30% to 50% in East Asians [@bb0025], most commonly in East Asian women that have never smoked. ", "Unlike SCLC, which is strongly linked to smoking behavior, a history of never or minimal smoking is the strongest predictor of harboring the EGFR mutation in NSCLC, which strongly suggests that EGFR mutagenesis arises from nontobacco carcinogens: in fact, the total number of pack-years smoked has been found in multiple studies to inversely correlate with the rate of EGFR TK mutations [@bb0030], [@bb0035]. ", "In addition, the high mutation burden typically induced by carcinogens in cigarette smoke, which putatively leads to a higher quantity of neoantigens [@bb0040], may underlie the generally poorer response to PD-1 inhibition in EGFR^+^ NSCLC. ", "According to the Surveillance, Epidemiology, and End Results database of the National Institutes of Health [@bb0045], lung cancer accounts for approximately 6.4% of all malignancies, and since \\~10% to 15% of these are EGFR mutated, the lifetime prevalence of EGFR-mutated tumors is between 88,300 and 132,400, making it an orphan disease in the United States from a prevalence count perspective (\\<200,000 prevalent cases).", "\n\nEGFR, a transmembrane glycoprotein, is part of the ErbB/HER family of receptor tyrosine kinases, which includes three other members: HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4) [@bb0050]. ", "The presence of activating EGFR mutations in advanced NSCLC confers sensitivity to standard-of-care TKIs such as afatinib, gefitinib, erlotinib [@bb0055], dacomitinib, and osimertinib and predicts a better prognosis as compared to EGFR wild-type NSCLC. ", "While the use of TKIs, which are superior to chemotherapy, has resulted in substantial benefits including an initial response rate of approximately 70% and an overall survival from 1 to nearly 3 years [@bb0060], the universality of treatment resistance limits the duration of their use.", "\n\nClinical management of TKI-failed patients constitutes an uncertain \"no man\\'s land\" since, to date, there are no clear guidelines, and new accepted strategies to improve outcomes are lacking [@bb0065], [@bb0070]. ", "A retrospective analysis of 521 EGFR TKI-failed patients by Song et al. [", "@bb0075] highlights the poor prognosis in this population since of the 223 patients who previously received long-term TKI therapy (\\>6 months), overall survival was a dismal 5 months. ", "In the absence of satisfactory therapeutic options and treatment guidelines after failure of subsequent salvage second- and third-line chemotherapy EGFR-positive NSCLC is an area of high unmet medical need. ", "A systematic review of the available literature highlights a wealth of data from high-quality clinical trials on clinical outcomes with TKIs and a corresponding paucity of information and evidence pertaining to treatment of tumors that have exhausted TKI options. ", "With the focus of attention on treatment with TKIs, a hotspot of clinical research, the question of how to manage patients that exhaust TKI and chemotherapy options is an open one. ", "Despite the relative paucity of available data on this subject, this review aims to summarize current and alternative treatment strategies as well as potential future directions in advanced TKI-failed EGFR-mutated NSCLC.", "\n\nCurrent treatment strategies {#s0010}\n============================\n\nFirst-line TKIs {#s0015}\n---------------\n\nSeveral randomized trials including EURTAC [@bb0080] and OPTIMAL [@bb0085] for erlotinib; NEJGSG\\_ 002 [@bb0090], WJTOG 3405 [@bb0095], and IPASS [@bb0100] for gefitinib; and LUX LUNG 3 [@bb0105] and LUX LUNG 6 [@bb0110] for afatinib have demonstrated the superiority of EGFR TKIs to chemotherapy in terms of overall response rates and progression-free survival (PFS) for first-line therapy (see [Figure 1](#f0005){ref-type=\"fig\"}).Figure 1Patterns of clinical relapse and algorithm for EGFR mutation--positive NSCLC. ", "Abbreviations: WBRT, whole brain radiotherapy; M+, mutation positive.", "Figure 1\n\nErlotinib and gefitinib are first-generation reversible TKIs, while afatinib and lapatinib are second-generation irreversible pan-HER TKIs [@bb0115] that are reported to be superior to gefitinib in EGFR exon 19 deleted tumors and other less common mutations (see [Figure 2](#f0010){ref-type=\"fig\"}).Figure 2Mechanism of different EGFR TKIs. ", "Abbreviations: HER-2, human epidermal growth factor receptor 2.Figure 2\n\nDespite strikingly high initial response rates with these TKIs, the development after 11 to 14 months of acquired resistance, as defined by the Jackman criteria [@bb0120] (disease progression after objective response or durable stable disease for \\>6 months on a TKI), is a virtual *fait accompli* [@bb0125]. ", "In over 60% of patients that have progressed on first- and second-generation TKIs, the mechanism of resistance is an acquired threonine-to-methionine amino acid substitution at the gatekeeper position 790 of EGFR in exon 20 or T790M [@bb0130], which increases the affinity of the EGFR kinase domain for ATP and thereby outcompetes the binding of EGFR TKIs; the T790M-resistant tumor cells may arise from the selective pressure of a TKI or present *de novo*. ", "Based on data from the Phase II AURA 2 trial and the AURA extension cohort, T790M-positive tumors are responsive to treatment with the third-generation TKI osimertinib [@bb0135]. ", "However, secondary mutations have also been described as a mechanism of acquired resistance to osimertinib. ", "In addition to T790M, the occurrence of other resistance mechanisms including activation of the MET pathway, HER2 amplification, mutations in Pi3kinase and BRAF, and transformation to small cell lung cancer supports rebiopsy at clinical progression to determine the molecular/morphologic changes and to personalize the therapy accordingly.", "\n\nChemotherapy {#s0020}\n------------\n\nAfter progression on osimertinib, despite a lack of strong supporting evidence (no prospective trials comparing the efficacy of chemotherapy regimens have been conducted), platinum doublets, e.g., cisplatin/carboplatin plus paclitaxel, nab-paclitaxel or pemetrexed × 4 to 6 cycles +/− bevacizumab, are routinely recommended for patients without any targetable mutations followed by the option of single-agent pemetrexe, docetaxel, or erlotinib. ", "For so-called T790M-negative tumors, second-line therapy is a chemotherapy doublet. ", "Options for patients with T790M mutation--negative tumors that progress on chemotherapy are limited.", "\n\nEGFR Inhibition Beyond Progression {#s0025}\n----------------------------------\n\nBased on the concept of \"oncogene addiction\" in which tumors, dependent on oncogenes such as EGFR for their continued proliferation and survival, experience accelerated regrowth or \"flare\" after stopping TKI therapy, progressive disease on a TKI does not necessarily equate with exhausted benefit. ", "Accordingly, one option is to continue TKIs beyond progression in asymptomatic patients. ", "In a 2013 study, Yang et al. [", "@bb0140], having stratified TKI-failed patients according to three types of progression (dramatic, gradual, and local), demonstrated that the continuation of EGFR TKI is feasible for gradual and local progression (+ local modalities such as surgical resection, stereotactic radiotherapy, and cryotherapy); continued sensitivity to therapy is suggested. ", "For dramatic progression, chemotherapy, not EGFR TKI continuation, is indicated as well as a biopsy to rule out histologic transformation from NSCLC to small cell lung cancer, which constitutes an additional resistance mechanism to TKI therapy [@bb0145].", "\n\nThe effect of TKI continuation past true progression in EGFR^+^ NSCLC was also explored in the ASPIRATION \"Asian Pacific Trial of Tarceva as First-Line in EGFR Mutation\" and IMPRESS \"IRESSA Mutation-Positive Multicenter Treatment Beyond Progression Study.\" ", "In the nonrandomized ASPIRATION (Asian Pacific trial of Tarceva as first‐line in EGFR mutation) study, patients with indolent, small-volume asymptomatic growth, i.e., gradual progressors and oligometastatic progressors, selected at investigators\\' discretion, that were continued on single-agent erlotinib beyond RECIST progression showed an improvement in PFS by 3.1 months [@bb0150] from 11.0 to 14.1.", "\n\nHowever, in the randomized Phase 3 IMPRESS (IRESSA Mutation‐Positive Multicenter Treatment Beyond Progression Study), patients that remained on gefitinib during doublet chemotherapy did not experience improved response rates or PFS, which established doublet chemotherapy as the standard of care after progression on EGFR TKIs [@bb0155]. ", "Nevertheless, the overall consensus is that while dramatic progression mandates a change in treatment strategy, EGFR TKI continuation in the setting of oligometastatic disease is a feasible option [@bb0160] to delay the time to progression and the need for subsequent platinum-based treatments, eventually with the addition of local therapy.", "\n\nContinuation of EGFR TKI with Brain Metastases {#s0030}\n----------------------------------------------\n\nThe incidence of brain metastases in NSCLC is 25% to 30%, and that incidence is increased in EGFR-mutated NSCLC to 44% to 63% [@bb0165], possibly because patients live longer on TKIs and the risk of brain metastases increases with lifespan or possibly because the propensity to metastasize is greater in EGFR-mutated cancers. ", "For patients with oligometastatic progression in the brain after EGFR TKI therapy, the consensus is to continue EGFR TKI with local therapies such as radiotherapy, surgery, and stereotactic ablative radiotherapy on the suspicion that poor blood brain barrier penetration of the TKI rather than cellular resistance [@bb0170] is to blame; in this case, EGFR TKI continuation may serve to maintain systemic remission. ", "Jackman et al. [", "@bb0120]. ", "demonstrated that high-dose gefitinib penetrates the blood-brain barrier more effectively, and likewise, pulsatile high-dose erlotinib was found to overcome acquired resistance to standard-dose erlotinib [@bb0175].", "\n\nTreatment-Free Interval (Drug Holiday) {#s0035}\n--------------------------------------\n\nDespite the potential for disease flare during an EGFR TKI--free period, restoration of TKI sensitivity, which may be epigenetically mediated, has been documented after a drug holiday. ", "In a study of 23 patients who were rechallenged with gefitinib after a median 7-month break, during which time they received cytotoxic anticancer therapy, Tomizawa et al. [", "@bb0180] reported a partial response rate of 22% and a disease control rate of 65%. ", "In a retrospective study of 14 patients [@bb0185], reintroduction of erlotinib after a median 9.5-month holiday resulted in 36% (*n* = 5) partial response, 50% stable disease (*n* = 7) ,and 14% progressive disease (*n* = 2). ", "However, these were small-scale studies, and further investigation from larger prospective trials is required to confirm these outcomes.", "\n\nAlternative Treatment Strategies/Future Directions {#s0040}\n==================================================\n\nImmunotherapy + TKI {#s0045}\n-------------------\n\nFour randomized phase III trials have reported a statistically significant improvement in response rate (RR) and overall survival (OS) with immune checkpoint inhibitors such as nivolumab and pembrolizumab over standard second-line docetaxel chemotherapy in platinum-refractory NSCLC [@bb0190]. ", "By contrast, EGFR-mutant advanced NSCLC patients gained no overall survival (OS) benefit from immune checkpoint inhibitors over docetaxel [@bb0195], which may be related to the general lack of tobacco use in this population since smoking is associated with a higher mutational burden, a biomarker of response to immunotherapy [@bb0200].", "\n\nNonetheless, PD-L1 expression has been associated with EGRF mutation [@bb0205], which has been reported to correlate with a higher likelihood of response to PD-1 blockade, suggesting that immunotherapy in EGFR-mutant NSCLC may still hold promise. ", "However, despite evidence of clinical activity, combinations of nivolumab plus erlotinib, gefitinib plus durvalumab, and osimertinib plus durvalumab (anti--PD-L1 monoclonal antibody) resulted in a relatively high incidence of treatment-related grade 3 to 4 toxicities [@bb0210], and in fact, two trials with the osimertinib plus durvalumab combination were halted due to an excess of pulmonary toxicity. ", "However, many new immunotherapy agents are under development including the inhibitory molecules TIM-3, LAG-3, IDO (indoleamine-pyrrole 2,3-dioxygenase), BTLA (B- and T-lymphocyte attenuator), adenosine, and VISTA (V-domain immunoglobulin containing suppressor of T cell activation) and the stimulatory molecules 4-1BB, OX40, CD40, and CD27. ", "Therefore, the \"jury is still out\" on the clinical feasibility of immunotherapy in this population.", "\n\nMesenchymal-Epidermal Transition (MET) Inhibition {#s0050}\n-------------------------------------------------\n\nAmplification (but probably not mutation) of MET, a receptor tyrosine kinase, occurs in up to 20% of tumors [@bb0215] with acquired resistance to EGFR TKIs, which suggests the potential for synergistic benefit from combination treatment with an EGFR and MET inhibitor [@bb0220]. ", "MET amplification and T790M mutation are not mutually exclusive; both may coexist, or MET amplification may occur on its own. ", "Therefore, concomitant inhibition of MET and EGFR is likely required. ", "Several published case reports with a TKI + crizotinib, a known MET and ALK inhibitor that has demonstrated activity in MET-amplified patients, and other clinical data [@bb0130] support this assumption [@bb0225], [@bb0230]. ", "In a Phase 2 study with erlotinib + tivatinib, a selective c-MET inhibitor, in a TKI-failed EGFR-positive population, a subgroup of patients with high MET expression responded to the combination therapy, although the study as a whole did not meet its endpoint [@bb0235]. ", "In a Phase 1b/2 study ([NCT01610336](ctgov:NCT01610336){#ir0005}), the combination of capmatinib (INC280), another MET inhibitor, and gefitinib in 65 high-MET EGFR TKI-resistant NSCLC patients yielded a disease control rate of 80% (overall response rate 18%; stable disease 62%) [@bb0240]. ", "In a Phase 1 study of tepotinib (MSC2156119J) plus gefitinib, 18 patients were treated, and 5 had a partial response [@bb0245]. ", "While the combination of MET inhibitors and EGFR TKIs seems promising, the potential for overlapping or additive toxicities based on the mechanisms of action of these agents is an important consideration, which requires testing in large clinical trials.", "\n\nOncolytic Virotherapy {#s0055}\n---------------------\n\nSince nonsmoking EGFR-mutated NSCLC patients may resist checkpoint therapy due to a low mutational load, treatments like radiotherapy or virotherapy that induce the release of tumor antigens may augment the activity of PD-1/L1 inhibitors. ", "As cancer-specific lytic agents, with or without therapeutic transgenes to augment the immune response, locally injected replicating oncolytic viruses that liberate nonself neoantigens for T-cell priming may elicit abscopal effects at distant metastatic sites; however, unlike radiotherapy, which also is associated with abscopal effects but may induce pneumonitis and scarring in the lungs, oncolytic viruses have been genetically engineered for attenuation and nonpathogenicity in normal cells and are, hence, in general, minimally host toxic.", "\n\nThe mechanism by which oncolytic viruses even in the absence of therapeutic transgenes kill tumor cells and elicit a systemic immune effect involves direct lysis of tumor cells and cell death via synthesis of new viral particles with subsequent spread of tumor-associated antigens and epitopes after the cell lysis [@bb0250]. ", "When the virus is armed with therapeutic immunomodulatory transgenes, which theoretically enhance the immune response, the infected tumor cell serves as a \"factory\" for protein synthesis such that the beneficial transgene is overproduced and may spread to distant tumor sites via the circulation.", "\n\nTalimogene laherparepvec (Imlygic), commonly referred to as T-VEC, an attenuated herpes simplex virus type 1 virus armed with a GM-CSF transgene that is approved for the treatment of melanoma [@bb0255], has the potential to overcome tumor-induced T-cell anergy and thereby enhance the activity of anti-CTLA and PD-1 antibodies in EGFR-mutated NSCLC. ", "Several oncolytic adenoviruses carrying different immunomodulatory [@bb0260] transgenes and theoretically safer than herpes virus appear poised to enter the clinic in early 2018 as potential treatments for multiple tumor types including EGFR^+^ NSCLC.", "\n\nEpigenetic Resensitization {#s0060}\n--------------------------\n\nThe term \"epigenetics\" refers to reversible modifications that influence gene expression without directly changing or affecting the DNA coding sequence [@bb0265]. ", "Epigenetic alterations, which include DNA methylation, microRNA regulation, and histone/nucleosome modifications, influence multiple cellular processes such as transcription, replication, and repair and are implicated in tumorigenesis and chemotherapy resistance [@bb0270], [@bb0275]. ", "Epigenetic mechanisms have been proposed to explain the reversion to TKI sensitivity after a drug holiday. ", "Epigenetic inhibitors such as histone deacetylators and DNA methyltransferases, which dynamically reprogram the epigenome, the collective name for chromatin and DNA modification patterns, have been associated with resensitization of several refractory tumor types including EGFR+ NSCLC to conventional therapies such as cisplatin and carboplatin. ", "One such agent is the experimental tumor-associated macrophage and neutrophil-repolarizing agent RRx-001, which in Phase 2 clinical trials has been shown to resensitize refractory TKI- and chemotherapy-failed EGFR-positive NSCLC patients [@bb0135] to subsequently administered platinum doublets. ", "If successful, the potential to reverse resistance to chemotherapy and possibly TKIs as well might significantly improve overall survival in this last-line population.", "\n\nConclusion and discussion {#s0065}\n=========================\n\nWhile EGFR TKI inhibitors yield impressive and durable responses, prolonged PFS, and improved quality of life when compared to chemotherapy, inevitable resistance to them as well as to subsequent platinum doublets is a \"no man\\'s land\" of unmet medical need, as patients at this terminal stage have exhausted all available lines of treatment. ", "Careful analysis of resistance mechanisms and mutation status at the time of clinically significant disease progression may guide the selection of subsequent treatment, if one exists; but if not, the only options that remain to patients are local ablative therapies, clinical trials, or hospice with poor quality of life and death at the end of their palliative care. ", "New strategies to prevent or reverse the development of resistance are therefore urgently needed and include immunotherapy, concomitant EGFR + MET inhibition, oncolytic virotherapy, epigenetic resensitization with subsequent administration of previously failed chemotherapies, and potentially the discovery of currently unknown driver mutations that synergize with all of the above especially immunotherapy.", "\n\nThe key advantage of immunotherapy in NSCLC is the durability of responses. ", "Where resistance development is a near-universal feature of chemotherapy and targeted agents, the tumor-specific memory function of the immune system has the potential to confer lasting remission/regression of metastatic disease. ", "However, as stated earlier in this review, EGFR-mutated tumors seem not to benefit from checkpoint inhibitors possibly due to a relatively low mutation burden despite higher levels of PD-L1 expression, which has been shown to correlate with response. ", "Since it is infeasible to increase the mutational load in EGFR+ cancers, one strategy to refocus the immune response is to selectively increase the exposure/release of tumor neoantigens, inflammatory cytokines, and particular damage-associated molecular patterns that can stimulate the immune system and potentiate the efficacy of formerly inactive checkpoint inhibitors. ", "If successful, targeted therapies such as dual EGFR + MET inhibition and particularly oncolytic virotherapy will mediate release of tumor neoantigens from lysed cells along with cytotoxics in epigenetically resensitized tumors.", "\n\nOn this basis, potentially optimal sequential immunotherapeutic priming strategies to trigger the release of immunogenic antigens from dying cancer cells in TKI- and chemotherapy-failed tumors might include 1) pretreatment of a non--MET-amplified tumor for several weeks with an epigenetic inhibitor before starting a cytotoxic like cisplatin or carboplatin for four to six cycles followed by checkpoint inhibition and 2) administration of oncolytic viruses in combination with EGFR TKI + MET targeted therapy in MET-amplified tumors followed by checkpoint inhibition (see [Figure 3](#f0015){ref-type=\"fig\"}).Figure 3Lytic-inducing strategies in EGFR+ NSCLC are anticipated to result in the release of multiple tumor neoantigens. ", "Tumor neoantigens are engulfed by antigen-presenting cells and processed and presented to T cells in the context of B7 costimulatory molecules and major histocompatibility complex. ", "T cells express checkpoint inhibitory molecules such as PD-1 and CTLA-4, which prevent full activation. ", "Immune checkpoint blockade relieves immune suppression, effectively taking the brakes off the T cells and restoring their effector function to effectively attack the tumor. ", "Abbreviations: CTLA-4, cytotoxic T lymphocyte--associated protein 4; MCH, major histocompatibility complex; PD1, programmed cell death protein 1; PD-L1, PD1 ligand; TCR, T-cell receptor. ", "Adapted from Sharma P, Allison JP. ", "Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. *", "Cell* 2015;161:205-14.Figure 3\n\nThe cancer-immunity cycle proposed by Chen and Mellman consists of seven steps [@bb0280]: 1) release of cancer antigens, 2) cancer antigen presentation, 3) priming and activation, 4) T-cell trafficking to tumors, 5) T-cell tumor infiltration, 6) recognition of cancer cells by T cells, and 7) killing of cancer cells.", "\n\nIn this cycle, the induction of an immune response begins when professional APCs, such as dendritic cells, engulf apoptotic or necrotic tumor cells and present tumor-associated antigens on their surface to their cognate T cells. ", "A prerequisite for immune cell--mediated tumor cell destruction is interaction of the antigen-specific T cells with MHC-I-peptide complexes. ", "Since NSCLC, like melanoma, kidney, and urothelial cancers, typically (although not always) presents as inflamed or T-cell rich, steps 1, 2, and 3 (i.e., release of cancer antigens, cancer antigen presentation, and priming and activation) arguably play the most important role in EGFR-mutated NSCLC.", "\n\nIn summary, while possibly an oversimplification of complex oncoimmunology, the overall low mutation load in EGFR+ NSCLC may render these tumors preferentially susceptible to lytic-inducing strategies that amplify intratumoral T cells against undefined antigens prior to administration of checkpoint inhibitors. ", "Besides viruses, targeted therapies, epigenetic inhibitors, and cytotoxic chemotherapies other potentially lytic-inducing agents may include adoptive cell transfer therapies such as CAR-T, cytokines such as IL-2 and IL-15, bacteria and yeast vectors, and personalized polyepitope DNA vaccines that are selected on the basis of mutation status and MHC binding affinity.", "\n\nThe opposite of no man\\'s land is a fertile plain. ", "It is hoped that, in the near future, new, innovative strategies will be available to overcome resistance mechanisms, especially immunologically based resistance mechanisms, and thereby transform the no man\\'s land of TKI- and chemotherapy-failed EGFR+ NSCLC into a vast fertile plain, rich with promising therapeutic options that result in meaningful improvements to quality of life and survival.", "\n\nFunding {#s0070}\n=======\n\nNone.", "\n\nEthical Approval {#s0075}\n================\n\nThis review article does not contain any studies with human participants or animals.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Chelsea player ratings : Eden Hazard impressed for Chelsea (Image: Reuters). ", "Eden Hazard inspired Chelsea to a narrow 2-1 victory over Newcastle to maintain their 100 per N'Golo Kante was joined by new signings Mateo Kovacic and Jorginho, though only one of them stood out during the game.", "\n\nChelsea are now comfortably ahead of Arsenal in the race for the top four, but their performance was anything but comfortable as they struggled past Newcastle in Saturday’s late kick-off.", "\n\nGoals either side of half-time from under fire forwards Pedro and Willian were enough to secure the three points necessary to heap further misery upon Unai Emery’s Arsenal side, following their third loss in five away games against West Ham United earlier in the day.", "\n\nChelsea were out of blocks quickly and raced ahead within nine minutes as Pedro latched onto David Luiz’s ball in behind to lob the onrushing Martin Dubravka. ", "As quickly as they started the game, however, Maurizio Sarri’s men soon enough sank into their typical air of ponderous complacency, gifting Newcastle a route back into the game through static off the ball movement, which allowed the Magpies to man-mark all over the pitch. ", "Ciaran Clark was to be the man to make Chelsea pay when he headed in unmarked from a corner with five minutes of the first-half to play.", "\n\nChelsea vs Newcastle: Sarri out to silence the critics\n\nMaurizio Sarri will be hoping to silence his critics as the Blues play Newcastle and reunite with their former manager Rafa Benitez this weekend. ", "Chelsea – who come into the game following a 1-0 loss to Spurs – have looked shaky in recent weeks with a lack of a frontman causing significant problems for ‘Sarriball’. ", "With Alvaro Morata’s exit looming large, and Giroud often featuring as a substitute, it is no wonder Chelsea have scored just three goals in four matches. ", "To put that into perspective the league’s current whipping boys, 20th-placed Huddersfield have scored four goals in that time – arguably against harder opposition.", "\n\nOn Saturday Chelsea will play the 900th match since Roman Abramovich bought the club in 2003. ", "Two Newcastle players , goalkeeper Martin Dubravka and Mohamed Diame have started every Premier League match this term.", "\n\nIt was our wide players ’ day at Stamford Bridge in the tea-time kick-off, with Pedro and Willian N’Golo Kante robbed Newcastle of the ball high up the field but the best Willian could win was a corner. ", "The teams: Chelsea v Newcastle . ", "There are three changes from the side which played at\n\nPedro - 8\n\nEden Hazard - 6\n\nWillian - 7.5\n\nSubs:\n\n13/13 SLIDES\n\nDespite persistent criticism of his end product, and rumours of him leaving for Barcelona, Brazilian winger Willian proved his quality to restore his side’s lead when he cut in from the left-hand edge of the box to curl the ball in off the post.", "\n\nRelief was hanging in the air come the final whistle as Chelsea created very few chances to put the game beyond doubt, hanging on to move six points clear of Arsenal.", "\n\nSimilar from the Web\n\nChelsea player ratings vs Newcastle : Eden Hazard | Express.co.uk\n\nChelsea player ratings : Eden Hazard impressed for Chelsea (Image: Reuters). ", "Eden Hazard inspired Chelsea to a narrow 2-1 victory over Newcastle to maintain their 100 per N'Golo Kante was joined by new signings Mateo Kovacic and Jorginho, though only one of them stood out during the game.", "\n\nThe teams: Chelsea v Newcastle | Official Site | Chelsea Football Club\n\nOn Saturday Chelsea will play the 900th match since Roman Abramovich bought the club in 2003. ", "Two Newcastle players , goalkeeper Martin Dubravka and Mohamed Diame have started every Premier League match this term.", "\n\nReport: Chelsea 2 Newcastle 1 | Official Site | Chelsea Football Club\n\nIt was our wide players ’ day at Stamford Bridge in the tea-time kick-off, with Pedro and Willian N’Golo Kante robbed Newcastle of the ball high up the field but the best Willian could win was a corner. ", "The teams: Chelsea v Newcastle . ", "There are three changes from the side which played at\n\nNewcastle 3-0 Chelsea | Player Ratings | \"10th In The League \"\n\nBig Renty & Keg give their verdict on the Newcastle players ratings in the end of the season win over Chelsea at St James Park. ", "Follow us on all social\n\nPMB: Chelsea v Newcastle - talking points | Official Site\n\nChelsea have won our last six matches at Stamford Bridge against Newcastle in all competitions, scoring 18 while conceding just two goals. ", "As we are back in Premier League mode, we thought it would be interesting to look at minutes played so far this season. ", "Nine Blues players have been\n\nPMB: Chelsea v Newcastle - history | Official Site | Chelsea Football\n\nPMB: Chelsea v Newcastle - history. ", "10 MIN AGO. ", "Former FIFA World Player of the Year George Weah, making his debut for the Blues as substitute for Gus Poyet, scored a late goal that beat Tottenham Hotspur and sent Stamford Bridge Maurizio Sarri’s verdict if Chelsea played England.", "\n\nChelsea player ratings : Newcastle (A) - Read Chelsea\n\nChelsea continued to probe a deep Newcastle side throughout the encounter and eventually found a breakthrough as Marcos Alonso was brought down in the box. ", "Here are our Chelsea player ratings from Maurizio Sarri’s third consecutive win as boss.", "\n\nNewcastle Player Ratings v Chelsea\n\nThere are loads of player ratings being thrown around by various media outlets. ", "Some of them are way off the mark and others are half decent. ", "I’ve decided to start doing my own after Newcastle matches and comparing them to what the media say.", "\n\nChelsea Player Ratings : PAOK ( H )\n\nChelsea Player Ratings : PAOK ( H ). ", "Read Sport 29/11/2018 Ryan Darby. ", "Chelsea took their Europa League campaign to five wins from five in the group stage, with the Blues dominating Greek outfit PAOK.", "\n\nBenson released a statement on the team's website after the 26-23 overtime loss to the Rams. \"", "Yesterday’s result is still difficult to accept for all of us,\" Benson wrote. \"", "I am thoroughly disappointed by the events that led to the outcome of yesterday’s game. ", "Getting to the Super Bowl is […]\n\nIt was reported last week that Liverpool had made an offer for Benfica star Joao Felix, but the Reds could have competition in their pursuit of the young forward. ", "Portuguese outlet Record, as cited by the Star, claims that Manchester United are also interested in signing the attacking […]\n\nDespite suggestions in various media outlets claiming otherwise, Tottenham Hotspur have got no interest in signing West Ham United striker Andy Carroll this month, according to a report from Sky Sports. ", "Harry Kane’s ankle injury, combined with Heung-Min Son being away on international […]\n\nPepijn Lijnders has officially been named as Liverpool’s assistant manager, replacing Zeljko Buvac, who has been absent from the club since the Spring of 2018. ", "As displayed on the official Liverpool website, Lijnders’ job role has been switched to ‘Assistant manager’, thus reflecting the […]" ]

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[ "\nTest HN: Briggs & Myers' 16 personality types - galfarragem\nhttps://www.16personalities.com/\n======\nZolomon\nThis test is quite criticised[1].", "\n\n[1]\n[https://en.wikipedia.org/wiki/Myers%E2%80%93Briggs_Type_Indi...](https://en.wikipedia.org/wiki/Myers%E2%80%93Briggs_Type_Indicator#Criticism)\n\n~~~\npfooti\nAlso:\n\n[https://www.psychologytoday.com/blog/give-and-\ntake/201309/go...](https://www.psychologytoday.com/blog/give-and-\ntake/201309/goodbye-mbti-the-fad-won-t-die)\n[http://rationalwiki.org/wiki/Myers-\nBriggs_Type_Indicator](http://rationalwiki.org/wiki/Myers-\nBriggs_Type_Indicator) [http://www.smithsonianmag.com/smart-news/the-myers-\nbriggs-pe...](http://www.smithsonianmag.com/smart-news/the-myers-briggs-\npersonality-test-is-pretty-much-meaningless-9359770/)\n\nThe MBTI is about as valid as a horoscope, and people actually make hiring\ndecisions based on it.", "\n\nIt is probably useful to help introverts understand extroverts and so on, and\nmaybe help people have _conversations about_ personality differences, but it\nis pretty bad at diagnosing actual personalities beyond \"a dark-haired\nstranger will meet you\"\n\n~~~\nnyc640\nI don't see how you can say an assessment based on people's actual behavior is\nabout as valid as completely made up predictions based on the alignment of the\nstars when you were born. ", "I think it's pretty obvious your MBTI can say more\nabout you than your horoscope can.", "\n\nNot that I disagree with you that hiring decisions should not be made based on\nMBTI, nor can we categorize all people into 16 personality types.", "\n\n~~~\npfooti\nThe point is more along the lines of: the MBTI really can't tell you much. ", "It\nhas very bad psychometric properties (people regular test differently on\ndifferent days, or show as a mix of two supposed opposing factors). ", "As a\ntheoretical framework, there is little in the way of peer reviewed work to\neven support anything other than introversion - extroversion as a measure.", "\nMBTI is pretty much pseudoscience that we keep using because it Feels Correct.", "\n\nPsychics and astrologers do the same thing - make broad and generic claims to\nmake you think they're talking to you because you fill the gaps in the story.", "\n\nSo, it's an aggressive claim I make yes. ", "Partly (perhaps largely) driven by\nthe fact that too many otherwise reasonable people do not treat the MBTI with\nthe skepticism it deserves (again, hiring decisions are made and justified\nbased on this pseudoscience). ", "But partly because I've been through both the\nlong form MBTI test and explanation (with subfactors, where I was thoroughly\nmixed with stuff that wasn't supposed to correlate) and the explanation phase\nfelt precisely like a psychic reading.", "\n\n------\nat-fates-hands\nI've taken it several times and always come back as an INTJ.", "\n\nAt my last gig, the manager was an expert on all the Briggs-Myers types. ", "He\nmade everybody on the team take the test and then put up the chart where it\nshows where everybody on the team is.", "\n\nTBH, it helped a LOT in how the team communicated with each other as well as\nconflict resolution because it gave you a really good insight into their\npersonality.", "\n\n~~~\nmiguelrochefort\nThat's fantastic!", "\n\n------\ntravjones\nAlthough it is fun to try to categorize ourselves into 16 personality types,\nwhat these categories really describe are behavior, which is dependent on way\nmore than personality traits alone (e.g., what about context? ", "What about\nreinforcement contingencies?). ", "I'm not trying to be a hater, I just want\npeople to take the test and read the questions with a critical eye. ", "Behavioral\nscience has come a long way scince this test was published over 60 years ago.", "\nYour personality type does not define you and does not determine how you\nbehave in real world situations.", "\n\n------\ngalfarragem\nINTP. ", "It really hits home. ", "The suggested jobs are exactly the ones that I see\nmyself doing professionally and amateurly: architect, software designer,\nfinancial analyst, ..\n\n------\nmiguelrochefort\nShould we turn this post into a poll?", "\n\nIf not, here's one: [http://www.polljunkie.com/poll/wrtqqk/whats-your-mbti-\ntype](http://www.polljunkie.com/poll/wrtqqk/whats-your-mbti-type)\n\n------\ngadders\nI was an INTJ when I did it before.", "\n\n------\nmiguelrochefort\nINTP\n\n------\nlsorese\nINFP\n\n" ]

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[ "Ontogenetic variations in the diet of two invasive gobies, Neogobius melanostomus (Pallas, 1814) and Ponticola kessleri (Günther, 1861), from the middle Danube (Slovakia) with notice on their potential impact on benthic invertebrate communities.", "\nIn this study, ontogenetic variations in diet of invasive bighead goby Ponticola kessleri and round goby Neogobius melanostomus from the middle Danube were analysed. ", "Index of stomach fullness, Fulton's condition factor, index of food importance, frequency of occurrence, biomass, electivity, and proportions of invasive organisms in their diet were examined. ", "Changes in the diet during ontogeny of both species emphasise the differences in their trophic niches. ", "Our results combined with literary data suggest that bighead goby may threaten small native benthic fish species as a predator (especially in the invasion front), whereas round goby can potentially impact native fish species of all ontogenetic phases by competing for food. ", "Round goby appear to have strong impact on bivalves, especially in the invasion front. ", "High consumption of invasive organisms by bighead goby may help the native macroinvertebrate community. ", "Thus, in contrast to round goby, bighead goby does not seem to be a hot candidate for being a nuisance invader." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Chlortetracycline\n\nChlortetracycline (trade name Aureomycin, Lederle Laboratories) is a tetracycline antibiotic, the first tetracycline to be identified. ", "It was discovered in 1945 at Lederle Laboratories under the supervision of scientist Yellapragada Subbarow and his junior Benjamin Minge Duggar. ", "Duggar identified the antibiotic as the product of an actinomycete he cultured from a soil sample collected from Sanborn Field at the University of Missouri. ", " The organism was named Streptomyces aureofaciens and the isolated drug, Aureomycin, because of their golden color.", "\n\nMedical uses\nIn veterinary medicine, chlortetracycline is commonly used to treat conjunctivitis in cats, dogs and horses. ", "It is also used to treat infected wounds in cattle, sheep an pigs, and respiratory tract infections in calves, pigs and chickens.", "\n\nA combination cream with triamcinolone acetonide is available for the treatment of infected allergic dermatitis in humans.", "\n\nContraindications\nChlortetracycline for systemic use is contraindicated in animals with severe hepatic or renal impairment. ", "Topical chlortetracycline must not be used on the udder of animals whose milk is intended for human consumption.", "\n\nAdverse effects\nLike other tetracyclines, chlortetracyclin can inhibit bone and tooth mineralisation in growing and unborn animals, and colour their teeth yellow or brown. ", "It can also impair liver and kidney function. ", "Allergic reactions are rare.", "\n\nInteractions\nChlortetracycline may increase the anticoagulant activities of acenocoumarol. ", "The risk or severity of adverse effects can be increased when chlortetracycline is combined with acitretin, adapalene, or alitretinoin. ", "Aluminum phosphate and aluminum hydroxide can cause decreases in the absorption of chlortetracycline resulting in a reduced serum concentration and potentially a decrease in efficacy. ", "The therapeutic efficacy of mecillinam (amdinocillin), amoxicillin, and ampicillin can be decreased when used in combination with chlortetracycline. ", "Chlortetracycline may increase the neuromuscular blocking activities of atracurium besilate.", "\n\nPharmacology\n\nMechanism of action\n\nReferences\n\nCategory:Chloroarenes\nCategory:Tetracycline antibiotics" ]

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

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[ "CamperVanTastic website or its third-party tools use cookies, which are necessary to its functioning and required to achieve the purposes illustrated in the privacy policy. ", "If you want to know more or withdraw your consent to all or some of the cookies, please refer to the Cookie Policy paragraph of the Privacy Policy.", "\nBy clicking 'Continue', scrolling this page, clicking a link or continuing to browse otherwise, you agree to the use of cookies.", "\n\nuser pic of the month\n\ncampsite of the month\n\nAIR VENTS AND INSECT NETS\n\n102 150 224 BRANDRUP FLYOUT tailgate Mercedes-Benz V-Class Marco Polo (2014 ➞)Brandruphttps://campervantastic.com/uploads/pics/products/big800/bee0205313_1197.jpg139.49InStockhttps://campervantastic.com/product/air-vents-and-insect-nets/marco-polo/102-150-224-brandrup-flyout-tailgate-mercedes-benz-v-class-marco-polo-2014/102 150 224https://campervantastic.com/product/air-vents-and-insect-nets/marco-polo/102-150-224-brandrup-flyout-tailgate-mercedes-benz-v-class-marco-polo-2014/\nFLYOUT protects against mosquitos and the like, by fitting the netting perfectly to the shape of the tailgate. ", "It is simply attached with self adhesive velcro.", "\n&nbsp;\nAll areas of the tailgate are easily accessible when the FLYOUT is in use through all the easy access zippers, including the shower outlet. ", "When the main zip is opened the net can be rolled up out of the way just to the left of the tailgate.", "\nThe FLYOUT for tailgate also offers the very practical function of&nbsp;adjustable fixation of the tailgate window blind via reinforced loops, allowing the tailgate blind and FLYOUT to be used&nbsp;\nsimultaneously.", "\n\nFLYOUT protects against mosquitos and the like, by fitting the netting perfectly to the shape of the tailgate. ", "It is simply attached with self adhesive velcro.", "\n\nAll areas of the tailgate are easily accessible when the FLYOUT is in use through all the easy access zippers, including the shower outlet. ", "When the main zip is opened the net can be rolled up out of the way just to the left of the tailgate.", "\n\nThe FLYOUT for tailgate also offers the very practical function of adjustable fixation of the tailgate window blind via reinforced loops, allowing the tailgate blind and FLYOUT to be used simultaneously." ]

{ "pile_set_name": "Pile-CC" }

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[ "Friends Attending\n\nFriends Attending\n\nFriends Attending\n\nDescription\n\nIntermediate WordPress - with Mike Little (WP co-founder)\n\nDue to exceptional demand, we have announced an extra Intermediate WordPress course. ", "Please note, places are limited and are likely to go soon.", "\n\nThursday 3rd and Friday 4th November, 10:00am - 4:30pm\n\nTake your WordPress site to the next level!", "\n\nOver the course of two days you’ll dig deep into theme customisation and learn how to make your site work perfectly on mobile devices. ", "You’ll begin to unleash the full potential of the platform: from search engine optimisation (SEO) to security, caching to e-commerce.", "\n\nWho is this course for?", "\n\nThe course is aimed at those who’ve already got to grips with WordPress. ", "You don’t need any programming experience, but a little CSS knowledge is useful. ", "If you want to work on an existing WordPress site you are more than welcome, but we will provide a pre-installed site for up to a month for all attendees.", "\n\nCourse syllabus\n\nDay one\n\nIntroduction To WordPress: What is WordPress? ", "A little history\n\nRecap of the WordPress basics: Posts, pages and all that jazz\n\nSettings in depth: More ways to configure your site\n\nAdvanced posts and pages: Featured images, the kitchen sink, paging and more\n\nExercise: Getting to grips with the WordPress Editor\n\nThe Image Editor: Make your own thumbnails\n\nThemes, Widgets and Menus in depth: Learning the building blocks\n\nCSS introduction: An overview and some useful tools\n\nPulling it all together: Improving the look of your site\n\nExercise: Customising your theme with CSS\n\nDay two\n\nSecurity: Hosting, plugins and good habits\n\nCaching: Make your site fly!", "\n\nExercise: Security and caching plugins\n\nSEO – an overview: The strange art of Search Engine Optimisation\n\nAnti-spam techniques: Akismet and beyond\n\nJetpack in depth: Juicy goodness form WordPress.com\n\nExercise: Getting to know Jetpack\n\nE-commerce – an overview: An intro to selling your stuff\n\nMore useful tools and plugins\n\nQuestion and Answer session with Mike\n\nPlease note: This course does not teach WordPress development (PHP coding).", "\n\nEquipment you’ll need\n\nSample images that you will be able to upload to your website as the course progresses.", "\n\nAn external mouse if you prefer using one.", "\n\nIf you don’t have access to a computer please let us know in advance of the course so we can arrange one for you.", "\n\nCost\n\nThe cost is £300 (inclusive of VAT).", "\n\nThis covers:\n\nTwo days tuition\n\nLunch and refreshments on both days\n\nAn electronic copy of the teaching materials\n\nOne month’s free hosting courtesy of MadLab to test and refine your site (you’re welcome to work on your own site if you prefer)\n\nWe have a limited number of bursary places available on this course for a reduced rate of £220. ", "These are open to people who are underemployed, unemployed or full-time students. ", "Please contact us (details below) for more information.", "\n\nAbout the course tutor\n\nMike is the co-founder of WordPress. ", "He’s also the founder and CEO of WordPress consultancy zed1.com, has a portfolio including prominent government sites, is a published author, technical editor and member of the Usability Professionals Association… but let’s face it, we had you at ‘co-founder of WordPress’." ]

{ "pile_set_name": "Pile-CC" }

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[ "Q:\n\nTwilio Trial Account does not get incoming call\n\nI'm developing my iOS Voip Application with Twilio.", "\nI got free trial account and am working on call from my iphone to the Voip Application(Installed to another iphone). ", "I'm confident that the capability token I issued on my server is right though there is no way to confirm if the capability token is right or not as the issued TCDevice class in my iOS application. ", "\nThe problem is, when I call from my phone to the trial phone number, the call log on console shows me warning that says \"'To' phone number not verified\". ", "I'm sure 'To' phone number is the one I got on Twilio and have no way to verify it.", "\nDoes anyone know Twilio trial number can get incoming call?", "\nAre there any ways can I confirm the capability token is right?", "\nThank you\n\nA:\n\nTwilio developer evangelist here.", "\nYou do not need to set the capability token in the <Dial> in your TwiML.", "\nYou need to generate a capability token on your server and setup your TCDevice object with it. ", "The capability token should set a name for the client when you declare allow_incoming_connections on it: https://www.twilio.com/docs/api/client/capability-tokens#allow-incoming-connections\nfrom twilio.util import TwilioCapability\n\naccount_sid = \"ACXXXXXXXXXXXXXXX\"\nauth_token = \"secret\"\n\ncapability = TwilioCapability(account_sid, auth_token)\ncapability.allow_client_incoming(\"tommy\")\nprint(capability.generate())\n\nThen, when you call your Twilio number, you need to use <Dial> with a nested <Client> with the name you set in the capability token. ", "Like:\n<Response>\n <Dial>\n <Client>tommy</Client>\n </Dial>\n</Response>\n\nThen Twilio can direct the call into your client application.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Download her lucky cowboy a montana men novel in pdf or read her lucky cowboy a montana men novel in pdf online books in PDF, EPUB and Mobi Format. ", "Click Download or Read Online button to get her lucky cowboy a montana men novel in pdf book now. ", "This site is like a library, Use search box in the widget to get ebook that you want.", "\n\nAuthor: Jennifer RyanPublisher: HarperCollinsISBN: 0062334964Size: 58.52 MBFormat: PDF, ePub, DocsView: 2834Download and Read\nEverything's bigger in Big Sky country, including the hearts of the Montana Men Champion rodeo rider Dane Bowden is eight seconds from winning under the Vegas lights, one last hurrah before reluctantly returning to his family's Montana ranch. ", "But his bull has other plans. ", "When Dane wakes up, he's sure he's died and gone to heaven . . . ", "because the doctor who comes to his aid is the same girl who saved his life and disappeared years ago. ", "Bell would do anything for Dane. ", "He's the fantasy that always kept her going. ", "A child genius hidden away by her family, Bell was the secret no one talked about, the girl no one wanted. ", "Despite finding success as a young surgeon, she's still the awkward girl who's never had a boyfriend. ", "So why does Dane, a notorious playboy and sizzling-hot cowboy, insist on taking her on a real date? ", "Bell is the only woman in Dane's heart. ", "When a rodeo rivalry turns deadly, it's his turn to save Bell's life—because he sure as hell won't lose his guardian angel again.", "\n\nAuthor: Leeanna MorganPublisher: Rogan PressISBN:Size: 73.70 MBFormat: PDF, DocsView: 6067Download and Read\nShe came to Montana looking for answers...and found forever. ", "When Gracie Donnelly, a school teacher from New Zealand, arrives on a Montana cattle ranch, she has more on her mind than mending fences and feeding chickens. ", "She's secretly searching for her father and answers to questions that could destroy a family. ", "Just one look at the fiery five-foot-one redhead and Trent McKenzie knows Gracie is going to be trouble. ", "Ever since the failure of his first marriage, he promised never to listen to his heart again. ", "Especially when his heart is saying he's falling in love - and the one thing Gracie's searching for is the one thing that could take her away from him forever. ", "Forever Dreams is the first book in the Montana Brides series and can easily be read as a standalone. ", "Each of Leeanna's series are linked so you can find out what happens to your favorite characters in other books. ", "For more information about Leeanna and her new releases, please visit: www.leeannamorgan.com. ", "Happy reading! ", "Other Contemporary Romances by Leeanna Morgan: Montana Brides: Book 1: Forever Dreams (Gracie and Trent) Book 2: Forever in Love (Amy and Nathan) Book 3: Forever After (Nicky and Sam) Book 4: Forever Wishes (Erin and Jake) Book 5: Forever Santa (A Montana Brides Christmas Novella) Book 6: Forever Cowboy (Emily and Alex) Book 7: Forever Together (Kate and Dan) Book 8: Forever and a Day (Sarah and Jordan) The Bridesmaids Club: Book 1: All of Me (Tess and Logan) Book 2: Loving You (Annie and Dylan) Book 3: Head Over Heels (Sally and Todd) Book 4: Sweet on You (Molly and Jacob) Emerald Lake Billionaires: Book 1: Sealed with a Kiss (Rachel and John) Book 2: Playing for Keeps (Sophie and Ryan) Book 3: Crazy Love (Holly and Daniel) Book 4: One And Only (Elizabeth and Blake) The Protectors: Book 1: Safe Haven (Hayley and Tank) Book 2: Just Breathe (Kelly and Tanner) Book 3: Always (Mallory and Grant) Book 4: The Promise (Ashley and Matthew) Book 5: Coming Home (Mia and Stan) Book 6: The Gift (Hannah and Brett) Book 7: The Wish (Claire and Jason) Sapphire Bay: Book 1: Falling For You (Natalie and Gabe) Book 2: Once In A Lifetime (Sam and Caleb) Book 3: A Christmas Wish (Megan and William) Book 4: Before Today (Brooke and Levi) Book 5: The Sweetest Thing (Cassie and Noah) Praise for the Montana Brides series: “A wonderful series that you can't stop reading. ", "It will make you laugh and cry but mostly sigh. ", "I enjoyed the whole series but could have read each one separately. ", "Leeanna Morgan made the love flow. ", "A great read for everyone who loves romance!” “", "Every one of the books in The Montana Brides Series is filled with laughter, joy and tears. ", "The family and friendship ties are so special. ", "The romance and loving relationships are the best. ", "I read these 7 books in 5 days. ", "I couldn’t put these books down. ", "You have to read the following series, The Bridesmaid Club Series. ", "AWESOME! ", "I'm almost done with the books.” “", "I enjoyed this story! ", "It was hard to put the book down and I didn't unless I had to. ", "The storyline and characters were perfect and the scenic descriptions were wonderful. ", "Such a lovely romantic story.” ", "Keywords: Heartwarming, small town romance, western, ranch, cowboy, friendship, family life, series, Montana, relationships, love, wedding, bride, bridesmaid, family saga, second chance, New Zealand, international, marriage of convenience, vacation, holiday, teacher, baby, children.", "\n\nAuthor: Leeanna MorganPublisher: Rogan PressISBN:Size: 73.97 MBFormat: PDF, ePub, MobiView: 1844Download and Read\nBig dreams in Big Sky country. ", "Emily Scotson's dream is to open her own fashion boutique in downtown Bozeman. ", "Finding the perfect building isn't a problem. ", "Finding one she can afford is impossible. ", "For Alex Green, World Bull Riding Champion, his luck has finally run out. ", "Being thrown by 1500 pounds of prime bull hurt his body as well as his pride. ", "When he returns to Montana to recover, he ends up inside a burned out shell of a building, with a hammer in his hand and a pesky redhead ordering him around. ", "He doesn't know much about fashion, but he does know about property. ", "And the commercial building that Emily wants to buy has dollar signs written all over it. ", "He needs a project to keep him busy and Emily needs a business partner. ", "It could be a match made in heaven, but only if a cowboy with a broken heart lets himself believe in forever. ", "Forever Cowboy is the sixth book in the Montana Brides series and can easily be read as a standalone. ", "Each of Leeanna's series are linked so you can find out what happens to your favorite characters in other books. ", "Happy reading! ", "Other Contemporary Romances by Leeanna Morgan: Montana Brides: Book 1: Forever Dreams (Gracie and Trent) Book 2: Forever in Love (Amy and Nathan) Book 3: Forever After (Nicky and Sam) Book 4: Forever Wishes (Erin and Jake) Book 5: Forever Santa (A Montana Brides Christmas Novella) Book 6: Forever Cowboy (Emily and Alex) Book 7: Forever Together (Kate and Dan) Book 8: Forever and a Day (Sarah and Jordan) The Bridesmaids Club: Book 1: All of Me (Tess and Logan) Book 2: Loving You (Annie and Dylan) Book 3: Head Over Heels (Sally and Todd) Book 4: Sweet on You (Molly and Jacob) Emerald Lake Billionaires: Book 1: Sealed with a Kiss (Rachel and John) Book 2: Playing for Keeps (Sophie and Ryan) Book 3: Crazy Love (Holly and Daniel) Book 4: One And Only (Elizabeth and Blake) The Protectors: Book 1: Safe Haven (Hayley and Tank) Book 2: Just Breathe (Kelly and Tanner) Book 3: Always (Mallory and Grant) Book 4: The Promise (Ashley and Matthew) Book 5: Coming Home (Mia and Stan) Book 6: The Gift (Hannah and Brett) Book 7: The Wish (Claire and Jason) Sapphire Bay: Book 1: Falling For You (Natalie and Gabe) Book 2: Once In A Lifetime (Sam and Caleb) Book 3: A Christmas Wish (Megan and William) Book 4: Before Today (Brooke and Levi) Book 5: The Sweetest Thing (Cassie and Noah) Praise for the Montana Brides series: “A wonderful series that you can't stop reading. ", "It will make you laugh and cry but mostly sigh. ", "I enjoyed the whole series but could have read each one separately. ", "Leeanna Morgan made the love flow. ", "A great read for everyone who loves romance!” “", "Every one of the books in The Montana Brides Series is filled with laughter, joy and tears. ", "The family and friendship ties are so special. ", "The romance and loving relationships are the best. ", "I read these 7 books in 5 days. ", "I couldn’t put these books down. ", "You have to read the following series, The Bridesmaid Club Series. ", "AWESOME! ", "I'm almost done with the books.” “", "I enjoyed this story! ", "It was hard to put the book down and I didn't unless I had to. ", "The storyline and characters were perfect and the scenic descriptions were wonderful. ", "Such a lovely romantic story.” ", "Keywords: Heartwarming, small town romance, western, ranch, cowboy, friendship, family life, series, Montana, relationships, love, wedding, bride, bridesmaid, family saga, second chance, vacation, bull rider, champion, competition, doctor, hospital, wealthy, rich, medical.", "\n\nAuthor: Lee ServerPublisher: Infobase PublishingISBN: 1438109121Size: 56.92 MBFormat: PDF, MobiView: 1099Download and Read\nProvides an introduction to American pulp fiction during the twentieth century with brief author biographies and lists of their works.", "\n\nAuthor: B. M. BowerPublisher: e-artnowISBN: 8026876407Size: 48.53 MBFormat: PDFView: 4756Download and Read\nFlying U is a ranch in the Bear Paw country of Montana where lives and rides the unusual Happy Family of cowboys. ", "We are introduced to Chip, Andy, Weary, Irish, Pink, Slim, Happy Jack, Big Medicine and the other members of this bunch, and we follow them in their various adventures and escapades. ", "Table of Contents: Chip of the Flying U The Flying U Ranch The Flying U's Last Stand The Phantom Herd The Heritage of the Sioux Rodeo Dark Horse The Flying U Strikes The Happy Family: Ananias Green Blink Miss Martin's Mission Happy Jack, Wild Man A Tamer of Wild Ones Andy, the Liar \"Wolf! ", "Wolf!\" ", "Fool's Gold Lords of the Pots and Pans The Lonesome Trail and Other Stories: The Lonesome Trail First Aid to Cupid When the Cook Fell Ill The Lamb The Spirit of the Range The Reveler The Unheavenly Twins Bertha Muzzy Bower (1871-1940) was an American author who wrote novels and short stories about the American Old West. ", "She is best known for her first novel “Chip of the Flying U” about Flying U Ranch and the \"Happy Family\" of cowboys who lived there. ", "The novel rocketed Bower to fame, and she wrote an entire series of novels set at the Flying U Ranch. ", "Several of Bower's novels were turned into films.", "\n\nAuthor: Breanna ConePublisher: iUniverseISBN: 1532035233Size: 77.55 MBFormat: PDF, ePub, DocsView: 5611Download and Read\nGrant Lord contemplates the status of his life, both professionally and personally. ", "His cattle ranch needs another pair of hands to handle the day-to-day duties that will free up his time to pursue his lovely fiance. ", "His new hired hand is an Afghanistan veteran who needs to find a new purpose in life after recovering from injuries suffered from an IED blast. ", "Together, the two men forge a partnership that has unlimited possibilities, challenges, and a few surprises. ", "What will the future bring? ", "Lord only knows what will happen next." ]

{ "pile_set_name": "Pile-CC" }

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[ "With the advent of highly active antiretroviral therapy (HAART), HIV transformed from a progressive fatal illness to a manageable chronic condition ([@bibr14-1557988318797790]). ", "Life expectancy among treated HIV-positive individuals has increased during this time and is approaching that of HIV-negative individuals ([@bibr3-1557988318797790]; [@bibr42-1557988318797790]). ", "HIV symptoms, however, which may be physical (e.g., pain, diarrhea), psychological (e.g., depression, anxiety), and cognitive (e.g., memory loss) continue to be a major concern ([@bibr40-1557988318797790]). ", "These symptoms may result from the disease process itself as well as secondary complications (e.g., medication side effects, common comorbidities). ", "Such symptoms, which may occur regardless of CD4+ count ([@bibr28-1557988318797790]; [@bibr51-1557988318797790]), may affect quality of life ([@bibr17-1557988318797790]; [@bibr30-1557988318797790]; [@bibr50-1557988318797790]) as well as ART adherence ([@bibr19-1557988318797790]; [@bibr23-1557988318797790]).", "\n\nMen of color continue to be disproportionately represented among HIV-positive heterosexual men living in the United States ([@bibr11-1557988318797790]). ", "Almost no studies have examined the determinants of HIV symptom burden among heterosexual men of color; however, the socioecological model suggests that HIV outcomes must be understood in the context of social and structural factors ([@bibr4-1557988318797790]). ", "One such factor that may influence HIV symptom burden is discrimination. ", "For example, in a study of men who have sex with men, [@bibr5-1557988318797790] reported that a combination of discrimination types (racial, homophobic, and serostatus related) predicted the number of HIV symptoms (e.g., fever, diarrhea) among both Blacks and Latinos ([@bibr5-1557988318797790]).", "\n\nMediators and moderators of the relationship between discrimination and negative physical health outcomes among HIV-positive individuals of color are also unknown. ", "Scholars have suggested that associations between perceived discrimination and self-reported physical health, as well as a number of chronic health conditions (e.g., diabetes), may be at least partially mediated by poor mental health ([@bibr8-1557988318797790]; [@bibr10-1557988318797790]; [@bibr16-1557988318797790]; [@bibr35-1557988318797790]). ", "Anxiety, in particular, may mediate the relationship between discrimination and HIV symptom burden through its effects on stress. ", "Social support may act as a moderator of the relationship between discrimination and physical health as well as of the mediating role of anxiety. ", "Studies have demonstrated mixed evidence regarding the buffering effects of social support on the relationship between discrimination and mental (e.g., depression, anxiety) and physical health (e.g., self-rated health, cardiovascular reactivity to stress) among men and women of color ([@bibr2-1557988318797790]; [@bibr9-1557988318797790]; [@bibr20-1557988318797790]; [@bibr33-1557988318797790]; [@bibr37-1557988318797790]); however, no studies have explored these associations in regard to HIV symptom burden.", "\n\nThe aim of this study was to explore whether experiences of multiple lifetime discrimination events affect HIV somatic symptom burden (i.e., the number of HIV symptoms experienced) among heterosexual HIV-positive Black and Latino men. ", "This study also explored the degree to which anxiety explained the relationship between discrimination and HIV symptom burden and assessed whether social support modified the relationship between discrimination and anxiety. ", "Study hypotheses were as follows: (a) discrimination will be positively associated with HIV somatic symptom burden; (b) anxiety will partially mediate the relationship between self-reported discrimination and HIV-related somatic symptom burden; and (c) this mediation relationship will be stronger among those who reported low social support.", "\n\nMethods {#section1-1557988318797790}\n=======\n\nSample and Procedures {#section2-1557988318797790}\n---------------------\n\nData for this study were drawn from the \"Men's Talk on HIV Risk\" (MENTOR) Project, a cross-sectional survey of heterosexual HIV-positive primarily Black and Latino men. ", "Participants (*N* = 317) were recruited from health and social service agencies located in the South Bronx and Harlem, New York, in 2011 and 2012. ", "Participants had to fulfill the following eligibility criteria: (a) male; (b) HIV-positive; (c) 18--60 years old; (d) English or Spanish fluency; (e) heterosexually identified; and (f) had vaginal or anal sex with a woman in the past 3 months. ", "Prior to completing the survey, participants signed a consent form detailing study procedures. ", "Surveys were administered in English or in Spanish by interviewers using Computer-Assisted Personal Interview (CAPI) software (QDS version 6.2.1, Nova Research). ", "Participants were compensated \\$50 for their time. ", "The Institutional Review Board of the University of Rochester approved all study procedures.", "\n\nMeasures {#section3-1557988318797790}\n--------\n\nHIV-related symptoms were assessed using 15 items pertaining to somatic HIV symptoms drawn from an HIV symptom index developed by [@bibr26-1557988318797790], which asked about symptoms men experienced during the past month. ", "Dichotomous response affirmative answers were summed to obtain a total symptom score.", "\n\nSix items reflecting lifetime experience of major discrimination events were drawn from the Major Experiences of Discrimination scale ([@bibr52-1557988318797790]). ", "Men were asked if they were ever unfairly fired from a job; had not been hired for a job for unfair reasons; were unfairly stopped, searched, questioned, physically threatened, or abused by the police; were unfairly discouraged by a teacher or advisor from continuing education; were unfairly prevented from moving into a neighborhood because the landlord or a realtor refused to sell or rent a house or apartment; or had moved into a neighborhood where neighbors made life difficult for the participant or his family. ", "Dichotomous response affirmative answers were summed to obtain a total discrimination score.", "\n\nAnxiety was assessed using seven items from the Client Diagnostic Questionnaire ([@bibr1-1557988318797790]). ", "Men were asked if they had experienced any of the following symptoms over the past 4 weeks: feeling nervous, anxious, on edge, or worrying a lot about different things; feeling restless so that it is hard to sit still; getting tired very easily; muscle tension, aches, or soreness; trouble falling or staying asleep; trouble concentrating on things; and becoming easily annoyed or irritable. ", "Participants responded to these items on a 4-point Likert scale, where 1 = *not at all* and 4 = *nearly every day*. ", "Response scores were then averaged to create a total anxiety score.", "\n\nSocial support was assessed using 12 items taken from the Lubben Social Network Scale---Revised ([@bibr31-1557988318797790]). ", "Participants were asked about the number of friends/relatives seen during the past month; how often they saw the friend/relative that they had the most contact with; how many friends/relatives they felt comfortable talking about personal matters with; how many friends/relatives that they felt they could call on for help; how often a friend/relative would reach out to the participant when he had an important decision to make; and how often at least one of their friends/relatives was available to talk when the participant had an important decision to make. ", "Questions regarding number of supportive others were answered on a 6-point Likert scale, with anchors of 0 = *none* and 5 = *9 or more.* ", "Questions regarding frequency of contact were answered on a 6-point Likert scale, with 0 = *less than monthly* and 5 = *daily*. ", "Finally, questions regarding communication with supportive others were answered on a 6-point Likert scale, ranging from 0 = *never* to 5 = *always*. ", "Items were averaged to create a total social support score.", "\n\nSociodemographic variables were included in the models as covariates due to their hypothesized association with health. ", "These variables included self-reported race/ethnicity (Black vs. Latino vs. Other), age, monthly household income, and education (completed high school or obtained general equivalency diploma \\[GED\\] vs. not). ", "CD4+ count and diagnosis of AIDS were also included in the model.", "\n\nAnalysis {#section4-1557988318797790}\n--------\n\nStandard data cleaning methods were conducted; outliers were Winsorized by setting all outlying values to the value of the highest or lowest non-outlying value. ", "Descriptive analyses (central tendency, dispersion) were performed to characterize the sample. ", "A correlation matrix was generated to examine the correlational structure of the data. ", "Path analysis (moderated mediation) was performed to test the hypothesis that anxiety mediates the relationship between perceived discrimination and HIV-related symptom burden and that this mediation effect will tend to be weaker among those who reported greater social support. ", "The direct and indirect effects (via anxiety) of discrimination on HIV symptom burden were calculated, and an interaction term was included to test the moderating effects of social support on the relationship between discrimination and anxiety. ", "The effects of selected covariates on HIV-related symptoms were adjusted for in the model. ", "Analyses were performed using PROCESS macro (Model 7) for SPSS (v. 2.16; [@bibr24-1557988318797790]). ", "Individuals with missing data (*n* = 10) were removed from the dataset via list-wise deletion, resulting in a final sample size of 307.", "\n\nResults {#section5-1557988318797790}\n=======\n\n[Table 1](#table1-1557988318797790){ref-type=\"table\"} presents descriptive data for the sample of 307 HIV-positive self-identified heterosexual men. ", "On average, men reported experiencing about two lifetime discrimination events (mode = 1), and nearly four HIV symptoms in the past month. ", "Discrimination was positively associated with anxiety (*r* = .204; *p* ⩽ .001) and number of HIV symptoms (*r* = .279; *p* ⩽ .001). ", "Social support was negatively associated with anxiety (*r* = −.129; *p* = .022) and HIV symptoms (*r* = −.168; *p* = .003).", "\n\n###### \n\nParticipant Characteristics (*n* = 307).", "\n\n![](", "10.1177_1557988318797790-table1)\n\n Total (*n* = 307) Black (*n* = 199) Latino (*n* = 92) Other^[a](#table-fn1-1557988318797790){ref-type=\"table-fn\"}^ (*n* = 16) \n ------------------------------------------ ------------------- ------------------- ------------------- ------------------------------------------------------------------------- ----------------- ------- ----------------- -------\n Age \n  Mean (±*SD*) 47.9 (5.9) -- 48.51 (5.95) -- 46.53 (5.75) -- 47.69 (6.24) --\n  Range 33--59 -- 33--59 -- 33--56 -- 33--57 --\n High school diploma/GED 177 57.7 116 58.29 52 56.52 9 56.25\n Monthly income \n  Mean (±*SD*) \\$ 815.13 (399.82) -- 828.26 (401.66) -- 775.64 (376.0) -- 878.81 (508.46) --\n  Range 0--1,670 -- 0--1,670 -- 100--1,670 -- 0--1,670 --\n Number of lifetime discrimination events \n  0 42 13.7 26 13.07 15 16.3 1 6.25\n  1 111 36.2 70 35.18 33 35.87 8 50\n  2 63 20.5 42 21.11 18 19.57 3 18.75\n  3+ 91 29.6 59 29.65 24 26.09 4 25\n Number of HIV symptoms in past month \n  Mean (±*SD*) 3.83 (2.68) -- 3.72 (2.73) -- 3.95 (2.63) -- 4.5 (2.34) \n  Range 0--11 -- 0--11 -- 0--11 -- 0--9 \n Social support score (scored 1--5) \n  Mean (±*SD*) 2.58 (0.85) -- 2.59 (0.81) -- 2.52 (0.91) -- 2.79 (1.01) \n  Range 0.5--4.75 -- 0.5--4.75 -- 0.64--4.58 -- 0.58--4.42 \n Anxiety score (scored 1--4) \n  Mean (±*SD*) 1.95 (0.67) -- 1.9 (0.65) -- 2.07 (0.67) -- 1.89 (0.63) \n  Range 1.0--3.5 -- 1.0--3.5 -- 1.0--3.5 -- 1.14--3.43 \n CD4+ \n  Mean (±*SD*) 446.77 (259.0) -- 454.4 (262.3) -- 437.02 (256.12) -- 407.94 (242.6) \n  Range 4--995 -- 4--995 -- 20--995 -- 50--792 \n Ever diagnosed with AIDS 162 52.8 102 51.26 50 54.35 10 62.5\n\n*Note*. ", "^a^ \"Other\" racial/ethnic category consisted of nine self-identified mixed racial/ethnic participants (all included Black/African American or Latino); one Native American; and six Caucasian participants. ", "GED = general equivalency diploma.", "\n\nThe path model ([Figure 1](#fig1-1557988318797790){ref-type=\"fig\"}; [Table 2](#table2-1557988318797790){ref-type=\"table\"}) identified that after adjusting for anxiety and other covariates, the number of discrimination events experienced in one's lifetime was positively associated with the number of HIV-related somatic symptoms experienced in the past month (*B* = 0.404, 95% CI \\[0.190, 0.619\\]). ", "Results further indicate that anxiety partially mediated the relationship between discrimination and HIV somatic symptoms and that the strength of this indirect effect is conditional on the level of social support. ", "As social support increased, the magnitude of the mediation effect of discrimination on HIV symptoms via anxiety decreased. ", "For every one-unit increase in social support, the effect of discrimination on HIV somatic symptoms through anxiety decreased by 0.164 (95% CI \\[--.0351, --0.012\\]). ", "The model *R*^2^ was .41, indicating that the model explained a substantial portion of the variance in number of HIV-related somatic symptoms.", "\n\n{#fig1-1557988318797790}\n\n###### \n\nPath Analysis Results Showing Unstandardized Coefficients (95% CI) and *p* Values for Moderated Mediation of Discrimination on HIV Symptoms Through Anxiety, Moderated by Social Support^[a](#table-fn2-1557988318797790){ref-type=\"table-fn\"}^.\n\n![](", "10.1177_1557988318797790-table2)\n\n Predictor variable Anxiety (mediator) HIV symptoms (outcome variable) \n -------------------------------------------------------------------------------------------- ------------------------------ --------------------------------- -------------------------------\n Discrimination 0.230 \\[0.082, 0.377\\] .002 0.404 \\[0.190, 0.619\\] \\<.001 0.664 \\[0.409, 0.919\\] \\<.001\n Social Support (SS) 0.018 \\[−0.119, 0.154\\] .801 -- --\n Discrimination × SS −0.056 \\[−0.112, 0.00\\] .049 -- --\n Anxiety -- 2.924 \\[2.462, 3.386\\] \\<.001 3.119 \\[2.668, 3.570\\] \\<.001\n Conditional indirect effects of discrimination on HIV symptoms through anxiety \n Level of social support (moderator)^[b](#table-fn3-1557988318797790){ref-type=\"table-fn\"}^ Indirect effect \n 1.333 0.452 \\[0.239, 0.706\\] \n 2.000 0.342 \\[0.201, 0.514\\] \n 2.583 0.246 \\[0.113, 0.393\\] \n 3.167 0.150 \\[−0.044, 0.335\\] \n 3.583 0.082 \\[−0.176, 0.313\\] \n\n*Note.* ", "^a^Model adjusted for age, race/ethnicity, education, income, CD4 count, and AIDS diagnosis.", "\n\nValues for moderator are 10th, 25th, 50th, 75th, and 90th percentiles.", "\n\nDiscussion {#section6-1557988318797790}\n==========\n\nConsistent with study hypotheses, the results of this study suggest a positive association between number of lifetime discrimination events and HIV symptom burden among HIV-positive heterosexual Black and Hispanic men. ", "Furthermore, the relationship between number of discrimination events and HIV symptom burden was partially mediated by anxiety. ", "Although not measured in this study, one hypothesis to explain these results involves the effects of discrimination on anxiety-induced stress. ", "Although the minority stress theory has been most often applied to sexual minority populations, it may be a useful tool to understand the effects of discrimination on heterosexual, HIV-positive men of color. [", "@bibr34-1557988318797790] defines minority stress as \"excess stress to which individuals from stigmatized social categories are exposed as a result of their social, often a minority, position\" and suggests that expectations of future discriminatory events, as well as the internalization of society's negative valuations, play a role in the development of such stress ([@bibr34-1557988318797790]). ", "Studies have indicated that exposure to discrimination is associated with higher allostatic load (i.e., adverse physiological effects incurred by chronic stress; [@bibr7-1557988318797790]). ", "Furthermore, research indicates that anxiety mediates the relationship between discrimination and markers of physiological stress (e.g., cortisol; [@bibr27-1557988318797790]). ", "Anticipating discrimination due to past experiences may lead to heightened vigilance against future discrimination, which in turn leads to increased anxiety and threat-related cognitions, as well as a heightened physiological stress response ([@bibr43-1557988318797790]).", "\n\nResults also provide evidence consistent with the study hypothesis that social support may moderate the relationship between lifetime discrimination and anxiety, such that the effect of discrimination on anxiety decreases at higher levels of social support, indicating that social support may help to buffer the adverse effects of discrimination on anxiety and, by extension, HIV symptoms. ", "Studies have suggested that social support is associated with increased viral load suppression ([@bibr18-1557988318797790]) and ART adherence ([@bibr41-1557988318797790]; [@bibr45-1557988318797790]), suggesting one pathway by which social support may affect HIV symptom burden. ", "Additionally, [@bibr48-1557988318797790] suggests several plausible mechanisms by which social support may influence health outcomes, including (a) the provision of advice or assistance in implementing emotion-focused or problem-solving coping strategies; and (b) the demonstration of caring, acceptance, and (particularly among those with similar experiences) understanding, which can lead to a sense of belonging and increased self-worth ([@bibr48-1557988318797790]). ", "In addition, social support has been linked to the development of in-group identity ([@bibr44-1557988318797790]), which in turn has been linked to increased physical and mental health ([@bibr32-1557988318797790]). ", "Physiologically, social support has been linked to the release of oxytocin, which in turn has been associated with lower anxiety and decreased stress markers ([@bibr25-1557988318797790]). ", "In addition, social support has been associated with better immune functioning and immune-mediated inflammatory processes ([@bibr49-1557988318797790]). ", "Interventions to reduce HIV symptom burden, therefore, might focus on anxiety reduction by building support networks and encouraging active communication within such networks.", "\n\nStructural interventions focusing on the reduction of mutually reinforcing forms of institutional and social discrimination are also necessary to reduce not only HIV somatic symptom burden but a wide array of negative physical and mental health outcomes affecting individuals of color. ", "For example, policies that eliminate racial profiling, disproportionate arrests and incarceration of Black and Latino men, and violence experienced at the hands of the police may greatly reduce anxiety and thus contribute to better health among individuals of color. ", "Similarly, enforcement of fair housing laws and social initiatives aimed at reducing \"white flight\" may reduce residential segregation, which has also been tied to adverse health outcomes among Blacks and Latinos. ", "Enforcement of fair labor laws and programs to improve job opportunities may help to reduce economic disparities among Whites and individuals of color, making such individuals less anxious and better able to address HIV somatic symptoms as they arise. ", "Finally, intervening in all of these areas may ultimately reduce chronic stress and maladaptive coping above and beyond the protection offered by social support. ", "Without intervening on the structural level, efforts to address discrimination through individual-level interventions may only be a superficial and ultimately unsustainable solution to health problems experienced by HIV-positive men of color.", "\n\nIn interpreting these results, it is important to distinguish between major discrimination events (as explored in this study) and day-to-day discrimination, as everyday unfair treatment and microaggressions (i.e., subtle or casual degradation or dismissal of marginalized individuals; [@bibr53-1557988318797790]) may also play a role in increasing HIV-related symptoms among HIV-positive Black and Latino men. ", "For example, [@bibr38-1557988318797790] have reported that chronic exposure to day-to-day racial mistreatment is associated with increased allostatic load ([@bibr38-1557988318797790]). ", "Studies have indicated that everyday discrimination is associated with poor self-rated health ([@bibr15-1557988318797790]; [@bibr36-1557988318797790]), chronic illness ([@bibr15-1557988318797790]; [@bibr36-1557988318797790]), pain ([@bibr46-1557988318797790]), and the degree to which chronic illnesses interfere with daily life ([@bibr36-1557988318797790]) or create role limitations ([@bibr46-1557988318797790]). ", "Given that higher allostatic load has been associated with exposure to repeated or chronic stressors, the experience of day-to-day discrimination may in fact play a greater role in perpetuating negative health outcomes than major discrimination events ([@bibr13-1557988318797790]).", "\n\nFuture research should examine whether associations between discrimination and HIV symptomology hold for other groups, such as women of color. ", "Intersectionality theory suggests that social identities are multiple and interdependent and that these intersections of identity are mirrored by interlocking systems of oppression and privilege on the macro level ([@bibr6-1557988318797790]). ", "Although men are privileged due to their gender, this privilege increases and decreases in accordance with membership in other social groups (e.g., racial/ethnic minorities, those with low socioeconomic status; those who are HIV positive; men who have sex with men; [@bibr5-1557988318797790]). [", "@bibr22-1557988318797790] has demonstrated that members of multiple stigmatized groups had poorer health outcomes than singly disadvantaged or privileged individuals and that this relationship was partially mediated by multiple forms of discrimination ([@bibr22-1557988318797790]). ", "The findings of [@bibr29-1557988318797790], for example, suggest that gendered racial microaggressions are associated with negative mental and physical health outcomes among Black women ([@bibr29-1557988318797790]). ", "Thus, women might face additional or different types of discrimination that play a unique role in perpetuating health disparities in this group.", "\n\nFinally, following the work of [@bibr5-1557988318797790], future research should further examine associations between discrimination and objective measures of health among HIV-positive Black and Latino men (e.g., CD4+, viral load; [@bibr5-1557988318797790]) as well as explore mediators and moderators of these relationships. ", "Other potential mediators of the relationship between discrimination and physical health might include anger ([@bibr8-1557988318797790]; [@bibr20-1557988318797790]; [@bibr21-1557988318797790]), depression ([@bibr20-1557988318797790]; [@bibr21-1557988318797790]), or negative health behaviors (e.g., substance use)/failure to engage in healthy behaviors ([@bibr47-1557988318797790]). ", "Alternative moderators of this relationship might include other coping mechanisms than seeking social support (e.g., spirituality; [@bibr20-1557988318797790]; [@bibr39-1557988318797790]; [@bibr47-1557988318797790]).", "\n\nThis study has several limitations. ", "The cross-sectional design of the study precludes making causal inferences, and these results should be viewed as hypothesis generating rather than hypothesis testing. ", "The measure of discrimination used assessed the number of different types of discrimination events experienced, not the frequency of each type of discrimination event or the context of discrimination experienced (e.g., due to race or HIV status); thus, it was not possible to determine if one source of discrimination might have had greater consequences than another. [", "@bibr36-1557988318797790] have reported that both racial discrimination and non-attributed discrimination predicted poorer health outcomes among Blacks, while nonracial discrimination demonstrated no effect ([@bibr36-1557988318797790]). ", "Thus, future research should compare the specific effects of racial discrimination on HIV-related symptoms with other forms of discrimination, as Bogart and colleagues did when exploring the effects of discrimination on health outcomes among men who have sex with men ([@bibr5-1557988318797790]). ", "Furthermore, items relating to symptom severity were not included; thus, it was not possible to determine the degree to which symptoms interfered with individuals' quality of life or which symptoms were most problematic to participants. ", "Finally, this study did not succeed in recruiting younger men (i.e., those below age 33 years). ", "Given high rates of HIV infection among men aged 18--24 years---particularly young men of color ([@bibr12-1557988318797790])---future research should focus on how discrimination affects HIV somatic symptom burden among young adults.", "\n\nConclusion {#section7-1557988318797790}\n==========\n\nHIV-positive heterosexual men of color are vulnerable to the effects of discrimination on physical health outcomes. ", "Self-reported lifetime discrimination is positively associated with HIV symptomology, both directly and indirectly via increased anxiety. ", "Social support, however, may have a buffering effect on this relationship. ", "Future research should explore how discrimination produces negative health outcomes among individuals of color and how social support and other forms of coping can mitigate adverse effects.", "\n\n**Declaration of Conflicting Interests:** The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.", "\n\n**Funding:** The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes of Health, National Institute of Child Health and Human Development \\[grant number R01HD057793\\] and by the University of Rochester Center for AIDS Research \\[grant number NIH P30AI078498\\].", "\n\n**ORCID iD:** Amy Braksmajer ![](", "10.1177_1557988318797790-img1.jpg) <https://orcid.org/0000-0002-4307-3141>\n\nMuscle aches or joint pain\n\nFevers, chills, or sweats\n\nFeeling dizzy or lightheaded\n\nPain, numbness or tingling in the hands or feet\n\nProblems with sex\n\nNausea or vomiting\n\nDiarrhea\n\nSkin problems, such as rash, dryness or itching\n\nCough or trouble catching breath\n\nProblems with weight loss or wasting\n\nHeadache\n\nHair loss or changes in the way hair look\n\nFatigue\n\nDifficulty sleeping\n\nLoss of appetite\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "#!", "/usr/bin/env node\n// -*- js -*-\n\nglobal.sys = require(/^v0\\.[012]/.test(process.version) ? \"", "sys\" : \"util\");\nvar fs = require(\"fs\");\nvar uglify = require(\"uglify-js\"), // symlink ~/.node_libraries/uglify-js.js to ../uglify-js.js\n jsp = uglify.parser,\n pro = uglify.uglify;\n\nvar options = {\n ast: false,\n mangle: true,\n mangle_toplevel: false,\n no_mangle_functions: false,\n squeeze: true,\n make_seqs: true,\n dead_code: true,\n verbose: false,\n show_copyright: true,\n out_same_file: false,\n max_line_length: 32 * 1024,\n unsafe: false,\n reserved_names: null,\n defines: { },\n lift_vars: false,\n codegen_options: {\n ascii_only: false,\n beautify: false,\n indent_level: 4,\n indent_start: 0,\n quote_keys: false,\n space_colon: false,\n inline_script: false\n },\n make: false,\n output: true // stdout\n};\n\nvar args = jsp.slice(process.argv, 2);\nvar filename;\n\nout: while (args.length > 0) {\n var v = args.shift();\n switch (v) {\n case \"-b\":\n case \"--beautify\":\n options.codegen_options.beautify = true;\n break;\n case \"-i\":\n case \"--indent\":\n options.codegen_options.indent_level = args.shift();\n break;\n case \"-q\":\n case \"--quote-keys\":\n options.codegen_options.quote_keys = true;\n break;\n case \"-mt\":\n case \"--mangle-toplevel\":\n options.mangle_toplevel = true;\n break;\n case \"-nmf\":\n case \"--no-mangle-functions\":\n options.no_mangle_functions = true;\n break;\n case \"--no-mangle\":\n case \"-nm\":\n options.mangle = false;\n break;\n case \"--no-squeeze\":\n case \"-ns\":\n options.squeeze = false;\n break;\n case \"--no-seqs\":\n options.make_seqs = false;\n break;\n case \"--no-dead-code\":\n options.dead_code = false;\n break;\n case \"--no-copyright\":\n case \"-nc\":\n options.show_copyright = false;\n break;\n case \"-o\":\n case \"--output\":\n options.output = args.shift();\n break;\n case \"--overwrite\":\n options.out_same_file = true;\n break;\n case \"-v\":\n case \"--verbose\":\n options.verbose = true;\n break;\n case \"--ast\":\n options.ast = true;\n break;\n case \"--unsafe\":\n options.unsafe = true;\n break;\n case \"--max-line-len\":\n options.max_line_length = parseInt(args.shift(), 10);\n break;\n case \"--reserved-names\":\n options.reserved_names = args.shift().split(\",\");\n break;\n case \"--lift-vars\":\n options.lift_vars = true;\n break;\n case \"-d\":\n case \"--define\":\n var defarg = args.shift();\n try {\n var defsym = function(sym) {\n // KEYWORDS_ATOM doesn't include NaN or Infinity - should we check\n // for them too ?? ", "We don't check reserved words and the like as the\n // define values are only substituted AFTER parsing\n if (jsp.", "KEYWORDS_ATOM.hasOwnProperty(sym)) {\n throw \"Don't define values for inbuilt constant '\"+sym+\"'\";\n }\n return sym;\n },\n defval = function(v) {\n if (v.match(/^\"(.*)\"$/) || v.match(/^'(.*)'$/)) {\n return [ \"string\", RegExp.$1 ];\n }\n else if (!", "isNaN(parseFloat(v))) {\n return [ \"num\", parseFloat(v) ];\n }\n else if (v.match(/^[a-z\\$_][a-z\\$_0-9]*$/i)) {\n return [ \"name\", v ];\n }\n else if (!", "v.match(/\"/)) {\n return [ \"string\", v ];\n }\n else if (!", "v.match(/'/)) {\n return [ \"string\", v ];\n }\n throw \"Can't understand the specified value: \"+v;\n };\n if (defarg.match(/^([a-z_\\$][a-z_\\$0-9]*)(=(.*))?$/i)) {\n var sym = defsym(RegExp.$1),\n val = RegExp.$2 ? ", "defval(RegExp.$2.substr(1)) : [ 'name', 'true' ];\n options.defines[sym] = val;\n }\n else {\n throw \"The --define option expects SYMBOL[=value]\";\n }\n } catch(ex) {\n sys.print(\"ERROR: In option --define \"+defarg+\"\\n\"+ex+\"\\n\");\n process.exit(1);\n }\n break;\n case \"--define-from-module\":\n var defmodarg = args.shift(),\n defmodule = require(defmodarg),\n sym,\n val;\n for (sym in defmodule) {\n if (defmodule.hasOwnProperty(sym)) {\n options.defines[sym] = function(val) {\n if (typeof val == \"string\")\n return [ \"string\", val ];\n if (typeof val == \"number\")\n return [ \"num\", val ];\n if (val === true)\n return [ 'name', 'true' ];\n if (val === false)\n return [ 'name', 'false' ];\n if (val === null)\n return [ 'name', 'null' ];\n if (val === undefined)\n return [ 'name', 'undefined' ];\n sys.print(\"ERROR: In option --define-from-module \"+defmodarg+\"\\n\");\n sys.print(\"ERROR: Unknown object type for: \"+sym+\"=\"+val+\"\\n\");\n process.exit(1);\n return null;\n }(defmodule[sym]);\n }\n }\n break;\n case \"--ascii\":\n options.codegen_options.ascii_only = true;\n break;\n case \"--make\":\n options.make = true;\n break;\n case \"--inline-script\":\n options.codegen_options.inline_script = true;\n break;\n default:\n filename = v;\n break out;\n }\n}\n\nif (options.verbose) {\n pro.set_logger(function(msg){\n sys.debug(msg);\n });\n}\n\njsp.set_logger(function(msg){\n sys.debug(msg);\n});\n\nif (options.make) {\n options.out_same_file = false; // doesn't make sense in this case\n var makefile = JSON.parse(fs.readFileSync(filename || \"Makefile.uglify.js\").toString());\n output(makefile.files.map(function(file){\n var code = fs.readFileSync(file.name);\n if (file.module) {\n code = \"!", "function(exports, global){global = this;\\n\" + code + \"\\n;this.\" ", "+ file.module + \" = exports;}({})\";\n }\n else if (file.hide) {\n code = \"(function(){\" + code + \"}());\";\n }\n return squeeze_it(code);\n }).join(\"\\n\"));\n}\nelse if (filename) {\n fs.readFile(filename, \"utf8\", function(err, text){\n if (err) throw err;\n output(squeeze_it(text));\n });\n}\nelse {\n var stdin = process.openStdin();\n stdin.setEncoding(\"utf8\");\n var text = \"\";\n stdin.on(\"data\", function(chunk){\n text += chunk;\n });\n stdin.on(\"end\", function() {\n output(squeeze_it(text));\n });\n}\n\nfunction output(text) {\n var out;\n if (options.out_same_file && filename)\n options.output = filename;\n if (options.output === true) {\n out = process.stdout;\n } else {\n out = fs.createWriteStream(options.output, {\n flags: \"w\",\n encoding: \"utf8\",\n mode: 0644\n });\n }\n out.write(text.replace(/;*$/, \";\"));\n if (options.output !", "== true) {\n out.end();\n }\n};\n\n// --------- main ends here.", "\n\nfunction show_copyright(comments) {\n var ret = \"\";\n for (var i = 0; i < comments.length; ++i) {\n var c = comments[i];\n if (c.type == \"comment1\") {\n ret += \"//\" + c.value + \"\\n\";\n } else {\n ret += \"/*\" + c.value + \"*/\";\n }\n }\n return ret;\n};\n\nfunction squeeze_it(code) {\n var result = \"\";\n if (options.show_copyright) {\n var tok = jsp.tokenizer(code), c;\n c = tok();\n result += show_copyright(c.comments_before);\n }\n try {\n var ast = time_it(\"parse\", function(){ return jsp.parse(code); });\n if (options.lift_vars) {\n ast = time_it(\"lift\", function(){ return pro.ast_lift_variables(ast); });\n }\n if (options.mangle) ast = time_it(\"mangle\", function(){\n return pro.ast_mangle(ast, {\n toplevel : options.mangle_toplevel,\n defines : options.defines,\n except : options.reserved_names,\n no_functions : options.no_mangle_functions\n });\n });\n if (options.squeeze) ast = time_it(\"squeeze\", function(){\n ast = pro.ast_squeeze(ast, {\n make_seqs : options.make_seqs,\n dead_code : options.dead_code,\n keep_comps : !", "options.unsafe\n });\n if (options.unsafe)\n ast = pro.ast_squeeze_more(ast);\n return ast;\n });\n if (options.ast)\n return sys.inspect(ast, null, null);\n result += time_it(\"generate\", function(){ return pro.gen_code(ast, options.codegen_options) });\n if (!", "options.codegen_options.beautify && options.max_line_length) {\n result = time_it(\"split\", function(){ return pro.split_lines(result, options.max_line_length) });\n }\n return result;\n } catch(ex) {\n sys.debug(ex.stack);\n sys.debug(sys.inspect(ex));\n sys.debug(JSON.stringify(ex));\n process.exit(1);\n }\n};\n\nfunction time_it(name, cont) {\n if (!", "options.verbose)\n return cont();\n var t1 = new Date().getTime();\n try { return cont(); }\n finally { sys.debug(\"// \" + name + \": \" + ((new Date().getTime() - t1) / 1000).toFixed(3) + \" sec.\"); }", "\n};\n" ]

{ "pile_set_name": "Github" }

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[ "/*\n * Copyright 2019 NXP\n * All rights reserved.", "\n *\n *\n * SPDX-License-Identifier: BSD-3-Clause\n */\n\n#ifndef _FSL_CODEC_I2C_H_\n#define _FSL_CODEC_I2C_H_\n\n#include \"fsl_common.h\"\n#include \"i2c.h\"\n\n/*******************************************************************************\n * Definitions\n ******************************************************************************/\n/*! ", "@brief codec i2c handler */\n#ifndef CODEC_I2C_MASTER_HANDLER_SIZE\n#define CODEC_I2C_MASTER_HANDLER_SIZE HAL_I2C_MASTER_HANDLE_SIZE\n#endif\n\n/*! ", "@brief CODEC device register address type. */", "\ntypedef enum _codec_reg_addr\n{\n kCODEC_RegAddr8Bit = 1U, /*!", "< 8-bit register address. ", " */\n kCODEC_RegAddr16Bit = 2U, /*!", "< 16-bit register address. */", "\n} codec_reg_addr_t;\n\n/*! ", "@brief CODEC device register width. */", "\ntypedef enum _codec_reg_width\n{\n kCODEC_RegWidth8Bit = 1U, /*!", "< 8-bit register width. ", " */\n kCODEC_RegWidth16Bit = 2U, /*!", "< 16-bit register width. */", "\n kCODEC_RegWidth32Bit = 4U, /*!", "< 32-bit register width. */", "\n} codec_reg_width_t;\n\n/*! ", "@brief CODEC I2C configurations structure */\ntypedef struct _codec_i2c_config\n{\n uint32_t codecI2CInstance; /*!", "< i2c bus instance */\n uint32_t codecI2CSourceClock; /*!", "< i2c bus source clock frequency */\n} codec_i2c_config_t;\n\n/*******************************************************************************\n * API\n ******************************************************************************/\n#if defined(__cplusplus)\nextern \"C\" {\n#endif\n\n/*!", "\n * @brief Codec i2c bus initilization.", "\n *\n * @param handle i2c master handle.", "\n * @param i2CInstance instance number of the i2c bus, such as 0 is corresponding to I2C0.", "\n * @param i2cBaudrate i2c baudrate.", "\n * @param i2cSourceClockHz i2c source clock frequency.", "\n * @return kStatus_HAL_I2cSuccess is success, else initial failed.", "\n */\nstatus_t CODEC_I2C_Init(void *handle, uint32_t i2cInstance, uint32_t i2cBaudrate, uint32_t i2cSourceClockHz);\n\n/*!", "\n * @brief Codec i2c de-initilization.", "\n *\n * @param handle i2c master handle.", "\n * @return kStatus_HAL_I2cSuccess is success, else deinitial failed.", "\n */\nstatus_t CODEC_I2C_Deinit(void *handle);\n\n/*!", "\n * @brief codec i2c send function.", "\n *\n * @param handle i2c master handle.", "\n * @param deviceAddress codec device address.", "\n * @param subAddress register address.", "\n * @param subaddressSize register address width.", "\n * @param txBuff tx buffer pointer.", "\n * @param txBuffSize tx buffer size.", "\n * @return kStatus_HAL_I2cSuccess is success, else send failed.", "\n */\nstatus_t CODEC_I2C_Send(void *handle,\n uint8_t deviceAddress,\n uint32_t subAddress,\n uint8_t subaddressSize,\n uint8_t *txBuff,\n uint8_t txBuffSize);\n\n/*!", "\n * @brief codec i2c receive function.", "\n *\n * @param handle i2c master handle.", "\n * @param deviceAddress codec device address.", "\n * @param subAddress register address.", "\n * @param subaddressSize register address width.", "\n * @param rxBuff rx buffer pointer.", "\n * @param rxBuffSize rx buffer size.", "\n * @return kStatus_HAL_I2cSuccess is success, else receive failed.", "\n */\nstatus_t CODEC_I2C_Receive(void *handle,\n uint8_t deviceAddress,\n uint32_t subAddress,\n uint8_t subaddressSize,\n uint8_t *rxBuff,\n uint8_t rxBuffSize);\n\n#if defined(__cplusplus)\n}\n#endif\n\n#endif /* _FSL_CODEC_I2C_H_ */\n" ]

{ "pile_set_name": "Github" }

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[ "Q:\n\nVignere Cipher in C: Space not being ignored\n\nA general explanation of the Vignere Cipher: \nThe Vignere Cipher is a method of encryption that is similar to the Caesar Cipher. ", "This Cipher takes in a word as an argument and interprets the alphabets of the word as follows- a as 0, b as 1, c as 2 and so on. ", "\nSo if your input key is 'abc' and you want something like \"hi hello\" to be encrypted, the output would entail h remaining the same, i shifting by 1 place, h shifting by 2 places, e again remaining the same (as it is being shifted by 0), l shifting by 1 place, the other l by 2 and so on so forth. ", "\nThe basic idea is that each letter shifts by the corresponding letter in the argument and the spaces and other punctuation marks are ignored. ", "If the argument is shorter than the message (as it is in most cases), the argument simply loops around the message. ", "\n\nMy problem:\nThe only problem which persists is that it just seems to be doing the correct thing for the first word of the sentence. ", "It is not ignoring the spaces.", "\nI have pasted my new code below. ", "\nFor example, for the program ./vigenere bacon and message Meet me at the park at eleven am, I would expect Negh zf av huf pcfx bt gzrwep oz as the output. ", "However, what I get is Negh ne og tjs qaty bt svfvgb bm. ", "Or for example, when I run the program ./vignere bc on ABCD ABCD, I would expect BDDF BDDF. ", "What I instead get is BDDF CCEE (the output when it applies something like bcbcbcbcb as opposed to bcbc bcbc.", "\nWhile the first word is changing correctly, it seems to be encrypting the entire sentence whereas it should just encrypt the alphabets-- I have specified this using the isalpha command. ", "\nThis is why it seems a little puzzling. ", "\nCODE: \n# include <cs50.h> \n# include <stdio.h> \n# include <stdlib.h>\n# include <string.h>\n# include <ctype.h>\n\nint main(int argc, string argv[])\n\n{\n string word = argv[1];\n int i = 0;\n int j = 0;\n\n if (argc !", "= 2 || isalpha(word[j]) == false)\n {\n printf(\"Please enter a valid command line argument! ", "\\n\");\n return 1;\n }\n\n else if (isalpha(word[j]))\n {\n printf(\"Message: \"); \n string message = GetString();\n\n for (int n = strlen(message); i < n; i++)\n {\n int plaintext = message[i];\n int ciphertext = word[j]; \n int uppcb = (plaintext - 65 + ciphertext - 65);\n int upcipher1 = (uppcb) % 26;\n int uplc = (plaintext - 65 + ciphertext - 97);\n int upcipher2 = (uplc) % 26;\n int lopcb = (plaintext - 97 + ciphertext - 97);\n int locipher1 = (lopcb) % 26;\n int lolp = (plaintext - 97 + ciphertext - 65);\n int locipher2 = (lolp) % 26;\n\n if (isupper(word[j]) && isupper(message[i])) \n {\n j = (j+1)%strlen(word);\n int upcode = (upcipher1 + 65); \n printf(\"%c\", upcode);\n }\n\n else if (isupper(message[i]) && islower(word[j]))\n {\n j = (j+1)%strlen(word);\n int upcode1 = (upcipher2 + 65);\n printf(\"%c\", upcode1);\n }\n\n else if (islower(message[i]) && islower(word[j]))\n {\n j = (j+1)%strlen(word);\n int locode = (locipher1 + 97); \n printf(\"%c\", locode);\n }\n\n else if (islower(message[i]) && isupper(word[j]))\n {\n j = (j+1)%strlen(word);\n int locode1 = (locipher2 +97);\n printf(\"%c\", locode1);\n }\n\n else \n {\n printf(\"%c\", message[i]);\n } \n\n }\n printf(\"\\n\"); \n }\n\n}\n\nNOTE: This is in fact C and not C++ and some of the commands like GetInt() and GetString() are available in the CS50 library I'm using. ", "\n\nA:\n\nYou need another index variable for the variable word such as j since word and message are two different variables which may be of different lengths.", "\nSo instead of if (isupper(word[i]) && isupper(message[i])) you would instead have something like if (isupper(word[j]) && isupper(message[i])) in which the index variable j counts up from zero to the strlen(word) - 1 and then start back over at zero.", "\nThe reason it works for your special case is because message and word are the same length so there is no need to restart the index of word over at zero again when the end of the string in word is reached.", "\n\n" ]

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[ "# 설치\n\n### 직접 다운로드 / CDN\n\n[https://unpkg.com/vuex](https://unpkg.com/vuex)\n\n<!", "--email_off-->\n[Unpkg.com](https://unpkg.com)은 NPM 기반 CDN 링크를 제공합니다. ", "위의 링크는 항상 NPM의 최신 릴리스를 가리킵니다. ", "`https://unpkg.com/vuex@2.0.0`과 같은 URL을 통해 특정 버전/태그를 사용할 수도 있습니다.", "\n<!", "--/email_off-->\n\nVue 뒤에 `vuex`를 추가하면 자동으로 설치됩니다:\n\n``` html\n<script src=\"/path/to/vue.js\"></script>\n<script src=\"/path/to/vuex.js\"></script>\n```\n\n### NPM\n\n``` bash\nnpm install vuex --save\n```\n\n### Yarn\n\n``` bash\nyarn add vuex\n```\n\n모듈 시스템과 함께 사용하면 `Vue.use()`를 통해 Vuex를 명시적으로 추가해야 합니다.", "\n\n``` js\nimport Vue from 'vue'\nimport Vuex from 'vuex'\n\nVue.use(Vuex)\n```\n\n전역 스크립트 태그를 사용할 때는 이 작업을 할 필요가 없습니다.", "\n\n### Promise\n\nVuex는 [Promise](https://developer.mozilla.org/en-US/docs/Web/JavaScript/Guide/Using_promises)를 필요로 합니다. ", "만약 지원 대상 브라우저가 아직 Promise를 구현하지 않았다면(예를 들어 IE), [es6-promise](https://github.com/stefanpenner/es6-promise)와 같은 polyfill 라이브러리를 사용할 수 있습니다.", "\n\nCDN을 통해서 포함할 수 있습니다:\n\n``` html\n<script src=\"https://cdn.jsdelivr.net/npm/es6-promise@4/dist/es6-promise.auto.js\"></script>\n```\n\n그러면 자동으로 `window.", "Promise`를 사용할 수 있습니다.", "\n\nNPM 이나 Yarn 같은 패키지 매니저를 사용한다면, 아래 명령어로 설치할 수 있습니다:\n\n``` bash\nnpm install es6-promise --save # NPM\nyarn add es6-promise # Yarn\n```\n\n또한 Vuex를 사용하기 전에 아래 코드를 아무 곳에나 추가하십시오.", "\n\n``` js\nimport 'es6-promise/auto'\n```\n\n\n### 개발용 빌드\n\n최신 dev 빌드를 사용하고 싶은 경우 직접 GitHub에서 클론하고 `vuex`를 직접 빌드 해야합니다.", "\n\n\n``` bash\ngit clone https://github.com/vuejs/vuex.git node_modules/vuex\ncd node_modules/vuex\nnpm install\nnpm run build\n```\n" ]

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[ "Washington (CNN) Chief Justice John Roberts , who presided over Senate impeachment trial until around 2 a.m. ET Wednesday morning, was in his usual seat at the center of the Supreme Court bench at 10:00 a.m. to preside over a major dispute that could open the door to more state funds going toward religious education.", "\n\nWearing his black robe with glasses perched on his nose, Roberts showed no outward signs of fatigue after his marathon day serving the political branches.", "\n\nThe handful of questions he did ask in court, however, reflected that his ultimate vote, as it often is, could be key.", "\n\nThe dispute involving a Montana ruling blocking government subsidies for religious schools is the latest high-profile case religious freedom supporters, including the Trump administration, hope the newly solidified conservative majority will expand rights under the free exercise clause of the Constitution.", "\n\nCritics of the lawsuit fear the court could blur the line between church and state and they see the case as an attack on public education.", "\n\nJustice Ruth Bader Ginsburg led the charge arguing the case should be dismissed on procedural grounds, as she has in several cases this term . ", "Liberal Justices Elena Kagan and Sonia Sotomayor seemed firmly in agreement. ", "One of Roberts' questions did reflect he thought there might be grounds for dismissal, but it's unclear if that would be his ultimate vote. ", "If the court were to dismiss the case, it would put off a significant religious liberty ruling, at least for now.", "\n\nConservative Justices Samuel Alito and Brett Kavanaugh, on the other hand, suggested that they were poised to expand rights under the free exercise clause of the Constitution. ", "It is likely that Justices Neil Gorsuch and Clarence Thomas would vote the same way.", "\n\nKavanaugh noted that many state laws barring government funds for religious education stem from an early trend dating back to the 1800s directed against Catholics during a period of widespread hostility to Catholic schools. ", "Kavanaugh called the trend a symptom of \"grotesque\" religious bigotry.", "\n\nThe controversy stems from a program created by the Montana legislature in 2015 that allowed residents to receive a tax credit of up to $150 for a contribution to a scholarship program. ", "The donations were then used to fund tuition scholarships for children seeking to attend the private school of their choice. ", "In Montana, the majority of private schools are religiously affiliated.", "\n\nSoon after, however, the Montana Department of Revenue excluded religiously affiliated schools from the program, citing the fact that the state Constitution bars state funds for religious education.", "\n\nThree low-income mothers, Kendra Espinoza, Jeri Ellen Anderson and Jaime Schaefer, sued, saying they were counting on the scholarships so that they could keep their children at the Stillwater Christian School in Kalispell, Montana.", "\n\nTheir lawyers from the non-profit Institute for Justice argued that they couldn't be denied public benefits that were widely available to others for non religious, private schools.", "\n\nThe Montana Supreme Court invalidated the whole program holding that it violated the state constitution that bars state funds to aid religious schools.", "\n\n\"A state's constitutional prohibition against aide to sectarian schools may be broader and stronger than the First Amendment's prohibition against the establishment of religion,\" the court held.", "\n\nIn their appeal, the Institute for Justice wants the justices to rule that the state Supreme Court opinion violates the federal Constitution.", "\n\nIn court, Ginsburg seized on the fact that Montana's program is no longer on the books and questioning whether there is the necessary live case or controversy currently before the court.", "\n\n\"What is the harm that the parents are suffering right now?\" ", "she asked. ", "Kagan noted that the parents are currently in the \"same boat\" as other parents seeking to use the funds for secular private schools. ", "Sotomayor expressed similar sentiments. ", "And at one point, Roberts suggested that the case should have been brought, not by the parents, but the school. ", "The injury, he said, \"flows through the school.\"", "\n\nRichard Komer, a lawyer for the mothers, said that they had been injured because of the \"wholesale exclusion\" of religious schools from a program available to other private schools.", "\n\n\"The Free Exercise, Establishment and Equal Protection Clauses all demand that the government show neutrality -- not hostility -- toward religion in student-aid programs,\" he wrote in court briefs.", "\n\nHe said that Montana's amendment that bars state funds for religious schools violates the equal protection clause because it is rooted in religious animus. ", "They argue it stems from an early trend dating back to the 1800s directed against Catholics during a period of widespread hostility to Catholic schools.", "\n\nThe case is a follow-on to a 2017 opinion when the Supreme Court -- in an opinion penned by Roberts -- ruled that a Missouri policy that excluded a church-run preschool from a grant program used to resurface playgrounds was unconstitutional. ", "In a footnote, however, Roberts said that the opinion did not concern funds used for religious purposes -- leaving that issue for another day.", "\n\nNow challengers in the case at hand want the justices to take the next step.", "\n\n\"In this case, we are asking the Court to declare that the First Amendment requires government to be neutral -- not hostile -- toward religion,\" Institute for Justice lawyer Timothy Keller said.", "\n\nIn court, Alito and Kavanaugh suggested the Montana case should be governed by the court's ruling in 2017. ", "But Kagan stressed that the two cases are different and that in the Montana case the government funds go to a religious activity. ", "That's a \"far cry\" she said from the earlier case which simply dealt with the surface of a playground.", "\n\nSome 37 other states have similar amendments barring public funds for religious affiliated education although they vary in stringency. ", "For example, while Montana's provision bars \"any direct or indirect\" payment from any public fund, other states only prohibit funds direct from the public treasury.", "\n\nRepresenting the Trump administration, Solicitor General Noel Francisco sides with the parents arguing that the state's Constitutional Amendment violates the federal Constitution's Free Exercise Clause because it discriminates on the basis of \"religious status in the distribution of public benefits.\"", "\n\nIn essence Francisco argues, the state can't impose a \"special disability\" on religious schools.", "\n\nIf he prevails, the ruling will be a victory for supporters of public funding for religious education and a bitter loss for those who say it will undermine public education.", "\n\n\"It would require the diversions of scarce resources from public school systems all across the country into religious schools,\" said Randi Weingarten, president of the American Federation of Teachers.", "\n\nJessica Levinson, a professor at Loyola Law School, says the case might appeal to the conservative majority on the Supreme Court.", "\n\n\"Make no mistake, the current court is conservative and the case could be part of a steady march toward interpreting the Free Exercise Clause to require states to treat some secular and religious institutions as equally deserving of public funds\" Levinson said. \"", "Church, meet a very welcoming state.\"", "\n\nLawyers for Montana argue that the amendment is valid because states are finding a balance -- protecting the free exercise of religion while ensuring the separation of church and state.", "\n\n\"States should have the latitude to decide whether to enact school-choice programs that support religious schools,\" Adam Unikowsky, lawyer for the state, wrote in briefs. \"", "They should also have latitude to decide not to enact them—which includes the latitude to bar such programs at the state constitutional level.\"", "\n\nUnikowsky said that the Montana's Supreme Court decision ensured that \"no one would be penalized for exercising their religion,\" because the entire program was struck down.", "\n\nColorado and eight other states that have similar constitutional provisions that bar government funds to religious schools support Montana. \"", "The Framers recognized that no single solution would work for all states, and left room for individual states to make decisions about the issue of aid to religion,\" Philip J. Weiser, Colorado's attorney general argued. ", "Weiser noted that the Supreme Court has \"never suggested that the Free Exercise Clause compels the States to fund religious schools in the same manner or to the same extent as public schools.\"", "\n\nBut Oklahoma and 17 other states counter that courts in nine states with similar constitutional provisions have already construed the provision in a way that permits tax credit programs similar to that of Montana. ", "Some have noted that providing the tax credits is not the same thing as using money directly from the state's coffer. ", "The states are fearful if the Supreme Court upholds the Montana Supreme Court's opinion it would trigger other states to eliminate similar tax-credit scholarship programs.", "\n\n\"This would risk harming students in those states, many of whom are low income or have disabilities,\" Oklahoma Attorney General Mike Hunter wrote in a court brief." ]

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[ "PR Squared\n\nWednesday, February 23, 2005\n\nRSA (& other Tradeshows ) Point To Industry Priorities\n\nThis month my staff and I got to see a couple of different trade events in action.", "\n\nThe first was RSA's big security show, at the Moscone Center in San Francisco. ", "Wow. ", "If there were a clever way of combining \"Security\" and \"Lollapalooza,\" I'd try it. ", "Lollasecuralooza? ", "Hmm. ", "Can't make that work - but, I digress.", "\n\nThe show was packed. ", "We had many clients there, all of which were literally thrilled by the number of quality leads they got at the show. ", "CIOs, CSOs, CISOs - all the C-suite suits were there, apparently. ", "And one of our clients threw a kickin' party, complete with \"Bacardi Girls\" and hot-pepper-eating-contests, which always helps set a nice tone, if you ask me.", "\n\nAt another show, this week, the vibe at SpeechTek was more subdued. ", "My staffers were literally mobbed at each booth they visited, by over-eager salespeople desperate for a whiff of a scrap of a lukewarm lead.", "\n\nThis makes me curious.", "\n\nCertainly, \"Security\" is hot. ", "No question. ", "Just ask Paris (\"That's Hot\") Hilton about the need for tighter security.", "\n\nBut, did you know that more than 85% of all consumer contact with corporate brands occurs via phone? ", "Not email, not Web self-service. ", "Nope, the phone is still far-and-away Numero Uno when it comes to customer service and other inquiries.", "\n\nSo many millions of $$$ have been spent on CRM, you'd think that companies would be keen on ensuring that their call center (the most common point of customer contact) is rockin'. ", "But by the looks of things at SpeechTek, apparently this ain't the case.", "\n\nIt's good to know, as a consumer, that our customer data will eventually be totally secure. ", "But if we hate all of the vendors, due to their cruddy customer service, who's going to want to BE a customer in the first place?", "\n\nTuesday, February 08, 2005\n\nPuffery & Tomfoolery\n\nApparently the company lost a big hunk of market-cap when it yanked a promising drug from its pipeline - a drug that had been highly touted by top BMS execs, for several months beforehand, as a potential blockbuster. ", "Now, the company faces a big, honkin' shareholders' lawsuit.", "\n\nMake no mistake (not that I thought you would!) - ", "this is a lawsuit premised on the power of PR.", "\n\nWhat do these brands have in common? (", "Except for Al-Jazeera; more on that later.)", "\n\nI'm going to say, \"design.\"", "\n\nApple is renowned for the sleek, user-friendly design of all its products. ", "They feel good in the hand and are easy on the eye.", "\n\nGoogle is notable for its LACK of design. ", "In a cluttered world, in which we are barraged by too much damn information, Google's lack of pretense has made it a favorite. ", "Old-time Net users may recall that Yahoo rose to prominence with a similarly uncluttered site. ", "As its homepage swelled to \"Life Engine\" proportions, it stumbled. ", "Have you noticed, as I have, that Google's actual results are not as spot-on as in the past? ", "Don't matter, folks. ", "It's so damn clean, its popularity persists.", "\n\nIkea? ", "Wide-open aisles and store displays designed to show you how rooms in your own home might look, if you bought all their (pretty cheap) stuff. ", "It just feels good to walk in there.", "\n\nStarbucks? ", "How cool do you feel walking into the mahogany clutches of overpriced caffeine? ", "It's not because the coffee is soooo good, my friends. ", "It's because the experience has been designed to evoke that special feeling.", "\n\nIn my own experience, I can't tell you how often I've told an enterprise software company that their user interface is so \"kludgey\" that it's a PR embarassment. ", "Few of these engineering types like to admit it, yet even these gearheads like to go to Starbucks; they all use Google and have an iPod strapped to their belt.", "\n\nIt's not a matter of \"Style Over Substance\" (as they defensively suggest), it's \"Style Suggests Substance.\"" ]

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[ "Extension of N-Heteroacenes through a Four-Membered Ring.", "\nThe synthesis of novel π-extended N-heteroacenes, which have a large tetraazaacene subunit and a quinoxaline subunit connected through a four-membered ring, is reported. ", "They were studied with experimental and computational methods in comparison to the corresponding tetraazaacenes. ", "As found from the DFT calculation, the four-membered ring is a better linker than a five-membered ring or a C-C single bond to extend N-heteroacenes for a new design of n-type semiconductors in terms of the spatial delocalization and energy level of LUMO as well as the reorganization energy. ", "In solution-processed thin film transistors, the π-extended N-heteroacenes are found to function as n-type semiconductors with field effect mobility of up to 0.02 cm(2) V(-1) s(-1) under ambient conditions." ]

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[ "“From as far back as I can remember, I was under ‘the spell of poetry,’ as Laura Riding put it, but unlike her I never really thought to ‘break the spell.’ ", "My project, rather, was to join with others in an attempt to open and enlarge the field of poetry, by tactics of our own devising or by an exploration of actual poetic worlds, wherever and whenever found.”", "\n\nI’ll admit I hesitated before opening up Jerome Rothenberg’s most recent book, Writing Through: Translations and Variations (Wesleyan University Press, 2004). ", "Rothenberg, after all, is well known for his interest in poetry’s fringes, and while his efforts to bring the marginalized into the center of the page are certainly noble, the neglected, potent work he favors is best taken like a good drink—sipped slowly, in small amounts. ", "I wasn’t sure I could make it through an entire bottle by myself.", "\n\nHappily, Writing Through lends itself to just this type of modulated inebriation. ", "Spanning a breathtaking range of styles, movements and cultures (including, among others, Native American songs, Dadaist texts and Jewish gematria), Writing Through comes together like one of Joseph Cornell’s boxes; a careful assemblage of the forgotten that, accumulated, develops a kind of arcane, eclectic resonance.", "\n\nRothenberg has structured Writing Through in three parts: “Translating the New,” “Translating the Old” and “Otherings and Variations.” ", "Each of these sections features a selection of translations (or “variations”) that Rothenberg has created over the past 40 years. ", "Each sampling, in turn, is prefaced by a short introduction in which he discusses context and provides a theoretical framework for the work at hand. ", "Throughout, Rothenberg’s affection for the poems is self-evident, and nowhere more so than in these introductions, which give the reader a glimpse into his life and sensibilities.", "\n\nThe interaction of each section and their constituent styles and poets builds energy and creates interesting tensions and contrasts; Rothenberg’s translations of the relatively straightforward Neruda and Huidobro, for example, find themselves sandwiched between the more outwardly unconventional poems of “Four Dada Poets: Tzara, Arp, Huelsenbeck and Picabia” and “From Kurt Schwitters’ PPPPPP.” ", "Such juxtapositions, while common in this eclectic collection, are less jarring than they might initially seem; to the contrary, to the reader they soon become a vital part of the book-as-assemblage, illuminating heretofore undiscovered patterns among disparate poetics simply by virtue of their unusual proximity to one another.", "\n\nIf the poems in Writing Through are dissimilar in their origins, cultures and philosophies, they are united by a shared element of obscurity. ", "However, it is a testament to Rothenberg’s selective ability that a typical reader can absorb and appreciate the majority of these poems after only one reading. ", "Rothenberg is at his best with poems like Tristan Tzara’s “The Great Lament of My Obscurity Three,” the simple melancholy of which rightly restores the balance between poem and Dada. ", "His translation builds rapidly from the sparking ignition of the surreal initial images into a deeply human lament:\n\nwhere we are the flowers in our clocks flare up their feathers ring the light on a distant sulfur morning cows are licking the salt lilieso my son my son we are always brought down by the color of the world it’s blue more blue than subways than astronomy we are too thin we have no mouths our legs are stiff & knock together faces shapeless like the stars\n\n“Make it simple and sad,” James Tate said of poetry, and here the prosaic diction, quiet desperation and forceful imagery combine to fit the bill nicely.", "\n\nAmong the many great discoveries Rothenberg reveals in his collection are the poems from Picasso’s Ecrits. ", "Rothenberg aptly describes the results of Picasso’s experimentation with poetry as “unpunctuated breathless blocks of prose” representing a “faux surrealism—a simulation of spontaneity,” and the poems themselves are compelling and fearless in the same manner as his paintings. ", "Indeed, “when I began to write [poems] I wanted to prepare myself a palette of words, as if I were dealing with colors,” Rothenberg quotes Picasso, whose famous work “Guernica” arguably finds its corollary in the poem “The Dream & Lie of General Franco,” a riotous mob of words that begins:\n\nowl fandango escabeche swords of octopus of evil omen furry dishrag scalps afoot in middle of the skillet bare balls popped into a cone of codfish sherbet fried in scabies of his oxen heart—mouth full of marmalade of bedbugs of his words—silver bells and cockle shells and guts braided in a row—a pinky in erection not a grape and not a fig—commedia del arte of bad weaving and smudged clouds—cosmetics of a garbage truck—the rape of las meninas cries and outcries—casket on shoulders crammed with sausages and mouths…\n\nHere, it is the pure fury, visual evocation and artistry of composition that makes the poem and allows it to move beyond mere exercise. ", "Ultimately, whether it is surrealism or “faux surrealism” is beside the point.", "\n\nWhile there are many such discoveries in Writing Through, not all of them are as compelling. ", "Rothenberg’s translations of the German language poet Eugen Gomringer’s experimental work, for instance, suffer from the limitations of their inherently abstract nature. ", "Although I am certain one can make arguments for the theoretical worthiness of such works as this one:\n\n… as a reader I find such studies entirely vacuous; pointlessness dressed up in the ill-fitting costume of profundity.", "\n\nAs Rothenberg moves on to “Translating the Old” and “Otherings and Variations,” the work grows more obscure and, consequently, more provocative. ", "Increasingly, questions arise as to the boundaries of poetry: What defines those boundaries? ", "Do they matter? ", "Where does poetry end and visual art (or performance art, or prose, or babble) begin?", "\n\nRothenberg clearly is intent on toeing these boundaries, and nowhere more so than in his translations and variations on native cultures’ poetry. ", "For example, his translations of the Seneca tribe’s songs from the “Shaking the Pumpkin” ceremony rely on intricate arrangements of the text and carefully choreographed patterns of words and pure sound to achieve their effects.", "\n\nWhile some of these translations require a more academic sensibility to be appreciated, what saves so many of them is their surprising humor and simple humanity. ", "What’s not to like about a poem titled, “Another Song About That Same Dead Person Or Mole—Whichever It Was”? ", "Similarly, Rothenberg’s short translation of “Three Ways to Screw Up on Your Way to the Doings Three Ways” takes on the frank simplicity and bittersweet humor of a classic blues song:\n\n(1) I fell down\n\n(2) I got lost\n\n(3) I lost my bucket\n\nIn this case, ending with the lost bucket bestows on the line an emphasis that cuts through the more purely dire tone of the preceding statements; this emphasis is not only comic (I, for one, laughed out loud at the end), but also honest and indelibly human. ", "That was a good bucket.", "\n\nWhile many of these poems are fascinating (and funny), as Rothenberg enters the realm of “Total Translation,” one cannot help but wonder why, if sound and gesture are so critical to the full realization of these poems, he did not instead translate them into English and record their performance rather than transcribe them. ", "As Rothenberg himself writes in his essay on “Total Translation,”\n\nI also realized… that there were more than simple refrains involved: that we, as translators and poets, had been taking a rich oral poetry & translating it to be read primarily for meaning, thus denuding it to say the least.", "\n\nRothenberg goes on to discuss his efforts to restore the primacy of sound to the translations, but after reading his elaborate introductions about the performance of these songs and the seeming inadequacy of the text, the task of appreciating them (and it is, at times, a task) feels akin to trying to experience the Rolling Stones by reading the liner notes.", "\n\nIn the same essay, Rothenberg states, “I don’t want to set English words to Indian music, but to respond poem for poem in an attempt to work out a ‘total’ translation—not only of the words but of all sounds connected with the poem, including finally the music itself.” ", "Yet why not “set English words to Indian music”? ", "It seems to me that such an act would approach “total translation” far better, and the act of setting English words to the native music hardly threatens the integrity of the original work any more than writing it down does.", "\n\nThis question only becomes more insistent when, in his discussion of the process of translating Navajo poetry, Rothenberg writes that it “seemed important to get as far away as I could from writing. ", "So I began to speak, then sing my own words over Mitchell’s tape, replacing his vocables with sounds relevant to me, then putting my version on a fresh tape, having now to work it in its own terms.” ", "It is a pity that these audio recordings cannot accompany the text.", "\n\nUltimately, of course, this is an argument about the fundamental purpose and method of translation for a relatively small number of poems, and it should be noted that Rothenberg’s goal is often not the fastidious reproduction of the original in English (“I have never thought of myself as a professional translator,” he confesses in the preface). ", "In fact, perhaps the most fascinating portion of Writing Through is Rothenberg’s “Variations and Otherings,” in which the act of translation and the act of composition become indistinguishable.", "\n\nThe poems from “The Lorca Variations” provide some of the best examples of the way Rothenberg creates entirely new poems in the process of translating another’s, in this case by allowing himself, “a margin of flexibility, with total freedom in the case of verbs and adverbs, with occasional addresses to Lorca himself.” ", "The “variation” of the poem “Lorca’s Spain: A Homage” illustrates how this flexibility alters the original and results in something novel. ", "The poem ends with the lines:\n\nBeginning with needles. ", "Insomnia.", "Beginning with baskets. ", "The Moon. ", "Who is naked? ", "The imagination (wrote Lorca) is seared. ", "This is a homage to water. ", "Beginning & end.", "\n\nHere, the reference to Lorca within Lorca’s poem (or what used to be Lorca’s poem) is startling in the way it forces the reader to directly confront questions of authorship and (once again) translation, violating the unwritten rule that the translator must be subsumed by the work itself. ", "In the end, “variations” like this one constitute the most artistically interesting works in Writing Through; in fact, a book comprised entirely of such variations could easily stand on its own as a collection and give these works the space they deserve.", "\n\nIn the preface to Writing Through, Rothenberg describes his use of translation and the techniques by which he practices his particular version of it as “ways of opening our individual or personal poetry to the presence of other voices and other visions besides our own,” and regardless of what one thinks of those other voices and visions, Writing Through indisputably accomplishes this goal. ", "Indeed, Rothenberg deserves praise not only for his efforts to open up the field of poetry (both through this book and as the central project of his career), but also for his ability to do it in a way that is compelling and accessible (or at least not completely unaccessible).", "\n\nYet in the end, Writing Through may be best appreciated as an extended meditation on translation in all its guises. ", "In many ways, this meditation is also a deeply personal one, as Rothenberg guides the reader through a variegated landscape of poetics and disparate modes of translation. ", "Evidence of Rothenberg’s devoted touch (in his introductory mini-essays and in the selection of the material itself) pervades this collection and often pulls the reader ahead when the poems themselves grow treacherous. ", "If Writing Through is truly like a good drink, it is this quality—the way it warms us even as it dizzies us—that makes it so." ]

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[ "Art Schools in Texas\n\nIn Texas an estimated 2,910 students graduate from art schools every year.", "\nIf you too are interested in a career in art, Texas has 103 art schools for you to choose from.", "\nYearly tuition at art schools in Texas for a degree in art is $8,813 per year.", "\n\nLocated in Richardson, The University of Texas at Dallas is the largest art school in Texas, based on student population.", "\nApproximately 146 students graduated with a art degree from The University of Texas at Dallas in 2009, which is 5% of the total state art graduates for that year.", "\nIn 2009, tuition at The University of Texas at Dallas, was approximately $9,510 per year.", "\n\nArt Salaries and Career Outlook in Texas\n\nA majority of art graduates choose to work as artists.", "\nIf after graduation, you are planning on working in Texas, it is important to know that the job outlook for art graduates in the state is good.", "\nThere are currently an estimated 4,860 artists working in Texas.", "\nThe government expects, by 2018, for this number to increase by 18%, or to 5,770 artists.", "\n\nIf you work as an artist in Texas, your yearly salary can range from less than $33,575 to more than $87,340.", "\nBut the median salary for artists earn $54,868 per year, in Texas.", "\n\nNearby States\n\nArt Schools in Texas\n\nArt Schools in Texas\n\nIn Texas an estimated 2,910 students graduate from art schools every year.", "\nIf you too are interested in a career in art, Texas has 103 art schools for you to choose from.", "\nYearly tuition at art schools in Texas for a degree in art is $8,813 per year.", "\n\nLocated in Richardson, The University of Texas at Dallas is the largest art school in Texas, based on student population.", "\nApproximately 146 students graduated with a art degree from The University of Texas at Dallas in 2009, which is 5% of the total state art graduates for that year.", "\nIn 2009, tuition at The University of Texas at Dallas, was approximately $9,510 per year.", "\n\nArt Salaries and Career Outlook in Texas\n\nA majority of art graduates choose to work as artists.", "\nIf after graduation, you are planning on working in Texas, it is important to know that the job outlook for art graduates in the state is good.", "\nThere are currently an estimated 4,860 artists working in Texas.", "\nThe government expects, by 2018, for this number to increase by 18%, or to 5,770 artists.", "\n\nIf you work as an artist in Texas, your yearly salary can range from less than $33,575 to more than $87,340.", "\nBut the median salary for artists earn $54,868 per year, in Texas." ]

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[ "Mr. Bunny & Pancakes Too in Richland\n\nJanet Hill of North Carolina holds up granddaughter Olivia Hill, 3 of Kennewick, as they give the Easter bunny a high five Saturday during the City of Richland’s annual Mr. Bunny & Pancakes Too event at the Richland Community Center.", "\n\nJanet Hill of North Carolina holds up granddaughter Olivia Hill, 3 of Kennewick, as they give the Easter bunny a high five Saturday during the City of Richland’s annual Mr. Bunny & Pancakes Too event at the Richland Community Center. ", "For a full list of local Easter egg hunts and events visit http://www.tri-cityherald.com/2014/04/10/2920723/easter-egg-hunts.html" ]

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[ "I feel I will be able to by no means get married. ", "And I do not perceive folks who say they discovered their 2nd part and do not wish to cheat anymore. ", "One in every of my closest mates is getting married day after today, so I am tossing for him a stag-party with undress taunt and different special joys like suck oral pleasure and highly rigid lovemaking with buttfuck and actual double penetration. ", "I expect when he watches this totally jaw-dropping light-haired stripper on prime high-heeled shoes and in supah sumptuous garb… Possibly he’s going to leave behind about marriage. ", "This light-haired is the …" ]

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[ " IN THE UNITED STATES COURT OF APPEALS\n FOR THE FIFTH CIRCUIT\n\n\n\n No. ", "02-10819\n Conference Calendar\n\n\n\nALVIN TODD POINTER,\n\n Plaintiff-Appellant,\n\nversus\n\nGARY L. JOHNSON, DIRECTOR, TEXAS DEPARTMENT OF CRIMINAL\nJUSTICE, INSTITUTIONAL DIVISION; JOHN MIDDLETON UNIT, MEDICAL\nFACILITY; JIM RUDD UNIT MEDICAL FACILITY; GONZALEZ, Doctor,\n\n Defendants-Appellees.", "\n\n - - - - - - - - - -\n Appeal from the United States District Court\n for the Northern District of Texas\n USDC No. ", "5:01-CV-181-BG\n - - - - - - - - - -\n February 19, 2003\nBefore WIENER, EMILIO M. GARZA, and CLEMENT, Circuit Judges.", "\n\nPER CURIAM:*\n\n Alvin Todd Pointer appeals the magistrate judge’s dismissal\n\nwith prejudice in part, and the dismissal without prejudice for\n\nfailure to exhaust, of his 42 U.S.C. § 1983 claims regarding\n\nmedical treatment and work assignment. ", " In light of his receipt\n\nof physical therapy for five months, surgery on his shoulder, and\n\nreinstatement of medical restrictions, he cannot claim deliberate\n\n\n\n *\n Pursuant to 5TH CIR. ", "R. 47.5, the court has determined\nthat this opinion should not be published and is not precedent\nexcept under the limited circumstances set forth in 5TH CIR.", "\nR. 47.5.4.", "\n\f No. ", "02-10819\n -2-\n\nindifference to his medical needs. ", " See McCormick v. Stalder, 105\n\nF.3d 1059, 1061 (5th Cir. ", "1997). ", " In fact, he refers to the\n\nhospital’s “negligence,” for which 42 U.S.C. § 1983 relief is\n\nunavailable. ", " Daniels v. Williams, 474 U.S. 327 (1986).", "\n\n Insofar as Pointer is arguing that his lack of medical\n\nrestrictions was unconstitutional, this amounts, at most, to a\n\nclaim of negligence. ", " See Varnado v. Lynaugh, 920 F.2d 320, 321\n\n(5th Cir. ", "1991). ", " Such allegations do not amount to deliberate\n\nindifference to his serious medical needs. ", " Id. The district\n\ncourt did not err in dismissing Pointer’s claims regarding\n\ndisagreement with his classification.", "\n\n Pointer’s assertion that he filed a grievance refers to the\n\ngrievance filed in January 2001. ", " Although it does not mention\n\nthe hoe squad, the work assignment of which he complained, it\n\ndoes mention work in the fields during the same period. ", " Assuming\n\nthat the hoe squad and the fields are the same or related work\n\nassignments, the magistrate judge erred in finding that Pointer\n\nfailed to file any grievances concerning his assignment to the\n\nhoe squad prior to June 2001. ", " Nonetheless, as Pointer has failed\n\nto show that prison officials knew that work assignment would\n\nsignificantly aggravate his shoulder condition, he has failed to\n\nshow a violation of the Eighth Amendment. ", " Jackson v. Cain, 864\n\nF.2d 1235, 1246 (5th Cir. ", "1989).", "\n\n Pointer’s claim that the missing pages of his medical file\n\nwas a constitutional violation is frivolous.", "\n\f No. ", "02-10819\n -3-\n\n This appeal is without arguable merit and is hereby\n\nDISMISSED as frivolous. ", " See Howard v. King, 707 F.2d 215, 219-20\n\n(5th Cir. ", "1983); 5th Cir. ", "R. 42.2. ", " The magistrate judge’s\n\ndismissal of the present case as frivolous and for failure to\n\nexhaust and this court’s dismissal of Pointer’s appeal as\n\nfrivolous count as two strikes against him for purposes of\n\n28 U.S.C. § 1915(g). ", " See Adepegba v. Hammons, 103 F.3d 383, 387-\n\n88 (5th Cir. ", "1996); 28 U.S.C. § 1915(e)(2)(B)(i). ", " Pointer is\n\nhereby warned that if he accumulates three “strikes” under\n\n28 U.S.C. § 1915(g), he will not be able to proceed IFP in any\n\ncivil action or appeal filed while he is incarcerated or detained\n\nin any facility unless he is under imminent danger of serious\n\nphysical injury. ", " See 28 U.S.C. § 1915(g).", "\n\n APPEAL DISMISSED.", "\n\f" ]

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[ "/* WARNING: This file is generated by combine.pl from combine.inc.", "\n Please edit one of those files rather than this one. */", "\n\n#line 1 \"pixman-combine.c.template\"\n\n#define COMPONENT_SIZE 8\n#define MASK 0xff\n#define ONE_HALF 0x80\n\n#define A_SHIFT 8 * 3\n#define R_SHIFT 8 * 2\n#define G_SHIFT 8\n#define A_MASK 0xff000000\n#define R_MASK 0xff0000\n#define G_MASK 0xff00\n\n#define RB_MASK 0xff00ff\n#define AG_MASK 0xff00ff00\n#define RB_ONE_HALF 0x800080\n#define RB_MASK_PLUS_ONE 0x10000100\n\n#define ALPHA_8(x) ((x) >> A_SHIFT)\n#define RED_8(x) (((x) >> R_SHIFT) & MASK)\n#define GREEN_8(x) (((x) >> G_SHIFT) & MASK)\n#define BLUE_8(x) ((x) & MASK)\n\n/*\n * Helper macros.", "\n */\n\n#define MUL_UN8(a, b, t)\t\t\t\t\t\t\\\n ((t) = (a) * (b) + ONE_HALF, ((((t) >> G_SHIFT ) + (t) ) >> G_SHIFT ))\n\n#define DIV_UN8(a, b)\t\t\t\t\t\t\t\\\n (((uint16_t) (a) * MASK) / (b))\n\n#define ADD_UN8(x, y, t)\t\t\t\t \\\n ((t) = x + y,\t\t\t\t\t \\\n (uint32_t) (uint8_t) ((t) | (0 - ((t) >> G_SHIFT))))\n\n#define DIV_ONE_UN8(x)\t\t\t\t\t\t\t\\\n (((x) + ONE_HALF + (((x) + ONE_HALF) >> G_SHIFT)) >> G_SHIFT)\n\n/*\n * The methods below use some tricks to be able to do two color\n * components at the same time.", "\n */\n\n/*\n * x_rb = (x_rb * a) / 255\n */\n#define UN8_rb_MUL_UN8(x, a, t)\t\t\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tt = ((x) & RB_MASK) * (a);\t\t\t\t\t\\\n\tt += RB_ONE_HALF;\t\t\t\t\t\t\\\n\tx = (t + ((t >> G_SHIFT) & RB_MASK)) >> G_SHIFT;\t\t\\\n\tx &= RB_MASK;\t\t\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_rb = min (x_rb + y_rb, 255)\n */\n#define UN8_rb_ADD_UN8_rb(x, y, t)\t\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tt = ((x) + (y));\t\t\t\t\t\t\\\n\tt |= RB_MASK_PLUS_ONE - ((t >> G_SHIFT) & RB_MASK);\t\t\\\n\tx = (t & RB_MASK);\t\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_rb = (x_rb * a_rb) / 255\n */\n#define UN8_rb_MUL_UN8_rb(x, a, t)\t\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tt = (x & MASK) * (a & MASK);\t\t\t\t\t\\\n\tt |= (x & R_MASK) * ((a >> R_SHIFT) & MASK);\t\t\t\\\n\tt += RB_ONE_HALF;\t\t\t\t\t\t\\\n\tt = (t + ((t >> G_SHIFT) & RB_MASK)) >> G_SHIFT;\t\t\\\n\tx = t & RB_MASK;\t\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_c = (x_c * a) / 255\n */\n#define UN8x4_MUL_UN8(x, a)\t\t\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tuint32_t r1, r2, t;\t\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr1 = (x);\t\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r1, a, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr2 = (x) >> G_SHIFT;\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r2, a, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tx = r1 | (r2 << G_SHIFT);\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_c = (x_c * a) / 255 + y_c\n */\n#define UN8x4_MUL_UN8_ADD_UN8x4(x, a, y)\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tuint32_t r1, r2, r3, t;\t\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr1 = (x);\t\t\t\t\t\t\t\\\n\tr2 = (y) & RB_MASK;\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r1, a, t);\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr2 = (x) >> G_SHIFT;\t\t\t\t\t\t\\\n\tr3 = ((y) >> G_SHIFT) & RB_MASK;\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r2, a, t);\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tx = r1 | (r2 << G_SHIFT);\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_c = (x_c * a + y_c * b) / 255\n */\n#define UN8x4_MUL_UN8_ADD_UN8x4_MUL_UN8(x, a, y, b)\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tuint32_t r1, r2, r3, t;\t\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr1 = x;\t\t\t\t\t\t\t\t\\\n\tr2 = y;\t\t\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r1, a, t);\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r2, b, t);\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr2 = (x >> G_SHIFT);\t\t\t\t\t\t\\\n\tr3 = (y >> G_SHIFT);\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r2, a, t);\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r3, b, t);\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tx = r1 | (r2 << G_SHIFT);\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_c = (x_c * a_c) / 255\n */\n#define UN8x4_MUL_UN8x4(x, a)\t\t\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tuint32_t r1, r2, r3, t;\t\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr1 = x;\t\t\t\t\t\t\t\t\\\n\tr2 = a;\t\t\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr2 = x >> G_SHIFT;\t\t\t\t\t\t\\\n\tr3 = a >> G_SHIFT;\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tx = r1 | (r2 << G_SHIFT);\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_c = (x_c * a_c) / 255 + y_c\n */\n#define UN8x4_MUL_UN8x4_ADD_UN8x4(x, a, y)\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tuint32_t r1, r2, r3, t;\t\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr1 = x;\t\t\t\t\t\t\t\t\\\n\tr2 = a;\t\t\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\tr2 = y & RB_MASK;\t\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr2 = (x >> G_SHIFT);\t\t\t\t\t\t\\\n\tr3 = (a >> G_SHIFT);\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\tr3 = (y >> G_SHIFT) & RB_MASK;\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tx = r1 | (r2 << G_SHIFT);\t\t\t\t\t\\\n } while (0)\n\n/*\n * x_c = (x_c * a_c + y_c * b) / 255\n */\n#define UN8x4_MUL_UN8x4_ADD_UN8x4_MUL_UN8(x, a, y, b)\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tuint32_t r1, r2, r3, t;\t\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr1 = x;\t\t\t\t\t\t\t\t\\\n\tr2 = a;\t\t\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\tr2 = y;\t\t\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r2, b, t);\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr2 = x >> G_SHIFT;\t\t\t\t\t\t\\\n\tr3 = a >> G_SHIFT;\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\tr3 = y >> G_SHIFT;\t\t\t\t\t\t\\\n\tUN8_rb_MUL_UN8 (r3, b, t);\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tx = r1 | (r2 << G_SHIFT);\t\t\t\t\t\\\n } while (0)\n\n/*\n x_c = min(x_c + y_c, 255)\n */\n#define UN8x4_ADD_UN8x4(x, y)\t\t\t\t\t\t\\\n do\t\t\t\t\t\t\t\t\t\\\n {\t\t\t\t\t\t\t\t\t\\\n\tuint32_t r1, r2, r3, t;\t\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr1 = x & RB_MASK;\t\t\t\t\t\t\\\n\tr2 = y & RB_MASK;\t\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r1, r2, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tr2 = (x >> G_SHIFT) & RB_MASK;\t\t\t\t\t\\\n\tr3 = (y >> G_SHIFT) & RB_MASK;\t\t\t\t\t\\\n\tUN8_rb_ADD_UN8_rb (r2, r3, t);\t\t\t\t\t\\\n\t\t\t\t\t\t\t\t\t\\\n\tx = r1 | (r2 << G_SHIFT);\t\t\t\t\t\\\n } while (0)\n" ]

{ "pile_set_name": "Github" }

[ 0.0006454431568272412, 0.0005991716752760112, 0.0012144128559157252, 0.0014383298112079501, 0.025654233992099762 ]

[ "stream\n\nLime Suite is a collection of software supporting several hardware platforms including the LimeSDR, drivers for the LMS7002M transceiver RFIC, and other tools for developing with LMS7-based hardware. ", "This post will cover the components of Lime Suite, how it supports LimeSDR, how it fits with the SDR application ecosystem, and how users can use Lime…\n\nWe are excited to announce that three new designs have been published to GitHub for boards that extend the Reference Development Kit and STREAM projects. ", "These together provide an incredibly compact and low cost solution for prototyping wireless applications that are based on an Altera FPGA and Lime Microsystems FPRF.", "\n\nWhen I was contacted last year about making an OpenRISC-based SoC for an SDR platform I didn’t have to think twice. ", "I have been curious about SDR and being able to combine that with my knowledge of Open Source FPGA work seemed like a great opportunity. ", "After having talked to Ebrahim Bushehri, CEO of Lime…\n\nWe are thrilled to announce that the STREAM board is the latest project to join the Myriad-RF family. ", "A feature-packed FPGA development platform built around an Altera Cyclone IV device, this includes RFDIO and FMC connectors, enabling use with the Myriad-RF 1 transceiver, future modules and other FMC cards. ", "Stream with the LMS7002M EVB attached…" ]

{ "pile_set_name": "Pile-CC" }

[ 0.0006787875900045037, 0.0005780642386525869, 0.0008305605151690543, 0.0005673419218510389, 0.0005522744031623006, 0.0006459431606344879, 0.0006981025799177587, 0.0010218272218480706 ]

[ "Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosisTB patients.", "\nT-cells and T-cell-derived cytokines are crucial mediators of protection against Mycobacterium tuberculosis infection, but these factors are insufficient as biomarkers for disease susceptibility. ", "In order to define T-cell molecules involved in tuberculosis (TB), we compared gene expression profiles of T-cells from patients with active TB, healthy donors with latent M. tuberculosis infection (LTBIs) and non-infected healthy donors (NIDs) by microarray analysis. ", "Pathway-focused analyses identified a prevalent subset of candidate genes involved in the Janus kinase (JAK)-signal transducer and activator of transcription signalling pathway, including those encoding suppressor of cytokine signalling (SOCS) molecules, in the subset of protection-associated genes. ", "Differential expression was verified by quantitative PCR analysis for the cytokine-inducible SH2-containing protein (CISH), SOCS3, JAK3, interleukin-2 receptor α-chain (IL2RA), and the proto-oncogene serine/threonine protein kinase (PIM1). ", "Classification analyses revealed that this set of molecules was able to discriminate efficiently between T-cells from TB patients and those from LTBIs, and, notably, to achieve optimal discrimination between LTBIs and NIDs. ", "Further characterization by quantitative PCR revealed highly variable candidate gene expression in CD4(+) and CD8(+) T-cells from TB patients and only minor differences between CD4(+) and CD8(+) T-cell subpopulations. ", "These results point to a role of cytokine receptor signalling regulation in T-cells in susceptibility to TB." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Weather and place-based human behavior: recreational preferences and sensitivity.", "\nThis study examines the links between biometeorological variables and the behavior of beach recreationists along with their rating of overall weather conditions. ", "To identify and describe significance of on-site atmospheric conditions, two separate forms of response are examined. ", "The first is sensory perception of the immediate atmospheric surround expressed verbally, which was the subject of earlier work. ", "In the research reported here, on-site observations of behavior that reflect the effects of weather and climate are examined. ", "By employing, independently, separate indicators of on-site experience, the reliability of each is examined and interpreted and apparent threshold conditions verified. ", "The study site is King's Beach located on the coast of Queensland, Australia. ", "On-site observations of atmospheric variables and beach user behavior are made for the daylight hours of 45 days spread over a 12-month period. ", "The results show that behavioral data provide reliable and meaningful indications of the significance of the atmospheric environment for leisure. ", "Atmospheric conditions within the zone of acceptability are those that the beach users can readily cope with or modify by a range of minor behavioral adjustments. ", "Optimal weather conditions appear to be those requiring no specific behavioral adjustment. ", "Attendance levels reflect only the outer limits of acceptability of the meteorological environment, while duration of visit enables calibration of levels of approval in so far as it reflects rating of on-site weather within a broad zone of tolerance. ", "In a broad theoretical sense, the results add to an understanding of the relationship between weather and human behavior. ", "This information is potentially useful in effective tourism management and planning." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Online Wedding Loans - Simple Solution for Your Needs\n\nSo you’re one of an increasing number of Americans that are turning to wedding loans to fund your big day?", "\n\nIt’s no surprise; the bride, groom and their families can easily spend tens of thousands of dollars. ", "In fact the average wedding cost for 2016 was $35,329 – who can afford that upfront?", "\n\nFortunately there is a solution: We can help you fulfill all of your dream plans with an affordable wedding loan.", "\n\nRead on to find out what wedding loans are, how they work, and most importantly – how to get one!", "\n\nEasy Online Personal Loans Up To $35,000\n\nWhether you need a wedding loan or funding for other personal expenses, weddingloansonline.biz can help you match with a lender offering a maximum of $35,000 for a period of up to 7 years.", "\n\nWhat’s more, no collateral is required – so if you struggle making repayments you won’t lose any valuable property.", "\n\nAll you have to do is use our simple loan request form and you could be connected with a lender matter of minutes!", "\n\nImagine the feeling of walking down the aisle, secure in the knowledge that everything you could have dreamed of is now a reality, because you didn’t have to worry about scrimping and saving or cutting corners to meet a tight budget.", "\n\nWith some simple steps you don’t have to imagine any longer:\n\nAre You A US Adult? ", "Then You’re Eligible\n\nIf you are over the age of 18 and a legal US citizen, then you are ready for an online loan. ", "The only other requirement is that you have a stable source of income through employment, self-employment, or an accepted form of government welfare.", "\n\nChances are, if you’re planning to get married then you meet these requirements anyway and just need the right solution for everything to fall in to place.", "\n\nOne Form, Multiple Lenders\n\nWe know that planning a wedding is stressful enough without going through a tedious loan application. ", "Fortunately with our savvy loan request form you don’t have to worry about going to the bank or storefront lender, or even applying one by one with different lenders – everything is carried out stress-free online, with no need for face to face or telephone meetings!", "\n\nIt’s simple:\n\nWe take your personal details, income information and note how much you wish to borrow, and pass this through our automated system that includes a large network of reputable direct lenders.", "\n\nYou can know on-screen in a matter of minutes whether there are any offers, and you just have to click through to view these more closely. ", "You won’t get instant approval, but it’s one of the fastest legitimate solutions available on the web.", "\n\nFurthermore, should you choose to complete a full application with a lender, you could see the money in your bank account in as soon as one business day!", "\n\nAnd if that’s not good enough…\n\nThose With Bad Credit Can Apply\n\nWe recognize that many people become disheartened when they’ve been rejected for loans by banks or other large lenders due to a poor credit history, and nothing could be worse than if your big day is at stake. ", "That’s why the lenders in our network do not automatically discriminate if you have struggled with debt in the past.", "\n\nAlthough they cannot promise no credit check, your application will still be fairly assessed after they do one. ", "The ultimate decision is made based on numerous factors, including your current income status and each lender’s own policies.", "\n\nIt gets even better with these…\n\nRealistic and Flexible Terms\n\nThere is a lot of wiggle room up to the $35,000 maximum and 7 year duration, and lenders will work with you to form the ideal loan package for your married life.", "\n\nOnce your information is submitted they will carry out an assessment and make you an offer as close to the amount you desire, while ensuring it’s not beyond your means.", "\n\nAt this point you may wish to revise the amount or change the duration, and you are also free to walk away with no obligation. ", "The loan is only legally binding once you digitally sign the agreement, so don’t fret when you see offers pop up on the screen – that’s all they are until you decide otherwise.", "\n\nNo Hidden Fees or Secret Catches\n\nNote: Lenders you have matched with are legally required to provide you with a digital copy of the full loan terms, which will include the amount you can borrow, interest, repayment schedule, other possible rates and fees, and all the fine print.", "\n\nIt is important that you make time to read and digest these, as a loan of this magnitude is very important regardless of how easy it was to apply for. ", "Failure to repay will result in all of the same repercussions that you would face from a bank loan, such as a reduced credit rating, collection proceedings and your account being passed on to a collection agency.", "\n\nBottom Line: Your Dream Wedding\n\nYou could borrow up to $35,000 over 7 years, with no collateral, for your wedding or other costly purpose (even with bad credit), and see the funds in your account in as fast as one business day – all you have to do to get started is submit your personal info free of charge!", "\n\nUseful Information:\n\nWhat You Get - You may be wondering what exactly you get with a wedding loan and whether it’s suitable for you..." ]

{ "pile_set_name": "Pile-CC" }

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[ "Generalized argyria in two chronic hemodialysis patients.", "\nSilver can be absorbed through ingestion, topical administration, or inhalation. ", "Generalized argyria results from deposition of silver in the skin, nails, mucous membranes, and internal organs and is characterized by a diffuse bluish-gray discoloration in sun-exposed areas. ", "We report two cases of generalized argyria in patients on maintenance hemodialysis (HD) therapy for more than 15 years. ", "They presented with diffuse hyperpigmentation of the face that was mistaken to be related to uremia and bluish-gray discoloration of all nails believed to be cyanosis. ", "Histopathologic examination of skin biopsy specimens showed characteristic findings of argyria, which was further confirmed by radiograph microanalysis. ", "Their serum silver levels were also elevated. ", "No definite silver source could be determined. ", "However, their argyria might be related to their long-term HD therapy because (1) they had been on HD therapy for more than 15 years and the discoloration appeared several years afterward, and (2) the water used for HD was not well processed in the early 1980s in TAIWAN: Argyria should be suspected in chronic HD patients presenting with a diffuse bluish-gray discoloration of the skin and nails and evaluated carefully by skin biopsy." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nUpdate applications with another users AppleID - possible bug?", "\n\nThe situations is this.", "\n\nI installed all the the relevant apps from the App Store on my MacBook Pro using my AppleID and the apps could be updated for a long time using my AppleID.", "\nSome time ago I created a user account on my machine for my daughter and for unrelated reasons made it an admin account.", "\nSome apps installed as per 1. ", "now require my daughters AppleID to update.", "\n\nFrom reading lots of answers on this site it seems that apps installed by other users must be uninstalled/reinstalled to work resolve this issue. ", "As this is not the case for me, does anyone know what might be causing this change of AppleIDs and if it is possible to revert back? ", "As far as I can see this must be a bug.", "\nHave anyone experienced this and is there a way to resolve this other than the uninstall/reinstall solution?", "\n\nA:\n\nIf you are on High Sierra or before, you can navigate to the app in the Applications folder, then right click the app and choose Show Package Contents. ", "From the folder that pops up, expand the _MASReceipt folder and delete the receipt file. ", "The app will now update properly.", "\nIf you're on Mojave you have to uninstall and reinstall the app. ", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Converting Japan to Communism One Manga at a Time\n\nI reported previously that Japanese youth is turning to communism lately. ", "The book Kanikōsen was a hit, and it looks like we might see another one. ", "The “publishing phenomenon of the year” will be unleashed next month: manga based on Das Kapital by Karl Marx…\n\nThe comic, which goes on sale early next month, plays into a growing fascination among Japan’s hard-working labour force with socialist literature and joins a collection of increasingly fierce literary critiques of the global capitalist system.", "\n\nIn recent decades, while Japan Inc was still delivering collective prosperity to the nation, public criticism of companies has been muted. ", "Unions were weak and acquiescent. ", "But now, as the country sinks into its second recession in seven year, the sackings begin and the gap widens between rich and poor, a growing number of Japanese believe the problem lies with capitalism itself.", "\n\nThe ambitious comic rendering of Das Kapital is designed to parcel the complex economic theories of Marx’s hefty original in a format which Japanese adore digesting their information from; it will also be compressed into a size that can be slipped discretely into a Chanel evening bag, or slid into the top drawer of a desk when the bosses are looking.", "\n\nPublished by Kitsune\n\n6 thoughts on “Converting Japan to Communism One Manga at a Time”\n\nFunnily enough, I had a massive argument with my History teacher the other day who claimed that Japan was communist during the war.", "\nSocialism is lovely in theory but the fact if human greed will never allow it to flourish without shady methods of enforcement." ]

{ "pile_set_name": "Pile-CC" }

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[ "Technical Field\nThe present disclosure relates to a microelectromechanical sensing structure for a pressure sensor, which includes a test structure that is at least in part deformable.", "\nDescription of the Related Art\nAs is known, there are today available pressure sensors such as, for example, the so-called sensors of the MEMS (microelectromechanical systems) type.", "\nEach MEMS pressure sensor comprises a sensitive structure of a MEMS type and a reading electronics.", "\nThe sensitive structure, which is also known as “sensing structure”, typically forms a cavity delimited in part by a membrane and is designed to generate an electrical quantity (for example, a capacitive or resistive variation) indicating a pressure. ", "Instead, the reading electronics are designed to carry out appropriate operations of processing of this electrical quantity for supplying an electrical output signal, whether analog (for example, a voltage) or digital. ", "The electrical output signal is then made available, possibly after prior further processing by an electronic interface circuit, to an external electronic system, such as for example the microcontroller of an electronic apparatus that incorporates the pressure sensor.", "\nIn greater detail, typically the sensing structure comprises two or more piezoresistive elements, which are arranged in the proximity of the membrane. ", "In this way, the piezoresistive elements undergo deformation following upon deformation of the membrane, and thus modify their own values of resistance as a function of the deformation of the membrane, and consequently of the pressure exerted on the membrane itself.", "\nGiven this, there is particularly felt the need to be able to effectively test the aforementioned sensing structures. ", "In this connection, automatic test equipment (ATE) is known, which is designed to test a number of sensing structures, provided, for example, in a same wafer of semiconductor material. ", "For instance, some test systems envisage exerting forces on the membrane, thus from above the wafer, or else applying a pressure from beneath the wafer. ", "Again, other systems envisage arranging the sensing structure in an environment the pressure of which may be varied in a controlled way. ", "Purely by way of example, U.S. Pat. ", "No. ", "4,708,012 describes a test system that enables exertion of a pressure on a diaphragm for simulating the presence of a desired pressure, and determination of whether the corresponding electrical output signal assumes correct values. ", "In general, the test systems so far known enable effective testing of sensing structures of a known type; however, according to the cases, they may be characterized by a reduced capacity to parallelize the test, or else by high costs." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Jarod \"CycloneSpin\" Nguyen, the current solo laner for Team Allegiance, gave us some of his time to discuss some of his experiences with SMITE and the current meta after the recent changes made in Patch 4.10.", "\n\n\n\nImage Courtesy of esports.smitegame.com\n\nIn Season 2 of SMITE, you were well-known as the hard carry for your team on AFK Gaming. ", "Now, in Season 4, obviously a lot of things, such as the meta, have shifted. ", "On this team, ALG, what do you think your role is in these important team fight scenarios? ", "What's your main focus as the solo laner?", "\n\nCycloneSpin: My role essentially is like any other conventional solo laners role - disrupting and diving the carries in the back and making their lives as miserable as possible. ", "Drawing as many cooldowns and relics onto me to create space and allow my team to come in and clean up. ", "My main focus as a solo laner is to get as much farm to be as relatively tanky before teamfights begin.", "\n\n\n\n\n\nDuring the spring split (last split), Team Allegiance, along with all the other NA SPL teams in general, found themselves struggling against EU teams. ", "This split, it's obvious that your team performance is a lot better. ", "What do you think was the biggest difference between this split and the last one?", "\n\nCycloneSpin: I think the biggest difference between this split and last split for us was more of a focus on objective control. ", "Last split most of NA was basically playing for more kills and brawling, rather than focusing on objective control. ", "I also think we refined our play more, and have stopped pretty poor habits such as getting picked off and not really working as a unit.", "\n\n\n\nPreviously this split, in the game versus Flash Point eSports, your team decided to get 5 Aegis relics. ", "Do you think that would still be useful after the recent Sunder nerf? ", "Or was it strictly to counter Sunder?", "\n\nCycloneSpin: In my opinion, Aegis is extremely busted. ", "It allows you to bait ults and gives you a free pass from damage for 2 seconds. ", "Against heavy burst comps, it really hurts their fight potential. ", "This was even more emphasized from the burst meta due to Sunder's prominence. ", "After the nerfs to Sunder, it probably won't be bought like that too often, but it definitely can still be a viable option.", "\n\n\n\n\n\nIn the current meta, Bellona and Osiris were dominant solo lane characters just a while ago because of Death's Toll and the incredible amount of sustain it provides for these cleave-autoing gods. ", "How much do you think Bellona and Osiris will be impactful after the Death’s Toll nerf in the latest patch? ", "Will it make other characters more viable? ", "If so, how much more viable compared to these two?", "\n\nCycloneSpin: I think the Death's Toll nerfs impacts Bellona and Osiris in very niche scenarios, like where you're in a 1v2 scenario and you're cleaving the entire wave and the enemies. ", "Otherwise, I still think they still have too much sustain and boxing/out clearing potential in the early game where early pressure is still extremely important. ", "Other warriors are starting to be played a little more, because Osiris and Bellona are generally getting banned out to get the other or banned in the second phase.", "\n\n\n\n\n\nSo you think they'll still be the top pick solo laners moving forward from the latest patch?", "\n\nCycloneSpin: Yeah.", "\n\n\n\nMoving to team ALG, like you've said earlier, you're focusing more on objective control. ", "The answer to that for you guys specifically seem to be the goddess, Isis. ", "Why is it that no one else is prioritizing Isis more than you guys with her high early pressure and objective control? ", "Do you think other teams will take it away from you guys because of it or start picking it up for themselves?", "\n\nCycloneSpin: I think teams aren't really favoring Isis because of how the god works. ", "She's very snowball or you're going to lose the game. ", "Isis from ahead provides a lot of control and insta-kill potential, but from behind she's competing for one of the worst mages in the game so it's kind of like a gamble when picking Isis. ", "I don't think teams will try to ban it or take it away because there's so many priority picks in the meta that it's not really worth trying to steal a mid pick.", "\n\n\n\n\n\nMoving back to you being a solo laner, who do you think is the hardest solo laner you've laned against this season and overall?", "\n\nCycloneSpin: The hardest solo laner I've faced this season is probably Benj1, I think he's been one of the more consistent solo laner in NA aside from Aquarius. ", "His stronger gods right now are the best solo laners (Bellona and Osiris) so the meta really suits him. ", "Benj1's play style also gears towards farming and bullying in solo which always makes it tricky to play against him because he can punish you pretty often for your mistakes.", "\n\n\n\nFrom all four seasons I've played competitive SMITE, the hardest solo laner I've ever faced was Baskin. ", "Baskin is probably the greatest the solo laner NA would ever have; he had extremely good knowledge of matchups and the mechanical skills to back that up. ", "In season 3, he was very hard to play against because he'd capitalize on every mistake you made and create a massive gold lead because he would strip you of everything if he was able to get pressure.", "\n\n\n\n\n\nWe all know you’ve been in the competitive SMITE scene for quite some time now, all 4 seasons to be exact. ", "What gives you the drive and motivation to stay and compete for such a long time?", "\n\nCycloneSpin: I think what drives me to keep playing SMITE is that I like to win. ", "SMITE is the first game I've ever been competitive in and I really do still enjoy playing this game.", "\n\n\n\n\n\nSo, you've been through all the seasons of SMITE so far. ", "Is there anything you like more about this season compared to the previous ones?", "\n\nCycloneSpin: This season kind of plays like the other seasons, so there's not really much that I'd like more compared towards the previous one. ", "So my favorite part about this season is being on a team with Met and Neil because they're awesome to play with.", "\n\n\n\n\n\nNothing about how the different time of camp spawning you wanna touch?", "\n\nCycloneSpin: No, it really makes this game one dimensional.", "\n\n\n\nNow obviously this summer split you want your team to move on to Dreamhack Valencia for the finals. ", "A lot of people have been saying that after watching the dominating performance by ALG, you guys are very likely one of the top 3 teams in NA. ", "However, after the unfortunate 0-2 loss to Noble eSports, many begin to doubt your team's potential. ", "What do you think your team needs to do to prove everyone wrong and make it to Dreamhack Valencia?", "\n\nCycloneSpin: The games against Noble were very poor and uncharacteristic to the game style we like to run, we like did everything incorrect. ", "If we go back to playing our game we'll show everyone that we are a top 3 team and make it Dreamhack Valencia.", "\n\n\n\n\n\nWant to give some quick shoutouts?", "\n\nCycloneSpin: Shoutouts to ALG for being an awesome org, and my teammates for bouncing back after a pretty bad spring split.", "\n\n\n\n\n\nCheck out Cyclone's Twitch and Twitter!" ]

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[ "J&K quake survivors asked to move to shelters\n\nThe Jammu and Kashmir government has asked earthquake survivors living in damaged houses to urgently shift to the shelter-homes and community halls especially constructed for them.", "\n\nChief Minister Ghulam Nabi Azad, who airdashed to the city to take stock of the situation after snowfall, urged quake survivors to move to shelters, concerned over reports that many were still living in damaged structures.", "\n\n\"Under present weather conditions, living in unsafe and damaged structures is risky and dangerous. ", "As such, they should necessarily avail themselves of the facility for which the government has provided them additional amount of Rs 35,000 each family,\" Azad said.", "\n\n\"They must shift to the temporary shelters. ", "Otherwise the very purpose of protecting quake survivors from vagaries of the weather gets defeated,\" he said.", "\n\nAzad asked the administration, mediapersons, social workers and non-go working in the earthquake-affected areas to drive home among the quake survivors the necessity of shifting.", "\n\nThe chief minister was informed that all families in quake-affected areas were safe and sufficient stocks of essentials were available in these areas." ]

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