3,569 research outputs found

    Turning up by turning over : the change of scenery effect in major league baseball

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    Purpose: This study examined a “change of scenery” effect on performance in major league baseball (MLB). We also tested this effect for voluntary versus involuntary employee departures, as well as employees returning to a past employer. Design/Methodology/Approach: This study uses publicly available MLB performance data from 2004 to 2015. The data comprise 712 team changes for players following two consecutive years with the same organization. Data were analyzed using MANCOVA to assess the impact of changing teams on player performance. Findings: Results indicate players with declining performance benefited significantly from a change of scenery. Following a team change, these players experienced a significant increase in their performance that remained stable through a subsequent season. The effect was not different for players who changed teams via trade and free agency and was modest for those returning to a past organization. Analysis also showed that players leaving while their performance was improving suffered a subsequent performance drop-off in the new organization. Implications: As the war for talent escalates and employees change jobs more frequently, extending our understanding of how performance can be influenced by work context may provide new insight into organization staffing policies. Originality/Value: Results extend field theory by highlighting how past performance interacts with new work contexts to influence performance. This is one of the few studies evaluating the job change-performance relationship, and perhaps the first to account for the effects of performance trends prior to exit

    Structural characterization of the catalytic domain of the human 5-lipoxygenase enzyme

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    Leukotrienes are inflammatory mediators involved in several diseases. The enzyme 5-lipoxygenase initiates the synthesis of leukotrienes from arachidonic acid. Little structural information is available regarding 5-lipoxygenase. In this study, we found that the primary structure of the catalytic domain of human 5-lipoxygenase is similar to that of the rabbit 15-lipoxygenase. This similarity allowed the development of a theoretical model of the tertiary structure of the 5-lipoxygenase catalytic domain, using the resolved structure of rabbit 15-lipoxygenase as a template. This model was used in conjunction with primary and secondary structural information to investigate putative nucleotide binding sites, a MAPKAP kinase 2 phosphorylation site, and a Src homology 3 binding site on the 5-lipoxygenase protein, further. Results indicate that the putative nucleotide binding sites are spatially distinct, with one on the β-barrel domain and the other(s) on the catalytic domain. The MAPKAP kinase 2 phosphorylation site involves a four amino acid insertion in mammalian 5-lipoxygenases that significantly alters molecular structure. This target for post-translational modification is both common and unique to 5-lipoxygenases. The Src homology 3 binding site, found in all lipoxygenases, appears to lack the characteristic left-handed type II helix structure of known Src homology 3 binding sites. These results, which highlight the unique nature of the MAPKAP kinase site, underscore the utility of structural information in the analysis of protein function. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00894-002-0076-y.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47877/1/894_2002_Article_76.pd

    Can Medication Free, Treatment-Resistant, Depressed Patients Who Initially Respond to TMS Be Maintained Off Medications? A Prospective, 12-Month Multisite Randomized Pilot Study

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    AbstractBackgroundRepetitive transcranial magnetic stimulation (TMS) is efficacious for acute treatment of resistant major depressive disorder (MDD), but there is little information on maintenance TMS after acute response.Objective/hypothesisThis pilot feasibility study investigated 12-month outcomes comparing two maintenance TMS approaches – a scheduled, single TMS session delivered monthly (SCH) vs. observation only (OBS).MethodsAntidepressant-free patients with unipolar, non-psychotic, treatment-resistant MDD participated in a randomized, open-label, multisite trial. Patients meeting protocol-defined criteria for improvement after six weeks of acute TMS were randomized to SCH or OBS regimens. TMS reintroduction was available for symptomatic worsening; all patients remained antidepressant-free during the trial.ResultsSixty-seven patients enrolled in the acute phase, and 49 (73%) met randomization criteria. Groups were matched, although more patients in the SCH group had failed ≥2 antidepressants (p = .035). There were no significant group differences on any outcome measure. SCH patients had nonsignificantly longer time to first TMS reintroduction, 91 ± 66 days, vs. OBS, 77 ± 52 days; OBS patients were nonsignificantly more likely to need reintroduction (odds ratio = 1.21, 95% CI .38–3.89). Reintroduction lasted 14.3 ± 17.8 days (SCH) and 16.9 ± 18.9 days (OBS); 14/18 (78%) SCH and 17/27 (63%) OBS responded to reintroduction. Sixteen patients (32.7%) completed all 53 weeks of the study.ConclusionsMaintaining treatment-resistant depressed patients off medications with periodic TMS appears feasible in some cases. There was no statistical advantage of SCH vs. OBS, although SCH was associated with a nonsignificantly longer time to relapse. Those who initially respond to TMS have a strong chance of re-responding if relapse occurs

    Comprehensive translational assessment of human-induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias

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    Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the comprehensive in vitro proarrhythmia assay (CiPA). We studied the effects of 26 drugs and 3 drug combinations on 2 commercially available iPSC-CM types using high-throughput voltage-sensitive dye and microelectrode-array assays being studied for the CiPA initiative and compared the results with clinical QT prolongation and torsade de pointes (TdP) risk. Concentration-dependent analysis comparing iPSC-CMs to clinical trial results demonstrated good correlation between drug-induced rate-corrected action potential duration and field potential duration (APDc and FPDc) prolongation and clinical trial QTc prolongation. Of 20 drugs studied that exhibit clinical QTc prolongation, 17 caused APDc prolongation (16 in Cor.4U and 13 in iCell cardiomyocytes) and 16 caused FPDc prolongation (16 in Cor.4U and 10 in iCell cardiomyocytes). Of 14 drugs that cause TdP, arrhythmias occurred with 10 drugs. Lack of arrhythmic beating in iPSC-CMs for the four remaining drugs could be due to differences in relative levels of expression of individual ion channels. iPSC-CMs responded consistently to human ether-a-go-go potassium channel blocking drugs (APD prolongation and arrhythmias) and calcium channel blocking drugs (APD shortening and prevention of arrhythmias), with a more variable response to late sodium current blocking drugs. Current results confirm the potential of iPSC-CMs for proarrhythmia prediction under CiPA, where iPSC-CM results would serve as a check to ion channel and in silico modeling prediction of proarrhythmic risk. A multi-site validation study is warranted

    Progress on large area GEMs

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    In 2008, a triple GEM detector prototype with an area of ~2000 cm2 has been constructed, based on foils of 66*66 cm. GEMs of such dimensions had not been made before, and innovations to the existing technology were introduced to build this detector. This paper discusses these innovations and presents further work on large area GEM development. A single-mask technique overcomes the cumbersome practice of alignment of two masks, which limits the achievable lateral size. The holes obtained with this technique are conical, and have a so-called rim, a small insulating clearance around the hole in the substrate. Further refinements of this technique allow greater control over the shape of holes and the size of rims. Also, an improvement in homogeneity over large areas is expected. Simulation studies have been done to examine the effect of hole shape on the behavior of GEMs. Such studies can help understanding how to use new enhancements of the technique to optimize performance. Many potential applications for large area GEMs foresee large production volumes. Production issues have been studied, and single-mask GEMs turn out to be much more suitable for large scale production than standard GEMs.Comment: Contribution to the MPGD'09 conference, Crete, Greec

    Making spherical GEMs

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    We developed a method to make GEM foils with a spherical geometry. Tests of this procedure and with the resulting spherical GEMs are presented. Together with a spherical drift electrode, a spherical conversion gap for x-rays can be formed. This would eliminate the parallax error in an x-ray diffraction setup, which limits the spatial resolution at wide diffraction angles. The method is inexpensive and flexible towards possible changes in the design. We show advanced plans to make a prototype of an entirely spherical triple-GEM detector, including a spherical readout structure. This detector will have a superior position resolution, also at wide diffraction angles, and a high rate capability. A completely spherical gaseous detector has never been made before.Comment: Contribution to the proceedings of the MPGD'09 conference, Cret

    Accelerating Bayesian hierarchical clustering of time series data with a randomised algorithm

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    We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/

    The solvation and dissociation of 4-benzylaniline hydrochloride in chlorobenzene

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    A reaction scheme is proposed to account for the liberation of 4-benzylaniline from 4-benzylaniline hydrochloride, using chlorobenzene as a solvent at a temperature of 373 K. Two operational regimes are explored: “closed” reaction conditions correspond to the retention of evolved hydrogen chloride gas within the reaction medium, whereas an “open” system permits gaseous hydrogen chloride to be released from the reaction medium. The solution phase chemistry is analyzed by 1H NMR spectroscopy. Complete liberation of solvated 4-benzylaniline from solid 4-benzylaniline hydrochloride is possible under “open” conditions, with the entropically favored conversion of solvated hydrogen chloride to the gaseous phase thought to be the thermodynamic driver that effectively controls a series of interconnecting equilibria. A kinetic model is proposed to account for the observations of the open system

    No severe genetic bottleneck in a rapidly range-expanding bumblebee pollinator

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    Genetic bottlenecks can limit the success of populations colonizing new ranges. However, successful colonizations can occur despite bottlenecks, a phenomenon known as the genetic paradox of invasion. Eusocial Hymenoptera such as bumblebees (Bombus spp.) should be particularly vulnerable to genetic bottlenecks, since homozygosity at the sex-determining locus leads to costly diploid male production (DMP). The Tree Bumblebee (Bombus hypnorum) has rapidly colonized the UK since 2001 and has been highlighted as exemplifying the genetic paradox of invasion. Using microsatellite genotyping, combined with the first genetic estimates of DMP in UK B. hypnorum, we tested two alternative genetic hypotheses ('bottleneck' and 'gene flow' hypotheses) for B. hypnorum's colonization of the UK. We found that the UK population has not undergone a recent severe genetic bottleneck and exhibits levels of genetic diversity falling between those of widespread and range-restricted Bombus species. Diploid males occurred in 15.4% of reared colonies, leading to an estimate of 21.5 alleles at the sex-determining locus. Overall, the findings show that this population is not bottlenecked, instead suggesting that it is experiencing continued gene flow from the continental European source population with only moderate loss of genetic diversity, and does not exemplify the genetic paradox of invasion
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