889 research outputs found

    PMH53 Measuring Real World Outcomes by Incorporating PRO Data Collection into Patient Access Support Programs

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    ISPIDER Central: an integrated database web-server for proteomics

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    Despite the growing volumes of proteomic data, integration of the underlying results remains problematic owing to differences in formats, data captured, protein accessions and services available from the individual repositories. To address this, we present the ISPIDER Central Proteomic Database search (http://www.ispider.manchester.ac.uk/cgi-bin/ProteomicSearch.pl), an integration service offering novel search capabilities over leading, mature, proteomic repositories including PRoteomics IDEntifications database (PRIDE), PepSeeker, PeptideAtlas and the Global Proteome Machine. It enables users to search for proteins and peptides that have been characterised in mass spectrometry-based proteomics experiments from different groups, stored in different databases, and view the collated results with specialist viewers/clients. In order to overcome limitations imposed by the great variability in protein accessions used by individual laboratories, the European Bioinformatics Institute's Protein Identifier Cross-Reference (PICR) service is used to resolve accessions from different sequence repositories. Custom-built clients allow users to view peptide/protein identifications in different contexts from multiple experiments and repositories, as well as integration with the Dasty2 client supporting any annotations available from Distributed Annotation System servers. Further information on the protein hits may also be added via external web services able to take a protein as input. This web server offers the first truly integrated access to proteomics repositories and provides a unique service to biologists interested in mass spectrometry-based proteomics

    Quantum computation with two-level trapped cold ions beyond Lamb-Dicke limit

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    We propose a simple scheme for implementing quantum logic gates with a string of two-level trapped cold ions outside the Lamb-Dicke limit. Two internal states of each ion are used as one computational qubit (CQ) and the collective vibration of ions acts as the information bus, i.e., bus qubit (BQ). Using the quantum dynamics for the laser-ion interaction as described by a generalized Jaynes-Cummings model, we show that quantum entanglement between any one CQ and the BQ can be coherently manipulated by applying classical laser beams. As a result, universal quantum gates, i.e. the one-qubit rotation and two-qubit controlled gates, can be implemented exactly. The required experimental parameters for the implementation, including the Lamb-Dicke (LD) parameter and the durations of the applied laser pulses, are derived. Neither the LD approximation for the laser-ion interaction nor the auxiliary atomic level is needed in the present scheme.Comment: 12 pages, no figures, to appear in Phys. Rev.

    Retrogressive thaw slump susceptibility in the northern hemisphere permafrost region

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    Mean annual temperatures in the Arctic and subarctic have increased in recent decades, increasing the number of permafrost hazards. Retrogressive thaw slumps (RTSs), triggered by the thawing of ground ice in permafrost soil, have become more common in the Arctic. Many studies report an increase in RTS activity on a local or regional scale. In this study, the primary goals are to: (i) examine the spatial patterns of the RTS occurrences across the circumpolar permafrost region, (ii) assess the environmental factors associated with their occurrence and (iii) create the first susceptibility map for RTS occurrence across the Northern Hemisphere. Based on our results, we predicted high RTS susceptibility in the continuous permafrost regions above the 60th latitude, especially in northern Alaska, north-western Canada, the Yamal Peninsula, eastern Russia and the Qinghai-Tibetan Plateau. The model indicated that air temperature and soil properties are the most critical environmental factors for the occurrence of RTSs on a circumpolar scale. Especially, the climatic conditions of thaw season were highlighted. This study provided new insights into the circumpolar susceptibility of ice-rich permafrost soils to rapid permafrost-related hazards like RTSs and the associated impacts on landscape evolution, infrastructure, hydrology and carbon fluxes that contribute to global warming.</p

    Disentangling the interplay between genes, cognitive skills, and educational level in adolescent and young adult smoking – The TRAILS study

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    Recent studies suggest that smoking and lower educational attainment may have genetic influences in common. However, little is known about the mechanisms through which genetics contributes to educational inequalities in adolescent and young adult smoking. Common genetic liabilities may underlie cognitive skills associated with both smoking and education, such as IQ and effortful control, in line with indirect health-related selection explanations. Additionally, by affecting cognitive skills, genes may predict educational trajectories and hereby adolescents’ social context, which may be associated with smoking, consistent with social causation explanations. Using data from the Dutch TRAILS Study (N = 1581), we estimated the extent to which polygenic scores (PGSs) for ever smoking regularly (PGSSMOK) and years of education (PGSEDU) predict IQ and effortful control, measured around age 11, and whether these cognitive skills then act as shared predictors of smoking and educational level around age 16, 19, 22, and 26. Second, we assessed if educational level mediated associations between PGSs and smoking. Both PGSs were associated with lower effortful control, and PGSEDU also with lower IQ. Lower IQ and effortful control, in turn, predicted having a lower educational level. However, neither of these cognitive skills were directly associated with smoking behaviour after controlling for covariates and PGSs. This suggests that IQ and effortful control are not shared predictors of smoking and education (i.e., no indirect health-related selection related to cognitive skills). Instead, PGSSMOK and PGSEDU, partly through their associations with lower cognitive skills, predicted selection into a lower educational track, which in turn was associated with more smoking, in line with social causation explanations. Our findings suggest that educational differences in the social context contribute to associations between genetic liabilities and educational inequalities in smoking

    Searching for star-planet magnetic interaction in CoRoT observations

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    Close-in massive planets interact with their host stars through tidal and magnetic mechanisms. In this paper, we review circumstantial evidence for star-planet interaction as revealed by the photospheric magnetic activity in some of the CoRoT planet-hosting stars, notably CoRoT-2, CoRoT-4, and CoRoT-6. The phenomena are discussed in the general framework of activity-induced features in stars accompanied by hot Jupiters. The theoretical mechanisms proposed to explain the activity enhancements possibly related with hot Jupiter are also briefly reviewed with an emphasis on the possible effects at photospheric level. The unique advantages of CoRoT and Kepler observations to test these models are pointed out.Comment: Invited review paper accepted by Astrophysics and Space Science, 13 pages, 5 figure

    In vivo fiber optic raman spectroscopy of muscle in preclinical models of amyotrophic lateral sclerosis and Duchenne muscular dystrophy

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    Neuromuscular diseases result in muscle weakness, disability, and, in many instances, death. Preclinical models form the bedrock of research into these disorders, and the development of in vivo and potentially translational biomarkers for the accurate identification of disease is crucial. Spontaneous Raman spectroscopy can provide a rapid, label-free, and highly specific molecular fingerprint of tissue, making it an attractive potential biomarker. In this study, we have developed and tested an in vivo intramuscular fiber optic Raman technique in two mouse models of devastating human neuromuscular diseases, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy (SOD1G93A and mdx, respectively). The method identified diseased and healthy muscle with high classification accuracies (area under the receiver operating characteristic curves (AUROC): 0.76–0.92). In addition, changes in diseased muscle over time were also identified (AUROCs 0.89–0.97). Key spectral changes related to proteins and the loss of α-helix protein structure. Importantly, in vivo recording did not cause functional motor impairment and only a limited, resolving tissue injury was seen on high-resolution magnetic resonance imaging. Lastly, we demonstrate that ex vivo muscle from human patients with these conditions produced similar spectra to those observed in mice. We conclude that spontaneous Raman spectroscopy of muscle shows promise as a translational research tool

    Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks.

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    The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8 &lt;sup&gt;+&lt;/sup&gt; T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy

    Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

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    We report a high precision measurement of the transverse single spin asymmetry ANA_N at the center of mass energy s=200\sqrt{s}=200 GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The ANA_N was measured in the four-momentum transfer squared tt range 0.003t0.0350.003 \leqslant |t| \leqslant 0.035 \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of ANA_N and its tt-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this s\sqrt{s}, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure
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