3,507 research outputs found

    Eigenvector sensitivity under general and structured perturbations of tridiagonal Toeplitz-type matrices

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    The sensitivity of eigenvalues of structured matrices under general or structured perturbations of the matrix entries has been thoroughly studied in the literature. Error bounds are available and the pseudospectrum can be computed to gain insight. Few investigations have focused on analyzing the sensitivity of eigenvectors under general or structured perturbations. The present paper discusses this sensitivity for tridiagonal Toeplitz and Toeplitz-type matrices.Comment: 21 pages, 4 figure

    Help-Seeking Attitudes and Distress Disclosure Among Syrian Refugees in Germany

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    Many refugees experience a wide range of mental health problems, but typically use mental health services less often than settled residents. Practical constraints like limited access to mental health care and language barriers largely account for this discrepancy. However, little is known about the psychological aspects explaining this difference in mental health service usage, like attitudes toward psychological help-seeking and the disclosure of distress. The present study compares German residents’ and Syrian refugees’ attitudes toward seeking professional psychological help ( N = 384). Refugees reported more depressive symptoms and functional impairment than residents. Crucially, refugees also held more negative attitudes toward professional psychological help-seeking than residents. These group differences in attitudes were to a large part mediated by distress disclosure. We conclude that it is important to achieve a thorough understanding of how to address help-seeking attitudes and to encourage distress disclosure to promote treatment of mental health issues among many refugees.</jats:p

    SADI, SHARE, and the in silico scientific method

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    <p>Abstract</p> <p>Background</p> <p>The emergence and uptake of Semantic Web technologies by the Life Sciences provides exciting opportunities for exploring novel ways to conduct <it>in silico</it> science. Web Service Workflows are already becoming first-class objects in “the new way”, and serve as explicit, shareable, referenceable representations of how an experiment was done. In turn, Semantic Web Service projects aim to facilitate workflow construction by biological domain-experts such that workflows can be edited, re-purposed, and re-published by non-informaticians. However the aspects of the scientific method relating to explicit discourse, disagreement, and hypothesis generation have remained relatively impervious to new technologies.</p> <p>Results</p> <p>Here we present SADI and SHARE - a novel Semantic Web Service framework, and a reference implementation of its client libraries. Together, SADI and SHARE allow the semi- or fully-automatic discovery and pipelining of Semantic Web Services in response to <it>ad hoc</it> user queries.</p> <p>Conclusions</p> <p>The semantic behaviours exhibited by SADI and SHARE extend the functionalities provided by Description Logic Reasoners such that novel assertions can be automatically added to a data-set without logical reasoning, but rather by analytical or annotative services. This behaviour might be applied to achieve the “semantification” of those aspects of the <it>in silico</it> scientific method that are not yet supported by Semantic Web technologies. We support this suggestion using an example in the clinical research space.</p

    Regulation of Transgene Expression in Tumor Cells by Exploiting Endogenous Intracellular Signals

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    Recently, we have proposed a novel strategy for a cell-specific gene therapy system based on responses to intracellular signals. In this system, an intracellular signal that is specifically and abnormally activated in the diseased cells is used for the activation of transgene expression. In this study, we used protein kinase C (PKC)α as a trigger to activate transgene expression. We prepared a PKCα-responsive polymer conjugate [PPC(S)] and a negative control conjugate [PPC(A)], in which the phosphorylation site serine (Ser) was replaced with alanine (Ala). The phosphorylation for polymer/DNA complexes was determined with a radiolabel assay using [γ-32P]ATP. PPC(S)/DNA complexes were phosphorylated by the addition of PKCα, but no phosphorylation of the PPC(A)/DNA complex was observed. Moreover, after microinjection of polymer/GFP-encoding DNA complexes into HepG2 cells at cation/anion (C/A) ratios of 0.5 to 2.0, significant expression of GFP was observed in all cases using PPC(S)/DNA complexes, but no GFP expression was observed in the negative control PPC(A)/DNA complex-microinjected cells at C/A ratios of 1.0 and 2.0. On the other hand, GFP expression from PPC(S)/DNA complexes was completely suppressed in cells pretreated with PKCα inhibitor (Ro31-7549). These results suggest that our gene regulation system can be used for tumor cell-specific expression of a transgene in response to PKCα activity

    Mixed precision bisection

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    We discuss the implementation of the bisection algorithm for the computation of the eigenvalues of symmetric tridiagonal matrices in a context of mixed precision arithmetic. This approach is motivated by the emergence of processors which carry out floating-point operations much faster in single precision than they do in double precision. Perturbation theory results are used to decide when to switch from single to double precision. Numerical examples are presente

    Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by HCMV US2 in cooperation with UL141.

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    Human cytomegalovirus (HCMV) US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules (MHC-I). Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane Profiling revealed US2 was unique in downregulating additional cellular targets, including: five distinct integrin α-chains, CD112, the interleukin-12 receptor, PTPRJ and thrombomodulin. US2 recruited the cellular E3 ligase TRC8 to direct the proteasomal degradation of all its targets, reminiscent of its degradation of MHC-I. Whereas integrin α-chains were selectively degraded, their integrin β1 binding partner accumulated in the ER. Consequently integrin signaling, cell adhesion and migration were strongly suppressed. US2 was necessary and sufficient for degradation of the majority of its substrates, but remarkably, the HCMV NK cell evasion function UL141 requisitioned US2 to enhance downregulation of the NK cell ligand CD112. UL141 retained CD112 in the ER from where US2 promoted its TRC8-dependent retrotranslocation and degradation. These findings redefine US2 as a multifunctional degradation hub which, through recruitment of the cellular E3 ligase TRC8, modulates diverse immune pathways involved in antigen presentation, NK cell activation, migration and coagulation; and highlight US2's impact on HCMV pathogenesis.This study was financially supported by grant 101-2917-I-564-035 from the Taiwan National Science Council to JLH; by a Wellcome Trust Fellowship (093966/Z/10/Z) to MPW; an MRC Project Grant and Wellcome Trust Programme Grant (G1000236, WT090323MA) to GWW and PT, European Regional Development Fund and the State Budget of Czech Republic (RECAMO, CZ.1.05/ 2.1.00/03.0101) to ER; a Wellcome Trust Principal Research Fellowship (084957/Z/08/Z) to PJL; and a Medical Research Council (MRC) grant (MC_UU_12014/3) to GSW and AJD. This study was additionally supported by the Cambridge Biomedical Research Centre, UK.This is the final published version. It first appeared at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004811
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