158 research outputs found

    Oscillator quantization of the massive scalar particle dynamics on AdS spacetime

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    The set of trajectories for massive spinless particles on AdSN+1AdS_{N+1} spacetime is described by the dynamical integrals related to the isometry group SO(2,N). The space of dynamical integrals is mapped one to one to the phase space of the NN-dimensional oscillator. Quantizing the system canonically, the classical expressions for the symmetry generators are deformed in a consistent way to preserve the so(2,N)so(2,N) commutation relations. This quantization thus yields new explicit realizations of the spin zero positive energy UIR's of SO(2,N) for generic NN. The representations as usual can be characterized by their minimal energy α\alpha and are valid in the whole range of α\alpha allowed by unitarity.Comment: Latex, 14 pages, version to appear in PL

    Electrochemical titrations and reaction time courses monitored in situ by magnetic circular dichroism spectroscopy

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    Magnetic circular dichroism (MCD) spectra, at ultraviolet–visible or near-infrared wavelengths (185–2000 nm), contain the same transitions observed in conventional absorbance spectroscopy, but their bisignate nature and more stringent selection rules provide greatly enhanced resolution. Thus, they have proved to be invaluable in the study of many transition metal-containing proteins. For mainly technical reasons, MCD has been limited almost exclusively to the measurement of static samples. But the ability to employ the resolving power of MCD to follow changes at transition metal sites would be a potentially significant advance. We describe here the development of a cuvette holder that allows reagent injection and sample mixing within the 50-mm-diameter ambient temperature bore of an energized superconducting solenoid. This has allowed us, for the first time, to monitor time-resolved MCD resulting from in situ chemical manipulation of a metalloprotein sample. Furthermore, we report the parallel development of an electrochemical cell using a three-electrode configuration with physically separated working and counter electrodes, allowing true potentiometric titration to be performed within the bore of the MCD solenoid

    Addressing the challenges of knowledge co-production in quality improvement:learning from the implementation of the researcher-in-residence model

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    The concept of knowledge co-production is used in health services research to describe partnerships (which can involve researchers, practitioners, managers, commissioners or service users) with the purpose of creating, sharing and negotiating different knowledge types used to make improvements in health services. Several knowledge co-production models have been proposed to date, some involving intermediary roles. This paper explores one such model, researchers-in-residence (also known as ‘embedded researchers’). In this model, researchers work inside healthcare organisations, operating as staff members while also maintaining an affiliation with academic institutions. As part of the local team, researchers negotiate the meaning and use of research-based knowledge to co-produce knowledge, which is sensitive to the local context. Even though this model is spreading and appears to have potential for using co-produced knowledge to make changes in practice, a number of challenges with its use are emerging. These include challenges experienced by the researchers in embedding themselves within the practice environment, preserving a clear focus within their host organisations and maintaining academic professional identity. In this paper, we provide an exploration of these challenges by examining three independent case studies implemented in the UK, each of which attempted to co-produce relevant research projects to improve the quality of care. We explore how these played out in practice and the strategies used by the researchers-in-residence to address them. In describing and analysing these strategies, we hope that participatory approaches to knowledge co-production can be used more effectively in the future

    Ресурсоэффективные системы в управлении и контроле: взгляд в будущее (т. 2): сборник научных трудов VII Международной конференции школьников, студентов, аспирантов, молодых ученых, 8 -13 октября 2018 г., г. Томск

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    В сборнике представлены материалы VII Международной конференции школьников, студентов, аспирантов, молодых ученых "Ресурсоэффективные системы в управлении и контроле: взгляд в будущее". Более 500 авторов из 35 вузов, предприятий и научных исследовательских университетов России, ближнего и дальнего зарубежья представили тезисы своих докладов, в которых рассматриваются актуальные проблемы неразрушающего контроля и технической диагностики, внедрения систем менеджмента, качества образования, управления в современной экономике. Материалы предназначены для специалистов, преподавателей, аспирантов и студентов вузов, а также для всех интересующихся проблемами ресурсоэффективных технологий

    Report from the second cytomegalovirus and immunosenescence workshop.

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    The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    The Changing Landscape of Naive T Cell Receptor Repertoire With Human Aging

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    Human aging is associated with a profound loss of thymus productivity, yet naïve T lymphocytes still maintain their numbers by division in the periphery for many years. The extent of such proliferation may depend on the cytokine environment, including IL-7 and T-cell receptor (TCR) “tonic” signaling mediated by self pMHCs recognition. Additionally, intrinsic properties of distinct subpopulations of naïve T cells could influence the overall dynamics of aging-related changes within the naïve T cell compartment. Here, we investigated the differences in the architecture of TCR beta repertoires for naïve CD4, naïve CD8, naïve CD4+CD25−CD31+ (enriched with recent thymic emigrants, RTE), and mature naïve CD4+CD25−CD31− peripheral blood subsets between young and middle-age/old healthy individuals. In addition to observing the accumulation of clonal expansions (as was shown previously), we reveal several notable changes in the characteristics of T cell repertoire. We observed significant decrease of CDR3 length, NDN insert, and number of non-template added N nucleotides within TCR beta CDR3 with aging, together with a prominent change of physicochemical properties of the central part of CDR3 loop. These changes were similar across CD4, CD8, RTE-enriched, and mature CD4 subsets of naïve T cells, with minimal or no difference observed between the latter two subsets for individuals of the same age group. We also observed an increase in “publicity” (fraction of shared clonotypes) of CD4, but not CD8 naïve T cell repertoires. We propose several explanations for these phenomena built upon previous studies of naïve T-cell homeostasis, and call for further studies of the mechanisms causing the observed changes and of consequences of these changes in respect of the possible holes formed in the landscape of naïve T cell TCR repertoire

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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