485 research outputs found

    The landscape of viral associations in human cancers

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    Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer

    Modelling stereotyping in cooperation systems

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    Cooperation is a sophisticated example of collective intelligence. This is particularly the case for indirect reciprocity, where benefit is provided to others without a guarantee of a future return. This is becoming increasingly relevant to future technology, where autonomous machines face cooperative dilemmas. This paper addresses the problem of stereotyping, where traits belonging to an individual are used as proxy when assessing their reputation. This is a cognitive heuristic that humans frequently use to avoid deliberation, but can lead to negative societal implications such as discrimination. It is feasible that machines could be equally susceptible. Our contribution concerns a new and general framework to examine how stereotyping affects the reputation of agents engaging in indirect reciprocity. The framework is flexible and focuses on how reputations are shared. This offers the opportunity to assess the interplay between the sharing of traits and the cost, in terms of reduced cooperation, through opportunities for shirkers to benefit. This is demonstrated using a number of key scenarios. In particular, the results show that cooperation is sensitive to the structure of reputation sharing between individuals

    Predicting the Lay Preventive Strategies in Response to Avian Influenza from Perceptions of the Threat

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    Background: The identification of patterns of behaviors that lay people would engage in to protect themselves from the risk of infection in the case of avian influenza outbreak, as well as the lay perceptions of the threat that underlie these risk reduction strategies. Methodology/Principal Findings: A population-based survey (N = 1003) was conducted in 2008 to understand and describe how the French public might respond to a possible outbreak. Factor analyses highlighted three main categories of risk reduction strategies consisting of food quality assurance, food avoidance, and animal avoidance. In combination with the fear of contracting avian influenza, mental representations associated with the manifestation and/or transmission of the disease were found to significantly and systematically shape the behavioral responses to the perceived threat. Conclusions/Significance: This survey provides insight into the nature and predictors of the protective patterns that might be expected from the general public during a novel domestic outbreak of avian influenza

    Quantum Dots for Tracking Dendritic Cells and Priming an Immune Response In Vitro and In Vivo

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    Dendritic cells (DCs) play a key role in initiating adaptive immune response by presenting antigen to T cells in lymphoid organs. Here, we investigate the potential of quantum dots (QDs) as fluorescent nanoparticles for in vitro and in vivo imaging of DCs, and as a particle-based antigen-delivery system to enhance DC-mediated immune responses. We used confocal, two-photon, and electron microscopies to visualize QD uptake into DCs and compared CD69 expression, T cell proliferation, and IFN-γ production by DO11.10 and OT-II T cells in vivo in response to free antigen or antigen-conjugated to QDs. CD11c+ DCs avidly and preferentially endocytosed QDs, initially into small vesicles near the plasma membrane by an actin-dependent mechanism. Within 10 min DCs contained vesicles of varying size, motion, and brightness distributed throughout the cytoplasm. At later times, endocytosed QDs were compartmentalized inside lysosomes. LPS-induced maturation of DCs reduced the rate of endocytosis and the proportion of cells taking up QDs. Following subcutaneous injection of QDs in an adjuvant depot, DCs that had endocytosed QDs were visualized up to 400 µm deep within draining lymph nodes. When antigen-conjugated QDs were used, T cells formed stable clusters in contact with DCs. Antigen-conjugated QDs induced CD69 expression, T cell proliferation, and IFN-γ production in vivo with greater efficiency than equivalent amounts of free antigen. These results establish QDs as a versatile platform for immunoimaging of dendritic cells and as an efficient nanoparticle-based antigen delivery system for priming an immune response

    Search for the Decays B^0 -> D^{(*)+} D^{(*)-}

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    Using the CLEO-II data set we have searched for the Cabibbo-suppressed decays B^0 -> D^{(*)+} D^{(*)-}. For the decay B^0 -> D^{*+} D^{*-}, we observe one candidate signal event, with an expected background of 0.022 +/- 0.011 events. This yield corresponds to a branching fraction of Br(B^0 -> D^{*+} D^{*-}) = (5.3^{+7.1}_{-3.7}(stat) +/- 1.0(syst)) x 10^{-4} and an upper limit of Br(B^0 -> D^{*+} D^{*-}) D^{*\pm} D^\mp and B^0 -> D^+ D^-, no significant excess of signal above the expected background level is seen, and we calculate the 90% CL upper limits on the branching fractions to be Br(B^0 -> D^{*\pm} D^\mp) D^+ D^-) < 1.2 x 10^{-3}.Comment: 12 page postscript file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review Letter

    The Hubbard model within the equations of motion approach

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    The Hubbard model has a special role in Condensed Matter Theory as it is considered as the simplest Hamiltonian model one can write in order to describe anomalous physical properties of some class of real materials. Unfortunately, this model is not exactly solved except for some limits and therefore one should resort to analytical methods, like the Equations of Motion Approach, or to numerical techniques in order to attain a description of its relevant features in the whole range of physical parameters (interaction, filling and temperature). In this manuscript, the Composite Operator Method, which exploits the above mentioned analytical technique, is presented and systematically applied in order to get information about the behavior of all relevant properties of the model (local, thermodynamic, single- and two- particle ones) in comparison with many other analytical techniques, the above cited known limits and numerical simulations. Within this approach, the Hubbard model is shown to be also capable to describe some anomalous behaviors of the cuprate superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference

    'Why don't you block them?' Police officers' constructions of the ideal victim when responding to reports of interpersonal cybercrime

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    This chapter explores police officers' responses to reports of interpersonal cybercrime by considering their construction of the 'ideal victim'. It contributes to knowledge on police officers' perceptions of cybercrime and their support for victims. The discussion draws on Nils Christie's (1986) concept of the 'ideal victim' to explore which individuals police officers most readily give the legitimate status of victim to. Three themes are discussed including: police officers' constructions of the 'ideal victim'; their attitudes towards victims in relation to prevention of cybercrime (i.e. 'block them') and; negotiations over responsibility for dealing with the emerging issue of cybercrime. The chapter argues that police forces must advance beyond an approach which entails victim-blaming and instead recognise the centrality of social media and online spaces in individuals' lives
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