9,415 research outputs found

    A Cluster Elastic Net for Multivariate Regression

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    We propose a method for estimating coefficients in multivariate regression when there is a clustering structure to the response variables. The proposed method includes a fusion penalty, to shrink the difference in fitted values from responses in the same cluster, and an L1 penalty for simultaneous variable selection and estimation. The method can be used when the grouping structure of the response variables is known or unknown. When the clustering structure is unknown the method will simultaneously estimate the clusters of the response and the regression coefficients. Theoretical results are presented for the penalized least squares case, including asymptotic results allowing for p >> n. We extend our method to the setting where the responses are binomial variables. We propose a coordinate descent algorithm for both the normal and binomial likelihood, which can easily be extended to other generalized linear model (GLM) settings. Simulations and data examples from business operations and genomics are presented to show the merits of both the least squares and binomial methods.Comment: 37 Pages, 11 Figure

    Expression and functional characterisation of Variola and Monkeypox virus tumour necrosis factor receptor (TNFR) proteins

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    University of Technology, Sydney. Faculty of Science.Tumour necrosis factor-a (TNFα) is a pleiotropic cytokine that plays a critical role in cellular response to virus infection. Virtually all poxviruses encode genes that are homologous to human tumour necrosis factor receptors (TNFRs). The viral "T2" TNFR proteins are well characterized from Leporipox viruses, myxoma (Myx) and shape fibroma virus. MyxT2 has previously been shown to bind to and inhibit rabbit TNFα in a species-specific manner and, more recently, has been shown to bind to human cellular TNFRs and inhibit TNFR1-induced cell death in a non species-specific manner. In contrast, the human-tropic Orthopoxviruses TNFR proteins have been poorly characterised, since variola virus (VAR) existed before molecular virology capabilities and the monkeypox virus (MPV) is restricted for research . This study sought to characterize the TNFR proteins, VARG4R and MPVJ2R, encoded by strict species - specific variola virus and the broad host range monkeypox virus, and compare them to the well characterized MyxT2 protein . W ith WHO Smallpox Committee approval, codon optimised cDNAs for VARG4R and MPVJ2R were constructed and these proteins were expressed as C -terminal myc-Histagged fusion proteins by transient transfection in HEK293T cells. Both VARG4R and MPVJ2R are expressed and detectable in cell lysates and culture supernatants, exactly as occurs for MyxT2. However, while MyxT2 is both a dimer and a monomer, VARG4R is predominantly a dimer and MPVJ 2R is exclusively a monomer. Secreted VARG4R and MPVJ2R are heavily glycosylated consistent with their numerous N-linked glycosylation sites. In TNFα neutralization L929 cytotoxicity assays, VARG4R inhibits rabbit, mouse, human and rhesus macaque TNFα. Although monkeypox virus has an extremely broad host range, surprisingly MPVJ2R has no TNFα inhibitory activity against rabbit, human, or rhesus macaque TNFα. Consistent with MyxT2, VARG4R and MPVJ2R inhibit TNFR1-induced cell death. It has previously been demonstrated that the viral pre-ligand association domain (PLAD) is essential for MyxT2 inhibition of TNFRl-induced cell death. Interestingly, MyxT2 PLAD, VARG4R PLAD and MPVJ2R PLAD proteins also inhibit TNFRl-induced cell death, confirming the critical role of the viral PLAD domain in the function of these viral TN FR proteins. Collectively these data suggest that, like MyxT2, secreted VARG4R protein acts as a functional TNFα-inhibitory factor during variola infection, but poxviruses with a broad host range, such as monkeypox, use other non species-specific mechanisms for host immune evasion . Overall, this study expands on our limited knowledge of variola and monkeypox viruses' mechanisms of immune evasion and further confirms the pivotal role of the viral PLAD in viral inhibition of TNFα-TN FR signaling

    Three applications for mobile epidemic algorithms

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    This paper presents a framework for the pervasive sharing of data using wireless networks. 'FarCry' uses the mobility of users to carry files between separated networks. Through a mix of ad-hoc and infrastructure-based wireless networking, files are transferred between users without their direct involvement. As users move to different locations, files are then transmitted on to other users, spreading and sharing information. We examine three applications of this framework. Each of these exploits the physically proximate nature of social gatherings. As people group together in, for example, business meetings and cafés, this can be taken as an indication of similar interests, e.g. in the same presentation or in a type of music. MediaNet affords sharing of media files between strangers or friends, MeetingNet shares business documents in meetings, and NewsNet shares RSS feeds between mobile users. NewsNet also develops the use of pre-emptive caching: collecting information from others not for oneself, but for the predicted later sharing with others. We offer observations on developing this system for a mobile, multi-user, multi-device environment

    Understanding the Role of Relationship Maintenance in Enduring Couple Partnerships in Later Adulthood

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    Intimate relationships in later adulthood are understudied despite their positive association with health and well-being. This cross-sectional mixed methods study sought to redress this gap by investigating relationship maintenance in later adulthood. Our international sub-sample comprised 1,565 participants aged 55 + and in an ongoing relationship. Results from hierarchical multiple regression indicated that overall happiness with the relationship had the largest effect size on relationship maintenance, with 53% of the variance explained. Content analyses of open-ended questions identified companionship and laughter as some of the “best liked” aspects of the relationship. Housework/cooking and saying “I love you” were among the behaviors that made participants feel appreciated. Results illustrated the types of maintenance behaviors adults in later adulthood who are in enduring partnerships employ

    Climate Change in the High Andes:implications and adaptation strategies for small-scale farmers

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    Abstract: Global climate change represents a major threat to sustainable farming in the Andes. Farmers have used local ecological knowledge and intricate production systems to cope, adapt and reorganize to meet climate uncertainty and risk, which have always been a fact of life. Those traditional systems are generally highly resilient, but the predicted effects, rates and variability of climate change may push them beyond their range of adaptability. This article examines the extent of actual and potential impacts of climate variability and change on small-scale farmers in the highland Andes of Bolivia, Ecuador and Peru. It describes how climate change impacts agriculture through deglaciation, changes in hydrology, soil and pest and disease populations. The article highlights some promising adaptive strategies currently in use by or possible for producers, rural communities and local institutions to mitigate climate change effects while preserving the livelihoods and environmental and social sustainability of the regio

    Parcel model simulations of aerosol ? warm phase cloud microphysics interactions over the Amazon

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    International audienceRecent observational studies have shown that biomass burning aerosol can modify the microstructure of convective clouds in tropical regions such as Indonesia and the Amazon. In such regions warm rain development is evidently suppressed during the burning season 5 relative to the wet season, as numerous condensation nuclei produce more numerous but smaller cloud droplets. It is not clear, however, whether rain formation is affected only by CCN or whether other factors such as giant CCN, updraft speeds, and atmospheric moisture also play important roles in the observed differences. These issues are addressed here using a simple parcel model to explain data collected during 10 the LBA-SMOCC-EMfiN! field campaign. The results suggest that polluted clouds in particular tend to be sensitive to each of these factors. When droplet concentrations exceed 500?1000 per cc, giant CCN (GCCN) become important by generating droplets that may eventually grow to precipitation size, though in cleaner environments warm rain occurs readily regardless of GCCN. Variations in the vertical velocity and in the 15 low-level moisture are also shown to affect polluted clouds, and should be taken into account in interpreting microphysical differences observed among continental clouds
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