10 research outputs found

    Runtime analysis of evolutionary multi-objective algorithms optimising the degree and diameter of spanning trees

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    Motivated by the telecommunication network design, we study the problem of finding diverse set of minimum spanning trees of a certain complete graph based on the two features which are maximum degree and diameter. In this study, we examine a simple multi-objective EA, GSEMO, in solving the two problems where we maximise or minimise the two features at the same time.With a rigorous runtime analysis, we provide understanding of how GSEMO optimize the set of minimum spanning trees in these two different feature spaces.Wanru Gao, Mojgan Pourhassan, Vahid Roostapour, and Frank Neuman

    Identification of Key Processes that Control Tumor Necrosis Factor Availability in a Tuberculosis Granuloma

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    Tuberculosis (TB) granulomas are organized collections of immune cells comprised of macrophages, lymphocytes and other cells that form in the lung as a result of immune response to Mycobacterium tuberculosis (Mtb) infection. Formation and maintenance of granulomas are essential for control of Mtb infection and are regulated in part by a pro-inflammatory cytokine, tumor necrosis factor-α (TNF). To characterize mechanisms that control TNF availability within a TB granuloma, we developed a multi-scale two compartment partial differential equation model that describes a granuloma as a collection of immune cells forming concentric layers and includes TNF/TNF receptor binding and trafficking processes. We used the results of sensitivity analysis as a tool to identify experiments to measure critical model parameters in an artificial experimental model of a TB granuloma induced in the lungs of mice following injection of mycobacterial antigen-coated beads. Using our model, we then demonstrated that the organization of immune cells within a TB granuloma as well as TNF/TNF receptor binding and intracellular trafficking are two important factors that control TNF availability and may spatially coordinate TNF-induced immunological functions within a granuloma. Further, we showed that the neutralization power of TNF-neutralizing drugs depends on their TNF binding characteristics, including TNF binding kinetics, ability to bind to membrane-bound TNF and TNF binding stoichiometry. To further elucidate the role of TNF in the process of granuloma development, our modeling and experimental findings on TNF-associated molecular scale aspects of the granuloma can be incorporated into larger scale models describing the immune response to TB infection. Ultimately, these modeling and experimental results can help identify new strategies for TB disease control/therapy

    Global Search for Diverse Competitive Designs

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