368 research outputs found

    Parallel Aerodynamic Simulation on Open Workstation Clusters. Department of Aerospace Engineering Report no. 9830

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    The parallel execution of an aerodynamic simulation code on a non-dedicated, heterogeneous cluster of workstations is examined. This type of facility is commonly available to CFD developers and users in academia, industry and government laboratories and is attractive in terms of cost for CFD simulations. However, practical considerations appear at present to be discouraging widespread adoption of this technology. The main obstacles to achieving an efficient, robust parallel CFD capability in a demanding multi-user environment are investigated. A static load-balancing method, which takes account of varying processor speeds, is described. A dynamic re-allocation method to account for varying processor loads has been developed. Use of proprietary management software has facilitated the implementation of the method

    Approximate Jacobians for the Solution of the Euler and Navier-Stokes Equations. G.U. Aero Report 9705

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    This paper describes a method for efficiently solving the steady-state Euler and Navier-Stokes equations. Robustness is achieved through the use of an upwind TVD scheme for discretising the convective terms. The approximate solution is advanced in time implicitly and the linear system arising at each implicit step is solved using a Conjugate Gradient type method. The main emphasis of this paper is on the use of Jacobian matrices associated with a simpler spatial discretisation. This leads to better conditioned linear systems. The resulting method has lower memory and CPU-time requirements when compared with the one using exact Jacobians

    Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells

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    The final published version can be found here: http://dx.doi.org/10.1073/pnas.1411390111M.C. is the recipient of a Bennett Fellowship from Leukaemia and Lymphoma Research (ref. 12002). M.A.B. is supported by a GlaxoSmithKline Oncology–Biotechnology and Biological Sciences Research Council Collaborative Awards in Science and Engineering PhD studentship. This work was supported by National Institutes of Health Grants GM087507 and GM102336 (to T.E.D.)

    Health promotion and screening for people with an intellectual disability

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    People with intellectual disability have significantly worse health than those without, and have a higher level of complex health needs. The life expectancy for men and women is 13 and 20 years shorter, respectively, than the general population. The increasing role of general practice in delivering and coordinating care across health and social care settings requires expert generalist skills to implement an integrated approach to care. This article explores how general practice can improve the health of people with intellectual disability, by making reasonable adjustments within health promotion, disease prevention, screening and detection

    Co-activation of NF-κB and MYC renders cancer cells addicted to IL6 for survival and phenotypic stability

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    NF-κB and MYC are found co-deregulated in human B and plasma-cell cancers. In physiology, NF-κB is necessary for terminal B-to-plasma cell differentiation, whereas MYC repression is required. It is thus unclear if NF-κB/MYC co-deregulation is developmentally compatible in carcinogenesis and/or impacts cancer cell differentiation state, possibly uncovering unique sensitivities. Using a mouse system to trace cell lineage and oncogene activation we found that NF-κB/MYC co-deregulation originated cancers with a plasmablast-like phenotype, alike human plasmablastic-lymphoma and was linked to t(8;14)[MYC-IGH] multiple myeloma. Notably, in contrast to NF-κB or MYC activation alone, co-deregulation rendered cells addicted to IL6 for survival and phenotypic stability. We propose that conflicting oncogene-driven differentiation pressures can be accommodated at a cost in poorly-differentiated cancers. SIGNIFICANCE: Our studies improve the understanding of cancer pathogenesis by demonstrating that co-deregulation of NF-κB and MYC synergize in forming a cancer with a poorly-differentiated state. The cancers in the mouse system share features with human Plasmablastic lymphoma that has a dismal prognosis and no standard of care, and with t(8;14)[MYC-IGH] Multiple myeloma, which is in overall resistant to standard therapy. Notably, we found that NF-κB and MYC co-deregulation uniquely render cells sensitive to IL6 deprivation, providing a road-map for patient selection. Because of the similarity of the cancers arising in the compound mutant mouse model with that of human Plasmablastic lymphoma and t(8;14)[MYC-IGH] Multiple myeloma, this model could serve in preclinical testing to investigate novel therapies for these hard-to-treat diseases

    Gene Expression Profiling of B Cell Lymphoma in Dogs Reveals Dichotomous Metabolic Signatures Distinguished by Oxidative Phosphorylation

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    Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health
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