19 research outputs found

    The Integrated WRF/Urban Modeling System: Development, Evaluation, and Applications to Urban Environmental Problems

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    To bridge the gaps between traditional mesoscale modeling and microscale modeling, the National Center for Atmospheric Research (NCAR), in collaboration with other agencies and research groups, has developed an integrated urban modeling system coupled to the Weather Research and Forecasting (WRF) model as a community tool to address urban environmental issues. The core of this WRF/urban modeling system consists of: 1) three methods with different degrees of freedom to parameterize urban surface processes, ranging from a simple bulk parameterization to a sophisticated multi-layer urban canopy model with an indoor outdoor exchange sub-model that directly interacts with the atmospheric boundary layer, 2) coupling to fine-scale Computational Fluid Dynamic (CFD) Reynolds-averaged Navier–Stokes (RANS) and Large-Eddy Simulation (LES) models for Transport and Dispersion (T&D) applications, 3) procedures to incorporate high-resolution urban land-use, building morphology, and anthropogenic heating data using the National Urban Database and Access Portal Tool (NUDAPT), and 4) an urbanized high-resolution land-data assimilation system (u-HRLDAS). This paper provides an overview of this modeling system; addresses the daunting challenges of initializing the coupled WRF/urban model and of specifying the potentially vast number of parameters required to execute the WRF/urban model; explores the model sensitivity to these urban parameters; and evaluates the ability of WRF/urban to capture urban heat islands, complex boundary layer structures aloft, and urban plume T&D for several major metropolitan regions. Recent applications of this modeling system illustrate its promising utility, as a regional climate-modeling tool, to investigate impacts of future urbanization on regional meteorological conditions and on air quality under future climate change scenarios

    Melanoma Spheroids Grown Under Neural Crest Cell Conditions Are Highly Plastic Migratory/Invasive Tumor Cells Endowed with Immunomodulator Function

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    International audienceBACKGROUND: The aggressiveness of melanoma tumors is likely to rely on their well-recognized heterogeneity and plasticity. Melanoma comprises multi-subpopulations of cancer cells some of which may possess stem cell-like properties. Although useful, the sphere-formation assay to identify stem cell-like or tumor initiating cell subpopulations in melanoma has been challenged, and it is unclear if this model can predict a functional phenotype associated with aggressive tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the molecular and functional phenotypes of melanoma spheroids formed in neural crest cell medium. Whether from metastatic or advanced primary tumors, spheroid cells expressed melanoma-associated markers. They displayed higher capacity to differentiate along mesenchymal lineages and enhanced expression of SOX2, NANOG, KLF4, and/or OCT4 transcription factors, but not enhanced self-renewal or tumorigenicity when compared to their adherent counterparts. Gene expression profiling attributed a neural crest cell signature to these spheroids and indicated that a migratory/invasive and immune-function modulating program could be associated with these cells. In vitro assays confirmed that spheroids display enhanced migratory/invasive capacities. In immune activation assays, spheroid cells elicited a poorer allogenic response from immune cells and inhibited mitogen-dependent T cells activation and proliferation more efficiently than their adherent counterparts. Our findings reveal a novel immune-modulator function of melanoma spheroids and suggest specific roles for spheroids in invasion and in evasion of antitumor immunity. CONCLUSION/SIGNIFICANCE: The association of a more plastic, invasive and evasive, thus a more aggressive tumor phenotype with melanoma spheroids reveals a previously unrecognized aspect of tumor cells expanded as spheroid cultures. While of limited efficiency for melanoma initiating cell identification, our melanoma spheroid model predicted aggressive phenotype and suggested that aggressiveness and heterogeneity of melanoma tumors can be supported by subpopulations other than cancer stem cells. Therefore, it could be constructive to investigate melanoma aggressiveness, relevant to patients and clinical transferability

    Etude de la régulation de l'expression des molécules du complexe d'histocompatibilitéde classe II et de ses altérations pathologiques

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    Les molécules du CMH II constituent un élément essentiel à la mise en place de la réponse immunitaire. La régulation des gènes du CMH II s'exerce au niveau transcriptionnel. Quatre facteurs (RFXANK, RFX5, RFXAP et CIITA) sont impliqués dans la régulation, mais la spécifité de tissu est conférée par CIITA. Des initiations différentielles de la traduction sont responsables de l'existence des isoformes F-et B-CIITA. Qui plus est, les altérations de l'expression du CMH II observées dans plusieurs types cellulaires tumoraux proviennent de la dérégulation de l'expression de CIITA. Ainsi, l'expression du CMH dans les mélanomes est due à l'expression constitutive de B-CHTA, et l'absence d'expression de la lignée de lymphome B Rec-1 provient d'une altération dans MHC2TAPARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
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