16 research outputs found

    Visual Exploration of Combined Architectural and Metric Information

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    We present MetricView, a software visualization and exploration tool that combines traditional UML diagram visualization with metric visualization in an effective way. MetricView is very easy and natural to use for software architects and developers yet offers a powerful set of mechanisms that allow fine customization of the visualizations for getting specific insights. We discuss several visual and architectural design choices which turned out to be important in the construction of MetricView, and illustrate our approach with several results using real-life datasets

    Hyaluronate Fragments Reverse Skin Atrophy by a CD44-Dependent Mechanism

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    BACKGROUND: Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present. METHODS AND FINDINGS: Atrophic skin displays a decreased hyaluronate (HA) content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF) on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000–400,000 Da) but not with small-size HAF (HAFs; <50,000 Da) or large-size HAF (HAFl; >400,000 Da) induced wild-type (wt) but not CD44-deficient (CD44(−/−)) keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44(−/−) mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF) and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3), and by tissue inhibitor of metalloproteinase-3 (TIMP-3). CONCLUSIONS: Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy

    Spegling av barns identitet. Pedagogers syn på hur de i samspel påverkar barns identitetsskapande

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    We present MetricView, a software visualization and exploration tool that combines traditional UML diagram visualization with metric visualization in an effective way. MetricView is very easy and natural to use for software architects and developers yet offers a powerful set of mechanisms that allow fine customization of the visualizations for getting specific insights. We discuss several visual and architectural design choices which turned out to be important in the construction of MetricView, and illustrate our approach with several results using real-life datasets.

    Oligosaccharides of hyaluronan activate dendritic cells via tolllike receptor 4

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    Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow–derived DCs from C3H/ HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHAinduced phenotypic and functional maturation. Conversely, DCs from TLR-2–deficient mice were still susceptible to sHA. In accordance, addition of an anti–TLR-4 mAb to human monocyte–derived DCs blocked sHA-induced tumor necrosis factor � production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAPkinases and nuclear translocation of nuclear factor (NF)-�B, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHAinduced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on th

    Induction of CD4 +

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