4,767 research outputs found

    A Lesson in the Development of the Law

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    VOSpace: a Prototype for Grid 2.0

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    As Grid 1.0 was characterized by distributed computation, so Grid 2.0 will be characterized by distributed data and the infrastructure needed to support and exploit it: the emerging success of Amazon S3 is already testimony to this. VOSpace is the IVOA interface standard for accessing distributed data. Although the base definition (VOSpace 1.0) only relates to flat, unconnected data stores, subsequent versions will add additional layers of functionality. In this paper, we consider how incorporating popular web concepts such as folksonomies (tagging), social networking, and data-spaces could lead to a much richer data environment than provided by a traditional collection of networked data stores

    Technology benefits and ground test facilities for high-speed civil transport development

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    The advanced technology base necessary for successful twenty-first century High-Speed Civil Transport (HSCT) aircraft will require extensive ground testing in aerodynamics, propulsion, acoustics, structures, materials, and other disciplines. This paper analyzes the benefits of advanced technology application to HSCT concepts, addresses the adequacy of existing groundbased test facilities, and explores the need for new facilities required to support HSCT development. A substantial amount of HSCT-related ground testing can be accomplished in existing facilities. The HSCT development effort could also benefit significantly from some new facilities initially conceived for testing in other aeronautical research areas. A new structures testing facility is identified as critically needed to insure timely technology maturation

    Cancer immunology and canine malignant melanoma: a comparative review

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    Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current “gold standard” treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics

    A metastatic secretory gastric plasmacytoma with aberrant CD3 expression in a dog

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    A 10-year-old crossbred dog was presented with a 6-week history of hematemesis, melena, anorexia, and lethargy. Clinical evaluation revealed a gastric mass with a regional lymphadenomegaly as well as a monoclonal gammopathy manifesting as hyperglobulinemia. Cytologic and histopathologic analyses were consistent with a round cell neoplasm; neoplastic cells showed nuclear immunoreactivity for MUM1 and diffuse cytoplasmic reactivity for CD3. Polymerase chain reactions performed on fixed and fresh tissue identified a clonal rearrangement with an IgH primer set. An extramedullary plasmacytoma (EMP) was confirmed by cellular morphology and molecular diagnostics. Following an objective response to chemotherapy, the dog was euthanized 8 months after diagnosis, and a postmortem examination confirmed the clinical findings. This is the first reported case of a monoclonal gammopathy secondary to a gastric EMP coupled with aberrant expression of CD3 in an aggressive plasmacytic tumor, and highlights the utility of molecular diagnostics for classifying atypical hemolymphoid neoplasms

    Optimizing astrophotonic spatial reformatters using simulated on-sky performance

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    One of the most useful techniques in astronomical instrumentation is image slicing. It enables a spectrograph to have a more compact angular slit, whilst retaining throughput and increasing resolving power. Astrophotonic components like the photonic lanterns and photonic reformatters can be used to replace bulk optics used so far. This study investigates the performance of such devices using end-to-end simulations to approximate realistic on-sky conditions. It investigates existing components, tries to optimize their performance and aims to understand better how best to design instruments to maximize their performance. This work complements the recent work in the field and provides an estimation for the performance of the new components.Comment: Conference proceedings in SPIE 2018 Austin Texa

    The receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis

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    PTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here we demonstrate that PTPRB negatively regulates branching morphogenesis in the mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in estrogen receptor positive luminal cells. During mammary development Ptprb expression is down-regulated during puberty, a period of extensive of ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of FGFR activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology
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