516 research outputs found

    The Lawyers and N.R.A.

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    Regulation of Ccr5 ise on Primary Cd4+ Lymphocytes by R5X4 HIV-1

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    HIV-1 strains that use CCR5 predominate after transmission and during the asymptomatic period of disease. However, in up to half of infected people, variants that use CXCR4 emerge, coincident with accelerated disease progression. The earliest CXCR4 using strains to appear, called R5X4 viruses, usually retain CCR5 use. Prototype R5X4 HIV-1 isolates infect macrophages using CCR5 and CXCR4, but CD4+ lymphocyte infection by these viruses is mediated predominantly by CXCR4. Here, we sought to identify obstacles to CCR5 use on CD4+ lymphocytes by R5X4 HIV-1. Using a panel of R5X4 Envs we found that, although CXCR4 was the predominant coreceptor used to infect CD4+ lymphocytes, there was a spectrum of CCR5 use. Greater CCR5 use on lymphocytes correlated with relative resistance to inhibition by CCR5 mAbs and small molecule antagonists in CCR5+ indicator cells. Increasing CCR5 expression on primary lymphocytes through cytokine stimulation or lentiviral transduction increased the proportion of entry mediated by CCR5 for all R5X4 isolates except 89.6. Env dependence on CCR5 density was then evaluated using a cell line in which levels of CD4 and CCR5 could be independently regulated. At non-limiting CD4 levels, strains with greater lymphocyte CCR5 use were better able to exploit limiting levels of CCR5, whereas those that used lymphocyte CCR5 poorly were more sensitive to reductions in CCR5 levels. Evaluation of the V3 sequences of the R5X4 viruses using algorithms that ..

    An observational study of children interacting with an augmented story book

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    We present findings of an observational study investigating how young children interact with augmented reality story books. Children aged between 6 and 7 read and interacted with one of two story books aimed at early literacy education. The books pages were augmented using animated virtual 3D characters, sound, and interactive tasks. Introducing novel media to young children requires system and story designers to consider not only technological issues but also questions arising from story design and the design of interactive sequences. We discuss findings of our study and implications regarding the implementation of augmented story books

    Range Flight Safety Requirements

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    The purpose of this NASA Technical Standard is to provide the technical requirements for the NPR 8715.5, Range Flight Safety Program, in regards to protection of the public, the NASA workforce, and property as it pertains to risk analysis, Flight Safety Systems (FSS), and range flight operations. This standard is approved for use by NASA Headquarters and NASA Centers, including Component Facilities and Technical and Service Support Centers, and may be cited in contract, program, and other Agency documents as a technical requirement. This standard may also apply to the Jet Propulsion Laboratory or to other contractors, grant recipients, or parties to agreements to the extent specified or referenced in their contracts, grants, or agreements, when these organizations conduct or participate in missions that involve range flight operations as defined by NPR 8715.5.1.2.2 In this standard, all mandatory actions (i.e., requirements) are denoted by statements containing the term shall.1.3 TailoringTailoring of this standard for application to a specific program or project shall be formally documented as part of program or project requirements and approved by the responsible Technical Authority in accordance with NPR 8715.3, NASA General Safety Program Requirements

    TB207: A Manual for Remote Sensing of Maine Lake Clarity

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    The purpose of this manual is to support use of satellite-based remote sensing for statewide lake water-quality monitoring in Maine. The authors describe step-by-step methods that combine Landsat and MODIS satellite data with field-collected Secchi disk data for statewide assessment of lake water clarity. Landsat can be simul­taneously used to assess more than Maine 1,000 lakes ≥ 8 ha, whereas MODIS can be used to assess a maximum of 364 lakes ≥ 100 ha (250-m image resolution) or 83 lakes ≥ 400 ha (500-m image resolution). Although the methods were specifically developed for Maine, other states or non-Maine agen­cies may find these methods as useful starting points in developing their own protocols for regional remote lake monitoring.https://digitalcommons.library.umaine.edu/aes_techbulletin/1012/thumbnail.jp

    R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies

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    Entry coreceptor use by HIV-1 plays a pivotal role in viral transmission, pathogenesis and disease progression. In many HIV-1 infected individuals, there is an expansion in coreceptor use from CCR5 to include CXCR4, which is associated with accelerated disease progression. While targeting HIV-1 envelope interactions with coreceptor during viral entry is an appealing approach to combat the virus, the methods of determining coreceptor use and the changes in coreceptor use that can occur during disease progression are important factors that may complicate the use of therapies targeting this stage of HIV-1 replication. Indicator cells are typically used to determine coreceptor use by HIV-1 in vitro, but the coreceptors used on these cells can differ from those used on primary cell targets. V3 based genetic sequence algorithms are another method used to predict coreceptor use by HIV-1 strains. However, these algorithms were developed to predict coreceptor use in cell lines and not primary cells and, furthermore, are not highly accurate for some classes of viruses. This article focuses on R5X4 HIV-1, the earliest CXCR4-using variants, reviewing the pattern of coreceptor use on primary CD4+ lymphocytes and macrophages, the relationship between primary cell coreceptor use and the two principal approaches to coreceptor analysis (genetic prediction and indicator cell phenotyping), and the implications of primary cell coreceptor use by these strains for treatment with a new class of small molecule antagonists that inhibit CCR5-mediated entry. These are important questions to consider given the development of new CCR5 blocking therapies and the prognosis associated with CXCR4 use
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