283 research outputs found

    Security by Spatial Reference:Using Relative Positioning to Authenticate Devices for Spontaneous Interaction

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    Spontaneous interaction is a desirable characteristic associated with mobile and ubiquitous computing. The aim is to enable users to connect their personal devices with devices encountered in their environment in order to take advantage of interaction opportunities in accordance with their situation. However, it is difficult to secure spontaneous interaction as this requires authentication of the encountered device, in the absence of any prior knowledge of the device. In this paper we present a method for establishing and securing spontaneous interactions on the basis of emphspatial references that capture the spatial relationship of the involved devices. Spatial references are obtained by accurate sensing of relative device positions, presented to the user for initiation of interactions, and used in a peer authentication protocol that exploits a novel mechanism for message transfer over ultrasound to ensures spatial authenticity of the sender

    Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity

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    Norovirus gastroenteritis is amajor public health burden worldwide. Although fecal shedding is important for transmission of enteric viruses, little is known about the immune factors that restrict persistent enteric infection. We report here that although the cytokines interferon-α (IFN-α) and IFN-β prevented the systemic spread of murine norovirus (MNoV), only IFN-λcontrolled persistent enteric infection. Infection-dependent induction of IFN-λ was governed by the MNoV capsid protein and correlated with diminished enteric persistence. Treatment of established infection with IFN-λ cured mice in a manner requiring nonhematopoietic cell expression of the IFN-λ receptor, Ifnlr1, and independent of adaptive immunity. These results suggest the therapeutic potential of IFN-λ for curing virus infections in the gastrointestinal tract

    Experimental Transmission of Kaposi's Sarcoma–Associated Herpesvirus (Kshv/Hhv-8) to Scid-Hu Thy/Liv Mice

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    Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) is a novel human lymphotropic herpesvirus linked to several human neoplasms. To date, no animal model for infection by this virus has been described. We have examined the susceptibility of C.B-17 scid/scid mice implanted with human fetal thymus and liver grafts (SCID-hu Thy/Liv mice) to KSHV infection. KSHV virions were inoculated directly into the implants, and viral DNA and mRNA production was assayed using real-time quantitative polymerase chain reaction. This revealed a biphasic infection, with an early phase of lytic replication accompanied and followed by sustained latency. Ultraviolet irradiation of the inoculum abolished all DNA- and mRNA-derived signals, and infection was inhibited by ganciclovir. Viral gene expression was most abundant in CD19+ B lymphocytes, suggesting that this model faithfully mimics the natural tropism of this virus. Short-term coinfection with HIV-1 did not alter the course of KSHV replication, nor did KSHV alter levels of HIV-1 p24 during the acute phase of the infection. Although no disease was evident in infected animals, SCID-hu Thy/Liv mice should allow the detailed study of KSHV tropism, latency, and drug susceptibility

    Multi-stakeholder consensus on a target product profile for an HIV cure

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    Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures

    Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART

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    The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates

    Temporal dynamics of the shrub and herbaceous layer of an area of moist grassland in Alto Paraíso de Goiás, Brazil

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    Este trabalho avaliou a dinâmica estrutural e fl orística de uma comunidade de espécies herbáceo-arbustivas de uma área de campo limpo úmido em Alto Paraíso de Goiás, o primeiro inventário realizado em 2000 (T0) e o segundo em 2007 (T1). A diversidade de Shannon entre os períodos foi comparada pelo teste-t de Hutcheson e a similaridade fl orística, pelo índice de similaridade de Chao-Sørensen. As relações fl orísticas e a cobertura, entre os períodos e as linhas, foram avaliadas por meio de análises de correspondência retifi cada (DCA). Foram amostradas 98 espécies, 88 no T0 e 67 no T1, sendo 31 exclusivas do T0 e 10 do T1. A diversidade fl orística na comunidade foi elevada nos dois períodos, porém diferente entre esses (t = 7,12; p < 0,001), devido a variação no número e cobertura das espécies. A similaridade entre os dois inventários foi alta (Chao-Sørensen ± IC = 0,841 ± 0,074). A ordenação por DCA indicou relações entre a composição fl orística e a cobertura com o gradiente de umidade e de matéria orgânica no solo identifi cados em T0. Houve modifi cações nas linhas em zonas sazonais, as quais se tornaram mais semelhantes às linhas constantemente saturadas por água. Em um intervalo de sete anos o campo limpo úmido apresentou mudanças na composição fl orística e, principalmente na estrutura devido o aumento da cobertura de espécies perenes, cespitosas e entouceiradas, que foram favorecidas pela maior umidade no solo em resposta à elevação da pluviosidade da região. __________________________________________________________________________________________ ABSTRACTTh is study evaluated the fl oristic and structural dynamics of a community of herbaceous-shrub species in an area of moist grassland in Alto Paraíso de Goiás. Th e fi rst inventory was undertaken in 2000 (T0) and the second in 2007 (T1). Shannon’s diversity between the periods was compared by Hutchesons´s t-test, and the fl oristic similarity by the Chao-Sørensen similarity index. Floristic composition and cover, between periods and lines, were evaluated by detrended correspondence analysis (DCA). We sampled 98 species, 88 at T0 and 67 at T1; 31 were unique to T0 and 10 to T1. Floristic diversity in the community was high in both periods, but diff erent between them (t = 7.12, p <0.001), due to variation in species number and coverage. Similarity between the two surveys was high (Chao-Sørensen CI = ± 0.841 ± 0.074). Th e DCA ordination indicated relationships between the fl oristic composition and cover with a gradient of moisture and organic matter in the soil identifi ed in T0. Th ere were changes in the lines in the seasonal zones, which became more similar in those constantly saturated with water. During an interval of seven years the moist grassland showed changes in fl oristic composition and mainly in structure due to increased cover of the clumped tussock perennial species, which were favored by higher soil moisture due to high rainfall in the region

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
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