247 research outputs found

    Spatial snow water equivalent estimation for mountainous areas using wireless-sensor networks and remote-sensing products

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    We developed an approach to estimate snow water equivalent (SWE) through interpolation of spatially representative point measurements using a k-nearest neighbors (k-NN) algorithm and historical spatial SWE data. It accurately reproduced measured SWE, using different data sources for training and evaluation. In the central-Sierra American River basin, we used a k-NN algorithm to interpolate data from continuous snow-depth measurements in 10 sensor clusters by fusing them with 14 years of daily 500-m resolution SWE-reconstruction maps. Accurate SWE estimation over the melt season shows the potential for providing daily, near real-time distributed snowmelt estimates. Further south, in the Merced-Tuolumne basins, we evaluated the potential of k-NN approach to improve real-time SWE estimates. Lacking dense ground-measurement networks, we simulated k-NN interpolation of sensor data using selected pixels of a bi-weekly Lidar-derived snow water equivalent product. k-NN extrapolations underestimate the Lidar-derived SWE, with a maximum bias of −10 cm at elevations below 3000 m and +15 cm above 3000 m. This bias was reduced by using a Gaussian-process regression model to spatially distribute residuals. Using as few as 10 scenes of Lidar-derived SWE from 2014 as training data in the k-NN to estimate the 2016 spatial SWE, both RMSEs and MAEs were reduced from around 20–25 cm to 10–15 cm comparing to using SWE reconstructions as training data. We found that the spatial accuracy of the historical data is more important for learning the spatial distribution of SWE than the number of historical scenes available. Blending continuous spatially representative ground-based sensors with a historical library of SWE reconstructions over the same basin can provide real-time spatial SWE maps that accurately represents Lidar-measured snow depth; and the estimates can be improved by using historical Lidar scans instead of SWE reconstructions

    Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

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    BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

    Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

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    Background:Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route.Methodology/Principal Findings:Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease.Conclusions/Significance:Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug. © 2014 Caroline et al
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