1,334 research outputs found

    NewsPad: Designing for Collaborative Storytelling in Neighborhoods

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    This paper introduces design explorations in neighborhood collaborative storytelling. We focus on blogs and citizen journalism, which have been celebrated as a means to meet the reporting needs of small local communities. These bloggers have limited capacity and social media feeds seldom have the context or readability of news stories. We present NewsPad, a content editor that helps communities create structured stories, collaborate in real time, recruit contributors, and syndicate the editing process. We evaluate NewsPad in four pilot deployments and find that the design elicits collaborative story creation.Comment: NewsPad: designing for collaborative storytelling in neighborhoods. In Proceedings of the extended abstracts of the 32nd annual ACM conference on Human factors in computing systems (CHI EA 2014

    In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi.

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    BackgroundCruzain, the major cysteine protease of Trypanosoma cruzi, is an essential enzyme for the parasite life cycle and has been validated as a viable target to treat Chagas' disease. As a proof-of-concept, K11777, a potent inhibitor of cruzain, was found to effectively eliminate T. cruzi infection and is currently a clinical candidate for treatment of Chagas' disease.Methodology/principal findingsWRR-483, an analog of K11777, was synthesized and evaluated as an inhibitor of cruzain and against T. cruzi proliferation in cell culture. This compound demonstrates good potency against cruzain with sensitivity to pH conditions and high efficacy in the cell culture assay. Furthermore, WRR-483 also eradicates parasite infection in a mouse model of acute Chagas' disease. To determine the atomic-level details of the inhibitor interacting with cruzain, a 1.5 A crystal structure of the protease in complex with WRR-483 was solved. The structure illustrates that WRR-483 binds covalently to the active site cysteine of the protease in a similar manner as other vinyl sulfone-based inhibitors. Details of the critical interactions within the specificity binding pocket are also reported.ConclusionsWe demonstrate that WRR-483 is an effective cysteine protease inhibitor with trypanocidal activity in cell culture and animal model with comparable efficacy to K11777. Crystallographic evidence confirms that the mode of action is by targeting the active site of cruzain. Taken together, these results suggest that WRR-483 has potential to be developed as a treatment for Chagas' disease

    Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection

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    In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (−10%; range: −52.2% to 4.0%; P < 0.01), 20 minutes (−17.4%; −27.9% to 0.0%; P < 0.01), and 30 minutes (−8.5%; −34.4% to 2.0%; P < 0.01) after CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold

    The total assessment profile, volume 2

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    Appendices are presented which include discussions of interest formulas, factors in regionalization, parametric modeling of discounted benefit-sacrifice streams, engineering economic calculations, and product innovation. For Volume 1, see

    The total assessment profile, volume 1

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    A methodology is described for the evaluation of societal impacts associated with the implementation of a new technology. Theoretical foundations for the methodology, called the total assessment profile, are established from both the economic and social science perspectives. The procedure provides for accountability of nonquantifiable factors and measures through the use of a comparative value matrix by assessing the impacts of the technology on the value system of the society

    Using ecological propensity score to adjust for missing confounders in small area studies

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    Small area ecological studies are commonly used in epidemiology to assess the impact of area level risk factors on health outcomes when data are only available in an aggregated form. However, the resulting estimates are often biased due to unmeasured confounders, which typically are not available from the standard administrative registries used for these studies. Extra information on confounders can be provided through external data sets such as surveys or cohorts, where the data are available at the individual level rather than at the area level; however, such data typically lack the geographical coverage of administrative registries. We develop a framework of analysis which combines ecological and individual level data from different sources to provide an adjusted estimate of area level risk factors which is less biased. Our method (i) summarizes all available individual level confounders into an area level scalar variable, which we call ecological propensity score (EPS), (ii) implements a hierarchical structured approach to impute the values of EPS whenever they are missing, and (iii) includes the estimated and imputed EPS into the ecological regression linking the risk factors to the health outcome. Through a simulation study, we show that integrating individual level data into small area analyses via EPS is a promising method to reduce the bias intrinsic in ecological studies due to unmeasured confounders; we also apply the method to a real case study to evaluate the effect of air pollution on coronary heart disease hospital admissions in Greater London

    Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay.

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    Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes

    A Sensitivity Study on the Effects of Particle Chemistry, Asphericity and Size on the Mass Extinction Efficiency of Mineral Dust in the Earth's Atmosphere: From the Near to Thermal IR

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    To determine a plausible range of mass extinction efficiencies (MEE) of terrestrial atmospheric dust from the near to thermal IR, sensitivity analyses are performed over an extended range of dust microphysical and chemistry perturbations. The IR values are subsequently compared to those in the near-IR, to evaluate spectral relationships in their optical properties. Synthesized size distributions consistent with measurements, model particle size, while composition is defined by the refractive indices of minerals routinely observed in dust, including the widely used OPAC/Hess parameterization. Single-scattering properties of representative dust particle shapes are calculated using the T-matrix, Discrete Dipole Approximation and Lorenz-Mie light-scattering codes. For the parameterizations examined, MEE ranges from nearly zero to 1.2 square meters per gram, with the higher values associated with non-spheres composed of quartz and gypsum. At near-IR wavelengths, MEE for non-spheres generally exceeds those for spheres, while in the thermal IR, shape-induced changes in MEE strongly depend on volume median diameter (VMD) and wavelength, particularly for MEE evaluated at the mineral resonant frequencies. MEE spectral distributions appear to follow particle geometry and are evidence for shape dependency in the optical properties. It is also shown that non-spheres best reproduce the positions of prominent absorption peaks found in silicates. Generally, angular particles exhibit wider and more symmetric MEE spectral distribution patterns from 8-10 micrometers than those with smooth surfaces, likely due to their edge-effects. Lastly, MEE ratios allow for inferring dust optical properties across the visible-IR spectrum. We conclude the MEE of dust aerosol are significant for the parameter space investigated, and are a key component for remote sensing applications and the study of direct aerosol radiative effects
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