2,220 research outputs found

    The Role of Organizational and Interorganizational Factors on Planned Adoption of Electronic Commerce

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    Internet technologies, especially the World Wide Web, are predicted to lead to changes in the transfer of information between trading partners. This paper focuses on identifying organizational and interorganizational factors which will impact the planned adoption of electronic commerce. The interorganizational system will become successfulonly if those factors which are found to have an impact on the adoption of the innovation are handled effectively by the system. Prior to the planned adoption these factors need to be evaluated and managed to ensure a successful adoptio

    High-Affinity Small Molecule Inhibitors of T Cell Costimulation: Compounds for Immunotherapy

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    SummaryCostimulatory molecules are important regulators of T cell activation and thus favored targets for therapeutic manipulation of immune responses. One of the key costimulatory receptors is CD80, which binds the T cell ligands, CD28, and CTLA-4. We describe a set of small compounds that bind with high specificity and low nanomolar affinity to CD80. The compounds have relatively slow off-rates and block both CD28 and CTLA-4 binding, implying that they occlude the shared ligand binding site. The compounds inhibit proinflammatory cytokine release in T cell assays with submicromolar potency, and as such, they represent promising leads for the development of novel therapeutics for immune-mediated inflammatory disease. Our results also suggest that other predominantly β proteins, such as those that dominate the cell surface, may also be accessible as potentially therapeutic targets

    Microbial Lag Phase can be Indicative of, or Independent From, Cellular Stress

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    Measures of microbial growth, used as indicators of cellular stress, are sometimes quantified at a single time-point. In reality, these measurements are compound representations of length of lag, exponential growth-rate, and other factors. Here, we investigate whether length of lag phase can act as a proxy for stress, using a number of model systems (Aspergillus penicillioides; Bacillus subtilis; Escherichia coli; Eurotium amstelodami, E. echinulatum, E. halophilicum, and E. repens; Mrakia frigida; Saccharomyces cerevisiae; Xerochrysium xerophilum; Xeromyces bisporus) exposed to mechanistically distinct types of cellular stress including low water activity, other solute-induced stresses, and dehydration-rehydration cycles. Lag phase was neither proportional to germination rate for X. bisporus (FRR3443) in glycerol-supplemented media (r2 = 0.012), nor to exponential growth-rates for other microbes. In some cases, growth-rates varied greatly with stressor concentration even when lag remained constant. By contrast, there were strong correlations for B. subtilis in media supplemented with polyethylene-glycol 6000 or 600 (r2 = 0.925 and 0.961), and for other microbial species. We also analysed data from independent studies of food-spoilage fungi under glycerol stress (Aspergillus aculeatinus and A. sclerotiicarbonarius); mesophilic/psychrotolerant bacteria under diverse, solute-induced stresses (Brochothrix thermosphacta, Enterococcus faecalis, Pseudomonas fluorescens, Salmonella typhimurium, Staphylococcus aureus); and fungal enzymes under acid-stress (Terfezia claveryi lipoxygenase and Agaricus bisporus tyrosinase). These datasets also exhibited diversity, with some strong- and moderate correlations between length of lag and exponential growth-rates; and sometimes none. In conclusion, lag phase is not a reliable measure of stress because length of lag and growth-rate inhibition are sometimes highly correlated, and sometimes not at all

    Robustness of potential biological removal to monitoring, environmental, and management uncertainties

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    Support for this project was provided by the Lenfest Ocean Program.The potential biological removal (PBR) formula used to determine a reference point for human-caused mortality of marine mammals in the United States has been shown to be robust to several sources of uncertainty. This study investigates the consequences of the quality of monitoring on PBR performance. It also explores stochastic and demographic uncertainty, catastrophic events, sublethal effects of interactions with fishing gear, and the situation of a marine mammal population subject to bycatch in two fisheries, only one of which is managed. Results are presented for two pinniped and two cetacean life histories. Bias in abundance estimates and whether there is a linear relationship between abundance estimates and true abundance most influence conservation performance. Catastrophic events and trends in natural mortality have larger effects than environmental stochasticity. Managing only one of two fisheries with significant bycatch leads, as expected, to a lower probability of achieving conservation management goals, and better outcomes would be achieved if bycatch in all fisheries were managed. The results are qualitatively the same for the four life histories, but estimates of the probability of population recovery differ.Publisher PDFPeer reviewe

    A Provenance-Based Infrastructure to Support the Life Cycle of Executable Papers

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    AbstractAs publishers establish a greater online presence as well as infrastructure to support the distribution of more varied information, the idea of an executable paper that enables greater interaction has developed. An executable paper provides more information for computational experiments and results than the text, tables, and figures of standard papers. Executable papers can bundle computational content that allow readers and reviewers to interact, validate, and explore experiments. By including such content, authors facilitate future discoveries by lowering the barrier to reproducing and extending results. We present an infrastructure for creating, disseminating, and maintaining executable papers. Our approach is rooted in provenance, the documentation of exactly how data, experiments, and results were generated. We seek to improve the experience for everyone involved in the life cycle of an executable paper. The automated capture of provenance information allows authors to easily integrate and update results into papers as they write, and also helps reviewers better evaluate approaches by enabling them to explore experimental results by varying parameters or data. With a provenance-based system, readers are able to examine exactly how a result was developed to better understand and extend published findings

    Incorporating Hydrologic Data and Ecohydrologic Relationships into Ecological Site Descriptions

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    The purpose of this paper is to recommend a framework and methodology for incorporating hydrologic data and ecohydrologic relationships in Ecological Site Descriptions (ESDs) and thereby enhance the utility of ESDs for assessing rangelands and guiding resilience-based management strategies. Resilience-based strategies assess and manage ecological state dynamics that affect state vulnerability and, therefore, provide opportunities to adapt management. Many rangelands are spatially heterogeneous or sparsely vegetated where the vegetation structure strongly influences infiltration and soil retention. Infiltration and soil retention further influence soil water recharge, nutrient availability, and overall plant productivity. These key ecohydrologic relationships govern the ecologic resilience of the various states and community phases on many rangeland ecological sites (ESs) and are strongly affected by management practices, land use, and disturbances. However, ecohydrologic data and relationships are often missing in ESDs and state-and-transition models (STMs). To address this void, we used literature to determine the data required for inclusion of key ecohydrologic feedbacks into ESDs, developed a framework and methodology for data integration within the current ESD structure, and applied the framework to a select ES for demonstrative purposes. We also evaluated the utility of the Rangeland Hydrology and Erosion Model (RHEM) for assessment and enhancement of ESDs based in part on hydrologic function. We present the framework as a broadly applicable methodology for integrating ecohydrologic relationships and feedbacks into ESDs and resilience-based management strategies. Our proposed framework increases the utility of ESDs to assess rangelands, target conservation and restoration practices, and predict ecosystem responses to management. The integration of RHEM technology and our suggested framework on ecohydrologic relations expands the ecological foundation of the overall ESD concept for rangeland management and is well aligned with resilience-based, adaptive management of US rangelands. The proposed enhancement of ESDs will improve communication between private land owners and resource managers and researchers across multiple disciplines in the field of rangeland management

    Genetic signal maximization using environmental regression

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    Joint analyses of correlated phenotypes in genetic epidemiology studies are common. However, these analyses primarily focus on genetic correlation between traits and do not take into account environmental correlation. We describe a method that optimizes the genetic signal by accounting for stochastic environmental noise through joint analysis of a discrete trait and a correlated quantitative marker. We conducted bivariate analyses where heritability and the environmental correlation between the discrete and quantitative traits were calculated using Genetic Analysis Workshop 17 (GAW17) family data. The resulting inverse value of the environmental correlation between these traits was then used to determine a new β coefficient for each quantitative trait and was constrained in a univariate model. We conducted genetic association tests on 7,087 nonsynonymous SNPs in three GAW17 family replicates for Affected status with the β coefficient fixed for three quantitative phenotypes and compared these to an association model where the β coefficient was allowed to vary. Bivariate environmental correlations were 0.64 (± 0.09) for Q1, 0.798 (± 0.076) for Q2, and −0.169 (± 0.18) for Q4. Heritability of Affected status improved in each univariate model where a constrained β coefficient was used to account for stochastic environmental effects. No genome-wide significant associations were identified for either method but we demonstrated that constraining β for covariates slightly improved the genetic signal for Affected status. This environmental regression approach allows for increased heritability when the β coefficient for a highly correlated quantitative covariate is constrained and increases the genetic signal for the discrete trait
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