2,509 research outputs found

    Evaluating the Economic Response to Japan's Earthquake

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    This paper compares the 1995 Kobe earthquake with the more recent one in Tohoku. The impact of the recent earthquake on industrial production was much larger and long-lasting than that of the 1995 earthquake. We find that very little of this can be explained by differences in government expenditures or private consumption. However, we find very substantial differences in energy production in the wake of the two earthquakes. The substantial and persistent drop in energy output is likely to have exacerbated supply disruptions and may continue to slow the pace of recovery. Moreover, we provide some evidence that Japan's increasing reliance on fossil fuel sources of energy is likely to result in a large number of deaths and increases in morbidity due to increased air pollution. These results highlight the difficulties that Japan is likely to face in its move away from nuclear power.

    CellMiner: a relational database and query tool for the NCI-60 cancer cell lines

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    <p>Abstract</p> <p>Background</p> <p>Advances in the high-throughput omic technologies have made it possible to profile cells in a large number of ways at the DNA, RNA, protein, chromosomal, functional, and pharmacological levels. A persistent problem is that some classes of molecular data are labeled with gene identifiers, others with transcript or protein identifiers, and still others with chromosomal locations. What has lagged behind is the ability to integrate the resulting data to uncover complex relationships and patterns. Those issues are reflected in full form by molecular profile data on the panel of 60 diverse human cancer cell lines (the NCI-60) used since 1990 by the U.S. National Cancer Institute to screen compounds for anticancer activity. To our knowledge, CellMiner is the first online database resource for integration of the diverse molecular types of NCI-60 and related meta data.</p> <p>Description</p> <p>CellMiner enables scientists to perform advanced querying of molecular information on NCI-60 (and additional types) through a single web interface. CellMiner is a freely available tool that organizes and stores raw and normalized data that represent multiple types of molecular characterizations at the DNA, RNA, protein, and pharmacological levels. Annotations for each project, along with associated metadata on the samples and datasets, are stored in a MySQL database and linked to the molecular profile data. Data can be queried and downloaded along with comprehensive information on experimental and analytic methods for each data set. A Data Intersection tool allows selection of a list of genes (proteins) in common between two or more data sets and outputs the data for those genes (proteins) in the respective sets. In addition to its role as an integrative resource for the NCI-60, the CellMiner package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types.</p> <p>Conclusion</p> <p>CellMiner is a relational database tool for storing, querying, integrating, and downloading molecular profile data on the NCI-60 and other cancer cell types. More broadly, it provides a template to use in providing such functionality for other molecular profile data generated by academic institutions, public projects, or the private sector. CellMiner is available online at <url>http://discover.nci.nih.gov/cellminer/</url>.</p

    Bayesian Bounds on Parameter Estimation Accuracy for Compact Coalescing Binary Gravitational Wave Signals

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    A global network of laser interferometric gravitational wave detectors is projected to be in operation by around the turn of the century. Here, the noisy output of a single instrument is examined. A gravitational wave is assumed to have been detected in the data and we deal with the subsequent problem of parameter estimation. Specifically, we investigate theoretical lower bounds on the minimum mean-square errors associated with measuring the parameters of the inspiral waveform generated by an orbiting system of neutron stars/black holes. Three theoretical lower bounds on parameter estimation accuracy are considered: the Cramer-Rao bound (CRB); the Weiss-Weinstein bound (WWB); and the Ziv-Zakai bound (ZZB). We obtain the WWB and ZZB for the Newtonian-form of the coalescing binary waveform, and compare them with published CRB and numerical Monte-Carlo results. At large SNR, we find that the theoretical bounds are all identical and are attained by the Monte-Carlo results. As SNR gradually drops below 10, the WWB and ZZB are both found to provide increasingly tighter lower bounds than the CRB. However, at these levels of moderate SNR, there is a significant departure between all the bounds and the numerical Monte-Carlo results.Comment: 17 pages (LaTeX), 4 figures. Submitted to Physical Review

    High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID)

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    BACKGROUND: We previously developed GoMiner, an application that organizes lists of 'interesting' genes (for example, under-and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. The original version of GoMiner was oriented toward visualization and interpretation of the results from a single microarray (or other high-throughput experimental platform), using a graphical user interface. Although that version can be used to examine the results from a number of microarrays one at a time, that is a rather tedious task, and original GoMiner includes no apparatus for obtaining a global picture of results from an experiment that consists of multiple microarrays. We wanted to provide a computational resource that automates the analysis of multiple microarrays and then integrates the results across all of them in useful exportable output files and visualizations. RESULTS: We now introduce a new tool, High-Throughput GoMiner, that has those capabilities and a number of others: It (i) efficiently performs the computationally-intensive task of automated batch processing of an arbitrary number of microarrays, (ii) produces a human-or computer-readable report that rank-orders the multiple microarray results according to the number of significant GO categories, (iii) integrates the multiple microarray results by providing organized, global clustered image map visualizations of the relationships of significant GO categories, (iv) provides a fast form of 'false discovery rate' multiple comparisons calculation, and (v) provides annotations and visualizations for relating transcription factor binding sites to genes and GO categories. CONCLUSION: High-Throughput GoMiner achieves the desired goal of providing a computational resource that automates the analysis of multiple microarrays and integrates results across all of the microarrays. For illustration, we show an application of this new tool to the interpretation of altered gene expression patterns in Common Variable Immune Deficiency (CVID). High-Throughput GoMiner will be useful in a wide range of applications, including the study of time-courses, evaluation of multiple drug treatments, comparison of multiple gene knock-outs or knock-downs, and screening of large numbers of chemical derivatives generated from a promising lead compound

    Effect of daily chlorhexidine bathing on hospital-acquired infection

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    BACKGROUND Results of previous single-center, observational studies suggest that daily bathing of patients with chlorhexidine may prevent hospital-acquired bloodstream infections and the acquisition of multidrug-resistant organisms (MDROs). METHODS We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired bloodstream infections. Nine intensive care and bone marrow transplantation units in six hospitals were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine– impregnated washcloths or with nonantimicrobial washcloths for a 6-month period, exchanged for the alternate product during the subsequent 6 months. The incidence rates of acquisition of MDROs and the rates of hospital-acquired bloodstream infections were compared between the two periods by means of Poisson regression analysis. RESULTS A total of 7727 patients were enrolled during the study. The overall rate of MDRO acquisition was 5.10 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.03), the equivalent of a 23% lower rate with chlorhexidine bathing. The overall rate of hospital-acquired bloodstream infections was 4.78 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.007), a 28% lower rate with chlorhexidine-impregnated washcloths. No serious skin reactions were noted during either study period. CONCLUSIONS Daily bathing with chlorhexidine-impregnated washcloths significantly reduced the risks of acquisition of MDROs and development of hospital-acquired bloodstream infections. (Funded by the Centers for Disease Control and Prevention and Sage Products; ClinicalTrials.gov number, NCT00502476.

    Gene conversion in human rearranged immunoglobulin genes

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    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V&lt;sub&gt;H&lt;/sub&gt; segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V&lt;sub&gt;H&lt;/sub&gt; replacements with no addition of untemplated nucleotides at the V&lt;sub&gt;H&lt;/sub&gt;–V&lt;sub&gt;H&lt;/sub&gt; joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V&lt;sub&gt;H&lt;/sub&gt; replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

    HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

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    Background: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year (/QALY)gained.Strategiesweredeemedcosteffectivewithincrementalcosteffectivenessratios</QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <100,000/QALY. Results: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were 591,400.GeneTherapywascosteffectivewithefficacyof10591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost 54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost 12,400/monthfor24months.At12,400/month for 24 months. At 150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV
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