121 research outputs found

    High prevalence and two dominant host-specific genotypes of Coxiella burnetii in U.S. milk

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    BackgroundCoxiella burnetii causes Q fever in humans and Coxiellosis in animals; symptoms range from general malaise to fever, pneumonia, endocarditis and death. Livestock are a significant source of human infection as they shed C. burnetii cells in birth tissues, milk, urine and feces. Although prevalence of C. burnetii is high, few Q fever cases are reported in the U.S. and we have a limited understanding of their connectedness due to difficulties in genotyping. Here, we develop canonical SNP genotyping assays to evaluate spatial and temporal relationships among C. burnetii environmental samples and compare them across studies. Given the genotypic diversity of historical collections, we hypothesized that the current enzootic of Coxiellosis is caused by multiple circulating genotypes. We collected A) 23 milk samples from a single bovine herd, B) 134 commercial bovine and caprine milk samples from across the U.S., and C) 400 bovine and caprine samples from six milk processing plants over three years.ResultsWe detected C. burnetii DNA in 96% of samples with no variance over time. We genotyped 88.5% of positive samples; bovine milk contained only a single genotype (ST20) and caprine milk was dominated by a second type (mostly ST8).ConclusionsThe high prevalence and lack of genotypic diversity is consistent with a model of rapid spread and persistence. The segregation of genotypes between host species is indicative of species-specific adaptations or dissemination barriers and may offer insights into the relative lack of human cases and characterizing genotypes

    AVID: An integrative framework for discovering functional relationships among proteins

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    BACKGROUND: Determining the functions of uncharacterized proteins is one of the most pressing problems in the post-genomic era. Large scale protein-protein interaction assays, global mRNA expression analyses and systematic protein localization studies provide experimental information that can be used for this purpose. The data from such experiments contain many false positives and false negatives, but can be processed using computational methods to provide reliable information about protein-protein relationships and protein function. An outstanding and important goal is to predict detailed functional annotation for all uncharacterized proteins that is reliable enough to effectively guide experiments. RESULTS: We present AVID, a computational method that uses a multi-stage learning framework to integrate experimental results with sequence information, generating networks reflecting functional similarities among proteins. We illustrate use of the networks by making predictions of detailed Gene Ontology (GO) annotations in three categories: molecular function, biological process, and cellular component. Applied to the yeast Saccharomyces cerevisiae, AVID provides 37,451 pair-wise functional linkages between 4,191 proteins. These relationships are ~65–78% accurate, as assessed by cross-validation testing. Assignments of highly detailed functional descriptors to proteins, based on the networks, are estimated to be ~67% accurate for GO categories describing molecular function and cellular component and ~52% accurate for terms describing biological process. The predictions cover 1,490 proteins with no previous annotation in GO and also assign more detailed functions to many proteins annotated only with less descriptive terms. Predictions made by AVID are largely distinct from those made by other methods. Out of 37,451 predicted pair-wise relationships, the greatest number shared in common with another method is 3,413. CONCLUSION: AVID provides three networks reflecting functional associations among proteins. We use these networks to generate new, highly detailed functional predictions for roughly half of the yeast proteome that are reliable enough to drive targeted experimental investigations. The predictions suggest many specific, testable hypotheses. All of the data are available as downloadable files as well as through an interactive website at . Thus, AVID will be a valuable resource for experimental biologists

    Measurement of the ttˉproductioncrosssectionint\bar{t} production cross section in p\bar{p}collisionsat collisions at \sqrt{s}$ = 1.8 TeV

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    We update the measurement of the top production cross section using the CDF detector at the Fermilab Tevatron. This measurement uses ttˉt\bar{t} decays to the final states e+νe+\nu+jets and μ+ν\mu+\nu+jets. We search for bb quarks from tt decays via secondary-vertex identification or the identification of semileptonic decays of the bb and cascade cc quarks. The background to the ttˉt\bar{t} production is determined primarily through a Monte Carlo simulation. However, we calibrate the simulation and evaluate its uncertainty using several independent data samples. For a top mass of 175 GeV/c2GeV/c^2, we measure σttˉ=5.1±1.5\sigma_{t\bar{t}}=5.1 \pm 1.5 pb and σttˉ=9.2±4.3\sigma_{t\bar{t}}=9.2 \pm 4.3 pb using the secondary vertex and the lepton tagging algorithms, respectively. Finally, we combine these results with those from other ttˉt\bar{t} decay channels and obtain σttˉ=6.51.4+1.7\sigma_{t\bar{t}} = 6.5^{+1.7}_{-1.4} pb.Comment: The manuscript consists of 130 pages, 35 figures and 42 tables in RevTex. The manuscript is submitted to Physical Review D. Fixed typo in author lis

    Neutrophils in cancer: neutral no more

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    Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

    Blood culture status and mortality among patients with suspected community-acquired bacteremia: a population-based cohort study

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    <p>Abstract</p> <p>Background</p> <p>Comparison of mortality among patients with positive and negative blood cultures may indicate the contribution of bacteremia to mortality. This study (1) compared mortality among patients with community-acquired bacteremia with mortality among patients with negative blood cultures and (2) determined the effects of bacteremia type and comorbidity level on mortality among patients with positive blood cultures.</p> <p>Methods</p> <p>This cohort study included 29,273 adults with blood cultures performed within the first 2 days following hospital admission to an internal medical ward in northern Denmark during 1995-2006. We computed product limit estimates and used Cox regression to compute adjusted mortality rate ratios (MRRs) within 0-2, 3-7, 8-30, and 31-180 days following admission for bacteremia patients compared to culture-negative patients.</p> <p>Results</p> <p>Mortality in 2,648 bacteremic patients and 26,625 culture-negative patients was 4.8% vs. 2.0% 0-2 days after admission, 3.7% vs. 2.7% 3-7 days after admission, 5.6% vs. 5.1% 8-30 days after admission, and 9.7% vs. 8.7% 31-180 days after admission, corresponding to adjusted MRRs of 1.9 (95% confidence interval (CI): 1.6-2.2), 1.1 (95% CI: 0.9-1.5), 0.9 (95% CI: 0.8-1.1), and 1.0 (95% CI: 0.8-1.1), respectively. Mortality was higher among patients with Gram-positive (adjusted 0-2-day MRR 1.9, 95% CI: 1.6-2.2) and polymicrobial bacteremia (adjusted 0-2-day MRR 3.5, 95% CI: 2.2-5.5) than among patients with Gram-negative bacteremia (adjusted 0-2-day MRR 1.5, 95% CI 1.2-2.0). After the first 2 days, patients with Gram-negative bacteremia had the same risk of dying as culture-negative patients (adjusted MRR 0.8, 95% CI: 0.5-1.1). Only patients with polymicrobial bacteremia had increased mortality within 31-180 days following admission (adjusted MRR 1.3, 95% CI: 0.8-2.1) compared to culture-negative patients. The association between blood culture status and mortality did not differ substantially by level of comorbidity.</p> <p>Conclusions</p> <p>Community-acquired bacteremia was associated with an increased risk of mortality in the first week of medical ward admission. Higher mortality among patients with Gram-positive and polymicrobial bacteremia compared with patients with Gram-negative bacteremia and negative cultures emphasizes the prognostic importance of these infections.</p

    Energy security and shifting modes of governance

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    The concept of energy security fits uneasily into contemporary security debates. It is neither a clearly traditional nor a fully ‘non-traditional’ security issue. There are also limits to the social constructedness of the concept. This article argues that, while it is important to identify the differing securitizations of energy, these must be contextualized within the material realities and the differing historical modes of governance of the political economy of resources. This is essential for understanding the differing meanings accorded to energy security, the shifting modes through which energy is governed, and the extent to which energy security concerns drive international politics. In this context, contemporary concerns over energy security have both material and ideological dimensions: anxiety over the dual shift of power from West to East and from resource-importing to resource-exporting countries; and concern over the normative weakening of the neo-liberal mode of energy governance

    Study of the heavy flavor content of jets produced in association with W bosons in ppˉp\bar{p} collisions at s\sqrt{s} = 1.8 TeV

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    We present a detailed examination of the heavy flavor content of the WW + jet data sample collected with the CDF detector during the 1992-1995 collider run at the Fermilab Tevatron. Jets containing heavy flavor quarks are selected via the identification of secondary vertices or semileptonic decays of bb and cc quarks. There is generally good agreement between the rates of secondary vertices and soft leptons in the data and in the standard model simulation including single and pair production of top quarks. An exception is the number of events in which a single jet has both a soft lepton and a secondary vertex tag. In W+W + 2,3 jet data, we find 13 such events where we expected 4.4 ±\pm 0.6 events. The kinematic properties of this small sample of events are statistically difficult to reconcile with the simulation of standard model processes.Comment: 77 pages, 19 tables, 23 figure
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