263 research outputs found

    Unsupervised Bayesian linear unmixing of gene expression microarrays

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    Background: This paper introduces a new constrained model and the corresponding algorithm, called unsupervised Bayesian linear unmixing (uBLU), to identify biological signatures from high dimensional assays like gene expression microarrays. The basis for uBLU is a Bayesian model for the data samples which are represented as an additive mixture of random positive gene signatures, called factors, with random positive mixing coefficients, called factor scores, that specify the relative contribution of each signature to a specific sample. The particularity of the proposed method is that uBLU constrains the factor loadings to be non-negative and the factor scores to be probability distributions over the factors. Furthermore, it also provides estimates of the number of factors. A Gibbs sampling strategy is adopted here to generate random samples according to the posterior distribution of the factors, factor scores, and number of factors. These samples are then used to estimate all the unknown parameters. Results: Firstly, the proposed uBLU method is applied to several simulated datasets with known ground truth and compared with previous factor decomposition methods, such as principal component analysis (PCA), non negative matrix factorization (NMF), Bayesian factor regression modeling (BFRM), and the gradient-based algorithm for general matrix factorization (GB-GMF). Secondly, we illustrate the application of uBLU on a real time-evolving gene expression dataset from a recent viral challenge study in which individuals have been inoculated with influenza A/H3N2/Wisconsin. We show that the uBLU method significantly outperforms the other methods on the simulated and real data sets considered here. Conclusions: The results obtained on synthetic and real data illustrate the accuracy of the proposed uBLU method when compared to other factor decomposition methods from the literature (PCA, NMF, BFRM, and GB-GMF). The uBLU method identifies an inflammatory component closely associated with clinical symptom scores collected during the study. Using a constrained model allows recovery of all the inflammatory genes in a single factor

    The demography of fine roots in response to patches of water and nitrogen

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    Fine root demography was quantified in response to patches of increased water and nitrogen availability in a natural, second-growth, mixed hardwood forest in northern Michigan, USA. As expected, the addition of water and water plus nitrogen resulted in a significant overall increase in the production of new fine roots. New root production was much greater in response to water plus nitrogen when compared with water alone, and the duration of new root production was related to the length of resource addition in the water plus nitrogen treatments; the average difference in new root length between the 20 vs. 40 d additions of water plus nitrogen amounted to almost 600%. Roots produced in response to the additions of water and water plus nitrogen lived longer than roots in the control treatments. Thus, additions of water and water plus nitrogen influenced both the proliferation of new roots and their longevity, with both proliferation and longevity related to the type and duration of resource supply. Results suggest that root longevity and mortality may be plastic in response to changes in soil resource availability, as is well known for root proliferation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65770/1/j.1469-8137.1993.tb03905.x.pd

    Magnetic Resonance Imaging Assessment of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia in Children

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    Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetically determined disease that progresses continuously from conception and throughout life. ARVC/D manifests predominantly in young adulthood. Early identification of the concealed cases in childhood is of utmost importance for the prevention of sudden cardiac death later in life. Magnetic resonance imaging (MRI) is routinely requested in patients with a confirmed or suspected diagnosis of ARVC/D and in family members of the patients with ARVC/D. Although the utility of MRI in the assessment of ARVC/D is well recognized in adults, MRI is a low-yield test in children as the anatomical, histological, and functional changes are frequently subtle or not present in the early phase of the disease. MRI findings of ARVC/D include morphologic changes such as right ventricular dilatation, wall thinning, and aneurismal outpouchings, as well as abnormal tissue characteristics such as myocardial fibrosis and fatty infiltration, and functional abnormalities such as global ventricular dysfunction and regional wall motion abnormalities. Among these findings, regional wall motion abnormalities are the most reliable MRI findings both in children and adults, while myocardial fibrosis and fat infiltration are rarely seen in children. Therefore, an MRI protocol should be tailored according to the patient's age and compliance, as well as the presence of other findings, instead of using the protocol that is used for adults. We propose that MRI in children with ARVC/D should focus on the detection of regional wall motion abnormalities and global ventricular function by using a cine imaging sequence and that the sequences for myocardial fat and late gadolinium enhancement of the myocardium are reserved for those who show abnormal findings at cine imaging. Importantly, MRI should be performed and interpreted by experienced examiners to reduce the number of false positive and false negative readings

    Origin and Evolution of Prebiotic Organic Matter as Inferred from the Tagish Lake Meteorite

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    The complex suite of organic materials in carbonaceous chondrite meteorites probably originally formed in the interstellar medium and/or the solar protoplanetary disk, but was subsequently modified in the meteorites' asteroidal parent bodies. The mechanisms of formation and modification are still very poorly understood. We carried out a systematic study of variations in the mineralogy, petrology, and soluble and insoluble organic matter in distinct fragments of the Tagish Lake meteorite. The variations correlate with indicators of parent body aqueous alteration and at least some molecules of pre-biotic importance formed during the alteration

    Performance of the BioPlex 2200 HIV Ag-Ab assay for identifying acute HIV infection

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    Background: Assays that detect HIV antigen (Ag) and antibody (Ab) can be used to screen for HIV infection. Objectives: To compare the performance of the BioPlex 2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of acute HIV infection. Study Design: Samples were obtained from 24 individuals (18 from the US, 6 from South Africa); these individuals were classified as having acute infection based on the following criteria: positive qualitative RNA assay; two negative rapid tests; negative discriminatory test. The samples were tested with the BioPlex assay, the ARCHITECT HIV Ag/Ab Combo test, the Bio-Rad GS HIV Combo Ag-Ab EIA test, and a viral load assay. Results: Twelve (50.0%) of 24 samples had RNA detected only (>40 to 13,476 copies/mL). Ten (43.5%) samples had reactive results with all three Ag/Ab assays, one sample was reactive with the ARCHITECT and Bio-Rad assays, and one sample was reactive with the Bio-Rad and BioPlex assays. The 11 samples that were reactive with the BioPlex assay had viral loads from 83,010 to >750,000 copies/mL; 9/11 samples were classified as Ag positive/Ab negative by the BioPlex assay. Conclusions: Detection of acute HIV infection was similar for the BioPlex assay and two other Ag/Ab assays. All three tests were less sensitive than a qualitative RNA assay and only detected HIV Ag when the viral load was high. The BioPlex assay detected acute infection in about half of the cases, and identified most of those infections as Ag positive/Ab negative

    Freedom, Servitude and Voluntary Labor

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    We present an economic framework to revisit and reframe some important debates over the nature of free versus unfree labor and the economic consequences of emancipation. We use a simple general equilibrium model in which labor can be either free or coerced and where land and labor will be exchanged on markets that can be competitive or manipulated or via other non-market collusive arrangements. By working with variants of the same basic model under different assumptions about initial economy-wide factor endowments and asset ownership we can compare equilibrium distributional outcomes under different institutional and contractual arrangements including markets with free labor and free tenancy, slavery, and tenancy arrangements with tied labor-service obligations. Analysis of these different contractual and organizational forms yields insights that accord with common sense, but that are often overlooked or downplayed in academic debates, particularly amongst economists
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