36,021 research outputs found

    Encoding of low-quality DNA profiles as genotype probability matrices for improved profile comparisons, relatedness evaluation and database searches

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    Many DNA profiles recovered from crime scene samples are of a quality that does not allow them to be searched against, nor entered into, databases. We propose a method for the comparison of profiles arising from two DNA samples, one or both of which can have multiple donors and be affected by low DNA template or degraded DNA. We compute likelihood ratios to evaluate the hypothesis that the two samples have a common DNA donor, and hypotheses specifying the relatedness of two donors. Our method uses a probability distribution for the genotype of the donor of interest in each sample. This distribution can be obtained from a statistical model, or we can exploit the ability of trained human experts to assess genotype probabilities, thus extracting much information that would be discarded by standard interpretation rules. Our method is compatible with established methods in simple settings, but is more widely applicable and can make better use of information than many current methods for the analysis of mixed-source, low-template DNA profiles. It can accommodate uncertainty arising from relatedness instead of or in addition to uncertainty arising from noisy genotyping. We describe a computer program GPMDNA, available under an open source license, to calculate LRs using the method presented in this paper.Comment: 28 pages. Accepted for publication 2-Sep-2016 - Forensic Science International: Genetic

    Sensitivity of optimum solutions to problem parameters

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    Derivation of the sensitivity equations that yield the sensitivity derivatives directly, which avoids the costly and inaccurate perturb-and-reoptimize approach, is discussed and solvability of the equations is examined. The equations apply to optimum solutions obtained by direct search methods as well as those generated by procedures of the sequential unconstrained minimization technique class. Applications are discussed for the use of the sensitivity derivatives in extrapolation of the optimal objective function and design variable values for incremented parameters, optimization with multiple objectives, and decomposition of large optimization problems

    In situ analysis for intelligent control

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    We report a pilot study on in situ analysis of backscatter data for intelligent control of a scientific instrument on an Autonomous Underwater Vehicle (AUV) carried out at the Monterey Bay Aquarium Research Institute (MBARI). The objective of the study is to investigate techniques which use machine intelligence to enable event-response scenarios. Specifically we analyse a set of techniques for automated sample acquisition in the water-column using an electro-mechanical "Gulper", designed at MBARI. This is a syringe-like sampling device, carried onboard an AUV. The techniques we use in this study are clustering algorithms, intended to identify the important distinguishing characteristics of bodies of points within a data sample. We demonstrate that the complementary features of two clustering approaches can offer robust identification of interesting features in the water-column, which, in turn, can support automatic event-response control in the use of the Gulper

    Automated parameters for troubled-cell indicators using outlier detection

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    In Vuik and Ryan (2014) we studied the use of troubled-cell indicators for discontinuity detection in nonlinear hyperbolic partial differential equations and introduced a new multiwavelet technique to detect troubled cells. We found that these methods perform well as long as a suitable, problem-dependent parameter is chosen. This parameter is used in a threshold which decides whether or not to detect an element as a troubled cell. Until now, these parameters could not be chosen automatically. The choice of the parameter has impact on the approximation: it determines the strictness of the troubled-cell indicator. An inappropriate choice of the parameter will result in detection (and limiting) of too few or too many elements. The optimal parameter is chosen such that the minimal number of troubled cells is detected and the resulting approximation is free of spurious oscillations. In this paper we will see that for each troubled-cell indicator the sudden increase or decrease of the indicator value with respect to the neighboring values is important for detection. Indication basically reduces to detecting the outliers of a vector (one dimension) or matrix (two dimensions). This is done using Tukey's boxplot approach to detect which coefficients in a vector are straying far beyond others (Tukey, 1977). We provide an algorithm that can be applied to various troubled-cell indication variables. Using this technique the problem-dependent parameter that the original indicator requires is no longer necessary as the parameter will be chosen automatically

    IL-17 can be protective or deleterious in murine pneumococcal pneumonia

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    Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains
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