3,283 research outputs found

    Novel Distances for Dollo Data

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    We investigate distances on binary (presence/absence) data in the context of a Dollo process, where a trait can only arise once on a phylogenetic tree but may be lost many times. We introduce a novel distance, the Additive Dollo Distance (ADD), which is consistent for data generated under a Dollo model, and show that it has some useful theoretical properties including an intriguing link to the LogDet distance. Simulations of Dollo data are used to compare a number of binary distances including ADD, LogDet, Nei Li and some simple, but to our knowledge previously unstudied, variations on common binary distances. The simulations suggest that ADD outperforms other distances on Dollo data. Interestingly, we found that the LogDet distance performs poorly in the context of a Dollo process, which may have implications for its use in connection with conditioned genome reconstruction. We apply the ADD to two Diversity Arrays Technology (DArT) datasets, one that broadly covers Eucalyptus species and one that focuses on the Eucalyptus series Adnataria. We also reanalyse gene family presence/absence data on bacteria from the COG database and compare the results to previous phylogenies estimated using the conditioned genome reconstruction approach

    The Regulation of Aggrecanase ADAMTS-4 Expression in Human Achilles Tendon and tendon-Derived Cells

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    Several members of the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family have been identified as aggrecanases, whose substrates include versican, the principal large proteoglycan in the tendon extracellular matrix. We have characterized the expression of ADAMTS-4 in human Achilles tendon and tendon-derived cells. ADAMTS-4 mRNA levels were higher in ruptured tendon compared with normal tendon or chronic painful tendinopathy. In tissue extracts probed by Western blotting, mature ADAMTS-4 (68 kDa) was detected only in ruptured tendons, while processed ADAMTS-4 (53 kDa) was detected also in chronic painful tendinopathy and in normal tendon. In cultured Achilles tendon cells, transforming growth factor-ß (TGF-ß) stimulated ADAMTS-4 mRNA expression (typically 20-fold after 24 h), while interleukin-1 induced a smaller, shorter-term stimulation which synergised markedly with that induced by TGF-ß. Increased levels of immunoreactive proteins consistent with mature and processed forms of ADAMTS-4 were detected in TGF-ß-stimulated cells. ADAMTS-4 mRNA was expressed at higher levels by tendon cells in collagen gels than in monolayer cultures. In contrast, the expression of ADAMTS-1 and -5 mRNA was lower in collagen gels compared with monolayers, and these mRNA showed smaller or opposite responses to growth factors and cytokines compared with that of ADAMTS-4 mRNA. We conclude that both ADAMTS-4 mRNA and ADAMTS-4 protein processing may be differentially regulated in normal and damaged tendons and that both the matrix environment and growth factors such as TGF-ß are potentially important factors controlling ADAMTS aggrecanase activities in tendon pathology

    Springs of Florida

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    bulletin which documented the major and important springs in the state (Ferguson et al., 1947). This publication was revised in 1977, with many previously undocumented springs and many new water-quality analyses being added (Rosenau et al., 1977). The Florida Geological Survey's report on first magnitude springs (Scott et al., 2002) was the initial step in once again updating and revising the Springs of Florida bulletin. The new bulletin includes the spring descriptions and water-quality analyses from Scott et al. (2002). Nearly 300 springs were described in 1977. As of 2004, more than 700 springs have been recognized in the state and more are reported each year. To date, 33 first magnitude springs (with a flow greater than 100 cubic feet per second or approximately 64.6 million gallons of water per day) have been recognized in Florida, more than any other state or country (Rosenau et al., 1977). Our springs are a unique and invaluable natural resource. A comprehensive understanding of the spring systems will provide the basis for their protection and wise use. (Document pdf contains 677 pages

    Robust MR-based approaches to quantifying white matter structure and structure/function alterations in Huntington's disease

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    Background: Huge advances have been made in understanding and addressing confounds in diffusion MRI data to quantify white matter microstructure. However, there has been a lag in applying these advances in clinical research. Some confounds are more pronounced in HD which impedes data quality and interpretability of patient-control differences. This study presents an optimised analysis pipeline and addresses specific confounds in a HD patient cohort. Method: 15 HD gene-positive and 13 matched control participants were scanned on a 3T MRI system with two diffusion MRI sequences. An optimised post processing pipeline included motion, eddy current and EPI correction, rotation of the B matrix, free water elimination ( FWE ) and tractography analysis using an algorithm capable of reconstructing crossing fibres. The corpus callosum was examined using both a region-of-interest and a deterministic tractography approach, using both conventional diffusion tensor imaging ( DTI )-based and spherical deconvolution analyses. Results: Correcting for CSF contamination significantly altered microstructural metrics and the detection of group differences. Reconstructing the corpus callosum using spherical deconvolution produced a more complete reconstruction with greater sensitivity to group differences, compared to DTI-based tractography. Tissue volume fraction ( TVF ) was reduced in HD participants and was more sensitive to disease burden compared to DTI metrics. Conclusion: Addressing confounds in diffusion MR data results in more valid, anatomically faithful white matter tract reconstructions with reduced within-group variance. TVF is recommended as a complementary metric, providing insight into the relationship with clinical symptoms in HD not fully captured by conventional DTI metrics

    The inevitable drift to triple therapy in COPD : an analysis of prescribing pathways in the UK

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    Acknowledgments The analyses reported in this study were funded by Novartis Pharma AG (Basel, Switzerland) and were conducted by Research in Real-Life Ltd (Cambridge, UK), an independent company. The authors also thank David Bergin, Danielle Corbett, and Vivek Khanna (professional medical writers; Novartis) for assistance in the preparation of this paper. Writing support was funded by Novartis Pharma AG.Peer reviewedPublisher PD

    The Influence Of Neutron Capture Rates On The Rare Earth Region Of The r-Process Abundance Pattern

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    We study the sensitivity of the r-process abundance pattern to neutron capture rates along the rare earth region (A~150 to A~180). We introduce the concepts of large nuclear flow and flow saturation which determine the neutron capture rates that are influential in setting the rare earth abundances. We illustrate the value of the two concepts by considering high entropy conditions favorable for rare earth peak production and identifying important neutron capture rates among the rare earth isotopes. We also show how these rates influence nuclear flow and specific sections of the abundance pattern.Comment: 14 pages, 7 figures, submitted to PR
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