302 research outputs found

    RLZAP: Relative Lempel-Ziv with Adaptive Pointers

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    Relative Lempel-Ziv (RLZ) is a popular algorithm for compressing databases of genomes from individuals of the same species when fast random access is desired. With Kuruppu et al.'s (SPIRE 2010) original implementation, a reference genome is selected and then the other genomes are greedily parsed into phrases exactly matching substrings of the reference. Deorowicz and Grabowski (Bioinformatics, 2011) pointed out that letting each phrase end with a mismatch character usually gives better compression because many of the differences between individuals' genomes are single-nucleotide substitutions. Ferrada et al. (SPIRE 2014) then pointed out that also using relative pointers and run-length compressing them usually gives even better compression. In this paper we generalize Ferrada et al.'s idea to handle well also short insertions, deletions and multi-character substitutions. We show experimentally that our generalization achieves better compression than Ferrada et al.'s implementation with comparable random-access times

    Evaluation of Mode I Fracture Toughness Assisted by the Numerical Determination of K-Resistance

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    The fracture toughness of a rock often varies depending on the specimen shape and the loading type used to measure it. To investigate the mode I fracture toughness using semi-circular bend (SCB) specimens, we experimentally studied the fracture toughness using SCB and chevron bend (CB) specimens, the latter being one of the specimens used extensively as an International Society for Rock Mechanics (ISRM) suggested method, for comparison. The mode I fracture toughness measured using SCB specimens is lower than both the level I and level II fracture toughness values measured using CB specimens. A numerical study based on discontinuum mechanics was conducted using a two-dimensional distinct element method (DEM) for evaluating crack propagation in the SCB specimen during loading. The numerical results indicate subcritical crack growth as well as sudden crack propagation when the load reaches the maximum. A K-resistance curve is drawn using the crack extension and the load at the point of evaluation. The fracture toughness evaluated by the K-resistance curve is in agreement with the level II fracture toughness measured using CB specimens. Therefore, the SCB specimen yields an improved value for fracture toughness when the increase of K-resistance with stable crack propagation is considered

    Viral-mediated oncolysis is the most critical factor in the late-phase of the tumor regression process upon vaccinia virus infection

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    <p>Abstract</p> <p>Background</p> <p>In principle, the elimination of malignancies by oncolytic virotherapy could proceed by different mechanisms - e.g. tumor cell specific oncolysis, destruction of the tumor vasculature or an anti-tumoral immunological response. In this study, we analyzed the contribution of these factors to elucidate the responsible mechanism for regression of human breast tumor xenografts upon colonization with an attenuated vaccinia virus (VACV).</p> <p>Methods</p> <p>Breast tumor xenografts were analyzed 6 weeks post VACV infection (p.i.; regression phase) by immunohistochemistry and mouse-specific expression arrays. Viral-mediated oncolysis was determined by tumor growth analysis combined with microscopic studies of intratumoral virus distribution. The tumor vasculature was morphologically characterized by diameter and density measurements and vessel functionality was analyzed by lectin perfusion and extravasation studies. Immunological aspects of viral-mediated tumor regression were studied in either immune-deficient mouse strains (T-, B-, NK-cell-deficient) or upon cyclophosphamide-induced immunosuppression (MHCII<sup>+</sup>-cell depletion) in nude mice.</p> <p>Results</p> <p>Late stage VACV-infected breast tumors showed extensive necrosis, which was highly specific to cancer cells. The tumor vasculature in infected tumor areas remained functional and the endothelial cells were not infected. However, viral colonization triggers hyperpermeability and dilatation of the tumor vessels, which resembled the activated endothelium in wounded tissue. Moreover, we demonstrated an increased expression of genes involved in leukocyte-endothelial cell interaction in VACV-infected tumors, which orchestrate perivascular inflammatory cell infiltration. The immunohistochemical analysis of infected tumors displayed intense infiltration of MHCII-positive cells and colocalization of tumor vessels with MHCII<sup>+</sup>/CD31<sup>+ </sup>vascular leukocytes. However, GI-101A tumor growth analysis upon VACV-infection in either immunosuppressed nude mice (MHCII<sup>+</sup>-cell depleted) or in immune-deficient mouse strains (T-, B-, NK-cell-deficient) revealed that neither MHCII-positive immune cells nor T-, B-, or NK cells contributed significantly to VACV-mediated tumor regression. In contrast, tumors of immunosuppressed mice showed enhanced viral spreading and tumor necrosis.</p> <p>Conclusions</p> <p>Taken together, these results indicate that VACV-mediated oncolysis is the primary mechanism of tumor shrinkage in the late regression phase. Neither the destruction of the tumor vasculature nor the massive VACV-mediated intratumoral inflammation was a prerequisite for tumor regression. We propose that approaches to enhance viral replication and spread within the tumor microenvironment should improve therapeutical outcome.</p

    Co-Inoculation with Rhizobia and AMF Inhibited Soybean Red Crown Rot: From Field Study to Plant Defense-Related Gene Expression Analysis

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    Background: Soybean red crown rot is a major soil-borne disease all over the world, which severely affects soybean production. Efficient and sustainable methods are strongly desired to control the soil-borne diseases. Principal Findings: We firstly investigated the disease incidence and index of soybean red crown rot under different phosphorus (P) additions in field and found that the natural inoculation of rhizobia and arbuscular mycorrhizal fungi (AMF) could affect soybean red crown rot, particularly without P addition. Further studies in sand culture experiments showed that inoculation with rhizobia or AMF significantly decreased severity and incidence of soybean red crown rot, especially for coinoculation with rhizobia and AMF at low P. The root colony forming unit (CFU) decreased over 50 % when inoculated by rhizobia and/or AMF at low P. However, P addition only enhanced CFU when inoculated with AMF. Furthermore, root exudates of soybean inoculated with rhizobia and/or AMF significantly inhibited pathogen growth and reproduction. Quantitative RT-PCR results indicated that the transcripts of the most tested pathogen defense-related (PR) genes in roots were significantly increased by rhizobium and/or AMF inoculation. Among them, PR2, PR3, PR4 and PR10 reached the highest level with co-inoculation of rhizobium and AMF. Conclusions: Our results indicated that inoculation with rhizobia and AMF could directly inhibit pathogen growth and reproduction, and activate the plant overall defense system through increasing PR gene expressions. Combined wit

    Preclinical Evaluation of Caprylic Acid-Fractionated IgG Antivenom for the Treatment of Taipan (Oxyuranus scutellatus) Envenoming in Papua New Guinea

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    articulo (arbitrado) -- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado, 2011Background: Snake bite is a common medical emergency in Papua New Guinea (PNG). The taipan, Oxyuranus scutellatus, inflicts a large number of bites that, in the absence of antivenom therapy, result in high mortality. Parenteral administration of antivenoms manufactured in Australia is the current treatment of choice for these envenomings. However, the price of these products is high and has increased over the last 25 years; consequently the country can no longer afford all the antivenom it needs. This situation prompted an international collaborative project aimed at generating a new, low-cost antivenom against O. scutellatus for PNG. Methodology/Principal Findings: A new monospecific equine whole IgG antivenom, obtained by caprylic acid fractionation of plasma, was prepared by immunising horses with the venom of O. scutellatus from PNG. This antivenom was compared with the currently used F(ab’)2 monospecific taipan antivenom manufactured by CSL Limited, Australia. The comparison included physicochemical properties and the preclinical assessment of the neutralisation of lethal neurotoxicity and the myotoxic, coagulant and phospholipase A2 activities of the venom of O. scutellatus from PNG. The F(ab’)2 antivenom had a higher protein concentration than whole IgG antivenom. Both antivenoms effectively neutralised, and had similar potency, against the lethal neurotoxic effect (both by intraperitoneal and intravenous routes of injection), myotoxicity, and phospholipase A2 activity of O. scutellatus venom. However, the whole IgG antivenom showed a higher potency than the F(ab’)2 antivenom in the neutralisation of the coagulant activity of O. scutellatus venom from PNG. Conclusions/Significance: The new whole IgG taipan antivenom described in this study compares favourably with the currently used F(ab’)2 antivenom, both in terms of physicochemical characteristics and neutralising potency. Therefore, it should be considered as a promising low-cost candidate for the treatment of envenomings by O. scutellatus in PNG, and is ready to be tested in clinical trials.This study was supported by Vicerrectoría de Investigación, Universidad de Costa Rica (project 741-A9-003); the PNG Office of Higher Education, CTP Limited (Milne Bay Estates), and the Australian Venom Research Unit (University of Melbourne), which is funded by the Australian Government Department of Health and Ageing, the Australia Pacific Science Foundation and Snowy Nominees. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

    Measurement of the double-differential muon-neutrino charged-current inclusive cross section in the NOvA near detector

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    We report cross-section measurements of the final-state muon kinematics for νμ charged-current interactions in the NOvA near detector using an accumulated 8.09×1020 protons on target in the NuMI beam. We present the results as a double-differential cross section in the observed outgoing muon energy and angle, as well as single-differential cross sections in the derived neutrino energy, Eν, and square of the four-momentum transfer, Q2. We compare the results to inclusive cross-section predictions from various neutrino event generators via χ2 calculations using a covariance matrix that accounts for bin-to-bin correlations of systematic uncertainties. These comparisons show a clear discrepancy between the data and each of the tested predictions at forward muon angle and low Q2, indicating a missing suppression of the cross section in current neutrino-nucleus scattering models
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