3,693 research outputs found

    CLUDE: An Efficient Algorithm for LU Decomposition Over a Sequence of Evolving Graphs

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    Session: Matrix Factorization, Clustering and Probabilistic DataIn many applications, entities and their relationships are represented by graphs. Examples include the WWW (web pages and hyperlinks) and bibliographic networks (authors and co-authorship). A graph can be conveniently modeled by a matrix from which various quantitative measures are derived. Some example measures include PageRank and SALSA (which measure nodes’ importance), and Personalized PageRank and Random Walk with Restart (which measure proximities between nodes). To compute these measures, linear systems of the form Ax = b, where A is a matrix that captures a graph’s structure, need to be solved. To facilitate solving the linear system, the matrix A is often decomposed into two triangular matrices (L and U). In a dynamic world, the graph that models it changes with time and thus is the matrix A that represents the graph. We consider a sequence of evolving graphs and its associated sequence of evolving matrices. We study how LU-decomposition should be done over the sequence so that (1) the decomposition is efficient and (2) the resulting LU matrices best preserve the sparsity of the matrices A’s (i.e., the number of extra non-zero entries introduced in L and U are minimized.) We propose a cluster-based algorithm CLUDE for solving the problem. Through an experimental study, we show that CLUDE is about an order of magnitude faster than the traditional incremental update algorithm. The number of extra non-zero entries introduced by CLUDE is also about an order of magnitude fewer than that of the traditional algorithm. CLUDE is thus an efficient algorithm for LU decomposition that produces high-quality LU matrices over an evolving matrix sequence.published_or_final_versio

    β2 integrin LFA1 mediates airway damage following neutrophil trans-epithelial migration during RSV infection

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    RSV bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease and no specific anti-viral treatment. Using a novel in vitro primary trans-epithelial neutrophil migration model and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil trans-epithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage, reduced ciliary beat frequency, but also a reduction in infectious viral load. Following migration, RSV infection results in greater neutrophil activation, degranulation and release of neutrophil elastase into the airway surface media compared to neutrophils that migrated across mock-infected nasal epithelial cells. Blocking of the interaction between the ligand on neutrophils (the β2 integrin LFA-1) for intracellular adhesion molecule-1 (ICAM-1) on epithelial cells reduced neutrophil adherence to RSV infected cells and epithelial cell damage to pre-infection levels, but did not reduce the numbers of neutrophils which migrated or prevent the reduction in infectious viral load. These findings have provided important insights into the contribution of neutrophils to airway damage and viral clearance, which are relevant to pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative pre-clinical model that will further elucidate mechanisms that drive disease severity and has utility in anti-viral drug discovery

    Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

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    Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

    Primary skin fibroblasts as a model of Parkinson's disease

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    Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

    A First Generation BAC-Based Physical Map of the Asian Seabass (Lates calcarifer)

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    BACKGROUND: The Asian seabass (Lates calcarifer) is an important marine foodfish species in Southeast Asia and Australia. Genetic improvement of this species has been achieved to some extent through selective breeding programs since 1990s. Several genomic tools such as DNA markers, a linkage map, cDNA and BAC libraries have been developed to assist selective breeding. A physical map is still lacking, although it is essential for positional cloning of genes located in quantitative trait loci (QTL) and assembly of whole genome sequences. METHODOLOGY/PRINCIPAL FINDINGS: A genome-wide physical map of the Asian seabass was constructed by restriction fingerprinting of 38,208 BAC clones with SNaPshot HICF FPC technique. A total of 30,454 were assembled into 2,865 contigs. The physical length of the assembled contigs summed up to 665 Mb. Analyses of some contigs using different methods demonstrated the reliability of the assembly. CONCLUSIONS/SIGNIFICANCE: The present physical map is the first physical map for Asian seabass. This physical map will facilitate the fine mapping of QTL for economically important traits and the positional cloning of genes located in QTL. It will also be useful for the whole genome sequencing and assembly. Detailed information about BAC-contigs and BAC clones are available upon request

    Location of chlorogenic acid biosynthesis pathway and polyphenol oxidase genes in a new interspecific anchored linkage map of eggplant

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    © Gramazio et al.; licensee BioMed Central. 2014. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

    Direct Measurement of Nuclear Dependence of Charged Current Quasielastic-like Neutrino Interactions using MINERvA

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    Charged-current νμ\nu_{\mu} interactions on carbon, iron, and lead with a final state hadronic system of one or more protons with zero mesons are used to investigate the influence of the nuclear environment on quasielastic-like interactions. The transfered four-momentum squared to the target nucleus, Q2Q^2, is reconstructed based on the kinematics of the leading proton, and differential cross sections versus Q2Q^2 and the cross-section ratios of iron, lead and carbon to scintillator are measured for the first time in a single experiment. The measurements show a dependence on atomic number. While the quasielastic-like scattering on carbon is compatible with predictions, the trends exhibited by scattering on iron and lead favor a prediction with intranuclear rescattering of hadrons accounted for by a conventional particle cascade treatment. These measurements help discriminate between different models of both initial state nucleons and final state interactions used in the neutrino oscillation experiments

    Recent changes of water discharge and sediment load in the Yellow River basin, China

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    The Yellow River basin contributes approximately 6% of the sediment load from all river systems globally, and the annual runoff directly supports 12% of the Chinese population. As a result, describing and understanding recent variations of water discharge and sediment load under global change scenarios are of considerable importance. The present study considers the annual hydrologic series of the water discharge and sediment load of the Yellow River basin obtained from 15 gauging stations (10 mainstream, 5 tributaries). The Mann-Kendall test method was adopted to detect both gradual and abrupt change of hydrological series since the 1950s. With the exception of the area draining to the Upper Tangnaihai station, results indicate that both water discharge and sediment load have decreased significantly (p<0.05). The declining trend is greater with distance downstream, and drainage area has a significant positive effect on the rate of decline. It is suggested that the abrupt change of the water discharge from the late 1980s to the early 1990s arose from human extraction, and that the abrupt change in sediment load was linked to disturbance from reservoir construction.Geography, PhysicalGeosciences, MultidisciplinarySCI(E)43ARTICLE4541-5613

    GPS-ARM: Computational Analysis of the APC/C Recognition Motif by Predicting D-Boxes and KEN-Boxes

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    Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase incorporated with Cdh1 and/or Cdc20 recognizes and interacts with specific substrates, and faithfully orchestrates the proper cell cycle events by targeting proteins for proteasomal degradation. Experimental identification of APC/C substrates is largely dependent on the discovery of APC/C recognition motifs, e.g., the D-box and KEN-box. Although a number of either stringent or loosely defined motifs proposed, these motif patterns are only of limited use due to their insufficient powers of prediction. We report the development of a novel GPS-ARM software package which is useful for the prediction of D-boxes and KEN-boxes in proteins. Using experimentally identified D-boxes and KEN-boxes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted. By extensive evaluation and comparison, the GPS-ARM performance was found to be much better than the one using simple motifs. With this powerful tool, we predicted 4,841 potential D-boxes in 3,832 proteins and 1,632 potential KEN-boxes in 1,403 proteins from H. sapiens, while further statistical analysis suggested that both the D-box and KEN-box proteins are involved in a broad spectrum of biological processes beyond the cell cycle. In addition, with the co-localization information, we predicted hundreds of mitosis-specific APC/C substrates with high confidence. As the first computational tool for the prediction of APC/C-mediated degradation, GPS-ARM is a useful tool for information to be used in further experimental investigations. The GPS-ARM is freely accessible for academic researchers at: http://arm.biocuckoo.org
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