554 research outputs found

    Computing Scalable Multivariate Glocal Invariants of Large (Brain-) Graphs

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    Graphs are quickly emerging as a leading abstraction for the representation of data. One important application domain originates from an emerging discipline called "connectomics". Connectomics studies the brain as a graph; vertices correspond to neurons (or collections thereof) and edges correspond to structural or functional connections between them. To explore the variability of connectomes---to address both basic science questions regarding the structure of the brain, and medical health questions about psychiatry and neurology---one can study the topological properties of these brain-graphs. We define multivariate glocal graph invariants: these are features of the graph that capture various local and global topological properties of the graphs. We show that the collection of features can collectively be computed via a combination of daisy-chaining, sparse matrix representation and computations, and efficient approximations. Our custom open-source Python package serves as a back-end to a Web-service that we have created to enable researchers to upload graphs, and download the corresponding invariants in a number of different formats. Moreover, we built this package to support distributed processing on multicore machines. This is therefore an enabling technology for network science, lowering the barrier of entry by providing tools to biologists and analysts who otherwise lack these capabilities. As a demonstration, we run our code on 120 brain-graphs, each with approximately 16M vertices and up to 90M edges.Comment: Published as part of 2013 IEEE GlobalSIP conferenc

    Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate

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    AbstractIn humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthralgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent

    Should outbreak response immunization be recommended for measles outbreaks in middle- and low-income countries? An update.

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    Measles caused mortality in >164,000 children in 2008, with most deaths occurring during outbreaks. Nonetheless, the impact and desirability of conducting measles outbreak response immunization (ORI) in middle- and low-income countries has been controversial. World Health Organization guidelines published in 1999 recommended against ORI in such settings, although recently these guidelines have been reversed for countries with measles mortality reduction goals

    Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

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    Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

    Geoantineutrino Spectrum, 3He/4He-ratio Distribution in the Earth's Interior and Slow Nuclear Burning on the Boundary of the Liquid and Solid Phases of the Earth's Core

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    The description problem of geoantineutrino spectrum and reactor antineutrino experimental spectrum in KamLAND, which takes place for antineutrino energy \~2.8 MeV, and also the experimental results of the interaction of uranium dioxide and carbide with iron-nickel and silicaalumina melts at high pressure (5-10 GP?) and temperature (1600-2200C) have motivated us to consider the possible consequences of the assumption made by V.Anisichkin and coauthors that there is an actinid shell on boundary of liquid and solid phases of the Earth's core. We have shown that the activation of a natural nuclear reactor operating as the solitary waves of nuclear burning in 238U- and/or 232Th-medium (in particular, the neutron- fission progressive wave of Feoktistov and/or Teller-Ishikawa-Wood) can be such a physical consequence. The simplified model of the kinetics of accumulation and burnup in U-Pu fuel cycle of Feoktistov is developed. The results of the numerical simulation of neutron-fission wave in two-phase UO2/Fe medium on a surface of the Earth's solid core are presented. The georeactor model of 3He origin and the 3He/4He-ratio distribution in the Earth's interior is offered. It is shown that the 3He/4He ratio distribution can be the natural quantitative criterion of georeactor thermal power. On the basis of O'Nions-Evensen-Hamilton geochemical model of mantle differentiation and the crust growth supplied by actinid shell on the boundary of liquid and solid phases of the Earth's core as a nuclear energy source (georeactor with power of 30 TW), the tentative estimation of geoantineutrino intensity and geoantineutrino spectrum on the Earth surface are given.Comment: 28 pages, 12 figures. Added text, formulas, figures and references. Corrected equations. Changed content of some section

    Functional selectivity of dopamine D1 receptor agonists in regulating the fate of internalized receptors

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    Recently, we demonstrated that D1 agonists can cause functionally selective effects when the endpoints of receptor internalization and adenylate cyclase activation are compared. The present study was designed to probe the phenomenon of functional selectivity at the D1 receptor further by testing the hypothesis that structurally dissimilar agonists with efficacies at these endpoints that equal or exceed those of dopamine would differ in ability to influence receptor fate after internalization, a functional endpoint largely unexplored for the D1 receptor. We selected two novel agonists of therapeutic interest that meet these criteria (the isochroman A-77636, and the isoquinoline dinapsoline), and compared the fates of the D1 receptor after internalization in response to these two compounds with that of dopamine. We found that dopamine caused the receptor to be rapidly recycled to the cell surface within 1 h of removal. Conversely, A-77636 caused the receptor to be retained intracellularly up to 48 h after agonist removal. Most surprisingly, the D1 receptor recovered to the cell surface 48 h after removal of dinapsoline. Taken together, these data indicate that these agonists target the D1 receptor to different intracellular trafficking pathways, demonstrating that the phenomenon of functional selectivity at the D1 receptor is operative for cellular events that are temporally downstream of immediate receptor activation. We hypothesize that these differential effects result from interactions of the synthetic ligands with aspects of the D1 receptor that are distal from the ligand binding domain

    Prediction and estimation of effective population size

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    Effective population size (Ne) is a key parameter in population genetics. It has important applications in evolutionary biology, conservation genetics, and plant and animal breeding, because it measures the rates of genetic drift and inbreeding and affects the efficacy of systematic evolutionary forces such as mutation, selection and migration. We review the developments in predictive equations and estimation methodologies of effective size. In the prediction part, we focus on the equations for populations with different modes of reproduction, for populations under selection for unlinked or linked loci, and for the specific applications to conservation genetics. In the estimation part, we focus on methods developed for estimating the current or recent effective size from molecular marker or sequence data. We discuss some underdeveloped areas in predicting and estimating Ne for future research
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