1,647 research outputs found

    Numerical Computation of Exponential Functions of Nabla Fractional Calculus

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    In this article, we illustrate the asymptotic behaviour of exponential functions of nabla fractional calculus. For this purpose, we propose a novel matrix technique to compute these functions numerically

    Towards Automatic Extraction of Social Networks of Organizations in PubMed Abstracts

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    Social Network Analysis (SNA) of organizations can attract great interest from government agencies and scientists for its ability to boost translational research and accelerate the process of converting research to care. For SNA of a particular disease area, we need to identify the key research groups in that area by mining the affiliation information from PubMed. This not only involves recognizing the organization names in the affiliation string, but also resolving ambiguities to identify the article with a unique organization. We present here a process of normalization that involves clustering based on local sequence alignment metrics and local learning based on finding connected components. We demonstrate the application of the method by analyzing organizations involved in angiogenensis treatment, and demonstrating the utility of the results for researchers in the pharmaceutical and biotechnology industries or national funding agencies.Comment: This paper has been withdrawn; First International Workshop on Graph Techniques for Biomedical Networks in Conjunction with IEEE International Conference on Bioinformatics and Biomedicine, Washington D.C., USA, Nov. 1-4, 2009; http://www.public.asu.edu/~sjonnal3/home/papers/IEEE%20BIBM%202009.pd

    HETEROGENEITY IN PLATELET EXOCYTOSIS

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    Platelet exocytosis is essential for hemostasis and for many of its sequelae. Platelets release numerous bioactive molecules stored in their granules enabling them to exert a wide range of effects on the vascular microenvironment. Are these granule cargo released thematically in a context-specific pattern or via a stochastic, kinetically-controlled process? My work describes platelet exocytosis using a systematic examination of platelet secretion kinetics. Platelets were stimulated for increasing times with different agonists (i.e. thrombin, PAR1-agonist, PAR4-agonist, and convulxin) and micro-ELISA arrays were used to quantify the release of 28 distinct α-granule cargo molecules. Agonist potency directly correlated with the speed and extent of release. PAR4-agonist induced slower release of fewer molecules while thrombin rapidly induced the greatest release. Cargo with opposing actions (e.g. pro- and anti-angiogenic) had similar release profiles, suggesting limited thematic response to specific agonists. From the release time-course data, rate constants were calculated and used to probe for underlying patterns. Probability density function and operator variance analyses were consistent with three classes of release events, differing in their rates. The distribution of cargo into these three classes was heterogeneous suggesting that platelet secretion is a stochastic process potentially controlled by several factors such as cargo solubility, granule shape, and/or granule-plasma membrane fusion routes. Sphingosine 1 phosphate (S1P) is a bioactive lipid that is stored in platelets. S1P is essential for embryonic development, vascular integrity, and inflammation. Platelets are an abundant source of S1P due to the absence of the enzymes that degrade it. Platelets release S1P upon stimulation. My work attempts to determine how this bioactive lipid is released from platelets. Washed platelets were stimulated with agonists for defined periods of time and the supernatant and pellet fractions were separated by centrifugation. Lipids were separated by liquid phase extraction and S1P was quantified with a triple quadrapole mass spectrometer. A carrier molecule (BSA) is required to detect release of S1P. Further, there is a dose-dependent increase in total S1P with increasing BSA. S1P release shows characteristics similar to other platelet granule cargo e.g. platelet factor IV (PF4). Platelets from Unc13-d Jinx mice and VAMP8-/- mice, which are secretion-deficient (dense granule, alpha granule and lysosome), were utilized to understand the process of S1P release. S1P release was more affected in Unc13-d Jinx mice mirroring their dense granule secretion defect. Fluorescence microscopy and sub-cellular fractionation were used to examine localization of S1P in platelets. S1P was observed to be enriched in a granule population. These studies indicate the existence of two pools of S1P, a readily extractable agranular pool, sensitive to BSA, and a granular pool that requires the secretion machinery for release. The secretion machinery of platelets in addition to being involved in the release of normal granule cargo is thus proved to be involved in the release of bioactive lipid molecules like S1P
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