971 research outputs found

    Cloning of Slc26a6 from murine small intestine for cystic fibrosis studies [abstract]

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    Faculty Mentor: Dr. Lane Clarke, Dalton Cardiovascular Research Center and DepartmentAbstract only availableBicarbonate secretion in the small intestine is important for protecting the intestinal epithelium against stomach acid and providing the proper pH for digestive enzymes and mucus. In the disease cystic fibrosis, bicarbonate secretion is deficient and contributes to the pathogenesis of intestinal disease. Bicarbonate transport is mediated by the cystic fibrosis transmembrane regulator (CFTR), the Cl channel that is defective in cystic fibrosis and that works in concert with a Cl/HCO exchanger. However, the specific identity of the Cl/HCO exchanger working with CFTR is unknown. Recently, studies have localized 2 members of the sulfate permease family (Slc26a3, Slc26a6) to the apical membrane and these proteins have Cl/HCO activity. Because of the difficulties in studying intestinal transport in humans, a CF mouse model was developed that has intestinal disease similar to CF patients. However less is known about the murine homologues of CFTR and these Cl/HCO exchanger proteins. Slc26a3 has been successfully cloned, expressed, and examined in isolation for interactions with mCFTR. Murine Slc26a6 has also been cloned from the mouse kidney, but different splice variants are expressed in the intestine. Therefore, to allow the study of the properties of Slc26a6 in isolation, primers modified from published sequences and Accuprime Pfx DNA Polymerase were used to amplify a single band approximately 2700 base pairs in length from murine small intestinal cDNA. Sequencing primers were designed every 500 bp based on the published sequence of Slc26a6 and the overlapping sequences combined to generate the entire sequence. This sequence was blasted to the published sequence of Slc26a6 to confirm the identity of the clone. The sequence will be subcloned into a bicistronic plasmid expressing DsRed2 and transiently expressed in CHO cells. The ion transport substrates, sensitivity to known inhibitors of Cl/HCO exchangers, and electrogenicity of the transporter will be tested by measuring changes in intracellular pH.Life Sciences Undergradute Research Opportunity Progra

    Budget Constrained Auctions with Heterogeneous Items

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    In this paper, we present the first approximation algorithms for the problem of designing revenue optimal Bayesian incentive compatible auctions when there are multiple (heterogeneous) items and when bidders can have arbitrary demand and budget constraints. Our mechanisms are surprisingly simple: We show that a sequential all-pay mechanism is a 4 approximation to the revenue of the optimal ex-interim truthful mechanism with discrete correlated type space for each bidder. We also show that a sequential posted price mechanism is a O(1) approximation to the revenue of the optimal ex-post truthful mechanism when the type space of each bidder is a product distribution that satisfies the standard hazard rate condition. We further show a logarithmic approximation when the hazard rate condition is removed, and complete the picture by showing that achieving a sub-logarithmic approximation, even for regular distributions and one bidder, requires pricing bundles of items. Our results are based on formulating novel LP relaxations for these problems, and developing generic rounding schemes from first principles. We believe this approach will be useful in other Bayesian mechanism design contexts.Comment: Final version accepted to STOC '10. Incorporates significant reviewer comment

    Algorithms for â„“p Low Rank Approximation

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    We consider the problem of approximating a given matrix by a low-rank matrix so as to minimize the entry-wise ℓp-approximation error, for any P ≥ 1; the case p = 2 is the classical SVD problem. We obtain the first provably good approximation algorithms for this version of low-rank approximation that work for every value of p ≥ 1, including p = σ. Our algorithms are simple, easy to implement, work well in practice, and illustrate interesting tradeoffs between the approximation quality, the running time, and the rank of the approximating matrix

    Online Set Cover with Set Requests

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    We consider a generic online allocation problem that generalizes the classical online set cover framework by considering requests comprising a set of elements rather than a single element. This problem has multiple applications in cloud computing, crowd sourcing, facility planning, etc. Formally, it is an online covering problem where each online step comprises an offline covering problem. In addition, the covering sets are capacitated, leading to packing constraints. We give a randomized algorithm for this problem that has a nearly tight competitive ratio in both objectives: overall cost and maximum capacity violation. Our main technical tool is an online algorithm for packing/covering LPs with nested constraints, which may be of interest in other applications as well
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