888 research outputs found

    Violator Spaces: Structure and Algorithms

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    Sharir and Welzl introduced an abstract framework for optimization problems, called LP-type problems or also generalized linear programming problems, which proved useful in algorithm design. We define a new, and as we believe, simpler and more natural framework: violator spaces, which constitute a proper generalization of LP-type problems. We show that Clarkson's randomized algorithms for low-dimensional linear programming work in the context of violator spaces. For example, in this way we obtain the fastest known algorithm for the P-matrix generalized linear complementarity problem with a constant number of blocks. We also give two new characterizations of LP-type problems: they are equivalent to acyclic violator spaces, as well as to concrete LP-type problems (informally, the constraints in a concrete LP-type problem are subsets of a linearly ordered ground set, and the value of a set of constraints is the minimum of its intersection).Comment: 28 pages, 5 figures, extended abstract was presented at ESA 2006; author spelling fixe

    Generalized Shortest Path Kernel on Graphs

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    We consider the problem of classifying graphs using graph kernels. We define a new graph kernel, called the generalized shortest path kernel, based on the number and length of shortest paths between nodes. For our example classification problem, we consider the task of classifying random graphs from two well-known families, by the number of clusters they contain. We verify empirically that the generalized shortest path kernel outperforms the original shortest path kernel on a number of datasets. We give a theoretical analysis for explaining our experimental results. In particular, we estimate distributions of the expected feature vectors for the shortest path kernel and the generalized shortest path kernel, and we show some evidence explaining why our graph kernel outperforms the shortest path kernel for our graph classification problem.Comment: Short version presented at Discovery Science 2015 in Banf

    New insight into breast cancer cells involving drug combinations for dopamine and serotonin receptors

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    The breast cancer therapies available are insufficient, especially since first-line treatments, such as paclitaxel, result in drug resistance and their toxicity often limits their concentration. Strategies like drug repurposing are beneficial, and novel treatments can emerge by repurposing drugs that interfere with the dopamine and serotonin receptors, and thus influence tumor growth. In this study, the MTT assay was used to test the efficacy of such repurposed drugs commonly used for neurodegenerative disorders that act on the dopamine and serotonin receptors to reduce the MCF7 cell’s viability, either by their single use or in combination with the reference drug paclitaxel. Furthermore, the expression of vimentin and E-cadherin was assayed by immunofluorescence. The dopamine receptor-altering drugs benztropine and thioridazine resulted in the strongest reduction of cell viability when combined with paclitaxel, which may be connected to the alteration of E-cadherin rather than vimentin expression. More studies are needed to understand the mechanism of action of the combinations tested and the efficacious role of dopamine and serotonin.This work was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operational Programme for Competitiveness and Internationalisation (POCI), Portugal, in the framework of the project IF/00092/2014/CP1255/CT0004. N.V. thanks Fundação para a Ciência e a Tecnologia (FCT, Portugal) for supporting these studies through nationally-funded projects within the CINTESIS R&D unit (reference UIDB/4255/2020). The contents of this report are solely the responsibility of the authors and do not necessarily represent the official view of the FCT

    Inhibition of the formation in vitro of putatively carcinogenic metabolites derived from S. Haematobium and O. Viverrini by Combination of Drugs with Antioxidants

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    Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as carcinogenic. Although carcinogenesis might be a multifactorial process, it has been postulated that these helminth produce/excrete oxysterols and estrogen-like metabolites that might act as initiators of their infection-associated carcinogenesis. Current treatment and control of these infections rely on a single drug, praziquantel, that mainly targets the parasites and not the pathologies related to the infection including cancer. Thus, there is a need to search for novel therapeutic alternatives that might include combinations of drugs and drug repurposing. Based on these concepts, we propose a novel therapeutic strategy that combines drugs with molecule antioxidants. We evaluate the efficacy of a novel therapeutic strategy to prevent the formation of putative carcinogenic metabolites precursors and DNA adducts. Firstly, we used a methodology previously established to synthesize metabolites precursors and DNA adducts in the presence of CYP450. Then, we evaluated the inhibition of their formation induced by drugs and antioxidants alone or in combination. Drugs and resveratrol alone did not show a significant inhibitory effect while N-acetylcysteine inhibited the formation of most metabolite precursors and DNA adducts. Moreover, the combinations of classical drugs with antioxidants were more effective rather than compounds alone. This strategy might be a valuable tool to prevent the initiation of helminth infection-associated carcinogenesis.This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia, in the framework of the projects "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). N.V. also acknowledges support from FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004. FUNDING TEXT 2: Funding: This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia, in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). N.V. also acknowledges support from FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004

    On group properties and reality conditions of UOSp(1|2) gauge transformations

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    For osp(1|2;C) graded Lie algebra, which proper Lie subalgebra is su(2), we consider the Baker-Campbell-Hausdorff formula and formulate a reality condition for the Grassmann-odd transformation parameters that multiply the pair of odd generators of the graded Lie algebra. Utilization of su(2)-spinors clarifies the nature of Grassmann-odd transformation parameters and allow us an investigation of the corresponding infinitesimal gauge transformations. We also explore action of the corresponding group element of UOSp(1|2) on an appropriately graded representation space and find that the graded generalization of hermitian conjugation is compatible with the Dirac adjoint. Consistency of generalized (graded) unitary condition with the proposed reality condition is shown.Comment: 14 page
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