11 research outputs found

    A survey of approximation results for local search algorithms

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    International audienceIn this chapter we review the main results known on local search algorithms with worst case guarantees. We consider classical combinatorial optimization problems: satisfiability problems, traveling salesman and quadratic assignment problems, set packing and set covering problems, maximum independent set, maximum cut, several facility location related problems and finally several scheduling problems. A replica placement problem in a distributed file systems is also considered as an example of the use of a local search algorithm in a distributed environment. For each problem we have provided the neighborhoods used along with approximation results. Proofs when too technical are omitted, but often sketch of proofs are provided

    Influence of Distal Residue B10 on CO Dynamics in Myoglobin and Neuroglobin

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    For many years, myoglobin has served as a paradigm for structure–function studies in proteins. Ligand binding and migration within myoglobin has been studied in great detail by crystallography and spectroscopy, showing that gaseous ligands such as O2, CO, and NO not only bind to the heme iron but may also reside transiently in three internal ligand docking sites, the primary docking site B and secondary sites C and D. These sites affect ligand association and dissociation in specific ways. Neuroglobin is another vertebrate heme protein that also binds small ligands. Ligand migration pathways in neuroglobin have not yet been elucidated. Here, we have used Fourier transform infrared temperature derivative spectroscopy at cryogenic temperatures to compare the influence of the side chain volume of amino acid residue B10 on ligand migration to and rebinding from docking sites in myoglobin and neuroglobin

    A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

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    Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10 -8) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10 -10). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes. © 2016 Nature America, Inc

    Congenital Defects Or Adverse Developmental Effects In Vertebrate Wildlife: The Wildlife-Human Connection

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