567 research outputs found

    Generalized partition crossover for the traveling salesman problem

    Get PDF
    2011 Spring.Includes bibliographical references.The Traveling Salesman Problem (TSP) is a well-studied combinatorial optimization problem with a wide spectrum of applications and theoretical value. We have designed a new recombination operator known as Generalized Partition Crossover (GPX) for the TSP. GPX is unique among other recombination operators for the TSP in that recombining two local optima produces new local optima with a high probability. Thus the operator can 'tunnel' between local optima without the need for intermediary solutions. The operator is respectful, meaning that any edges common between the two parent solutions are present in the offspring, and transmits alleles, meaning that offspring are comprised only of edges found in the parent solutions. We design a hybrid genetic algorithm, which uses local search in addition to recombination and selection, specifically for GPX. We show that this algorithm outperforms Chained Lin-Kernighan, a state-of-the-art approximation algorithm for the TSP. We next analyze these algorithms to determine why the algorithms are not capable of consistently finding a globally optimal solution. Our results reveal a search space structure which we call 'funnels' because they are analogous to the funnels found in continuous optimization. Funnels are clusters of tours in the search space that are separated from one another by a non-trivial distance. We find that funnels can trap Chained Lin-Kernighan, preventing the search from finding an optimal solution. Our data indicate that, under certain conditions, GPX can tunnel between funnels, explaining the higher frequency of optimal solutions produced by our hybrid genetic algorithm using GPX

    α-Elapitoxin-Aa2a, a long-chain snake α-neurotoxin with potent actions on muscle (α1)<inf>2</inf>βγδ nicotinic receptors, lacks the classical high affinity for neuronal α7 nicotinic receptors

    Full text link
    In contrast to all classical long-chain α-neurotoxins possessing the critical fifth disulfide bond, α-elapitoxin-Aa2a (α-EPTX-Aa2a), a novel long-chain α-neurotoxin from the common death adder Acanthophis antarcticus, lacks affinity for neuronal α7-type nicotinic acetylcholine receptors (nAChRs) α-EPTX-Aa2a (8850 Da; 0.1-1 μM) caused a concentration-dependent inhibition of indirect twitches, and blocked contractures to cholinergic agonists in the isolated chick biventer cervicis nerve-muscle preparation, consistent with a postsynaptic curaremimetic mode of action. α-EPTX-Aa2a (1-10 nM) produced a potent pseudo-irreversible antagonism of chick muscle nAChRs, with an estimated pA2 value of 8.311 ± 0.031, which was not reversed by monovalent death adder antivenom. This is only 2.5-fold less potent than the prototypical long-chain α-neurotoxin, α-bungarotoxin. In contrast, α-EPTX-Aa2a produced complete, but weak, inhibition of 125I-α-bungarotoxin binding to rat hippocampal α7 nAChRs (pKI = 3.670), despite high sequence homology and similar mass to a wide range of long-chain α-neurotoxins. The mostly likely cause for the loss of α7 binding affinity is a leucine substitution, in loop II of α-EPTX-Aa2a, for the highly conserved Arg33 in long-chain α-neurotoxins. Arg 33 has been shown to be critical for both neuronal and muscle activity. Despite this substitution, α-EPTX-Aa2a retains high affinity for muscle (α1)2βγδ nAChRs. This is probably as a result of an Arg29 residue, previously shown to be critical for muscle (α1)2βγδ nAChR affinity, and highly conserved across all short-chain, but not long-chain, α-neurotoxins. α-EPTX-Aa2a therefore represents a novel atypical long-chain α-neurotoxin that includes a fifth disulfide but exhibits differential affinity for nAChR subtypes. Copyright © 2010 Published by Elsevier Inc. All rights reserved

    The ecology of a new invasion by Bellamya japonica in the Savannah basin

    Get PDF
    The first known infestation of Bellamya japonica in the Savannah River Basin was discovered in 2006. Investigations of this population led to questions regarding their distribution and behavior. We have completed experiments on behavior and concluded that there exists a significant negative phototactic but no detectable geotactic response. In addition, a study of their dispersal using mark-recapture methods concluded that, while this technique was useful to follow the life history of individual snails, they did not meet the method assumptions and therefore this method could not produce a reliable population estimate. Studies of fecundity have shown a seasonal trend with an unsurprising correlation to water temperatures and time-of-year. Fecundity rates are still being assessed. Age is difficult to determine and the life history studies using marked snails will assist with this as well. Metabolism is unknown for this species but methods are currently being developed. Anecdotal observations suggested a possible circadian rhythm with regard to fecundity. A systematic study of this phenomenon is also in progress. If successful our studies may help with management of this infestation in the future

    SO2 Emissions and Lifetimes: Estimates from Inverse Modeling Using In Situ and Global, Space-Based (SCIAMACHY and OMI) Observations

    Get PDF
    Top-down constraints on global sulfur dioxide (SO2) emissions are inferred through inverse modeling using SO2 column observations from two satellite instruments (SCIAMACHY and OMI). We first evaluated the S02 column observations with surface SO2 measurements by applying local scaling factors from a global chemical transport model (GEOS-Chem) to SO2 columns retrieved from the satellite instruments. The resulting annual mean surface SO2 mixing ratios for 2006 exhibit a significant spatial correlation (r=0.86, slope=0.91 for SCIAMACHY and r=0.80, slope = 0.79 for OMI) with coincident in situ measurements from monitoring networks throughout the United States and Canada. We evaluate the GEOS-Chem simulation of the SO2 lifetime with that inferred from in situ measurements to verity the applicability of GEOS-Chem for inversion of SO2 columns to emissions. The seasonal mean SO2 lifetime calculated with the GEOS-Chem model over the eastern United States is 13 h in summer and 48 h in winter, compared to lifetimes inferred from in situ measurements of 19 +/- 7 h in summer and 58 +/- 20 h in winter. We apply SO2 columns from SCIAMACHY and OMI to derive a top-down anthropogenic SO2 emission inventory over land by using the local GEOS-Chem relationship between SO2 columns and emissions. There is little seasonal variation in the top-down emissions (<15%) over most major industrial regions providing some confidence in the method. Our global estimate for annual land surface anthropogenic SO2 emissions (52.4 Tg S/yr from SCIAMACHY and 49.9 Tg S / yr from OMI) closely agrees with the bottom-up emissions (54.6 Tg S/yr) in the GEOS-Chem model and exhibits consistency in global distributions with the bottom-up emissions (r = 0.78 for SCIAMACHY, and r = 0.77 for OMI). However, there are significant regional differences

    Implementation of a Renal Precision Medicine Program: Clinician Attitudes and Acceptance

    Get PDF
    A precision health initiative was implemented across a multi-hospital health system, wherein a panel of genetic variants was tested and utilized in the clinical care of chronic kidney disease (CKD) patients. Pharmacogenomic predictors of antihypertensive response and genomic predictors of CKD were provided to clinicians caring for nephrology patients. To assess clinician knowledge, attitudes, and willingness to act on genetic testing results, a Likert-scale survey was sent to and self-administered by these nephrology providers (N = 76). Most respondents agreed that utilizing pharmacogenomic-guided antihypertensive prescribing is valuable (4.0 ± 0.7 on a scale of 1 to 5, where 5 indicates strong agreement). However, the respondents also expressed reluctance to use genetic testing for CKD risk stratification due to a perceived lack of supporting evidence (3.2 ± 0.9). Exploratory sub-group analyses associated this reluctance with negative responses to both knowledge and attitude discipline questions, thus suggesting reduced exposure to and comfort with genetic information. Given the evolving nature of genomic implementation in clinical care, further education is warranted to help overcome these perception barriers

    Techniques for accurate protein identification in shotgun proteomic studies of human, mouse, bovine, and chicken lenses

    Get PDF
    Analysis of shotgun proteomics datasets requires techniques to distinguish correct peptide identifications from incorrect identifications, such as linear discriminant functions and target/decoy protein databases. We report an efficient, flexible proteomic analysis workflow pipeline that implements these techniques to control both peptide and protein false discovery rates. We demonstrate its performance by analyzing two-dimensional liquid chromatography separations of lens proteins from human, mouse, bovine, and chicken lenses. We compared the use of International Protein Index databases to UniProt databases and no-enzyme SEQUEST searches to tryptic searches. Sequences present in the International Protein Index databases allowed detection of several novel crystallins. An alternate start codon isoform of βA4 was found in human lens. The minor crystallin γN was detected for the first time in bovine and chicken lenses. Chicken γS was identified and is the first member of the γ-crystallin family observed in avian lenses
    • …
    corecore