3,290 research outputs found

    A multiple type bike repositioning problem

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    This paper investigates a new static bicycle repositioning problem in which multiple types of bikes are considered. Some types of bikes that are in short supply at a station can be substituted by other types, whereas some types of bikes can occupy the spaces of other types in the vehicle during repositioning. These activities provide two new strategies, substitution and occupancy, which are examined in this paper. The problem is formulated as a mixed-integer linear programming problem to minimize the total cost, which consists of the route travel cost, penalties due to unmet demand, and penalties associated with the substitution and occupancy strategies. A combined hybrid genetic algorithm is proposed to solve this problem. This solution algorithm consists of (i) a modified version of a hybrid genetic search with adaptive diversity control to determine routing decisions and (ii) a proposed greedy heuristic to determine the loading and unloading instructions at each visited station and the substitution and occupancy strategies. The results show that the proposed method can provide high-quality solutions with short computing times. Using small examples, this paper also reveals problem properties and repositioning strategies in bike sharing systems with multiple types of bikes.published_or_final_versio

    A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

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    A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals

    Phase Shifting Capacity of the Circadian Pacemaker Determined by the SCN Neuronal Network Organization

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    In mammals, a major circadian pacemaker that drives daily rhythms is located in the suprachiasmatic nuclei (SCN), at the base of the hypothalamus. The SCN receive direct light input via the retino-hypothalamic tract. Light during the early night induces phase delays of circadian rhythms while during the late night it leads to phase advances. The effects of light on the circadian system are strongly dependent on the photoperiod to which animals are exposed. An explanation for this phenomenon is currently lacking.We recorded running wheel activity in C57 mice and observed large amplitude phase shifts in short photoperiods and small shifts in long photoperiods. We investigated whether these different light responses under short and long days are expressed within the SCN by electrophysiological recordings of electrical impulse frequency in SCN slices. Application of N-methyl-D-aspartate (NMDA) induced sustained increments in electrical activity that were not significantly different in the slices from long and short photoperiods. These responses led to large phase shifts in slices from short days and small phase shifts in slices from long days. An analysis of neuronal subpopulation activity revealed that in short days the amplitude of the rhythm was larger than in long days.The data indicate that the photoperiodic dependent phase responses are intrinsic to the SCN. In contrast to earlier predictions from limit cycle theory, we observed large phase shifting responses in high amplitude rhythms in slices from short days, and small shifts in low amplitude rhythms in slices from long days. We conclude that the photoperiodic dependent phase responses are determined by the SCN and propose that synchronization among SCN neurons enhances the phase shifting capacity of the circadian system

    Dynamical R-parity Breaking at the LHC

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    In a class of extensions of the minimal supersymmetric standard model with (B-L)/left-right symmetry that explains the neutrino masses, breaking R-parity symmetry is an essential and dynamical requirement for successful gauge symmetry breaking. Two consequences of these models are: (i) a new kind of R-parity breaking interaction that protects proton stability but adds new contributions to neutrinoless double beta decay and (ii) an upper bound on the extra gauge and parity symmetry breaking scale which is within the large hadron collider (LHC) energy range. We point out that an important prediction of such theories is a potentially large mixing between the right-handed charged lepton (ece^c) and the superpartner of the right-handed gauge boson (W~R+\widetilde W_R^+), which leads to a brand new class of R-parity violating interactions of type μc~νμcec\widetilde{\mu^c}^\dagger\nu_\mu^c e^c and \widetilde{d^c}^\dagger\u^c e^c. We analyze the relevant constraints on the sparticle mass spectrum and the LHC signatures for the case with smuon/stau NLSP and gravitino LSP. We note the "smoking gun" signals for such models to be lepton flavor/number violating processes: ppμ±μ±e+ejjpp\to \mu^\pm\mu^\pm e^+e^-jj (or τ±τ±e+ejj\tau^\pm\tau^\pm e^+e^-jj) and ppμ±e±bbˉjjpp\to\mu^\pm e^\pm b \bar{b} jj (or τ±e±bbˉjj\tau^\pm e^\pm b \bar{b} jj) without significant missing energy. The predicted multi-lepton final states and the flavor structure make the model be distinguishable even in the early running of the LHC.Comment: 30 pages, 13 figures, 6 tables, reference adde

    Membrane Deformability and Membrane Tension of Single Isolated Mitochondria

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    Mitochondria dynamics is crucial to many biological processes such as mitochondria fusion and fission, which is highly correlated to the mechanics of single mitochondria. However, the mechanobiological coupling of mitochondria has been poorly understood. Here membrane deformability and membrane tension of individual mitochondria isolated from MtDsRed labeled human embryonic T-Rex-293 kidney cells were measured using a micropipette aspiration assay. The results demonstrated that membrane deformation of isolated mitochondria exhibited an elastic transition phase followed by an equilibrium phase, and mitochondrial membrane tension was proportional to the area compressibility. It was also indicated that mitochondrial membrane deformability was significantly affected by physical chemical factors such as osmotic pressure or pH value, and was further correlated to mitochondrial functionality in different respiratory states and Ca2+ regulation. These findings provide a new insight into understanding the mechanical regulation of mitochondrial physiology.</p

    Primary extraskeletal osteosarcoma of omentum majus

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    Extraskeletal osteosarcoma is a rare malignant soft tissue tumor. Here we present a case of a primary extraskeletal osteosarcoma arising from omentum majus in a 40-year-old Chinese woman. Ultrasonography of the pelvic cavity showed a large soft tissue mass with marked calcification. Complete surgical resection of the primary tumor was performed and the histopathological diagnosis was extraskeletal osteosarcoma of omentum majus. She was followed up without adjuvant radiotherapy and chemotherapy, and died from widespread intra-abdominal, lung and liver metastases 7 months postoperatively

    Enhancing Symbolic Execution of Heap-based Programs with Separation Logic for Test Input Generation

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    Symbolic execution is a well established method for test input generation. Despite of having achieved tremendous success over numerical domains, existing symbolic execution techniques for heap-based programs are limited due to the lack of a succinct and precise description for symbolic values over unbounded heaps. In this work, we present a new symbolic execution method for heap-based programs based on separation logic. The essence of our proposal is context-sensitive lazy initialization, a novel approach for efficient test input generation. Our approach differs from existing approaches in two ways. Firstly, our approach is based on separation logic, which allows us to precisely capture preconditions of heap-based programs so that we avoid generating invalid test inputs. Secondly, we generate only fully initialized test inputs, which are more useful in practice compared to those partially initialized test inputs generated by the state-of-the-art tools. We have implemented our approach as a tool, called Java StarFinder, and evaluated it on a set of programs with complex heap inputs. The results show that our approach significantly reduces the number of invalid test inputs and improves the test coverage

    Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

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    Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides
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