4,601 research outputs found

    Completeness and Incompleteness of Synchronous Kleene Algebra

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    Synchronous Kleene algebra (SKA), an extension of Kleene algebra (KA), was proposed by Prisacariu as a tool for reasoning about programs that may execute synchronously, i.e., in lock-step. We provide a countermodel witnessing that the axioms of SKA are incomplete w.r.t. its language semantics, by exploiting a lack of interaction between the synchronous product operator and the Kleene star. We then propose an alternative set of axioms for SKA, based on Salomaa's axiomatisation of regular languages, and show that these provide a sound and complete characterisation w.r.t. the original language semantics.Comment: Accepted at MPC 201

    Experiences of diagnosis, stigma, culpability, and disclosure in male patients with hepatitis C virus: an interpretative phenomenological analysis

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    The current study aimed to explore the lived experience of patients with hepatitis C virus infection. Semi-structured interviews were conducted with seven male participants living with hepatitis C virus and were analysed using interpretative phenomenological analysis. Two master themes were identified: (1) diagnosis and the search for meaning and (2) impact of stigma on disclosure. Participants reported fears of contaminating others, feelings of stigma and concerns of disclosing the condition to others. Response to diagnosis, stigma and disclosure among the participants appeared to be interrelated and directly related to locus of blame for virus contraction. More specifically, hepatitis C virus transmission via medical routes led to an externalisation of culpability and an openness to disclosure. Transmission of hepatitis C virus as a direct result of intravenous drug use led to internalised blame and a fear of disclosure. The inter- and intra-personal consequences of hepatitis C virus explored in the current study have potential implications for tailoring future psychological therapy and psychoeducation to the specific needs of the hepatitis C virus population

    The large terminase DNA packaging motor grips DNA with its ATPase domain for cleavage by the flexible nuclease domain

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    Many viruses use a powerful terminase motor to pump their genome inside an empty procapsid shell during virus maturation. The large terminase (TerL) protein contains both enzymatic activities necessary for packaging in such viruses: the adenosine triphosphatase (ATPase) that powers DNA translocation and an endonuclease that cleaves the concatemeric genome at both initiation and completion of genome packaging. However, how TerL binds DNA during translocation and cleavage remains mysterious. Here we investigate DNA binding and cleavage using TerL from the thermophilic phage P74-26. We report the structure of the P74-26 TerL nuclease domain, which allows us to model DNA binding in the nuclease active site. We screened a large panel of TerL variants for defects in binding and DNA cleavage, revealing that the ATPase domain is the primary site for DNA binding, and is required for nuclease activity. The nuclease domain is dispensable for DNA binding but residues lining the active site guide DNA for cleavage. Kinetic analysis of DNA cleavage suggests flexible tethering of the nuclease domains during DNA cleavage. We propose that interactions with the procapsid during DNA translocation conformationally restrict the nuclease domain, inhibiting cleavage; TerL release from the capsid upon completion of packaging unlocks the nuclease domains to cleave DNA

    Local versus Global Strategies in Multi-parameter Estimation

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    We consider the problem of estimating multiple phases using a multi-mode interferometer. In this setting we show that while global strategies with multi-mode entanglement can lead to high precision gains, the same precision enhancements can be obtained with mode-separable states and local measurements. The crucial resource for quantum enhancement is shown to be a large number variance in the probe state, which can be obtained without any entanglement between the modes. This has important practical implications because local strategies using separable states have many advantages over global schemes using multi-mode-entangled states. Such advantages include a robustness to local estimation failure, more flexibility in the distribution of resources, and comparatively easier state preparation. We obtain our results by analyzing two different schemes: the first uses a set of interferometers, which can be used as a model for a network of quantum sensors, and the second looks at measuring a number of phases relative to a reference, which is concerned primarily with quantum imaging

    The glyoxal budget and its contribution to organic aerosol for Los Angeles, California, during CalNex 2010

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    Recent laboratory and field studies have indicated that glyoxal is a potentially large contributor to secondary organic aerosol mass. We present in situ glyoxal measurements acquired with a recently developed, high sensitivity spectroscopic instrument during the CalNex 2010 field campaign in Pasadena, California. We use three methods to quantify the production and loss of glyoxal in Los Angeles and its contribution to organic aerosol. First, we calculate the difference between steady state sources and sinks of glyoxal at the Pasadena site, assuming that the remainder is available for aerosol uptake. Second, we use the Master Chemical Mechanism to construct a two-dimensional model for gas-phase glyoxal chemistry in Los Angeles, assuming that the difference between the modeled and measured glyoxal concentration is available for aerosol uptake. Third, we examine the nighttime loss of glyoxal in the absence of its photochemical sources and sinks. Using these methods we constrain the glyoxal loss to aerosol to be 0-5 × 10-5 s-1 during clear days and (1 ± 0.3) × 10-5 s-1 at night. Between 07:00-15:00 local time, the diurnally averaged secondary organic aerosol mass increases from 3.2 μg m-3 to a maximum of 8.8 μg m -3. The constraints on the glyoxal budget from this analysis indicate that it contributes 0-0.2 μg m-3 or 0-4% of the secondary organic aerosol mass. Copyright 2011 by the American Geophysical Union

    Cohort-Specific Peptide Reagents Broaden Depth and Breadth Estimates of the CD8 T Cell Response to HIV-1 Gag Potential T Cell Epitopes

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    An effective HIV vaccine will need to stimulate immune responses against the sequence diversity presented in circulating virus strains. In this study, we evaluate breadth and depth estimates of potential T-cell epitopes (PTEs) in transmitted founder virus sequence-derived cohort-specific peptide reagents against reagents representative of consensus and global sequences. CD8 T-cells from twenty-six HIV-1+ PBMC donor samples, obtained at 1-year post estimated date of infection, were evaluated. ELISpot assays compared responses to 15mer consensus (n = 121), multivalent-global (n = 320), and 10mer multivalent cohort-specific (n = 300) PTE peptides, all mapping to the Gag antigen. Responses to 38 consensus, 71 global, and 62 cohort-specific PTEs were confirmed, with sixty percent of common global and cohort-specific PTEs corresponding to consensus sequences. Both global and cohort-specific peptides exhibited broader epitope coverage compared to commonly used consensus reagents, with mean breadth estimates of 3.2 (global), 3.4 (cohort) and 2.2 (consensus) epitopes. Global or cohort peptides each identified unique epitope responses that would not be detected if these peptide pools were used alone. A peptide set designed around specific virologic and immunogenetic characteristics of a target cohort can expand the detection of CD8 T-cell responses to epitopes in circulating viruses, providing a novel way to better define the host response to HIV-1 with implications for vaccine development

    Comparison of small-sample standard-error corrections for generalised estimating equations in stepped wedge cluster randomised trials with a binary outcome: A simulation study.

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    Generalised estimating equations with the sandwich standard-error estimator provide a promising method of analysis for stepped wedge cluster randomised trials. However, they have inflated type-one error when used with a small number of clusters, which is common for stepped wedge cluster randomised trials. We present a large simulation study of binary outcomes comparing bias-corrected standard errors from Fay and Graubard; Mancl and DeRouen; Kauermann and Carroll; Morel, Bokossa, and Neerchal; and Mackinnon and White with an independent and exchangeable working correlation matrix. We constructed 95% confidence intervals using a t-distribution with degrees of freedom including clusters minus parameters (DFC-P), cluster periods minus parameters, and estimators from Fay and Graubard (DFFG), and Pan and Wall. Fay and Graubard and an approximation to Kauermann and Carroll (with simpler matrix inversion) were unbiased in a wide range of scenarios with an independent working correlation matrix and more than 12 clusters. They gave confidence intervals with close to 95% coverage with DFFG with 12 or more clusters, and DFC-P with 18 or more clusters. Both standard errors were conservative with fewer clusters. With an exchangeable working correlation matrix, approximated Kauermann and Carroll and Fay and Graubard had a small degree of under-coverage

    California Current seascape influences juvenile salmon foraging ecology at multiple scales

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    Juvenile salmon Oncorhynchus spp. experience variable mortality rates during their first few months in the ocean, and high growth during this period is critical to minimize size selective predation. Examining links between the physical environment and foraging ecology is important to understand mechanisms that drive growth. These mechanisms are complex and include interactions among the physical environment, forage availability, bioenergetics, and salmon foraging behavior. Our objectives were to explore how seascape features (biological and physical) influence juvenile Chinook salmon O. tshawytscha foraging at annual and feedingevent scales in the California Current Ecosystem. We demonstrate that forage abundance was the most influential determinant of mean salmon stomach fullness at the annual scale, while at the feeding-event scale, fullness increased with greater cumulative upwelling during the 10 d prior and at closer distances to thermal fronts. Upwelling promotes nutrient enrichment and productivity, while fronts concentrate organisms, likely resulting in available prey to salmon and increased stomach fullness. Salmon were also more likely to consume krill when there was high prior upwelling,andswitchedtonon-krillinvertebrates(i.e.amphipods,decapods,copepods)inweaker upwelling conditions. As salmon size increased from 72−250 mm, salmon were more likely to consume fish, equal amounts of krill, and fewer non-krill invertebrates. Broad seascape processes determined overall prey availability and fullness in a given year, while fine- and meso-scale processes influenced local accessibility of prey to individual salmon. Therefore, processes occurring at multiple scales will influence how marine organisms respond to changing environment

    Raising argument strength using negative evidence: A constraint on models of induction

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    Both intuitively, and according to similarity-based theories of induction, relevant evidence raises argument strength when it is positive and lowers it when it is negative. In three experiments, we tested the hypothesis that argument strength can actually increase when negative evidence is introduced. Two kinds of argument were compared through forced choice or sequential evaluation: single positive arguments (e.g., “Shostakovich’s music causes alpha waves in the brain; therefore, Bach’s music causes alpha waves in the brain”) and double mixed arguments (e.g., “Shostakovich’s music causes alpha waves in the brain, X’s music DOES NOT; therefore, Bach’s music causes alpha waves in the brain”). Negative evidence in the second premise lowered credence when it applied to an item X from the same subcategory (e.g., Haydn) and raised it when it applied to a different subcategory (e.g., AC/DC). The results constitute a new constraint on models of induction
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