133 research outputs found

    From Network Interface to Multithreaded Web Applications: A Case Study in Modular Program Verification

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    Many verifications of realistic software systems are monolithic, in the sense that they define single global invariants over complete system state. More modular proof techniques promise to support reuse of component proofs and even reduce the effort required to verify one concrete system, just as modularity simplifies standard software development. This paper reports on one case study applying modular proof techniques in the Coq proof assistant. To our knowledge, it is the first modular verification certifying a system that combines infrastructure with an application of interest to end users. We assume a nonblocking API for managing TCP networking streams, and on top of that we work our way up to certifying multithreaded, database-backed Web applications. Key verified components include a cooperative threading library and an implementation of a domain-specific language for XML processing. We have deployed our case-study system on mobile robots, where it interfaces with off-the-shelf components for sensing, actuation, and control.National Science Foundation (U.S.) (Grant CCF-1253229)United States. Defense Advanced Research Projects Agency (Agreement FA8750-12-2-0293

    From Network Interface to Multithreaded Web Applications: A Case Study in Modular Program Verification

    Get PDF
    Many verifications of realistic software systems are monolithic, in the sense that they define single global invariants over complete system state. More modular proof techniques promise to support reuse of component proofs and even reduce the effort required to verify one concrete system, just as modularity simplifies standard software development. This paper reports on one case study applying modular proof techniques in the Coq proof assistant. To our knowledge, it is the first modular verification certifying a system that combines infrastructure with an application of interest to end users. We assume a nonblocking API for managing TCP networking streams, and on top of that we work our way up to certifying multithreaded, database-backed Web applications. Key verified components include a cooperative threading library and an implementation of a domain-specific language for XML processing. We have deployed our case-study system on mobile robots, where it interfaces with off-the-shelf components for sensing, actuation, and control.National Science Foundation (U.S.) (NSF grant CCF-1253229)United States. Defense Advanced Research Projects Agency (DARPA, agreement number FA8750-12-2-0293

    Morphometry and growth of sea pen species from dense habitats in the Gulf of St. Lawrence, eastern Canada

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    We examined four species of sea pen (Anthoptilum grandiflorum, Halipteris finmarchica, Pennatula aculeata and Pennatula grandis) collected from the Gulf of St. Lawrence and mouth of the Laurentian Channel, eastern Canada. An exponential length–weight relationship was found for all four species, where growth in weight was progressively greater than growth in length with increasing colony size. Halipteris finmarchica, P. grandis and P. aculeata presented the better allometric fits, explaining over 80% of the variance. In addition, a count of growth increments visible in transverse sections in 86 A. grandiflorum and 80 P. aculeata samples was made. Presumed ages ranged between 5 and 28 years for A. grandiflorum and 2 and 21 years for P. aculeata. Radiocarbon assays were inconclusive and could not be used to confirm these ages; further age validation is required. Radial growth of the rod is slow during the first years, increasing at intermediate sizes of the colony and slowing down again for large colonies. Similar results were obtained from the relationship between colony length and number of growth increments where a logistic model was the best fit to the data. On average Spearman’s rank correlations showed 11% of shared variance between sea pen length or weight and environmental variables. Bottom temperature and salinity, depth and summer primary production were significantly correlated to sea pen size for most species.En prensa1,48

    PIN6 is required for nectary auxin response and short stamen development

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/1/tpj12184-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/2/tpj12184.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/3/tpj12184-sup-0004-FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/4/tpj12184-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/5/tpj12184-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/6/tpj12184-sup-0005-FigS5.pd

    COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls

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    Copyright \ua9 2024 The Author(s).Objectives: Obeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in PBC patients improve with OCA therapy. Methods: Patients randomized to OCA (5–10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC). The primary composite endpoint was time to death, liver transplant, model for end-stage liver disease score ≥15, uncontrolled ascites, or hospitalization for hepatic decompensation. A prespecified propensity score–weighted EC group was derived from a US healthcare claims database. Results: In the RCT, the primary endpoint occurred in 28.6% of OCA (n=168) and 28.9% of placebo patients (n=166; intent-to-treat [ITT] analysis hazard ratio [HR]=1.01, 95% CI=0.68–1.51), but functional unblinding and crossover to commercial therapy occurred, especially in the placebo arm. Correcting for these using inverse probability of censoring weighting (IPCW) and as-treated analyses shifted the HR to favor OCA. In the EC (n=1051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR=0.39; 95% CI=0.22–0.69; P=0.001). No new safety signals were identified in the RCT. Conclusions: Functional unblinding and treatment crossover, particularly in the placebo arm, confounded the ITT estimate of outcomes associated with OCA in the RCT. Comparison with the real-world EC showed that OCA treatment significantly reduced the risk of negative clinical outcomes. These analyses demonstrate the value of EC data in confirmatory trials and suggest that treatment with OCA improves clinical outcomes in patients with PBC

    Identification of a sex-linked SNP marker in the salmon louse (Lepeophtheirus salmonis) using RAD sequencing

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    The salmon louse (Lepeophtheirus salmonis (Krøyer, 1837)) is a parasitic copepod that can, if untreated, cause considerable damage to Atlantic salmon (Salmo salar Linnaeus, 1758) and incurs significant costs to the Atlantic salmon mariculture industry. Salmon lice are gonochoristic and normally show sex ratios close to 1:1. While this observation suggests that sex determination in salmon lice is genetic, with only minor environmental influences, the mechanism of sex determination in the salmon louse is unknown. This paper describes the identification of a sex-linked Single Nucleotide Polymorphism (SNP) marker, providing the first evidence for a genetic mechanism of sex determination in the salmon louse. Restriction site-associated DNA sequencing (RAD-seq) was used to isolate SNP markers in a laboratory-maintained salmon louse strain. A total of 85 million raw Illumina 100 base paired-end reads produced 281,838 unique RAD-tags across 24 unrelated individuals. RAD marker Lsa101901 showed complete association with phenotypic sex for all individuals analysed, being heterozygous in females and homozygous in males. Using an allele-specific PCR assay for genotyping, this SNP association pattern was further confirmed for three unrelated salmon louse strains, displaying complete association with phenotypic sex in a total of 96 genotyped individuals. The marker Lsa101901 was located in the coding region of the prohibitin-2 gene, which showed a sex-dependent differential expression, with mRNA levels determined by RT-qPCR about 1.8-fold higher in adult female than adult male salmon lice. This study's observations of a novel sex-linked SNP marker are consistent with sex determination in the salmon louse being genetic and following a female heterozygous system. Marker Lsa101901 provides a tool to determine the genetic sex of salmon lice, and could be useful in the development of control strategies
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