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

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

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

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

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

Preliminary Design of the SAFE Platform

SAFE is a clean-slate design for a secure host architecture. It integrates advances in programming languages, operating systems, and hardware and incorporates formal methods at every step. Though the project is still at an early stage, we have assembled a set of basic architectural choices that we believe will yield a high-assurance system. We sketch the current state of the design and discuss several of these choices.Engineering and Applied Science

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

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

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

ObjectivesObeticholic 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.MethodsPatients 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.ResultsIn 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.ConclusionsFunctional 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