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

KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo

Abstract Histone deacetylase (HDAC) inhibitors have garnered significant attention as cancer drugs. These therapeutic agents have recently been clinically validated with the market approval of vorinostat (SAHA, Zolinza) for treatment of cutaneous T-cell lymphoma. Like vorinostat, most of the small-molecule HDAC inhibitors in clinical development are hydroxamic acids, whose inhibitory activity stems from their ability to coordinate the catalytic Zn 2+ in the active site of HDACs. We sought to identify novel, nonhydroxamate-based HDAC inhibitors with potentially distinct pharmaceutical properties via an ultra-high throughput small molecule biochemical screen against the HDAC activity in a HeLa cell nuclear extract. An A-mercaptoketone series was identified and chemically optimized. The lead compound, KD5170, exhibits HDAC inhibitory activity with an IC 50 of 0.045 Mmol/L in the screening biochemical assay and an EC 50 of 0.025 Mmol/L in HeLa cell -based assays that monitor histone H3 acetylation. KD5170 also exhibits broad spectrum classe

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe