Certification of SAT Solvers in Coq

International audienceWe describe a fully portable, open source certifier for traces of SAT problems produced by zChaff. It can also be easily adapted for MiniSat, PicoSat or BooleForce, and we have done it for PicoSat. Our certifier has been developed with the proof assistant Coq. We give some figures based on the pigeon hole, comparing both PicoSat and zChaff on the one hand, and our certifier with another certifier also developed with Coq

Compositional Abstraction Refinement for Component-Based Systems

The efficiency of the compositional verification of invariants depends on the abstraction, which may lead to verification incompleteness. The invariant strengthening and state partitioning techniques are proposed in this paper. The former could refine the overapproximation by removing the unreachable states, and the latter is a variant of counterexample-guided abstraction refinement. Integrated with these two refinement techniques, a unified compositional verification framework is presented to strengthen the abstraction and find counterexamples. Some examples are included to show that the verification of the safety properties in component-based systems has been achieved by our framework

Certification of SAT Solvers in Coq

International audienceWe describe a fully portable, open source certifier for traces of SAT problems produced by zChaff. It can also be easily adapted for MiniSat, PicoSat or BooleForce, and we have done it for PicoSat. Our certifier has been developed with the proof assistant Coq. We give some figures based on the pigeon hole, comparing both PicoSat and zChaff on the one hand, and our certifier with another certifier also developed with Coq

Receptor-interacting protein kinase 4 and interferon regulatory factor 6 function as a signaling axis to regulate keratinocyte differentiation

Receptor-interacting protein kinase 4 (RIPK4) and interferon regulatory factor 6 (IRF6) are critical regulators of keratinocyte differentiation, and their mutation causes the related developmental epidermal disorders Bartsocas-Papas syndrome and popliteal pterygium syndrome, respectively. However, the signaling pathways in which RIPK4 and IRF6 operate to regulate keratinocyte differentiation are poorly defined. Here we identify and mechanistically define a direct functional relationship between RIPK4 and IRF6. Gene promoter reporter and in vitro kinase assays, coimmunoprecipitation experiments, and confocal microscopy demonstrated that RIPK4 directly regulates IRF6 trans-activator activity and nuclear translocation. Gene knockdown and overexpression studies indicated that the RIPK4-IRF6 signaling axis controls the expression of key transcriptional regulators of keratinocyte differentiation, including Grainyhead-like 3 and OVO-like 1. Additionally, we demonstrate that the p.Ile121Asn missense mutation in RIPK4, which has been identified recently in Bartsocas-Papas syndrome, inhibits its kinase activity, thereby preventing RIPK4-mediated IRF6 activation and nuclear translocation. We show, through mutagenesis-based experiments, that Ser-413 and Ser-424 in IRF6 are important for its activation by RIPK4. RIPK4 is also important for the regulation of IRF6 expression by the protein kinase C pathway. Therefore, our findings not only provide important mechanistic insights into the regulation of keratinocyte differentiation by RIPK4 and IRF6, but they also suggest one mechanism by which mutations in RIPK4 may cause epidermal disorders (e.g. Bartsocas-Papas syndrome), namely by the impaired activation of IRF6 by RIPK4

PubChem3D: a new resource for scientists

<p>Abstract</p> <p>Background</p> <p>PubChem is an open repository for small molecules and their experimental biological activity. PubChem integrates and provides search, retrieval, visualization, analysis, and programmatic access tools in an effort to maximize the utility of contributed information. There are many diverse chemical structures with similar biological efficacies against targets available in PubChem that are difficult to interrelate using traditional 2-D similarity methods. A new layer called PubChem3D is added to PubChem to assist in this analysis.</p> <p>Description</p> <p>PubChem generates a 3-D conformer model description for 92.3% of all records in the PubChem Compound database (when considering the parent compound of salts). Each of these conformer models is sampled to remove redundancy, guaranteeing a minimum (non-hydrogen atom pair-wise) RMSD between conformers. A diverse conformer ordering gives a maximal description of the conformational diversity of a molecule when only a subset of available conformers is used. A pre-computed search per compound record gives immediate access to a set of 3-D similar compounds (called "Similar Conformers") in PubChem and their respective superpositions. Systematic augmentation of PubChem resources to include a 3-D layer provides users with new capabilities to search, subset, visualize, analyze, and download data.</p> <p>A series of retrospective studies help to demonstrate important connections between chemical structures and their biological function that are not obvious using 2-D similarity but are readily apparent by 3-D similarity.</p> <p>Conclusions</p> <p>The addition of PubChem3D to the existing contents of PubChem is a considerable achievement, given the scope, scale, and the fact that the resource is publicly accessible and free. With the ability to uncover latent structure-activity relationships of chemical structures, while complementing 2-D similarity analysis approaches, PubChem3D represents a new resource for scientists to exploit when exploring the biological annotations in PubChem.</p

Low-Frequency Variability and the Unusual Indian Ocean Dipole Events in 2015 and 2016

An unusual positive Indian Ocean Dipole (IOD) event occurred in 2015 associated with the 2015/2016 extreme El Nino. Unlike the canonical IOD, sea surface temperature (SST) warming in the west central tropical Indian Ocean (TIO) dominated the strong zonal SST gradient as cooling off Sumatra-Java was weak. Over the southeastern TIO, deeper thermocline has suppressed the upwelling cooling since 2012. Such deepened thermocline related to a low-frequency adjustment and curtailed cool anomalies in the 2015 positive IOD but favored warm anomalies in the 2016 negative IOD. Based on statistical analyses, ocean assimilation data confirm that an IOD-like pattern exists in the TIO on decadal timescale. During a negative decadal IOD-like phase, thermocline is deeper in the southeastern TIO; the thermocline-SST feedback is unfavorable for positive IOD occurrence and intensity, but conducive to negative IOD events. Thus, we propose that the 2015-2016 IOD events are modulated by the low-frequency variability of thermocline

Clinical Effect of Hufu Copper Scraping on Shoulder-Hand Syndrome after Stroke

Objective. To explore the clinical effect of Hufu copper scraping on shoulder-hand syndrome after stroke. Methods. A total of 60 patients with shoulder-hand syndrome after stroke admitted to the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine were enrolled between January 2020 and June 2021. According to the random number table method, they were divided into the control group (n = 30) and the intervention group (n = 30). The control group was given routine rehabilitation intervention, while the intervention group was additionally given Hufu copper scraping. The intervention effect, occurrence of adverse reactions during the intervention, pain, swelling degree of affected hands, serum calcitonin gene-related peptide (CGRP), substance P (SP), and Barthel index before and after 2 months of intervention were compared between the two groups. Results. After intervention, the total response rate of the intervention group was significantly higher than that of the control group (96.67% vs 80.00%) (P<0.05). After intervention, the score of the visual analogue scale (VAS) and water displacement in the intervention group were lower than those in the control group (P<0.05). After intervention, levels of CGRP and SP in the intervention group were lower than those in the control group, while the Barthel index was higher compared to the control group (P<0.05). Conclusion. The intervention effect of Hufu copper scraping is good, which can promote the recovery of related symptoms, relieve pain and swelling of affected hands, downregulate levels of disease-promoting markers, and accelerate recovery of related function in patients with shoulder-hand syndrome after stroke