Danger Invariants

Static analysers search for overapproximating proofs of safety commonly known as safety invariants. Conversely, static bug finders (e.g. Bounded Model Checking) give evidence for the failure of an assertion in the form of a counterexample trace. As opposed to safety invariants, the size of a counterexample is dependent on the depth of the bug, i.e., the length of the execution trace prior to the error state, which also determines the computational effort required to find them. We propose a way of expressing danger proofs that is independent of the depth of bugs. Essentially, such danger proofs constitute a compact representation of a counterexample trace, which we call a danger invariant. Danger invariants summarise sets of traces that are guaranteed to be able to reach an error state. Our conjecture is that such danger proofs will enable the design of bug finding analyses for which the computational effort is independent of the depth of bugs, and thus find deep bugs more efficiently. As an exemplar of an analysis that uses danger invariants, we design a bug finding technique based on a synthesis engine. We implemented this technique and compute danger invariants for intricate programs taken from SV-COMP 2016

A Configurable CEGAR Framework with Interpolation-Based Refinements

International audienceCorrectness of software components in a distributed system is a key issue to ensure overall reliability. Formal verification techniques such as model checking can show design flaws at early stages of development. Abstraction is a key technique for reducing complexity by hiding information, which is not relevant for verification. Counterexample-Guided Abstraction Refinement (CEGAR) is a verification algorithm that starts from a coarse abstraction and refines it iteratively until the proper precision is obtained. Many abstraction types and refinement strategies exist for systems with different characteristics. In this paper we show how these algorithms can be combined into a configurable CEGAR framework. In our framework we also present a new CEGAR configuration based on a combination of abstractions, being able to perform better for certain models. We demonstrate the use of the framework by comparing several configurations of the algorithms on various problems, identifying their advantages and shortcomings

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

BACKGROUND: The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. CONCLUSIONS/SIGNIFICANCE: The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD conferred by the M235T variant of the AGT gene. However, the relevance of this weakly positive overall association remains uncertain because it may be due to various residual biases, including HWE-violation and publication biases

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000

Wild species of vaccinium composition, nutritional value and utilization

There are still, in many parts of the globe, some edible fruit collects from the wild for human feeding and other uses. These fruits are utilised either in their raw nature or after some form of processing. One of these wild fruits are Vaccinium species such as Vaccinium myrtoides (Blume) Miq., Vaccinium cylindraceum, Vaccinium padifolium, Vaccinium corymbosum, Vaccinium myrtillus and others from the plant family Ericaceae. The term wild infers non-cultivated plants found in plantation felids or the forest. The species Vaccinium myrtoides and the others are small trees (shrubs) that are well known in Southeast Asian countries such as Philippines, Indonesia and other neighbouring islands. The plants classified as wild growing shrubs. However, the locals have made it be fully utilized in some areas as the wood that are used in grafting utensils and cutleries, or as fuel and fruits. The small-sized berry-like fruits with an average diameter of about 4–5 mm turn black when ripe. They have a delicious flavour that makes it edible and used in the making of other delicacies such as tart and pies to add flavour and as preservatives as well. A few published researches were done on Vaccinium myrtoides showing that it is still used in folkloric medicine. Leaves and fruits extracts showed strong antioxidant activity when tested in-vitro using DPPH (2, 2-diphenyl-1-picrylhydrazyl) free radical scavenging activity as part of a preliminary phytochemical screening for V. myrtoides. The study revealed that the antioxidant activity is due to the presence of flavonoids and other phenolic compounds in the plant leaves and fruit extracts