Strengthening Model Checking Techniques with Inductive Invariants

This paper describes optimized techniques to efficiently compute and reap benefits from inductive invariants within SAT-based model checking. We address sequential circuit verification, and we consider both equivalences and implications between pairs of nodes in the logic networks. First, we present a very efficient dynamic procedure, based on equivalence classes and incremental SAT, specifically oriented to reduce the set of checked invariants. Then, we show how to effectively integrate the computation of inductive invariants within state-of-the-art SAT-based model checking procedures. Experiments (on more than 600 designs) show the robustness of our approach on verification instances on which stand-alone techniques fai

Circuit Based Quantification: Back to State Set Manipulation within Unbounded Model Checking

In this paper a non-canonical circuit-based state set representation is used to efficiently perform quantifier elimination. The novelty of this approach lies in adapting equivalence checking and logic synthesis techniques, to the goal of compacting circuit based state set representations resulting from existential quantification. The method can be efficiently combined with other verification approaches such as inductive and SAT-based pre-image verifications

A paperfluidic platform to detect Neisseria gonorrhoeae in clinical samples

Globally, the microbe Neisseria gonorrhoeae (NG) causes 106 million newly documented sexually transmitted infections each year. Once appropriately diagnosed, NG infections can be readily treated with antibiotics, but high-risk patients often do not return to the clinic for treatment if results are not provided at the point of care. A rapid, sensitive molecular diagnostic would help increase NG treatment and reduce the prevalence of this sexually transmitted disease. Here, we report on the design and development of a rapid, highly sensitive, paperfluidic device for point-of-care diagnosis of NG. The device integrates patient swab sample lysis, nucleic acid extraction, thermophilic helicase-dependent amplification (tHDA), an internal amplification control (NGIC), and visual lateral flow detection within an 80 min run time. Limits of NG detection for the NG/NGIC multiplex tHDA assay were determined within the device, and clinical performance was validated retroactively against qPCR-quantified patient samples in a proof-of-concept study. This paperfluidic diagnostic has a clinically relevant limit of detection of 500 NG cells per device with analytical sensitivity down to 10 NG cells per device. In triplicate testing of 40 total urethral and vaginal swab samples, the device had 95% overall sensitivity and 100% specificity, approaching current laboratory-based molecular NG diagnostics. This diagnostic platform could increase access to accurate NG diagnoses to those most in need.This work was funded by the National Institute of Health National Institute of Allergy and Infectious Diseases award number R01 AI113927 to Boston University and the NIH National Institute of Biomedical and Bioengineering award number U54 EB007958 to Johns Hopkins University. (R01 AI113927 - National Institute of Health National Institute of Allergy and Infectious Diseases; U54 EB007958 - NIH National Institute of Biomedical and Bioengineering)Accepted manuscrip

Does brief physician counseling promote weight loss?

While physician counseling alone isn't more effective for weight loss than usual care (strength of recommendation [SOR]: A, larger randomized controlled trials [RCTs]), counseling (adults) as part of a multidisciplinary intervention may promote modest (2-3 kg) weight loss over 1 year (SOR: B, a single RCT)

Dbl oncogene expression in MCF-10 A epithelial cells disrupts mammary acinar architecture, induces EMT and angiogenic factor secretion.

The proteins of the Dbl family are guanine nucleotide exchange factors (GEFs) of Rho GTPases and are known to be involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders, neoplastic transformation, and tumor metastasis. We have previously demonstrated that expression of Dbl oncogene in lens epithelial cells modulates genes encoding proteins involved in epithelial-mesenchymal-transition (EMT) and induces angiogenesis in the lens. Our present study was undertaken to investigate the role of Dbl oncogene in epithelial cells transformation, providing new insights into carcinoma progression. To assess how Dbl oncogene can modulate EMT, cell migration, morphogenesis, and expression of pro-apoptotic and angiogenic factors we utilized bi- and three-dimensional cultures of MCF-10░A cells. We show that upon Dbl expression MCF-10░A cells undergo EMT. In addition, we found that Dbl overexpression sustain

Relations entre la microstructure 3D et les propriétés mécaniques dans des réfractaires électrofondus à très haute teneur en zircone

National audienceLe THTZ (réfractaire électrofondu à Très Haute Teneur en Zircone) est un matériau utilisé pour la construction de fours verriers. Il est composé d'un squelette dendritique de zircone imprégné de phase vitreuse. L'objectif de l'étude est d'étudier l'influence de la composition sur les propriétés des phases, la topologie microstructurale et les propriétés mécaniques du THTZ. Les microstructures 3D ont été investiguées par tomographie X à l'ESRF (synchrotron de Grenoble). Les clichés obtenus ont donné lieu à des analyses d'images permettant de caractériser la topologie microstructurale des différents matériaux. Une relation entre la vitesse d'attaque par l'acide fluorhydrique (HF) et la densité de surface a été identifiée. Parallèlement, des calculs par éléments finis tridimensionnels, réalisées à partir de volumes élémentaires représentatifs de la microstructure réelle, ont permis d'estimer l'influence de la morphologie sur les propriétés mécaniques macroscopiques

p130Cas is an essential transducer element in ErbB2 transformation

The ErbB2 oncogene is often overexpressed in breast tumors and associated with poor clinical outcome. p130Cas represents a nodal scaffold protein regulating cell survival, migration, and proliferation in normal and pathological cells. The functional role of p130Cas in ErbB2-dependent breast tumorigenesis was assessed by its silencing in breast cancer cells derived from mouse mammary tumors overexpressing ErbB2 (N202-1A cells), and by its reexpression in ErbB2-transformed p130Cas-null mouse embryonic fibroblasts. We demonstrate that p130Cas is necessary for ErbB2-dependent foci formation, anchorage-independent growth, and in vivo growth of orthotopic N202-1A tumors. Moreover, intranipple injection of p130Cas-stabilized siRNAs in the mammary gland of Balbc-NeuT mice decreases the growth of spontaneous tumors. In ErbB2-transformed cells, p130Cas is a crucial component of a functional molecular complex consisting of ErbB2, c-Src, and Fak. In human mammary cells, MCF10A.B2, the concomitant activation of ErbB2, and p130Cas overexpression sustain and strengthen signaling, leading to Rac1 activation and MMP9 secretion, thus providing invasive properties. Consistently, p130Cas drives N202-1A cell in vivo lung metastases colonization. These results demonstrate that p130Cas is an essential transducer in ErbB2 transformation and highlight its potential use as a novel therapeutic target in ErbB2 positive human breast cancers.-Cabodi, S., Tinnirello, A., Bisaro, B., Tornillo, G., Camacho-Leal, M. P., Forni, G., Cojoca, R., Iezzi, M., Amici, A., Montani, M., Eva, A., Di Stefano, P., Muthuswamy, S. K., Tarone, G., Turco, E., Defilippi, P. p130Cas is an essential transducer element in ErbB2 transformation

Stepping forward with interpolates in unbounded model checking

This paper addresses SAT-based Unbounded Model Checking based on Craig Interpolants. This recently introduced methodology is often able to outperform BDDs and other SAT-based techniques on large verification instances. Based on refutation proofs generated by SAT solvers, interpolants provide compact circuit representations of state sets, and abstract away several details non relevant for proofs. We propose three main contributions, aimed at controlling interpolant size and traversal depth. First of all, we introduce interpolant-based dynamic abstraction to reduce the support of the computed interpolant. Second, we propose new advances in interpolant compaction by redundancy removal. Both techniques rely on an effective application of the incremental SAT paradigm. Finally, we also introduce interpolant computation exploiting circuit quantification, instead of SAT refutation proofs. Experimental results are specifically oriented to prove properties, rather than disproving them (bug hunting). They show how the methodology is able to extend the applicability of interpolant based Model Checking to larger and deeper verification instances. Copyright 2006 ACM