An investigation of composite failure analyses and damage evolution in finite element models

This paper presents a composite conical structure used commonly in flight-qualification testing. This structure’s overall load-displacement behavioral response is characterized. Mixed-mode multidelamination in a layered composite specimen is considered in Abaqus/Explicit through both the Virtual Crack Closure Technique and Cohesive Elements. The Virtual Crack Closure Technique and Cohesive Elements are compared against experimental test results presented in literature. Further, a thorough comparison in which the effects of failure criteria type, through-thickness mesh density, and finite element type on the progressive failure response of this composite assembly is discussed. Lastly, Abaqus/Standard and Helius PFA are compared in order to gain confidence into which analytical model’s failure theories best predicts the different scales of failure, both local/microscale and global/macroscale

A First Step in the Translation of Alloy to Coq

International audienceAlloy is both a formal language and a tool for software mod-eling. The language is basically first order relational logic. The analyzer is based on instance finding: it tries to refute assertions and if it succeeds it reports a counterexample. It works by translating Alloy models and instance finding into SAT problems. If no instance is found it does not mean the assertion is satisfied. Alloy relies on the small scope hypothesis: examining all small cases is likely to produce interesting counterexamples. This is very valuable when developing a system. However, Alloy cannot show their absence. In this paper, we propose an approach where Alloy can be used as a first step, and then using a tool we develop, Alloy models can be translated to Coq code to be proved correct interactively

AXES at TRECVid 2011

Abstract The AXES project participated in the interactive known-item search task (KIS) and the interactive instance search task (INS) for TRECVid 2011. We used the same system architecture and a nearly identical user interface for both the KIS and INS tasks. Both systems made use of text search on ASR, visual concept detectors, and visual similarity search. The user experiments were carried out with media professionals and media students at the Netherlands Institute for Sound and Vision, with media professionals performing the KIS task and media students participating in the INS task. This paper describes the results and findings of our experiments

Open drug discovery in Alzheimer\u27s disease.

Alzheimer\u27s disease (AD) drug discovery has focused on a set of highly studied therapeutic hypotheses, with limited success. The heterogeneous nature of AD processes suggests that a more diverse, systems-integrated strategy may identify new therapeutic hypotheses. Although many target hypotheses have arisen from systems-level modeling of human disease, in practice and for many reasons, it has proven challenging to translate them into drug discovery pipelines. First, many hypotheses implicate protein targets and/or biological mechanisms that are under-studied, meaning there is a paucity of evidence to inform experimental strategies as well as high-quality reagents to perform them. Second, systems-level targets are predicted to act in concert, requiring adaptations in how we characterize new drug targets. Here we posit that the development and open distribution of high-quality experimental reagents and informatic outputs-termed target enabling packages (TEPs)-will catalyze rapid evaluation of emerging systems-integrated targets in AD by enabling parallel, independent, and unencumbered research

The Herpesvirus Associated Ubiquitin Specific Protease, USP7, Is a Negative Regulator of PML Proteins and PML Nuclear Bodies

The PML tumor suppressor is the founding component of the multiprotein nuclear structures known as PML nuclear bodies (PML-NBs), which control several cellular functions including apoptosis and antiviral effects. The ubiquitin specific protease USP7 (also called HAUSP) is known to associate with PML-NBs and to be a tight binding partner of two herpesvirus proteins that disrupt PML NBs. Here we investigated whether USP7 itself regulates PML-NBs. Silencing of USP7 was found to increase the number of PML-NBs, to increase the levels of PML protein and to inhibit PML polyubiquitylation in nasopharyngeal carcinoma cells. This effect of USP7 was independent of p53 as PML loss was observed in p53-null cells. PML-NBs disruption was induced by USP7 overexpression independently of its catalytic activity and was induced by either of the protein interaction domains of USP7, each of which localized to PML-NBs. USP7 also disrupted NBs formed from some single PML isoforms, most notably isoforms I and IV. CK2α and RNF4, which are known regulators of PML, were dispensable for USP7-associated PML-NB disruption. The results are consistent with a novel model of PML regulation where a deubiquitylase disrupts PML-NBs through recruitment of another cellular protein(s) to PML NBs, independently of its catalytic activity

Interactions of the Human MCM-BP Protein with MCM Complex Components and Dbf4

MCM-BP was discovered as a protein that co-purified from human cells with MCM proteins 3 through 7; results which were recapitulated in frogs, yeast and plants. Evidence in all of these organisms supports an important role for MCM-BP in DNA replication, including contributions to MCM complex unloading. However the mechanisms by which MCM-BP functions and associates with MCM complexes are not well understood. Here we show that human MCM-BP is capable of interacting with individual MCM proteins 2 through 7 when co-expressed in insect cells and can greatly increase the recovery of some recombinant MCM proteins. Glycerol gradient sedimentation analysis indicated that MCM-BP interacts most strongly with MCM4 and MCM7. Similar gradient analyses of human cell lysates showed that only a small amount of MCM-BP overlapped with the migration of MCM complexes and that MCM complexes were disrupted by exogenous MCM-BP. In addition, large complexes containing MCM-BP and MCM proteins were detected at mid to late S phase, suggesting that the formation of specific MCM-BP complexes is cell cycle regulated. We also identified an interaction between MCM-BP and the Dbf4 regulatory component of the DDK kinase in both yeast 2-hybrid and insect cell co-expression assays, and this interaction was verified by co-immunoprecipitation of endogenous proteins from human cells. In vitro kinase assays showed that MCM-BP was not a substrate for DDK but could inhibit DDK phosphorylation of MCM4,6,7 within MCM4,6,7 or MCM2-7 complexes, with little effect on DDK phosphorylation of MCM2. Since DDK is known to activate DNA replication through phosphorylation of these MCM proteins, our results suggest that MCM-BP may affect DNA replication in part by regulating MCM phosphorylation by DDK