42,156 research outputs found

    Microcracks closure effects in initially orthotropic materials

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    Microcracking is one of the basic mechanisms of inelastic deformation for a large class of anisotropic materials such as brittle matrix composites. Even at fixed microcracks density, the macroscopic behavior of these materials is very complex due to the combination of two specific features of such deteriorating phenomenon. First, the oriented nature of microcracks induces an evolution of the material symmetry (interaction between the initial anisotropy and the microcracks induced one). Secondly, a change in the elastic response of the material is expected, based on whether microcracks are open or closed in response to specific loading situations (the so-called “unilateral effect”). The present paper is devoted to a continuum micromechanics-based investigation of the resulting e generally fully e anisotropic multilinear response of orthotropic materials containing microcracks. The procedure leads to the proposal of a closed-form expression of the macroscopic free energy corresponding to 2D initially orthotropic materials weakened by arbitrarily oriented microcracks systems. The established results provide a complete quantification of both coupling effects of anisotropies and elastic moduli recovery phenomena induced by microcracks closure. A particular emphasis is put on the importance of Hill lemma for the derivation of these results which constitute a basis to the micro-macro modeling of damage process in initially orthotropic media

    Characterization of gasoline/ethanol blends by infrared and excess infrared spectroscopy

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    This work was supported by the Northern Research Partnership (NRP) in Scotland and the Scottish Sensor Systems Centre (SSSC) funded by the Scottish Funding Council (SFC).Peer reviewedPostprin

    M2I-1 disrupts the in vivo interaction between CDC20 and MAD2 and increases the sensitivities of cancer cell lines to anti-mitotic drugs via MCL-1s

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    Background Drugs such as taxanes, epothilones, and vinca alkaloids are widely used in the treatment of breast, ovarian, and lung cancers but come with major side effects such as neuropathy and loss of neutrophils and as single agents have a lack of efficacy. M2I-1 (MAD2 inhibitor-1) has been shown to disrupt the CDC20-MAD2 interaction, and consequently, the assembly of the mitotic checkpoint complex (MCC). Results We report here that M2I-1 can significantly increase the sensitivity of several cancer cell lines to anti-mitotic drugs, with cell death occurring after a prolonged mitotic arrest. In the presence of nocodazole or taxol combined with M2I-1 cell death is triggered by the premature degradation of Cyclin B1, the perturbation of the microtubule network, and an increase in the level of the pro-apoptotic protein MCL-1s combined with a marginal increase in the level of NOXA. The elevated level of MCL-1s and the marginally increased NOXA antagonized the increased level of MCL-1, a pro-survival protein of the Bcl-2 family. Conclusion Our results provide some important molecular mechanisms for understanding the relationship between the mitotic checkpoint and programmed cell death and demonstrate that M2I-1 exhibits antitumor activity in the presence of current anti-mitotic drugs such as taxol and nocodazole and has the potential to be developed as an anticancer agent

    A Bibliometric Analysis of the Top 100 Cited Articles on Hepatic Magnetic Resonance Imaging.

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    The purpose of this study is to guide the readers to the impact of the articles published on hepatic magnetic resonance imaging (MRI). We searched Scopus using 10 different search terms for hepatic MRI. The selected studies were thoroughly reviewed by two independent authors and any disagreement was sorted out by mutual consensus. The list of articles and journals was downloaded into an excel spreadsheet. Only the top 100 cited articles were selected by mutual consensus among all the authors. These articles were further read in the full-text form and were further categorized into subgroups. Three authors independently reviewed the top 100 selected articles, and subsequently data was extracted from them and analyzed. Our study showed that the highest number of top 100 cited articles on hepatic MRI were from Radiology (30 articles) followed by European Radiology (14 articles). The American Journal of Roentgenology, Radiographics, and Journal of Magnetic Resonance had seven articles each. The United States had the highest number of articles by region. Nineteen other journals contributed only one article each to the list of top 100 cited articles. The contribution of authors to the top 100 cited articles was reviewed; all the authors contributing with more than two articles to the highly cited articles are given in Table 3 in the supplementary material. The maximum number of articles were published during 2009 (14 articles), and for a five-year period, the maximum contribution was made during 2008-2013 (44 articles). Our analysis gives an insight on the frequency of citations of top articles on hepatic MRI, categorizes the subtopics, the timeline of the publications, and contributions from different geographic distributions

    Ciz1 cooperates with cyclin-A-CDK2 to activate mammalian DNA replication in vitro

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    Initiation of mammalian DNA replication can be reconstituted from isolated G1-phase nuclei and cell extracts, supplemented with cyclin-dependent protein kinases (CDKs). Under these conditions, cyclin E supports pre-replication complex assembly, whereas cyclin-A-associated kinase acts later to terminate assembly and activate DNA replication. The mechanism by which these events are coordinated is unknown. Here, we show that the replication factor Ciz1 interacts with cyclins E and A sequentially through distinct cyclin-binding motifs. Cyclin A displaces cyclin E from Ciz1 in a manner that is dependent on functional domains that are essential for its role in DNA replication. Furthermore, in cell-free assays, recombinant cyclin-A-CDK2 complexes and recombinant Ciz1 cooperate to promote initiation of DNA replication in late G1-phase nuclei. In addition, Ciz1 supports immobilization of cyclin A in isolated nuclei and depletion of Ciz1 by RNAi impairs immobilization, suggesting that Ciz1 promotes initiation by helping to target the kinase to a specific subnuclear compartment. We propose that Ciz1 acts to coordinate the functions of cyclins E and A in the nucleus, by delivering cyclin-A-associated kinase to sites that are specified by cyclin E, helping to ensure that they execute their functions in the same place and in the correct order

    The Audit Logic: Policy Compliance in Distributed Systems

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    We present a distributed framework where agents can share data along with usage policies. We use an expressive policy language including conditions, obligations and delegation. Our framework also supports the possibility to refine policies. Policies are not enforced a-priori. Instead policy compliance is checked using an a-posteriri auditing approach. Policy compliance is shown by a (logical) proof that the authority can systematically check for validity. Tools for automatically checking and generating proofs are also part of the framework.\u
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