3,507 research outputs found

    Experimental analysis of CFRP laminates subjected to Compression After Impact: the role of impact-induced cracks in failure

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    This paper presents an experimental analysis of composite laminates subjected to low velocity impact and compression after impact (CAI). Two types of CFRP specimens are studied: a highly oriented laminate and a quasi-isotropic laminate. Impact energy is chosen to obtain a dent depth less than or around the BVID level. 3D digital image correlation is used to make detailed analyses of plates behaviour during CAI. Even if the damage morphologies are very different, the study shows that, in both cases, classical global buckling of the plate and local buckling of the delaminated sublaminates are accompanied by a crack on the impact face of the laminate. This crack appears in the highly damaged zone, under the impactor, and propagates in the direction transverse to the loading direction in a stable way. It is shown to play an essential role in the final failure of the laminate under compression

    Non-elemental processing in olfactory discrimination tasks need bilateral input in honeybees

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    Abstract In patterning discriminations, animals have to differentiate a compound stimulus AB from each of its elements A and B. In positive patterning (PP), the compound is reinforced whilst the single elements are non-reinforced. In negative patterning (NP), single elements are reinforced whilst the compound is non-reinforced. Using olfactory conditioning of the proboscis extension response (PER), we asked whether honeybees (Apis mellifera) can solve these patterning problems when odorants are given unilaterally as well as bilaterally to the antennae. Separating the olfactory input space of bees into two independent zones using plastic walls placed between the antennae, we conditioned bees in PP and NP procedures, with input on one side, on both sides, or in an ambiguous problem where bees had to solve PP on one side and NP on the other side. We found that bees with simultaneous bilateral input solve both patterning tasks efficiently. In contrast, PP but not NP was learned by bees receiving unilateral olfactory input. Bees subjected to the ambiguous NP/PP problem only solved PP. As PP can be solved through mere elemental processes, but NP is critically dependent on the use of non-elemental learning processes, our results suggest that bilateral olfactory input is necessary for non-elemental processing to take place in the bee brain

    Matrix metalloproteinase 9 and cellular fibronectin plasma concentrations are predictors of the composite endpoint of length of stay and death in the intensive care unit after severe traumatic brain injury

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    BACKGROUND: The relationship between severe traumatic brain injury (TBI) and blood levels of matrix metalloproteinase-9 (MMP-9) or cellular fibronectin (c-Fn) has never been reported. In this study, we aimed to assess whether plasma concentrations of MMP-9 and c-Fn could have predictive values for the composite endpoint of intensive care unit (ICU) length of stay (LOS) of survivors and mortality after severe TBI. Secondary outcomes were the state of consciousness measured with the Glasgow Coma Scale (GCS) of survivors at 14 days and Glasgow Outcome Scale Extended (GOSE) at 3 months. METHODS: Forty-nine patients with abbreviated injury scores of the head region ≄ 4 were included. Blood was sampled at 6, 12, 24 and 48 hours after injury. MMP-9 and c-Fn concentrations were measured by ELISA. The values of MMP-9 and c-Fn, and, for comparison, the value of the GCS on the field of the accident (fGCS), as predictors of the composite outcome of ICU LOS and death were assessed by logistic regression. RESULTS: There was a linear relationship between maximal MMP-9 concentration, measured during the 6-12-hour period, and maximal c-Fn concentration, measured during the 24-48-hour period. The risk of staying longer than 9 days in the ICU or of dying was increased in patients with a maximal early MMP-9 concentration ≄ 21.6 ng/ml (OR = 5.0; 95% CI: 1.3 to 18.6; p = 0.02) or with a maximal late c-Fn concentration ≄ 7.7 ÎŒg/ml (OR = 5.4; 95% CI: 1.4 to 20.8; p = 0.01). A similar risk association was observed with fGCS ≀8 (OR, 4.4; 95% CI, 1.2-15.8; p = 0.02). No relationship was observed between MMP-9, c-Fn concentrations or fGCS and the GCS at 14 days of survivors and GOSE at 3 months. CONCLUSIONS: Plasma MMP-9 and c-Fn concentrations in the first 48 hours after injury are predictive for the composite endpoint of ICU LOS and death after severe TBI but not for consciousness at 14 days and outcome at 3 months

    Porcine model elucidates function of p53 isoform in carcinogenesis and reveals novel circTP53 RNA

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    Recent years have seen an increasing number of genetically engineered pig models of human diseases including cancer. We previously generated pigs with a modified TP53 allele that carries a Cre-removable transcriptional stop signal in intron 1, and an oncogenic mutation TP53R167H (orthologous to human TP53R175H) in exon 5. Pigs with the unrecombined mutant allele (flTP53R167H) develop mainly osteosarcoma but also nephroblastomas and lymphomas. This observation suggested that TP53 gene dysfunction is itself the key initiator of bone tumorigenesis, but raises the question which aspects of the TP53 regulation lead to the development of such a narrow tumour spectrum. Molecular analysis of p53 revealed the presence of two internal TP53 promoters (Pint and P2) equivalent to those found in human. Consequently, both pig and human express TP53 isoforms. Data presented here strongly suggest that P2-driven expression of the mutant R167H-Δ152p53 isoform (equivalent to the human R175H-Δ160p53 isoform) and its circular counterpart circTP53 determine the tumour spectrum and play a critical role in the malignant transformation in flTP53R167H pigs. The detection of Δ152p53 isoform mRNA in serum is indicative of tumorigenesis. Furthermore, we showed a tissue-specific p53-dependent deregulation of the p63 and p73 isoforms in these tumours. This study highlights important species-specific differences in the transcriptional regulation of TP53. Considering the similarities of TP53 regulation between pig and human, these observations provide useful pointers for further investigation into isoform function including the novel circTP53 in both the pig model and human patients.ISSN:0950-9232ISSN:1476-559

    Progress and challenges in predicting protein interfaces

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    *These authors contributed equally to this work. The majority of biological processes are mediated via protein–protein interactions. Determination of residues participating in such interactions improves our understanding of molecular mechanisms and facilitates the development of therapeutics. Experimental approaches to identifying interacting residues, such as mutagenesis, are costly and time-consuming and thus, computational methods for this purpose could streamline conventional pipelines. Here we review the field of computational protein interface prediction. We make a distinction between methods which address proteins in general and those targeted at antibodies, owing to the radically different binding mechanism of antibodies. We organize the multitude of currently available methods hierarchically based on required input and prediction principles to provide an overview of the field. Key words: protein–protein interaction; protein interface prediction; antibody antigen interaction Protein interfaces Proteins interact with other proteins, DNA, RNA and small mol-ecules to perform their cellular tasks. Knowledge of protein interfaces and the residues involved is vital to fully understand molecular mechanisms and to identify potential drug target

    BOFdat: Generating biomass objective functions for genome-scale metabolic models from experimental data

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    <div><p>Genome-scale metabolic models (GEMs) are mathematically structured knowledge bases of metabolism that provide phenotypic predictions from genomic information. GEM-guided predictions of growth phenotypes rely on the accurate definition of a biomass objective function (BOF) that is designed to include key cellular biomass components such as the major macromolecules (DNA, RNA, proteins), lipids, coenzymes, inorganic ions and species-specific components. Despite its importance, no standardized computational platform is currently available to generate species-specific biomass objective functions in a data-driven, unbiased fashion. To fill this gap in the metabolic modeling software ecosystem, we implemented BOFdat, a Python package for the definition of a <b>B</b>iomass <b>O</b>bjective <b>F</b>unction from experimental <b>dat</b>a. BOFdat has a modular implementation that divides the BOF definition process into three independent modules defined here as steps: 1) the coefficients for major macromolecules are calculated, 2) coenzymes and inorganic ions are identified and their stoichiometric coefficients estimated, 3) the remaining species-specific metabolic biomass precursors are algorithmically extracted in an unbiased way from experimental data. We used BOFdat to reconstruct the BOF of the <i>Escherichia coli</i> model <i>i</i>ML1515, a gold standard in the field. The BOF generated by BOFdat resulted in the most concordant biomass composition, growth rate, and gene essentiality prediction accuracy when compared to other methods. Installation instructions for BOFdat are available in the documentation and the source code is available on GitHub (<a href="https://github.com/jclachance/BOFdat" target="_blank">https://github.com/jclachance/BOFdat</a>).</p></div

    Permafrost is warming at a global scale

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    Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007-2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged
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