1,476 research outputs found

    Initiation and final failure via environmentally assisted cracking in high strength aluminium

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    Environmentally assisted cracking (EAC) is particularly important to understand and control in high strength aluminium used in engineering applications as moist air provides a suitable environment to assist cracking in these materials. Propagation of EAC has been widely investigated but initiation has been difficult to follow due to it’s stochastic nature. We show that time-lapse 3D imaging using X-ray computed tomography offers a way to survey large surface areas whilst maintaining site specific high resolution information giving new insights into this process. In addition the final failure of these materials occurs when the environmentally assisted cracks of intergranular or transgranular type grow to a critical length from the initiation sites. We show through mechanical testing assessment and high resolution fractography that the rapid fracture that follows is also assisted by the environment leading to reduced ductility during the final failure. Examples from AA5083-H131 and AA7085-T7651 are shown which appear to show the same general behaviour. Round dog bone specimens prepared in the Short Transverse direction were subjected to slow strain rate testing (SSRT) at different strain rates and in different environments. Samples were also pre-exposed to different environments to introduce small corrosion sites to act as ‘realistic’ stress raisers in the specimens

    Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

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    Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative

    Finite-size effects for anisotropic bootstrap percolation: logarithmic corrections

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    In this note we analyze an anisotropic, two-dimensional bootstrap percolation model introduced by Gravner and Griffeath. We present upper and lower bounds on the finite-size effects. We discuss the similarities with the semi-oriented model introduced by Duarte.Comment: Key words: Bootstrap percolation, anisotropy, finite-size effect

    Multifluorescence High‐Resolution Episcopic Microscopy for 3D Imaging of Adult Murine Organs

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    3D microscopy of large biological samples (>0.5 cm^{3})is transforming biological research. Many existing techniques require trade-offs between image resolution, sample size, and method complexity. A simple robust instrument with the potential to conduct large-volume 3D imaging currently exists in the form of the optical high-resolution episcopic microscopy (HREM). However, the development of the instrument to date is limited to single-fluorescent wavelength imaging with nonspecific eosin staining. Herein, developments to realize the potential of the HREM to become multifluorescent high-resolution episcopic microscopy (MF-HREM) are presented. MF-HREM is a serial-sectioning and block-facing wide-field fluorescence imaging technique, which does not require tissue clearing or optical sectioning. Multiple developments are detailed in sample preparation and image postprocessing to enable multiple specific stains in large samples and show how these enable segmentation and quantification of the data. The application of MF-HREM is demonstrated in a variety of biological contexts: 3D imaging of whole tumor vascular networks and tumor cell invasion in xenograft tumors up to 7.5 mm^{3} at resolutions of 2.75 μm, quantification of glomeruli volume in the adult mouse kidney, and quantification of vascular networks and white-matter track orientation in adult mouse brain

    Dissociation of Response and Feedback Negativity in Schizophrenia: Electrophysiological and Computational Evidence for a Deficit in the Representation of Value

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    Contrasting theories of schizophrenia propose that the disorder is characterized by a deficit in phasic changes in dopamine activity in response to ongoing events or, alternatively, by a weakness in the representation of the value of responses. Schizophrenia patients have reliably reduced brain activity following incorrect responses but other research suggests that they may have intact feedback-related potentials, indicating that the impairment may be specifically response-related. We used event-related brain potentials and computational modeling to examine this issue by comparing the neural response to outcomes with the neural response to behaviors that predict outcomes in patients with schizophrenia and psychiatrically healthy comparison subjects. We recorded feedback-related activity in a passive gambling task and a time estimation task and error-related activity in a flanker task. Patients’ brain activity following an erroneous response was reduced compared to comparison subjects but feedback-related activity did not differ between groups. To test hypotheses about the possible causes of this pattern of results, we used computational modeling of the electrophysiological data to simulate the effects of an overall reduction in patients’ sensitivity to feedback, selective insensitivity to positive or negative feedback, reduced learning rate, and a decreased representation of the value of the response given the stimulus on each trial. The results of the computational modeling suggest that schizophrenia patients exhibit weakened representation of response values, possibly due to failure of the basal ganglia to strongly associate stimuli with appropriate response alternatives

    Multiscale correlative characterization of environmentally assisted crack initiation, propagation and failure in a high strength AA5083 H131 alloy

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    Environmentally assisted cracking in a high strength AA5083 H131 alloy has been investigated using a multiscale correlative characterization approach to understand the surface intergranular corrosion to environmentally assisted crack (EAC) transition. Time-lapse 3D synchrotron X-ray tomography was employed during slow strain testing of a sensitized AA5083 sample sensitized at 80 °C for 250 h. In addition, several of the specimens tested were pre-exposed to a chloride containing environment to induce corrosion sites which could act as ‘realistic’ stress raisers in the subsequent straining. Reconstructed volumes of the X-ray CT time-lapse series allowed us to track and follow crack propagation in the material during slow strain rate testing at high resolution \u3c5 µm. Volumes of interest from the test samples identified from the X-ray CT reconstructions were further analyzed post-mortem using electron microscopy and spectroscopy based techniques to study the presence and chemistry of secondary phases such as those based on Mg-Si, and their role in the initiation, propagation and/or arrest of crack tips/fronts

    Textiles as Material Gestalt: Cloth as a Catalyst in the Co-designing Process

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    Textiles is the common language within Emotional Fit, a collaborative research project investigating a person-centred, sustainable approach to fashion for an ageing female demographic (55+). Through the co-designing of a collection of research tools, textiles have acted as a material gestalt for exploring our research participants' identities by tracing their embodied knowledge of fashionable dress. The methodology merges Interpretative Phenomenological Analysis, co-design and a simultaneous approach to textile and garment design. Based on an enhanced understanding of our participants textile preferences, particular fabric qualities have catalysed silhouettes, through live draping and geometric pattern cutting to accommodate multiple body shapes and customisation. Printedtextiles have also been digitally crafted in response to the contours of the garment and body and personal narratives of wear. Sensorial and tactile interactions have informed the engineering and scaling of patterns within zero-waste volumes. The article considers the functional and aesthetic role of textiles

    On Bootstrap Percolation in Living Neural Networks

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    Recent experimental studies of living neural networks reveal that their global activation induced by electrical stimulation can be explained using the concept of bootstrap percolation on a directed random network. The experiment consists in activating externally an initial random fraction of the neurons and observe the process of firing until its equilibrium. The final portion of neurons that are active depends in a non linear way on the initial fraction. The main result of this paper is a theorem which enables us to find the asymptotic of final proportion of the fired neurons in the case of random directed graphs with given node degrees as the model for interacting network. This gives a rigorous mathematical proof of a phenomena observed by physicists in neural networks

    Collaboration of MYC and RUNX2 in lymphoma simulates T‐cell receptor signaling and attenuates p53 pathway activity

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    MYC and RUNX oncogenes each trigger p53‐mediated failsafe responses when overexpressed in vitro and collaborate with p53 deficiency in vivo. However, together they drive rapid onset lymphoma without mutational loss of p53. This phenomenon was investigated further by transcriptomic analysis of premalignant thymus from RUNX2/MYC transgenic mice. The distinctive contributions of MYC and RUNX to transcriptional control were illustrated by differential enrichment of canonical binding sites and gene ontology analyses. Pathway analysis revealed signatures of MYC, CD3, and CD28 regulation indicative of activation and proliferation, but also strong inhibition of cell death pathways. In silico analysis of discordantly expressed genes revealed Tnfsrf8/CD30, Cish, and Il13 among relevant targets for sustained proliferation and survival. Although TP53 mRNA and protein levels were upregulated, its downstream targets in growth suppression and apoptosis were largely unperturbed. Analysis of genes encoding p53 posttranslational modifiers showed significant upregulation of three genes, Smyd2, Set, and Prmt5. Overexpression of SMYD2 was validated in vivo but the functional analysis was constrained by in vitro loss of p53 in RUNX2/MYC lymphoma cell lines. However, an early role is suggested by the ability of SMYD2 to block senescence‐like growth arrest induced by RUNX overexpression in primary fibroblasts

    Metastability threshold for anisotropic bootstrap percolation in three dimensions

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    In this paper we analyze several anisotropic bootstrap percolation models in three dimensions. We present the order of magnitude for the metastability threshold for a fairly general class of models. In our proofs we use an adaptation of the technique of dimensional reduction. We find that the order of the metastability threshold is generally determined by the "easiest growth direction" in the model. In contrast to the anisotropic bootstrap percolation in two dimensions, in three dimensions the order of the metatstability threshold for anisotropic bootstrap percolation can be equal to that of isotropic bootstrap percolation.Comment: 19 page
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