143 research outputs found

    Investigation of shock waves in explosive blasts using fibre optic pressure sensors

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    The published version of this article may be accessed at the link below. Copyright @ IOP Publishing, 2006.We describe miniature all-optical pressure sensors, fabricated by wafer etching techniques, less than 1 mm(2) in overall cross-section with rise times in the mu s regime and pressure ranges typically 900 kPa (9 bar). Their performance is suitable for experimental studies of the pressure-time history for test models exposed to shocks initiated by an explosive charge. The small size and fast response of the sensors promises higher quality data than has been previously available from conventional electrical sensors, with potential improvements to numerical models of blast effects. Results from blast tests are presented in which up to six sensors were multiplexed, embedded within test models in a range of orientations relative to the shock front.Support from the UK Engineering&Physical Sciences Research Council and Dstl Fort Halstead through the MoD Joint Grants Scheme are acknowledged. WN MacPherson is supported by an EPSRC Advanced Research Fellowship

    The International-Trade Network: Gravity Equations and Topological Properties

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    This paper begins to explore the determinants of the topological properties of the international - trade network (ITN). We fit bilateral-trade flows using a standard gravity equation to build a "residual" ITN where trade-link weights are depurated from geographical distance, size, border effects, trade agreements, and so on. We then compare the topological properties of the original and residual ITNs. We find that the residual ITN displays, unlike the original one, marked signatures of a complex system, and is characterized by a very different topological architecture. Whereas the original ITN is geographically clustered and organized around a few large-sized hubs, the residual ITN displays many small-sized but trade-oriented countries that, independently of their geographical position, either play the role of local hubs or attract large and rich countries in relatively complex trade-interaction patterns

    NetMets: software for quantifying and visualizing errors in biological network segmentation

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    One of the major goals in biomedical image processing is accurate segmentation of networks embedded in volumetric data sets. Biological networks are composed of a meshwork of thin filaments that span large volumes of tissue. Examples of these structures include neurons and microvasculature, which can take the form of both hierarchical trees and fully connected networks, depending on the imaging modality and resolution. Network function depends on both the geometric structure and connectivity. Therefore, there is considerable demand for algorithms that segment biological networks embedded in three-dimensional data. While a large number of tracking and segmentation algorithms have been published, most of these do not generalize well across data sets. One of the major reasons for the lack of general-purpose algorithms is the limited availability of metrics that can be used to quantitatively compare their effectiveness against a pre-constructed ground-truth. In this paper, we propose a robust metric for measuring and visualizing the differences between network models. Our algorithm takes into account both geometry and connectivity to measure network similarity. These metrics are then mapped back onto an explicit model for visualization

    Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 Multiple Osteochondromas families

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    <p>Abstract</p> <p>Background</p> <p>Osteochondromas (cartilage-capped bone tumors) are by far the most commonly treated of all primary benign bone tumors (50%). In 15% of cases, these tumors occur in the context of a hereditary syndrome called multiple osteochondromas (MO), an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped bone tumors at children's metaphyses. MO is caused by various mutations in <it>EXT1 </it>or <it>EXT2</it>, whereby large genomic deletions (single-or multi-exonic) are responsible for up to 8% of MO-cases.</p> <p>Methods</p> <p>Here we report on the first molecular characterization of ten large <it>EXT1</it>- and <it>EXT2</it>-deletions in MO-patients. Deletions were initially indentified using MLPA or FISH analysis and were subsequently characterized using an MO-specific tiling path array, allele-specific PCR-amplification and sequencing analysis.</p> <p>Results</p> <p>Within the set of ten large deletions, the deleted regions ranged from 2.7 to 260 kb. One <it>EXT2 </it>exon 8 deletion was found to be recurrent. All breakpoints were located outside the coding exons of <it>EXT1 </it>and <it>EXT2</it>. Non-allelic homologous recombination (NAHR) mediated by <it>Alu</it>-sequences, microhomology mediated replication dependent recombination (MMRDR) and non-homologous end-joining (NHEJ) were hypothesized as the causal mechanisms in different deletions.</p> <p>Conclusions</p> <p>Molecular characterization of <it>EXT1</it>- and <it>EXT2</it>-deletion breakpoints in MO-patients indicates that NAHR between <it>Alu-</it>sequences as well as NHEJ are causal and that the majority of these deletions are nonrecurring. These observations emphasize once more the huge genetic variability which is characteristic for MO. To our knowledge, this is the first study characterizing large genomic deletions in <it>EXT1 </it>and <it>EXT2</it>.</p

    Disease-Causing 7.4 kb Cis-Regulatory Deletion Disrupting Conserved Non-Coding Sequences and Their Interaction with the FOXL2 Promotor: Implications for Mutation Screening

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    To date, the contribution of disrupted potentially cis-regulatory conserved non-coding sequences (CNCs) to human disease is most likely underestimated, as no systematic screens for putative deleterious variations in CNCs have been conducted. As a model for monogenic disease we studied the involvement of genetic changes of CNCs in the cis-regulatory domain of FOXL2 in blepharophimosis syndrome (BPES). Fifty-seven molecularly unsolved BPES patients underwent high-resolution copy number screening and targeted sequencing of CNCs. Apart from three larger distant deletions, a de novo deletion as small as 7.4 kb was found at 283 kb 5β€² to FOXL2. The deletion appeared to be triggered by an H-DNA-induced double-stranded break (DSB). In addition, it disrupts a novel long non-coding RNA (ncRNA) PISRT1 and 8 CNCs. The regulatory potential of the deleted CNCs was substantiated by in vitro luciferase assays. Interestingly, Chromosome Conformation Capture (3C) of a 625 kb region surrounding FOXL2 in expressing cellular systems revealed physical interactions of three upstream fragments and the FOXL2 core promoter. Importantly, one of these contains the 7.4 kb deleted fragment. Overall, this study revealed the smallest distant deletion causing monogenic disease and impacts upon the concept of mutation screening in human disease and developmental disorders in particular
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