With an estimated incidence of 1.5 million each year, traumatic brain injury (TBI) is a major cause of mortality and morbidity in the United States. Opening of the mitochondrial permeability transition pore (mPTP) is a key event contributing to TBI pathology. Cyclophilin D (CypD), a matrix peptidyl-prolyl cis-trans isomerase, is believed to be the regulating component of the mPTP. Cyclosporin A, an immunosuppressant drug, inhibits CypD and blocks mPTP formation and has been shown to be neuroprotective following TBI. However, it is unclear if CsA’s neuroprotective mechanism is due to inhibition of CypD and/or immuno-suppression. Therefore to directly assess the contribution of CypD to TBI pathology, CypD knockout mice were subjected to a controlled cortical impact model of TBI. CypD ablation resulted in increased tissue sparing, hippocampal protection, and improved mitochondrial complex I driven respiration. Next a dose-response study of the Cyclophilin D inhibitor, NIM811, was performed. NIM811 administration following TBI resulted in improved cognition, increased tissue sparing, and improved mitochondrial function. These results suggest a major role for CypD in TBI pathology and validate CypD as a potential therapeutic target for TBI. TBI has been proposed to be the signature injury of the current Middle Eastern conflicts with an estimated prevalence of 15-60 % among combat soldiers. Although the brain does appear to be vulnerable to blast, the exact mechanisms underlying the injury remain unclear. Adult male Sprague-Dawley rats were exposed to a moderate level of blast overpressure. Following blast, blood brain barrier disruption was evident at 3 and 24 h post-exposure, oxidative damage increased at 3 h post-exposure, and microglia were activated in the hippocampus at 5 and 10 days post-exposure. This may widen future neuroprotective avenues for blast since blast brain injury appears to share similar mechanisms of injury with other TBI models.

Thesis (M.E. (Res.))--University of New South Wales, 2001. / Optical disc inserted in pocket on p. [3] of cover. Includes bibliographical references. Also available online.

For many years, terrorism has threatened life, property and business. Targets are largely in urban areas where there is a greater density of life and economic value. Governments, insurers and engineers have sought to mitigate these threats through understanding the effects of urban bombings, increasing the resilience of buildings and improving estimates of financial loss for insurance purposes. This has led to a desire for an improved approach to the prediction of blast propagation in urban cityscapes. Urban geometry has a significant impact on blast wave propagation. Presently, only computational fluid dynamics (CFD) methods adequately simulate these effects. However, for large-scale urban domains, these methods are both challenging to use and are computationally expensive. Adaptive mesh refinement (AMR) methods alleviate the problem, but are difficult to use for the non-expert and require significant tuning. We aim to make CFD urban blast simulation a primary choice for governments, insurers and engineers through improvements to AMR and by studying the performance of CFD in relation to other methods used by the industry. We present a new AMR flagging approach based on a second derivative error norm for compressive shocks (ENCS). This is compared with existing methods and is shown to lead to a reduction in overall refinement without affecting solution quality. Significant improvements to feature tracking over long distances are demonstrated, making the method easier to tune and less obtuse to non-experts. In the chapter that follows, we consider blast damage in urban areas. We begin with a validation and a numerical study, investigating the effects of simple street geometry on blast resultants. We then investigate the sensitivity of their distribution to the location of the charge. We find that moving the charge by a small distance can lead to a significant change in peak overpressures and creates a highly localised damage field due to interactions between the blast wave and the geometry. We then extend the investigation to the prediction of insured losses following a large-scale bombing in London. A CFD loss model is presented and compared with simpler approaches that do not account for urban geometry. We find that the simpler models lead to significant over-predictions of loss, equivalent to several hundred million pounds for the scenario considered. We use these findings to argue for increased uptake of CFD methods by the insurance industry. In the final chapter, we investigate the influence of urban geometry on the propagation of blast waves. An earlier study on the confinement effects of narrow streets is repeated at a converged resolution and we corroborate the findings. We repeat the study, this time introducing a variable porosity into the building facade. We observe that the effect of this porosity is as significant as the confinement effect, and we recommend to engineers that they consider porosity effects in certain cases. We conclude the study by investigating how alterations to building window layout can improve the protective effects of a facade. Maintaining the window surface area constant, we consider a range of layouts and observe how some result in significant reductions to blast strength inside the building.

Expressed Sequence Tags (ESTs) são amostras de trechos de genes, que funcionam como moldes na síntese de proteínas. Como a quantidade de ESTs coletados nos últimos anos é muito grande, o uso de computadores tornou-se imprescindível para a identificação de genes, proteínas e para a descoberta de genes homólogos. Este trabalho propõe uma metodologia e implementa uma ferramenta para a visualização de ESTs através de um grafo para auxiliar biólogos na exploração e na descoberta de conhecimento sobre estas seqüências. A metodologia inclui agrupamento usando um programa montador de seqüências e, conseqüentemente, a transformação dos grupos em nós de um grafo. O algoritmo BLAST é usado para procurar alinhamentos entre seqüências, representando-os posteriormente por arestas entre as seqüências mais similares. Para a visualização do grafo utilizamos e modificamos a ferramenta TG WikiBrowser conectada a um banco de dados. O resultado é uma ferramenta interativa baseada em código livre e robusto que funciona em ambientesWindows e Linux. Ela possibilita a fácil exploração do grafo, com diversas funcionalidades como, por exemplo: a expansão e filtragem do grafo, a busca por rótulos ou trechos de seqüências e a visualização detalhada de seqüências e grupos de seqüências. Com isso, os biólogos e especialistas em bioinformática ganham mais uma alternativa de investigação da genética / Expressed Sequence Tags (ESTs) are samples of gene stretches, which play the role of templates in synthesis of proteins. Since the amount of collected ESTs on the past few years is enormous, the use of computers has become essential to fields like gene and protein identification, and gene homology. This work proposes a methodology and a tool for visualization of ESTs as a graph for aiding biologists on exploration and on knowledge discovery about these sequences. The methodology includes clustering of ESTs using an assembly program and, consequently, the transformation of the groups in nodes of a graph. BLAST algorithm is used to search alignments among sequences, later representing them as edges between the most similar sequences. For the graph visualization, we adapted TGWikiBrowser software connected to a database. The result is a robust and open source interactive tool forWindows and Linux. It allows easy graph exploration, with various functionalities, for example: graph expansion and filtering, searching for label or sequence stretches, and detailed visualization of sequences and groups of sequences. Therefore, we hope biologists can count on one more option in genetics research

No description available.

The behavior of cryogenic double-walled pressure vessels, such as thoseused in space launch vehicle infrastructure, under blast loading is a somewhatunderstudied topic. This is of interest due its implications on, among otherthings, launch site design and safety in the event of a launch vehicle failure.The detonation of a 100 kg charge of TNT at a distance of 1 m from a simplifiedmodel of a horizontal cryogenic (double-walled) pressure vessel was simulatedusing Ansys Mechanical and AUTODYN. As a result, the inner and outershells of the pressure vessel underwent significant deformation which, in thecase of the outer shell, reached one third of its radius. No rupture occurred.Various other structural parameters, such as von Mises equivalent stress, strain,and element velocity were also studied. The results presented in this reportimply that cylindrical cryogenic pressure vessels are highly resistant to blastoverpressure, but does not take surrounding piping, valves, supports, and other infrastructure into account.

Thesis: Sc. D., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 1980 / Vita. / Includes bibliographical references. / by Balkishan Agrawal. / Sc. D. / Sc. D. Massachusetts Institute of Technology, Department of Materials Science and Engineering

京都大学 / 新制・課程博士 / 博士(農学) / 甲第24680号 / 農博第2563号 / 新制||農||1100(附属図書館) / 学位論文||R5||N5461(農学部図書室) / 京都大学大学院農学研究科応用生物科学専攻 / (主査)教授 寺内 良平, 教授 髙野 義孝, 教授 吉田 健太郎 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Recently, numerous flexible structures have been employed in various fields of industry. Loading conditions sustained by these flexible structures are often not described well enough for engineering analyses even though these conditions are important. Here, a flexible tent with an interior Collective Protection System, which is subjected to an explosion, is analyzed. The tent protects personnel from biological and chemical agents with a pressurized liner inside the tent as an environmental barrier. Field tests showed unexpected damage to the liner, and most of the damage occurred on tent's leeward side. To solve this problem, various tests and analyses have been performed, involving material characteristics of the liner, canvas, and zip seals, modeling of the blast loading over the tent and inside the tent, and structural response of the tent to the blast loading as collaborative research works with others. It was found that the blast loading and the structural response can not be analyzed separately due to the interaction between the flexible structure and the dynamic pressure loading. In this dissertation, the dynamic loadings imposed on both the interior and the exterior sides of the tent structure due to the airblasts and the resulting dynamic responses were studied. First, the blast loadings were obtained by a newly proposed theoretical method of analytical/empirical models which was developed into a FORTRAN program. Then, a numerical method of an iterative Fluid-Structure Interaction using Computational Fluid Dynamics and Computational Structural Dynamics was employed to simulate the blast wave propagation inside and outside the flexible structure and to calculate the dynamic loads on it. All the results were compared with the field test data conducted by the Air Force Research Laboratory. The experimental pressure data were gathered from pressure gauges attached to the tent surfaces at different locations. The comparison showed that the proposed methods can be a good design tool to analyze the loading conditions for rigid or flexible structures under explosive loads. In particular, the causes of the failure of the liner on the leeward were explained. Also, the results showed that the effect of fluid-structure interaction should be considered in the pressure load calculation on the structure where the structural deflection rate can influence the solution of the flow field surrounding the structure. / Ph. D.

The response of submerged structures subject to loading by underwater blast waves is governed by complex interactions between the moving or deforming structure and the surrounding fluid and these phenomena need to be thoroughly understood in order to design structural components against underwater blast. This thesis has addressed the response of simple structural systems to blast loading in shallow or deep water environment. Analytical models have been developed to examine the one-dimensional response of both water-backed and air-backed submerged rigid plates, supported by linear springs and loaded by underwater shock waves. Cavitation phenomena as well as the effect of initial static fluid pressure are explicitly included in the models and their predictions were found in excellent agreement with detailed FE simulations. Then, a novel experimental apparatus has been developed, to reproduce controlled blast loading in initially pressurised liquids. It consists of a transparent water shock tube and allows observing the structural response as well as the propagation of cavitation fronts initiated by fluid-structure interaction in a blast event. This experimental technique was then employed to explore the one-dimensional response of monolithic plates, sandwich panels and double-walled structures subject to loading by underwater shock waves. The performed experiments provide great visual insight into the cavitation process and the experimental measurements were found to be in good agreement with analytical predictions and dynamic FE results. Finally, underwater blast loading of circular elastic plates has been investigated by theoretically modelling the main phenomena of dynamic plate deformation and fluid-structure interaction. In addition, underwater shock experiments have been performed on circular composite plates and the obtained measurements were found in good correlation with the corresponding analytical predictions. The validated analytical models were then used to determine the optimal designs of circular elastic plates which maximise the resistance to underwater blast.