Explosions cause the majority of injuries in the current conflicts, accounting for 79% of combat related injuries (Ramasamy et al. 2008). Blast overpressure from explosions can cause barotrauma to the lungs and the brain. Blast-induced mild traumatic brain injury has been labeled the "signature wound" of current military conflicts in Iraq and Afghanistan (Snell and Halter 2010). In addition to elevated number of blast-induced traumatic brain injuries due to increased military conflicts overseas and the usage of improvised explosive devices, the incidence of blast-induced polytrauma has risen due to the prevalence of terrorist events around the world (Arnold et al. 2004, Rodoplu et al. 2004). Blast-induced polytrauma is a major concern as lung injury can cause immediate mortality and brain injury causes long-lasting neurocognitive impairment. There is a critical lack of understanding the pathology of blast-induced polytrauma since the needs are multifaceted and therefore few options for treatment. Thus, the research presented in this dissertation required the development of a military-relevant blast polytrauma model to examine injury pathology and subsequently study the effects of hemostatic nanoparticle therapy after blast-induced polytrauma. The pre-clinical model was characterized and static overpressure thresholds were determined for lethality risk. It was confirmed to have many of the classic hallmarks of primary blast lung injury (PBLI), as well as blast-induced neurotrauma (BINT) (Clemedson 1950). Global hemorrhaging was found in the lungs and well as reduced oxygen saturation. Markers of astrogliosis and blood-brain barrier disruption were examined in the amygdala after blast. The novel nanoparticle configuration (hemostatic dexamethasone-loaded nanoparticles (hDNP) functionalized with a peptide that binds with activated platelets) was investigated and hypothesized to increase survival, reduce cellular injury and reduce anxiety-like disorders after blast polytrauma. After investigating hDNP, it was found that the hDNP treatment benefited survival percentage after injury as well as reduced percent hemorrhage in the lungs and improved physiology. Elevated anxiety parameters found in the controls were lower as compared to the hDNP group. Glial fibrillary acidic protein (GFAP) and cleaved caspase-3 were significantly elevated in the controls compared to the hDNP group in the amygdala. SMI-71 was also significantly elevated with the hDNP and hemostatic nanoparticle (hNP) treatments, similar to sham. In addition to the nanoparticles offering immediate life-saving qualities, administration of hemostatic nanoparticles improved amygdala pathology attributed to secondary mechanisms of blast injury, including blood-brain barrier disruption. This model of polytrauma can serve as a foundation for detailed pathological studies as well as testing therapeutics for injury modalities. References (Abstract) Arnold, J. L., P. Halpern, M. C. Tsai and H. Smithline (2004). "Mass casualty terrorist bombings: a comparison of outcomes by bombing type." Ann Emerg Med 43(2): 263-273. Clemedson, C. J., Granstom, S.A. (1950). "Studies on the genesis of "rib markings" in lung blast injury." Acta Physiol Scand. 21: 131-144. Ramasamy, A., S. E. Harrisson, J. C. Clasper and M. P. Stewart (2008). "Injuries from roadside improvised explosive devices." J Trauma 65(4): 910-914. Rodoplu, U., Arnold, J. L., Tokyay, R., Ersoy, G., Cetiner, S., Yucel, T. (2004) "Mass-casualty terrorist bombings in Istanbul, Turkey, November 2003: reports of the events and the prehospital emergency response." Prehosp Disaster Med 19(2):133-145. Snell, F. I. and M. J. Halter (2010). "A signature wound of war: mild traumatic brain injury." J Psychosoc Nurs Ment Health Serv 48(2): 22-28. / Ph. D.

The ability to compare two biological sequences is extremely valuable, as matches can suggest evolutionary origins of genes or the purposes of particular amino acids. Results of such comparisons can be used in the creation of drugs, can help combat newly discovered viruses, or can assist in treating diseases. Unfortunately, the rate of sequence acquisition is outpacing our ability to compute on these data. Further, traditional dynamic programming algorithms are too slow to meet the needs of biologists, who wish to compare millions of sequences daily. While heuristic algorithms improve upon the performance of these dated applications, they still cannot keep up with the steadily expanding search space. Parallel sequence search implementations were developed to address this issue. By partitioning databases into work units for distributed computation, applications like mpiBLAST are able to achieve super-linear speedup over their sequential counterparts. However, such implementations are limited to clusters and require significant effort to work in a grid environment. Further, their parallelization strategies are typically specific to the target sequence search, so future applications require a reimplementation if they wish to run in parallel. This thesis analyzes the performance of two versions of mpiBLAST, noting trends as well as differences between them. Results suggest that these embarrassingly parallel applications are dominated by the time required to search vast amounts of data, and not by the communication necessary to support such searches. Consequently, a framework named gridRuby is introduced which alleviates two main issues with current parallel sequence search applications; namely, the requirement of a tightly knit computing environment and the specific, hand-crafted nature of parallelization. Results show that gridRuby can parallelize an application across a set of machines through minimal implementation effort, and can still exhibit super-linear speedup. / Master of Science

Blast-induced neurotrauma (BINT) is a major societal concern due to the complex expression of neuropathological disorders after exposure to blast. Disruptions in neuronal function, proximal in time to the blast exposure, may eventually contribute to the late emergence of the clinical deficits. Besides complications with differential clinical diagnosis, the biomolecular mechanism underlying BINT that gives rise to cognitive deficits is poorly understood. Some pre-clinical studies have demonstrated cognitive deficits at an acute stage following blast overpressure (BOP) exposure. However, the behavioral deficit type (e.g., short term memory) and the mechanism underlying injury prognosis that onsets the cognitive deficits remains to be further investigated. An established rodent model of blast neurotrauma was used in order to study impaired behavioral and neuropathological outcomes following blast. Anesthetized rats were exposed to a calibrated BOP using a blast simulator while control animals were not exposed to BOP. Behavioral changes in short term memory and anxiety were assessed with standard behavioral techniques (novel objected recognition paradigm and light and dark box test) at acute and chronic stages (range: 3 hours -- 3 months). In addition, brains were assayed for neurochemical changes using proton magnetic resonance spectroscopy (MRS) and neuropathology with immunohistochemistry in cognitive regions of brain (hippocampus, amygdala, frontal cortex and nucleus accumbens) Early metabolic changes and oxidative stress were observed along with a compromise in energy metabolism associated with sub-acute (7 days following BOP exposure) active neurodegeneration and glial scarring. Data suggested GABA shunting pathway was activated and phospholipase A2 regulated arachadonic acid pathway may be involved in cellular death cascades. In addition, increased myo-inositol levels in medial pre-frontal cortex (PFC) further supported the glial scarring and were associated with impaired working memory at a sub-acute stage (7 days) following BOP exposure. Chronic working memory issues and anxiety associated behavior could be related to chronic activation of microglia in hippocampus and astrocytes in amygdala respectively. Furthermore, these results from MRS could be directly translated into clinical studies to provide a valuable insight into diagnosis of BINT, and it is speculated that gliosis associated markers (myo-inositol) may be a potential biomarker for blast-induced memory impairment. / Ph. D.

In this experiment, average calcaneal fracture force is measured across male and female groups. The purpose of this experiment is an analysis of alternatives exploring the importance of sex-based criteria in models representing injuries typical in underbody blast environments. Seventeen (17) right legs were harvested at the knee from cadavers representing three anthropometries: 50th percentile male (6), 75th percentile female (6), and 5th percentile female (5). Care was taken to preserve anatomically correct geometry as the legs were cut to equal lengths, the tibia and fibula were potted in Dyna-Cast®, flesh and ligaments were excised from the inferior surface of the calcaneus, and a small Dyna-Cast® pad was poured and sanded flat – interfacing with the exposed calcaneal surface. Each test specimen was mounted in a custom fixture and exposed once to high-rate axial loading characterized by a constant acceleration and 25.4mm intrusion, achieving an average speed of 4.7m/s (σ = 0.3m/s) in 10ms. Input acceleration was measured by an Endevco 7264c accelerometer and a Denton 2513 six-axis load cell measured reaction force proximal to the specimen. A VR Phantom v9.1 camera recorded x-ray imagery at 2k frames per second. Data were collected by a TDAS Pro data acquisition system at 20k samples per second and filtered in accordance with SAE J211. Time of fracture, established through x-ray imagery, was used to determined fracture force from the electronically synchronized load-cell data. 100% injury was recorded. Average calcaneus fracture forces were reported as follows: 5406N (σ = 780N) for 50th percentile males, 4130N (σ = 1061N) for 75th percentile females, and 2873N (σ = 1293N) for 5th percentile females. Statistical significance was established between the reported averages according to three ANOVA tests: One-way (p = 0.0054), Brown-Forsythe (p = 0.0091), and Welch's (p = 0.0156). Unpaired Student's t-test confirmed significant differences between 50th percentile male vs 75th percentile female (p = 0.0469) and 50th percentile male vs 5th percentile female (p = 0.0030); the t-test did not show significance between the two female groups (p = 0.1315). Average impulse-to-fracture was calculated for each group and found to be not statistically significant. / Master of Science / A marked shift can be found in combat wound epidemiology towards a predominance of extremity injuries sustained from explosives. The Warrior Injury Assessment Mannequin (WIAMan) Project sought to develop a baseline dataset of post-mortem human surrogate responses to realistic explosive loading and correlate it to a highly instrumented mannequin for the further development of combat vehicles and personal protective gear. The following experiment exists within the WIAMan paradigm as an analysis of alternatives exploring the adequacy of the above mentioned baseline dataset in directly representing both male and female injuries. More specifically, this experiment interrogates the differences in average fracture forces between male and female calcanei across three anthropometries: 50th percentile male, 75th percentile female, and 5th percentile female. Testing was carried out on 17 right cadaver legs cut to equal lengths, potted proximally in Dyna-Cast®, with the inferior surface of their calcanei exposed; a small Dyna-Cast® pad was poured for each calcaneus and sanded flat. Each test specimen was fixed to a Denton 2513 six-axis load cell proximally and exposed to a high-rate, constant acceleration, 25.4mm displacement aligned with the calcaneus along the long axis of the leg bones. Fracture time, established through x-ray images recorded at 2k frames per second with a VR Phantom V9.1 camera, was used to determine load cell force measurement at fracture. Average calcaneus fracture forces were reported as follows: 5406N (σ = 780N) for 50th percentile males, 4130N (σ = 1061N) for 75th percentile females, and 2873N (σ = 1293N) for 5th percentile females. Statistical significance was established between the reported averages according to three ANOVA tests: One-way (p = 0.0054), Brown-Forsythe (p = 0.0091), and Welch's (p = 0.0156). Unpaired Student's t-test confirmed significant differences between 50th percentile male vs 75th percentile female (p = 0.0469) and 50th percentile male vs 5th percentile female (p = 0.0030); the t-test did not show significance between the two female groups (p = 0.1315). Average impulse-to-fracture was calculated for each group and found to be not statistically significant.

As improving technology is making it easier to select or engineer DNA sequences that produce dangerous proteins, it is important to be able to predict whether a novel DNA sequence is potentially dangerous by determining its taxonomic identity and functional characteristics. These tasks can be facilitated by the ever increasing amounts of available biological data. Unfortunately, though, these growing databases can be difficult to take full advantage of due to the corresponding increase in computational and storage costs. Entropy scaling algorithms and data structures present an approach that can expedite this type of analysis by scaling with the amount of entropy contained in the database instead of scaling with the size of the database. Because sets of DNA and protein sequences are biologically meaningful instead of being random, they demonstrate some amount of structure instead of being purely random. As biological databases grow, taking advantage of this structure can be extremely beneficial. The entropy scaling sequence similarity search algorithm introduced here demonstrates this by accelerating the biological sequence search tools BLAST and DIAMOND. Tests of the implementation of this algorithm shows that while this approach can lead to improved query times, constructing the required entropy scaling indices is difficult and expensive. To improve performance and remove this bottleneck, I investigate several ideas for accelerating building indices that support entropy scaling searches. The results of these tests identify key tradeoffs and demonstrate that there is potential in using these techniques for sequence similarity searches. / Master of Science / As biological organisms are created and discovered, it is important to compare their genetic information to known organisms in order to detect possible harmful or dangerous properties. However, the collection of published genetic information from known organisms is huge and growing rapidly, making it difficult to search. This thesis shows that it might be possible to use the non-random properties of biological information to increase the speed and efficiency of searches; that is, because genetic sequences are not random but have common structures, the increase of known data does not mean a proportional increase in complexity, known as entropy. Specifically, when comparing a new sequence to a set of previously known sequences, it is important to choose the correct algorithms for comparing the similarity of two sequences, also known as the distance between them. This thesis explores the performance of entropy scaling algorithm compared to several conventional tools.

The research presented in this thesis investigates eye injuries caused by blunt impacts and blast overpressure. This research represents part of an ongoing investigation to accurately quantify and predict eye injuries and injury mechanisms for various loading schemes. It has been shown that blunt trauma can cause severe eye injuries but it remains undecided whether blast overpressure alone can cause eye injury. Presented herein are four experimental studies that quantify eye injuries and implement a technique for predicting injury risk. Isolated porcine or human eyes were subjected to various loading conditions consisting of blunt projectiles, water streams, remote control helicopter blades, and blast overpressure. All eyes were prepared in a similar manner that required the insertion of a miniature pressure sensor into the globe through the optic nerve. This sensor measured intraocular pressure throughout each event. Using previously published injury risk curves, this intraocular pressure data was used to predict the injury risk for four eye injuries: hyphema, lens damage, retinal damage, and globe rupture. Injuries sustained were quantified upon direct inspection of the globe following testing. No serious eye injuries were observed for any of the tests and all tests resulted in low predicted injury risks consistent with the lack of observed injury. The research presented in this thesis provides a robust low injury level dataset for eye injuries. This data could be useful for designing and validating computational models and anthropomorphic test device eyes, and serves as a basis for future work with more dangerous projectiles and higher pressure levels. / Master of Science

<p>Between October 2001 and May 2012 approximately 70% of U.S. military personnel killed in action and 75% wounded in action were the direct result of exposure to an explosion. As of 2008, it was estimated that close to 20% of all Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF) veterans had sustained some form of traumatic brain injury (TBI). Further, blast exposure is also a civilian problem due to the increased usage of explosives in terrorist attacks. Blast injury research has historically focused on the pulmonary system and the other air-containing organs which have been shown through extensive experimentation to be susceptible to blast overpressure injury. A shift in injury pattern during recent conflicts is characterized by decreased incidence of pulmonary injuries with an increase in TBI thought to be associated with blast exposure. This increase in observation of blast TBI has resulted in a large research effort to understand mechanisms and thresholds. However, due to the relatively sudden shift, much of this research is being conducted without a proper understanding and consideration of blast mechanics and interspecies scaling effects.</p><p>This dissertation used experimental and computational finite element (FE) analysis to investigate some large questions surrounding blast TBI research. An experimental investigation was conducted to determine the effects of modern thoracic body armor usage on blast pressure exposure seen by the body. To improve FE modeling capabilities, brain tissue mechanics in common blast TBI animal model species were investigated experimentally and computationally to determine viscoelastic constitutive behavior and measure interspecies variation. Meta-analysis of blast pulmonary literature was conducted to update interspecies scaling and injury risk models. To derive interspecies scaling and injury risk models for blast neurotrauma endpoints a meta-analysis of existing experimental data was used.</p><p>This dissertation makes major contributions to the field of injury biomechanics and blast injury research. Research presented in this dissertation showed that modern thoracic body armor has the ability to lower the risk of pulmonary injury from blast exposure by attenuating and altering blast overpressure. The study shows that the use of soft body armor results in the pulmonary injury threshold being similar to that for neurotrauma. The use of hard body armor results in the threshold for pulmonary injury occurring at higher levels than that of neurotrauma. This finding is important, as it helps to explain the recent shift in injury types observed and highlights the importance of continued widespread usage of body armor not only for ballistic protection but for protection from blast as well.</p><p>This dissertation also shows the importance of interspecies scaling for investigation of blast neurotrauma. This work looks at existing in vivo animal model data to derive appropriate scaling across a wide range of brain size. Appropriate scaling for apnea occurrence and fatality for blast isolated to the head was found to be approximately equal to a characteristic length scaling of brain size, assuming similar brain geometry. By combining the interspecies scaling developed and existing tests data, injury risk models were derived for short duration blast exposures.</p><p>The contributions and conclusions of this dissertation serve to inform the injury biomechanics field and to improve future research efforts. The consideration by researchers of the recommendations presented in this dissertation for in vivo animal model testing will serve to maximize the value gained from experimentation and improve our understanding of blast injury mechanisms and thresholds. The injury risk models presented in this work help to improve our ability to prevent, diagnose, and treat blast neurotrauma.</p> / Dissertation

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

This thesis recounts the study of contour blasting practices in the Appalachia coal region. Contour blasting practices vary widely and problems are often encountered. Several different sites were visited and contour blasting practices at each were studied. Based on the information gathered, a comprehensive plan was developed for blasting operations to follow and then was tested and compared to an example of blasting practices without use of the plan. The blasting practices were compared by examining monthly production rates as well as a time study to measure the efficiency a contour blast could be loaded and hauled away and a cost per cubic yard of material determined. The plan was found to be successful in keeping safety while increasing profitability. However, the plan will need to be backed and understood by management in order to achieve the same success.

Terrorism has been an international threat to high occupancy civilian structures, government buildings, and military installations for many years. Statistical data from past terrorist attacks show that transportation infrastructure has been widely targeted, and a bombing of an ordinary highway bridge is a realistic scenario. Recent threats to bridges in the U.S. confirm this concern and have caught the attention of the bridge engineering community. Given that many ordinary highway bridges in the United States support critical emergency evacuation routes, military transportation plans, and vital economic corridors, the loss of a key bridge could result in severe national security, economic, and socioeconomic consequences. Therefore, in this research, a simplified procedure is developed to predict blast loads on bridge columns, and an understanding of the mechanisms that cause damage and ultimately failure of blast-loaded reinforced concrete bridge columns is advanced. To that end, computational fluid dynamics models are constructed and validated using experimental data. These numerical models are used to characterize the structural loads experienced by square and circular bridge columns subjected to blast loads, which is followed by the formulation of a simplified load prediction procedure. Additionally, nonlinear, three-dimensional, dynamic finite element models of blast-loaded reinforced concrete bridge columns are developed and validated using qualitative and quantitative data from recent experimental tests. The results of these analyses illustrate the fact that circular columns cannot be assumed to experience less base shear demand than a square column simply because they experience less net resultant impulse. Furthermore, the column response models developed in this research are used to identify and explain the mechanisms that lead to the spalling of side cover concrete off blast-loaded reinforced concrete members observed in recent experimental tests. Therefore, the results of this research advance the understanding of the structural loads on and the resulting response of reinforced concrete bridge columns subjected to blast loads, and as such these contributions to the structural engineering community enhance the security of the U.S. transportation infrastructure. / text