The purpose of this thesis project was to elucidate the immune transcriptomic changes in the diaphragm of mdx mice treated with microdystrophin gene therapy with and without running wheel activity. Mdx mice are a model of Duchenne Muscular Dystrophy (DMD). Similar to DMD, mdx pathophysiology is associated with chronic inflammation due to sarcolemma fragility and cellular membrane leakage. Immune modulation has not yet been described when endurance exercise and AAV-microdystrophin gene therapy have been combined in mdx mice. An increase of physical activity in DMD individuals is a potential outcome of current clinical studies investigating microdystrophin treatment; therefore, understanding the impacts of physical activity on the immune system, particularly for the diaphragm, may be important to minimize risk. Recently, the Grange lab published the endurance and contractile property outcomes of combined microdystrophin gene therapy and running wheel activity in mdx mice.1 Diaphragm RNA-seq transcriptomic data were also collected from this study for gene expression analysis. Using this dataset, I tested the hypothesis that relative to mdxGT (mdx mice treated with gene therapy), transcripts related to the immune response such as immune cell recruitment, activation, and downstream signals that promote fibrosis deposition were unchanged or downregulated in mdxRGT (mdx mice treated with gene therapy and access to running wheel). DEGs (differentially expressed genes) were analyzed with Microsoft Excel, R, and bioinformatic tools such as KEGG and DAVID to explain immune system adaptations in response to combined microdystrophin treatment and running in mdx mice. Two major inflammatory signaling pathways, the IL-6/JAK/STAT and NF-kB signaling pathways translationally relevant to DMD patients were rescued by gene therapy towards WT expression levels. Although running maintained the majority of the rescued transcriptome profile (691 of 724 genes), some immune response-related gene expressions (33 of 724 genes) were modulated including genes related to chemotaxis and cellular migration. These changes suggested potential signaling for angiogenesis and a fast to slow fiber type shift; however, unbiased analysis with bioinformatic tools did not confirm either of these possibilities. The data from this study revealed inflammatory and fibrotic signaling pathways commonly observed in DMD patients and mdx mice were rescued by the AAV microdystrophin gene therapy and were maintained by voluntary wheel running / Master of Science / Duchenne Muscular Dystrophy (DMD) is an X chromosome-linked muscular dystrophy, a genetic disease that affects around 1 in 14,000 boys globally. DMD is lethal and currently there is no cure. Mutations in the DMD gene results in the absence of the protein dystrophin. The dystrophin protein and other proteins associated with it provide structural support to the skeletal muscle membrane. Without it, muscles are more easily damaged during contraction. This damage promotes recruitment of immune cells which initiates the first stage of muscle repair. Under normal circumstances, this inflammatory reaction caused by immune cells restores the skeletal muscles. However, in DMD patients, repeated breakdown and regeneration of skeletal muscles leads to abnormal inflammation which promotes negative outcomes such as increased fibrosis. Fibrosis impairs muscle function, especially the diaphragm . Hamm et al., 2021 from the Grange lab investigated the effects of microdystrophin gene therapy and increased physical activity in mdx mice, a mouse model of DMD, with the idea that some of the negative changes with muscular dystrophy could be improved. The results showed a positive increase of endurance capacity in mdx mice treated with gene therapy alone (mdxGT group) and a greater increase if the mice also used a running wheel (mdxRGT group) compared to untreated mdx mice (mdx group). These findings suggested that gene therapy can increase a DMD patient's ability to become more physically active. However, the effects of running and microdystrophin gene therapy on the damaging inflammatory response in the diaphragm were not reported. To address this question, gene expression data from diaphragm muscles of all treatment groups were collected in the Hamm et al., 2021 study for later analysis. In my study, these diaphragm gene expression data were used to compare inflammatory signals between the various treatment groups. Indicators of skeletal muscle damage, immune cell accumulation and fibrosis deposition were rescued (i.e., returned to healthy mice levels) by microdystrophin gene therapy (mdxGT group). Running did not exert any negative effects on the majority of genes rescued by the microdystrophin therapy (mdxRGT group). These results indicated that voluntary wheel running could maintain the reduced inflammatory signals due to the microdystrophin gene therapy in mdx mice. If the function of the skeletal muscle of dystrophic boys was similarly improved by microdystrophin gene therapy and exercise did not interfere with its positive effects, DMD boys could potentially be physically active similar to normal boys of their age.

The onset of a yellow indication is typically associated with the risk of vehicle crashes resulting from dilemma-zone and red-light-running problems. Such risk of vehicle crashes is greater for high-speed signalized intersection approaches. The research presented in this dissertation develops statistical as well as behavioral frameworks for modeling driver behavior while approaching high-speed signalized intersection approaches at the onset of a yellow indication. The analysis in this dissertation utilizes two sources of data. The main source is a new dataset that was collected as part of this research effort during the summer of 2008. This experiment includes two instructed speeds; 72.4 km/h (45 mph) with 1727 approaching trials (687 running and 1040 stopping), and 88.5 km/h (55 mph) with 1727 approaching trials (625 running and 1102 stopping). The complementary source is an existing dataset that was collected earlier in the spring of 2005 on the Virginia Smart Road facility. This dataset includes a total of 1186 yellow approaching trials (441 running and 745 stopping). The adopted analysis approach comprises four major parts that fulfill the objectives of this dissertation. The first part is concerned with the characterization of different driver behavioral attributes, including driver yellow/red light running behavior, driver stop-run decisions, driver perception-reaction times (PRT), and driver deceleration levels. The characterization of these attributes involves analysis of variance (ANOVA) and frequency distribution analyses, as well as the calibration of statistical models. The second part of the dissertation introduces a novel approach for computing the clearance interval duration that explicitly accounts for the reliability of the design (probability that drivers do not encounter a dilemma zone). Lookup tables are developed to assist practitioners in the design of yellow timings that reflects the stochastic nature of driver PRT and deceleration levels. An extension of the proposed approach is presented that can be integrated with the IntelliDriveSM initiative. Furthermore, the third part of the dissertation develops an agent-based Bayesian statistics approach to capture the stochastic nature of the driver stop-run decision. The Bayesian model parameters are calibrated using the Markov Chain Monte Carlo (MCMC) slice procedure implemented within the MATLAB® software. In addition, two procedures for the Bayesian model application are illustrated; namely Cascaded regression and Cholesky decomposition. Both procedures are demonstrated to produce replications that are consistent with the Bayesian model realizations, and capture the parameter correlations without the need to store the set of parameter realizations. The proposed Bayesian approach is ideal for modeling multi-agent systems in which each agent has its own unique set of parameters. Finally, the fourth part of the dissertation introduces and validates a state-of-the-art behavioral modeling framework that can be used as a tool to simulate driver behavior after the onset of a yellow indication until he/she reaches the intersection stop line. The behavioral model is able to track dilemma zone drivers and update the information available to them every time step until they reach a final decision. It is anticipated that this behavioral model will be implemented in microscopic traffic simulation software to enhance the modeling of driver behavior as they approach signalized intersections. / Ph. D.

It is estimated that as many as 2.7 million crashes occur each year at intersections or are intersection related; resulting in over 8500 fatalities each year. These statistics have prompted government and corporate sponsored research into collision countermeasure systems that can enhance safety at intersections. Researchers are investigating technologies to provide an infrastructure-based or infrastructure-cooperative Intersection Decision Support (IDS) systems. Such systems would use pre-specified algorithms to identify drivers that have a high likelihood of violating the traffic signal and thus increase the risk of a collision. The system would subsequently warn the violating driver to stop though an in-vehicle or infrastructure-mounted interface. An IDS algorithm must be designed to provide adequate time for the driver to perceive, react, and stop the vehicle, while simultaneously avoiding a high false alarm rate. Prior to developing these algorithms, scientists must understand how drivers respond to traffic signals. Little research has focused on the influence of driver state on red-light running behavior or methods for distinguishing red light violators from non-violators. The objective of the present study was to define trends associated with intersection crossings under different driver states and to explore the point detection method of predicting red light running upstream of the intersection. This was accomplished through a test-track mixed-factor experiment with 28 participants. Each participant experienced a baseline (complete a full stop at the red light), distracted (misses signal phase change due to inattention), and willful (driver knowingly makes a late crossing in an attempt to 'beat the light') driver state conditions. To provide the opportunity for red-light running behavior from participants, the amber change interval began at five different distances from the intersection. These distances were located near and within the dilemma zone, a region in which drivers have a difficult time deciding whether to go or to stop. Data collected from in-vehicle sensors was statistically analyzed to determine significant effects between driver states, and to investigate point detection algorithms. / Master of Science

The phenotypes of hatchling reptiles are influenced by the environmental conditions that embryos experience during incubation, by yolk invested into the egg, and by the genetic contributions of the parents. Phenotypic traits are influenced by these factors in ways that potentially affect the fitness of hatchlings. The physical conditions that embryos experience within the nest affects development, hatching success, and hatchling phenotypes. Thus, the nest site that a female selects can influence the survival of her offspring as well as her overall fitness. In Chapter 1, I addressed this issue through a nest site selection experiment designed to determine the substrate temperature and moisture conditions that female eastern fence lizards (Sceloporus undulatus) select when provided a range of conditions from which to choose. In general, I found that females selected nest sites with conditions that yield high hatching success. In Chapter two, I investigated the relative contributions of incubation moisture conditions, maternal yolk investment, and clutch (genotype) to variation in hatchling phenotypes and survival under field conditions. Eggs from 28 clutches were distributed among two moisture treatments; wet (-150 kPa) and dry (-530 kPa). In another treatment, yolk was removed from eggs to determine the affect of yolk quantity on hatchling phenotypes. After hatching, several phenotypic traits (mass, snout-vent length, tail length, body shape, thermal preference, running speed, desiccation rate, and growth rate) were measured. Hatchlings were subsequently marked and released at a field site in southwest Virginia. Hatchlings were recaptured twice weekly prior to winter and the following spring to monitor growth and survival. I found that incubation moisture and yolk removal affected only hatchling body size; individuals from the dry and yolk removed treatments were smaller in body size than those from the wet treatment. However, clutch was the most important source of phenotypic variation; all phenotypes were affected by clutch. Significant clutch effects suggested the possibility that phenotypic variation had at least some genetic basis. In the field, survival was not affected by incubation moisture and yolk removal, and overall survival was not associated with hatchling body size. Survivors and nonsurvivors differed only in growth rate in the field and running speed measured in the laboratory. Survivors ran faster and grew more slowly than nonsurvivors. To examine the association of clutch with survival, I used clutch mean values to look at the relationship between phenotype and survival. Clutches that produced relatively slow growing individuals and fast runners had higher survival rates than clutches that produced relatively rapid growing individuals and slow runners. In order to grow rapidly, an individual must eat more than slowly growing individuals. Thus, rapid growth rate may increase risk of predation through its association with foraging activity. Individuals that run fast should be capable of capturing prey and evading predators more effectively than individuals that run slowly. Overall, these results emphasize the importance of clutch to variation in phenotypes and survival in hatchling Sceloporus undulatus. / Master of Science

The purpose of the study was to evaluate the generalisability of the heart rate-blood lactate relationship determined in laboratory testing in comparison to running over ground. This plays a crucial role to prescribe exercise intensity from laboratory results. Ten well trained runners performed a maximal oxygen uptake (VO2max) pre-test and an incremental submaximal test performed at a two degrees inclined treadmill and a running track. Statistical analysis included student’s t-test of heart rate at interpolated blood lactate levels and comparison of second order polynomial regression lines. VO2max was 60,4 ± 6 ml/kg/min for men and 56,3 ± 4,3 ml/kg/min for women. There was no significant difference in heart rate at interpolated blood lactate of 3 and 4 mmol/L. There was no significant difference between heart rate values at any running velocity. A significant difference between blood lactate values was observed 14km/h (p=0,04). When considering blood lactate values up to 6mmol/L, heart rate-blood lactate relationships were similar. In conclusion, lactate threshold testing on treadmill through incremental test protocols on a two degrees incline gives similar heart rate- blood lactate relationship as running over ground and may be used to prescribe intensity in training performed over ground.

As an investigation of the evolution of the minimalist shoes, the purpose of this thesis was to examine popularity trends of the rise and fall of the minimalist movement. By evaluating the history and research behind the designs of the minimalist shoes, this thesis viewed the peak in popularity when minimalist shoes first made their debut. Initially, footwear sales skyrocketed upon its introduction. Its popularity grew due the prospective effects of improving athletic performance and the possibility of decreasing the prevalence of running-related injuries. To understand the sales trends of the footwear industry, various shoe examples from the different categories of footwear padding were also examined. Hence, after learning more about each type of footwear, it is crucial to understand how to transition safely and without injury. Injury prevalence has been suggested to be associated with the change in biomechanics involved with changing a runner’s footwear. Through the review of research literature on the subject, 33 sources of peerreviewed studies, found via Google Scholar or EBSCOHost using select key word searches, were taken into account. After reviewing the results and conclusions, a common finding suggest that more research is needed to come to clear consensus. There is not enough evidence to suggest that the use of minimalist shoes either lowered the risk of injury or improved performance. Hence, the decline of minimalist movement may have been due to the unfulfilled benefits that were proposed. After consumers did not reap the benefits of transitioning to minimalist shoes, sales trends continued to fall.

As formigas se adaptam as diferentes situações que encontram no seu ambiente em parte por apresentarem flexibilidade comportamental. Um exemplo é o uso de mais de uma estratégia durante a exploração de um recurso alimentar. No caso da Ponerinae Pachycondyla striata, as formigas podem forragear solitariamente ou fazer recrutamento por tandem running. Apesar desta espécie estar presente em diversas áreas verdes em ambiente urbano, pouco se sabe sobre o seu comportamento durante o forrageamento nessas áreas. Por isso, o objetivo deste trabalho foi analisar as estratégias de forrageamento e os comportamentos de P. striata em ambiente urbano. O estudo foi realizado em um jardim da Cidade Universitária (USP, campus Butantã). No local foram observadas 96 formigas de 12 colônias. Como iscas alimentares foram usadas proteína (atum) e carboidrato (maçã com mel) em duas quantidades (3g e 7g) e em duas distâncias do ninho (0,5 m e 4,0 m). Durante 90 minutos foram registrados: as estratégias de forrageamento; os comportamentos das forrageadoras; as interações com espécies competidoras; o tempo de trajeto entre o ninho e a isca. Verificou-se que o forrageamento solitário foi a principal estratégia, sendo utilizada por todas as forrageadoras e que a atividade solitária aumentava quando o alimento próximo ao ninho era proteína. O recrutamento foi realizado por 81% das forrageadoras, mas as formigas perderam o contato em 27% dos recrutamentos. As chances de uma forrageadora recrutar eram maiores em três situações: quando o alimento era proteína; estava perto do ninho; e a umidade do ar era alta (70% UR). Cerca de 72% das forrageadoras tiveram competição nas iscas, sendo a competição interespecífica mais frequente que a intraespecífica. Durante as interações com as competidoras, as forrageadoras apresentaram, principalmente, comportamento agressivo. Quanto ao tempo de trajeto, o forrageamento solitário era percorrido em menos tempo que o recrutamento, independente da distância. Por fim, verificou-se uma correlação negativa entre a ordem das viagens e o tempo do trajeto em ambas as distâncias e estratégias de forrageamento. Conclui-se que os dados coletados neste trabalho reforçam a prevalência do forrageamento solitário como principal estratégia da espécie e também trazem novas informações, como a tomada de decisão baseada no tipo do alimento, a variação na atividade de forrageamento devido a fatores abióticos, as interações competitivas no ambiente urbano e o aprendizado individual e social entre as forrageadoras / The ants adapt to different environmental contexts exhibiting behavioral flexibility. An example of behavioral flexibility is the use of more than one foraging strategy. In the case of Ponerinae Pachycondyla striata, the ants can forage solitarily or recruit and guide nestmates to a food sorce by tandem running. This species is found in various green areas in urban environment, but little is known about its foraging behaviour in this area. The aim of this research was to analyze the foraging strategies and the behaviors of P. striata in urban environment. The study was performed in a garden of the University City (USP campus Butantã). At this site we observed 96 ants of 12 colonies. As feeding baits were used protein (tuna) and carbohydrate (apple with honey) in two quantities (3g and 7g) and at two distances from the nest (0,5m and 4,0m). During 90 minutes we registered: the foraging strategies; the behaviors of the foragers; the interactions with competing species; and the travel time from the nest to the bait. It was found that the solitary foraging was the main strategy used by all the foragers. The solitary foraging activity was especially frequent when protein was close to the nest. The recruitment was performed by 81% of the foragers, but the ants lost contact in 27% of the recruitments. The frequency of recruitment increased in three foraging contexts: when the food was protein; was close to the nest; and with high air humidity (70% UR). About 72% of the foragers found competitors at the baits, and interspecific competition was more frequent than intraspecific competition. The foragers presented during the interactions with the competitors, mainly, aggressive behavior. Traveling time during solitary foraging foraging went through in less time that recruitment, regardless the distance. Lastly, it was verified a negative correlation between the traveling order and the traveling time at both distances and foraging strategies. Our data lead us to conclude that the solitary foraging is the main strategy of P. striata, adding new information as the decision making based on food characteristics, the variation in foraging activity due to abiotic factors and the competing interactions in urban environment and individual and social learning between ants

The accuracy in determined energy consumption and runningtime of trains, by means of computer simulation, is dependent upon the various models used. This thesis aims at developing validated models of running resistance, train and of a generaldriver, all based on full scale testing. A partly new simple methodology for determining running resistance, called by energy coasting method is developed and demonstrated. An error analysis for this methodis performed. Running resistance of high speed train SJ X2000, conventional loco hauled passenger trains and freight trains is systematically parameterised. Influence of speed, number of axles, axle load, track type, train length,and train configuration is studied. A model taking into account the ground boundary layer for determining the influence ofmeasured head and tail wind is developed. Different factors and parameters of a train, that are vital for the accuracy in computed energy consumption and runningtime are identified, analysed and finally synthesized into a train model. Empirical models of the braking and the traction system, including the energy efficiency, are developed for the electrical locomotive of typeSJ Rc4, without energy regeneration. Driver behaviour is studied for freight trains and a couple of driving describing parametersare proposed. An empirical model of freight train driver behaviour is developed from fullscale testing and observations. A computer program, a simulator, is developed in Matlabcode, making use of the determined runningresistance and the developed models of train and driver. The simulator calculates the energy consumption and running time ofa single train. Comparisons between simulations and corresponding measurements are made. Finally, the influence of driving on energy consumption and running time is studied and demonstrated in some examples. The main conclusions are that: The method developed for determining running resistanceis quite simple and accurate. It can be used on any train andon any track. The running resistance of tested trains includes some interesting knowledge which is partly believed to be new. Mechanical running resistance is less than proportional to the actual axle load. Air drag increases approximately linearly with train length and the effect of measured head and tail wind on the air drag can be calculated if the groundboundary layer is considered. The developed train model, including running resistance, traction, braking etc. is quite accurate, as verified for the investigated trains. The driver model together with the train model insimulations, is verified against measurements and shows good agreement for energy consumption and running time. It is recommended to use a driver model, when calculating energy consumption and running times for trains. Otherwise, the energy consumption will most likely be over-estimated.This has been demonstrated for Swedish ordinary freighttrains. / QC 20100526

M.Tech. / OBJECTIVE: To determine the most effective treatment protocol in the treatment of Lower-Crossed Syndrome by comparing objective results gained from a Rehabilitation program (group one), Spinal Manipulative Therapy (group two) and a combination of these therapies (group three) directed at the sacroiliac joints and lumbar spine. DESIGN: The study was a clinical trial in which three experimental groups of sixteen participants each were compared to each other. These participants were recruited from the local general population and were selected on the basis of inclusion and exclusion criteria, presenting with Lower-Crossed Syndrome and demonstrating unremarkable clinical and radiological findings. INTERVENTION AND DURATION: After randomisation, group one received a Rehabilitation program which consisted of a stretching and strengthening program only, group two received Spinal Manipulative Therapy only whereas group three received a combination of Spinal Manipulative Therapy and a Rehabilitation program. The frequency of the follow up consultations for this study was two consultations over the first two weeks of the trial and once a week for the following four weeks of the trial. MEASUREMENTS: Objective measurements included lumbar spine flexion and extension ranges of motion, hip flexor flexibility (hip extension), active and passive hamstring flexibility, gluteus maximus and abdominal strength tests and Sorenson’s Test (static back extensor strength test). Subjective measurements were the Oswestry Low Back Pain and Disability Index and McGill’s Questionnaire. Measurements were taken before (pre-) and after (post-) the first (initial), third, fifth and eighth (last) consultations. CONCLUSIONS: The aim of the study was to determine the most effective treatment protocol in the management of Lower Back Pain in athletes presenting with Lower-Crossed Syndrome. Although the combined group (group three) showed the greatest improvement these findings were statistically no greater than the statistical findings in group one and group two. All groups showed a statistically significant improvement over the trial period. This illustrates that both Spinal Manipulative Therapy and a Rehabilitation program (including stretching and strengthening) was effective in the management of Lower-Crossed Syndrome. From this study it can therefore be concluded that one treatment protocol did not prove to be more effective than that of the others.

China Run is a 92 1/2 minute documentary film which portrays an ultramarathon runner's record-setting 2,125 mile run across China in 53 days, starting at the Great Wall north of Beijing and concluding in Guangjhou (Canton). It is a story of the difficulties, both physical and emotional, suffered by the runner, as well as the story of his encounters with the people of China.