This thesis reports on a numerical investigation into the three-dimensional flow divergence around a high solidity vertical axis wind turbine. Three-dimensional unsteady Reynolds averaged Navier-Stokes simulations of an H-type vertical axis wind turbine were used to examine the impact of turbine aspect ratio and tip speed ratio on the flow divergence. The turbine height was changed to alter the turbine aspect ratio, while keeping the diameter constant, to ensure that the solidity and tip speed ratio values were comparable between the different aspect ratios tested. The power output of the turbine consistently increased with aspect ratio and the optimal tip speed ratio for peak performance was negligibly affected. The flow divergence results showed that larger aspect ratio turbines had significantly more flow divergence with a 1 m/s entrance velocity difference between the smallest and largest cases. These two results where contradictory as a larger aspect ratio turbine was more efficient even though it had a smaller fraction of the upstream flow entering the upwind pass. The reason for this result was that impact of the tip effects, which caused a power reduction near the end of the blades. The distance from the blade tips that experienced a power reduction was constant for turbines of aspect ratio one and greater, resulting in a smaller turbine having a greater fraction of its height effected by the tips. This caused the overall power output for a smaller aspect ratio turbine to be lower even though its centre performance was higher, due to an increased entrance velocity. The change in flow divergence with tip speed ratio was also examined to better understand the driving force behind the divergence. It was found that the turbine power output was not the direct cause of flow divergence. The blade forces, specifically the force generated in the upstream direction had a strong linear correlation with the upstream flow divergence. / Thesis / Master of Applied Science (MASc)

The human gut and brain have a bidirectional communication that has shown to play a pivotal role in our health and disease. Literature has shown that microbiota composition and diversity can be influenced by both genetic and environmental factors, contributing to shaping an individual’s microbial composition. The current work includes analysis of the microbiome of several mouse models to better understand how gene-environmental interactions during early development can influence the composition of microbiota within the gut. Here, male and female mice from several strains (C57BL/6, Balb/C, FVB, CD1) and genetically modified mice including T-cell receptor knock out mice (TCRβ-/-δ-/-) and Fragile-X-mice (FMR1-KO) were exposed to early life stressors including lipopolysaccharide (LPS) injection on postnatal day 3 (P3) and/or overnight maternal separation on P9. Fecal samples were collected at P24 and microbiota composition was determined by amplifying the 16s rRNA gene variable 3(v3) region and sequenced using the MiSeq Illumina platform. DADA2, was used to analyze this data in R software. Among the group, strain was found to be significant among alpha and beta diversity metrics while sex and stress were found to contribute to within strain variation, which demonstrated that both genetic and environmental factors are important in shaping an individual’s microbial composition. Secondly, we also explored the role of gut microbiota on the development of the immune system in TCRβ-/-δ-/- and C57BL/6 mice. Mice that lack T-lymphocytes were found to have a lower alpha diversity, as well as separated from their wild-type controls by beta diversity. Several bacterial taxa were found to be influenced by the immune system, demonstrating a bidirectional communication between the gut and T-cells. Lastly, the influence of litter, an environmental factor on microbial composition was explored within inbred mouse strains, C57BL/6 and Balb/C. Litter was found to influence alpha diversity, in which litters among C57BL/6 exhibited the greatest variation in such diversity. Beta diversity was also found to be influenced by litter, as related litters were found to cluster together. Differences in bacterial taxa between the inbred strains were observed and a subset of those taxa were found to be influenced by litter. Hierarchical clustering and co-occurrence analysis revealed different clusters of co-occurring taxa between both strains. These findings demonstrate that environmental factors can contribute to influence the composition of microbiota. / Thesis / Master of Science (MSc)

Individuals living with depression and anxiety show systemic increases of the bacterial endotoxin lipopolysaccharide (LPS), which induces an inflammatory cascade, resulting in negative effects across the gut-brain axis (GBA). LPS administration in mice has previously been used as a rodent model of depression/anxiety. Flaxseed (FS) contains key bioactives, including an omega-3 fatty-acid, dietary fibre, and a poly-phenolic compound which all may attenuate the effects of LPS through modulation of the GBA. The objectives of this thesis were to examine the effects of LPS on the GBA in C57Bl/6 mice and to determine if dietary supplementation with FS and/or FS oil (FO) provided protection against the LPS challenge. The LPS-induced negative effects across the GBA were partially attenuated by dietary supplementation with FS, but not FO, through changes in microbiota composition/function and systemic-/neuro-inflammation. Therefore, the potential benefits of FS are independent of the oil or are synergistic of all bioactives.

This study examined links of cumulative and present depressive symptoms with present cortisol diurnal profiles in oldest-old adults. Five waves of data from 50 older adults (M age = 89.05 years; 64% women) who participated in the Australian Longitudinal Study of Ageing were used to combine 15 years of longitudinal data with seven cortisol samples per day over a one-week period. Findings revealed that individuals with more past depressive symptoms showed a lower cortisol awakening response (CAR). Interestingly, present depressive symptoms were not associated with the CAR. These findings inform our understanding of distal health factors in very old age.

Epilepsy is a complex, chronic neurological disorder with diverse underlying etiologies characterized by the spontaneous occurrence of seizures. Epilepsy affects all ages from neonates to elderly adults, with the most recent CDC estimates stating that ~3 million adults and over 400,000 children are currently suffering from active epilepsy in the U.S. alone. In adults, the leading cause of epilepsy worldwide in central nervous system (CNS) infection, while in neonates the most common cause of seizures is hypoxic/ischemic encephalopathy (HIE). However, in both adults and neonates, current antiepileptic drugs (AEDs) are ineffective in 30-50% of patients, despite the availability of over 20 FDA approved AEDs with diverse molecular targets. This disparity highlights a critical need for novel therapeutics in seizure-susceptibility and epilepsy. The microbes that inhabit gut mucosal surfaces, termed the gut microbiota, have been increasingly implicated in the pathology of neurological diseases including epilepsy. This gut-brain axis is an intriguing therapeutic target in epilepsy as gut microbes can affect the CNS through multiple mechanisms including vagus nerve signaling, immune-gut interactions, and through production of microbial-metabolites including neurotransmitters, short chain fatty acids (SCFAs), lactate, vitamins, and S-equol. Furthermore, the gut microbiota is crucial for neurodevelopment, indicating that the gut-brain axis may be involved in pediatric seizure-susceptibility. This dissertation reviews current evidence on the role of gut metabolites in seizure-susceptibility in epilepsy, highlighting the microbial-derived metabolite S-equol as a potential novel AED. We then evaluate gut microbiome alterations in the Theiler's murine encephalomyelitis virus (TMEV) adult mouse model of CNS infection-induced seizures and find decreases in S-equol-producing bacteria in the gut microbiomes of TMEV-infected mice with seizure phenotypes. We characterize the effect of exogenous S-equol on neuronal function in vitro, demonstrating a reduction in neuronal excitation following S-equol exposure. We additionally characterize entorhinal cortex (ECTX) pyramidal neuronal hyperexcitability, and demonstrate the ability of exogenous S-equol to ameliorate CNS-infection-induced ECTX neuronal hyperexcitability ex vivo. Finally, we demonstrate that perinatal and postnatal exposure to antibiotics alters the gut microbiome and increases seizure-susceptibility following HIE exposure in p9/p10 mice, potentially via sex-specific alterations in neuronal function. Together, this dissertation evaluates the gut-brain axis in pediatric and adult mouse models of seizure-susceptibility and identifies the gut metabolite S-equol as a potential target for the treatment of seizures. / Doctor of Philosophy / Epilepsy, a disease defined by the occurrence of two or more spontaneous seizures, affects over 50 million people worldwide. This makes epilepsy one of the most common chronic neurological disorders across the globe. People with epilepsy suffer increased mortality, lower quality of life, and increased social stigma. There is currently a crisis in the treatment and management of epilepsy, because although over 20 different anti-epileptic drugs (AEDs) are available to patients, these drugs only work in ~70% of individuals with epilepsy, leaving 30% of patients with uncontrolled seizures. Currently available AEDs are designed to target classical central nervous system (CNS) components. However, a growing body of evidence suggests that epilepsy is related to complex systems throughout the body. Therefore, in this manuscript we explore novel therapeutic targets outside of the CNS for the management of seizures. Over 1000 species of bacteria live in the in the human gut, and are termed the gut microbiota. Gut microbes produce a variety of chemicals that circulate through the body and can even reach the brain. Interaction of chemicals produced by the gut microbiota and brain chemistry have been shown to affect disease outcomes in Autism Spectrum Disorder, Parkinson Disease, and other brain disorders. However, very few studies have examined the possibility of a role for the gut microbiota in epilepsy. In this dissertation, we review chemicals produced by the gut microbiota that may alter epilepsy biology. We additionally examine gut microbiota alterations in a rodent model of epilepsy, and identify a novel chemical, S-equol, that is produced by the gut microbiota and impacts epilepsy biology in our rodent model. Lastly, we explore how altering the maternal gut microbiota in rodents can influence seizure-susceptibility in infants.

While both social information processing and cortisol secretion in childhood aggression have generated a great deal of interest and research in the past few decades, these social-cognitive and physiological components of aggressive behavior have not been examined in the context of an integrative model. This lack of an integrative framework may underlie some of the inconsistencies that have plagued the literature in this area to date, especially with respect to hypothalamic-pituitary-adrenal (HPA) axis functioning in aggressive children. This investigation tested a mediational model of the relationship between social-information processing, cortisol secretion, and reactive and proactive aggression. Specifically, it was hypothesized that social-information processing variables would mediate the proposed relationship between reactive and proactive aggression and cortisol secretion. One hundred and twenty-six children between the ages of 13 and 18 were administered the Child Behavior Rating Form (CBR), the Home Interview with Child (HIC), the Response Decision and Social Goals Instrument (RDSGI), the Antisocial Processes Screening Device (APSD), the Buss-Durkee Hostility Inventory (BDHI), the Children's Depression Inventory (CDI), and the Revised Children's Manifest Anxiety Scale (RCMAS). Each child also contributed two samples of saliva for cortisol assay, and each child's teacher completed a teacher-version of the APSD and the CBR. Regression analyses revealed no significant associations between proactive or reactive aggression and cortisol secretion, or between any of the social-information processing variables and cortisol secretion. Predicted associations between proactive and reactive aggression and social-information processing variables were found. Overall, therefore, the mediational model was not supported. However, cortisol secretion was found to be associated with both anxiety and depression, and exploratory analyses revealed significant associations between cortisol secretion and Psychopathy as measured by the APSD. Taken together, the findings suggest that while the specific relationship proposed here among social-cognitive, psychophysiological, and behavioral variables was not found, an integrative model examining each of these components may be useful in further investigations of the complex phenomenon of childhood aggression. / Ph. D.

The effectiveness of exercise has been increasingly studied as exercise has been popular for the improvement of physical performance and rehabilitation of lumbar spine. A variety of exercises have been used to reduce back pain or spinal degeneration. However, there are no studies to determine effects of exercise on lumbar spine kinematics, including lumbar-pelvic coordination and instantaneous axis of rotation. The current study aimed to examine these lumbar spine kinematical changes due to exercise and therapy. We hypothesized that exercise and therapy will affect the changes of lumbar spine kinematics. Lumbar-Pelvic motions were recorded from 86 healthy subjects while performing lifting and lowering tasks of 10% and 25% of body weight. The influence of exercise was quantified from coefficients of curve-fitting for pelvic and lumbar angles. There was a significant difference (p<0.05) for the range of lumbar motion (distribution, D) between the control group and the cardiovascular exercise group after 12-week program. However, there was no significance for lumbar-pelvic coordination, C. A second study was performed to investigate the changes of instantaneous axis of rotation (IAR) at which trunk angle reached 25º. Results indicated that a superior-inferior location of IAR was significantly (p<0.05) modified by the cardiovascular exercise after 12 weeks, but there was no significant effectiveness of the physical therapy exercise. Finding of lumbar spine kinematics during lifting and lowering a weight which are the most popular manual handling activities may provide great understanding of the exercise effectiveness. Future studies are recommended to assess whether the changes of lumbar spine kinematics lead to the decrease instances of lumbar spine injuries or low back pain. / Master of Science

This project focuses on the wall as a cross-axis form, one which gives an order to the landscape and a reference for the rest of the building to be set against. The intersections of these walls produce four corners housing four pavilions for dwelling. As the walls extend over the landscape, it culminates with a tower, a dwelling space for a guest, overlooking the surrounding landscape. / Master of Architecture

No / The purpose of this study was to ascertain whether or not spreading depression (CSD) propagates symmetrically along the anteroposterior axis of the cortex of mice, and to determine where CSD should be elicited to achieve a uniform exposure of the cortex to this phenomenon. Experiments were performed in halothane-anesthetized mice, with three different locations aligned 1.5 mm from the midline used for either KCl elicitation of CSD or the recording of its propagation. Our results demonstrated that, at least in the mouse cortex, CSD propagated much more effectively from posterior to anterior regions than in the opposite direction. This feature was due to a different efficacy of propagation in the two opposite directions, and not to a reduced susceptibility of occipital regions to CSD elicitation. Heterogeneous CSD propagation constitutes a potential pitfall for neurochemical studies of post-CSD changes in mice, as brain tissue samples collected for this purpose should be uniformly exposed to CSD. Occipital sites for CSD induction are clearly optimal for this purpose. If CSD propagation is confirmed to be more effective from posterior to anterior regions in other species, this may be relevant to the pathophysiology of classical migraine because the most frequent aura symptoms (i.e., visual disturbances) originate in the occipital cortex.

The project is for the central building of a community center used by the communities of Blacksburg and Christiansburg. The building is a space configured as a hub that uses axes to determine entering, exiting and vertical movement. The hub configuration of the building is in concentric rings around the atrium in both space and materials. As materials were brought into the building, they enhanced the strong axial configuration and emphasized the layers surrounding the central hub space of the atrium. There are two pairs of axes in the building. The entrance axes are perpendicular to the faces of the building and provide lines of sight through it. They also establish the paths of entering and exiting the building. The diagonal axes regulate the vertical movement throughout the building. / Master of Architecture