Solar radiation offers phenomenal potential for energy conversion with energy densities on the order of 1000W/m2 in locations with regularly clear skies. As always, the difficulty lies in finding a solar-electric conversion technology capable of producing electricity at a competitive cost. The SolarCAT (Solar Compressed Air Turbine) system produces electricity by releasing stored compressed air through a series of turbines with solar dish concentrators providing the required heat for efficient conversion to electricity. To minimize impact on capital cost, high recuperator effectiveness targets are sought but unlike typical fuel-fired micro-turbines, raising the recuperator effectiveness of the solar power system yields a benefit in overall system capital cost. Improving efficiency lowers the size and cost of the largest element of the system, namely the dish. In this study potential techniques for achieving a highly compact heat-transfer media were reviewed. Folded fin, packed beds, micro-tubes, lattice frame structures, metal foams, woven textile, and micro-machining techniques were assessed. Textile structures were selected as an appropriate medium to replace the internal folded fin of the SolarCAT recuperator. The relatively long flow (>150mm) path through the proposed screen wafers requires a model for fully-developed forced convective flow between parallel plates. A mathematical model was developed by integrating the results from the work of several authors in the field of textiles and porous media. #100 mesh sintered screen wafers were brazed between two 0.25mm stainless steel sheets and destructively tested to assess their tensile strength. Although iii optimization of the braze parameters was not completed, it was found that many samples survived exposure to internal pressures in excess of 50MPa. This study found that the use of sintered screen wafers to replace the internal folded fin of the SolarCAT recuperator would have advantages over the current design with respect to both overall recuperator effectiveness, size, and cost. Textile structures can be tailored to have wide range of fluid and heat-transfer properties depending on the application. The manufacturing process is relatively simple and could be cost-effective for high-volume production.

OBJECTIVES: To determine the relationship between composite FMS score and the risk of time-loss injury in experienced male rugby union athletes, and in addition, to determine the relationship between FMS-determined bilateral movement asymmetries and the risk of time-loss injury in these athletes. DESIGN: Analytical cohort study. SETTING: Rugby union on-field training and competition, and athletic therapy rooms at the University of Victoria or at Rugby Canada’s Center of Excellence, Victoria BC. PARTICIPANTS: 76 experienced, male rugby union athletes (mean age 21.6±2.7 years). MEASUREMENTS: Participants completed surveys pertaining to demographic, anthropometric, injury history, and involvement in rugby union information. The main outcome measures were time-loss injury incidence and FMS scores. RESULTS: Odds ratio analyses revealed that when compared to those scoring at least 14.5, players with FMS scores below 14.5 were 10.42 times (95%CI: 1.28-84.75, Fisher’s exact test, one-tailed, p=0.007) more likely to have sustained time-loss injury (+LR=7.08, -LR=0.72, specificity=0.95, sensitivity=0.35) in Season One and 4.97 times (95%CI: 1.02-24.19, Fisher’s exact test, one-tailed, p=0.029) more likely in Season Two (+LR=3.56, -LR=0.71 specificity=0.90, sensitivity=0.36). Participants scoring below 15.5 on the FMS were also at significantly greater risk of injury, exhibiting a risk of injury 3.37 times (95%CI: 1.12-10.14, Fisher’s exact test, one-tailed, p=0.027) greater than players with higher FMS scores in Season Two (+LR=1.84, -LR=0.55, specificity=0.65, sensitivity=0.64), but not in Season One. The presence of bilateral asymmetries was not associated with increased likelihood of time-loss injury. CONCLUSIONS: Experienced male rugby union athletes with preseason FMS scores below 14.5 are 5-10 times more likely to sustain one or more time-loss injuries in a competitive season when compared to athletes with FMS scores of at least 14.5. The quality of fundamental movement, as assessed by the FMS, is predictive of time-loss injury risk in experienced rugby union athletes and should be considered an important preseason player assessment tool. / Graduate

This wide-ranging study explored various parameters of visual search in relation to computer screen displays. Its ultimate goal was to help identify factors which could result in improvements in commercially available displays within the 'real world’. Those improvements are generally reflected in suggestions for enhancing efficiency of locatabolity of information through an acknowledgement of the visual and cognitive factors involved. The thesis commenced by introducing an ergonomics approach to the presentation of information on VDUs. Memory load and attention were discussed. In the second chapter, literature on general and theoretical aspects of visual search (with particular regard for VDUs) was reviewed. As an experimental starting point, three studies were conducted involving locating a target within arrays of varying configurations. A model concerning visual lobes was proposed. Two text-editing studies were then detailed showing superior user performances where conspicuity and the potential for peripheral vision are enhanced. Relevant eye movement data was combined with a keystroke analysis derived from an automated protocol analyser. Results of a further search task showed icons to be more quickly located within an array than textual material. Precise scan paths were then recorded and analyses suggested greater systematicity of search strategies for complex items. This led on to a relatively 'pure' search study involving materials of varying spatial frequencies. Results were discussed in terms of verbal material generally being of higher spatial frequencies and how the ease of resolution and greater cues available in peripheral vision can result in items being accessed more directly. In the final (relatively applied) study, differences in eye movement indices were found across various fonts used. One main conclusion was that eye movement monitoring was a valuable technique within the visual search/VDU research area in illuminating precise details of performance which otherwise, at best, could only be inferred.

Background: The prevalence of childhood overweight and obesity is increasing worldwide. One main determinant of overweight and obesity is inactivity. Little is known about the factors that influence physical activity and sedentary behaviour among young children. Seasonal variation was examined as a correlate of physical activity in both a literature review and in a sample of pre-school children in Edmonton, Alberta. Neighbourhood socioeconomic status (SES) was examined as a correlate of screen time use in the same sample of children. Methods: For study 1, databases were searched for studies on seasonal variation in physical activity levels. Studies 2 and 3 involved a sample of 4- and 5-year-old children, who were attending a health center in and around Edmonton, Alberta for preschool immunization between November, 2005 and August, 2007. Parents provided proxy reports of their children’s screen time viewing and physical activity. Height and weight were measured by a trained health assistant and body mass index (BMI) was calculated. Children’s postal codes were retrieved from health records to calculate neighbourhood SES through census data. The month the proxy report was completed was used to determine seasonality. Several regression models were constructed to examine relationships between variables in studies 2 and 3. Results: The review of literature revealed that 83% (29/35) of the studies found seasonal variation in physical activity among children and/or adolescents. For study 2, total physical activity as well as active play, weekday and weekend minutes were highest in the summer and lowest in the winter. Finally, neighbourhood SES was a predictor of screen time and TV/video use for girls but not for boys in study 3. Conclusion: Some consideration should be given to increasing physical activity opportunities in the winter for children, especially in areas of the world that experience extreme winter conditions. As well some consideration should be given to providing alternative activity opportunities for young girls who live in lower SES neighbourhoods.

Acute myeloid leukemia (AML) is a disease characterized by overproduction of abnormally differentiated, hyper-proliferative myeloid cells known as blasts in bone-marrow and blood. Our laboratory has previously demonstrated that loss of epigenetic repression by the polycomb repressive complex 2 (PRC2), which is mediated by complex member metal response element binding transcription factor 2 (MTF2), drives chemo-resistance resulting in refractory AML. In this study, to identify MTF2-specific synthetic lethal interactions, a genome-scale CRISPR Knock-out (GeCKO) synthetic lethal screen was performed in matched MTF2-deficient and rescued THP-1 cells both in the absence and presence of the induction chemotherapeutic cytarabine. Following careful analysis of screening data using specialized software, 104 highly significant MTF2-specific synthetic lethal interactions as well as 15 cytarabine-specific synthetic lethal interactions were identified. Reduced stringency upon analysis helped to identify an additional seven MTF2-specific synthetic lethal interactions that could be targeted with commercially available small-molecule inhibitors. Among eight small molecule inhibitors, two DNA Polymerase A/Ribonucleotide Reductase Catalytic Subunit M1 (POLA/RRM1) dual inhibitors (clofarabine and fludarabine) were shown to induce toxicity with specificity for MTF2-deficient THP-1 cells at low concentrations only in the absence of cytarabine. In the future, further testing of the therapeutic potential of clofarabine and fludarabine in treating MTF2-deficient AML will be conducted in patient derived bone-marrow aspirates which better represent the true clonal and hierarchical nature of this life-threatening malignancy. Furthermore, lentiviral delivery of short-hairpin RNAs (shRNAs) targeting highly significant, non-enzymatic MTF2 and cytarabine-specific synthetic lethal interactions will be performed in both THP-1 cells as well as in patient derived bone-marrow aspirates. Eventually, in vitro validated targets will be validated under in vivo conditions using a patient derived xenograft (PDX) preclinical animal model of AML using immunocompromised NOD scid gamma (NSG) mice.

Solar radiation offers phenomenal potential for energy conversion with energy densities on the order of 1000W/m2 in locations with regularly clear skies. As always, the difficulty lies in finding a solar-electric conversion technology capable of producing electricity at a competitive cost. The SolarCAT (Solar Compressed Air Turbine) system produces electricity by releasing stored compressed air through a series of turbines with solar dish concentrators providing the required heat for efficient conversion to electricity. To minimize impact on capital cost, high recuperator effectiveness targets are sought but unlike typical fuel-fired micro-turbines, raising the recuperator effectiveness of the solar power system yields a benefit in overall system capital cost. Improving efficiency lowers the size and cost of the largest element of the system, namely the dish. In this study potential techniques for achieving a highly compact heat-transfer media were reviewed. Folded fin, packed beds, micro-tubes, lattice frame structures, metal foams, woven textile, and micro-machining techniques were assessed. Textile structures were selected as an appropriate medium to replace the internal folded fin of the SolarCAT recuperator. The relatively long flow (>150mm) path through the proposed screen wafers requires a model for fully-developed forced convective flow between parallel plates. A mathematical model was developed by integrating the results from the work of several authors in the field of textiles and porous media. #100 mesh sintered screen wafers were brazed between two 0.25mm stainless steel sheets and destructively tested to assess their tensile strength. Although iii optimization of the braze parameters was not completed, it was found that many samples survived exposure to internal pressures in excess of 50MPa. This study found that the use of sintered screen wafers to replace the internal folded fin of the SolarCAT recuperator would have advantages over the current design with respect to both overall recuperator effectiveness, size, and cost. Textile structures can be tailored to have wide range of fluid and heat-transfer properties depending on the application. The manufacturing process is relatively simple and could be cost-effective for high-volume production.

Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, Factor VII and in small amounts in its activated form, Factor VIIa. However, the mechanism of initial generation of Factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases Factor VII activating protease, and hepsin play a role in activating Factor VII, however, it has remained controversial. In this work I estimated the levels of Factor VIIa and Factor VII for the first time in adult zebrafish plasma and also reevaluated the role of the above two serine proteases in activating Factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease did not reduce Factor VIIa levels while hepsin knockdown reduced Factor VIIa levels. After identifying role of hepsin in Factor VII activation in zebrafish, I wanted to identify novel serine proteases playing a role in Factor VII activation. However, a large scale knockdown of all serine proteases in zebrafish genome using available knockdown techniques is prohibitively expensive. Hence, I developed an inexpensive gene knockdown method which was validated with IIb gene knockdown, and knockdown all serine proteases in zebrafish genome. On performing the genetic screen I identified 2 novel genes, hepatocytes growth factor like and prostasin involved in Factor VII activation.

Adolescence is a period of dynamic behavioural and emotional development that can increase young people's vulnerability to mental health problems. With 70% of mental disorders having their onset during childhood or adolescence, identifying modifiable factors of these disorders among adolescents can help inform future interventions aiming to improve mental health. One of these factors is electronic technology which has become pervasive in our modern society, occupying an important portion of young people's days and changing their lifestyle. This has created serious concerns regarding the impact of heavy recreational screen use on adolescents' health, especially with the vast majority exceeding the sedentary recreational screen time recommendations of 2 hours or less per day. Evidence suggests that screen time can be associated with adolescent mental health problems. However, little is known about how the extent, nature, and types of recreational screen engagement among adolescents are associated with mental health problems as the body of evidence is very mixed, and many questions remain unanswered. Accordingly, the aims of this dissertation were: i) to summarize the evidence regarding correlates of sedentary screen pursuits among youth, ii) to examine how different types of screens, incorporating their newer forms, are associated with adolescents' mental health cross-sectionally and longitudinally, iii) to examine the nature of screen use and its association with suicidal behaviours; and iv) to explore the moderating role of sex, age, and parental support in the association between screen time and different mental health problems. To achieve these objectives, we completed four manuscripts, all prepared for submission to peer-reviewed scientific journals: 1. A narrative review on the psychological correlates of sedentary screen time behaviour among children and adolescents. 2. Heavy social media use and psychological distress among adolescents: the moderating role of sex, age, and parental support. 3. Problematic technology use, suicidal ideation, and suicide attempt among adolescents: the moderating role of sex. 4. Longitudinal associations between different types of screen use and depression and anxiety symptoms in adolescents. Collectively, our results identified that high levels of sedentary screen behaviour are associated with more severe anxiety, depressive symptoms, and suicidality among adolescents. However, the strength of associations varied between some screen types. Additionally, the findings of this dissertation indicate that a further increase in screen time is associated with increased mental health problems. Lastly, an important role of sex and age in this association was identified. These results can be used to inform future research in this field and guide future interventions designed to manage screen use among adolescents and improve their mental health.

Lipid droplet (LD) autophagy (lipophagy) is a recently discovered selective form of autophagy and is a pathway for LD catabolism through the lysosome or vacuole. Therefore, lipophagy has therapeutic potential in the treatment of a variety of lipid related diseases in which increased cellular LDs are associated with pathophysiologies, such as obesity or atherosclerosis. This ubiquitous process has been an ongoing area of research within the budding yeast, Saccharomyces cerevisiae. However, there remains a need to better understand the regulators of this process. I have developed and validated a lipophagy library in yeast for the assessment of novel genetic regulators of stationary phase induced lipophagy. Through the screening of my library for roles in lipophagy I have identified many genetic regulators of lipophagy which include CUE1, UBC7, LHS1, HSP31, PLN1, TFS1, LAM6, OSH3, OSH4 and OSH7, among others. My screen highlights the power of this library to identify lipophagy regulators in S. cerevisiae, which can be utilised in the future to further the understanding of lipophagy.

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