Thesis (Ph. D.)--Stanford University, 2005. / Includes bibliographical references (leaves 73-77).

Thesis (Ph. D.)--Southern Methodist University, 1993. / Includes bibliographical references (leaves 88-96).

Thesis--Wisconsin. / Vita. Includes bibliographical references (leaves 685-717).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1994. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph.D.)--The Chinese University of Hong Kong, 2005. / Advisers: Chen Yongqin, Lam Kin-che. Includes bibliographical references (p. 174-190)

Thesis (M.Sc.)(Entomology)--University of Pretoria, 2006. / Includes summary. Includes bibliographical references. Available on the Internet via the World Wide Web.

Catalyseurs de la dégradation de polysaccharides dans le cadre de diverses applications industrielles, de nombreuses glycoside hydrolases (GH) possèdent également une activité de transglycosylation qui peut être exploitée pour la synthèse d'oligosaccharides. Afin d'augmenter cette activité, minoritaire par rapport à l'hydrolyse, des expériences de mutagenèse rationnelle peuvent être employées. Toutefois, l'ensemble des bases moléculaires régissant l’équilibre entre ces deux activités reste en revanche difficile a élucider. L'étude de quatre GH (Ttβgly, AgaD, TcTS, TrSA) par simulation de dynamique moléculaire a permis la découverte de canaux d'eau internes à leurs structures et connectant le site actif au milieu. Cette observation suggère que les canaux d'eau internes aux GH pourraient être impliqués dans leur activité d'hydrolyse. Plusieurs paires de résidus bordant deux de ces canaux ont été mis en évidence chez Ttβgly et AgaD et semblent contrôler le passage de l'eau du canal vers le site actif. La mutagenèse de ces résidus a été entreprise afin de tenter d'augmenter l'activité de transglycosylation chez ces deux enzymes. Une réduction de l'hydrolyse d'un facteur 7 et 50 au profit de l'activité de transglycosylation a été caractérisée chez les deux meilleurs mutants de Ttβgly et AgaD, respectivement. L'analyse des simulations a révélé que ces résultats étaient corrélés à une augmentation de la dynamique des molécules d'eau internes aux deux canaux étudiés. Cette étude souligne ainsi l'importance fonctionnelle de l'eau interne aux hydrolases et suggère que l'ingénierie de sa dynamique peut constituer une approche originale pour convertir les GH en transglycosidases. / Known for their ability to hydrolyse glycosidic linkages,numerous glycoside hydrolases (GH) are also able tocatalyse transglycosylation reaction which can beharnessed for the synthesis of oligosaccharides. Althoughin the vast majority of cases hydrolysis prevails overtransglycosylation reaction, the latter has already beenincreased through mutagenesis and directed evolutionexperiments. However, little is known about the regulationof the balance between both activities. We discover, viamolecular dynamics (MD) simulations, several potentialwater channels connecting the bulk to the active site infour GH: Ttβgly, AgaD and the pair of homologsTcTS/TrSA. This observation supports the hypothesis thatchannels could be involved in the hydrolytic activity of GH.Amino acid residues forming bottlenecks at the interfacebetween two water channels and the active site in Ttβglyand AgaD were suspected to control water access fromthe bulk to the channel interior and the active site.Mutagenesis of key amino acids in the vicinity of selectedchannels was performed in order to attempt to increasethe transglycosylation/hydrolysis ratio balance.Characterization of the best mutants showed a 7 and 50fold decrease of hydrolysis compared to the wild type forTtβgly and AgaD respectively, while the transglycosylaseactivity was improved. MD simulations showed that thesemodifications were correlated with greater water dynamicsin the corresponding channels. These results highlight theimportance of water dynamics in hydrolases catalysis andsuggest that modifying the protein internal water dynamicscould serve as a generic approach to engineertransglycosylase activity in GH.

Physical rehabilitation of individuals who are experiencing a disabling illness or have survived a traumatic injury (i.e. stroke) must seek to train the body’s structures and functions to reduce disability (activity limitations, participation restrictions) (Stucki, 2005). Figure 1 represents a modified version of the International Classification of Functioning (ICF), Disability and Health (World Health Organization, 2002). This figure illustrates how, for example, a stroke impacts the body structures and functions (e.g. muscle recruitment) which influences the ability to complete activities (e.g. gait) ultimately restricting participation in all areas of life (e.g. employment). The ICF model presents a framework for clinical practice and rehabilitation research studies. Although it has been shown to be strongly correlated (Schmid, Van Puymbroeck, et al., 2013) the concept of function cannot always be directly correlated with the concept of quality of life (Stucki, 2005) as the individual may not perceive, for example, impaired balance and mobility as detrimental to their quality of life. However, reduced function does put an individual at further risk of complications including falls and injuries from compensatory mechanisms and therefore must be addressed. The focus of this thesis is the study of the potential benefits of an exercise modality (virtual reality) to encourage restoration of the body’s structures and functions for individuals post-stroke. As the individuals engage in physical rehabilitation through exercise, there may be improvements on the individual’s abilities as seen through measurements of the control of posture and walking. The thesis comprises four studies, two of which have been published in peer reviewed journals. The progression of studies attempts to characterize outcomes following the use of virtual reality training in clinical populations (dementia and stroke) to address impairments to the body structures and functions (e.g. mobility) as measured by both clinical measures of activity and laboratory based measures of balance and to elucidate a possible mechanism (focus of attention) that makes training in a virtual environment effective.

INTRODUCTION: Canada has yet to conduct high quality, prospective, population-based surveys that measure incident visual impairment, its risk factors, and adverse consequences, creating an unmet need to obtain more rigorous analysis in this regard QUESTIONS: What is the 3-year incidence of visual impairment in each province? What are the risk factors for the 3-year incidence of visual impairment? Do they include geographic, sociodemographic, lifestyle, social, health and healthcare factors? Does vision loss increase the odds of balance problems after three years? METHODS: Baseline and 3-year follow-up data were used from the Canadian Longitudinal Study on Aging. The Comprehensive Cohort included 30,097 adults ages 45-85 years old recruited from 11 sites across 7 provinces. Presenting binocular visual acuity was measured using the Early Treatment of Diabetic Retinopathy Study chart. Incidence of VI was defined as the development at follow-up of visual acuity worse than 20/40 in those with acuity better than or equal to 20/40 at baseline. Balance was measured using the one-leg balance test. Those who could not stand on one leg for at least 60 seconds were classified as having failed the test. Participants were asked about the self-report of a diagnosis of cataract, macular degeneration, or glaucoma. RESULTS: 3.88% (95% Confidence Interval (CI) 3.61, 4.17) of Canadian adults developed VI over a 3-year period. There was a high degree of variability in the incidence between Canadian provinces with a low of 1.42% in Manitoba and a high of 7.33% in Nova Scotia. Uncorrected refractive error was the leading cause of incident VI. Risk factors for incident VI included older age (odds ratio (OR)=1.07, 95% CI 1.06, 1.07), Black race (OR=2.64, 95% CI 1.36, 5.14), lower household income (OR=1.73 for those making less than $20,000 per year, 95% CI 1.24, 2.40), current smoking (OR=1.78, 95% CI 1.37, 2.32), and province. Of the 12,158 people who could stand for 60 seconds on one leg at baseline, 18% were unable to do the same at follow-up 3 years later. After adjustment for demographic and health variables, those with worse visual acuity (per 1 line) were more likely to fail the balance test at follow-up (OR=1.15, 95% CI 1.10, 1.20). Those with a report of a former (OR=1.59, 95% CI 1.17, 2.16) or current cataract (OR=1.31, 95% CI 1.01, 1.68) were more likely to fail the test at follow-up. CONCLUSION: The incidence of visual impairment is common in older Canadian adults, varies markedly between provinces, and is largely due to treatable causes. Risk factors for VI suggest sub-groups that may benefit from interventions to improve access to eye care. These data provide longitudinal evidence that vision loss increases the odds of balance problems over a 3-year period. Efforts to prevent avoidable vision loss are needed as are efforts to improve the balance of visually impaired people.

Eskom produces approximately 90% of the electricity used in South Africa of which approximately 90.8% is from fossil fuel power plants. The process of electricity generation requires a significant quantity of raw water; therefore, Eskom is considered a strategic water user in South Africa. Water management is a growing focus area due to the increase in water usage and requires continuous improvement. Water management has been identified as an area lagging behind on the advanced analytics initiatives in Eskom. Excel based tools were used for the development of water balance models and water performance calculations in Eskom. This was attributed to the user-friendly functionality and availability to all users. However, the Excel tool posed challenges in allowing for standardisation and validation of calculations, tracking of model changes, continuous trending and storage of data as well as structured graphical user interfaces for screens and dashboard developments. There was therefore a need to develop a methodology on how to structure a water balance model for coal-fired power plants with standard calculation templates that allowed for customisation by each power plant within Eskom. It was required that the water balance model be implemented on a performance and monitoring tool allowing for comparison of power plant targets to actual online data in real time, enhancing the monitoring capabilities. It should have the ability to generate real time water performance data creating an opportunity for improved water management across the generation fleet. The approach adopted in this dissertation was to learn from existing Eskom Excel water balance tools and develop a standard mathematical model in the form of EtaPRO calculation templates. These templates are be structured such that they function as process components to develop water balances at power plants. The mathematical verification of the Excel calculations were to be conducted using Mathcad. The access to real time data, performance monitoring capabilities and availability at all Eskom Power plants, led to the selection of EtaPRO as the modelling platform. The research conducted led to the development of a methodology for setting up a water balance model for a wet-cooled coal-fired power plant. Calculation templates developed into EtaPRO were validated against the Mathcad mathematical model. The results included a well-documented mathematical model of a water balance in Mathcad and the development of 19 calculation templates that perform the function of standard process components. In addition to calculation templates, multiple Non Volatile (NV) records were created to allow the power plants to capture and track permanent data inputs. NV records also allow for creation of case studies, improving the process monitoring capabilities. A water balance model for a selected power plant was simulated in EtaPRO using the developed calculation templates and user defined formulae. Test screens and dashboards were created to illustrate how the calculation templates and water balance framework would be used to develop a typical water balance model and monitoring system. In conclusion, it is possible to develop process models within the EtaPRO software from well-defined mathematical models to address the performance monitoring concerns on water systems within Eskom.