The Synthesis of Imidazole Fatty Acid Conjugates as Inhibitors of Apoptosis

Ionizing radiation is known to initiate apoptosis in mammalian cells by causing the transformation of cytochrome c into a peroxidase, which results in the specific peroxidation of the mitochondrial phospholipid cardiolipin. Here we report the design and synthesis of 8 imidazole fatty acid derivatives that bind to the cyt c:CL complex and inhibit the peroxidase activity required for the initiation of apoptosis. We postulate that imidazole acts as a sixth ligand to the haem iron and stops the interaction with H2O2. Two mitochondrially directed analogues (3-hydroxypropyl)triphenylphosphonium esters) of 12-imidazole-stearic acid and 12-imidazole-oleic acid not only were demonstrated to be peroxidase inhibitors in vitro, but were also extraordinarily effective in protecting mice from lethal doses (9 Gy) of ionization radiation. We studied the structure activity relationship to a group of triphenyl phosphonium derivatives containing imidazole at different positions on the fatty acid chain, and observed that the C8-imidazole stearate analogue had marginally better activity than the others. But overall, the structure activity result were remarkable “flat” with all compounds prepared having rather similar inhibitory strength. We also synthesized carnitine mono and di-esters of 12-imidazole fatty acids but full biological data is not yet available for these compounds.

The Role of Membrane Lipid Composition on Sarco(endo)plasmic Reticulum Calcium ATPase Function in Rat Soleus Muscle

Sarco(endo)plasmic reticulum calcium ATPase (SERCA) is a transmembrane protein whose function is regulated by its immediate lipid environment (annulus). The composition of the annulus is currently unknown or it’s susceptibility to a high saturated fat diet (HSFD). Furthermore it is uncertain if HSFD can protect SERCA from thermal stress. The purpose of the study was to determine SERCA annular lipid composition, resulting impact of a HSFD, and in turn, influence on SERCA activity with and without thermal stress. The major findings were annular lipids were shorter and more saturated compared to whole homogenate and HSFD had no effect on annular lipid composition or SERCA activity with and without thermal stress. Both average chain length and unsaturation index were positively correlated with SERCA activity with and without thermal stress. These findings suggest that annular lipid composition is different than whole homogenate and its composition appears to be related to SERCA function.

The relationship between stem-form, stand-closure and site -conditions : the influence of environmental conditions on tree allometry and forest structure in west-central Alberta

Changes in the configuration of a tree stern result insignificant differences in its total volume and in the proportion of that volume that is merchantable timber. Tree allometry, as represented by stem-fo~, is the result of the vertical force of gravity and the horizontal force of wind. The effect of wind force is demonstrated in the relationship between stem-form, standclosure and site-conditions. An increase in wind force on the individual tree due to a decrease in stand density should produce a more tapered tree. The density of the stand is determined by the conditions that the trees are growing under. The ability of the tree to respond to increased wind force may also be a function of these conditions . This stem-form/stand-closure/site-conditions relationship was examined using a pre-existing database from westcentral Alberta. This database consisted of environmental, vegetation, soils and timber data covering a wide range of sites. There were 653 sample trees with 82 variables that formed the basis of the analysis. There were eight tree species consisting of Pinus contorta, Picea mariana, Picea engelmannii x glauca, Abies lasiocarpa, Larix laricina, Populus tremuloides, Betula papyrifera and Populus balsamifera plus a comprehensive all-species data set. As the actual conformation of the stern is very individual, stem-fo~was represented by the diameter at breast height to total height r~tio. The four stand-closure variables, crown closure, total basal area, total volume and total number of stems were reduced to total basal area and total number of stems utilizing a bivariate correlation matrix by species. Site-conditions were subdivided into macro, meso and micro variables and reduced in number 3 using cross-tabulations, bivariate correlation and principal components analysis as screening tools. The stem-fo~/stand-closure relationship was examined using bivariate correlation coefficients for stem-fo~ with total number of stems and stem-fo~ with total basal area. The stem-fo~/site-conditions and the stand-closure/site- conditions relationships were examined using multiple correlation coefficients. The stem-form/stand-closure/site-conditions relationship was examined using multiple correlation coefficients in separate analyses for both total number of stems and total basal area. An increase in stand-closure produced a decrease in stem-form for both total number of stems and total basal area for most species. There was a significant relationship between stem-form and site-conditions and between stand-closure and site-conditions for both total number of stems and total basal area for most species. There was a significant relationship between the stemform and site-conditions, including the stand-closure, for most species; total number of stems was involved independently of the site-conditions in the prediction of stem-form and total basal area was not. Larix laricina and Betula papyrifera were the exceptions to the trends observed with most species. The influence of both stand-closure (total number of stems in particular) and site-conditions (elevation in particular) suggest that forest management practices should include these- ecological parameters in determining appropriate restocking levels.

Melting the matrices : structure, anti-structure, and the emerging conversation /

This thesis investigates two cases of Christian churches, which as a part of their mission seek to accommodate people who would otherwise not be interested in church. One of these communities consider themselves a part of the global 'emerging church' movement, and the other does not. I argue that both communities are employing what I call 'de-compartmentalization' strategy in order to adopt a pragmatic relationship with social and political issues. Furthermore I discuss the case of the emerging church community as an example of 'paraliminal community '; a concept I develop from the work of Victor Turner and Arnold van Gennep.

Rights jurisprudence and the charter : evaluating the changing structure of Canadian federalism /

Abstract . Rights jiirisprudence in Canada dates back as far as Confederation in 1867. Between this date and 1982, the organizing principle of Confederation - federalism - has kept this jurisprudence solely within the supremacy of Parliament, subject to its confines and division of powers. After 1982, however, a new constitutional organizing principle was introduced, when Prime Minister Pierre Trudeau introduced the patriation initiative, touted as the "people's package". Individual rights and freedoms were now guaranteed by the Constitution. Citizens of Canada now had a direct link to the Constitution via the Charter and there were now two significantly different organizing principles within the constitutional order widch created an unstable coexistence. This instability has led to a clash between judicially enforced Charter rights and federalism. The Charter has since had both a nationalizing and centralizing effect on Canadian federalism. This thesis explores the relationship between rights and federalism in Canada fix)m Confederation to present day by comparing the jurisprudence of pre and post Charter Canada. An analysis of Supreme Court's (and its predecessor's, the JCPC) decisions shows the profound effect the Charter has had on Canadian federalism. The result has been an undermining of federalism in Canada, with Parliamentary Supremacy replaced by Constitutional supremacy, and ultimately. Judicial Supremacy. Moreover, rights discourse has largely replaced federalism discourse. Canadians have become very attached to their Charter, and are unwilling to allow any changes to the constitution that may affect their rights as political elites discovered the hard way after the collapse of the Meech and Charlottetown Accords. If federalism is to remain a relevant and viable organizing principle in the Constitution, then governments, especially at the provincial level, must find new and iimovative ways to assert their importance within the federation.

Relationship between photoperiod, plasma concentration of ionic calcium and the histology of the prolactin-secreting cells of the rostral pars distalis of the pituitary gland, the corpuscles of stannius and the ultimobranchial gland in the goldfish, Carassius auratus L. /

The relationship between photoperiod, plasma concentration of ionic calcium and the histology of the prolactin-secreting cells of the rostral pars distalis of the pituitary gland, the Corpuscles of Stannius and the Ultimobranchial gland were investigated. Neither the plasma concentration of ionic calcium nor histologically apparent prolactin cell activity could be correlated with photoperiod. Some evidence of a photoperiodic effect on both the Corpuscles of Stannius and the Ultimobranchial gland was obtained. The expected reciprocal relationship between the activity of these glands was not obvious at the histological level . Quantitative and qualitative analysis at the light microscope level revealed, however, that the hormone prolactin-secreting eta cells of the rostral pars distalis and the hypocalcin-secreting cells of the Corpuscles of Stannius may be arranged in a lamellar pattern comprized of synchronous bands of cells in like-phase of a secretory cycle consisting of four stages - synthesis, storage, release and reorganization. Such synchronized cell cycles in these glands have not heretofore been described in literature. It is suggested that the maintenance of at least 255? of the cells in any one phase of the cycle ensures a supply of the required hormone at all times.

Implementation of hospital-wide computer information system :a case study of this change process

This case study examines the impact of a computer information system as it was being implemented in one Ontario hospital. The attitudes of a cross section of the hospital staff acted as a barometer to measure their perceptions of the implementation process. With The Mississauga Hospital in the early stages of an extensive computer implementation project, the opportunity existed to identify staff attitudes about the computer system, overall knowledge and compare the findings with the literature. The goal of the study was to develop a greater base about the affective domain in the relationship between people and the computer system. Eight exploratory questions shaped the focus of the investigation. Data were collected from three sources: a survey questionnaire, focused interviews, and internal hospital documents. Both quantitative and qualitative data were analyzed. Instrumentation in the study consisted of a survey distributed at two points in time to randomly selected hospital employees who represented all staff levels.Other sources of data included hospital documents, and twenty-five focused interviews with staff who replied to both surveys. Leavitt's socio-technical system, with its four subsystems: task, structure, technology, and people was used to classify staff responses to the research questions. The study findings revealed that the majority of respondents felt positive about using the computer as part of their jobs. No apparent correlations were found between sex, age, or staff group and feelings about using the computer. Differences in attitudes, and attitude changes were found in potential relationship to the element of time. Another difference was found in staff group and perception of being involved in the decision making process. These findings and other evidence about the role of change agents in this change process help to emphasize that planning change is one thing, managing the transition is another.

The effect of age on the structure and compostition of the cell walls of Choanephora cucurbitarum

The effect of age on the structure and composition of isolated and purified cell walls from cultures of Choanephora cucurbitarum was investigated by microchemical analyses, visible and infrared spectrophotometry, x-ray diffractometry and electron microscopy. Qualitative evaluation revealed the presence of lipids, proteins, neutral sugars, strong alkali soluble sugars, chitin, chitosan and uronic acids in the cell walls of both the 1 and 7 day old cultures. As the mycelium aged, there was a slight but statistically significant increase in the protein content, and a pronounced rise in the chitin and neutral sugar constituents of the cell walls. Conversely, the decrease in the chitosan content during this period had the net effect of altering the chitin: chitosan ratio from near unity in the younger cultures, to a 2:1 ratio in the 7 day old cell wall samples. Glutaraldehyde-osmium fixed thin sections of the 1 day old vegetative hyphae of £. curbitarum revealed the presence of a monolayered cell wall, which upon aging became bilayered. Replicas of acid hydrolysed cell walls demonstrated that both the 1 and 7 day old samples possessed an outer layer which was composed of finely granular amorphous material and randomly distributed microfibrils. The deposition of an inner secondary layer composed of parallel oriented microfibrils in the older hypha was correlated with an increase in the chitin content in the cell wall. The significance of these results with respect to the intimate relationship between composition and structure is discussed.

Exploring Chinese-Canadians' perspectives on health : a quantitative study

Chinese have unique perspectives on health and illness, which is mostly umecognized by western medicine. Immigration may contribute to problems with health consultations, inconvenience, and dissatisfaction. As the largest visible minority in Canada, Chinese- Canadians' perspectives on health should be studied in order to help Chinese immigrants adapt to a new health-care and health-promotion system, and keep them healthy. A quantitative questionnaire was designed based on the findings from a pilot study and previous literature. A hundred participants were recruited from Toronto, Vancouver, Halifax, and St. Catharines. Descriptive analysis and correlation analysis were used to investigate the structure of the variables. Findings indicated that most oftheir attitudes and corresponding practices to the different health aspects were positive. The relation between dietary practices and attitude was only found in small cities. Their attitudes were impacted by their length of stay in Canada. Their attitudes to regularly timed meals and psychological consultation were related to their acculturation level, as was the regularity of their practice of dental flossing. Their self-evaluated general health levels were also found to be affected by their medical history, education level, feeling to talk about • sexual health, and smoking, particularly in the male subjects of the study. In conclusion, they realized that each health aspect w~s important to their health. However, their practices did not bear a strong relation to their beliefs. Traditional thoughts about health reseeded with time. Acculturation level did not affect most of their attitudes or practices. Under pressure, the priority of the daily health practices decreased. Older persons, those with low incomes, lower education levels or families under stress need to pay more attention to their health level. In-depth future research was recommended.

Examining the influence of the coach athlete relationship on motivation and performance in female rugby players

The purpose of the study was two-fold; first, the association between interpersonal coaching styles and self-determined motivation was examined, followed by the investigation of the motivation-performance relationship. Participants included 221 female Canadian Interuniversity Sport (CIS) rugby players, aged sixteen to thirty-three (M= 20.1: SD = 2.26), who reported the number of years they played CIS rugby (M= 2.3: SD = 1.37) and organized rugby (M= 5.9: SD = 2.31). Multiple and bivariate regressions were employed with autonomy-support, structure, and involvement accounting for 17%, 41 % and 22% of the variance of competence, autonomy and relatedness. The three basic needs accounted for 40% of the variance of motivation, and motivation accounted for 2% of the variance of athletes' perceptions of performance. Findings indicated that autonomy-support emerged as a predictor of all three basic needs, involvement predicted relatedness and competence, autonomy predicted motivation, and motivation predicted athletes' perception of performance.

The relationship of individual, team and organizational learning in Ontario hospital clinical labratories

I t is generally accepted among scholars that individual learning and team learning contribute to the concept we refer to as organizational learning. However, a small number of quantitative and qualitative studies that have investigated their relationship reported contradicting results. This thesis investigated the relationship between individual learning, team learning, and organizational learning. A survey instrument was used to collect information on individual learning, team learning, and organizational learning. The study sample comprised of supervisors from the clinical laboratories in teaching hospitals and community hospitals in Ontario. The analyses utilized a linear regression to investigate the relationship between individual and team learning. The relationship between individual and organizational learning, and team and organizational learning were simultaneously investigated with canonical correlation and set correlation. T-test and multivariate analysis of variance were used to compare the differences in learning scores of respondents employed by laboratories in teaching and those employed by community hospitals. The study validated its tests results with 1,000 bootstrap replications. Results from this study suggest that there are moderate correlations between individual learning and team learning. The correlation individual learning and organizational learning and team learning and organizational learning appeared to be weak. The scores of the three learning levels show statistically significant differences between respondents from laboratories in teaching hospitals and respondents from community hospitals.

Automatic Structure Generation using Genetic Programming and Fractal Geometry

Three dimensional model design is a well-known and studied field, with numerous real-world applications. However, the manual construction of these models can often be time-consuming to the average user, despite the advantages o ffered through computational advances. This thesis presents an approach to the design of 3D structures using evolutionary computation and L-systems, which involves the automated production of such designs using a strict set of fitness functions. These functions focus on the geometric properties of the models produced, as well as their quantifiable aesthetic value - a topic which has not been widely investigated with respect to 3D models. New extensions to existing aesthetic measures are discussed and implemented in the presented system in order to produce designs which are visually pleasing. The system itself facilitates the construction of models requiring minimal user initialization and no user-based feedback throughout the evolutionary cycle. The genetic programming evolved models are shown to satisfy multiple criteria, conveying a relationship between their assigned aesthetic value and their perceived aesthetic value. Exploration into the applicability and e ffectiveness of a multi-objective approach to the problem is also presented, with a focus on both performance and visual results. Although subjective, these results o er insight into future applications and study in the fi eld of computational aesthetics and automated structure design.

A Quantitative Study of Social Capital Components, Self-Reported Health Status and Social Determinants of Health

This quantitative descriptive co-relational study used telephone survey interviews and stratified random sampling to collect data related to Social Capital (SC) and its components (trust and safety, reciprocity, civic engagement and collective action) and selected determinants of health variables in Niagara Region, Canada. Among the four components of social capital, trust and safety levels were highest among all participants (m=5.42, SD=1.0), with community engagement yielding the lowest mean score for the sample (m=1.93, SD=.8). Reciprocity had the strongest association with all other components of SC (r=0.51). Those most likely to report low levels of SC and health were unattached and low-income females. Males were more likely to report higher trust and safety levels and higher levels of self-rated health. In this study, a linear relationship between self-reported health status and SC was not found. Marital and employment status were associated with differences in mean scores of SC and self-reported health.

New Building Blocks for Dual-Property Molecule-Based Magnets

Two classes of compounds have been prepared and characterized as building blocks for chiral magnets and ferromagnetic conductors. In the fIrst project, the organic framework of a pentadentate, (N302) macro cycle has been synthetically modifIed to introduce phenyl substituents into its organic framework and the synthesis of four new [Fe(In(N302)(CN)2] complexes (I) - (IV) is presented. [Molecular diagram availble in pdf] This work represents the fIrst structural and magnetic studies of a family of spin crossover macrocycles that comprise of both structural and stereo-isomers. Magnetic susceptibility and Mossbauer data for the R,R-complex (I) is consistent with both a thermal and a light induced spin crossover transition. The X-ray data supports a change in geometry accompanying the thermal spin transition, from a high spin (HS) 7 -coordinate complex at room temperature to a low spin (LS) 5-coordinate complex at 100 K. The crystal structure ofthe racemic complex (III) reveals a HS, 7-coordinate complex at 200 K that undergoes no signifIcant structural changes on cooling. In contrast, the magnetic - susceptibility and Mossbauer data collected on a powder sample of the racemic complex are consistent with a LS complex. Finally, the meso complex (IV) was prepared and its structure and magnetic properties are consistent with a 5-coordinate LS complex that remains low spin, but undergoes conformational changes on cooling in solution. The chiral [Fe(H)(N302)(CN)2] macro cycle (I), together with its Mn(H) and Fe(H) derivatives have also been exploited as building blocks for the self-assembly of chiral magnets. In the second project, a synthetic route for the preparation of tetrathiafulvalene (TTF) donors covalently attached to a diisopropyl verdazyl radical via a cross conjugated pyridyl linker IS presented. Following this strategy, four new TTF-py- (diisopropyl)verdazyl radicals have been prepared and characterized (V) - (VIII) . [Molecular diagram available in pdf] The first (2:1) charge transfer complex ofa TTF-py-(diisopropyl)verdazyl radical donor and a TCNQ acceptor has been prepared and structurally characterized. The crystal packing shows that the donor and acceptor molecules are organized in a mixed stacking arrangement consistent with its insulating behaviour. EPR and magnetic susceptibility data support intramolecular ferromagnetic interactions between the TTF and the verdazyl radicals and antiferromagnetic interactions between TTF donors within a stack. In an attempt to increase the intramolecular exchange interaction between the two radicals, a TTF-x-(diisopropyl)verdazyl radical (IX) was prepared, where the two radicals are connected ia a conjugated divinylene linker. The neutral radical donors stack in a more favourable head-to-head arrangement but the bulky isopropyl groups prevent the donor radicals from stacking close enough together to facilitate good orbital overlap. [Molecular diagram available in pdf].

The relationship between socioeconomic status, schools and bone health among adolescent females in Southern Ontario

We studied the association between socioeconomic status (SES), school attended and bone health measured by bone speed of sound (SOS) among adolescent females in Canada. 412 participants from six randomly selected schools in Southern Ontario were examined. Bone SOS was measured by quantitative ultrasound. Participant’s school and aggregate area-based census-derived (AABCD) SES were evaluated as predictors. Mean participant age was 15.7 (SD 1.0) years. Average median family income was $68,162 (SD $19,366). Median family income was non-linearly associated with bone SOS and restricted cubic splines described the relationship. Univariate regression, accounting for clustering of participants in schools, revealed a significant non-linear association between AABCD-median family income and non-dominant tibial SOS (LRT p = 0.031). Multivariable regression revealed school to have a significant impact (LRT p = 0.0001). High schools had a strong influence on the bone health of female students and this effect overrode the effect of SES.