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.

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.

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.

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.

The effect of 17-B estradiol therapy on bone mineral density and structure of alveolar bone in the ovariectomized rat model of postmenopausal osteoporosis

The ovariectomized (OVX) rat, a preclinical model for studying postmenopausal bone loss, may also be used to study differences in alveolar bone (AB). The objectives of this study were to quantify the differences in AB following estrogen replacement therapy (ERT), and to investigate the relationship between AB structure and density, and trabecular bone at the femoral neck (FN) and third lumbar vertebral body (LB3). Estrogen treated rats had a higher bone volume fraction (BV/TV) at the AB region (9.8% P < 0.0001), FN (12% P < 0.0001), and LB3 (11.5% P < 0.0001) compared to the OVX group. BV/TV of the AB was positively correlated with the BV/TV at the FN (r = 0.69 P < 0.0001) and the LB3 (r = 0.75 P < 0.0001). The trabecular number (Tb.N), trabecular separation (Tb.Sp), and structure model index (SMI) were also positively correlated (P < 0.05) between the AB and FN (r = 0.42, 0.49, and 0.73, respectfully) and between the AB and LB3 (r = 0.44, 0.63, and 0.69, respectfully). Given the capacity of AB to respond to ERT, future preclinical drug/nutritional intervention studies aimed at improving skeletal health should include the AB as a region of interest (ROI).

The Influence of Attentional Focus on the Self-Efficacy-Performance Relationship in a Continuous Running Task

The self-efficacy-performance relationship in continuous sport tasks has been shown to be significantly reciprocal yet unequal with stronger influences in the performance-to-self-efficacy pathway rather than self-efficacy-to-performance pathway (e.g., LaForge-MacKenzie & Sullivan, 2014b). Bandura (2012) suggested that sociocognitive variables may influence this relationship. Attention as a sociocognitve factor may bias the processing of performance and self-efficacy information (Bandura, 1982, 1997; Bandura & Jourden, 1991). As confidence and attention are important aspects of peak running performance (Brewer, Van Raalte, Linder, & VanRaalte, 1991), the primary purpose of the present study was to examine the self-efficacy-performance relationship under three conditions of attentional focus. The secondary purpose was to examine self-efficacy and performance as separate constructs under the same conditions of attention. Participants ran continuously for one kilometer in one of three randomly assigned attentional focus conditions: internal-focus (n = 51), external-focus (n = 50), and control (n = 49). Self-efficacy was assessed using a one-item measure every 200 meters. Path analyses examining the primary objective revealed significant self-efficacy-to-performance pathways in all conditions: external-focus (p < .05, βs ranging from -.17 to -.32), internal-focus (p < .05, βs ranging from -.26 to -.36), and control (p < .05, βs ranging from -.29 to -.42). Significant reciprocal relationships were absent in all conditions. ANOVAs examining the secondary objectives found significantly faster performance in the control condition at the start (F (2, 147) = 3.86, p < .05) and end of the task (F (2, 147) = 3.56, p < .05). Self-efficacy was significantly higher in the internal-focus condition at the end of the task (Self-Efficacy 4 (F (2, 147) = 3.21, p < .05) and Self-Efficacy 5 (F (2, 147) = 4.74, p < .05). In contrast to previous within-trial research (e.g., LaForge-MacKenzie & Sullivan, 2014b) self-efficacy-to-performance effects were more significant and robust than performance-to-self-efficacy effects. These results provided support for Bandura’s (2012) suggestion that sociocognitive factors may have the ability to alter the causal structure of the self-efficacy-performance relationship, proposing complexities in the self-efficacy-performance relationship (Sitzmann &Yeo, 2013). Results were discussed from both theoretical and applied perspectives.