A 3D wavelet based encoding spectroscopic method (WE-SI) is investigated and implemented on a 3 Tesla Siemens Scanner. Compared to CSI, the proposed method is able to reduce acquisition time, and preserves the spatial metabolite distribution. As expected, a decrease in Signal to Noise Ratio (SNR) is noticed in WE-SI data compared to CSI. The dissertation explores important physical principles in MRI and spectroscopic imaging as a background, following by introduction of the wavelet encoding theory and comparison to Fourier encoding.

This study uses content analysis of newspaper articles and athlete biographical/autobiographical sources to examine the constructions of masculinity of male and female athletes at the 2008 Paralympic Summer Games in Beijing, China. Based on the socially constructed tension between disability and masculinity and the connections between sport and masculinity, this study sought examples that support or challenge the portrayal of Paralympic athletes in hegemonic masculine terms. This study finds that in the majority of cases, both sets of data sources reflects and/or reinforces the association between sport and hegemonic masculinity. This public display of masculinity indicates the athletes’ attempt to attain mainstream acceptance and legitimacy as “real” athletes as much as it does a rejection of a collective disability identity. The few instances of rejection and reformulation of masculinity come from examples in which the realities of living with impairments are insurmountable barriers to attaining hegemonic masculinity.

Specific bacterial commensals demonstrating multidrug resistance (MDR) are opportunistic pathogens for immunocompromised patients, including Corynebacterium species (spp.). Severe infections due to MDR corynebacteria are being increasingly reported where several MDR phenotypes have been described. One such phenotype, the macrolide-lincosamide-streptogramin B phenotype (MLSB), is characterized by high-level resistance to macrolides, lincosamides, and streptogramin B. Resistance is thought to be attributable to acquisition of the ermX gene, a methyltransferase that alters the ribosomal macrolide binding site. Until recently, ermX had been reported in only six Corynebacterium spp. We have observed other corynebacteria can also display high-level resistance to MLSB antimicrobials and are ermX positive. Hypotheses being tested include: 1) high-level macrolide and lincosamide resistance in Corynebacterium spp. is caused by acquiring ermX; 2) distribution of ermX is more widespread than previously published; 3) ermX is associated with transposon Tn5432; 4) multidrug resistance has spread to Canadian C. afermentans and C. aurimucosum strains.

Mobility plays an important role in determining quality of life in older adults as it is closely tied to health, participation, and independence in later years. Although much of the literature to date has focused on walking and stair climbing, mobility also encompasses driving and the use of public transportation to access the community. Comprehensive definitions of mobility and techniques for objectively measuring community mobility are generally lacking. This thesis describes a new theoretical framework for mobility that illustrates how impairments can lead to limitations in accessing different life-spaces, and stresses the associations among determinants that influence mobility. The feasibility of using global positioning system (GPS) watches and accelerometers to monitor community mobility in older adults was also examined. Data acquired from the equipment were quite variable. While the technology offers promise for capturing detailed information (e.g., the timing, distances covered, and speeds reached on foot and in-vehicle), new GPS solutions are required to allow for data collection over an extended period of time. In addition, projects were conducted to examine ankle strength and power in older women because these muscle groups are important for physical function and mobility. Test-retest reliability on the dynamometer was found to be generally good for isotonic and isokinetic tests, but relatively poor for isometric rate of torque development. Measures of dorsiflexion (DF) and plantar flexion (PF) strength and power-related variables were significantly correlated with functional performance (gait speed, stair climb power, and foot movement time). An intervention study was conducted to determine the effects of ankle DF and PF resistance training performed concentrically “as fast as possible” on movement time in a brake response task. Power training with elastic bands resulted in the greatest reduction in movement time, which suggests that this low-cost, practical form of exercise may benefit older adults in circumstances when rapid generation of ankle torque is required. This thesis adds to the literature by examining mobility from a number of perspectives. Mobility determinants are comprehensively defined, community and laboratory-based measures are examined, and the effects of an intervention are evaluated to improve mobility assessment and treatment techniques in older adults.

Inflammatory bowel disease (IBD), comprises Crohn’s disease (CD) and ulcerative colitis (UC), and is a chronic relapsing inflammation of gastrointestinal tract without any known cause or cure. Currently, it is accepted that IBD is a result of a dysfunctional immune response to commensal bacteria in a genetically susceptible host, and that environmental factors can trigger the onset or reactivation of the disease. This thesis considers the possibility of a specific pathogenic agent as well as an imbalance in the composition of the normal microflora in the pathogenesis of IBD. Gut biopsy tissues were taken from a population-based case-control tissue bank held at the University of Manitoba. Automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphisms (T-RFLP) were employed to assess the diversity of gut microbiota. The phylogenetic, virulence and biochemical characteristics of Escherichia coli isolated from IBD biopsies were examined using multi-locus sequence typing (MLST), DNA microarray technology and API 20E system. Utilizing ARISA and T-RFLP, a remarkable increase in the order of unclassified Clostridia was detected in inflamed tissues, particularly in CD patients (P < 0.05). Moreover, species richness and diversity were the highest in non-inflamed IBD biopsies. Culture-based quantification detected a significantly higher number of E. coli in IBD tissues (P < 0.05). Phylogenetic analysis revealed the tendency of E. coli isolated from IBD patients to be grouped into separate clonal clusters based on their allelic profiles (P = 0.02). A link was detected between uropathogenic E. coli (UPEC) CFT073 and strains isolated from IBD, with regards to gene distribution and virulence, using microarray technology. Amino acid substitutions N91S and S99N in FimH, the adhesive subunit of E. coli type I fimbria, were significantly associated to IBD (P < 0.05). This study demonstrated an increase in the microbial diversity of non-inflamed IBD tissues and suggested a recruitment phase of bacterial adherence and colonization, before the inflammation sets in. Furthermore, E. coli isolated from IBD tissues were distinct from commensal strains in both clonal and virulence characteristics and shared remarkable traits with extraintestinal pathogenic E. coli. Features involved in bacterial adhesion to epithelial cells may hold the key to E. coli pathogenesis in IBD.

Administrative data was anonymously linked to a clinical registry, to evaluate the validity of diabetes algorithms in youth. In addition, incident youth with T2DM (n=342) in Manitoba (1-18 years) from Jan.1986-2009 identified from the clinical registry were anonymously linked to healthcare records in order to evaluate complications, compared to youth with type 1 diabetes (T1DM) (n=1011) and non-diabetes (non-DM) controls (n=1710). The algorithm including 1 or more hospitalizations or two or more outpatient claims over two years was the most valid. Youth with T2DM had a 47% increased risk of any complication and a 2.29 fold increased risk of renal complication. Age at diagnosis, HgA1c and ace inhibitor/angiotensin receptor blocker use (ACE/ARB) were significant risk factors for any complication. Risk factors for renal complications included ACE/ARB use, albuminuria and diagnosis prior to 2000. Survival at 10 years was 91.4% (T2DM) vs. 99.5% (T1DM) vs. 100% (non-DM); p<0.0001.

This thesis is about Cree people who many refer to themselves as Ininew and whose original language is Ininewin. The main focus of this thesis is to generate dialogue on the colonial legacies that affect the Ininewak at Pimicikamak today in the area of community governance and the community’s creative responses to colonialism. First this paper provides a synopsis of the colonial history of Pimicikamak, making reference to the First Written Law (Pimicikamak Okimawin Onasowewin) and how this is a step forward to decolonization. Pimicikamak Nation`s government is recently new. It empowers the four councils: the Elders Council, Women’s Council, Youth Council, and Executive Council to make and amend laws as direction from its citizens. Modern written Pimicikamak customary law is subject to acceptance by consensus of a general assembly of the Pimicikamak public. This thesis will also discuss methods of the current colonial-derived governance system to provide a critique of the mechanisms that continue to raise havoc on Indigenous peoples. As well, this thesis will discuss the concepts of self-governance and suggest that in order to decolonize and liberate Indigenous people from the colonial entrapment that binds them to a governance system foreign to their own, there must be a committed, intellectual awareness and comprehension of the roots that continue to undermine Indigenous peoples, including Pimicikamak. This awareness is needed to visualize and comprehend centuries of systematic displacement and to acknowledge that the current colonial system still represents its history.

PI3Ks (phosphoinositide 3-kinases), a family of enzymes expressed in immune cells, are activated in response to a wide variety of stimuli by generating second lipid messengers. A subset of singnaling molecules containing lipid-binding pleckstrin homology (PH) domains are downstream molecules of PI3K signaling pathway, essential to mediate the functional outcomes of PI3Ks. Bam32 / DAPP1 is a PH domain-containing adaptor protein, which was discovered from human tonsil germinal centers (GCs); however, its biological function related to GCs, where efficient T-cell-dependent (TD) antibody responses are generated, is unknown. This thesis is focused on the effect of genetic or pharmacological blockade of PI3K p110delta activity on T and B cells, and the role of Bam32 in GC responses. Type 2 cytokine responses are significantly decreased in p110delta-inactivated mice, whereas Type 1 cytokine responses are increased or comparable after primary and secondary immunization. Hallmarks of asthma, airway inflammation and respiratory hyper-responsiveness are dramatically reduced in those mice. Adoptive transfer of OVA-primed splenocytes from normal, but not p110delta-inactivated mice could induce airway eosinophilia in naïve, airway-challenged recipient mice. These data demonstrate a novel functional role for p110delta signaling in induction of Type 2 responses in vivo and may offer a new therapeutic target for Th2-mediated airway disease. Paradoxically, serum IgE levels are markedly increased in OVA-immunized p110delta-inactivated mice despite lower level of swich factor IL-4. In vitro studies showed that p110delta is required to restrain IgE class switch recombination in a B-cell intrinsic manner. Blockade of PI3K activity using broad-spectrum PI3K inhibitors PIK-90 and PI-103 generates similar results. In vivo administration of p110delta-selective inhibitor IC87114 into OVA-immunized mice results in selective elevation of antigen-specific IgE production. Disruption of p110delta signaling leads to increased germline transcription at the epsilon locus (epsilon GLT) and increased induction of activation induced cytidine deaminase (AID) enzyme, suggesting deregulation at the level of the isotype switch process. Moreover, p110delta signaling selectively regulates the expression level of transcription factor Bcl6 and IRF4, which may be responsible for the regulation of AID and epsilon GLT. PI3K signaling regulates multiple steps of GC development, and Bam32 may be involved. GCs dissipate prematurely in Bam32-deficient mice after immunization with OVA/alum. In vitro, Bam32-deficient B cells are functional competent in proliferation, chemotaxis, isotype switching and plasma cell differentiation in response to signals present in GCs. In vivo, Bam32-deficient GC B cells proliferate normally; however, they are more apoptotic. Adoptive transfer studies indicated that intrinsic defect of Bam32-/- B cells leads to premature GC dissolution. Additionally, GCs formed by Bam32-/- B cells contain fewer T cells, implying that Bam32 is required for B cell-dependant T cell accumulation within established GCs. Treatment of Bam32-/- mice with agonistic anti-CD40 fully restored GC persistence and IgG1 isotype switching, demonstrating that Bam32-deficient GC B cells are functionally competent when access to cognate signals is not limiting. Collectively, those data demonstrate that Bam32 is not required for GC initiation, but rather functions in a late checkpoint of GC progression associated with T cell recruitment and GC B cell survival. In general, by focusing on PI3K p110delta and its downstream adaptor protein Bam32, my studies clearly indicate that p110delta is a potential therapeutic target for the treatment of Th2-induced airway inflammation. The unexpected immunomodulatory acitivity on IgE switching associated with multiple PI3K inhibitor compounds is first discovered in this thesis, suggesting that more need to be investigated in this aspect before those inhibitor compounds are widely used in the clinic. Furthermore, the specific regulatory role of Bam32 in GCs represents a unique model for us to study the late GC checkpoint in regarding to in vivo GC B cell and T cell interaction, which is an important issue need to be clarified in order to fully understand GC responses.

Dendritic cell is one of the professional antigen presenting cells, and it bridges innate immunity and adaptive immunity. To fully activate naïve T cells, it requires DC to provide at least two signals, the interaction between T cell receptor and the MHC class II molecule loaded with antigen processed by DC, and the co-stimulatory signals provided by the co-stimulatory molecules expressed on DC. The identification of more and more co-stimulatory molecules expressed on DC and the studies on their functions highlight the importance of co-stimulatory molecules on the regulation of DC functions. We here hypothesized that different expression levels of co-stimulatory molecules expressed on DC is pivotal of directing DC function towards immunity, tolerance and polarization of Th1/Th2 immune response. Using CD40 as the model molecule to study the effect of its expression levels on DC functions, we found that no/low expression level of CD40 on DC induced antigen-specific immunological tolerance was due to the induction of CD4+CD25+Foxp3+ regulatory T cells, while the polarization of Th2 immune response induced by DC with medium expression level of CD40 was partially due to the impaired IL-12 production by DC during CD40 crosslinking. Our findings that different levels of co-stimulatory molecules have different regulations on DC functions has the significance in DC based immunotherapy for GVHD as well as the Th1 diseases.

The Millennium uranium deposit is located 35 km north of the Key Lake mine, Saskatchewan. Uranium mineralization occurs in a variety of styles including (1) massive replacement, (2) fracture filling veins, (3) fine-grain aggregates associated with “mini” roll fronts, and (4) disseminated grains. The chemical Pb and isotopic 207Pb/206Pb ages of the massive (style 1), vein-type (style 2), and fine-aggregate (style 3) uraninite cluster at 1400-1200 and 1100-900 Ma. The ~1400 Ma ages coincide with the primary mineralization event for many of the uranium deposits (1550-1400 Ma) within the Athabasca Basin. Unlike other uranium deposits from the Athabasca basin, disseminated uraninite (style 4) have 207Pb/206Pb ages from 1770-1650 Ma. These ages are older than the depositional age for the Athabasca sediments (~1710 Ma) and are similar to the ages from the Beaverlodge vein-type uranium deposits.