Purpose: The prevalence of diabetes (DM) is increasing globally with type 2 diabetes (T2DM) being primarily responsible for this alarming trend. Age and DM have been associated with an increased prevalence of AR cataract in earlier studies but T2DM has not been considered separately from type 1 diabetes. Furthermore, study results have been inconsistent in terms of whether nuclear sclerosis (NS), cortical cataract (CC) or posterior subcapsular (PSC) are specifically associated with DM. The purpose of this thesis was to provide Canadian data on these issues while considering the limitations found in earlier studies in terms of variable age group selection and cataract definition. Logistic regression analysis was extended beyond risk analysis to model the prevalence of AR cataract across the human age range. Finally, as statins are commonly prescribed for patients with T2DM, the impact of using this pharmaceutical on AR cataract prevalence was investigated. Methods: A file review of over 6397 clinic files was performed to create the Waterloo Eye Study (WatES) database. Abstracted data included patient age and sex, the presence of early to late AR cataract (NS, CC, PSC or related lens extraction-LE), systemic health diagnoses including a diagnosis of T2DM or type 1 diabetes, and any medication used. Data quality was looked at through repeatability with double-entry of files and calculation of missing data rates. Comparisons were done between the study population demographics (age and sex) and those available on the general population and representative Canadian optometric patients. Prevalence of AR cataract was determined for the entire study group and for yearly age-groups. The probability of AR cataract generated from logistic regression analysis was used to model the prevalence of AR cataract over the entire age range of patients. Similar functions were determined for T2DM and non-diabetic (ND) subgroups and then again after further subdividing them into patients who did and did not use statins. The age of 50% prevalence of AR cataract were determined for each of these functions. Distribution rates of mixed and uniform cataract were calculated and compared for the T2DM and ND subgroups. Age of first lens extraction and differences in LE rates were also determined for these groups. Multivariable logistic regression analysis was done to determine odds ratios (OR) for associations between variables (patient age, being female, having a diagnosis of T2DM, smoking, systemic hypertension, and statin use) and the outcome of AR cataracts or its subtypes. Results: Data abstraction repeatability was found to be high and missing data rates were found to be low. While significant differences existed between the demographics of the general population and this clinic population, the sex and age distributions were comparable to optometric practices in Canada. The overall prevalence of AR cataract, NS, CC,and PSC in this population was 35.3%, 28.8%, 9.9%, and 3.6% respectively. The yearly prevalence of AR cataract in this population was found to increase in a sigmoid trend over the course of the human age span that began to rise after 38 years of age and approached 100% by 75 years of age. When modelled into a probability of cataract function, 50% prevalence of AR cataract occurred at 56.6 years of age. T2DM was reported in 452 WatES patients; 97% of whom were over 38 years of age. The probability of 50% AR cataract, NS, and CC prevalence occurred almost four years earlier in the T2DM subgroup compared to those without diabetes. PSC was much less prevalent and did not reach 50% levels, but the age of 10% prevalence was eight year earlier in the T2DM group compared to the ND group. Patients with T2DM had more mixed cataract, a higher rate of LE and an earlier age of first LE than non-diabetics. Statin use was reported in 761 patients; 96% who were over 38 years of age. Statin use was 3.5 times more common in patients with T2DM compared to non-diabetics. When the diabetic subgroups were further subdivided by those who do and do not use statins, the age of 50% probability of AR cataracts was now almost eight years earlier in the T2DM patients using statins compared to the ND patients who did not. The probability functions were similar between T2DM patients not using statins and ND patients who did report statin use. Having a diagnosis of T2DM was significantly associated with early to late NS and CC when controlling for statin use, whereas statin use was significantly associated with NS and PSC when controlling for a diagnosis of T2DM. Conclusions: AR cataract, T2DM and statin use were prevalent conditions in this clinic population, especially over 38 years of age. Modelling the prevalence of AR cataract over a broad age range could assist predicting cataract in Canadian optometric patients. A diagnosis of T2DM resulted in an earlier development of all three cataract subtypes, resulting in increased rates of LE and mixed cataract. However, the association was only significant for NS and CC when controlling for statin use. Given the frequent use of statins in patients with T2DM, the significant association found between statin use and increased risk of AR cataract warrants further study.

The increase in waste heat after consuming energy or burning fossil fuels is an issue environmentally and economically. Thermoelectric (TE) materials are developed to use in various applications because of their ability in converting waste heat into electricity. However, the applications are limited due to a low efficiency of materials, and research on thermoelectric materials is an on-going project for future use. Type-I clathrates are one of the TE materials which are studied in depth since the proposal of Slack’s PGEC (Phonon-Glass-Electron-Crystal) concept in 1995 due to their excellent thermoelectric properties. In this study, development and optimization of quaternary type-I clathrates will be the focus because double substitution often leads to better figure-of-merit, ZT, but it hasn’t really been studied. Higher ZT value is necessary because the energy conversion efficiency of TE materials is depending on the ZT value along with a larger temperature difference. Addition of lanthanoid elements as 2nd guest atoms to the main type-I clathrate structure, realized in Ba8Ga16Ge30, will be attempted to form quaternary compounds. The formation of the quaternary clathrates will be analyzed through powder X-ray diffraction, single crystal analysis and energy dispersive X-ray analysis. Also, as the performance of TE materials is examined through the figure of merit, ZT = TS²σ/κ, various techniques will be used to determine the Seebeck coefficient, the electrical conductivity and the thermal conductivity. The quaternary clathrates, Ba8-xLnxGa16Ge30 and Ba8-xLnxGa16+xGe30-x, where Ln = La, Ce and Eu were synthesized from the pure elements in stoichiometric ratios at 1000°C with slow cooling to room temperature. The products were then annealed at 600°C to acquire homogeneous samples for analyses. The various compositions of lanthanoid were intercalated into the structure of clathrates, which resulted in the quaternary clathrates with homogeneity. The crystal structure of quaternary clathrates with the space group of Pm-3n exhibited the same structure type as the ternary clathrates. The successfully formed products were refined with Rietveld refinements to understand their structures. The Eu containing clathrates crystallized with a lattice parameter a = 10.78251(6) Å, V = 1253.60(2) ų, for x = 0.3. The Ce containing clathrates also adopted the same space group with a lattice parameter a = 10.77331(6) Å, V = 1250.40(2) ų, for x = 0.3. The La containing clathrates formed with a lattice parameter a = 10.78494(6) Å, V = 1254.45(2) ų, for x = 0.3. Between 0.2 and 1.0 lanthanoid elements per formula unit were substituted with decreasing amount of barium where the actual amount of Ln in clathrates was lower than nominal amount. All these quaternary clathrates were found to be n-type semiconductors as determined through the Seebeck coefficient and electrical conductivity measurements.

Compared to other Canadians, Aboriginal people suffer disproportionately from Type 2 diabetes and its complications. In an attempt to fill gaps in services for Aboriginal people to support better management of diabetes and to prevent further complications, the West Side Community Clinic launched a monthly outreach diabetes education program using an informal hands-on approach to learning about meal planning and other forms of diabetes management. The purpose of this qualitative study was to determine the impact that the program has had on the participants' health and well-being through the stories they shared in a group or individual interview. Out of the core group of 30 women, most of them Aboriginal, eleven participated in the group interview and five women participated in individual interviews.<p>Findings reveal that the program's impact on participants' health and well-being is embedded within the context of their lives. Diabetes is managed within multiple life realities in an individual, a familial and a community context. The women report learning management skills and sharing support among participants and staff of Diabetes Morning; and altered health status such as regulated blood glucose levels and weight loss. Opportunities for change include more programming like Diabetes Morning, more often, more information, access to low-cost diabetes-friendly foods, communication with health care practitioners, and integrating knowledge on a day-to-day basis. Domains for outcome indicators and contextual indicators are suggested for the program.

A novel and promising method of software development is the interactive style of development, where code is written and incrementally tested simultaneously. Interpreted dynamic languages such as Ruby, Python, and Lua support this interactive development style. However, because they lack semantic analysis as part of a compilation phase, they do not provide type-checking. The programmer is only informed of type errors when they are encountered in the execution of the programfar too late and often at a less-informative location in the code. We introduce a typing system for Ruby, where types will be determined before execution by inferring principal typings. This system overcomes the obstacles that interactive and dynamic program development imposes on type checking; yielding an effective type-checking facility for dynamic programming languages. Our development is embodied as an extension to irb, the Ruby interactive mode, allowing us to evaluate principal typings for interactive development.

<i>Salmonella enterica</i> serovar Enteritidis (<i>S.</i> Enteritidis) is a major cause of gastrointestinal disease in humans worldwide that is mainly associated with the consumption of contaminated poultry meat and eggs. During the course of infection, <i>S.</i> Enteritidis uses two Type 3 Secretion Systems (T3SS), one of which is encoded by <i>Salmonella</i> Pathogenicity Island-1 (SPI-1). SPI-1 plays a major role in the invasion process.<p> In order to study the role of SPI-1 in the colonization of chickens, we constructed deletion mutants affecting either the complete SPI-1 region (40 kb) or <i>invG</i>, a single gene located on this pathogenicity island. The mutants were impaired in the secretion of effector proteins and were less invasive compared to the wild type strain in polarized Caco-2 cells. Similarly, when chicken cecal and small intestinal explants were co-infected with the wild type and ÄSPI-1 mutant strains we found that the ÄSPI-1 mutant strain was less invasive relative to the wild type strain. Oral challenge of 1-week-old chickens with the wild type or ÄSPI-1 strains demonstrated that there was no difference in chicken cecal colonization. However, systemic infection, measured as levels of <i>Salmonella</i> in the liver and spleen, was delayed in birds that were challenged with the ÄSPI-1 strain. This demonstrates that SPI-1 facilitates systemic infection but is not essential for invasion and systemic spread of S. Enteritidis in chickens.<p> Based on the above results, we examined the effect of sera against SPI-1 T3SS components to <i>S.</i> Enteritidis invasion. Anti-SipD serum protected Caco-2 cells against entry of wild type <i>S.</i>Enteritidis, but not against invasion of a mutant strain lacking sipD. On the other hand, sera against InvG, PrgI, SipA, SipC, SopB, SopE and SopE2 did not affect S. Enteritidis entry. To illustrate the specificity of anti-SipD mediated inhibition, SipD specific antibodies were depleted from the serum. Depleted serum restored the invasion of S. Enteritidis, demonstrating that the SipD protein may be an important target in blocking SPI-1 mediated virulence.<p> To determine if SPI-1 T3SS proteins were protective against <i>S.</i> Enteritidis oral challenge, chickens were vaccinated subcutaneously twice at 14 and 28 days of age with PrgI and SipD. The results indicate that these proteins induce strong IgG antibody responses and confer significant protection against infection of the livers in vaccinated birds. In another study, we vaccinated hens with selected SPI-1 T3SS proteins to determine if their progeny could be protected from <i>S.</i> Enteritidis oral challenge. The proteins induced strong antibody responses but did not affect the levels of the challenge strain in the ceca or internal organs of the vaccinates. Taken together, our results establish that <i>S.</i> Enteritidis SPI-1 is an important virulence factor in chickens and that the proteins associated with this T3SS may form components of a subunit vaccine used for protection against colonization by <i>S.</i> Enteritidis in poultry.

In this study, a novel technique (TO-Butterfly package) for butterfly-type laser module packaging based on the coaxial type structure is proposed. By applying the low cost TO packaging technique, the cost and fabrication time can be reduced, and the yield rate can be increased. The achievement can be employed to package the novel butterfly-type laser module in the fiber optics communication. In traditional butterfly-type module package, the PWS was large while saddle clip and fiber ferrule being jointed by laser welding after the fiber ferrule and laser being aligned. Therefore, the coupling efficiency and the yield rate are low with long fabrication time. On the contrary, the TO-Butterfly package, similar to TO-Can laser module, includes upper part and lower part. The direction of the main PWS in TO-Butterfly laser module parallels to the optical axis, in which direction the components are constrained. Therefore, the PWS takes less influence on the coupling efficiency. Furthermore, the aligning process between the fiber and the laser and laser welding process is completed on Newport LW4000 workstation to build up a TO-Butterfly TOSA. After that, the TO-Butterfly TOSA is taken out of the workstation and combined with the case through solder. As a result, the fabrication time can be reduced to one-third. And the coupling efficiency and yield rate can also be improved. After several times of process modification, the coupling efficiency of the 19 TO-Butterfly TOSA modules by applying the novel packaging technology was all over 70%. The average and the highest coupling efficiency were 81.3% and 95.7%, respectively, and the standard deviation was 6.5%.

Protein-protein interactions regulate and drive biological processes and understanding the assembly of these interactions is important. The LysR-Type Transcriptional Regulators (LTTRs) are a large family of transcriptional regulators found in prokaryotes. I have used the LTTRs as a model for protein specificity. In order to understand a residue’s contribution to oligomerization, alanine-scanning mutagenesis was used to probe the contribution of residues identified from in silico analysis of two proteins: OxyR and CynR. The contribution of the residues to oligomerization was characterized using lcI repressor fusions. In OxyR, seven residues were identified as hot spots. Moreover, these hot spots are not especially conserved. The interaction surface of OxyR was mapped onto a multiple sequence alignment of the LTTR family. This mapping identified putative contacts in the CynR regulatory domain dimer interface. Combined with the in vivo testing, three residues were identified as hot spots. The residues identified in OxyR and CynR do not overlap. To investigate the assembly of the LTTRs I used a negative-dominance assay with lcI repressor fusions. Taken together, I show that the LTTRs in E. coli K-12 are mostly specific in their interactions.

Type IV secretion systems have been identified in several human pathogens including Bordetella pertussis, Helicobacter pylori, and Legionella pneumophila. These systems are responsible for the translocation of virulence proteins and/or DNA, thereby playing an important role in the pathogenesis of infection and plasticity of genomes. Burkholderia cenocepacia is an important opportunistic human pathogen, particularly in persons with cystic fibrosis (CF). Respiratory tract infection by B. cenocepacia in CF patients is often associated with a decline in respiratory function, and can result in acute systemic infection. Burkholderia cenocepacia strain K56-2 is part of the epidemic and clinically problematic ET12 lineage. Two type IV secretion systems have been identified in this strain; one system is plasmid encoded (designated the Ptw type IV secretion system) whereas the other is chromosomally encoded (designated the VirB/D type IV secretion system) and shows homology to the Agrobacterium tumefaciens VirB/D4 type IV secretion system. It was determined that the plasmid encoded Ptw system is a chimeric type IV secretion system composed of VirB/D4-like elements and F-specific subunits. More recently, it was found that this system translocates a protein effector (PtwE1) that is cytotoxic to plant cells. It was also determined that the positively charged C-terminal region of PtwE1 is important for translocation via the Ptw type IV secretion system. Strains of the epidemic B. cenocepacia PHDC lineage contain only a chromosomal VirB/D4-like type IV secretion system (designated BcVirB/D); and a putative effector protein associated with this system has been identified that has C-terminal transport signal and sequences different from the effectors of the Ptw type IV secretion system. It has also been shown that a competing plasmid substrate and a plasmid fertility inhibition factor act to render B. cenocepacia of the PHDC lineage incapable of expressing a plant phenotype. Thus, three type IV secretion systems have been identified in epidemic B. cenocepacia lineages. From two of these, an effector has been identified that has cytotoxic effects on eukaryotic cells, and at least one of these type IV secretion systems is able to translocate DNA substrates.

The purpose of this study was to examine the relationship between family functioning, health-related quality of life, and metabolic control in order to identify areas for intervention that can improve medical and psychosocial outcomes for children and adolescents with type 1 diabetes. Children (N = 45) ages 8-17, both male and female, with type 1 diabetes, along with one caregiver (parent or legal guardian) (N = 45) were asked to complete the Pediatric Quality of Life Inventory (PedsQL) generic and diabetes-specific form to assess health-related quality of life along with the Diabetes Family Behavior Checklist and the Family Relationship Index of the Family Environment Scale to assess family functioning. Recent Hemoglobin A1c (A1c) was obtained from the physician at their visit or by parent report to assess metabolic control. Results indicated a significant relationship with poorer metabolic control relating to poorer physical health-related quality of life, as reported by children. All reports indicated a significant correlation between metabolic control and both general and diabetes specific health-related quality of life. There was a significant relationship with mother’s educational level on the outcome variables; educational level was therefore used as a control variable in all regression analyses. Child-reported general family functioning accounted for a significant amount of variance in child reported general health-related quality of life. Parent score on the non-supportive scale for diabetes specific family functioning accounted for a significant amount of variance in parent reported general health-related quality of life and diabetes specific health-related quality of life for their child. Results demonstrated the importance of obtaining both child and parent perspectives on issues regarding general family functioning and health-related quality of life and diabetes specific family functioning and health-related quality of life. In addition, they illustrated the importance of assessing health-related quality of life for children with diabetes as opposed to merely looking at the physical effects.

Animal and clinical studies have shown an acceleration of bone healing by the application of pulsed low-intensity ultrasound (PLIUS). Several studies have reported that pulsed low-intensity ultrasound increase the synthesis of proteoglycan and type II collagen of cultured animal chondrocytes. The objectives of this study were to exam the bioeffect of pulsed low-intensity ultrasound on in vitro cultured human chondrocytes. Human chondrocytes were isolated from the amputated polydactyly digit of six different 1 to 10 years patients and cultured in agarose suspension for 3 days before treatment. PLIUS with intensities of 3.6, 18, 48, 72 and 98 mW/cm2was respectively applied to human chondrocytes for a single 10-min per day treatment. A control group was treated without PLIUS. The results demonstrated that PLIUS-treated human chondrocytes increased the proteoglycan synthesis compared with the control in a time-dependent manner. It is shown that the effect of 48 mW/cm2 is the most potent among a variety of PLIUS intensities tested determined by ELISA method. PLIUS at 48 mW/cm2 also increased type II collagen synthesis by up to 48.5+8.0% of the control determined by western blotting analysis. However, PLIUS has no significant influence on the cell proliferation of human chondrocytes compared with the control. It revealed that the PLIUS can enhance extracellular matrix synthesis. The response to PLIUS of chondrocytes harvested from 1 year old donor was significantly better than that of chondrocytes of 10 years old patient. These observations may lead to a better understanding of the bioeffect of PLIUS on in vitro cultured human chondrovytes.