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<p>Censoring arises quite often in lifetime data. Its presence may be planned or unplanned. In this project, we demonstrate progressive Type-II right censoring when the underlying distribution is log-logistic. The objective is to discuss inferential methods for the unknown parameters of the distribution based on the maximum likelihood estimation method. The Newton-Raphson method is proposed as a numerical technique to solve the pertinent non-linear equations. In addition, confidence intervals for the unknown parameters are constructed based on (i) asymptotic normality of the maximum likelihood estimates, and (ii) percentile bootstrap resampling technique. A Monte Carlo simulation study is conducted to evaluate the performance of the methods of inference developed here. Some illustrative examples are also presented.</p> / Master of Science (MSc)

<p> The Liver X receptor (LXR) is a type II nuclear receptor that is known to be a master regulator of cholesterol levels in the body through its transcriptional control of target genes involved in the handling of cholesterol. The regulation of LXR occurs at multiple levels including ligand and protein availability, post-translational modifications, protein-protein interactions with various cofactors and/or chaperones and a new concept of regulation that involves compartmentalization. This involves the establishment of regions where proteins can be active or inactive. Type II nuclear receptors have recently been found to shuttle between the cytoplasm and the nucleus, thus a compartmentalization component is likely to be involved. It was recently implicated that the centrosome-associated protein 350 (CAP350) can sequester PPARa. into nuclear bodies, and to regions in the cytoplasm. The significance of this appears to be the control of PPAR action. CAP350 is a large protein that has the ability to interact with nuclear receptors via an LXXLL motif, and with the cytoskeleton via a CAP-Giy motif. CAP350 is suggested to play a role in the organization of nuclear receptors in the nucleus, and their retention in compartments. In this report, LXRa. was confirmed to interact with CAP350 in vitro, using a GST-binding assay. Utilizing fluorescent protein chimeras with both nuclear receptors and CAP350 allowed the monitoring of this interaction in vivo. CAP350 was observed to form nuclear bodies that were capable of recruiting LXRa.. This recruitment was dependant on the integrity of the LXXLL motif. The mutated LXXLL motif of CAP350 was not able to colocalize with LXRa.. The significance of this interaction remains unknown. It is likely to be similar to that observed with PPARa., since the nuclear bodies formed by CAP350 seem to correspond to transcriptionally silent regions in the nucleus. </p> / Thesis / Master of Science (MSc)

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This study develops a computer-based interactive content design framework to guide the design of metacognitive scaffolds in ill-structured problem-solving instruction. It adopts Type II design and development research approach to create a comprehensive and generalizable instructional design framework. The framework was composed by synthesizing research and practical literature, and then evaluated by experts in related fields. The completed framework includes metacognitive strategies, instructional design strategies, interactive media types, question prompts, and feedback. Instructional designers, instructors, and other key stakeholders could follow the guidelines proposed in this framework to create metacognitive-based ill-structured problem-solving instruction using e-Learning authoring tools. On one hand, this study bridges the gap between theory and practice; on the other hand, it adds to literature in media research with focusing on utilizing various media types to create effective learning materials. / Doctor of Philosophy / This study aims to develop an interactive content design framework to guide the design of metacognitive scaffolds in ill-structured problem-solving instruction. It applies the Type II design and development research method. The framework was proposed by synthesizing pertinent literature, and then evaluated by experts in related fields. The completed framework includes metacognitive strategies, instructional design strategies, interactive media types, question prompts, and feedback. Instructional designers, instructors, and other key stakeholders could follow the guidelines to create computer-mediated instruction using e-Learning authoring tools. On one hand, this study bridges the gap between theory and practice; on the other hand, it adds to literature in media research with implementing various media types to create effective learning materials.

Bacterial persistence is considered as one of the primary reason for antibiotic tolerance besides genetically acquired antibiotic resistance. Persisters are the subpopulation of a clonal bacterial population, which can survive environmental extremes and become invulnerable to stresses due to limited metabolic activities and physiological functions. Cognate toxin and antitoxin (TA) pairs, which are transcribed simultaneously from the same or different operons within the bacterial chromosomes or plasmids, play an important role for bacterial survival during stressful growth environments. Pseudomonas aeruginosa PAO1 is one of the most versatile microorganisms in the environment. Despite its ubiquitous presence, no studies have shown the differential expression pattern of its toxin-antitoxins, and persistence related genes. The purpose of the following study is to analyze differential expression of P. aeruginosa PAO1 type II toxin-antitoxins and persistence related genes under different growth conditions and to show how their stoichiometric ratio changes during different growth conditions. Differential expression analysis indicated that the toxins and antitoxin pairs behave differently under different growth conditions. In addition, the genes related to persistence presented relatively consistent differential expression pattern under different growth environment. / Master of Science / Bacterial persistence is one of the main reason for antibiotic tolerance and recurrent infections. Toxin-antitoxin molecules play an important role during bacterial persistence. Change in the expression of toxin, antitoxins, and persistence related genes and the ratio of the toxin to antitoxin mRNA molecules are important for bacterial survival in stressful environments. Pseudomonas aeruginosa PAO1 is one of most ubiquitous bacteria and responsible for recurrent infection in patients with weaker and compromised immunity. This mRNA sequence (RNA-Seq) analysis study of P. aeruginosa PAO1 showed different expression levels of toxin, antitoxin, and persistence related genes in various stressful growth conditions. This expression also showed the different ratios of the toxin to antitoxin mRNA molecules under different stress conditions. These implicate the different hypothetical roles of these toxin and antitoxin molecules in different growth conditions.

Au Canada, nous remarquons une prédominance du diabète de type 2 au sein des communautés autochtones. Une approche ethnobotanique est utilisée en collaboration avec la Nation Crie de Eeyou Istchee afin de déterminer quels traitements à base de plantes peuvent être utilisés pour contrer les différentes conditions qui, collectivement, forment le diabète. Les pharmacopées de deux communautés cries, soit celles de Waskaganish et de Nemaska, ont été établies puis comparées à celles de étudiées antérieurement : communautés Whapmagoostui et Mistissini. Malgré les différences géographiques de ces groupes, leurs utilisations sont majoritairement semblables, avec pour seule exception le contraste entre les communautés de Nemaska et de Whapmagoostui. De plus, nous avons complété l’évaluation du taux cytoprotecteur des aiguilles, de l’écorce et des cônes de l’épinette noire (Picea mariana). Les extraits provenant de tous les organes des plantes démontrent une protection qui dépend de la concentration. La réponse spécifique d’organes peut varier selon l’habitat; ainsi, les plantes poussant dans les tourbières ou dans les forêts, sur le littoral ou à des terres l’intérieur démontrent des différences quant à leur efficacité. Bref, l’écorce démontre une relation dose-effet plus forte dans la forêt littorale, tandis que les aiguilles n’indiquent pas de changements significatifs selon leur environnement de croissance. La bioactivité observée démontre une corrélation avec le contenu phénolique et non avec l’activité de l’agent antioxydant. Ces résultats contribuent à péciser les activités antidiabétiques des plantes de la forêt boréale canadienne, telles qu’identifiées au niveau cellulaire par les guérisseurs Cries. / In Canada there is an overwhelming prevalence of type II diabetes in First Nations communities. Here an ethnobotanical approach has been used in cooperation with the Cree Nation of Eeyou Istchee to focus on finding plant based treatments for the conditions which collectively make up the symptoms of diabetes. The pharmacopoeias of two Cree communities (Waskaganish and Nemaska) are elucidated then compared with previously studied populations (Whapmagoostui and Mistissini). Despite differences in north-south east-west geography, plant ranking and use matrices were similar with the exception of Nemaska/Whapmagoostui. We have also completed the evaluation of Black spruce (Picea mariana) needle, bark and cone cytoprotectivity. Extracts from all organs exhibited concentration-dependent protection. Organ-specific response was habitat and growth environment dependent with plants grown either in bog or forest habitats in coastal or inland environments exhibiting differences in efficacy. Observed bioactivity correlated with total phenolic content but not with antioxidant activity. Together, these results contributed to the understanding of antidiabetic activity of Canadian boreal forest plants identified by the Cree of Eeyou Istchee healers at the cellular level.