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The fundamental objective of conservation genetics is the identification of the basic units of conservation. Central to this objective is the reconstruction of the adaptive and evolutionary history of populations to evaluate their conservation status. Evolutionary history involves both microevolutionary and macroevolutionary processes and adaptive history is the evolution of specific characters to selective ecological processes in differential heterogeneous environments. Neutral DNA markers such as mitochondrial DNA, minisatellites and microsatellites are most often used for reconstructing history and identifying conservation units. This thesis examined three biological systems: 1) an African cichlid, 2) Canadian moose populations and 3) eastern North American wolves and coyotes to test two hypotheses. Firstly, neutral DNA markers can be used to accurately reconstruct the evolutionary history of populations. Secondly, neutral DNA markers are concordant with adaptive distinctiveness in reconstructing the adaptive history of populations. Few studies have examined these relationships. Lake Magadi tilapia showed discordant patterns between adaptive morphological, physiological and behavioural characters and genetic structure assessed with mitochondrial DNA. I propose this discordance has resulted from selection acting on mitochondrial DNA that has often been assumed to be "neutral". Neutral DNA markers accurately reflected the known history of the moose populations but discordant patterns were observed between neutral and functional loci indicating the former may not accurately reflect adaptive variation. DNA profiles of eastern wolves and coyotes showed a significant conflict in the interpretation of mtDNA and microsatellite data compared to previous genetic studies that examined wolf taxonomy. The data were consistent with the hypothesis of a North American-evolved wolf. Coyote-like mtDNA was not of coyote origin but represented divergent but related sequences of a North American wolf lineage independent of the gray wolf (C. lupus). Under this new model of eastern wolf evolution, we also identified the hybrid origin of eastern coyotes, contrary to previous interpretations, and genetically characterised different wolf "types" within Ontario. These findings could not reject the first hypothesis as neutral markers were used to reconstruct the histories of the three biological systems. However, the findings identified that it is important to ensure the neutrality of DNA markers and that samples are representative of the taxa under investigation. The findings in this thesis did not support the second hypothesis, as neutral DNA markers were not concordant with adaptive characters, i.e. morphology, physiology and functional genetic markers. / Thesis / Candidate in Philosophy

Obstructive sleep apnea syndrome (OSAS) is a complex disorder characterized by repetitive bouts of upper airway collapse during sleep, causing subsequent intermittent hypoxia, hypercapnia, and fragmented sleep and is also associated with significant morbidity including daytime sleepiness, hypertension, and elevated cardiovascular risk. OSAS affects at least 4% of men and 2% of women; unfortunately, it is estimated that 80% to 90% of adults with OSAS remain undiagnosed. Both clinical characteristics and complex genetic and environmental interactions have made it difficult to understand OSAS disease etiology and identifying patients at risk is still elusive. A pattern of gene expression in cells or tissues related to a disease state for OSAS would provide beneficial information to be most effective in screening or diagnosing this disease. Objectives: The objectives of this study were to: 1) map out the study design and bench assay strategies by which to investigate this issue; 2) find out if there are specific differences in the global gene expression profiles of adult females with OSAS compared to those without OSAS, under conditions in which subjects were clinically similar (BMI, diabetes, cardiovascular disease, etc.); and 3) assess the protein expression differences that could potentially be linked via well-established molecular pathways associated with any differences found in global gene expression profiles in the presence and absence of OSAS. Methods: Subjects were overweight premenopausal Caucasian women with untreated OSAS (n=6; age = 40.7 ± 3.4; BMI = 49.04 ± 6.97; apnea-hypopnea index = 27.3 ± 16.02), and control subjects (n=10) (age = 38.2 ± 7.6; BMI = 47.94 ± 6.15; apnea-hypopnea index < 5), and matched for other clinical characteristics (diabetes, cardiovascular disease status, medications, etc.) recruited from either Carilion Clinic Pulmonary/Sleep Medicine or Carilion Clinic Bariatric Surgery practices. Subjects provided a fasting blood sample in which the monocytes were isolated from whole blood. The RNA was extracted from the monocytes, assessed for purity and quantity, frozen and shipped to collaborators at Dana-Farber Cancer Institute and hybridized to Affymetrix whole human genome chips on a gene chip. The initial computational evaluation and interpretation generated the hypothesis. Two-step quantitative real time polymerase chain reaction (qPCR) was performed to verify the results from the microarray analysis. The laminin enzyme immunoassay (EIA), and cellular adhesion assays were performed to determine if genomic changes resulted in proteomic and phenotypic assessments. Results: OSAS subjects had nine aberrantly regulated genes, of which three genes (LAMC-1, CDC42, and TACSTD2) showed a pattern in segregation between OSAS and controls subjects based on expression patterns. In addition, qPCR indicated a 2.1 fold increase in LAMC-1 and a 1.1 fold increase CDC42 expression unique to the tissue samples of patients with OSAS. Though the serum laminin EIA did not differ between groups, a statistically significant increase in peripheral blood mononuclear cells (PBMC) cellular adhesion in OSAS patients versus control subjects was found. The OSAS subjects had a well cell count of 9.27 ± 1.54 cells vs. controls 5.75 ± 0.78 cells (p Ë‚ 0.05), which is relative to the 103 cells/field that were plated. Conclusions: Cells isolated from women with moderate-severe OSAS show an abnormality in cellular adhesion, a process driven in part by the gene LAMC-1, which was also aberrantly expressed in these subjects. This suggests that inflammation may be linked to the pathogenesis of OSAS. This pilot study has provided the framework and preliminary data needed to propose a larger study with extramural research funding. / Ph. D.

As the demand for ever increasingly powerful machines continues, new architectures are sought to be the next route of breaking past the brick wall that currently stagnates the performance growth of modern multi-core CPUs. Due to physical limitations, scaling single-core performance any further is no longer possible, giving rise to modern multi-cores. However, the brick wall is now limiting the scaling of general-purpose multi-cores. Heterogeneous-core CPUs have the potential to continue scaling by reducing power consumption through exploitation of specialized and simple cores within the same chip. Heterogeneous-core CPUs join fundamentally different processors each which their own peculiar features, i.e., fast execution time, improved power efficiency, etc; enabling the building of versatile computing systems. To make heterogeneous platforms permeate the computer market, the next hurdle to overcome is the ability to provide a familiar programming model and environment such that developers do not have to focus on platform details. Nevertheless, heterogeneous platforms integrate processors with diverse characteristics and potentially a different Instruction Set Architecture (ISA), which exacerbate the complexity of the software. A brave few have begun to tread down the heterogeneous-ISA path, hoping to prove that this avenue will yield the next generation of super computers. However, many unforeseen obstacles have yet to be discovered. With this new challenge comes the clear need for efficient, developer-friendly, adaptable system software to support the efforts of making heterogeneous-ISA the golden standard for future high-performance and general-purpose computing. To foster rapid development of this technology, it is imperative to put the proper tools into the hands of developers, such as application and architecture profiling engines, in order to realize the best heterogeneous-ISA platform possible with available technology. In addition, it would be in the best interest to create tools to be as "timeless" as possible to expose fundamental concepts industry could benefit from and adopt in future designs. We demonstrate the feasibility of a compiler framework and runtime for an existing heterogeneous-ISA operating system (Popcorn Linux) for automatically scheduling compute blocks within an application on a given heterogeneous-ISA high-performance platform (in our case a platform built with Intel Xeon - Xeon Phi). With the introduced Profiler, Partitioner, and Runtime support, we prove to be able to automatically exploit the heterogeneity in an overlapping-ISA platform, being faster than native execution and other parallelism programming models. Empirically evaluating our compiler framework, we show that application execution on Popcorn Linux can be up to 52% faster than the most performant native execution for Xeon or Xeon Phi. Using our compiler framework relieves the developer from manual scheduling and porting of applications, requiring only a single profiling run per application. / Master of Science

This thesis presents an inspection method based on RGB-D profiling for the rail industry. The proposed approach uses inexpensive RGB-D cameras to generate color and geometrical information of the observations, and stitches each consecutive scan from the sensor to form a map, provided that the two scans contain the information from the same observation. Using a technique known as pairwise registration, the errors between these consecutive scans are minimized using error minimization algorithms such as Iterative Closest Point and Normal Distributions Transform. Once the error between each consecutive scan is minimized, the scans are then converted into a global co-ordinate frame work to form a global map of all the added scans. The proposed approach could be used as a map-based identification technique by comparing the past global map to newly acquired scans while also reducing computation time effectively. The effectiveness of this approach is demonstrated by developing a system that uses multiple RGB-D cameras to detect railway defects such as spikes. The applicability of the proposed approach to other applications is then evaluated by profiling long lengths of road. / Master of Science