title: Adhesion Proteins: Keeping Bacteria in Their Place

contributor:
Davies, Peter L.
Biomedical and Molecular Sciences

subject:
Structural Biology
RTX Adhesin
X-Ray Crystallography

abstract:
Many bacteria produce outer membrane-localized proteins that adhere them to varying biotic and abiotic substrates. Such interactions are crucial for the life-cycle of many microorganisms, promoting retention in high-nutrient locations and the formation of communities, called biofilms. From a human perspective, microbial adhesion and biofilm formation are often detrimental, causing chronic antibiotic-resistant infections, the corrosion and clogging of machinery, and the spoiling of resources. It is in the best interest of human health and industry to understand the molecular connections that allow these natural phenomena to take place, and how they can be augmented or sabotaged.
As such, the purpose of this thesis was to interrogate the structure/function of several adhesion proteins produced by Gram-negative bacteria. Two of the three adhesion protein examples chosen are part of the Repeats-In-Toxin family, which relies on the type I secretion system for proper localization and cell-membrane retention. The examples include: 1) The 1.5-MDa ice-binding protein from the Antarctic bacterium Marinomonas primoryensis. The protein’s remarkable size can be attributed to one region that holds ~120 tandem repeat domains. Structure determination of a four-repeat segment confirmed these domains to be immunoglobulin-like β-sandwiches that bind calcium ions for both proper folding and rigidity, facilitating the region’s proposed role of extension. 2) The adhesion protein from the oil-eating bacterium Marinobacter hydrocarbonoclasticus, which houses a proposed PA14 domain close to its C-terminal tip. This domain was shown to bind sugar through a combination of X-ray crystallography and a custom-made competition assay. Potential applications for this domain as a dextran-affinity tag were also explored. And 3) an example from a different protein family was characterized due to the incorporation of a DUF3494 – a well-known ice-binding domain – into its distal tip. The ice-binding activity of this DUF3494 was confirmed and characterized, adding to the ongoing intrigue of this widespread and functionally-variable domain.

abstract: PhD


title: Application of Pyrite Mineralogy and Chemistry to Determining Paleoredox, Hydrothermal History, and Target Vectoring in the MacMillan Pass Sedex District, Yukon, Canada

contributor: Geological Sciences and Geological Engineering

rights: Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada

rights: ProQuest PhD and Master's Theses International Dissemination Agreement

rights: Intellectual Property Guidelines at Queen's University

rights: This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.

rights: Attribution-NonCommercial-NoDerivs 3.0 United States

subject:
SEDEX
Yukon
Exploration
Pyrite
Trace elements
Geochemistry

abstract:
The MacMillan Pass district in Yukon, Canada, hosts the Tom and Jason sedimentary exhalative (SEDEX) Pb-Zn-Ag-(Ba) deposits. Pyrite-bearing drill core samples were collected from seven drill holes that intersected mineralization and time-stratigraphically equivalent rocks 2 – 3 km away. Detailed petrographic analyses reveal four pyrite textural varieties, each with distinct morphological characteristics: earliest diagenetic (Py1), early diagenetic (Py2a), late diagenetic (Py2b), and metamorphic (Py3). The timing for SEDEX Pb-Zn mineralization was syn- and/or post-late diagenesis (Py2b). A representative subset of pyrite grains was analysed for trace element contents and distributions by laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) using raster grids to create quantitative trace element composition maps. These were used to characterise the trace element composition of each pyrite generation and investigate how trace elements spatially vary. LA-ICP-MS analyses reveal each textural variety of pyrite has a distinct trace element composition that varies depending on the stratigraphic unit it is hosted in. A suite of SEDEX-mineralization-related elements (Zn, As, Pb, Tl, Bi) is incorporated into Py2 within mineralized units at greater abundances than in unmineralized units. Lead, Pb/Se and As/Mo contents in pyrite are the most robust potential vectors toward mineralization. Bulk geochemical paleo-redox proxies (Eu/Eu*, Ce/Ce*, Mo, Re/Mo, and Ni/Co) indicate that an anoxic – dysoxic water column and euxinic porewater conditions persisted during the deposition of the Lower Earn Group strata.
A Ba-horizon was identified in rocks that are distal and time-equivalent to Pb-Zn mineralization. The Ba-horizon contains Py2 with anomalous metal (Tl, Co, Mn, Cd, Zn, Sb) contents and abundant barite, and is interpreted to represent the distal expression of hydrothermal activity. Two models are proposed to explain the formation of the Ba-horizon. In the first model, venting hydrothermal fluid debouched into the water column, ponded at the seafloor and infiltrated downward into the sediment. In the other model, hydrothermal fluid did not vent into the water column, it travelled up the fluid conduit and then migrated laterally within the unconsolidated sediment column to the distal locations. Both models invoke hydrothermal fluid metal contributions to Py2 within the Ba-horizon, and barite formation is facilitated by biological activity that is stimulated by warm, hydrothermal fluid.

abstract: M.Sc.


title: Homogeneously-Catalyzed Coupling Reactions in Switchable Solvents

contributor:
Jessop, Prof. Dr. Philip
Chemistry

abstract:
Due to the increasing environmental impact of society, it is imperative that current industrial processes be modified and new industrial processes be implemented in order to reduce environmental harm. However, these new or modified processes must be more energy-efficient, materials-efficient, and cost-effective so that they are more economically beneficial than the other processes. The described research was inspired by these two ideas and is comprised of two projects, both focused on the creation of recyclable, CO2-switchable methods of separating organic products, inorganic byproduct and catalyst.
For the first part of the project, Suzuki-Miyaura cross-couplings were tested in switchable water, concentrating on the activation of aryl chlorides and product separation techniques. Switchable water, which is an aqueous solution of an amine, was used as solvent with the amine functioning as the base for the palladium-catalyzed Suzuki-Miyaura cross-coupling of activated aryl chlorides with phenyl boronic acid, using TPPTS (a water-soluble phosphine ligand). The use of Schlenk techniques resulted in conversion of 99% and isolated yields of 87% with the absence of homocoupling.
For the second part of the project, the development of an easily prepared CO2-switchable polymeric ligand is described. The polymeric ligand was used in the Suzuki-Miyaura cross-coupling reaction for the synthesis of a biaryl product using 4-iodobenzaldehyde and phenylboronic acid pinacol ester in water. With the help of this switchable polymeric ligand, organic product, inorganic byproduct, and catalyst were separated into three fractions.  A catalyst recycling system was developed for the Suzuki-Miyaura cross-coupling reaction. The catalyst was able to be recovered and reused, albeit with lower activity.

abstract: M.Sc.


title: The Impacts of Disruptive Technological Change in the Southern Ontario Automotive Parts Industry

contributor:
Holmes, John
Mabee, Warren
Geography and Planning

subject:
Global Production Networks
Economic Geography
Geography of R&D
Canadian Automotive Industry
Disruptive Technological Change

abstract:
In response to recent challenges facing the Southern Ontario automotive industry, including disruptive changes in vehicle product technologies, federal and provincial Canadian governments have sought to transition the sector’s strategic focus from manufacturing to innovation and new product development. In doing so, they have established numerous innovation programs and formulated a supercluster strategy designed to enhance levels of corporate automotive research and development (R&D). Consequently, several observers suggest that the Southern Ontario automotive industry has embarked on a new developmental path.
Employing the GPN 2.0 approach, this study evaluates these claims and the efficacy of current government policy by examining the regional-level impacts of recent technological advancements in the Southern Ontario automotive parts industry. A 2015 plant-level survey of parts producers competitive and innovation strategies and corporate interviews are used to investigate the extent to which the sector is adapting current products and processes, at what scale automotive innovation occurs and the location factors which attract new automotive technology investments. Three primary research findings follow from this analysis. First, regulatory, technological and safety concerns are inhibiting industry advancement and supplier investment in components for electrical propulsion and CAVs. Second, few auto parts producers engage in early-stage innovation or compete based on product differentiation. Third, global parts suppliers continue to locate their primary corporate R&D facilities outside of the province.
Subsequent chapters explore the implications of these findings for economic development in Southern Ontario. Corporate interviews reveal that automotive Original Equipment Manufacturers (OEMs) and global automotive suppliers shape which early-stage R&D investments are made, where associated automotive innovation activities occur, and how new
product design and engineering information is transferred within the sector. The overwhelming majority of new technology investments are observed to cluster in Michigan and serve to reinforce Southern Ontario's interconnection with the Great Lakes automotive region (GLR). Due to built-up manufacturing skill and expertise in the province, many parts suppliers continue to transfer product specification information both to their own plants in Ontario and those of their lower-tier suppliers. The concluding chapter identifies three pillars upon which the resiliency of Canadian automotive parts manufacturing can be secured.

abstract: PhD


title: Application of Molybdenum and Thallium Isotopes as Indicators of Paleoredox Conditions and Genesis of Hyper-Enriched Black Shale (HEBS) Deposits, Peel River, Yukon

subject:
Hyper-Enriched Black Shale
Molybdenum isotopes
Thallium isotopes
Paleoredox

abstract:
Hyper-enriched black shale (HEBS) deposits, such as those hosted in Devonian black shales of northern Yukon, are a globally significant source of a variety of economically important metals, particularly nickel, copper, zinc and platinum group elements (PGE). The Yukon HEBS occurs as a thin (<10 cm) but laterally extensive (1000s km) stratiform and stratabound mineralized horizon that is enriched in a number of metals, significantly, Ni-Mo-Zn-PGE. The genesis of such deposits and the ambient paleoenvironment in which they formed are the subject of vigorous debate. Two genetic models, seafloor hydrothermal alteration and seawater scavenging have the most traction. These models invoke euxinic conditions for the formation and preservation of semi-massive sulfides.
Non-traditional isotopes, particularly molybdenum and thallium, are robust paleoredox indicators, especially where bulk geochemical paleoredox indicators exhibit ambiguities. Systematic sampling and Mo and Tl isotopic analysis of a 200 m stratigraphic section through the Yukon HEBS mineralization and the footwall and hanging-wall strata at the Peel River north and south bank showings give δ98Mo -1.24 to -0.53‰ and ε205Tl -8.1 to -5.2 for the mineralization, and 0.05 to 0.60‰ and -4.8 to -4.4 for the unmineralized strata, respectively. These values preclude a hydrothermal origin, but, together with rare earth elements (REE) and several bulk geochemical redox indicators, indicate that the mineralization formed from seawater in a quiescent, euxinic basinal paleoenvironment.

abstract: M.Sc.


title: Improved recipes for leuco-crystal violet micelle gel dosimeters

contributor:
McAuley, Kim
Schreiner, L. John
Chemical Engineering

subject:
Micelle Gel Dosimeter
Radiation Therapy
Design of Experiments
Leuco Crystal Violet

abstract:
An optimized recipe for a radiochromic micelle (RM) leuco-crystal violet (LCV) gel dosimeter was proposed using full-factorial designed experiments and model-based optimization. Linear regression models were used to optimize gel recipes with regard to high dose sensitivity (DS) and minimal dose-rate dependence. The proposed gel recipe contains 35 mM cetyltrimethylammonium bromide (CTAB), 1.10 mM LCV, 173 mM 2,2,2-trichloroethanol (TCE), 25 mM trichloroacetic acid (TCAA), 96 wt% water and 4 wt% gelatin. Results from replicate cuvette experiments showed that the proposed gel recipe is dose-rate independent and has an average DS equal to 0.0141 Gy-1 cm-1. No statistically significant energy-dependence was observed in cuvette experiments involving 12 MeV electrons and 6 MV photons. Preliminary 3-D dosimetry experiments were conducted in 1 L jars to study dose responses of the proposed recipe in large phantoms. The DS was 0.0110 Gy-1 cm-1 for a 1 L phantom irradiated with 12 MeV electrons, and 0.0115 Gy-1 cm-1 for a 1 L phantom irradiated with 6 MV photons. Further work on 1 L phantoms is required to test gel reproducibility and the statistical significance of any dose-rate dependent or energy-dependent behavior.
A systematic study was performed testing the reusability and reproducibility of the optimized gel recipe. A large batch of gel material was made from replicates that were previously irradiated to doses up to 30 Gy. Three iterations of gel re-use were performed to study the effects of gel dosimeter recycling on initial background colour, DS and dose-rate-dependence. A statistically significant linear increase in background colour suggests that the proposed gel dosimeter might be suitable for storing and administering incremental radiation doses.  An apparent upward trend in DS with gel re-use was observed, which suggests that RM LCV gel dosimeters could benefit from a pre-irradiation step to help improve dosimeter sensitivity. Minor dose-rate dependent behavior was observed after multiple gel re-uses; however, no significant behavior was observed at the 95% confidence level. Additional testing on 1 L phantoms is required to determine the clinical relevance and reusability potential of the proposed gel dosimeter.

abstract: M.A.Sc.


title: Investigating the impact of endothelial BMPR2 loss on the proliferative response to bone morphogenetic protein 9 in pulmonary arterial hypertension

contributor:
Ormiston, Mark
Biomedical and Molecular Sciences

subject: Pulmonary Hypertension

subject: Endothelial

subject: Bone Morphogenetic Protein

subject: Proliferation

subject: Cell Signaling

subject: Bone Morphogenetic Protein Receptor Type II

abstract:
Objective: Pulmonary arterial hypertension (PAH) is a disease of proliferative vascular occlusion that is strongly linked to heterozygous mutations in BMPR2, the gene encoding the bone morphogenetic protein (BMP) type II receptor (BMPR-II). The endothelial-selective BMPR-II ligand, BMP9, has been shown to reverse disease in animal models of PAH and suppress the proliferation of healthy endothelial cells. However, the impact of BMPR2 loss on the antiproliferative actions of BMP9 has yet to be assessed in endothelial cells from PAH patients.

Approach: BMP9 responses were assessed in blood outgrowth endothelial cells (BOECs) from PAH patients and controls, as well as human pulmonary artery endothelial cells (HPAECs) with or without BMPR2 silencing. Mouse pulmonary endothelial cells (MPECs), bearing a wildtype genome or a heterozygous or homozygous deletion of Bmpr2, were isolated from endothelial-conditional knockout mice (Bmpr2EC+/+, Bmpr2EC+/- or Bmpr2EC-/-). These mice were also assessed in vivo for altered retinal and lung angiogenesis following post-natal BMP9 administration.

Results: BMP9 suppressed proliferation in control endothelial cells, but increased proliferation in PAH patient BOECs, BMPR2 silenced HPAECs and Bmpr2-/- MPECs. This proliferative shift was not linked to altered metabolic activity or interactions with canonical TGFβ signaling, but was associated with the prolonged induction of the canonical BMP targets, the inhibitor of DNA-binding/differentiation genes, ID1 and ID2. In vivo, BMP9 administration reduced neonatal retinal and pulmonary vascular density in controls, but enhanced both measures in Bmpr2EC-/- mice.

Conclusion: Loss of BMPR2 results in a shift of the endothelial BMP9 response towards enhanced proliferation. This finding has potential implications for the clinical translation of BMP9 for the treatment of PAH.

abstract: M.Sc.


title: Dynamic Representation of Anatomical Structures in Radiation Therapy Treatment Planning and Evaluation

contributor:
Fichtinger, Gabor
Computing

subject:
Segmentation
Software Library
Open-Source
3D Slicer
Voxelization
Clinical Translation
Radiation Therapy

abstract:
Segmentation is a ubiquitous operation in radiation therapy (RT) and in medical image computing (MIC) in general. Various data representations can describe segmentation results, such as binary volumes or surface models. Conversions between them are often required, which include complex data processing. There are challenges involved in managing multiple representations, which pose a hindrance to research application development and usability. The challenges are related to conversion method selection, data provenance, consistency, coherence of in-memory objects, and fidelity.
The fundamental contribution is a software methodology for dynamic management of multiple segmentation representations, which facilitates RT and MIC research software development and improves end-user experience. At the core, a complex data container preserves identity and provenance of the contained representations and ensures data coherence. Conversions from one representation to another are executed automatically. A graph containing the conversion algorithms determines each execution, ensuring consistency between representations. The accuracy of the core conversion algorithms was evaluated.
The software infrastructure is made available as an open-source library, based on which a manual and semi-automated segmentation application was created that has become one of the most versatile segmentation tools available, corroborated by the number of projects using it worldwide. Numerous clinical research applications have also been developed based on the proposed framework, facilitating different aspects of radiation therapy research: gel and film dosimetry analysis, MRI-ultrasound contour propagation, and external beam planning system.
An issue related to a typical conversion step is explored, focusing on the calculation of a universal RT plan evaluation metric. Accuracy depends on spatial resolution and thus the conversion parameters, which need to be different based on structure size and complexity. A fuzzy-based algorithm is presented to calculate the parameters for each structure.
In summary, a software methodology is proposed for dynamic management of representations in image segmentation, offering a solution to the challenges that arise when working with multiple representations. The implemented infrastructure facilitates rapid and robust application development, and allows creating more user-friendly software. The community impact of the applications developed using the framework and the ongoing research and education projects show its potential in the clinical and research community.

abstract: PhD


title: Studying the Integration Practices and the Evolution of Ad Libraries in the Google Play Store

contributor:
Hassan, Ahmed E.
Computing

subject:
Ad libraries
Android
Mobile app mining
Integration practices
Evolution analysis
Software engineering

abstract:
In-app advertisements have become a major revenue for app developers in the mobile app economy. Ad libraries play an integral part in this ecosystem as app developers integrate these libraries into their apps to display ads. However, little is known about how app developers integrate these libraries with their apps and how these libraries have evolved over time.

In this thesis, we study the ad library integration practices and the evolution of such libraries. To understand the integration practices of ad libraries, we manually study apps and derive a set of rules to automatically identify four strategies for integrating multiple ad libraries. We observe that integrating multiple ad libraries commonly occurs in apps with a large number of downloads and ones in categories with a high percentage of apps that display ads. We also observe that app developers prefer to manage their own integrations instead of using off the shelf features of ad libraries for integrating multiple ad libraries.

To study the evolution of ad libraries, we conduct a longitudinal study of the 8 most popular ad libraries. In particular, we look at their evolution in terms of size, the main drivers for releasing a new ad library version, and their architecture. We observe that ad libraries are continuously evolving with a median release interval of 34 days. Some ad libraries have grown exponentially in size (e.g., Facebook Audience Network ad library), while other libraries have worked to reduce their size. To study the main drivers for releasing an ad library version, we manually study the release notes of the eight studied ad libraries. We observe that ad library developers continuously update their ad libraries to support a wider range of Android versions (i.e., to ensure that more devices can use the libraries without errors). Finally, we derive a reference architecture for ad libraries and study how the studied ad libraries diverged from this architecture during our study period.

Our findings can assist ad library developers to understand the challenges for developing ad libraries and the desired features of these libraries.

abstract: M.Sc.


title: Ventricular Arrhythmia Risk Assessment with Novel Time-Frequency Analysis of Signal-Averaged Electrocardiograms

contributor:
Redfearn, Damian
Hashemi, Javad
Maurice, Donald
Biomedical and Molecular Sciences

subject:
Ventricular Arrhythmia
Implantable Cardioverter Defibrillator
Risk Stratification
Electrocardiogram

abstract:
Background: Ventricular arrhythmia is a prevalent and dangerous cause of sudden cardiac death. Implantable cardioverter defibrillators (ICD) are devices that can detect and terminate ventricular arrhythmia, but current risk stratification methods offer limited prediction of arrhythmic events when selecting patients for ICD implantation. Furthermore, better methods are needed to identify ICD patients at greater risk of ventricular arrhythmia than others. Layered Symbolic Decomposition frequency (LSDf) is a signal processing metric that quantifies abnormal frequency content in signal-averaged electrocardiogram recordings. The aims of this study were to 1) determine if LSDf is predictive of adverse outcomes in an ICD patient cohort 2) identify if LSDf is related to known electrical parameters.

Methods and Results: For Aim 1, fifty-two ICD patients were recruited from 2008-2009. These were followed for a mean 8.5±0.4 years for the primary outcome of first appropriately treated ventricular arrhythmia or death. Thirty-four subjects met the primary outcome. LSDf was significantly lower and 12-lead QRS duration was significantly greater in patients meeting the primary outcome (12.14±3.97%, n=34vs. 16.45±3.73% n=18; p=0.001) and (111.59±14.96 ms, n=34 vs. 97.69±13.51 ms, n=18; p=0.012) respectively. A 13.25% LSDf threshold (0.74 sensitivity and 0.85 specificity) was selected based on Receiver Operating Characteristic analysis. Kaplan-Meier analysis was conducted; patients above the 13.25% threshold demonstrated significantly better survival outcomes (p<0.001). Cox multivariate regression analysis compared the LSDf threshold (13.25%) to LVEF (28.5%), 12-lead QRSd (100 ms), age, % male sex, NYHA classification, and antiarrhythmic usage. LSDf was a predictor of the primary outcome (p=0.005) and just ventricular arrhythmia (p=0.002). Subsequent physiological experiments for Aim 2 were conducted to determine if LSDf was related to ventricular conduction velocity (n=7), ventricular effective refractory period (n=13), or the presence of abnormal substrate (n=10) These patients were recruited from June 2011, March 2018, and April 2018, respectively. LSDf did not significantly change in normal patients after administration of procainamide or ibutilide. Patients undergoing catheter ablation for ventricular arrhythmia had significant greater LSDf following ablation (7.78% vs 9.40%, n=10 p<0.001). Electroanatomic mapping of low-voltage areas indicated LSDf may have an association with low-voltage areas in the ventricles (Spearman r= -0.81).

abstract: M.Sc.


title: The Effect of Carbon Monoxide on Pregnancy Specific Adaptations in Mice

contributor:
Smith, Graeme
Biomedical and Molecular Sciences

subject:
Carbon monoxide
Preeclampsia
Murine pregnancy
Angiogenesis

abstract:
Preeclampsia (PE) is a multisystem disorder of pregnancy, characterized by new onset hypertension and the presence of specific organ dysfunction such as proteinuria. While the etiology remains elusive, it is believed to be a disease of placental origin. Carbon monoxide (CO) is actively being studied as a potential therapeutic for PE due to its vasodilatory, angiogenic, and anti-inflammatory properties, with the aim that CO can improve placental function and maternal vascular dysfunction during pregnancy. CO has been shown to increase uteroplacental vascular growth and prevent PE-like signs in mice. How CO acts to promote vascular changes during pregnancy is unclear. Thus, the objectives of this research were to determine the effect of low-dose CO on markers of angiogenesis and inflammation at both the maternal-fetal interface and systemically during mouse pregnancy, and to characterize the effect of CO on histomorphological changes at the implantation site.

The hypothesis that CO increases angiogenesis during pregnancy via modulation of major angiogenic/inflammatory pathways was tested using healthy, pregnant CD-1 mice. Following chronic administration of 250 ppm CO, genes encoding VEGF and angiopoietin receptors, eNOS, and cell adhesion molecules were upregulated at the implantation sites at gestation day (GD)10.5; no changes in gene expression were observed at GD16.5. Furthermore, CO treatment did not reveal any measurable changes in pro-inflammatory or angiogenic cytokines in the plasma or tissue lysates from implantation sites. Additionally, histological analysis at GD10.5 and GD16.5 implantation sites demonstrated no difference in cell markers characteristic of placental health and function, including trophoblast invasion (pan-cytokeratin), cellular proliferation (Ki67), and uterine natural killer cell abundance (Dolichos biflorus lectin).

Collectively, the data presented in this thesis suggest that CO acts to potentiate uteroplacental vascular growth via the angiogenic axis at midgestation, without impacting pregnancy specific adaptations including local/systemic immune function and histomorphological changes at the maternal-fetal interface. Understanding how low-dose CO modulates angiogenesis and inflammation during normal pregnancy is crucial prior to its use therapeutically. Future studies are required to validate the safety and efficacy of CO as a potential therapeutic for vascular insufficiency diseases such as PE.

abstract: M.Sc.


title: Two muscles are better than one: Co-contraction engages antagonistic muscles in response to perturbation

contributor:
Deluzio, Kevin J
Rainbow, Michael J
Mechanical and Materials Engineering

subject:
Biomechanics
Motor Control
Co-contraction

abstract: Co-contraction is a common strategy when performing difficult or unstable motor tasks. For example, we co-contract muscles of the arm when generating downward force to turn a screw and co-contract muscles of the leg when walking on a slippery surface. It is thought that the primary benefit of co-contraction is to directly increase the mechanical impedance (stiffness and damping) of muscle to generate greater instantaneous restoring forces when a limb or joint is perturbed. However, this explanation ignores the role of neural feedback in corrective responses. Characterizing the effects of co-contraction on motor function is important to understanding its use in common tasks and its role in pathologies such as knee osteoarthritis. A series of experiments were performed to investigate the effects of co-contraction on the motor response to physical perturbations. First, participants performed an upper limb postural control task in which a random torque pulse perturbed the elbow. Muscle activity was increased in the elbow flexors or extensors independently by resisting a background load or in both muscle groups simultaneously by co-contracting. Rapid corrective responses were generated without overshoot even at the lowest level of co-contraction, whereas activating a single muscle group more than double that amount resulted in poorer performance. Thus, it was not the total muscle activity, and thus the increase in limb impedance, that improved performance when co-contracting, but the fact that both muscle groups were simultaneously pre-activated before the disturbance. It was shown that the primary benefit of co-contraction was the ability to engage both the stretched and shortened muscles in the corrective response. This behavior was also observed in an upper limb tracking task, demonstrating that it was not a simple strategy invoked only for stationary postural control, but a strategy that also improved performance during movement. Further work expanded the generalizability of this behavior in the upper limb and extended it to the lower limb. Finally, the benefits of this strategy were examined using an optimal feedback control model. The results of this work indicate that co-contraction engages a unique motor strategy, providing new insight into its role in motor function.

abstract: PhD


title: Natural Product Inspired Synthesis of Heterocyclic Systems: Functionalized Dibenzoxepinones and Pyrrolic Compounds

contributor:
Snieckus, Victor A.
Ross, Avena C.
Chemistry

subject:
Natural Products
Cularine Alkaloids
Palladium-Catalyzed Alpha-Arylation
Dibenzoxepinones
Prodiginines and Tambjamines
Pyrroles
Biosynthetic Enzymes

abstract:
Plant and microbial alkaloids have a rich history stemming from their structural diversity and
medicinal applications. Accordingly, these natural products and their derivatives continue to pique interest
within the synthetic and biosynthetic communities. Heterocyclic motifs are common among the alkaloids;
the unique chemical transformations and biosynthetic origins of these systems thus present a versatile
platform for the generation of structurally diverse molecules.
Chapter one of this thesis describes the development of an efficient route to key cularine alkaloid
intermediate, Manske’s ketone. Optimization and scope studies were conducted leading to a robust and
general two-step synthesis of functionalized dibenzo[b,f]oxepin-10(11H)-ones via nucleophilic aromatic
substitution (SNAr) and palladium-catalyzed intramolecular α-arylation. We have demonstrated the utility
of these ubiquitous heterocyclic systems by further cross-coupling chemistry. The scope of the α-arylation
methodology was additionally expanded to provide 11-substituted dibenzoxepinones; application to benzofused nitrogen- and sulfur-containing 7-membered heterocycles is also described. Studies into the curious
formation of a trimethoxy-substituted xanthone, the major product under previously described
intramolecular α-arylation conditions, are currently ongoing.
Chapter two describes the evaluation and synthesis of two related classes of bioactive pyrrole-containing alkaloids, the prodiginines and tambjamines. The proton affinity of cyclic tambjamine MYP1
was compared to linear analogue BE-18591 through determination of the apparent pKa values. The
increased basicity of the macrocyclic derivative was rationalized by its structural rigidity. This chapter also
details adjacent investigations into the chemoenzymatic synthesis of prodiginines. The substrate tolerance
of the terminal condensation enzyme involved in prodigiosin biosynthesis, PigC, was demonstrated for a
brominated monopyrrolic substrate. In contrast, the production of this novel analogue was unsuccessful by
a purely synthetic approach. Preliminary studies into the functionalization of related pyrrolic compounds
are also described.

abstract: M.Sc.


title: The maternal effects of haemosporidian infection in red-winged blackbirds

contributor:
Bonier, Fran
Biology

subject:
Haemosporidia
Red-winged blackbird
maternal effects

abstract: Vector borne diseases present a substantial selective pressure to many animals, as they can impose direct fitness costs and intensify trade-offs between immune function and other life history traits, like reproduction. Haemosporidian parasites, a family of blood-borne parasites that include the causative agent of malaria (Plasmodium spp), are spread by insect vectors. In populations with endemic malaria, chronic infection can have a significant impact on individuals through changes to physiological condition, reproductive success, and survival. In addition to the individual effects on host physiology and success, there can also be associated impacts on the offspring of the host, where maternal infection can affect offspring in both negative and adaptive ways. The maternal effects of malaria on wild populations have not been studied extensively through experimental means, though they could play an important role in offspring success and phenotypic expression in future generations. We estimated the maternal effects of chronic haemosporidian infection in free-ranging red-winged blackbirds by medicating females with antimalarial medication or a control solution before reproduction. We measured egg mass, hatching success, and fledging success for each female, and a suite of measures to determine nestling condition. We found that females who received antimalarial medication laid heavier eggs, and fledged more young per nest, but we did not detect differences in hatching success between groups. We also found that nestlings from medicated mothers were heavier, and had higher haematocrit and lower plasma glucose when females were in good condition before treatment. This is one of the first studies to experimentally quantify the maternal effects of chronic malaria infection on offspring condition in birds, and one of few studies to describe fitness effects of chronic maternal infection in a population with endemic haemosporidian infection. This study demonstrates that the maternal effects of infection have the potential to shift individual and population phenotypes through changes to offspring size and physiological condition as a result of chronic maternal infection. Understanding the effects of maternal infection on offspring condition and fitness furthers our knowledge of the maternal effects of disease, which will continue to be important as pathogens colonize new areas and naïve hosts.

abstract: M.Sc.


title: Microwave Overlay Capacitor Fabrication on Printed Circuit Boards

contributor:
Freundorfer, Alois
Sayer, Michael
Antar, Yahia
Electrical and Computer Engineering

rights: Attribution-NonCommercial-ShareAlike 3.0 United States

subject:
Barium Strontium Titanate
PCB
Microwave Filter
Ferroelectric
Film Deposition

abstract:
A technique for making varactors in the form of parallel plate overlay capacitors, using barium strontium titanate (BST): a ferroelectric, polymer composite thick film, has been developed in this work. BST was selected due to the commercial availability of powder. This involves the use of standard air brush techniques to deposit ferroelectric thick films, and planarization of printed circuit boards (PCB) using soldermask to allow for film deposition which was not reported in the literature. A new method to have the PCB prepared appropriately at the manufacturing stage was employed. A bandpass filter on PCB was designed for high frequency measurements and BST composite material electrical characterization. This is due to relative permittivity changing with frequency. The BST composite film recipes were developed using commercial powder and two types of polymer. An existing recipe using cyclic olefin copolymer (COC) was adapted for spray coating, while a new recipe based on poly methyl methacrylate (PMMA) was designed for spray coating.
To complete the capacitors, a metal layer was deposited using a Voltera V-One printer with the Elegant Eel conductive ink of thickness 120 𝜇𝑚. Ferroelectric film thicknesses were measured using a Mitutoyo micrometer to be 15−120 𝜇𝑚. Surface profile sweeps were taken with a profilometer as high texture made the profilometer unsuitable for thickness measurements. The capacitor area was measured with a calibrated optical microscope. Low frequency measurements were conducted with a Solartron 1170 Frequency Response Analyzer and were consistent with capacitor theory. High frequency measurements used a TR5048 Vector Network Analyzer (VNA) from Copper Mountain to measure passband characteristics, during which a Sentry 500VA Hipot Tester was used to apply bias to the filters for tunability measurements. The structures were simulated using High Frequency Structure Simulator (HFSS), to provide a relationship between frequency shift and relative permittivity. The relative permittivity of the BST-COC films was 𝜀𝑟=11 at 1.98 𝐺𝐻𝑧, while the BST-PMMA film was 𝜀𝑟=20.5 at 2.09 𝐺𝐻𝑧. The tunability of the films was a 5% relative tuning at 17.5V/ 𝜇𝑚 for BST-PMMA films while the BST-COC films had a 3% tunability at the same field intensity.

abstract: M.A.Sc.


title: Who is Responsible?  Explaining How Contemporary Canadian Newspapers Frame Domestic Violence

contributor:
Little, Margaret
Goodyear-Grant, Elizabeth
Political Studies

subject:
Domestic Violence
News
Framing
News Production
Discourse Analysis
Canadian Feminism
Canadian Politics
Political Economy
Gender-Based Violence
Violence Against Women
Neoliberalism
Newspapers
Critical Race
Journalism
Anti-Violence Movement
Police Communication
Canadian Racism
Canadian Patriarchy
Family Violence
Sexual Violence
Intersectionality
Carceral State
Social Responsibility
Content Analysis
Carceral Feminism

abstract: Domestic violence is a pressing social issue in Canada. How the news media covers this violence has the potential to generate social responsibility or reinforce misconceptions about its causes, prevalence, and solutions. In this dissertation, I answer two questions. How are contemporary Canadian newspapers covering domestic violence? And, what explains the patterns of coverage? To answer the first question, I conducted an extensive content and discourse analyses of a sample of 823 domestic violence stories published between 2014 and 2016 in a range of English-language newspapers across Canada. To answer the second question, I interviewed over 120 news workers, police, and anti-violence advocates, shadowed five journalists, and observed three newsrooms in four select case study cities (Thunder Bay, Kingston, Toronto, and Ottawa) in Ontario, Canada. From these data, I argue that Canadian newspapers reinforce individualized notions of responsibility and racialized conceptions of belonging. The news communicates that Canada does not have a violence-against-women-cultural problem; there are just a few bad apples, women who make poor decisions, and violent Indigenous, immigrant, and non-Canadian ‘cultures’ that are responsible. The news subsequently focuses on depoliticized state and carceral state responses through ample attention to police, trials, prisons, and punishment. I further argue that that Canadian newspaper framing patterns of domestic violence are constrained, but not predetermined, by neoliberal logics. The reliance on market logics opens the door to strong source influence. Canadian police are able to take advantage of the weakening of newspapers with their increased communications sophistication, while anti-violence organizations receive insufficient funding to match police influence. Drawing together the political-economic realities of both the media and sources exposes the intimate link between neoliberalism and carceral expansion. Neoliberal economic and discursive restructuring, however, does not tell the whole story. Other factors also strongly influence domestic violence framing, including journalism’s ideology, newsroom culture, and women journalists as potential survivors of gendered violence. The implications are clear: Canadian newspapers are also not living up to their ideal role as the fourth estate and the framing patterns are not conducive for the social change needed to reduce and prevent domestic violence in Canada.

abstract: PhD


title: Polymeric Liquid Behavior in Oscillatory Shear Flow

contributor:
Giacomin, Alan Jeffrey
Chemical Engineering

subject:
polymer
rheology
small amplitude oscillatory shear flow
macromolecular architecture
complex viscosity
general. rigid bead-rod theory

abstract:
One of the great challenges in chemical engineering is to predict physical properties from molecular structure. Predicting transport properties presents special challenges, especially for macromolecular structures. This thesis focuses on the properties governing momentum transport in polymeric liquids, and specifically those properties conferring elasticity to such liquids.

In the first part of this thesis, we examine the second order orientation tensor for the simplest molecular model relevant to a polymeric liquid in large amplitude oscillatory shear flow (LAOS), the rigid dumbbell suspension. From the second invariant of the order parameter tensor, we calculate the scalar, the nematic order, and examine its evolution for a polymeric liquid in LAOS. We find this nematic order, our main result, to be even. We use Lissajous figures to illustrate the roles of the Weissenberg and Deborah numbers on the evolving order in LAOS. We use the low frequency limit of our main result to arrive at an expression for the nematic order in steady shear flow. This work gives a first glimpse into macromolecular order in LAOS.

In the second part of this thesis, we explore general rigid bead-rod theory, which explains polymer viscoelasticity from macromolecular orientation. By means of general rigid bead-rod theory, we relate the complex viscosity of polymeric liquids to the architecture of axisymmetric macromolecules. In this work, we explore the zero-shear and complex viscosities of 24 different axisymmetric polymer configurations. When non-dimensionalized with the zero-shear viscosity, the complex viscosity depends on the dimensionless frequency and the sole dimensionless architectural parameter, the macromolecular lopsidedness. In this work, in this way, we compare and contrast the elastic and viscous components of the complex viscosities of macromolecular chains that are straight, branched, ringed, or star-branched. We explore the effects of branch position along a straight chain, branched-chain backbone length, branched-chain branch-functionality, branch spacing along a straight chain (including pom-poms), the number of branches along a straight chain, ringed polymer perimeter, branch-functionality in planar stars, and branch dimensionality. In addition, we study diblock copolymers by exploring the effects of linear density, macromolecular length, and bead number ratio on relaxation time.

abstract: M.A.Sc.


title: Uncharted Paths: The Use of Traditional, Complementary and Alternative Medicine (TCAM) among Sub-Saharan Africans living in the Greater Toronto Area (GTA)

contributor:
Rosenberg, Mark Warren
Geography and Planning

subject: Sub-Saharan Africans

subject: Immigrants

subject: Greater Toronto Area

subject: Translocational positionality

subject: Mixed-methods

subject: Ethnicity

subject: Identity

abstract:
The appeal of traditional, complementary, and alternative medicine (TACM) is growing among persons living in developed countries. Personal beliefs and traditional values about health and healthcare are deemed significant motivations for the use of TCAM. While existing studies have focused on diverse population groups, including persons of European and Asian descent, TCAM use and behaviour among persons of sub-Saharan African (SSA) descent living in Canada and other developed countries remains unknown. Existing studies on TCAM and healthcare-seeking behaviour of racial or ethnic minorities suggests possible alienation due to sociocultural health beliefs and practices. These studies fail to investigate the role of context in the identity construction and sociocultural belonging and how this ultimately affects the choice of healing practices. Anthias' (2002, 2008, 2012a) asserts that immigrants and their descendants have complex relationships with different locales – country of residence (or naturalised countries) and country of origin. This complex relationship entails social, cultural, symbolic and material ties between homelands and destinations. This research seeks to examine TCAM use among persons of SSA origin living in the GTA and to understand how ethnocultural identity informs the use of TCAM remedies using Anthias’ translocational positionality as a theoretical framework.

The study uses a sequential mixed-method approach to garner data on sociodemographic characteristics, transnational relationships, health status and health care-seeking behaviours of persons of SSA origin living in the Greater Toronto Area. Lifetime prevalence of TCAM use among respondents of SSA descent is ~57.14% and 12-month prevalence of TCAM use is ~23.81%. About 48.72% of the respondents indicated the TCAM used are of their ethnocultural origin. A sizeable proportion of respondents had unmet TCAM need (~20.88%) and engaged in transnational healthcare-seeking behaviour or medical return (~39.56%).

The findings of the interview show the meaning associated with ethnocultural identity and the broader contextual factors that influence the utilisation of ethnocultural identity in health promotion or healthcare-seeking. The findings of the interviews challenge the alienation assumption and show the ability of participants to transcend and transition between ethnocultural identities in different contexts.

abstract: PhD


title: Dielectric Resonator Antenna on Printed Circuit Board

contributor:
Freundorfer, Alois
Electrical and Computer Engineering

subject:
Dielectric resonator antenna
Printed circuit board
RDRA
sol-gel

abstract:
With the increased demand for high efficiency wireless communication systems, there is a requirement to develop the antenna systems that are effective and dependable. Instead of a traditional metallic antenna, a dielectric resonator antenna (DRA) could be a better solution to meet these applications.
As a tiny and compact antenna is desired for current applications, more and more on-chip designs are being developed. A rectangular dielectric resonator antenna (RDRA) set on printed circuit board (PCB) with a finite ground plane is prototyped to demonstrate on-chip application. One benefit of the on-board RDRA is that it allows for circuits underneath, both for on-chip and multi-chip applications. This makes for an efficient design and a more compact system. For modeling purposes, the on-chip circuit was designed on printed circuit board.
The prototype DRA has a resonant frequency at 10GHz with a bandwidth about 200MHz. It is coupled by using coplanar feed under the DRA. The DRAs are made of Barium Strontium Titanate (𝐵𝑎2𝑇𝑖9𝑂20) ceramic. Two types of RDRA were prototyped, a full size circuit ground plane as an initial design but with possibly some undesired radiation, and a T-shaped circuit ground plane design to study the ground plane effect.
The two RDRA prototypes were optimized in HFSS to obtain the dimension of the PCB as well as the dielectric resonator. Then the RDRA was constructed from a 𝐵𝑎2𝑇𝑖9𝑂20 ceramic and a FR4 PCB.
The simulated S11 for both were around -25dB and the measured S11 for both RDRA were around -35dB. The resonant frequencies for constructed RDRAs shifted from 10GHz to around 10.6GHz when using wax to bond the DR. When using sol-gel composite to bond, the resonant frequency shifted to around 11GHz for T-shaped circuit ground RDRA. The gain was -4dB for the full circuit ground RDRA in TEδ21 mode at 10.5GHz, 0dB for the T-shaped circuit ground RDRA in TEδ21 resonant mode at 10.6GHz, and 3.6dB for the T-shaped circuit ground RDRA in TE1δ1 mode at 8.6GHz.

abstract: M.A.Sc.


title: The Multidimensional Forgiveness Inventory: Developing a Dimensional Measure of Forgiveness

contributor:
MacDonald, Tara
Psychology

subject:
Psychology
Forgiveness
Relationships
Positive Psychology
Interpersonal Conflict
Social Psychology

abstract: The present research sought to develop a dimensional model of forgiveness, and develop a questionnaire consistent with this model. Drawing from the tripartite theory of attitudes, this dimensional model focused on three aspects of forgiveness: behavioural, cognitive, and affective. In Study 1, I collected a set of 64 items from volunteers who generated potential items based on definitions of the three dimensions of forgiveness, and reduced the number of items to 43 by assessing item-total correlations. In Study 2, I reduced the items and assessed factor structure with factor analysis. I also assessed correlations between dimensions and transgression severity. In Study 3, I further reduced the scale while also assessing correlations with transgression severity (as rated by the participants and as rated by independent coders), self-esteem and attachment orientation. In Study 4, I assessed the fit of the reduced set of items with confirmatory factor analysis. I also assessed the convergent validity with the Transgression-Related Interpersonal Motivations and Rye forgiveness scales and further explored correlations with the big five personality traits. The hypothesized three-dimensional scale showed acceptable fit indices and convergent validity with other forgiveness measures. I refer to this final scale as the Multidimensional Forgiveness Inventory (MDFI). The dimensions of the MDFI also showed unique relationships with several individual difference variables. For instance, only affective forgiveness was consistently negatively correlated with subjective and objective transgression severity. As another example conscientiousness was correlated with behavioural and cognitive forgiveness but not affective forgiveness. These relationships demonstrate the merit of differentiating these three dimensions instead of measuring forgiveness as a global construct. Preliminary findings offer many future directions for the assessment of forgiveness, particularly the specification of existing associations (e.g., what specific dimensions of forgiveness correlate relationship satisfaction, commitment and longevity?). Future research could also use this dimensional model as a common language to integrate and contrast existing ideas of incongruent forgiveness.

abstract: M.Sc.


title: Evaluating the relationship between the RET receptor tyrosine kinase and TMEM127

contributor:
Mulligan, Lois
Pathology and Molecular Medicine

subject:
RET
TMEM127
Pheochromocytoma
Intracellular trafficking

abstract: Pheochromocytomas (PCC) are highly heritable neoplasms of the adrenal gland, carrying germline mutations in approximately 40% of cases. PCC susceptibility genes have been subdivided into two clusters: hypoxia-related genes, and kinase-signalling genes, which include the RET receptor tyrosine kinase and Transmembrane protein 127 (TMEM127). RET is an established oncogene that causes aberrant activation of PI3K-AKT and MAPK-ERK signalling in various neuroendocrine cancers. Both wildtype (WT) RET and TMEM127 localize to multiple subcellular compartments including the Golgi apparatus, early endosomes and lysosomes. TMEM127 has been suggested to play a role in endosomal transition, however the function of TMEM127 has yet to be elucidated. In this study we evaluated the relationship between the RET receptor tyrosine kinase and TMEM127. We have identified a potential role of TMEM127 in RET protein maturation and transport to the plasma membrane. We were able to rule out a relationship between RET and TMEM127 at the transcriptional level, and at the level of RET protein folding. We also observed a relationship with TMEM127 mutants and total RET protein expression, which may correlate with TMEM127 mutant diffuse localization. Overall, the findings presented here suggest a novel interplay between RET and TMEM127 that may lead to a more thorough understanding of aberrant protein trafficking in human neoplasms and contribute to our overall understanding of the molecular mechanisms of PCC susceptibility genes.

abstract: M.Sc.


title: Solar Ultraviolet Radiation and Breast Cancer Risk

contributor:
King, Will
Public Health Sciences

subject:
breast cancer
epidemiology
meta-analysis
prospective
ultraviolet radiation

abstract:
Background: A moderate amount of time spent in the sun has been hypothesized to be protective against several internal cancers, including breast cancer. This project summarized and synthesized existing literature on this topic and identified sources of heterogeneity (manuscript 1). Secondly, this project examined this relationship using data from Canadian prospective cohort studies (manuscript 2).

Methods: First, a meta-analysis of case-control and cohort studies was conducted to investigate the relationships between time spent in the sun, and ambient UVR with breast cancer risk. Heterogeneity was quantified with I-squared statistics and potential sources were investigated through subgroup analyses. Second, a prospective cohort study was conducted using self-reported questionnaire data from the Alberta Tomorrow Project (ATP) and Quebec’s CARTaGENE (CaG) that was linked to cancer registry (ATP) and administrative (CaG) data. Cox proportional hazards models, using age as the time-scale were employed to investigate the association between solar UVR exposure and pre- and postmenopausal breast cancer with control for relevant confounders.

Results: In a dose-response meta-analysis, spending 1-2 hours in the sun per day was protective against breast cancer, with no additional benefit for >2 hours per day. Few studies performed analyses stratified by menopausal status. In manuscript 2, a suggestive protective effect for greater than 2 hours spent in the sun per day during summer months was observed in postmenopausal women only. No significant interactions between time spent in the sun and ambient UVR, vitamin D intake, or skin tone were observed.

abstract: M.Sc.


title: Hays Gone By: The Proto-Feminism of Pre-Code Hollywood and the Films of Mae West

contributor:
Bertrand, Karine
Cultural Studies

subject:
Cultural Studies
Film
Media Studies
Classic Hollywood
Production Code
Mae West

abstract: Pre-Code Hollywood has famously been described as an alternative universe of American cinema, as looser censorship restrictions allowed filmmakers to explore adult themes of violence and sexuality far more openly than would be permissible under Joseph Breen and the Production Code Association. My thesis addresses how this era gave rise to a proto-feminist cinema through the transgression of Production Code rules pertaining to gender and sexuality. Though the Pre-Code era was no stranger to virulently misogynistic works, the lack of strict censorship allowed filmmakers to put forth depictions of independent women who were sexually active and in control of their lives. The epitome of this archetype is Mae West, who not only portrayed sex sirens with tremendous agency on-screen, but also took an active role behind-the-scenes as a screenwriter and should be considered the primary author of her films. Though West’s independence on and off-screen would diminish as the Pre-Code era ended, her work remains a trove of proto-feminist cinema through its subversion of male gaze and its consideration of a female spectator. Understanding West’s films, and the era which produced them, helps provide insight on the challenges faced by women in Hollywood, and more specifically, how women-centric art is often devalued and dismissed.

abstract: M.A.


title: Vocal behaviour of Song and Swamp sparrows upon arrival on shared breeding grounds

contributor:
Martin, Paul
Biology

subject:
biodiversity
species coexistence
animal communication

abstract: Closely related species interact often, typically competitively, aggressively, and asymmetrically, with a consistent dominance hierarchy among species. Competition for resources appears to be a rate-limiting step in diversification, but beyond this, we know little about the ecological role of aggression in facilitating or constraining the coexistence of species due to the difficulty in observing natural interactions. To examine how closely related species in a dominance hierarchy aggressively interact, and how those interactions may facilitate coexistence, we documented vocalizations of Song (Melospiza melodia) and Swamp (M. georgiana) sparrows during natural and simulated territory settlement to answer the question: How does vocal behaviour of a dominant species change when first faced with a subordinate competitor on shared breeding territory? Though sample sizes were too low for statistical testing, we saw slightly increased rates of “Swamp Sparrow-like” songs sung by Song Sparrows in relation to Swamp Sparrow presence, as well as trill syllable lengths of Song Sparrow songs approaching average lengths of Swamp Sparrow trill syllables. These trends may suggest syllable sharing or vocal shifts in Song Sparrows as a response to Swamp Sparrow competitors – this vocal convergence may be beneficial in mediating conflicts over shared resources. We also provide novel descriptions of Swamp Sparrow behaviour during settlement on territories overlapping Song Sparrows. Further descriptions of vocal interactions can inform how closely related species interact aggressively, and will contribute to our understanding of how aggression might relate to coexistence on shared territories.

abstract: M.Sc.


title: Study of Back-Stress and Void Damage in Dual Phase Steels Subjected to In-Plane Shear

contributor:
Pilkey, Keith
Mechanical and Materials Engineering

subject: Back-stress dual-phase steel martensite strain stress damage microstructure shear

abstract:
The objective of this thesis is two-fold: to study the relationship between microstructural parameters and the work hardening and back-stress that develops in dual-phase (DP) steels using an in-plane shear test, and to use tools such as micro-computed X-ray tomography and scanning electron micrography (SEM) to examine the potential effect of damage on back-stress at higher pre-strains. Five microstructural variants were prepared using various thermo-mechanical processing methods and inter-critical (IC) annealing. These variants were then subjected to uniaxial tension until failure to measure work-hardening behaviour, and to forward-reverse in-plane shear tests to measure the back-stresses at varying shear pre-strains.
The high-volume fraction of martensite in the DP steel microstructures meant that all variants exhibited continuous yielding in both uniaxial tension and in in-plane shear. Microstructures with uniform distributions of martensite particles exhibited the most uniform elongation, while higher strengths were observed when a mixture of large and small martensite particles was present. Similarly, the highest back-stress was observed in microstructures with mixtures of large and small martensite particles. In all microstructures, back-stress initially increased with increasing shear pre-strain. At higher shear pre-strains the rate of increase decreased until a plateau was reached. Historically, this saturation can be attributed to void damage in the microstructure, the annihilation of GNDs around the hard martensite particles, and plastic deformation of the martensite.
When examined with micro-CT imaging, no voids could be resolved in the deformed samples of the microstructures; hence, SEM imaging was conducted. While some voids were observed in all the microstructures, they were too few and too small to fully account for the saturation of the back-stress at high pre-strains. Furthermore, plastic deformation of martensite particles was not observed.

abstract: M.A.Sc.


title: A Study of Immigrant International Medical Graduates’ Re-Licensing in Ontario: Their Experiences, Reflections, and Recommendations

contributor:
Colgan, Lynda
Education

subject: Re-licensing in Ontario

abstract:
This study is about the lived re-licensing experiences of immigrant international physicians in Ontario who are commonly referred to as International Medical Graduates (IMGs). The study had a two-fold purpose, the first purpose was to investigate whether the conclusions of the previous research were still relevant at the time of this study, and the second purpose was to examine the re-licensing experiences of a specific subset of Immigrant IMGs.
A comprehensive systematic review identified 12 selected papers on IMG issues (2008 - 2017), and these research papers highlighted that some Immigrant IMGs were successful in becoming re-licensed and working as physicians in Ontario. However, many of them had to make unpalatable choices such as transitioning into other health-related careers, accepting entry-level jobs or returning to their home country due to the systemic and financial barriers, and the lack of training opportunities and residency positions.
This study used mixed methods design with two research instruments (survey and individual interviews), two theoretical frameworks (Self-Determination Theory and Transformative Learning Theory), two sampling methods (purposeful sampling and snowball sampling), and two samples of Immigrant IMGs for two research purposes.
The 31 participants in the survey were a sample of the heterogeneous Immigrant IMG population in Ontario whereas the four interview participants were a sample of subset Immigrant IMG population in Ontario who had not been researched in the previous literature.
The findings of this research verified that the barriers documented in the previous empirical literature still exist. The qualitative component of this research revealed some additional barriers.  The interview participants' perceptions of how the embedded systemic barriers disadvantaged them and set them up for failure added new information to the research. Based on the participants’ experiences, reflections and recommendations presented in this research, it seems that the current re-licensing system should undergo a fairness review in the light of Canadian/Ontarian policies of equality, inclusion and human rights to help Immigrant IMGs survive and thrive.

abstract: PhD


title: The Development and Use of a Test Facility for Large Diameter Pipes

contributor:
Moore, Ian
Hoult, Neil
Civil Engineering

subject:
deep burial
large diameter culvert
ultimate limit state
corrugated steel pipe
erosion void

abstract: This thesis examines the performance of a new deep burial facility through numerical modelling and physical experiments. A numerical investigation was conducted to investigate the influence of the loading scheme and boundary conditions on the pipe behaviour in this new facility using both two – dimensional and three – dimensional analyses. The numerical analyses suggested that two independent grillages on the surface produced a more uniformly distributed ‘overburden’ pressure and friction treatment must be used in this facility to minimize the impact of sidewall friction on the pipe response. Two large diameter culverts, a 3.05 m diameter composite pipe and a 2 m steel pipe, were tested to study their strength limit states while evaluating the facility. The 3.05 m diameter composite pipe supported a maximum overburden pressure of 224 kPa and reached its ultimate limit state at a total overburden pressure of 258 kPa. The pipe failed as a result of local buckling of the steel ribs in the vicinity of both springlines. The 2 m diameter corrugated steel pipe did not reach its ultimate limit state at a total applied pressure of 358 kPa, but plastic hinges were seen to have occurred in the vicinity of both haunches. The plastic hinges observed in this experiment could lead to a failure mechanism that is not considered in the existing design models for structures of this type. A series of model erosion void experiments were conducted to investigate the potential for using the new facility to investigate the development of erosion voids. The results indicated that an erosion void stabilized in the vicinity of the pipe shoulder when erosion occurred through holes in the pipe haunch due to groundwater infiltration. The erosion extended to the ground surface when it was driven by simulated rain water flow through the holes in the pipe haunch. The final geometry, width and height, of the erosion void also depended on the elevation of the groundwater table, initial condition of the backfill, and the backfill material.

abstract: PhD


title: Exploring Physical Activity Opportunities for Adolescents in Secondary Schools in Antigua

contributor:
Lévesque, Lucie
Kinesiology and Health Studies

subject:
Youth
Caribbean
ISAT
Physical Activity
School Environment

abstract: Despite the known benefits of physical activity (PA), only 22% of adolescents in Antigua are meeting the World Health Organization’s (WHO) 60 minute a day moderate to vigorous physical activity  (MVPA) guidelines (Aguilar-Farias et al., 2018); relatedly 28.5% of adolescents in Antigua are overweight or obese (Walwyn & Hunte, 2012). The school has been recognized as a critical environment for providing opportunities for youth to engage in PA. However, little information is known about the PA context in secondary schools in Antigua. The purpose of this study was to explore the current PA opportunities and related facilities and features available in schools, the barriers and facilitators to engaging in these physical activities and ultimately gather recommendations to promote student PA in secondary schools in Antigua. Nine secondary schools were identified by the Antiguan Ministry of Education. An assessment of the PA environment in schools was completed using the ISCOLE School Audit Tool (ISAT; Broyles, 2015). In addition, eight interviews and nine focus groups were conducted with Physical Education (PE) teachers and first form (grade 7) students from each school, respectively. A socioecological model (McLeroy, Bibeau, Steckler, & Glanz, 1988; Stokols, 1996) guided the development of the interview and focus group questions; this approach allowed for a comprehensive exploration of the individual, environmental and policy-level factors that can influence student engagement in PA opportunities at school. Descriptive statistics were used to analyse the ISAT data and thematic analysis was used to analyse the focus group and interview data. PA opportunities within secondary schools are influenced by factors within the social, physical and policy-level environments. More barriers than facilitators to student PA opportunities were identified by teachers and students, which was supported by the ISAT findings. To our knowledge, this study is the first to explore the PA environment in secondary schools in Antigua. Findings and associated recommendations serve as a call to action for school bodies and relevant Ministries in Antigua. Findings may be used to guide discussions on improving the PA opportunities within secondary schools in the Caribbean.

abstract: M.Sc.


title: “Planned to bring life back into living”

contributor:
den Otter, Sandra
History

subject:
Scotland
Scottish History
Identity
Postwar History
Britain
British History
Globalization

abstract: This thesis examines East Kilbride between 1968-1979. East Kilbride was the first New Town in Scotland, a postwar reform initiated by the British government in 1946 to relocate residents of Britain’s over-crowded cities into new suburban towns. Receiving this distinction in May 1947, the former village of East Kilbride grew from 2,500 residents to nearly 60,000 in 1968. This thesis utilizes East Kilbride as a case study through which to illuminate elements of postwar Scottish history. This is accomplished through an analysis of a key decade in postwar Scottish history from the perspective of three primary forms of identity: Scottish, British and global. Employing techniques from place marketing studies, analysis of these identities reveals the town’s connections to many well-studied events and phenomena in contemporary Scotland. The archival research conducted in this thesis principally examines sources found in the South Lanarkshire Council Archive’s East Kilbride facility, interrogating how these identities are portrayed and contested in these materials.

abstract: M.A.


title: Granulocyte macrophage colony stimulating factor and macrophage colony stimulating factor compete to differentially regulate bone marrow-derived macrophage activation and polarization

contributor:
Gee, Katrina
Basta, Sameh
Biomedical and Molecular Sciences

subject: macrophages gm-csf m-csf lcmv tlr7 polarization differentiation

abstract: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF) are two highly regulated cytokines with a variety of roles in the immune system. One of their most impactful roles is in influencing the proliferation, differentiation, and polarization of macrophages. These cytokines have been implicated in a variety of diseases ranging from autoimmune diseases such as lupus to inflammatory diseases like atherosclerosis or even viral infections like HIV. The CSFs can be used to differentiate murine macrophages in vitro, however the differences between these two types of macrophages have not been extensively studied, especially in the area of viral infection. Additionally, the nature of GM-CSF and M-CSF’s competing effects when administered to macrophages simultaneously has not been well defined. This work explores the differences between M-CSF and GM-CSF derived bone marrow macrophages in terms of innate immune signaling via TLR activation and cytokine production after infection with lymphocytic choriomeningitis virus (LCMV), a well-defined model of viral infection in mice. My results show that LCMV is capable of modulating phosphorylation of TLR associated signaling proteins in different ways between these two cell types, and that LCMV blocks further phosphorylation of these proteins by the TLR7 ligand resiquimod (R848). This work also shows the effects of mixing differing proportions of GM-CSF and M-CSF and administering them to macrophages differentiated using one CSF or the other, along with the effects of differentiating macrophages from bone marrow under these different CSF proportions. The data indicated that GM-CSF holds a partial dominance over the polarization of macrophages to produce certain proinflammatory cytokines and a strong dominance in governing macrophage morphology. This thesis contributes to the overall understanding of these two important cytokines, their differing influences on macrophage polarization, and how they can be used to modulate macrophage cytokine production and response to viral infection, potentially informing future study of these cytokines as treatments or targets for treatment in diseases where macrophages have been implicated.

abstract: M.Sc.


title: The role of surface fossil magnetic fields in massive star evolution

contributor: Physics, Engineering Physics and Astronomy

subject:
massive star
stellar evolution
fossil fields
surface magnetic fields
magnetic braking
mass-loss rate

abstract:
Models describing the evolution of massive stars have advanced significantly due to understanding and including key physical phenomena in the calculations, such as mass loss and rotation. As stellar magnetometry has progressed very rapidly in the past decade, recent efforts have begun to focus on characterizing magnetic properties of massive stars and including their effects in evolutionary model calculations.

By implementing established scaling relations of surface fossil magnetic fields, we account for magnetic braking, mass-loss quenching, and time evolution; using a simple, coherent prescription. In our study, we use two well-known hydrodynamical stellar evolution codes: the Modules for Experiments in Stellar Astrophysics (MESA) software instrument and the Geneva stellar evolution code (GENEC).

We show that the incorporation of the effects of surface fossil magnetic fields impacts the model predictions, and, as a consequence, implies that the previous analysis of observed magnetic massive stars, which utilized non-magnetic evolutionary models for comparison, may need to be revised. We reinforce that magnetic braking and rotational mixing produce stars that can be identified as Group~2 (slowly-rotating, nitrogen-enriched) stars on the Hunter diagram, and we place constraints on their observable magnetic field strengths. We identify a unique feature of initially fast-rotating magnetic stars: following their initial blueward evolution, their rapid spin-down leads to apparently similar evolutionary tracks as if the star initiated its evolution as a slow rotator. This can, amongst others, affect the age determination of magnetic massive stars.

Metallicity affects the stellar mass-loss rates, which are reduced if the star is in a low-metallicity environment. We show that surface fossil magnetic fields can also greatly reduce the mass-loss rate of the star. Therefore, even in high-metallicity environments, magnetic massive stars may follow an evolutionary path that resembles that of stars in a low-metallicity environment. As a consequence, astrophysical phenomena that are canonically attributed to massive stars in distant galaxies could potentially be produced by magnetic progenitors in the Milky Way.

We conclude that the inclusion of new physical ingredients advances state-of-the-art model predictions, and therefore these models provide a basis for a platform to further investigate the nature of magnetic massive stars.

abstract: PhD


title: Computer-assisted Workflow Recognition  for Central Venous Catheterization

contributor:
Fichtinger, Gabor
Ungi, Tamas
Computing

subject:
Workflow recognition
Surgical tool recognition
Convolutional neural networks
Central Venous Catheterization

abstract:
Purpose: The transition to competency-based medical education from an apprenticeship model requires a greater amount of human resources to evaluate trainees. Therefore, there is an increased need for tools that can evaluate trainees and provide feedback without the need for an expert observer. This thesis describes the development of a system for training central venous catheterization. The procedure includes many tasks that must be performed in a predetermined order. This system, Central Line Tutor, is able to provide trainees with feedback about their performance by evaluating their compliance to proper workflow when practicing in a simulated setting.
Methods: Central Line Tutor uses a combination of electromagnetic tracking and tool recognition from a webcam video to analyze trainees’ workflow compliance. Critical tasks such as inserting the needle into the vessel are recognized by tracking the tools’ positions. The remaining workflow tasks were recognized by identifying the tools used in the given tasks. In the proof of concept implementation of the system, we used a color-based approach. This method has some limitations including: insufficient accuracy, and a long setup time. To improve Central Line Tutor’s task recognition, we also implemented a more robust method for tool recognition that involved training a convolutional neural network. We evaluated two different networks, Inception-V3 and MobileNet, and compared their accuracy to the initial color-based approach.
Results: Central Line Tutor was designed, implemented, and tested. The system was able to successfully recognize all tasks in the central venous catheterization workflow with a delay of 1.46 ± 0.81s compared to human reviewers. The system was able to recognize all tools using a color-based method, but the convolutional neural networks recognized tools with significantly higher accuracy. Inception-V3 and MobileNet had an average accuracy of 79% and 77% respectively. The color-based method was only able to achieve 8% accuracy.
Conclusions: Central Line Tutor is capable of evaluating trainees based on their adherence to procedure workflow. While all tools can be recognized using a color-based method, the use of convolutional neural networks is far more accurate. Overall, Central Line Tutor shows promise as a useful adjunct in competency-based medical education.

abstract: M.Sc.


title: Neo-Victorian Women: The Other Side(s) of Jane Eyre

contributor:
Berg, Maggie
English Language and Literature

subject:
Literature
Nineteenth-Century Studies
Neo-Victorian
Charlotte Bronte
Victorian Studies

abstract: With Charlotte Brontë’s bicentennial in 2016, neo-Victorian texts that seek to retell the narratives of Jane Eyre’s marginalized characters have emerged. These texts engage with Brontë’s most famous novel in ways that address the triumphs and challenges of Brontë’s long-debated feminist sentiments. My thesis focuses on three of these neo-Victorian texts and questions why authors feel compelled to adapt Jane Eyre, and what about retelling Brontë’s nineteenth-century novel enables authors to see their own ideological conditions in a new or different way. I argue, based on Cora Kaplan’s assertion that the debate surrounding Brontë’s feminism is significant due to the emotion it evokes, that the tension between the feminist and non-feminist implications of Brontë’s text renders Jane Eyre an ideal site for revisiting the nineteenth century in terms of gender, race, and class. Focusing on gender in Lyndsay Faye’s Jane Steele (2016), race in Sarah Shoemaker’s Mr. Rochester (2017), and class in Helen Dunmore’s “Grace Poole Her Testimony” (2016), I argue that neo-Victorian texts that retell Jane Eyre critique nineteenth-century ideologies through a twenty-first century feminist lens and comment on modern female experience. Collectively, the novels analyzed here position themselves within the context of Jane Eyre’s ambiguous feminism to engage with the role of fallen women, racially different women, and women bound by class demarcations in order to ask questions about whose voices are heard and whose are silenced, and about the conditions of womanhood in both the Victorian age and the present-day.

abstract: M.A.


title: Bien Orgullosx: Communicating Narratives of Pride from Youth in El Alto

contributor:
Hosek, Jennifer
Cultural Studies

subject:
Pain Narratives
Pride
Youth
El Alto
Desire Narrative
PAR
Participant Action Research
Community Based Research
Grounded Theory
Photovoice
Cultural pride
Bolivia
Pride narrative
Selfreflexive
Humanizing research
Refusal
in situ categorization
constant comparative method
Community based
audio visual
visual narratives
pride narratives
communication

abstract:
El Alto is a young Bolivian city with a majority young population mainly formed by migrants of rural/indigenous origins. Historically, social research based on El Alto has focused on extracting pain narratives. Research focussing on pain requires such narratives from participant subjects as evidence of authenticity, and targets marginalized and at-risk groups. Methodologically, such research also extracts results and rarely disseminates them in formats that are accessible or appealing to the subjects. This thesis project articulates and communicates pride narratives. In so doing, it enables a framework of analysis in order to be able to engage with more complex and dynamic understandings of what one, or a community, comes to know through lived experience. This approach does not deny pain but brings motifs of pride and hope to the forefront as alternatives. To counterbalance this existing trend in subject and method, this project  adopted a Community-based approach to grant agency to participants in all stages of the project and to collectively design, deploy and disseminate its findings to answer the following questions: What are the narratives of pride amongst youth in El Alto? Does collectively constructing definitions of pride and pride narratives change participants' notions of pride? And what are the best channels to communicate and harness this newly constructed, shared knowledge?
The channel chosen for results dissemination was YouTube. Workshops were organized over ten weeks around audiovisual skill training and participants’ collection and categorization of data in the form of photographs and videos. We defined pride as a collection of interrelating categories showing the most important components: Nature & Landscape, Culture & Art, and Work & Family. With this definition, participants filmed and produce 5 shorts that would depict different elements of pride through visual narratives. Additionally, one making-of short documentary depicting the workshop process was also uploaded to the same YouTube channel. Interviews with the participants by the end of the project show that their notion of pride changed towards a broader more inclusive conception and that participation in the project ignited the spark in some of them to continue communicating narratives of pride through audiovisual media.

abstract: M.A.


title: Cognition, Plasticity, and Functioning After Childhood Adversity in Major Depressive Disorder

contributor:
Bowie, Christopher
Psychology

subject:
Childhood Adversity
Cognition
Cognitive Remediation
Functioning
Major Depressive Disorder

abstract: Background: There is a compelling association between childhood adversity and Major Depressive Disorder (MDD) in adulthood, including more severe and treatment-resistant presentations of illness. Childhood adversity is also related to deficits in neurocognition, smaller hippocampal volume, and changes in structural and functional brain connectivity. At the same time, neurocognitive impairment accompanies many cases of MDD, but the extent to which childhood adversity accounts for cognitive variance has not been investigated. Furthermore, it is unclear whether adversity is related to plasticity, indicated by response to neurocognitive treatment, and if the relationship between cognition and functioning differs among individuals based on their history of childhood adversity. Objective: The current research sought to clarify how early adversity and select characteristics of illness relate to cognitive differences in MDD, as well as response to Cognitive Remediation (CR), a treatment that promotes neurogenesis and plasticity through cognitive exercise and compensatory strategies. In addition, this project examined the moderating role of adversity in the relationship between cognition and skills required for everyday functioning. Method: Thirty-nine individuals with MDD who previously completed a 10-week CR intervention, as well as neurocognitive and functional skills testing, were re-recruited to engage in a retrospective interview on childhood adversity. Results: More adversity endured as a child and repeated depressive episodes were associated with poorer cognition in adulthood, B = -.45, t(36) = -3.34, p = .002, and B = -.33, t(36) = -2.53, p = .017, together accounting for 37.4% of variance in cognition. Childhood adversity was associated with more improvement following CR, but this relationship was small in magnitude, ∆R2 = .05, ∆F(2, 36) = 4.36, p = .044. A significant association between cognition and functional performance was apparent only among individuals who experienced high levels of adversity, b = .63, SE = .25, p = .018. Conclusions: Our findings highlight childhood adversity and multiple depressive episodes as factors associated with cognitive impairment in MDD. We emphasize early trauma as an important variable to be addressed in neurocognitive treatment and research.

abstract: M.Sc.


title: UGT2B17, exemestane metabolism, and their association with physical health-related quality of life in Caucasian postmenopausal women participating in the Mammary Prevention.3 Trial

contributor:
Richardson, Harriet
Public Health Sciences

subject:
Postmenopausal
Breast cancer prevention
Exemestane
Quality of life
Pharmacogenetics
UGT2B17

abstract:
Background: In the Mammary Prevention.3 (MAP.3) trial of exemestane (EXE) for breast cancer prevention, postmenopausal women commonly reported physical menopause-related symptoms, such as joint and muscle pain and fatigue. UGT2B17 contributes to the elimination of EXE-induced activity; however, approximately 10% of Caucasians are carriers of the UGT2B17 homozygous deletion and have impaired elimination of the active EXE metabolite, 17-DHE. This homozygous deletion is hypothesized to have a detrimental effect on physical health-related quality of life (HRQL) in Caucasian postmenopausal women randomized to EXE.

Objectives: The objectives of this thesis were to characterize the relationship between the UGT2B17 homozygous deletion and 1) very bothersome prevalent physical HRQL with effect modification by HRT use and 2) meaningful decline in physical HRQL with effect modification by EXE use. This thesis also explored the relationship between glucuronidation of 17-DHE and meaningful decline in physical HRQL.

Methods: HRQL data in MAP.3 was collected using the Menopause-Specific Quality of Life Questionnaire (MENQOL) at study entry, and at 6- and 12-month follow-up visits. Multivariate logistic regression and log-binomial regression was used to assess the association the UGT2B17 homozygous deletion and adverse prevalent and incident physical HRQL, respectively. Log-binomial regression was used to investigate the association between glucuronidation of 17-DHE and decline in physical HRQL.

Results: The UGT2B17 homozygous deletion was significantly associated with meaningful decline in physical HRQL among women in the EXE arm only (RR=1.30, 95% CI: 1.02-1.67), although effect modification by EXE was not significant (PEM=0.14). Higher glucuronidation of 17-DHE exhibited a significant linear association with meaningful decline in physical HRQL (RR=0.84, 95% CI: 0.74-0.94). There was no statistically significant association between the UGT2B17 homozygous deletion and prevalent very bothersome physical HRQL prior to treatment allocation (RR=0.79 95% CI: 0.39-1.62), nor was there significant effect modification by HRT use (PEM=0.51).

Conclusions: The UGT2B17 homozygous deletion appears to have a detrimental effect on physical HRQL among women taking EXE only, but not prior to treatment allocation. Furthermore, higher glucuronidation of the active metabolite, 17-DHE, is protective against meaningful decline among women using EXE. Further research is needed to support the utility of UGT2B17 screening for breast cancer chemoprevention.

abstract: M.Sc.


title: Alternative Sample Introduction Techniques to Nebulization of Solutions in Inductively Coupled Plasma Spectrometry

contributor:
Beauchemin, Diane
Chemistry

subject:
Sample Introduction
Inductively Coupled Plasma
Fusion
Fire Assay
Electrothermal Vaporization
Flow Injection
Mixed-Gas Plasma

abstract:
The objective of this thesis was to explore alternative sample introduction techniques for inductively coupled plasma mass spectrometry (ICPMS) and optical emission spectrometry (ICPOES). This work was conducted as part of a Collaborative Research and Development project with Activation Laboratories Ltd., Ancaster, Ontario.
1. The first approach involved the development of a sample preparation method for the direct analysis of lithium borate fused X-ray fluorescence (XRF) discs by ICPMS with a mixed-gas plasma and flow injection for the introduction of slurries into the ICP. Three dispersing agents were initially explored, however a 4% (m/m) solution of Triton-X in 2% HNO3 DDW was found to homogenously suspend the ground particulate in solution, yielding highly reproducible injection peaks. External calibration by aqueous standards did not yield consistent results to the certified values at high slurry concentrations, regardless if matrix matching of the standard was performed. Calibration by standard addition was also explored and was found to be most accurate when the slurry concentration was well diluted and that the flow rate of the carrier did not exceed 1 mL/min, as it was suspected that particle agglomeration was occurring at higher slurry concentration and higher flow rates.
2. The second approach involved electrothermal vaporization (ETV) coupled to ICPOES for the analysis of solid fire assay buttons. A nebulization/pre-evaporation system was initially explored to prevent plasma overloading due to the mass of the button, however a N2 sheath gas was selected as it provided higher plasma robustness conditions to that of the previous approach. External calibration by aqueous standards were improved upon through utilization of the internal ETV temperature program and a venting valve system for the drying of solution. Significant Ag2S deposition along the inner transfer tube prevented accurate agreement of calculated to certified values by both aqueous and solid external calibration due to the differences in transport efficiencies. The addition of an optimized H2 gas flow rate into the reaction gas aided in reducing Ag2S deposition along the transfer tube to the plasma, however non-proportional signal to mass intensities were still observed as Ag2S deposition was not eliminated.

abstract: M.Sc.


title: The associations between estrogens, the UGT2B17 gene deletion, and health-related quality of life in postmenopausal women in the MAP.3 chemoprevention trial

subject:
endogenous estrogen
estradiol
estrone
postmenopausal
breast cancer
chemoprevention
health-related quality of life
UGT2B17

abstract:
Background: Natural depletions of estrogens during menopause are likely associated with symptoms and declines in health-related quality of life (HRQL). For women taking exemestane in the Mammary Prevention 3 (MAP.3) trial, symptoms may have been exacerbated, as exemestane works to further suppress estrogen levels to prevent breast cancer. Women with the UGT2B17 gene deletion have limited ability to metabolize and eliminate steroid molecules and are therefore hypothesized to have elevated estrogen levels prior to randomization (baseline) and be at increased risk of worsened HRQL during treatment.

Objectives: This thesis project aimed to investigate the effects of natural estrogen levels and exemestane-induced estrogen suppression on HRQL in postmenopausal women. UGT2B17 genotype was assessed regarding its role in natural estrogen levels and effect modification between estrogen suppression and worsened HRQL during exemestane treatment.

Methods: Estrone (E1), estradiol (E2), and UGT2B17 genotype were characterized for a subsample of MAP.3 participants. HRQL was assessed from Menopause-Specific Quality of Life Questionnaire (MENQOL) responses at baseline and follow-up visits. Multiple logistic and log-binomial regression models were used to estimate the association between estrogen levels and HRQL at baseline and exemestane-induced estrogen suppression and worsened HRQL one year after randomization, respectively. The association between UGT2B17 genotype and natural log-transformed estrogen levels was tested with multiple linear regression.

Results: At baseline, overall vasomotor, physical, and sexual HRQL were not associated with E1, while E2 was significantly associated with sexual HRQL (p<0.05). Increasing E1 and E2 suppression during exemestane treatment was associated with increased risk of worsened vasomotor and sexual HRQL (p<0.01). E1 suppression was also associated with worsened physical HRQL (p<0.01). UGT2B17 genotype was not associated with natural estrogen levels and did not modify the effects of estrogen suppression on HRQL decline.

Conclusions: Natural estrogen levels may continue to play a role in HRQL of older postmenopausal women. Increasing estrogen suppression by exemestane is associated with increased risk of experiencing worsened HRQL. Future studies should determine if baseline estrogen levels can predict worsened HRQL during treatment with the goal of increased adherence of exemestane in the chemoprevention setting.

abstract: M.Sc.


title: Filter Stability, Observability and Robustness for Partially Observed Stochastic Dynamical Systems

contributor:
Yuksel, Serdar
Mathematics and Statistics

subject:
Filter Stability
Stochastic Dynamical Systems
Observability

abstract:
Filter stability refers to the correction of an incorrectly initialized filter for a partially observed stochastic dynamical system with increasing measurements. In this thesis, we study the filter stability problem, develop new methods and results for both controlled and control-free stochastic dynamical systems, and study the implications of filter stability on robustness of optimal solutions for partially observed stochastic control problems. We introduce a definition of non-linear stochastic observability and through this notion of observability, we provide sufficient conditions for when a falsely initialized filter merges with the correctly initialized filter over time. We study stability under different notions such as the weak topology, total variation, and relative entropy. Additionally, we investigate properties of the transition kernel and measurement kernel which result in stability with an exponential rate of merging. We generalize our results to the controlled case, which is an unexplored area in the literature, to our knowledge.

Stability results are then applied to stochastic control problems. Under filter stability, we bound the difference in the expected cost incurred for implementing an incorrectly designed control policy compared to an optimal policy and relate filter stability, robustness, and unique ergodicity of non-linear filters.

abstract: M.A.Sc.


title: Mechanisms Behind Directed Forgetting: Exploring the Selective Rehearsal and Attentional Inhibition Accounts Using the Double-Item Method Paradigm

contributor:
Wilson, Daryl
Psychology

subject:
intentional forgetting
selective rehearsal
attentional inhibition
item-method directed forgetting

abstract: In an item-method directed forgetting paradigm, participants are instructed to remember some items from the study list and forget others. On a subsequent memory test, participants demonstrate better memory for remember items than forget items. This difference in performance is referred to as the directed forgetting effect. Two major accounts have emerged to investigate the underlying mechanisms for this effect. The selective rehearsal account states that the elaborative rehearsal of remember items followed by the passive decay of forget items is the primary process of directed forgetting. The attentional inhibition account suggests that the directed forgetting effect arises from the inhibition of forget items, which allows for remember items to be further processed. The current thesis explored the extent to which both of these accounts may contribute to directed forgetting. We used a novel variant of the paradigm where we presented participants with unrelated word pairs: On pure trials, participants were instructed to remember or forget both words; on mixed trials, participants were instructed to remember one word but forget the other. In Experiment 1, we found evidence in support of a selective rehearsal process with no evidence for passive decay or active inhibition of forget items. In Experiment 2, we introduced a novel neutral condition, and replicated and supported our findings of Experiment 1. Our findings suggest that selective rehearsal is the primary account of directed forgetting but that it must be modified to account for the fact that selection of information to be rehearsed is flawed.

abstract: M.Sc.