title: IMPROVING THE UNDERSTANDING OF ENVIRONMENTAL STRESS CRACKING IN POLYETHYLENES BY MODIFICATION OF THE BELL TEST

contributor:
Thompson, Michael
Vlachopoulos, John
Chemical Engineering

abstract:
One of the most common failures of plastics while in use is environmental stress cracking (ESC). Studies were conducted in this thesis to improve our understanding of ESC, through experimentation to modify the existing and most-used standardized test for ESC, namely the Bell Test (ASTM D-1693). Given the large variability of failure times associated with the Bell Test, the first study consisted of developing a novel heat notching technique. This technique consisted of a heated blade used for notching and showed decreased variability compared to the standard method of notching. Given the success, this work further highlighted a growing theory that the local phase morphology of the notch was critically important to assessing environmental stress cracking resistance.
The second study in this thesis explored the ESC failure mechanism on this new viewpoint that the local region of the notch and the structural arrangement of polyethylene therein was critically influential. The work related the failure mechanism to the localized absorption of the typical stress cracking agent, IGEPAL CO-630, in conjunction with the localized stress development in the notch, using an organic dye tracer and computer vision aided analysis. The study reinforced the importance of the local amorphous and crystalline regions, seen in the heat notch study, and found a two-stage stress-dependent absorption mechanism for IGEPAL occurring as cracking developed in the polyethylene samples.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Plastic products and liquid chemicals interact every day, for example, shampoo bottles, gasoline jerrycans, and piping for water or oil. However, with many different polymer–chemical interactions possible, inconsistent and irregular behaviours can cause these polymers to fail prematurely. The project described in this thesis examined modifications to the most commonly used accelerated testing standard for estimating the lifetime of polyethylenes when in contact with chemicals. The first main study of this work considered changes to specimen preparation for the test, using a heat blade to produce more consistent failure times among repeats. The second main study examined the use of a colorimetric tracking dye and computer vision analysis system to monitor aspect of plastics while environmental cracking started and propagated, so that more could be learned about this important failure mechanism.


title: An investigation of the impact of sublingual immunotherapy in experimental models of food allergy and anaphylaxis

contributor:
Jordana, Manel
Health Sciences

subject:
Food Allergy
Immunotherapy
Sublingual Immunotherapy
SLIT
Murine Models of Food Allergy

abstract:
Food allergy is a potentially life-threatening disease affecting up to 10% of individuals in Western countries. Clinical reactivity to food allergens is primarily mediated by immunoglobulin (Ig) E, with symptoms ranging from mild urticaria to anaphylaxis. Currently, food allergy remains a disease without a cure. Oral immunotherapy (OIT), which involves consuming small amounts of allergen, remains an experimental treatment in Canada, although has been approved by the Food and Drug Administration (FDA) in the United States for treatment of peanut allergy. While efficacious to induce desensitization, OIT is accompanied by a significant rate of adverse effects. Sublingual immunotherapy (SLIT) is a novel route of treatment for food allergy, where small amounts of allergen are placed under the tongue and held for 2-3 minutes. In contrast to OIT, SLIT offers not only treatment efficacy but also promises an excellent safety profile.
The first objective of this thesis was to first develop a SLIT regimen in murine models of food allergy where sensitization is carried out either epicutaneously or intragastrically. Secondly, we investigated the efficacy of SLIT in modulating the clinical and humoral responses in prophylactic and semi-therapeutic settings. In the prophylactic setting, where SLIT was administered prior to sensitizing allergen exposures, SLIT-treated mice were completely protected from allergic sensitization including absent production of serum ovalbumin-specific IgE. In the semi-therapeutic setting, where SLIT was administered to mice primed to develop food allergy, it produced a partial protection against food-induced clinical reactivity. This was associated with lower levels of IgE production in comparison to non-treated, allergic mice. Together, this work provides both an optimized SLIT protocol, as well as evidence on the efficacy of SLIT in the treatment of food allergy in murine models. These findings will aid future work investigating the cellular and molecular mechanisms underlying SLIT-induced protection.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Food allergy is a potentially life-threatening disease which is primarily mediated by IgE antibodies. Strict allergen avoidance and use of rescue epinephrine upon accidental allergen exposure remain the standard of care. Oral immunotherapy, where individuals ingest small amounts of allergen, is currently the experimental treatment of reference to induce clinical tolerance; however, it is accompanied by a significant rate of adverse reactions. In contrast, sublingual immunotherapy (SLIT), which is less efficacious, upholds a superior safety profile. The primary objective of this thesis was to investigate the impact of SLIT in inducing clinical and immunological changes in murine models of food allergy. We demonstrated that when administered prophylactically, SLIT prevents mice from undergoing anaphylaxis. When administered to sensitized mice in a pre-allergic state, SLIT was protective against severe clinical reactivity after challenge. In conclusion, the work presented here establishes a useful platform to investigate the mechanisms underlying SLIT-mediated protection.


title: Maya Food Strategies at Macabilero: A Paleoethnobotanical Study of Ancient Maya Agriculture and Ethnoecology During the Formative and Classic Periods

contributor:
Morell-Hart, Shanti
Anthropology

abstract:
Current hypotheses argue that shifts in ethnoecological practice resulted in the abandonment of many Formative Period (1000 BCE – CE 250) sites in the Maya area (Inomata et al. 2017; Douglas et al. 2015; Webster et al. 2007; Dunning et al. 2012). By utilizing paleoethnobotanical methods to recover actual botanical remains, I address understandings of agriculture and consumption practices of Formative Period Maya people, the impact of these practices on the landscape, and abandonment of Formative sites in the Usumacinta River region.
This study is focused on the site of Macabilero, an ancient Maya community with residential, defensive, and ritual features, abandoned during the Early Classic Period (ca 400 CE). Using paleoethnobotanical methodology, I consider arguments targeting the abandonment of Formative Maya sites. Studying transitionary periods, such as that between the Formative and Classic Periods, greatly contributes to our understanding of social and political change and how it is reflected archaeologically as well as related to the broader landscape. My research questions focus on plant staples at Formative Period sites as compared to staples at Classic Period sites, how these differences may reflect changes in ethnoecology and the abandonment of Formative sites, and what the implications may be for hypotheses about the Formative Maya “collapse” that relate abandonment to ecological stress and potential crop failures.
This study establishes that the people at Macabilero consistently chose to grow more reliable root crops, perhaps especially in times of unrest, alongside crops such as maize, beans, and squash. People at Macabilero made use of a wide array of resources in the landscape, and grew a diverse portfolio of crops, without relying overly on any one food resource.

abstract: Thesis

abstract: Master of Arts (MA)


title: Using Motivation to Understand Treatment and Decision-Making

title: USING MOTIVATION TO UNDERSTAND TREATMENT AND DECISION-MAKING IN PSYCHIATRIC ILLNESS

contributor:
Samaan, Zainab
Neuroscience

subject:
mental health
opioid use disorder
major depressive disorder
randomized controlled trial
mixed-methods
vaping
behavioural activation
patient-important outcomes
quality of life
harm reduction

abstract:
Background: Mental health challenges continue to impact Canadians, with major depression, bipolar disorder and substance use among the leading causes of disability. Depressive disorders are often associated with diminished motivation. In contrast, substance use has been described as a “motivated behaviour”, where use of drugs is associated with specific goals; motivation may therefore help explain health behaviours like vaping. This thesis studies motivation and mental illness, by assessing treatments for patients who lack motivation, and characterizing motives for behaviour.

Methods: A pilot trial (RCT) was conducted to determine the feasibility of a trial to test the effects of behavioural activation (BA) in patients with major depressive disorder (MDD) (n=20). The full RCT was conducted to test the effectiveness of BA (n=169). Next, a protocol for a systematic review is described which explores outcomes used in trials for bipolar disorder type 1. Finally, a mixed-methods study was undertaken to identify vaping perceptions in patients with opioid use disorder (OUD) who vape (n=41).

Results: The pilot RCT demonstrated the feasibility for a full trial. The full RCT revealed that behavioural approaches may produce improvements in depression and quality of life (QoL) for patients with diminished motivation. Finally, the mixed-methods study identified 14 themes, revealing that vaping is convenient, common among youth, and a tool for smoking cessation.

Discussion: The pilot and full RCT trials reveal that BA has positive effects on depression and QoL in patients with depression, specifically showing significant improvements compared to waitlist. The mixed-methods study of vaping provides a lens through which vaping behaviours in the OUD population can be understood, generating evidence which can inform cessation efforts.

Conclusions: These works highlight how motivation can be intervened upon through treatment, and harnessed to better understand health decisions, with the overall objective of improving care within psychiatric populations.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Mental health challenges continue to impact Canadians, with major depression, bipolar disorder and substance use among the leading causes of disability. Depression and bipolar disorders are often associated with diminished motivation. Substance use, however, has been described as a “motivated behaviour”, where the use of drugs is associated with specific goals, such as motivations to reduce negative feelings, achieve pleasure, and perhaps most importantly, avoid withdrawal. By assessing potential treatments for patients who lack motivation, and characterizing patient motives for health decisions like vaping, the following thesis aims to study motivation and mental illness from several perspectives. Study findings suggest that behavioural approaches can produce meaningful improvements for patients with diminished motivation, and identify several motivators for engagement with vaping behaviours, both of which have implications for mental illness treatment and policy building. Taken together, this work aims to generate evidence to improve treatment and enhance harm reduction approaches.


title: Framing physical literacy through a rehabilitation lens: A health promotion role for physiotherapists

contributor:
Richardson, Julie
Rehabilitation Science

subject:
physical literacy
multimorbidity
older adults
physiotherapy

abstract: Increasing access to and improving knowledge of rehabilitation strategies is essential to address the adverse health outcomes related to the increased prevalence of multimorbidity with our aging population. Physical literacy is emerging as a strategy to increase lifelong participation in physical activity, however, there is limited research exploring how physical literacy can support optimal aging for adults with functional decline associated with chronic conditions. This thesis investigated how to frame physical literacy for adults through a rehabilitation lens and explored outcomes related to function, mobility, and health awareness as a result of a novel physical literacy intervention. The first study was an integrative review examining what is known about physical literacy for adults. Thirteen new physical literacy constructs emerged, that differed from the current physical literacy definition and addressed the needs of aging adults. Purposeful activities, knowledge of age-related changes, and social interaction were identified as the top three. The objective of the second expert consensus study was to understand what components are required when acquiring physical literacy as an adult from the perspectives of healthcare professionals and researchers in optimal aging. The third qualitative study explored how adults with multimorbidity describe physical literacy for adults while considering barriers and facilitators associated with fluctuating health status. The findings from the preceding qualitative studies helped inform the program development of the fourth physical literacy intervention study and fostered a new rehabilitation-focused Physical Literacy framework for Adults and adults with Chronic Conditions (PLACC).  A pre-post study involving 20 adults with 2 or more conditions (95% female, 59 + 6 years) participated in a 5-week multi-component, virtually delivered physical literacy group intervention. Post-intervention significant improvements were found for physical function (p=<0.001; cohen’s D=0.90), as measured by the patient specific functional scale, mobility with the 4-meter walk test at self-selected speed (p=0.03, cohen’s D=0.53) and all 3 physical literacy awareness questions (p=0.001, p=<0.001, p=0.001). The results of this program of research can inform future public health interventions, involving rehabilitation-focused physical literacy programs, designed by physiotherapists, and aimed at improving function and mobility for adults with chronic conditions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: In Ontario, almost 80% of adults over the age of 45 are living with at least one chronic condition, such as diabetes, high blood pressure or arthritis. These conditions require on-going management and can cause challenges with one’s function and mobility. Physical literacy is a term that is used commonly in schools and sports to describe the basic movement skills that children need to be active for life. It is unknown how physical literacy can help support adults with chronic conditions to improve their overall health. This thesis explored how physical literacy could improve function and mobility for adults and older adults with chronic conditions. The first study examined all the existing literature on adults and physical literacy. The second and third studies asked physiotherapy researchers and adults with chronic conditions what physical literacy means to them. The results of these studies found that there are different skills needed to become physically literate as an adult than what is needed to become a physically literate child. A new physical literacy model for adults was developed that guided an intervention study for adults with chronic conditions. Results of this intervention study found that a 5-week education program delivered virtually by a registered physiotherapist could improve adults’ awareness of what physical literacy is, improve function and mobility outcomes and positively impact behaviours. The results of this thesis have provided a new way of thinking about physical literacy for adults and older adults. Physical literacy for adults involves self-monitoring movement, having knowledge of age-related changes, participating in meaningful, safe, and social movement activities, and understanding the benefits of physical activity for the management of chronic conditions.


title: ἄριστον μέν ὕδωρ: URBAN PLANNING AND WATER IN AKRAGAS AND METAPONTO

contributor:
Pope, Spencer
Classical Studies

subject:
Classics
Archaeology
Metaponto
Akragas
Magna Graecia
Agrigento
Waterways
Athens
Archaic Period
Classical Period
Water Management
Water Systems
Tyranny
Democracy
Hippokrates
Hippodamos of Miletos
Enneakrounos
Southeast Fountain House
kolymbethra
division lines
canals
orthogonal planning
Urban Planning
grid streets
Pindar
Metapontine
chora
chora of Metaponto
Geology
Hydrogeology
karst
Klepsydra fountain
Great Drain
Asklepieion

abstract: This thesis examines the water resource management in two Greek colonies in Magna Graecia, Akragas and Metaponto, and the relationship between resource management and political regimes. It asks how similar ancient urban theory was to the practical reality, and if different forms of government made different provisions for water management. Chapter 1 outlines urban and health theories found in the works of ancient theorists. It debunks the idea that Hippodamos was the inventor of grid planning, while introducing the concept of ‘total’ city planning. The focus of Classical scholarship on Athens necessitates discussions of several Athenian water systems and how resource management changed (or continued) through different governments in Athens as a point of comparison for Akragas and Metaponto. This chapter focuses on literary analysis and introduces the controversial Southeast Fountain House, with an in-depth consideration of the fountain’s naming and dating problems. Chapter 2 contains the case studies of Akragas and Metaponto and an exploration of the hydrogeology at the two sites, with an introduction to the hydrological phenomenon of karst activity. A discussion of their unique water features—the kolymbethra at Akragas and the canals in the chora of Metaponto—connects the deliberate planning that occurred in both cities to Hippodamos and the urban theorists. Chapter 3 more fully explores the role of tyrants and democracies in water management. Regardless of authorship, water resource management and water systems are necessary for any city, and so most tyrannical water infrastructure continued to be used and expanded and improved upon even under different governments. Even under tyranny water management is a provision of the state and is engaged with and managed by the citizens of the city. Water management is an essential part of siting and establishing a city, so that it is inseparable from urban planning.

abstract: Thesis

abstract: Master of Arts (MA)


title: Functional genetic screening and therapeutic targeting of recurrent glioblastoma

contributor:
Singh, Sheila K
Biochemistry and Biomedical Sciences

subject:
Glioblastoma
Tumor relapse
CRISPR
Chimeric antigen receptor
Immunotherapy
Functional genomics
Patient-derived models

abstract:
Glioblastoma (GBM) remains the most aggressive and prevalent malignant primary brain tumor in adults. Unchanged since 2005, standard of care (SoC) consists of surgical resection, followed by radiation therapy (RT) with concurrent and adjuvant chemotherapy with temozolomide (TMZ). Despite these therapeutic efforts, patients succumb to recurrent disease with a median overall survival of 14.6 months and a five-year survival rate of 5.5-6.8%. Therapeutic failure is largely explained by ITH and the presence of treatment-resistant GBM stem-like cells (GSCs). Given the lack of understanding of recurrent GBM and absence of second line therapies patients, I hypothesize that genome-scale functional genetic interrogation will unravel recurrent GBM-specific tumor biology and inform development of novel therapeutics.

First, I compared primary and recurrent GBM at the genetic, transcriptomic, proteomic and functional genetic levels. These analyses map a multilayered genetic response to drive tumor recurrence, identifying protein tyrosine phosphatase 4A2 (PTP4A2) as a novel modulator of self-renewal, proliferation and tumorigenicity at GBM recurrence. Mechanistically, genetic perturbation and a small molecule inhibitor of PTP4A2 repress axon guidance activity through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1) and exploit a genetic dependency on ROBO signaling. Importantly, engineered anti-ROBO1 single-domain antibodies also mimic the effects of PTP4A2 inhibition.

Given the genetic dependency on ROBO signaling and enrichment of ROBO1 expression in GBM tissues, I undertook a campaign to evaluate ROBO1 as a therapeutic target in recurrent GBM and develop anti-ROBO1 chimeric antigen receptor T (CAR-T) cells using camelid single-domain antibodies targeting human ROBO1. I optimized the design of anti-ROBO1 CAR-T cells and tested the anti-tumor activity of these modalities in in vitro using patient-derived recurrent GBM lines and orthotopic patient-derived xenograft models. I present data to expand the repertoire of GBM-enriched antigens suitable for effective CAR-T cell therapy. Given that resistance to SoC and disease relapse are inevitable for GBM patients, pre-clinical and clinical advancement of immunotherapeutic modalities, combined with recent insights into the tumor immune microenvironment, are poised to improve clinical outcomes for this patient population.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Glioblastoma remains the most lethal and prevalent primary brain tumor in adults. Standard of care for patients remains unchanged since 2005, consisting of surgery to remove visible tumor at diagnosis (primary tumor), followed by radiation therapy and chemotherapy to treat remaining tumor cells. Despite these therapeutic efforts, tumor relapse (recurrent tumor) is inevitable with no standardized second-line therapy. Patients succumb to recurrent disease with a median overall survival of 14.6 months and only 5.5-6.8% of patients survive five years post diagnosis.

Therapy failure and tumor relapse are explained by immense diversity among tumor cells at the DNA and protein levels, giving rise to a subset of tumor cells with abilities to resist therapy and seed the recurrent tumor. Previous studies have presented evolution of tumor cells through therapy, with recurrent tumor cells harboring novel changes at the DNA and protein levels. However, the impact of these changes on tumor cell function has not been evaluated.

In this thesis, we developed and applied a genetic screening technique to determine the functional role of thousands of genes in primary and recurrent tumor cells from the same patient. This analysis revealed numerous genes that exhibit differential effects on survival of primary and recurrent tumor cells, including genes that drive recurrent tumor cell growth but are dispensable in primary tumor cells.

Functional remodeling of these genes and pathways revealed a new functional role of multiple proteins belonging to a process called axonal guidance in recurrent tumor cells. To evaluate the therapeutic potential of these findings, we deeply interrogated the mechanism by which axonal guidance drives recurrent tumor cells and targeted crucial molecular players using chemical and immunological therapies. Using models that predict clinical effectiveness, we engineered and tested a novel therapy that redirects immune cells to target recurrent tumor cells driven by dysfunctional axonal guidance activity. The goal of this thesis was to discover the functional differences between primary and recurrent tumor cells, thereby leveraging this information to engineer candidate therapies for treatment of recurrent glioblastoma.


title: INHIBITORS OF BRUTON’S TYROSINE KINASE ALTER NF-κB AND NLRP3 INFLAMMATION IN MACROPHAGES

contributor:
Schertzer, Jonathan
Biochemistry and Biomedical Sciences

abstract: Obesity-related inflammation increases one’s risk of developing cardiovascular disease, type 2 diabetes, among many other disorders. Energy imbalance during obesity overwhelms the adipose tissue leading to immune cell infiltration, elevations in pro-inflammatory cytokines, and consequent local and systemic insulin resistance. Certain potent pro-inflammatory cytokines are produced by the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. This metabolic danger sensor is involved in a variety of autoimmune and inflammatory conditions, hence regulation of this node as a therapeutic approach is a topic of great interest. To date, there is no clinically approved inhibitor of the inflammasome, which makes indirect targeting through endogenous molecules an attractive area of research. Bruton’s tyrosine kinase has been shown to physically interact with NLRP3 inflammasome components and is required for its production of pro-inflammatory cytokine, IL-1β. However, the consequences of BTK inhibition on metabolic tissues like adipose tissue remain largely unstudied. In vitro experiments showed that pharmacological BTK inhibitors lower NLRP3 inflammasome priming and activation in macrophages. Bone marrow-derived macrophages (BMDMs) from a Btk-null mice strain treated with BTK inhibitors demonstrated lowering of lipopolysaccharide (LPS) -induced elevations in inflammatory cytokines. This effect was interestingly observed in both BMDMs derived from wild-type and Btk-null mice, postulating the idea that pharmacological inhibitors of BTK have anti-inflammatory properties that do not require the presence of the BTK gene product. Further, the optimized conditions for testing the influence of BTK inhibitors on adipose tissue insulin signaling ex vivo is outlined. Future work should focus on pinpointing off-targets shared between BTK inhibitors to identify the node responsible for the observed anti-inflammatory effects. This research may lead to the development of an alternative therapeutic approach to treating inflammatory and autoimmune diseases mediated by the NLRP3 inflammasome.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Obesity overwhelms fat storage sites and causes inflammation, which can contribute to metabolic disease. An important part of this inflammation is the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. This sensor of stress detects danger signals and produces molecules involved in inflammation. However, overactivation of NLRP3 can cause inflammatory diseases. Blocking another protein, Bruton’s tyrosine kinase (BTK), can limit the activation of NLRP3 inflammasome. Our findings show that blocking BTK using drug inhibitors lowers inflammation caused by the NLRP3 inflammasome. Interestingly, we found that these drugs can lower inflammation without working on BTK, the protein that these drugs are designed to block. Understanding how these drugs are anti-inflammatory will help us understand the NLRP3 inflammasome, and how to lower inflammation during obesity and metabolic disease.


title: X10 expansion microscopy optimization for the lateral superior olive nucleus in the auditory brainstem

contributor:
Gillespie, Deda
Neuroscience

subject: neuroscience, brainstem, expansion microscopy, inhibition, refinement, super-resolution

abstract:
The diffraction limit of light hinders our ability to study the interactions between biomolecules. We are limited by conventional light microscopes to a lateral resolution of approximately 200 nm. Ways exist to image at nanometer scale resolution, such as with the use of electron microscopes, but electron microscopy is not appropriate for all questions. Innovations in light microscopy over the last few decades have created a new field of imaging, known as super-resolution microscopy, where both fixed and living tissue can be imaged using multiple markers past the resolution limit of light. An array of super-resolution techniques exist, each with its own advantages and disadvantages. Here, I set out to optimize the X10 expansion microscopy technique for use in the brainstem.
Located in the auditory brainstem is the superior olivary complex, where an intricate refinement process of inhibitory connections occurs between the surrounding auditory nuclei. Of interest is the inhibitory projection from the medial nucleus of the trapezoid body to the lateral superior olive, which releases the excitatory neurotransmitter glutamate during an early developmental period. For my Master of Science research project, I have worked on optimizing the X10 expansion microscopy protocol for the auditory brainstem, with a focus on the lateral superior olive nucleus.
After optimization, I was able to achieve an expansion factor close to 10 in both adult and juvenile tissue using the X10 expansion microscopy protocol. My results exhibited no obvious abnormalities in staining in co-stained expansion microscopy experiments of vesicular neurotransmitter transporters and synaptotagmin calcium sensors in the lateral superior olive nucleus. The workflow presented here is ready for use in brainstem with secondary nanobodies or directly conjugated primary antibodies.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
The ability to study molecules at nanometer resolution using conventional light microscopes is limited by the diffraction limit of light. Innovations in super-resolution microscopy have created techniques that permit visualization of molecules of interest past the 200-250 nm resolution limit of light. One super-resolution technique, X10 expansion microscopy, can be used alone, or in combination with other methods, to achieve resolution an order of magnitude better than that afforded by conventional light microscopy.
An immature circuit in the auditory brainstem presents interesting questions for super- resolution microscopy. As brainstem tissue differs from neocortical tissue in density and optical scattering, expansion microscopy techniques previously optimized for cortical tissue must be tested and reworked for use in the brainstem. My results show that the X10 expansion microscopy protocol can work with both adult and juvenile auditory brainstem nuclei, with no observable immunohistochemistry aberrations.


title: REGULATION OF LIPID OXIDATION DURING THERMOGENESIS AT HIGH ALTITUDE IN DEER MICE

contributor:
McClelland, Grant B.
Biology

subject: Peromyscus maniculatus, heat production, fat metabolism

abstract: Organisms are constantly balancing energy demand with an adequate supply of oxygen and substrates to sustain metabolic activity. Thermogenesis is an important metabolic process by which endotherms predominately burn lipids to regulate and maintain their body temperatures by balancing heat loss with heat production. Due to their high rates of heat loss, small winter-active mammals, like the North American deer mouse (Peromyscus maniculatus), are constantly challenged with thermogenesis. Deer mice are also native to high-altitude environments, conditions that further complicate the process of thermogenesis due to the inherent reduced oxygen availability. How metabolic substrates are used for fuelling and sustaining thermogenesis at high altitude remains unclear. The goal of my thesis was to examine how lipid metabolism has evolved to sustain heat production in animals living in high-altitude environments. This was achieved by using deer mice native to high- and low-altitudes acclimated to either standard lab conditions or simulated high altitude (cold hypoxia). I demonstrate that during thermogenic capacity (cold-induced V̇O2max), high-altitude deer mice have higher thermogenic lipid oxidation rates compared to their lowland counterparts, which is further increased after cold hypoxia acclimation. Interestingly, these high rates of lipid oxidation were associated with higher circulatory delivery rates of fatty acids and triglycerides to thermo-effector tissues. Specifically, I show that after a bout of cold-induced V̇O2max, fatty acid uptake occurs primarily in the skeletal muscle in control acclimated high-altitude deer mice, and then shifts to brown adipose tissue following acclimation to high altitude conditions. These findings clearly show that in high-altitude deer mice, maximal thermogenesis is reliant on elevated delivery of circulatory lipids to muscle and brown adipose tissue. This research further sheds light on the mechanistic underpinnings responsible for enhanced thermogenic capacity of high-altitude deer mice and capacity for the highest lipid oxidation rates observed in any mammal.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Thermogenesis, the metabolic production of heat, allows endotherms to maintain stable body temperatures in cold environments. However, it was not yet understood how small mammals fuel and sustain heat production in the cold and low oxygen environment of high altitude. My thesis has uncovered how deer mice native to high altitudes have adapted to burning fats at high rates in hypoxia to sustain thermogenesis. My findings show that high delivery rates of fats to heat-generating tissues are responsible for the elevated rates of heat production in high altitude deer mice. My work contributes to our understanding of the inner workings of the fat pathways and how it has evolved to ensure survival in extreme environmental conditions.


title: A multifaceted approach towards advancing the sterile filtration of therapeutic viruses

contributor:
Latulippe, David
Chemical Engineering

subject:
bioprocessing
viruses
sterile filtration
host cell impurities
microfabrication
nanoparticles

abstract: Therapeutic viruses are a class of biotherapeutic which have enabled new treatments and medical advances in the areas of vaccines, cancer treatment, gene therapy, and more. In the production and purification of these products, the sterile filtration unit operation is known to have poor yields and contribute to the high cost of the final product, significantly hampering the large-scale production of some therapeutic viruses. Thus, this thesis seeks to explore various aspects of process development and fundamental understanding in the sterile filtration of therapeutic viruses. This thesis explores the mechanisms and membrane properties which govern how bacteria are retained during filtration, and applies these insights to improve the sterile filtration recovery of a therapeutic virus through proper membrane selection. To better understand the factors which cause membrane fouling and loss of virus during sterile filtration, the effect of host cell impurities on filtration performance was investigated. This revealed that small amounts of host cell protein are a major factor in both membrane fouling and reduced virus yield, and that there is a synergistic effect between the virus and the host cell protein adsorbing to the membrane surface. Recognizing that conventional polymeric membranes have many limitations, a novel ultrathin, isoporous, microfabricated silicon nitride membrane was tested for suitability as a sterile filter. Finally, the application of nanoparticles as model virus particles in filtration testing was examined, and a process was developed through which nanoparticles could be fused together to create controlled amounts of particle aggregates, similar to how viruses can be prone to aggregation. The work described here will help enable the development of next generation sterile filtration membranes and provides both insights and methodologies for improving sterile filtration performance.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: While many people are aware that viruses can be used in medicine as vaccines, there are even more new and developing ways they can be used, such as in fighting cancer or treating previously uncurable diseases. However, testing of and patient access to these new treatments is often limited due to the challenges in producing and purifying enough of the virus. Viruses are highly complex and large relative to other products, and so many of the common methods and manufacturing processes which are standard in the industry need to be significantly adapted or improved to suit the production of viruses. This study investigates one step of the purification process, sterile filtration, and considers how a variety of factors from the materials used to the properties of the virus solution can be optimized to improve performance. With a deeper understanding of the sterile filtration process, recommendations can be made to help improve the production of future virus-based therapies.


title: Solidarity and Resistance at the Borders of EUrope: Civil Fleet Search and Rescue Operations in the Mediterranean Borderscape

contributor: Political Science - International Relations

subject:
Borders
Solidarity
Migration
Mediterranean Sea
NGO
Search and Rescue

abstract: The project examines the construction of state space and the contestation of the EUropean borderscape through the work of non-state actors in the Mediterranean Sea. In response to the precarity of irregularized migrant journeys, there has been a rise in Search and Rescue (SAR) NGOs committed to assisting people on the move through upholding the basic human rights and dignity of migrants. Increasingly, NGOs are criminalized for providing basic necessities like food, water and shelter to migrants passing through the peripheral spaces of the state. Not only does irregular migration through the borderlands of the Global North directly confront state efforts to exclude through violent bordering practices, but NGO acts of solidarity also transform the harsh environment of the sea into contested spaces of political action. The lifesaving actions of NGOs operating in the Mediterranean directly challenge state authority and governance at sea while laying bare the violence inherent in state bordering practices. Conversely, the disruptive politics of these NGOs serve as a form of resistance to these same bordering practices and operate as a means of contesting state exclusion. Situating NGO SAR operations within the wider context of the securitization of borders, the repression and criminalization of solidarity in the Mediterranean highlights state efforts to reassert sovereign authority over the sea. This ongoing research contextualises the spatial politics of the Mediterranean borderscape at the intersections of migration governance and acts of solidarity by European NGOs. The research conducted for my doctoral project was driven by an ethnographic methodology that included six months working with SAR NGOs active in the Central Mediterranean while gathering over 50 interviews with activists working in the region. More directly, this also involved three months living and working alongside the German SAR organization, Sea-Watch, in France and Italy during periods of legal and administrative detention. My work bridges the opportunity to write about these movements and resistance efforts, with direct involvement in these struggles for rights, recognition, and freedom of movement, in solidarity with people on the move.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Adaptation Of A Clinical Multiparameter Flow Cytometry Strategy For The Enrichment Of Measurable Residual Disease Cells In Acute Myeloid Leukemia

contributor:
Berg, Tobias
Biochemistry

abstract:
Acute myeloid leukemia (AML) is a heterogenous blood cancer originating in the bone marrow and arising from the abnormal growth and lack of differentiation of myeloid cells. Even after intense treatment, disease recurrence is a major problem in AML and is attributed to cells that remain following treatment. We are now able to detect these residual cells after treatment with sensitive assays. This is known as measurable residual disease cells (MRD).
The detection of MRD is possible using multiparameter flow cytometry assays and quantitative PCR (qPCR). The detection of MRD has been shown to be predictive of survival. However, there is very limited understanding of the biology of MRD as it is currently not possible to isolate MRD cells and study them in functional assay or by gene expression assays.
Our research now aimed to modify methods used for MRD detection to allow for the isolation and characterization of MRD cells from remission samples. To facilitate this, a recently published a multiparameter flow cytometry (MFC) panel based on the ELN recommendations was established and modified for use on frozen samples. This panel allows to the identification of early myeloid progenitor cells and the asynchronous expression of maturation markers as well as the aberrant expression of lineage markers. To identify patient samples with MRD, we used sensitive clinical qPCR assays for the detection of different NPM1 mutations as well as RUNX1-RUNX1T1. More than 160 samples from 86 patients were collected and samples with MRD identified from 3 patients. Based on our MFC panel we sorted these cells from the follow up samples through the use of either early myeloid progenitor markers, or aberrant marker expression. Using this approach, we could enrich for the level of MRD in these samples. This method is now available and could be a first step in the prospective isolation of MRD cells for functional studies and gene expression profiling.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Acute Myeloid Leukemia (AML) is a type of blood cancer originating in the bone marrow. Even after intense treatment, only 40-50% of AML patients maintain complete remission and the majority of AML patients will unfortunately experience an aggressive relapse. Measurable residual disease (MRD) cells are cells that remain in patients post-treatment. Our research goal is to understand the biology of these MRD cells better. We therefore aim to enrich MRD cells to study them at a molecular level to understand how they could be better targeted for future treatments. Our research may therefore aid in patient prognosis, development of personalized treatment, and reduction of relapse.


title: OPTIMIZATION OF AN IN VITRO MODEL OF BIOFILM FORMATION ON VAGINAL EPITHELIAL CELLS TO TEST STRATEGIES FOR PROTECTION AGAINST BACTERIAL VAGINOSIS

contributor:
Kaushic, Charu
Medical Sciences

subject:
HIV
Bacterial Vaginosis
Women's Health
Vaginal Microbiota
Biofilms
Biofilm Treatment

abstract:
Background: The composition of the vaginal microbiota (VMB) in the female genital tract (FGT) can impact the vaginal epithelium and protect against or increase risk of sexually transmitted viral infections. The VMB grows as a biofilm, a complex structure formed by bacteria for increased survival. When the VMB consists of a diverse bacterial community it correlates with pathogenic effects that lead to adverse health conditions and an increased risk of HIV infection. When the VMB contains Lactobacillus species, beneficial health effects and decreased susceptibility to infection are observed. The aim of this project is to optimize an in vitro model of biofilm formation for different bacteria associated with the VMB, identify the effects that biofilm has on vaginal epithelial cells and test biofilm treatment strategies. We hypothesize that a Lactobacillus biofilm will enhance barrier function and decrease cytotoxicity of vaginal epithelial cells whereas dysbiotic biofilm will decrease barrier function and induce cytotoxicity. We also hypothesize that various conditions, such as presence of estradiol and eubiotic short-chain fatty acids, will stimulate Lactobacillus biofilm growth and suppress dysbiotic biofilm growth in a vaginal epithelial cell model.                                                                                Methods: For optimization of the biofilm model, VK2/E6E7 cells were grown in air-liquid interface (ALI) or liquid-liquid interface (LLI) cultures in presence or absence of L. crispatus, L. iners, G. vaginalis or P. bivia bacteria. Biofilm formation was assessed using FilmTracerTM SYPRO® Ruby biofilm matrix protein stain. Hormone effects were tested by adding estradiol (10-9 M) and progesterone (10-7 M) to culture media. Short-chain fatty acid (SCFA) effects were tested by adding lactic acid, acetic acid, succinic acid and butyric acid in varying concentrations to culture media. Enzyme effects were tested by adding sialidase to Vk2 cells before bacteria inoculation.
Results: A novel in vitro model of biofilm formation on vaginal epithelial cells was created. Vk2 cells in ALI and LLI cultures remained viable in anaerobic conditions and showed mucin-1 production in aerobic and anaerobic conditions. Matrix protein staining provided a means to accurately visualize and quantify biofilm formation in this model. L. crispatus and L. iners biofilm growth maintained vaginal epithelial barrier integrity without cytotoxicity. G. vaginalis and P. bivia biofilm growth significantly reduced barrier integrity (p=0.0166, p=0.0115) and increased cytotoxicity (p=0.0024, p<0.0001). Estradiol significantly increased the growth of L. crispatus biofilm in the co-culture system (p<0.0001). Progesterone significantly increased G. vaginalis biofilm growth in the Vk2 cell co-culture (p=0.006). L. crispatus biofilm formation in the estradiol condition, G. vaginalis biofilm formation in the progesterone condition and P. bivia biofilm growth in the normal media condition were significantly decreased in the presence of sialidase (p<0.0001, p=0.0001, p=0.0380).
Conclusion: A novel in vitro model of biofilm formation on a vaginal epithelial cell line that can be used to visualize and quantify biofilm growth was generated. This model was used to test various strategies for biofilm enhancement or dissociation. Estradiol enhanced beneficial Lactobacillus biofilm growth, while progesterone enhanced dysbiotic biofilm growth. Mucin- digesting enzyme sialidase was effective at dissociating all biofilms. This model can be used in the future to test different strategies of dysbiotic biofilm dissociation and enhancement of Lactobacillus biofilm in order to investigate treatments for Bacterial Vaginosis (BV) and reduce susceptibility to HIV transmission in women.

abstract: Thesis

abstract: Master of Science (MSc)


title: Inclusion Evaluation for Calcium Treated Steel and Its Relation to Caster Behavior in Industry

title: Inclusion Evaluation for Calcium Treated Steel in Industry

contributor:
Dogan, Neslihan
Materials Science and Engineering

subject: inclusion steelmaking alumina caster

abstract: Undesirable solid oxides and sulphides, known as inclusions, are an inherent product of the steelmaking process that can clog the steel flow during casting. Caster operators can break up the clogged material to improve flow, but this reduces steel quality and yield. Modifying these inclusions using calcium treatment and its effects on industrial processing conditions are the focus of this study. To effectively improve calcium treatment, experimental and industrial data are required to develop models to predict inclusion behaviour. The advantage of experimental testing is that the precise control of chemistry, temperature, alloying elements, and sampling can help identify the effects of each variable. The difficulty, however, is correlating experimental results to real-time industrial processing, where these variables are difficult to control individually. In industry, indirect observations of caster behaviour may give an idea of the effectiveness of the treatment, but this is after the fact. In this study, liquid steel samples were taken at different processing steps without any modification to the process itself to ensure normal shop conditions. The inclusion analysis was conducted using an automated Scanning Electron Microscope (SEM) and AZtech feature analysis software to determine inclusion characteristics, including population, composition, and size. This study shows 8 sequential calcium-treated steel heats in an industrial setting and their associated clogging behaviour during a cast. The study indicated that a few heats with undermodified alumina inclusions immediately or subsequently affected the casting process leading to a severe clogging event.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Understanding Scalability In A Twin Screw Wet Granulation

contributor:
Thompson, Michael
Chemical Engineering

subject:
Continuous manufacturing
Twin-screw granulation
Wet granulation
Scaling-up
Formulation
Microcrystalline cellulose
Granule quality
Process variables

abstract: Continuous wet granulation using a twin-screw extruder has attracted considerable attentions in pharmaceutical industry as it ensures consistent tablet quality at a high production rate. However, challenge still exists in controlling desired granule properties especially when different sized twin-screw granulators are used. This study therefore explored the potential of scalability of two sized twin-screw extruders and the how raw materials affect granules properties in two twin-screw extruders. The first study focuses on aspects of scaling using two twin-screw extruders, 18mm and 27mm. Dimensionless groups including Fr Number, Powder Feed Number and Degree of Fill (<30%) were studied to observe their influences on granule attributes. It was found that these dimensionless groups demonstrated inconsistent effects on granule properties and the effect of Powder Feed Number was highly dependent on Degree of Fill. Different extruder still exerts significant impact on granule properties. A scaling rule was established for median granule size (d50) only, but only moderate degree of fit was found.          Although a considerable number of studies have been published on controlled-release and extended-release excipients, little attentions have been given to the influence of microcrystalline cellulose (MCC) grades in twin-screw wet granulation. The second study therefore investigated the processability of five grades MCC from the Avicel® PH family using two twin-screw extruders again, 18mm and 27mm. Granule attributes including particle size, density, moisture, and strength were tested and it was found that MCC inherent density has the most significant impact on granule properties while particle size of MCC has minor positive effect on granule size. This study also concluded that better granule flowability and uniformity can be achieved by using low moisture, larger particle size and high density MCC as excipients.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Twin Screw Wet Granulation With Various Hydroxypropyl Methylcellulose (HPMC) Grades

subject:
Hydroxypropyl methylcellulose
Twin screw granulation
Liquid to solid ratio
Wet granulation
Feed rate
Continuous process
Processibility
Particle size distribution
Molecular weight

abstract:
Twin screw wet granulation has been proved as a feasible alternative for traditional batch granulation process due to its continuous processing feature; considered as a significant processing method especially in the pharmaceutical industry. This thesis will explore the processibility of twin screw wet granulation with various formulations.

The first section of the thesis focused on examining the processibility of wet granulation in a twin screw while using various grades of hydroxypropyl methylcellulose (HPMC) as an extended-release excipient. The method to find the processibility was by modifying the liquid-to-solid ratio for each formulation. The process window was defined by examining the amount of granules that fall in a pre-determined acceptable size range. This part focused on three substitution types of HPMC (Type 2910, Type 2208, and Type 2906) that varied in molecular weights. It was found that only Type 2910 HPMC showed a shift in the process window (also known as granulation range) in relation to the molecular weight of the formulations. A higher demand for binder liquid was found for higher molecular weight Type 2910 HPMC in order to form granules with acceptable sizes.

The second part of this thesis was focused on understanding the process variables that might influence the processibility of the HPMC formulations. This part examined the impact of feed rate on the granulation range of Type 2910 HPMC specifically was examined. Multiple feed rates were tested, and it was found that the granulation range for lower molecular weight Type 2910 HPMC was easier to shrink when higher feed rates were applied. A transition in the granule formation method from liquid-bridging to compaction with respect to the feed rate was found for low molecular weight HPMC, whereas the high molecular weight HPMC always formed granules through compaction at all feed rates due to strong water retainability.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: EXAMINING THE ROLE OF OIP5 AND PCSK5 EXPRESSION IN PAPILLARY RENAL CELL CARCINOMA (pRCC) TUMORIGENESIS

contributor:
Tang, Damu
Medical Sciences

subject: OIP5

subject: pRCC

subject: PCSK5

subject: Cancer

subject: Tumorigenesis

abstract: Renal cell carcinoma (RCC) is a cancer that originates from renal tubular epithelial cells in the kidneys. Studies focusing on RCC are vital as it accounts for around 3% of all human cancers as of 2014 and accounts for over 90% of cancers affecting the kidneys. Being a heterogenous disease, RCC consists of multiple subtypes including papillary RCC (pRCC) with a 10% incidence rate. The heterogenous nature of RCC makes it difficult to determine biomarkers and therapeutic treatments that can provide adequate treatment targeting RCC in different patients, which stresses the need to discover as many therapeutic targets as possible. OIP5, also known as Mis18β, is a 25-kDa protein that is accumulated in the telophase-G1 centromere during mitosis and plays a role in centromere/kinetochore structure formation and functionality. As Mis18β, it interacts with Mis18α in a heterotetramer complex to bind and localize centromeric protein A (CENP-A) to the proper centromere region to allow for formation for centromere/kinetochore formation and function. OIP5 is normally highly expressed in the testes but recent studies have suggested that OIP5 overexpression is linked to the progression of some types of human cancers, including promoting pRCC cell proliferation and tumorigenesis. Furthermore, past studies have shown that other genes may impact RCC progression through regulation of cell growth and substrate activation extending past just the cell cycle. PCSK5 is another target of interest of focus in this study. Known also as PC6, it is a proprotein convertase which acts on precursor proteins to turn them into their active forms through post-translational modification and plays a role in cell growth and bone remodeling. This study aims to investigate the role of OIP5 during RCC progression both in vitro and in vivo with a focus on pRCC as well as investigate the expression of PCSK5 in conjunction with OIP5 and pRCC. In vitro studies confirmed previous results that OIP5 promotes colony formation in ACHN pRCC cells. Using a bioluminescent reporter alongside ACHN OIP5 and ACHN empty vector (EV) cell lines, mice were injected through renal subcapsule transplantation. It was seen that, while OIP5 produced larger tumors over a wider area after 12 weeks, metastasis did not appear to occur as largely as hoped though this may be due to limitations of the model. Analysis of the ACHN xenografts showed increased expression of PCSK5 and PLK1 in the OIP5 tumors. For PLK1, this is likely due to the close nature of its function with OIP5 during mitosis while PCSK5 may be regulated by OIP5 through an unknown mechanism or through microRNA miR-101-5p. Despite this, mRNA levels of PCSK5 were insignificant between OIP5 and EV groups. pRCC patient data showing PCSK5 expression levels showed a minor correlation with OIP5 expression, as well as higher expression at later pRCC stages and leading to reduced survival probability. Overall, this thesis analyzes the relationship of OIP5 in RCC, specifically pRCC, and introduces PCSK5 as another intriguing target for further study in treating pRCC.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: This project focuses on renal cell carcinoma (RCC) which is a cancer that originates from renal tubular epithelial cells in the kidneys. The elusive and vast nature of RCC leads to many subtypes that differ histologically and biologically and thus require different diagnoses and treatments. By investigating the papillary RCC (pRCC) subtype, the goal is to identify potential biomarkers for pRCC that may aid in future clinical diagnosis and treatment. OIP5 is a protein scarcely investigated and past studies have shown its overexpression linked to pRCC progression and tumorigenesis, but further metastatic investigation is warranted. This study aimed to confirm OIP5 overexpression plays a role in cancer as well as use a luciferase firefly reporter gene to monitor OIP5’s role in tumorigenesis and metastatic potential in vivo using a live mouse model. Results suggest that OIP5 overexpression plays a role in enhanced tumor growth in vivo. PCSK5 is another fairly novel gene of interest in this study, and while research involving PCSK5 and RCC is severely limited, recent studies imply it may be affected by different oncogenes such as OIP5 and specific microRNA during ccRCC and pRCC progression. Therefore, this study investigated the presence of PCSK5 in OIP5 pRCC tissue and tumors. The results suggest that PCSK5 has a higher presence in OIP5 overexpressed cells and tissue as well as a higher mRNA presence. Figures created using public genomic datasets show a correlation between PCSK5 and OIP5 expression during the later stages of pRCC progression and with lower survival probabilities. This indicates the possibility of interaction between OIP5 and PCSK5 and if true, provides a potential link for finding more biomarkers for potential future therapeutic targeting.


title: Toward an understanding of human caregiving: investigations of brain, affective, and attitudinal responses to infants and children

contributor:
Hall, Geoffrey B.
Neuroscience

subject:
amygdala
response to infants
attitudes about children
fMRI
pet ownership
sex differences
postpartum depression
depression
maternal brain
caregiving
caregiving experience
cuteness
affective response
PPD
parity
maternal status

abstract: Optimal responsiveness to infant cues, an integral component of parental caregiving, is thought to be determined by multiple factors including maternal mood, previous experiences of caregiving, and infant characteristics. This thesis builds on previous work and details novel investigations of brain, affective, and attitudinal responses to infants/children. In the first two studies, we investigated the effects of maternal mood and parity (previous experiences of caregiving) on brain response to affectively positive infant pictures using functional magnetic resonance imaging (fMRI). We found that mothers with postpartum depression showed an elevated right amygdala response to infant pictures in comparison to mothers without PPD and depressed non- mothers. Further, functional connectivity between the bilateral amygdalae and the right insular cortex was negatively correlated with clinical symptoms (self-reported depression and anxiety). Therefore, as depression and anxiety symptoms increased amygdala to insular cortex connectivity decreases and vice versa. In the third study, we developed a novel data-driven infant cuteness (DDIcute) metric using the infant pictures presented in the first two studies. In line with ethological postulations on cuteness (infant characteristics), we found that infant pictures with a higher DDIcute score were associated with increased positive/approach-related affective responses and decreased negative/avoidant-related affective responses. In the fourth study, we investigated whether the sex differences in attitudes about children and childcare were moderated by pet ownership/care (previous experiences of caregiving). We found that pet ownership and care eliminated sex differences in attitudes about children and childcare. This effect was driven by males; compared to males with low levels of experience caring for pets, males with high levels of experience caring for pets had more positive attitudes about children and childcare.

abstract: Thesis

abstract: Doctor of Science  (PhD)

abstract: The work presented in this thesis adds to literature on human caregiving. In different studies we investigated brain, emotional, and attitudinal responses to human babies and children in people with and without depression as well as in people with different levels of caregiving experience. In the first two studies, we measured brain response to smiling baby pictures in depressed and non-depressed mothers and non-mothers. The amygdala is a brain region that is involved in the neurobiology underlying both depression and maternal behaviour. We found that amygdala response was the highest among mothers with postpartum depression. We also found that the coupled activity of the left and right amygdalae and another brain region called the insula was altered in mothers with postpartum depression. In the third study, we measured facial features of the baby faces presented in the first two studies to develop a measure of cuteness. We also measured emotional responses to the baby faces. We found that cuter infants elicited more positive and less negative emotional responses. In the fourth study, we measured differences in attitudes about children and caregiving between men and women who did and did not own and care for pets—specifically dogs and/or cats. We found that compared to men who did not own and/or care for pets, men who had more experience caring for pets had more positive attitudes about children and childcare.


title: A Hybrid Mechanics-evolutionary Algorithm-derived Backbone Model for Unbonded Post-tensioned Concrete Block Shear Walls

contributor:
El-Dakhakhni, Wael
Civil Engineering

subject:
backbone model
concrete block wall
Analytical approach
multigene genetic programming

abstract: Unbonded post-tensioned concrete block (UPCB) shear walls are an effective seismic force resisting system due to their ability to contain expected damage attributed to their self-centering capabilities. A few design procedures were proposed to predict the in-plane flexural response of UPCB walls, albeit following only basic mechanics and/or extensive iterative methods. Such procedures, however, may not be capable of capturing the complex nonlinear relationships between different parameters that affect UPCB walls’ behavior or are tedious to be adopted for design practice. In addition, the limited datasets used to validate these procedures may render their accuracy and generalizability questionable, further hindering their adoption by practitioners and design standards. To address these issues, an experimentally-validated nonlinear numerical model was adopted in this study and subsequently employed to simulate 95 UPCB walls with different design parameters to compensate for the lack of relevant experimental data in the current literature. Guided by mechanics and using this database, an evolutionary algorithm, multigene genetic programming (MGGP), was adopted to uncover the relationships controlling the response of UPCB walls, and subsequently develop simplified closed-form wall behavior prediction expressions. Specifically, through integrating MGGP and basic mechanics, a penta-linear backbone model was developed to predict the load-displacement backbone for UPCB walls up to 20% strength degradation. Compared to existing predictive procedures, the prediction accuracy of the developed model and its closed-form nature are expected to enable UPCB wall adoption by seismic design standards and code committees.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: DEVELOPMENT OF A NOVEL SEISMIC FORCE RESISTING SYSTEM: CONTROLLED ROCKING MASONRY WALLS WITH ENERGY DISSIPATION ACCESSIBLE CONSTRUCTED ATOP A STEEL BASE

contributor:
Wiebe, Lydell
Ezzeldin, Mohamed
Civil Engineering

abstract:
Conventional seismic design practices for reinforced masonry shear walls rely on ductility within the system, typically in the form of yielding of bonded reinforcement within the wall. While this is effective at dissipating energy, it comes at the expense of signi ficant damage in the plastic hinge region, as well as substantial residual deformations. This results in costly repairs being required following a seismic event, and in some cases demolition. Controlled rocking systems have been garnering considerable attention as a design approach that can mitigate these shortcomings. In a controlled rocking wall system, the wall is permitted to uplift from the foundation, reducing the lateral stiffness of the wall and producing a nonlinear response without relying on ductility within the wall.  This response is typically controlled with the use of unbonded post-tensioning (PT) tendons within the wall to provide a restoring force to the system and eliminate residual drifts. These systems are considered favorable for resilient design as the repair costs and the corresponding service shutdowns are minimized. In application to masonry systems speci fically, the PT tendons impose additional compressive stresses on the rocking toes, resulting in damage in these regions of the wall. In addition to this, the construction process of a masonry wall with unbonded PT can have challenging detailing considerations. Meanwhile, previous studies have also indicated that controlled rocking masonry systems (CRMWs) have relatively low inherent damping. Recent studies have shown promising results by testing CRMWs that rely on gravity loading for a self-centering response, omitting PT, and introducing energy dissipation inside the walls. However, as the devices are within the wall, they are difficult or impossible to repair if needed following a
seismic event. In this respect, the current thesis begins with an investigation of an externally mounted, replaceable energy dissipation device in the form of a flexural yielding cantilever arm. Experimental tests of the devices are analyzed, and the experimental results are used together with numerical modelling of the devices to develop design equations. Following this, a numerical study is conducted to evaluate the effectiveness of the proposed flexural arm devices within a new CRMW system. A new damage index for
reinforced masonry walls is introduced and then applied to compare the effectiveness of innovative CRMW design alternatives. This work ultimately proposes a system that has Energy dissipation Accessible, constructed atop a Steel rocking base (EASt-CRMW), which has a desirable self-centering response relying on gravity loads, with the flexural arms adding supplemental energy dissipation to the system. Building on these developments, two large-scale experimental studies on EASt-CRMWs are presented. The  first study reports the results of six EASt-CRMWs with various parameters. The results display a highly favorable hysteretic response, able to withstand drifts as high as 5% with negligible damage and residual drifts of less than 0.1%. This study then proposes two procedures to predict the monotonic force-displacement response of the EASt-CRMW system. The second experimental study investigates the performance of two additional EASt-CRMWs in which the flexural yielding energy dissipation devices were replaced and the walls retested, showing that the system can produce nearly identical results upon retesting. The study then validates the previously discussed numerical modelling approach for the further application of EASt-CRMWs, indicating that the model developed is indeed capable of capturing the actual response of the system and that the damage index accurately predicts the location and severity of damage within EASt-CRMWs.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Modern buildings are designed to withstand earthquakes without collapsing
by allowing for damage in specific parts of the structure that will not lead to
collapse or loss of life. This design philosophy is effective at ensuring safety,
but it allows damage even for high-importance buildings like schools and
hospitals, and it can result in extensive economic losses where many
buildings need to be repaired or demolished following an earthquake. This
thesis works toward developing a novel structural system that will experience
significantly less damage during an earthquake and be easily repairable. In
this respect, the thesis  first evaluates a new device that can be installed
easily at the base of a wall designed to concentrate the damage and control
the response of the wall during an earthquake. The thesis then develops a
numerical model to predict the response of the new wall system, in order to
optimize the design and ensure that the low damage performance is obtained.
Finally, a group of these novel walls are constructed and tested in a
laboratory in order to demonstrate the expected performance.


title: The Empty Tomb and the Resurrection Debate: Can a Starting Point be Established for Studying the Easter Events?

contributor:
Pang, Francis
Divinity College

subject: Resurrection, Empty Tomb, Easter, Habermas, Licona, Historical Jesus, McCullagh's conditions

abstract:
Scholars Gary Habermas and Michael Licona have created a research approach to study the historicity of Jesus’s resurrection called “historical bedrock.” This approach seeks to gather highly attested information about the Easter events that are agreed upon by the majority of scholars and then use this information as a starting point in studying the resurrection. A piece of information noticeably missing from the historical bedrock list is the empty tomb.
By using the empty tomb as a case study, this thesis is a critical analysis of Habermas and Licona’s historical bedrock approach. In it, I propose that historical bedrock be amended to what I call “baseline information.” Baseline information differs from Habermas and Licona’s approach in that less emphasis is placed on the role of scholarly consensus and the title does not convey the notion that the data within it is unquestionably historical.

abstract: Thesis

abstract: Master of Theology (Th.M)


title: Sex-specific changes to androgen receptor content following exercise and its influence on skeletal muscle adaptions

title: Sex-based differences in the androgen receptor response to exercise

contributor:
Parise, Gianni
Kinesiology

subject:
androgen receptor
skeletal muscle
exercise
sex-based differences

abstract: The androgen hormone is responsible for the growth of secondary sex characteristics in humans, such as skeletal muscle. Upon an exercise stimulus, the androgen receptor (AR) plays a crucial role in transmitting the androgenic signal to the nucleus which upregulates transcription of target genes related to growth of skeletal muscle. AR content has been implicated in the hypertrophic response between high and low responders following resistance exercise training (RET) in males. Little is known of the impact of AR expression on acute skeletal muscle damage and whether AR may influence the adaptive response to RET in females. This study aimed to investigate acute changes to AR content following a single bout of muscle damage-inducing exercise as well as sex differences during skeletal muscle repair and hypertrophy. A skeletal muscle biopsy from the vastus lateralis was obtained from 26 healthy, young males (n=13) and females (n=13) at baseline and 48 hours following a single bout of 300 eccentric contractions of the quadriceps. Subsequently, participants performed whole-body RET 4 times a week for 10 weeks, followed by a final skeletal muscle biopsy under resting conditions. Females had greater AR mRNA than males at baseline (~53%) and post-damage (~126%; p<0.05) while AR protein content increased in both sexes similarly following a single bout of eccentric exercise (p<0.05). Damage- and RET-induced satellite cell response was associated with percent change in AR protein content in a sex-specific manner (p<0.05). RET-induced percent change in nuclear AR content was ~17% greater in males compared to females (p<0.05). Interestingly, following RET, males experiencing the highest percent change in myofibre cross sectional area (CSA) exhibited greater changes in nuclear-associated AR protein content compared to females with the highest percent change in CSA. Collectively, AR protein content is elevated following acute eccentric exercise and 10 weeks of RET. Findings from this study suggests that males are more reliant on AR-related mechanisms than females to induce skeletal muscle hypertrophy following RET.

abstract: Thesis

abstract: Master of Science in Kinesiology

abstract: Skeletal muscle is crucial for proper function and activities of daily living. Many factors can regulate the amount and quality of skeletal muscle such as the expression of a protein known as the androgen receptor (AR). The AR plays a role in many cellular pathways that can ultimately dictate the growth and size of a particular tissue like skeletal muscle. There is currently minimal research about AR during skeletal muscle damage and in female skeletal muscle. Understanding how exercise increases AR content in males and females could progress our knowledge of how muscle adapts differently to exercise between sexes. Therefore, the purpose of this study was to understand how the AR behaves in the muscle, in males and females, after a single session of exercise that damages the muscle or after long term resistance exercise (RE). We observed that the AR gene is more abundant in females than males at rest and following damaging exercise. Furthermore, we show that AR protein content increases in both sexes following a single session of damaging exercise and after chronic RE. Muscle stem cells are a component of the muscle that helps to heal muscle after exercise has been performed. In the current study, we demonstrate that AR has a closer relationship to muscle stem cells in males relative to females. Further, AR seems to be more closely linked to muscle growth in males than females. Altogether, AR is a component of the muscle that adapts to exercise differently in males and females. This study may, in part, explain how skeletal muscle responds differently between sexes after exercise.


title: Mental Fatigue, Motivation, and Physical Activity Decision-Making

contributor:
Bray, Steven R
Kinesiology

subject:
mental fatigue
motivation
physical activity
exercise
effort-based decision-making

abstract:
Previous research has demonstrated mental fatigue impairs subsequent physical performance, however, current understanding of the role of mental fatigue on physical activity and exercise decision-making is limited for several reasons. For example, research examining the relation between mental fatigue and physical activity behaviors has relied on experimental methods and physical tasks performed in controlled laboratory settings with limited applicability to everyday experiences. In addition, direct measures of motivation commonly used within the literature are subject to biases, highlighting the importance of alternate methods for assessing motivation using indirect measures. To address these limitations, methods with stronger ecological validity are needed to extend research from controlled, experimental settings to measure mental fatigue in naturalistic settings and provide a diverse range of physical activity and exercise task options. The purpose of this dissertation is to investigate the associations between mental fatigue, motivation, and physical activity behavior to further our understanding of the decision- processes behind choosing to engage or not engage in physical activity.
Study 1 examined the effects of mental fatigue on the decision to engage in an acute bout of moderate-to-vigorous intensity physical activity or a competing sedentary alternative using a mixed-methods study design. Results showed a sequential mediation effect of mental fatigue on choice through subjective perceptions of effort, benefits, and costs. Results of qualitative analyses highlight individual-level consequences of completing cognitively demanding and non-demanding tasks on physical activity decision-making. Findings are consistent with previous research and demonstrate subjective perceptions of engaging in physical activity account for acute choice.
Study 2 investigated the effects of intensity and duration on people’s subjective valuations of physical activity tasks using an effort discounting paradigm and the potential moderating effect of mental fatigue on subjective valuations of physical activity. Results showed a reduced willingness to engage in physical activities of higher intensities and longer durations. Further, there was partial evidence suggesting a reduced willingness to engage in vigorous-intensity physical activity with higher levels of mental fatigue. Findings provide novel insight towards factors influencing people’s motivation for engaging in physical activity with some evidence that mental fatigue affects people’s motivation to exert physical effort.
Study 3 examined the association between mental fatigue, subjective evaluations of perceived benefits and costs, and moderate-to-vigorous intensity physical activity using ecological momentary assessment and accelerometry. Results demonstrate significant associations between all study variables. Although a multilevel mediation model was not significant, evidence supports a partial mediation effect attributable to benefit vs. cost valuation on the relation between mental fatigue and physical activity. Results provide insight into real-time predictors of motivation and physical activity, highlighting the complex relationships between psychological variables and behavior in people’s everyday decision making.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Mental fatigue has been shown to impair subsequent physical performance, however, the effect of mental fatigue on the decision to engage or not engage in physical activity has received limited attention. This thesis addresses several gaps in the literature by examining potential mediators of the mental fatigue – physical activity decision- making relation, using qualitative methods to understand factors affecting people’s choices, and applying methods with strong ecological validity. Findings show perceived effort and benefit vs. cost valuations associated with engaging in physical activity predict the choice to engage in PA. Further, mental fatigue increases perceptions of effort and decreases benefit vs. cost valuations. Collectively, results from this dissertation align with and extend theoretical frameworks of behavioral economics, motivation, and effort-based decision-making.


title: Mapping the chemostratigraphy of the Upper Cretaceous Mancos Shale, New Mexico, USA, using high-resolution XRF core scanning techniques.

contributor:
Reinhardt, Eduard G
Earth Sciences

subject:
Sedimentology
Chemostratigraphy
Micro-X-ray fluorescence
Mancos Shale

abstract: High-resolution (500 um) elemental data were collected from marine sedimentary rocks of the Upper Cretaceous Western Interior Seaway of North America using an Itrax uXRF core scanner in order to create detailed chemofacies and chemostratigraphic profiles to aid in the construction of sequence-stratigraphic frameworks in mudstone successions. Chemofacies were created for several depositional environments associated with siliciclastic shorelines such as fluvial channels, delta front, prodelta, mudbelt, and sediment-starved shelf using an unsupervised, hierarchical clustering algorithm known as a Self-Organising Map, which is topologically invariant so the clusters could be further grouped into superclusters to investigate variability within the depositional environments at a number of scales. Chemostratigraphic mapping was done on a 94-metre long section of Mancos Shale from a single well. The high-resolution data showed marine transgressive-regressive cycles at several orders that could be correlated to shoreline trajectories established in near-shore facies. Both the point of maximum regression, which indicates the initial flooding during a relative sea-level rise, and maximum transgression (i.e., the maximum flooding surface), could be accurately identified indicating that a complete cycle was recorded at each order. The data between the two represents a correlative conformity, which can provide palaeoenvironmental information that is not retained in near-shore facies. This research proves that marine mudstones retain a more complete record than near-shore sandstones and that they contain a wealth of palaeoenvironmental information. The high-resolution sampling of a uXRF core scanner is the only method that can fully map the chemostratigraphy of these mudstones, which are often visually homogeneous. By applying these techniques to other mudstone cores from the Western Interior Seaway or another Upper Cretaceous epeiric sea, high-resolution sequence-stratigraphic frameworks can be developed that can be used to reconstruct palaeoclimates at local to global scales.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Elemental data were collected at high-resolution sampling (0.5 mm) from sedimentary rock core to determine environmental changes and shoreline trajectories during the Upper Cretaceous. Chemofacies, which group the intervals based on their elemental signature, were developed using a statistical clustering algorithm to investigate the character and variability of several depositional environments with respect to their proximity to shoreline and relative water depth. Chemostratigraphy, which maps the elemental variations through the core, was used to show shoreline advance and retreat due to relative changes in sea level, which could be correlated with previous studies. This is the first time in which these high-resolution shoreline trajectories could be established in marine mudstones that are typically visually homogeneous.


title: Identifying streamflow changes in western North America from 1979 to 2021 using Deep Learning approaches

contributor:
Carey, Sean
Earth and Environmental Sciences

subject:
Streamflow
Deep Learning
Climate Change
Trend Analysis

abstract: Streamflow in Western North America (WNA) has been experiencing pronounced changes in terms of volume and timing over the past century, primarily driven by natural climate variability and human-induced climate changes. This thesis advances on previous work by revealing the most recent streamflow changes in WNA using a comprehensive suite of classical hydrometric methods along with novel Deep Learning (DL) based approaches for change detection and classifica- tion. More than 500 natural streams were included in the analysis across western Canada and the United States. Trend analyses based on the Mann-Kendall test were conducted on a wide selection of classic hydrometric indicators to represent varying aspects of streamflow over 43 years from 1979 to 2021. A general geograph- ical divide at approximately 46◦N degrees latitude indicates that total streamflow is increasing to the north while declining to the south. Declining late summer flows (July–September) were also widespread across the WNA domain, coinciding with an overall reduction in precipitation. Some changing patterns are regional specific, including: 1) increased winter low flows at high latitudes; 2) earlier spring freshet in Rocky Mountains; 3) increased autumns flows in coastal Pacific North- west; and 4) dramatic drying in southwestern United States. In addition to classic hydrometrics, trend analysis was performed on Latent Features (LFs), which were extracted by Variation AutoEncoder (VAE) from raw streamflow data and are considered “machine-learned hydrometrics”. Some LFs with direct hydrological implications were closely associated with the classical hydrometric indicators such as flow quantity, seasonal distribution, timing and magnitude of freshet, and snow- to-rain transition. The changing patterns of streamflows revealed by LFs show direct agreement with the hydrometric trends. By reconstructing hydrographs from select LFs, VAE also provides a mechanism to project changes in streamflow patterns in the future. Furthermore, a parametric t-SNE method based on DL technology was developed to visualize similarity among a large number of hydro- graphs on a 2-D map. This novel method allowed fast grouping of hydrologically similar rivers based on their flow regime type and provides new opportunities for streamflow classification and regionalization.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Drivers of hydrological response for distinct wetland complexes in a high latitude alpine watershed

contributor:
Carey, Sean, K.
Earth and Environmental Sciences

subject:
Hydrology
Wolf Creek Research Basin
Wetland
Northern

abstract: Alpine wetlands provide important hydrological and ecological services, and in rapidly warming northern environments are at risk as frozen ground thaws and evaporation increases. The hydrological role of wetlands is highly variable depending on the season and their position in the landscape. Despite their extensive presence, there is limited understanding of cold, alpine wetlands due to logistical challenges. The objective of this research is to evaluate water table dynamics and seasonal water sources for two distinct wetland complexes in the Wolf Creek Research Basin (WCRB), Yukon: a valley-bottom wetland and a high-elevation isolated wetland. This study used hydrometric data and stable water isotopes to track the seasonal evolution of water table depth and source waters. Results showed that in high-elevation isolated wetlands, ponds were restored in the spring after snowmelt and then experienced progressive drying with open water areas never returning to spring extent. Pond waters were continually enriched and evaporated throughout the season suggesting little lateral inputs, and as the temperature warmed, exchanges were largely vertical with considerable water lost to evaporation. In the valley bottom wetland, water levels remained high throughout the year as the water was supplied continuously to the wetland from upland areas. While there were some small reversals in flow through the base of the wetland, stable isotopes suggest the continued supply of depleted meltwater throughout the course of the year. Implications from this suggest that isolated ponds in WCRB are susceptible to drying under climate warming as a longer snow-free season will increase evaporation and the window for drainage. In contrast, the valley-bottom wetlands are less vulnerable due to their position in the landscape and the presence of beaver ponds that impound water.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Alpine wetlands provide important hydrological and ecological services. This thesis examined two alpine wetland types in the Wolf Creek Research Basin, Yukon: a valley bottom wetland and a high elevation isolated wetland. Snowmelt was the main source of water for isolated ponds and in summer, exchanges were vertical as rainfall increased water level whereas evaporation and infiltration steadily lowered it. In the valley-bottom wetlands, hillslopes continuously supplied water to ponds, and water tables remained near the surface throughout the summer. The presence of beaver dams was important in retaining water and limiting water level response to rainfall. Results from this research enhances our understanding of the factors controlling the presence of wetlands and their sustainability under a warming climate.


title: The Right Tools for the Job: Design Choices of Parallel First Principle and Data-Driven Hybrid Modelling for Prediction and Control of Batch and Fed-Batch Reactors

contributor:
Mhaskar, Prashant
Chemical Engineering

subject:
Model
Predictive
Control
Hybrid
Subspace Identification
Batch
Reactor
Reaction
First Principle

abstract: Third submission of my master thesis, first one didn't finish for some reason, the second I think I forgot to include my name.

abstract: This thesis focuses on the creation of new parallel hybrid model designs for prediction and control in batch and fed-batch reactors within Model Predictive Control (MPC) frameworks. In the hybrid model, the first principle (FP) explains the dynamics and the residual Subspace Identification (SID) model explains the error between the FP and the process. Modifications to the structure of the hybrid model are motivated by limitations of MPC frameworks. MPCs need accurate models to explain the system dynamics to make informed control decisions, and mechanistic models can be difficult to implement due to challenges of solving the optimization problem in real time. Two tools are demonstrated to help solve these problems. The first tool, Residual First Principle 0 Hybrid (RFP0H) model, helps to deal with the intractability of a mechanistic model in a hybrid modelling framework. The input for the FP model is kept constant and the SID predicts the error between the first principle and the process. Allowing for the desired output to be subtracted by the predicted FP to create a desired error value. Thus, MPC control only needs to be solved using the linear SID model in a linear or quadratic framework. Making a potentially intractable problem, tractable in MPC. This is demonstrated using a simulated fed-batch crystallization process. The second tool, Scaling Factor First Principle 0 Hybrid (SFFP0H) model, modifies the hybrid model structure to multiple the sub-models’ outputs together. The SID data driven model predicts a factor to scale the FP output for the process prediction. The results demonstrate that the SFFP0H model has increased predictive ability and has smaller variability in control compared to the RFP0H model. Helping to solve the problem of needing accurate models within an MPC formulation. This is demonstrated by using a laboratory scale batch polymerization process.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Three Essays on Financial Volatility Modeling

contributor:
Maheu, John M.
Finance

subject:
Financial Volatility
Forecasting
Financial Returns
Risk Management

abstract:
This thesis studies three important topics in modeling financial volatility. First, the jump clustering in ex post variance and its implications on forecasting, second, the underlying distribution of stochastic volatility and third, the role of non-Gaussian multivariate return distribution combined with a realized GARCH framework.
     The first chapter is on variance jumps. Financial markets present unexpected and large jumps,
due to unobserved news flow. I focus on modeling the ex post variance jumps, their time-
dependent arrivals and their sizes. I use a discrete-time bivariate model, with two autoregressive
components which capture the long and short-run memory of the ex post variance measures. I
estimate contemporaneous and time-dependent jumps in the log-measures of realized variance
and bipower variation. The results from S&P500 show that the variance jumps are frequent
and persistent. I examine the ability of jumps to forecast returns and ex post variance densities
over horizons of up to 50 days out-of-sample. Modeling jumps significantly improves ex post
variance density forecasts for all horizons and improves forecasts of the returns density.
      In the second chapter I explore the empirical non-Gaussian features of stochastic volatility.
The standard assumption in a stochastic volatility specification is typically a restrictive Gaussian
AR(1) structure. I drop this assumption and instead I assume that latent log-volatility follows
an infinite mixture of normals with a Dirichlet process prior. The ex post measure of realized
variance is used as a source of information to help identify the unknown distribution of log-
volatility. Results from major stock indices show strong evidence of non-Gaussian distributional
behaviour of volatility. The proposed framework captures asymmetry and thick tails in returns
as well as realized variance. In out-of-sample forecasting, the new model provides improved
density forecasts for returns, negative returns and log-realized variance.
      In the third chapter a new approach for multivariate realized GARCH models is proposed.
Two new extensions that have non-Gaussian innovations are developed. The first one is a parametric version, with multivariate-t innovations. The second one is a nonparametric approximation of the return distribution using an infinite mixture of multivariate normals given a Dirichlet
process prior. The proposed models are based on the assumption that the realized covariance
follows an Inverse Wishart distribution with conditional mean set to the conditional covariance
of returns. The benefits of the proposed models are demonstrated from density forecasting and
portfolio applications. Results from two equity datasets indicate that modeling the tail behaviour
improves return density forecasting compared to the Gaussian assumption. The proposed models produce the least volatile global minimum variance portfolios out-of-sample and provide improved forecasts of Value-at-Risk and Expected Shortfall.

abstract: Thesis

abstract: Doctor of Business Administration (DBA)


title: DISMANTLING BIFURCATING DISCOURSES OF HOMELESSNESS: TOWARD AN ONTOLOGY OF LAND/BODY SIMULTANEITY AND RESISTANCE TO THE SEVERING VIOLENCE OF OCCUPATION, SETTLEMENT AND DEVELOPMENT

contributor:
Joseph, Ameil
Social Work

subject: Homelessness, Space/Place, Anti/De/Post Colonial, Ontology, Policy, Housing, Resistance, Institutionalization, Discourse, Historiography, Occupation/Settlement/Development

abstract: This thesis inquires into the transformative potentials and possibilities of attending specifically to matters of occupation, settlement and development for rearticulating discourses and knowledge relations on homelessness to undermine the projects of separation of land from body. Through an historiographical analysis applied to the National Housing Strategy (NHS), Reaching Home (RH), and Housing First (HF), as contemporary Canadian iterations of housing and homelessness policy and practice, this work critically examines representations, attentions, and omissions to understand, engage, and intervene on considerations of the common projects that constitute discourses on homelessness. This analysis found that contemporary understandings communicate and define the homeless body as an identity of lack, novel to the neoliberal contemporary that omit attentions to homelessness as a colonial capitalist process implicated in ongoing, relational, and severed histories of violence. This work also revealed that NHS, RH, and HF operationalize solutions to ending homelessness through abstracted/eugenic ‘expert’ medicalized, liberalized, and market-based systems/taxonomies of worth that reify/silo/silence/erase knowledges through and by embodied projects and discourses of ‘rights’, justice, care, and help. While NHS, RH, and HF claim ‘housing as a right’ and advocate deinstitutionalization via a discourse of ‘choice’ in a market system, this work revealed these discourses to be part of a redeveloped economic institutionalized politics severed, rearticulated, and managed in the social sphere. These findings are considered as a violence of Land/Body bifurcation possible through and by the imposition of claims on body and land in the creation and maintenance of ideal citizen subjects as settlement subjectivities becoming self-determined rights holders, consumers, tenants, and citizen placeholders in a commodified market for home. Overall, this project aims to contribute to a resistance of the severing violence of occupation, settlement, and development through an ontology of Land/Body simultaneity offering possibilities for transformational intervention into the context from which the ideas of homeless bodies and landscapes emerge.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Exploring the Meaningful Partnership of Elders in Indigenous STBBI Research

contributor:
Jackson, Randall
Social Work

subject: Indigenous, Métis, Inuit, First Nations, Elders, STBBI, HIV/AIDS research, engagement, partnership, collaboration, Indigenous and decolonizing methodologies, Indigenous ways of being, knowing, and doing, qualitative research

abstract: In collaboration with Elders, this study explores the great need for their meaningful partnership in STBBI (sexually transmitted and/or bloodborne infections) research.

abstract: Indigenous Elders are highly regarded as community leaders, traditional healers, and experts of Indigenous cultures and knowledges (Clark & Wylie 2021; Hadjipavlou et al., 2018; Lessard et al., 2021). The meaningful partnership of Elders in Indigenous STBBI (sexually transmitted and/or bloodborne infections) research has become increasingly recognized as an integral part of developing decolonial research processes, ensuring the implementation of Indigenous methods in STBBI research, and increasing the sexual health and wellbeing of Inuit, Métis, and First Nations communities through the development of culturally and ethically responsive research (Flicker et al., 2015; Hillier 2020; O’Brien et al., 2020). This study sought to expand upon and connect current literature with the expertise and guidance of Indigenous Elders who have been involved in STBBI research. Thirteen Elders were recruited nationwide to participate in three virtual Talking Circles to explore their meaningful partnership in Indigenous STBBI research and to offer guidance to researchers on how to strengthen these research partnerships in the future. Five overarching themes emerged from the thematic analysis of these Talking Circles: (1) Understanding the historical and ongoing impacts of colonialism and the need to decolonize STBBI research; (2) Prioritizing the knowledge and lived experience of Elders and Indigenous people living with STBBI throughout the research process;  (3) Centering spirituality and ceremony in Indigenous STBBI research; (4) The importance of implementing Indigenous methodologies in STBBI research; and (5) Foregrounding Indigenous ways of being, knowing, and doing in STBBI research. This study offers future Indigenous STBBI researchers a robust foundation to build meaningful research partnerships with Elders to improve STBBI research and benefit the sexual health and wellbeing of Métis, Inuit, and First Nations communities.

abstract: Thesis

abstract: Master of Social Work (MSW)