Restricted Theses and Dissertations
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This collection is the result of a joint project between the Faculty of Graduate Studies and Libraries and Cultural Resources which provides Graduate students with the opportunity to archive their thesis with University Archives in our digital repository.
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- ItemEmbargoAqueous Chemical Solution Deposition of Epitaxial Lead-Free Ferroelectric Sodium Potassium Niobate (KNN) thin films(2023-05-12) Mohammed, Ahmed Zaher; Dolgos, Michelle; Birss, Viola Ingrid; Shi, Yujun; Roberts, Edward; Shimizu, GeorgePotassium Sodium Niobate (KxNa1-xNbO3, KNN) thin films were fabricated on SrTiO3 (STO) substrates using an environmentally friendly aqueous Chemical Solution Deposition (CSD) approach, employing water-soluble Na, K, and Nb polyoxometalate precursors. This green route for KNN thin film fabrication offers reduced environmental impact and potential industrial scalability. The annealing recipe was optimized through a detailed investigation, finding that a one-minute annealing at 700°C after each deposition yielded the best structural properties. The impact of varying the K+/Na+ stoichiometry on the films' structural properties was systematically examined. The investigation demonstrated a trend between the K+/Na+ molar ratio in the precursor solution and the strain-state and lattice parameters of the resulting films, suggesting adding 50% excess potassium in the precursor solution is promising for optimal ferroelectric performance. Leveraging the versatility of the aqueous synthesis, lithium was incorporated as a dopant in the precursor solution. Different Li concentrations were investigated, and it was determined that a 6% Li concentration improved the films' structure compared to undoped samples. This demonstrates the potential of aqueous deposition for incorporating dopants to enhance material properties. The study further highlighted the potential for strain engineering and additional dopant incorporation using the aqueous CSD method, opening up avenues for further exploration and optimization of KNN thin films' properties.
- ItemEmbargoInvestigating the Mediating Fusion Machinery and Biological Role of a Novel Late-Stage Phagocytic Event(2023-05-16) Nguyen, Jenny Ai; Yates, Robin; Canton, Johnathan; Frank, Jirik; Humberto, JijonThis dissertation investigates eructophagy, a newly discovered process in which macrophages release soluble contents of the phagolysosome (PL) through fusion with the plasma membrane (PM). This study aims to determine the molecular machinery involved in membrane fusion during eructophagy and its role in antigen presentation. Macrophages play a crucial role in combating infections and maintaining homeostasis by phagocytosing invading pathogens and cellular debris into the phagolysosome (PL). It was believed that the contents of the PL that were not employed for antigen presentation were completely digested and recycled as primary building blocks, while indigestible material were stored in lysosomes. Therefore, how macrophages make immunostimulatory molecules, such as nucleic acids, polysaccharides, or lipids, available for immune detection is not well understood. Recently, eructophagy emerged as a novel process that allows macrophages to expel soluble components of the PL into the external environment, potentially serving as a form of intercellular communication to disseminates otherwise unavailable bioactive molecules during inflammation. The molecular machinery underlying membrane fusion during eructophagy has not been elucidated. To address this, we used a lentiviral short hairpin RNA knockdown library of conditionally immortalized monocytes to target genes involved in fusion, fission, and trafficking events to examine their potential role in eructophagy. A novel microscopy-based assay that reports eructophagy events as flashes of fluorescence was used, and it was found that eructophagy is dependent on genes involved in degradative and secretory autophagy. This led to further exploration of the role of autophagosomes in eructophagy. Vesicular blebs protruding from PLs were observed before eructophagy and vanished after resolution. Interfering with autophagosome-PL or autophagosome-PM fusion modulated the incidences of PL-associated blebs, thereby suggesting that these structures are autophagosomes. Immunofluorescence demonstrated that blebs colocalize with markers of the mature autophagosome ATG5 and LC3B. Furthermore, using supernatant transfer and triple cell coculture experiments, we demonstrate that eructophagy is used by macrophages to transfer antigens to vicinal APCs to enhance antigen presentation to T cells. Collectively, this dissertation reveals a novel mechanism of macrophage-mediated antigen transfer and suggests a putative model in which blebs are mature autophagosomes bridging the PL to the PM to facilitate eructophagy.
- ItemEmbargoMotor Learning after Stroke(2023-05-10) Moore, Robert Taylor; Cluff, Tyler; Dukelow, Sean; Kirton, Adam; Hill, MichaelMotor learning is a pillar of stroke rehabilitation. Indeed, many therapeutic protocols and interventions are based on principles of motor learning. One of the assumptions made in rehabilitation is that motor learning remains intact after stroke and can be leveraged to facilitate recovery. However, a growing body of evidence has shown that motor learning can be impaired after stroke. Our understanding of how stroke influences the neural and behavioural processes that support motor learning is incomplete. This raises questions about how well our current understanding of motor learning, derived predominantly from studies in healthy adults, applies to stroke rehabilitation. The following dissertation describes four studies that examine reaching movements and a specific type of motor learning known as motor adaptation. This type of learning encompasses the processes that help to maintain accurate movements amidst changes in the body, environment, and task demands. Across three experiments in healthy adults (Chapter Two) and three experiments in participants with stroke (Chapters Three, Four, and Five), we characterized motor adaptation in health and disease. Overall, the works in this dissertation demonstrate the utility of robotics for quantifying motor adaptation. Impaired adaptation after stroke was associated with several clinical variables including: the side of the stroke affected limb (i.e., dominant versus non-dominant), time post-stroke, movement performance, proprioceptive abilities, and clinical assessments of motor impairment and functional independence. Notably these variables accounted for only a small portion of the variance in motor adaptation after stroke, suggesting that other clinical variables (e.g., lesion characteristics or other types of impairments) may be associated with adaptation after stroke. Our results reveal widespread impairments in visuomotor adaptation after stroke and generate numerous questions about the basic mechanisms underlying motor adaptation and how adaptation applies to stroke rehabilitation.
- ItemEmbargoDesigning Peptide-Based Biosensors for the Diagnosis of Crystal Arthropathies(2023-05-15) Meyer, Jessica Marie; Derksen, Darren; MacCallum, Justin; Ling, Chang-Chun; Kimura-Hara, SusanaPeptides play a vital role in nature as they engage in many complex interactions which include forming proteins and binding with other biomolecules. The interactions between peptide and various biomolecules, such as proteins, carbohydrates, and enzymes, have been well-studied as they guide many processes in the human body. However, peptide interactions with solid surfaces are not well understood. This work explores the binding of peptides to the surfaces of monosodium urate (MSU) crystals. MSU crystals accumulate in the joints of patients with acute gout, one of several types of crystal arthropathy. Other arthritides, including pseudo-gout and osteoarthritis, present similar symptoms to gout, but are characterised by accumulation of calcium pyrophosphate and hydroxyapatite crystals respectively. Misdiagnosis between these diseases when using current methods of crystal analysis. This thesis aimed to produce a fluorescent, peptide-based biosensor with specific binding to MSU crystals for the purpose of future development of a more accurate and efficient method for diagnosing gout. This was accomplished by first analysing data provided by characterising the MSU surface, peptide binding interactions, and proposing optimal peptide sequence candidates through computational analysis. Methods were then developed to synthesise, fluorescently label, and purify the peptide candidates. Analytical methods, including RP-HPLC-UV, fluorescence spectrometry, and CD polarimetry, were employed to investigate the peptide’s binding affinities, fluorescent activity, and secondary structure. Finally, fluorescence microscopy images of the MSU-bound fluorescent peptides were analysed to compare relative binding of different peptide sequences to MSU crystals. Ultimately, this work was successful in identifying and synthesising fluorescent peptides that display strong, uniform binding to MSU crystals and enhance detection of the crystals via fluorescence microscopy. The findings of this thesis could be used in further studies to potentially develop an effective, peptide-based biosensor for gout.
- ItemEmbargoTibial-fibular morphology: variation, sexual dimorphism, and mechanical implications(2023-05-01) Bruce, Olivia Leigh; Edwards, William Brent; Boyd, Steven Kyle; Kuo, Arthur; Roach, Koren Elaine; Jordan, Matthew James; Lenz, Amy LorraineStress fractures are common injuries among runners and military personnel associated with the mechanical fatigue of load-bearing bone. The tibia is the most frequently fractured site and females are at much greater risk than males. Bone geometry and density are hypothesized risk factors for stress fracture and are thought to contribute to the disparity in risk between sexes via their influence on bone strain magnitude which is strongly related to the rate of mechanical fatigue. However, covariation between these two complex factors and their influence on the strain environment of the tibia are not well characterised. The overarching goal of this thesis was to develop a more nuanced understanding of the mechanical implications of tibial-fibular geometry and density variations present in young active adults. A series of studies were performed utilizing a combination of advanced medical imaging, statistical approaches, gait data, and the finite element method to characterise and quantify covariations in whole-bone tibial-fibular geometry and density distributions and their influence on bone strain. Transverse diaphyseal geometry and sagittal curvature were identified as key features that likely influence stress fracture risk, demonstrating substantial effects on finite element-predicted bone strain. Additionally, the average female illustrated a narrower tibia which resulted in elevated bone strain when compared to the average male, suggesting that bone geometry likely contributes to the disparity in stress fracture risk between sexes. As we work towards improving predictive models and developing effective screening tools for stress fracture risk, these findings provide insights into key features of bone geometry and density that will need to be accurately characterised. Landmark- and anthropometric-based predictions of tibial-fibular geometry and density were not sufficiently accurate, indicating that some level of advanced medical imaging data will be necessary to generate personalised models or characterise geometry and density features associated with stress fracture risk.