title: Limit Theorems and Applications of Time Series with Varying Coefficients

contributor:
Feng, Shui
Guo, Yiping
Mathematics and Statistics

abstract:
In this thesis, we study the asymptotic behaviour and applications of a class of time
series with varying coefficients. More specifically, we establish the large deviation principles
and the moderate deviation principles for the first-order autoregressive models.
The ADF and KPSS, two different methods, are then used to test the stationarity and
conintegration of the annual average temperature series for the hemispheric, continental,
and individual cities. We confirm that these series adhere to varying coefficient model.
Finally, we examine some regions’ extreme rainfall series and show that they should
follow the ARCH model.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: DIFFERENTIATING BETWEEN HEPARIN-INDUCED THROMBOCYTOPENIA AND VACCINE-INDUCED THROMBOTIC THROMBOCYTOPENIA ANTIBODY EPITOPES ON PF4

contributor:
Nazy, Ishac
Biochemistry and Biomedical Sciences

abstract:
ABSTRACT:
Introduction:
Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse event that occurs in approximately 5% of patients following heparin administration to prevent clotting during cardiac as well as orthopedic surgeries, kidney dialyses and blood transfusions. HIT is mediated by antibodies that bind complexes of platelet factor 4 (PF4 or CXCL4) and heparin that cross-link Fc receptors on platelets to cause platelet activation, thrombocytopenia with or without thrombosis, potentially leading to death. Recently, a new anti-PF4 disorder has emerged in response to COVID-19 adenoviral-vector based vaccines against SARS-CoV-2 known as vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT is a rare but serious adverse syndrome reported 5-30 days after administration of a COVID-19 adenoviral vector vaccine (Oxford-AstraZeneca ChAdOx1 nCoV-19 (AZ) and Johnson & Johnson/Janssen (J&J/Janssen)) and is characterized by thrombocytopenia and thrombosis in unusual locations, including cerebral sinus venous thrombosis (CVST). HIT and VITT are characterized by platelet-activating antibodies that bind to PF4 and often lead to thrombocytopenia and/or thrombosis.  There are two types of platelet-activating antibodies that lead to HIT, antibodies that activate platelets only in the presence of heparin (heparin-dependent (HD)) and antibodies that can activate platelets in the absence of heparin (heparin-independent (HI)). In VITT, the two types of platelet-activating antibodies are ones that only activate platelets in the presence of PF4 (PF4-dependent) and antibodies that can activate platelets in the absence of PF4 (PF4-independent).  We hypothesize that the binding sites of HIT and VITT antibodies on PF4 differ and that identifying these sites could be relevant to differentiate between both anti-PF4 disorders.

Methods:
All 70 PF4 mutants produced by alanine-scanning mutagenesis (ASM) were expressed and purified from E. coli BL21 (DE3) cells. ASM was performed using HIT (n=10) and VITT (n=14) patient samples to determine the binding sites of HIT and VITT antibodies on PF4. Clinical outcomes of CVST, DVT, PE incidences in VITT patients with PF4-dependent and PF4-independent antibodies were also analyzed. In addition, ASM was performed on the HIT-mimicking monoclonal antibodies (1E12, 1C12, 2E1, P4B1, P3D4, P3E10) to confirm the pathogenic antibody binding sites of HIT antibodies on PF4. Finally, all 70 PF4 mutants were screened against HIT (n=22), VITT (n=9) and non-HIT (n=12) patient samples and we identified 10 PF4 mutants that differentiate between HIT and VITT using an EIA.

Results:
We confirmed all 70 PF4 mutants were free of contaminants compared to bacterial lysate by visualizing the purity using gel electrophoresis.  Using a cut-off of 50% or greater reduction in antibody binding to PF4 mutants compared to wild-type PF4, we determined that most monoclonal antibodies that mimic platelet-activating HIT antibodies, as well as antibodies purified from HIT patients bind to a site on PF4 like the KKO site, a known monoclonal antibody against PF4/heparin complexes that mimics platelet-activating HIT antibodies. While most VITT antibodies recognize a site on PF4 overlapping the heparin-binding site, we found a subset of VITT patients have antibodies that recognize an additional site on PF4 that is like the KKO site. By observing the incidences of clinical thrombotic characteristics in VITT patients, it was determined that CVST (6/14, 42.9%), DVT (4/14, 28.6%), and PE (4/14, 28.6%) were the most common types of thrombosis. This unusually high incidence of VITT is not typically seen in HIT.  Information on the binding characteristics of HIT and VITT anti-PF4 antibodies have sparked interest on whether there are characteristics that can help differentiate between HIT and VITT. After screening the 70 PF4 mutants against HIT and VITT patient samples, we then identified 10 PF4 mutants (H23A, R20A, T25A, E28A, K46A, R49A, K50A, K62A, K65A, K66A) that help differentiate between HIT and VITT in an EIA. We also screened the 70 PF4 mutants against non-HIT patients, identified as individuals that have non-platelet activating anti-PF4/heparin antibodies. We found that 5 PF4 mutants (K14A, H23A, V29A, T38A, K50A, K66A) help differentiate HIT from non-HIT in an EIA.

Conclusion:
Purifying PF4 mutants reduced background reactivity likely caused by contaminants in assays using bacterial lysate. ASM using PF4 mutants revealed that there are 2 distinct binding sites on PF4 that are recognized by either HI and HD HIT or anti-PF4 VITT antibodies. We confirmed that the molecular characteristics of antibodies from VITT and HIT patients dictate the platelet activation profiles in these disorders and can be used to separate VITT from HIT antibodies in the EIA.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Characterization of VWF in Mouse and Human Endothelial Cells

contributor:
Matino, Davide
Medical Sciences

abstract: Von Willebrand factor (VWF) is a protein that secreted by endothelial cells and Weibel-Palade bodies of endothelial cells that mediates platelet adhesion and leads to the subsequent clotting at the site of injury. VWF plays a role in hemostatic diseases such as thrombosis. Due to its role in disease, it may be a novel target for the treatment of these diseases. RNA interference (RNAi) is a natural defence mechanism that is being investigated as a therapy for its ability to provide a precise and personalized treatment by silencing specific genes and preventing the translation of target proteins. This makes gene silencing promising for the treatment for many diseases, and VWF knockdown through siRNA could be a potential new strategy for VWF-associated disease. Current methods of in vitro study of VWF and ultimately VWD, comprise of the use of VWF-transfected heterologous cells or endothelial cells; however, there are no comprehensive studies investigating the regulation and secretion of VWF over time by endothelial cells, specifically murine endothelial cells that best translate in vivo conditions. Any current studies on VWF expression over time are at a shorter time scale that is not compatible with in vitro siRNA transfection protocols. To design siRNA transfection experiments to knockdown VWF in vitro, it is necessary to first investigate VWF expression in human and mouse endothelial cells at time points that can be applied to siRNA transfection. To investigate this aim, several cell lines (HUVEC, LSEC, LMEC and iMAEC) were grown in 24-well plates and treated with PMA, thrombin, or left untreated. RNA, protein lysates and supernatant samples were collected 48 hours post-treatment. Media was changed at 48h and 30-minute, 6h and 24h samples were collected after the media change for analysis through ELISA and qRT-PCR. VWF expression was also visualized in these cells using immunofluorescence. Our findings demonstrate that the expression of VWF in human versus mouse endothelial cells are different, with most similarities demonstrated between HUVECs and LSEC with the expected increase in VWF demonstrated at 48 hours. This data can be used to choose a cell line ideal for future experiments with a longer time scale and/or alter experimental designs depending on the cell line used.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Application of Telehealth Among Community-dwelling Adults with Spinal Cord Injury

contributor:
Richardson, Julie
Rehabilitation Science

abstract:
Spinal cord injury (SCI) is a complicated disorder that leads to considerable morbidity
and cost burden on the health system, primarily due to the wide range of long-term secondary
complications that frequently occur following SCI. Many SCI-associated secondary complications could be prevented or managed with improved access to care for individuals with SCI in the long term who live in the community. However, accessibility to community services for SCI has been further limited when considering accessibility barriers and constraints from the Covid-19 pandemic. Thus, applying telehealth services is one optimal solution for alleviating barriers to accessing rehabilitation services for community-dwelling adults with SCI. This thesis aimed to identify telehealth service models and explore essential characteristics and potential functions of a virtual clinic to improve the provision of care for community-dwelling adults with SCI. Study One was a scoping review of the literature to identify, describe, and compare models of telehealth services in community-dwelling adults with SCI. Study two is a qualitative
study using the interpretive description (ID) approach that consulted with various stakeholders to
identify what they regard as the feasible, essential characteristics, and potential functions of a
virtual clinic for community-dwelling adults with SCI. Findings from these two studies indicated that telehealth might offer an efficient and effective option for health service delivery for community-dwelling individuals with SCI, ensuring continuity of rehabilitation, follow-up after hospital discharge, and management of potential secondary complications following SCI. Findings suggest the benefits of virtual care in improving access over the long term, particularly for those living in rural areas. Additionally,
results highlighted the need for hybridized models of care and the uptake of multidisciplinary approaches within the virtual healthcare system to create efficient care pathways, leading to the continuum of care for community-dwelling adults with SCI. The information gained from these studies could be used to inform policymakers, HCPs, and stakeholders involved with SCI rehabilitation when establishing a virtual clinic for patients with SCI.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract:
The objective of this thesis was to identify telehealth service models and explore essential characteristics and potential functions of a virtual clinic to enhance the provision of care for
persons with SCI who live in their communities. Study One was a scoping review of the
literature to identify, describe, and compare models of telehealth services in persons with SCI
living in the community. Study Two is a qualitative study using the interpretive description (ID)
approach that consulted with various healthcare professionals to identify what they regard as the
feasible, essential characteristics, and potential functions of a virtual clinic for persons with SCI
living in the community. The information gained from these studies could be used to inform
various stakeholders involved in developing future virtual clinics for persons with SCI.


title: Simplified Dynamic Boundary Conditions for Numerical Models of Borehole Heat Exchangers

contributor:
Lightstone, Marilyn
Mechanical Engineering

subject:
Borehole Heat Exchanger
Computational Modelling

abstract:
This work describes the development and validation of a computational model for vertical borehole heat exchangers in residential ground-source heat pump energy systems. Due to the size and shape of vertical borehole heat exchangers, their operation thermally impacts a large volume of surrounding soil and thus discretized models have largely been confined to short-term transient simulations, such as the case of a thermal response test. The proposed model employs a computationally efficient physics-based models at variable spatial dimensions which can be used for long-time simulation of the ground heat transfer.
	The model can generally be considered as a composition of three separate domains: the borehole domain, which combines one-dimensional, three-dimensional and equations-based physics, the near-field soil domain, which resolves three-dimensional transient heat conduction and the far-field soil domain which is modelled as one-dimensional axisymmetric transient heat conduction. The main purpose of this work is to present each component of the model and validate their behaviours and assumptions through a combination of comparison to experimental data, highly cited published works, and well-known analytical models. The complete composite model ignores the three-dimensional effects of fluid heat transfer, and the axial heat transfer in the far-field in order to reduce the computational effort, and the level of uncertainty introduced by each simplification is explored.
	Finally, to support the composite model, a new method determining the thermal impact of the borehole operation mentioned previously was devised and presented alongside the model development and validations. This method, based on the previously defined thermal impacting radius, improves the consistency and theoretical foundation of the value’s definition based on a system energy balance, rather than local temperature conditions.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: EXPLORATION OF A BAYESIAN MODEL OF TACTILE SPATIAL PERCEPTION

title: EXPLORATION OF TACTILE SPATIAL PERCEPTION

contributor:
Goldreich, Daniel
Neuroscience

subject:
Computational Neuroscience
Bayesian Inference
Perception
Tactile Spatial
Illusion

abstract: The remarkable ability of the human brain to draw an accurate percept from imprecise sensory information is not well understood. Bayesian inference provides an optimal means for drawing perceptual conclusions from sensorineural activity. This approach has frequently been applied to visual and auditory studies but only rarely to studies of tactile perception. We explored whether a Bayesian observer model could replicate fundamental aspects of human tactile spatial perception. The model consisted of an encoder that simulated sensorineural responses with Poisson statistics followed by a decoder that interpreted the observed firing rates. We compared the performance of our Bayesian observer on a battery of tactile tasks to human participant data collected previously by our laboratory and others. The Bayesian observer replicated human performance trends on three spatial acuity tasks: classic two-point discrimination (C2PD), sequential two-point discrimination (S2PD), and two-point orientation discrimination (2POD). We confirmed the widely reported observation that C2PD is the least reliable method of assessing tactile acuity due presumably to the presence of non-spatial cues. Additionally, the Bayesian observer performed similarly to humans on raised letter and Braille character-recognition tasks. The Bayesian observer further replicated two illusions previously reported in humans: an adaptation-induced repulsion illusion and an orientation anisotropy illusion. Taken together, these results suggest that human tactile spatial perception may arise from a Bayesian-like decoder that is unaware of the precise characteristics of its inputs.

abstract: Thesis

abstract: Master of Science (MSc)


title: Prognosis of Cardiac Arrest in Patients Receiving Home Care

title: PROGNOSIS OF CARDIAC ARREST IN PATIENTS RECEIVING HOME CARE IN ONTARIO, CANADA

contributor:
Costa, Andrew
Health Research Methodology

subject:
frailty
geriatrics
cardiac arrest
prognosis

abstract: PhD Thesis

abstract:
Background: The home care population is a cohort of medically complex older adults at risk for cardiac arrest and poor post-cardiac arrest health outcomes.
Research Question: What is the prognosis of cardiac arrest among patients receiving home care, and what pre-arrest features and geriatric syndromes (e.g., frailty) are prognostic of survival and post-cardiac arrest health?
Methods: Following a systematic review and meta-analysis that evaluated the prognostic association between frailty and post-cardiac arrest outcomes, a population-based retrospective cohort was created of adults (≥18 years) who received cardiac arrest care at a hospital in Ontario, Canada, between 2006 and 2018. Patients receiving home care and nursing home residents were identified using the Home Care Dataset and the Continuing Care Reporting System. Arrests were analyzed overall and within distinct sub-groups of in-hospital (IHCA) and out-of-hospital cardiac arrests (OHCA). The primary outcome for this thesis was 30-day survival post-cardiac arrest. Frailty was measured using the Clinical Frailty Scale and a valid frailty index. The odds of survival from cardiac arrest were estimated using multivariable logistic regression. Prognostic models were internally validated using bootstrap resampling (n= 2000).
Results: We found high certainty evidence for an association between the Clinical Frailty Scale and death prior to hospital discharge after IHCA (OR = 2.93; 95% CI = 2.43 – 3.53) after adjusting for age as a minimum confounder. Our retrospective cohort contained 86,836 unique adult cardiac arrests, of which 39,610 were OHCA and 47,226 were IHCA. Patients receiving home care represented 10.7% of the cohort and were less likely to survive to hospital discharge (RD = -6.4; 95%CI = -7.4– -5.2) and one-year (RD = -12.8; 95%CI = -14.6 – -10.9) post-cardiac arrest compared to community-dwelling individuals receiving no support in the community. Frail patients receiving home care had worse odds of 30-day survival when measured with the CFS (OR=0.78; 95%CI = 0.61-0.98) and a frailty index (OR=0.89; 95%CI = 0.85-0.95), after adjusting for age, sex, and arrest setting. My prognostic model out-performed the two valid frailty measures and demonstrated fair discriminative accuracy (AUROC = 0.66; 95%CI=0.65-0.65) and good calibration (Slope = 0.95) for group-level prognostication when internally validated among patients receiving home care.
Conclusion:Patients receiving home care have a worse absolute risk of death when compared to community-dwelling individuals receiving no community-based support services. Frailty is associated with survival and post-cardiac arrest declines in cognition and function when evaluated in patients receiving home care. The prognostic model developed within my thesis outperformed the ability of frailty to predict 30-day survival and is suitable for group-level prognostication.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The proportion of older adults receiving home care is growing. The home care population is frail and medically complex, with a greater risk for cardiac arrest. This thesis aims to evaluate the prognosis and prognostic factors influencing survival and other health outcomes, to develop a statistical model that can predict 30-day survival post-cardiac arrest. Findings from my research demonstrate that patients receiving home care have worse survival outcomes post-cardiac arrest compared to well-being older adults living in the community. In my research, frailty was associated with survival and declines in post-cardiac arrest functional independence and cognitive performance among patients receiving home care. Our statistical model performed better than valid frailty measures and had respectable accuracy for group-level prognostication. The home care population is ideally positioned for proactive and shared decision-making about end-of-life care preferences, bearing in mind their receipt of detailed and routine health assessments.


title: Using Machine Learning Techniques to Improve Operational Flash Flood Forecasting

contributor:
Coulibaly, Paulin
Civil Engineering

subject:
Flash flood
Machine learning
Forecast
Inundation map

abstract:
Compared with other types of floods, timely and accurately predicting flash floods is particularly challenging due to the small spatiotemporal scales in which the hydrologic and hydraulic processes tend to develop, and to the short lead time between the causative event and the inundation scenario. With continuous increased availability of data and computational power, the interest in applying techniques based on machine learning for hydrologic purposes in the context of operational forecasting has also been increasing. The primary goal of the research activities developed in the context of this thesis is to explore the use of emerging machine learning techniques for enhancing flash flood forecasting. The studies presented start with a review on the state-of-the-art of documented forecasting systems suitable for flash floods, followed by an assessment of the potential of using multiple concurrent precipitation estimates for early prediction of high-discharge scenarios in a flashy catchment. Then, the problem of rapidly producing realistic highresolution flood inundation maps is explored through the use of hybrid machine learning models based on Non-linear AutoRegressive with eXogenous inputs (NARX) and SelfOrganizing Maps (SOM) structures as surrogates of a 2D hydraulic model. In this context, the use of k-fold ensemble is proposed and evaluated as an approach for estimating uncertainties related to the surrogating of a physics-based model.
The results indicate that, in a small and flashy catchment, the abstract nature of data processing in machine learning models benefits from the presentation of multiple concurrent precipitation products to perform rainfall-runoff simulations when compared to the business-as-usual single-precipitation approach. Also, it was found that the hybrid NARX-SOM models, previously explored for slowly developing flood scenarios, present acceptable performances for surrogating high-resolution models in rapidly evolving inundation events for the production of both deterministic and probabilistic inundation maps in which uncertainties are adequately estimated.

abstract: Thesis

abstract: Doctor of Science  (PhD)

abstract: Flash floods are among the most hazardous and impactful environmental disasters faced by different societies across the globe. The timely adoption of mitigation actions by decision makers and response teams is particularly challenging due to the rapid development of such events after (or even during) the occurrence of an intense rainfall. The short time interval available for response teams imposes a constraint for the direct use of computationally demanding components in real-time forecasting chains. Examples of such are high-resolution 2D hydraulic models based on physics laws, which are capable to produce valuable flood inundation maps dynamically. This research explores the potential of using machine learning models to reproduce the behavior of hydraulic models designed to simulate the evolution of flood inundation maps in a configuration suitable for operational flash flood forecasting application. Contributions of this thesis include (1) a comprehensive literature review on the recent advances and approaches adopted in operational flash flood forecasting systems with the identification and the highlighting of the main research gaps on this topic, (2) the identification of evidences that machine learning models have the potential to identify patterns in multiple quantitative precipitation estimates from different sources for enhancing the performance of rainfall-runoff estimation in urban catchments prone to flash floods, (3) the assessment that hybrid data driven structures based on self-organizing maps (SOM) and nonlinear autoregressive with exogenous inputs (NARX), originally proposed for large scale and slow-developing flood scenarios, can be successfully applied on flashy catchments, and (4) the proposal of using k-folding ensemble as a technique to produce probabilistic flood inundation forecasts in which the uncertainty inherent to the surrogating step is represented.


title: Bridging the Gap: Fragmentation, filamentary feeding and cluster formation in the ISM

contributor:
Pudritz, Ralph
Physics and Astronomy

subject:
astronomy
star formation
star clusters
interstellar medium

abstract: Star formation is an inherently multi-scale process, connecting scales from the kiloparsecs of the galactic disk to the single AU scale of a protostar. In the middle of these scales are star clusters and molecular clouds, the structures in which most stars form. The clouds and clusters are connected via the interstellar medium, the gas and dust making up the matter between stars. In the cold phases of this medium rests the first steps of star formation, the formation of molecular gas and networks of filaments. This cold, neutral medium (CNM) hosts a handful of physical mechanisms, all contributing to the structures that feeds star formation. In this thesis work, we present a suite of simulations using the magneto-hydrodynamical code Ramses to investigate the role of turbulence, magnetic fields and cooling on the formation of filaments and clusters in the CNM. Through 9 different models we find that velocity dispersions in the CNM play a significant role in the formation of structure, requiring a balance between turbulence, self gravity and cooling to form filaments. We find magnetic fields, initialized at strengths of 7 muG, affect the formation of filaments, creating higher percentages of star-forming dense gas and lower percentages of molecular gas. Both magnetic fields and velocity dispersion in the gas affect the formation rate of clusters early in the simulation. Our 8 km/s simulations present a good initial condition for star formation that can include multiple scales of the process and recreate accurate clouds and filamentary structure.

abstract: Thesis

abstract: Master of Science (MSc)


title: Seismic Performance Quantification of Reinforced Concrete Shear Walls with Different End Configurations: Experimental Assessment and Data-driven Performance Models

contributor:
Ezzeldin, Mohamed
Civil Engineering

subject:
Reinforced Concrete Shear Walls
Reinforced Masonry Shear Walls
Seismic
Ductility
Data-Analytics
Performance Models

abstract:
Well-detailed reinforced concrete (RC) shear walls did not achieve the expected seismic performance in the 2011 Christchurch earthquake as per the Canterbury earthquake royal commission report. Similarly, RC shear walls showed low seismic performance in the 2010 Maule earthquake. The two major seismic events intrigued this research dissertation, where six half-scaled RC shear walls were constructed and tested. The six walls were split into two phases, each phase had different end configurations (i.e., rectangular, flanged, and boundary elements). Phase II RC walls had 2.4 times the vertical reinforcement ratio of Phase I walls. The walls were detailed as per CSA A23.3-19, and they were tested laterally under a quasi-static cyclic fully-reversed loading while maintaining a constant axial load through the full test of the walls.
The overall seismic performance of the six walls is evaluated in Chapters 2 and 3 in terms of their load-displacement relationships, crack patterns, displacement ductility capacities, stiffness degradation trends, curvature profiles, end strains, energy dissipation capabilities, and equivalent viscous damping ratios. In addition, damage states are specified according to the Federal Emergency Management Assessment (FEMA P58) guidelines. The results came in agreement with the Canterbury earthquake royal commission report, where the test walls with low vertical reinforcement ratios showed lower-than-expected seismic performance due to the concentration of their plastic hinges at the primary crack locations. Moreover, the results validated the Christchurch (2011) and Maule (2010) earthquake findings as concentrating the rebars at the end zones and providing adequate confinement enhanced the seismic performance of the test walls, which was the case for Phase II flanged and boundary element walls.
	The displacement ductility variations of the test walls inspired the work of Chapter 4, where the objective is to develop a data-driven expression for RC shear walls to better quantify their displacement ductility capacities. In this respect, an analytical model is developed and experimentally validated using several RC walls.  The analytical model is then used to generate a dataset of RC walls with a wide range of geometrical configurations and design parameters, including cross-sectional properties, aspect ratios, axial loads, vertical reinforcement ratio, and concrete compressive strengths. This dataset is utilized to develop two data-driven prediction expressions for the displacement ductility of RC walls with rectangular and flanged/boundary element end configurations. The developed data-driven expressions accurately predicted the displacement ductility of such walls and they should be adopted by relevant building codes and design standards, instead of assigning a single ductility-related modification factor for all ductile RC shear walls, as per the 2020 National Building Code of Canada.
Several researchers tested well-detailed Reinforced Masonry (RM) shear walls and the results concluded that RM shear walls showed high seismic performance similar to that of RC shear walls. This intrigued the research efforts presented in Chapter 5, where a comparative analysis is performed between the six RC walls tested in this dissertation and three RM walls tested in a previous experimental program. The analysis focuses on comparing the seismic performance of both wall systems in terms of their crack patterns, load-displacement envelopes, curvature profiles, displacement ductility, normalized periods, and equivalent viscous damping ratios. In addition, an economic assessment is performed to compare such RC and RM shear walls using their total rebar weights and the total construction costs. Overall, RM shear walls achieved an acceptable seismic performance coupled with low rebar weights and low construction costs when compared to their RC counterparts.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Remapping Sanctuary: Political Theology and Ontario Border Enforcement

contributor:
Nyers, Peter
Political Science

subject: Sanctuary City, sovereignty, citizenship, borders, Toronto

abstract: State borders are often viewed as something faraway that demarcate a country’s frontier; however, whenever a teacher, nurse, social worker, or frontline city worker requires proof of citizenship to access services, they undertake the work of border guards. In Canada and abroad, Sanctuary City policies range from local governments issuing ID cards, schools clandestinely enrolling undocumented students, and domestic abuse shelters refusing entry to the Canada Border Services Agency (CBSA) conducting raids on their property. This activism and policymaking exemplify a case where municipal policy propels social change and analysis of how urban spatial politics interact with state borders that impede migrants’ access to outreach services. I apply an International Political Sociological (IPS) methodological framework to critically deconstruct academic and public narratives that emphasize the urban and religious character of Sanctuary Cities. Using IPS, I combine political theory that calls for abolishing state borders, critical cartography, and a political theology to deconstruct the foundational texts and mapping methods of critical -border, -citizenship, and -migration studies that research Sanctuary Cities. I argue that these subfields reproduce a narrative that cities, economic globalization, and religious movements are in-of-themselves antithetical to state borders. I challenge this narrative by conceptualizing a seeing like a zone approach to visualize the border in terms of deportation routes, inter-police networks, and how the Immigration Refugee Board (IRB) enacts self-deportations. Using Geographic Information System (GIS), I create six maps depicting CBSA, IRB, and local policing immigration infrastructure used in Ontario for the deportation, imprisonment, trials, and investigation of migrants. These maps and my seeing like a zone approach demonstrate that current Social Scientific literature overlook how Sanctuary Cities are ultimately compatible with state borders.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Sanctuary City movements involve community activists and stakeholders lobbying municipalities to deliver city services like schooling, local health clinics, or domestic abuse shelters, regardless of a person’s immigration status. Sanctuary helps people evade deportation in their everyday lives. To what extent do Sanctuary Cities challenge state borders? I challenge the conventional way that social scientists look at Sanctuary Cities. First, despite the religious moniker, Sanctuary Cities are a form of human rights activism which relies on state governments to provide migrants rights. Second, scholars assume Sanctuary Cities challenge borders, however, existing mapping methods do not exist to corroborate such claims. I use mapping software to show the different types of state borders that are enforced in Ontario, the home of Toronto’s Sanctuary City. Finally, I argue that Sanctuary and national borders only exist in specific zones (like in schools, clinics, or public transit) as opposed to entire cities or regions.


title: Top-down Fabrication of Indium Arsenide Antimonide Pillars for Infrared Detection

contributor:
LaPierre, Ray
Engineering Physics

subject: Nanowire, Infrared, Photodetector

abstract: My research regarded the fabrication of InSb and InAsSb large diameter nanowires for infrared applications.

abstract:
InSb and InAsSb pillars, which are large diameter nanowires (NWs), were investigated as an alternative infrared (IR) detector technology to HgCdTe (MCT) for tunable multispectral IR detection with optical properties manipulated by pillar diameter and pitch. Undoped InSb and InAsSb thin films were grown on undoped Si (100) substrates by molecular beam epitaxy (MBE) with a thin AlSb buffer layer. A top-down etching method was used to fabricate pillars of diameters ranging from 300 nm to 1500 nm for InSb, and 1700 nm to 4000 nm for InAsSb. Pillar arrays were analyzed optically by Fourier transform IR spectroscopy (FTIR). The InSb and InAsSb pillars produced narrow absorption peaks with wavelength ranging from 1.61 μm to 6.86 μm for InSb and 8.1 μm to 16.2 μm for InAsSb. A 100 nm increase in pillar diameter corresponded to a 0.495 μm increase in peak absorption wavelength.
InSb thin films were also grown on n-type (As doped, ≤ 0.005 Ω cm) Si (100) substrates to create a p-i-n junction, with an initial 2 μm thick undoped InSb region grown directly on the substrate, and a 0.5 μm thick p-type (Be doped, 2x1019 cm-3) InSb top layer. These films were used to create two devices; an interdigitated contact photoconductor with varying finger geometry, and a photovoltaic device with square top contacts of varying area. I-V characterization demonstrated trends in current with varying finger geometry. Photocurrent measurements were obtained for both the photoconductor and photovoltaic devices under IR and solar illumination. The photocurrent values were orders of magnitude higher for the photoconductive device compared to the photovoltaic device, indicative of potential photoconductive gain. Photocurrent generation in the InSb p-i-n structure introduces the possibility of diameter-dependent photocurrent generation in etched pillar devices.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Infrared light (IR) falls in the wavelength range of 0.75 μm to 1000 μm, with IR based technology having numerous applications in society. With uses in the sciences, research, medicine, and general everyday technology, common IR ranges for material analysis range from 1.4 to 3 μm in the short-wavelength IR (SWIR), 3-5 μm in the mid-wavelength IR (MWIR), and 8-15 μm in the long-wavelength IR (LWIR). These ranges include IR absorption due to molecular vibrations, and includes wavelengths corresponding to the bandgaps of relevant semiconductor materials for IR detectors. To aid in light absorption in semiconductor materials, nanometer scale cylindrical structures called nanowires or pillars can be used on the detector surface, enhancing light absorption, and allowing for absorption wavelength manipulation by adjusting nanowire diameter. This work focuses on developing IR detectors with wavelength absorption in the 1-16 μm range, dependent on nanowire geometry.


title: Development of Advanced Technologies for Mixed Natural Gas Detection

subject: Mixed natural gas, mid wave infrared laser, nonlinear optics, difference frequency generation, ultrasonic techniques.

abstract:
Advanced technologies for mixed gas detection are discussed. A calorific measurement technique for hydrogen-natural gas mixtures using ultrasonic transducers is examined. Measuring the speed of sound in the gas medium enables an accurate composition testing of mixed gas. At the beginning, different ultrasonic transducers are tested and a suitable one for gas testing is chosen. A jig is designed to conduct the testing with nitrogen/oxygen mixtures in a proof of principle experiment. Another jig is designed and manufactured to test a transit time ultrasonic method for flow rate calculation in order to obtain a full energy flow measurement.
A mixed gas leak detection technique based on laser spectroscopy is also studied. A Mid-Wave Infrared (MWIR) laser is implemented to be used as a source in a direct absorption measurement for methane detection. The implemented MWIR laser uses nonlinear optics to generate a MWIR output. A novel intracavity structure using periodically poled lithium niobate as the nonlinear crystal is implemented, and the highest blackbox efficiency for continuous wave difference frequency generation in the MWIR region is reported, to the best of our knowledge. Currently the output power is around 8.1 mW at 3.5 μm with a 1.058% W-1 blackbox efficiency. Watt level MWIR generation is expected using an optimized setup.
At last, a second laser source that operates in the long-wave infrared (LWIR) region was also studied. The discussed laser setup for LWIR generation is similar to the MWIR one with different pump and signal wavelengths and an orientation patterned gallium phosphide (OP-GaP) as the nonlinear crystal. Due to the absorption loss of GaP at the pump wavelength, only mW power level is expected out of the intracavity structure. Some alternative approaches for LWIR generation are discussed.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Effects of Caffeine on Fish Learning

contributor:
Balshine, Sigal
Wong, Bob
Psychology

subject: learning fish toxicology environment cognition anxiety pollution caffeine

abstract: Pollution is an increasing threat to health and biodiversity, especially chemical pollution in the air, land, and water. One such example is caffeine, which is a main active ingredient in coffee and is ingested by humans worldwide for its stimulant effects and cultural significance. This widespread caffeine ingestion coupled with incomplete removal during wastewater treatment results in high concentrations of caffeine in the environment. Aquatic organisms living in waterways receiving wastewater effluent are often exposed to caffeine continuously. Given this long-term and widespread exposure, caffeine is an emerging contaminant of concern. However, most research investigating the effects of caffeine on aquatic organisms use caffeine doses that are much higher and caffeine exposure durations that are much shorter than those found in the environment. Also, most caffeine exposure studies also rely on relatively simple behavioural endpoints and make use of neotropical species. In contrast, I exposed fathead minnow (Pimephales promelas), a common freshwater fish in North America, to environmentally relevant concentrations of caffeine (0 ng/L; 1,000 ng/L; 10,000 ng/l) for 35 days. Caffeine exposure did not affect morphology (e.g., length, mass, growth) or metabolism (maximum metabolic rate, resting metabolic rate, and aerobic scope), but decreased their hepatosomatic index (liver investment). While caffeine did not affect the number of trials taken to associative or reversal learn, or the latency of fish to avoid an aversive trawl, three weeks of exposure to low caffeine concentrations may have decreased anxiety. Taken together our results suggest that future studies perhaps with different endpoints are needed clarify our understanding of how caffeine influences metabolism, anxiety, and learning. Overall, our results provide evidence that complex behavioural endpoints such as aversive learning can be used in ecotoxicological studies.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Aquatic pollution has adverse effects on human and wildlife health, biodiversity and ecosystem function. One way aquatic pollution occurs is when the substances we consume, like caffeine, are not fully removed by wastewater treatment and enter water bodies. Concentrations of caffeine in the environment are high and yet caffeine’s effects on exposed organisms are seldom studied. To redress this, we investigated how environmentally relevant caffeine concentrations affected fathead minnow (Pimephales promelas), a common North American baitfish. Caffeine did not affect the growth rates, length, or mass of exposed fish, but exposure to low caffeine concentrations decreased liver investment. Caffeine did not influence fish metabolism or their ability to learn to avoid a negative stimulus (a trawl), but, at low concentrations, caffeine appeared to decrease anxiety. Our results show further research is needed to better understand caffeine’s effects on aquatic organisms.


title: Synthetic Dynamic Covalent Hydrogel Bioinks For Extrusion Bioprinting Applications

contributor:
Hoare, Todd
Chemical Engineering

abstract: Soft hydrogels provide a favorable environment for cells to grow, proliferate and differentiate. However, in the context of 3D bioprinting, hydrogels are often limited by templates, weak mechanics, and/or a need to work at non-physiological temperature/pH to enable gelation. Recently, we have developed in situ-gelling poly(oligoethylene glycol methacrylate) (POEGMA) and zwitterionic hydrogels based on dynamic hydrazone chemistry that occurs without UV crosslinking, templating, or catalysts, providing an excellent platform for directly incorporating cells during printing. However, the mixing of any dynamic covalent hydrogels presents a challenge to ensure sufficient crosslinking during the 3D printing process. This research highlights the first demonstration of using dynamic covalent POEGMA and zwitterionic hydrogels as a synthetic bioink platform for extrusion bioprinting using a customized extrusion printer. Three mixing strategies were employed: (1) using a modified coaxial needle for diffusion-based mixing of low-viscosity functional polymers; (2) using an embedded strategy via the FRESH (freeform reversible embedding of suspended hydrogels) bioprinting method to 3D print hydrazone-crosslinked POEGMA hydrogels; and (3) using a pre-mixing approach to print pre-formed zwitterionic hydrogels to fabricate small-scale liver mimics, which showed excellent cell viability (>90%, human hepatoma cells) after two weeks and improved albumin secretion when co-printed with fibroblast cells. The tunable gelation kinetics (from instantaneous to several minutes) allowed for these mixing modalities to be evaluated and optimized in terms of print fidelity, homogeneity of the printed constructs, and overall cell viability/functionality. To overcome the immiscibility of zwitterionic-only polymers with common ionic polysaccharides, a copolymer system (comprised of DMAPS and OEGMA) was developed and evaluated in terms of swelling, protein uptake, and anti-coagulant properties. Dual-crosslinked hydrogels based on ionic crosslinking (from calcium-crosslinked sodium alginate) and covalent crosslinking (from the functional synthetic copolymers) have potential benefits in creating cell-based therapeutics that maintain high cell viability and avoid fibrotic responses.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Modeling and simulation of gate leakage in pGaN HEMTs

contributor:
Haddara, Yaser
Electrical and Computer Engineering

subject:
Gate Leakage
pGaN
HEMT
Tunneling

abstract: PhD Thesis

abstract:
Recently, gallium nitride high electron mobility transistor [GaN HEMT] has evolved as a promising device in the field of power electronics. It has excellent material qualities such as high bandgap, high saturation velocity, and good thermal stability which is expected to give superior device performances compared to its Si counterparts. One of the major challenges in GaN technology is to achieve enhancement operation (or normally off mode) due to the presence of its inherent two-dimensional electron gas[2DEG]. Among many methods developed to realize this, pGaN HEMT has emerged as the most encouraging technique for power GaN technology due to its high threshold voltage and good reliability. However, one of the major issues in pGaN HEMTs is that it suffers from high gate leakage current which limits their device performance. In this thesis, we have made a detailed study of the gate leakage process in pGaN HEMTs in terms of modeling, TCAD simulations, and alternative methods being used to reduce gate leakage in pGaN devices.
A numerical model has been developed to model the gate leakage in pGaN HEMTs as a function of gate bias and temperature. This model is validated against 5 devices with different contact metals, geometries, and process conditions. A single model with a consistent set of parameters can fit the experimental data for all these 5 devices without the need to invoke multiple mechanisms to explain the gate leakage process.
The numerical model relied on some simplifications, such as ignoring series resistance, using the compact diode model, and using a simplified expression to describe trap-assisted tunneling. Using commercial TCAD simulations, can address these limitations since the simulator computes the electric field distribution throughout the structure. Furthermore, using TCAD some of the trap levels have been identified which accounts for leakage at low bias. We were able to calibrate our TCAD simulations against published data for the drain current and then used the calibrated simulation environment to accurately simulate gate leakage using parameters that closely correspond to the physical phenomena described, including interface trap parameters, which we identify with known trap levels in GaN.
Finally, we have examined different strategies that have been implemented so far to reduce leakage current. The pGaN layer is important in the whole device operation. Its doping concentration and thickness affect the leakage characteristics. Three modified structures have been studied through TCAD simulations which decrease gate leakage current. In each case, we used our calibrated TCAD model to study the impact on the drain current as well as the leakage current. Our results closely fit published experimental results and therefore provide confidence on the simulated dependence of leakage and drive current behavior on process modifications. The specific results, and our model overall, are expected to be of benefit to device designers in optimizing device structures for leakage while maintaining the required drive current.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: MENTAL STRESS AND OVERLOAD DETECTION FOR OCCUPATIONAL SAFETY

contributor:
Razavi, Saiedeh
Civil Engineering

subject:
Worker Safety
Data-Driven Health Monitoring
Stress and Overload
Wearable Sensors
Unsupervised Learning
Adaptive Neuro-Fuzzy Inference System

abstract: Stress and overload are strongly associated with unsafe behaviour, which motivated various studies to detect them automatically in workplaces. This study aims to advance safety research by developing a data-driven stress and overload detection method. An unsupervised deep learning-based anomaly detection method is developed to detect stress. The proposed method performs with convolutional neural network encoder-decoder and long short-term memory equipped with an attention layer. Data from a field experiment with 18 participants was used to train and test the developed method. The field experiment was designed to include a pre-defined sequence of activities triggering mental and physical stress, while a wristband biosensor was used to collect physiological signals. The collected contextual and physiological data were pre-processed and then resampled into correlation matrices of 14 features. Correlation matrices are used as an input to the unsupervised Deep Learning (DL) based anomaly detection method. The developed method is validated, offering accuracy and F-measures close to 0.98. The technique employed captures the input data attributes correlation, promoting higher interpretability of the DL method for easier comprehension. Over-reliance on uncertain absolute truth, the need for a high number of training samples, and the requirement of a threshold for detecting anomalies are identified as shortcomings of the proposed method. To overcome these shortcomings, an Adaptive Neuro-Fuzzy Inference System (ANFIS) was designed and developed. While the ANFIS method did not improve the overall accuracy, it outperformed the DL-based method in detecting anomalies precisely. The overall performance of the ANFIS method is better than the DL-based method for the anomalous class, and the method results in lower false alarms. However, the DL-based method is suitable for circumstances where false alarms are tolerated.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: State Space Geometry of Low Dimensional Quantum Magnets

contributor:
Sorensen, Erik S.
Physics and Astronomy

subject:
Quantum Information
Quantum Geometry
Condensed Matter Physics
Strongly Correlated Systems

abstract:
In recent decades enormous progress has been made in studying the geometrical
structure of the quantum state space. Far from an abstraction, this geometric struc-
ture is defined operationally in terms of the distinguishability of states connected by
parameterizations that can be controlled in a laboratory. This geometry is manifest
in the kinds of response functions that are measured by well established experimen-
tal techniques, such as inelastic neutron scattering. In this thesis we explore the
properties of the state space geometry in the vicinity of the ground state of two
paradigmatic models of low dimensional magnetism. The first model is the spin-1
anti-ferromagnetic Heisenberg chain, which is a central example of symmetry pro-
tected topological physics in one dimension, exhibiting a non-local string order, and
symmetry protected short range entanglement. The second is the Kitaev honeycomb
model, a rare example of an analytically solvable quantum spin liquid, characterized
by long range topological order.
In Chapter 2 we employ the single mode approximation to estimate the genuine
multipartite entanglement in the spin-1 chain as a function of the unaxial anisotropy
up to finite temperature. We find that the genuine multipartite entanglement ex-
hibits a finite temperature plateau, and recove the universality class of the phase
transition induced by negative anisotropy be examining the finite size scaling of the
quantum Fisher information. In Chapter 4 we map out the zero temperature phase
diagram in terms of the QFI for a patch of the phase space parameterized by the
anisotropy and applied magnetic field, establishing that any non-zero anisotropy en-
hances that entanglement of the SPT phase, and the robustness of the phase to
finite temperatures. We also establish a connection between genuine multipartite
entanglement and state space curvature.
In Chapter 3 we turn to the Kitaev honeycomb model and demonstrate that,
while the QFI associated to local operators remains trivial, the second derivative
of such quantities with respect to the driving parameter exhibit divergences. We
characterize the critical exponents associated with these divergences.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Systems composed of many bodies tend to order as their energy is reduced. Steam,
a state characterized by the complete disorder of the constituent water molecules,
condenses to liquid water as the temperature (energy) decreases, wherein the water
molecules are organized enough for insects to walk atop them. Water freezes to ice,
which is so ordered that it can hold sleds and skaters. Quantum mechanics allows for
patterns of organization that go beyond the solid-liquid-gas states. These patterns
are manifest in the smallest degrees of freedom in a solid, the electrons, and are
responsible for fridge magnets and transistors. While quantum systems still tend to
order at lower energies, they are characterized by omni-present fluctuations that can
conceal hidden forms of organization. One can imagine that the states of matter
live in a vast space, where each point represents a different pattern. In this thesis
we show that by probing the geometry of this space, we can detect hidden kinds of
order that would be otherwise invisible to us.


title: Investigating the effects of VEGF overexpression on hyperglycemia accelerated atherosclerosis

title: VEGF overexpression in atherosclerosis

contributor: Medical Sciences (Thrombosis & Haemostasis & Atherosclerosis)

abstract: Diabetes mellitus is a chronic disease that can lead to severe complications, including an increased risk of cardiovascular disease. The underlying mechanisms that link diabetes to the development of vascular complications are not fully understood. Previous research from our lab has shown that hyperglycemic mice have accelerated atherosclerosis progression, in addition to increased arterial hypoxia, inflammation, and expression of hypoxia-inducible factor 1 alpha (HIF1-α), a transcription factor for genes involved in angiogenesis. However, impaired signalling through the HIF1-α pathway is evidenced by reduced vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and impaired neovascularization of the vasa vasorum – a microvascular network of capillaries that supply the walls of large arteries. We hypothesize that impaired VEGF expression contributes to the accelerated development of atherosclerosis in hyperglycemia. The objective of this study is to test a model of VEGF overexpression on atherosclerosis in hyperglycemia. A macrophage-specific inducible system for VEGF transgene overexpression was established using Cre-Lox technology. Triple mutant apoE-/-ROSA26-FLOXSTOP-VEGF164tg/0 CSF1R-iCREtg/0 mice were generated in a C57BL/6 background. Hyperglycemia was induced in half of the mice with streptozotocin. Macrophage-specific Cre recombinase was activated with tamoxifen at early and later stages of atherosclerosis, and hearts/aortas were harvested at 15 weeks of age. Lesion volume and expression of key factors in hypoxia-mediated angiogenesis were quantified. Our results demonstrate that overexpression of VEGF during early atherosclerosis progression reduces plaque volume and expression of the hypoxic marker, HIF-1α, in female mice. Understanding the effects of VEGF expression on lesion development will help delineate the biochemical pathways that link diabetes and cardiovascular disease. Validation of this mechanism may lead to novel and more effective strategies to treat/prevent diabetic cardiovascular disease.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Diabetes is a chronic disease characterized by high blood sugar. A serious complication of diabetes is a higher risk for heart disease. However, we still do not entirely understand why this occurs. One of the causes of heart disease is the buildup of fats in the walls of large arteries. Mice with diabetes have fewer new small blood vessels supplying the wall of large arteries. We believe this is because of the lower production of a protein called vascular endothelial growth factor (VEGF). This study demonstrates that in diabetic mice, increasing VEGF during the early stages of fat buildup slows down the further progression of the disease. Future work on this project will focus on understanding how this happens. With the increasing prevalence of diabetes, understanding and developing new treatments for diabetic patients have never been more important.


title: EFFECTS OF SHORT-TERM, PHARMACOLOGICAL CARM1 INHIBITION ON SKELETAL MUSCLE MASS, FUNCTION, AND ATROPHY

contributor:
Ljubicic, Vladimir
Kinesiology

abstract: Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins critical for health and disease. The purpose of this study was to characterize the effects of short-term, pharmacological CARM1 inhibition on skeletal muscle size, function, and atrophy. Adult mice (n = 10-11/sex) were treated with either a CARM1 inhibitor (150 mg/kg EZM2302; EZM) or vehicle (Veh) via oral gavage for 11-13 days and muscle mass, function, and exercise capacity were assessed. Additionally, we investigated the effect of CARM1 suppression on unilateral hindlimb denervation (DEN)-induced muscle atrophy (n = 8/sex). We report that CARM1 inhibition caused significant reductions in the asymmetric dimethylation of known CARM1 substrates but no change in CARM1 protein or mRNA content in skeletal muscle. Reduced CARM1 activity did not affect body or muscle mass, however, we observed a decrease in exercise capacity and muscular endurance in male mice. CARM1 methyltransferase activity increased in the muscle of Veh-treated mice following 7 days of DEN and this response was blunted in EZM-dosed mice. Skeletal muscle mass and myofiber cross-sectional area were significantly reduced in DEN compared to contralateral, non-DEN limbs to a similar degree in both treatment groups. Furthermore, skeletal muscle atrophy and autophagy gene expression programs were elevated in response to DEN independent of CARM1 suppression. Collectively, these results suggest that short-term, pharmacological CARM1 inhibition in adult animals affects muscle performance in a sex-specific manner but does not impact the maintenance and remodeling of skeletal muscle mass during conditions of neurogenic muscle atrophy.

abstract: Thesis

abstract: Master of Science in Kinesiology

abstract: Coactivator-associated arginine methyltransferase 1 (CARM1) is an enzyme that alters the activity of other proteins. CARM1 plays an important role in several tissues, however, little is understood about its function in skeletal muscle. Recent research suggests that CARM1 could be involved in the process of skeletal muscle wasting and weakness, termed muscle atrophy. Therefore, we aimed to study the effects of short-term pharmacological CARM1 inhibition on skeletal muscle mass, function, and atrophy in adult mice. Our observations show that treatment with a CARM1-inhibiting compound was very effective at reducing CARM1 activity in muscle. CARM1 inhibition did not affect muscle mass, but it did decrease muscular endurance, particularly in male mice. Suppressed CARM1 activity had no impact on muscle wasting or molecular atrophy signalling following a period of denervation-evoked muscle disuse. Collectively, we demonstrate that short-term CARM1 inhibition impacts muscle performance without affecting the maintenance and plasticity of muscle mass.


title: Achieving native-like accuracy of French/English vowels for Canadian bilingual speakers: effects of language self-described proficiency, context of use and daily exposure time

contributor:
Pape, Daniel
Cognitive Science of Language

subject:
Language
Bilingualism
Language Production

abstract:
Studies on bilingual production have not come to a consensus on the possibility of bilinguals reaching native-like production. Some studies find that bilinguals can be close to native production while others have shown that even in simultaneous bilinguals, the production cannot reach native-likeness. Flege’s Speech Learning Model (Flege & Bohn, 2020) theorizes that acquiring a second language affects the production of the L1 and vice versa. The model also states that new phonemes are easier to acquire compared to existing phonemes with different production. This thesis seeks to research the production of French and English vowels in a general population of Canadians to give an accurate picture of second language learning in Canada. We also seek to determine the strength of second language effects on the production of the first language and, what factors influence proficiency in bilingual speakers.
	Participants were recruited in the Montréal region to have bilinguals of different proficiency and different backgrounds. They were given a sentence list to read out loud while being recorded. The recorded data was used to study the vowel formants produced by the bilinguals. These formants were then used to create a plot of the group average that was then compared to the production plots of monolinguals. The production data was also used to create a group average distance, with the help of the Mahalanobis distance calculations, to also compare to the production from the French and English monolingual groups. The plots and the calculations were used to compare the groups between themselves and the monolingual groups.
The results from the production data are within our expectations. The simultaneous bilinguals had the closest to native-like production in both English and French compared to the other bilinguals. The data also showed that for the English native bilinguals, the frequency of L2 use is the biggest factor in native-like production while for the French native bilinguals it was L2 proficiency. Regarding the SLM, the data we collected support the claim that bilinguals acquire and produce new phonemes with more ease than modify existing phonemes. It also partially supports the claim that knowledge of a second language will affect the production of the first language. The results from our experiment demonstrate that as the L1 French – L2 English bilinguals’ knowledge of English increased, their production of French veered away from the French monolinguals. However, this effect was not seen with the L1 English – L2 French bilinguals.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
The Speech Learning Model (SLM) theorizes that the acquisition of a second language will be affected by the production of the first/native language. In addition, it theorizes that the second language can simultaneously affect the first/native language (L1). By observing the production of French and English vowels in different groups of French native speakers who later acquire English (L2) and English native speakers who later acquire French, we hope to answer the following questions.
1.	How close do bilinguals get to native-like production?
2.	How strong is the bilateral (L1 → L2 and L2 → L1) effect in the different groups of bilinguals?
3.	Which vowels are harder for bilinguals to acquire?
4.	What factors influence native-like production?
We recorded pronunciation of French and English vowels by bilinguals to achieve the goals of this thesis. By studying the pronunciation of vowels in English and French, we hoped to get a clearer picture of second language learner in the context of Canada. These pronunciations are used to compare the bilinguals to speakers who only speak French or English. The data suggests that bilinguals are the closest second language learner group to the pronunciation of both French and English vowels. The results also point to frequency of L2 use being the strongest factor for native-like production for the English native bilinguals, and proficiency being the strongest factor for the French native bilinguals. L2 → L1 effects are strongest in the groups with high proficiency, with speakers that have both English and French as native languages.


title: The Impact of Online Product Presentation Interactivity on Product Innovativeness Perception

contributor:
Calic, Goran
Hassanein, Khaled
Business

subject:
Interactivity
Product Innovativeness
Crowdfunding
Resonance
Online Product Presentation

abstract: The emergence of online entrepreneurship platforms made it possible for entrepreneurs to fund their innovative ideas through financial support from business angels, venture capitalists, and crowds. Nevertheless, technology product development projects are the most difficult to fund on such platforms, with the least funding success and highest unsuccessful dollar value among all categories. One major factor affecting funding success on these platforms is the extent of perceived innovativeness of the presented technology products. The extant literature evinces that product innovativeness perception is influenced not only by novelty but also meaningfulness perception and that innovativeness brings higher funding success when novel projects are also perceived to be meaningful. By drawing on the theory of resonance, this study investigates the impact of interactivity on the extent of perceived innovativeness by creating an impact on resonance, which is proposed to represent all pre-identified aspects of meaningfulness. An online experiment was conducted to empirically validate the proposed research model, and increased interactivity was found to be positively associated with perceived product innovativeness through higher resonance. Theoretically, this study proposes the resonance concept to account for the meaningfulness perception regarding innovative product ideas and demonstrates the positive effect of increased interactivity on perceived innovativeness. For practitioners, the results provide evidence for the positive impact of interactive product presentation on the increased perception of resonance and, thus, innovativeness, which evinces a higher potential for funding success in highly innovative product development projects.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Product Development Collaborations: Implications for Marketing Strategy and Innovation

contributor:
Ray, Sourav
Business Administration

subject:
Product development collaborations
Collaboration governance
innovation performance
Firm capabilities
Positioning strategy
International Innovation collaborations
Competency trap

abstract: PhD thesis

abstract:
High-tech firms are no longer able to rely exclusively on their internal knowledge and technologies to respond effectively to current market dynamics. Instead, they frequently collaborate with external entities to access new technologies and share the costs and risks of the innovation process. However, the effectiveness of such collaborations is questioned by many executives. Yet, as these Product Development Collaborations (PDCs) become crucial for a firm’s growth and success in current times, executives and academics alike are paying growing attention to them. In marketing, PDC is an active research topic since 1999. However, the body of marketing knowledge on the PDC is scattered across several studies over an extended period of more than two decades. In addition, the extant marketing studies report results that are inconsistent on some PDC issues and have overlooked others. In particular, marketing strategy considerations, in terms of firm’s strategic capabilities and objectives, have received somewhat of a short shrift in the literature.
My dissertation contributes to our marketing literature with (a) a systematic review study that synthesizes the current state of marketing knowledge on the topic, identifies the research lacunas, and sets a future research agenda; and (b) two theory-driven empirical studies that provide new insights and novel implications to enrich our understanding of PDCs, their relation to the firm’s marketing strategy, and provide clear guidance to practitioners on how to benefit most from their supplier collaborations.
v
Grounding on several theories, creating and using a unique dataset, and utilizing multiple research and econometric techniques, my dissertation empirically addresses the following two general research questions:
RQ1. Can their functional (marketing, technological, and operations) capabilities lead firms into competency traps and hurt their innovation performance? How? Do international PDCs outperform domestic PDCs in combating the competency trap effect? When?
RQ2. What is the appropriate PDC governance mechanism (joint ventures, agreements, or licenses) that would enhance innovation performance? How do governance and capabilities simultaneously impact innovation performance? How does the firm’s product positioning strategy (differentiation versus cost-leadership) interact with governance and capabilities to affect innovation outcomes?

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Many firms establish Product Development Collaborations (PDCs) with suppliers to innovate new products. Although PDCs have numerous advantages, they are ladened by various contractual hazards and risks. This raises concerns of many executives about their effectiveness. In this dissertation, I systematically review the existing marketing studies on the PDC topic. Then, building on my review, I empirically investigate several marketing strategy factors that impact a PDC's effectiveness in terms of enhancing the innovation performance of focal firms.
Drawing on several theories, building and using a unique dataset, and utilizing multiple research and econometric techniques, I conduct two empirical studies to examine the impact of four strategic considerations (i.e., functional capabilities, international PDCs, PDC governance mechanisms, and positioning strategy) and their interactions on innovation performance of high-tech firms in PDCs.
My results reveal various interesting and important relationships and interactions that advance our understating of PDCs, their relation to marketing strategy, and provide important managerial implications to practitioners.


title: Unsupervised Classification for Skewed and Mixed-Type Data

contributor:
McNicholas, Paul D
Mathematics and Statistics

abstract: Clustering, also known as unsupervised classification, is a foundational machine learning technique  and is used to find underlying group structures in data. There are many well-established model-based techniques to analyze either categorical or continuous data in the clustering paradigm. However, there is a relative paucity of work for mixed-type data, especially mixed data where the continuous variables exhibit skewness and heavy tails. In this thesis,  different methodologies and models are presented for analyzing asymmetric and mixed-typed data. The first method is a mixture model for analyzing asymmetric mixed-type data. The second is modelling contaminated mixed-type data and identifying potential outliers.   Lastly, model averaging techniques are developed for skewed-data based on Occam’s window and parsimonious mixture models. The expectation-maximization algorithm is used here to estimate the model parameters. Both real and simulated data are used for illustration.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: SYNTHESIS, STRUCTURE, AND LUMINESCENT PROPERTIES OF NEW GERMANATE PHASES

contributor:
Mozharivskyj, Yurij
Chemistry

subject: Luminescence, crystal structure, X-ray diffraction

abstract:
A series of new germanates was prepared and their structures were characterized with X-ray diffraction (XRD). We employed solid-state synthesis, flux growth, and crystallization from melts to obtain crystals of the new materials. The crystals were studied by means of single crystal XRD, providing the information on the structure and composition of the new materials. Germanates suitable to accommodate Mn4+ – a well-known activator ion for the preparation of the rare-earth-free red phosphors – were of a particular interest. The Ge4+ substitution for Mn4+ is possible if the crystal structure features octahedrally coordinated germanium atoms, and we indeed were able to prepare such germanates.
The crystal structures of the following phases were characterized: Mg3Ge1-O4(1-)F2(1+2) ( ≈ 0.1), Mg14Ge4O20F4, Mg2Pb2Ge2O7F2, Sr3GeO4Cl2, Ba3GeO4Br2, Sr6Ge2O7Cl6, Ba5GeO4Br6, Na2BaGe8O18, Rb2BaGe8O18, Na0.36Sr0.82Ge4O9, Na2SrGe6O14, and K2SrGe8O18. Two phases, Mg3Ge1-O4(1-)F2(1+2) and Na0.36Sr0.82Ge4O9 demonstrate deficiency on certain crystallographic sites. We analyzed the connectivity of the GeO4 and GeO6 units in the new and reported tetra- and octagermanates. Despite the similar stoichiometry, the connectivity of GeOn polyhedra is different in RI2Ge4O9, RIIGe4O9 and RIRIIGe8O18 germanates (RI = alkali, RII = alkaline earth metal).
The Ge4+ substitution for Mn4+ was successfully done for the Na2BaGe8O18, Rb2BaGe8O18, Na2SrGe6O14, and K2SrGe8O18 phases yielding new red phosphors. Based on the powder XRD data, the optimal synthetic strategies were developed yielding high purity (≈ 99 wt. %) samples. The photoluminescent excitation and emission spectra were collected for the new phosphors. Strong absorption of the UV light and emission in the far-red region of the visible spectra were confirmed, which is in a good agreement with the literature. The Mn4+ doping level was optimized to achieve the highest luminescence in the studied phases. Temperature-dependent luminescence spectra were collected for the Na2SrGe6O14 : Mn4+ and K2SrGe8O18: Mn4+, and the K2SrGe8O18: Mn4+ showed the highest resistance to temperature quenching.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A Refusal of State-Driven Northern Destiny: Deconstructing the Mackenzie Valley Pipeline Inquiry Hearings

contributor:
Egan, Michael
History

subject: Berger Inquiry, Mackenzie Valley Pipeline Inquiry, Northwest Territories, North, Indigenous self-determination, State, Nation, Dene Nation

abstract:
This dissertation considers the incommensurable interests of people, fossil capital, federal
energy politics, and place in Northern Canada during the 1970s. By the late 1960s, the
insatiable North American appetite for fossil fuels had turned its attention toward the
Arctic region. After the discovery of rich deposits in Prudhoe Bay, Alaska, in 1968, largescale
energy projects were proposed to access and exploit these Arctic natural resources.
Canada participated in this northern oil rush; an exploration of oil and gas in the Arctic
regions was accelerated in the early 1970s. The next challenge involved transporting the
oil and gas to southern markets. In 1974, the Canadian federal government initiated the
Mackenzie Valley Pipeline Inquiry to investigate the social, environmental, and economic
effects of the pipeline routes proposed by a consortium of American and Canadian oil
companies through the Mackenzie River Valley in the Northwest Territories where it
would connect with existing pipeline infrastructure in northern Alberta. The Inquiry’s
report recommended against immediate construction, encouraging instead a ten-year
moratorium. Inquiry commissioner Thomas Berger’s report rationalized the delay to
make time for settling Indigenous land claims in the region and for taking conservation
measures to protect some key areas in the Mackenzie River Valley. In this dissertation, I
examine how the discussion around pipeline construction shaped the meaning of the
North, self-determination, and cultural recognition. In this dissertation, I particularly
focus on how Indigenous peoples asserted their claims by rejecting state-driven policies
and the interests of fossil-fuel capitalism in the North.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Through the close reading of the Mackenzie Valley Pipeline Inquiry hearings, I examine
how the discussion around energy development shaped the 1970s’ contentious Canadian
politics of nation and North. Central to this debate, I focus on how Indigenous peoples
asserted their land claims by challenging and refusing the settler state policies and the
interests of fossil-fuel capitalism in the western Northwest Territories in the 1970s. By
using the Inquiry process, northern Indigenous peoples challenged the idea that the state
had a legitimate authority to decide and control the future or destiny of a territory or
peoples in its defined borders.


title: Computational and Experimental Study of the Microstructure Evolution of Inconel 625 Processed by Laser Powder Bed Fusion

contributor:
Phillion, Andre
Materials Science and Engineering

subject: Rapid solidification, Solidification microstructure selection maps, Additive Manufacturing (AM), Columnar to Equiaxed Transition (CET), Inconel625, Laser Powder Bed Fusion (LPBF), Microsegregation, Microstructure heterogeneity

abstract:
This study aims to improve the Additive Manufacturing (AM) design space for the popular multi-component Ni alloy Inconel 625 (IN625) thorough investigating the microstructural evolution, namely the solidification microstructure and the solid-state phase transformations during the Laser Powder Bed Fusion (LPBF) process. Highly non-equilibrium solidification and the complex reheating conditions during the LPBF process result in the formation of various types of solidification microstructures and grain morphologies which consequently lead to a wide range of mechanical properties. Understanding the melt’s thermal conditions, alloy chemistry, and thermodynamics during the rapid solidification and solid-state phase transformation in AM process will help to control material properties and even produce a material with specific microstructural features suited to a given application. This research helps to better understand the process-microstructure-property relationships of LPBF IN625.
First, a set of simple but effective analytical solidification models were employed to evaluate their ability to predict the solidification microstructure in AM applications. As a case study, Solidification Microstructure Selection (SMS) maps were created to predict the solidification growth mode and grain morphology of a ternary Al-10Si-0.5Mg alloy manufactured by the LPBF process. The resulting SMS maps were validated against the experimentally obtained LPBF microstructure available in the literature for this alloy. The challenges, limitations, and potential of the SMS map method to predict the microstructural features in AM were comprehensively discussed.
Second, The SMS map method was implemented to predict the solidification microstructure and grain morphology in an LPBF-built multi-component IN625 alloy. A single-track LPBF experiment was performed utilizing the EOSINT M280 machine to evaluate the SMS map predictions. The resulting microstructure was characterized both qualitatively and quantitatively in terms of the solidification microstructure, grain morphology, and Primary Dendrite Arm Spacing (PDAS). Comparing the experimentally obtained solidification microstructure to the SMS map prediction, it was found that the solidification mode and grain morphology were correctly predicted by the SMS maps. Although the formation of precipitates was predicted using the CALculation of PHAse Diagrams (CALPHAD) approach, it was not anticipated from the analytical solution results.
Third, to further investigate the microsegregation and precipitation in IN625, Scanning Transmission Electron Microscopy (STEM) using Energy-Dispersive X-ray Spectroscopy (EDS), High-Angle Annular Dark-Field Scanning Transmission Electron Microscopy (HAADF-STEM), Scheil-Gulliver (with solute trapping) model, and DIffusion-Controlled TRAnsformations (DICTRA) method were employed. It was found that the microstructural morphology mainly consists of the Nickel-Chromium (gamma-FCC) dendrites and a small volume fraction of precipitates embedded into the interdendritic regions. The precipitates predicted with the computational method were compared with the precipitates identified via HAADF-STEM analysis inside the interdendritic region. The level of elemental microsegregation was overestimated in DICTRA simulations compared to the STEM-EDS results; however, a good agreement was observed between the Scheil and STEM-EDS microsegregation estimations.
Finally, the spatial variations in mechanical properties and the underlying microstructural heterogeneity of a multi-layer as-built LPBF part were investigated to complete the process-structure-properties relationships loop of LPBF IN625. Towards this end, numerical thermal simulation, electron microscopy, nano hardness test, and a CALPHAD approach were utilized to investigate the mechanical and microstructural heterogeneity in terms of grain size and morphology, PDAS, microsegregation pattern, precipitation, and hardness along the build direction. It was found that the as-built microstructure contained mostly columnar (Nickel–Chromium) dendrites were growing epitaxially from the substrate along the build direction. The hardness was found to be minimum in the middle and maximum in the bottom layers of the build’s height. Smaller melt pools, grains, and PDAS and higher thermal gradients and cooling rates were observed in the bottom layers compared to the top layers. Microsegregation patterns in multiple layers were also simulated using DICTRA, and the results were compared with the STEM-EDS results. The mechanism of the formation of precipitates in different regions along the build direction and the precipitates’ corresponding effects on the mechanical properties were also discussed.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Engineering Nanofiber Morphology in Electrospun Poly(Oligoethylene Glycol Methacrylate)-Based Tissue Scaffolds

subject:
Tissue Engineering
Biomaterials

abstract: Soft tissue engineering has become increasingly relevant in efforts to create complex, functional tissues for tissue replacement in tissue engineering applications or for the development of more complex tissue models for drug screening or fundamental research. Tissue engineering of micro- and nano-scale structures has been explored through a number of biofabrication techniques but most successfully on the nano-scale through electrospinning. Electrospun nanofibers represent one of the most similar structures to natural extracellular matrix (ECM), while electrospinning of hydrogel nanofibers is particularly relevant given that such nanofibers support the high water content environment required by cells to survive. Herein, a reactive cell electrospinning process is demonstrated based on dynamic hydrazone-crosslinked poly(oligoethylene glycol methacrylate (POEGMA) hydrogel nanofibers that can be electrospun from an aqueous solution, allowing for the generation of cell-loaded hydrogel nanofibers in a single fabrication/cell-seeding step. Using the proper collectors, the fabrication of aligned and/or multi-layered scaffolds is demonstrated without the risk of layer delamination due to the dynamic crosslinking of POEGMA hydrogels. Co-electrospun NIH 3T3 fibroblasts and Psi2 12S6 epithelial cells were found to proliferate over 14 days within the networks, while electrospun C2C12 myoblasts were found to align along the direction of aligned fibers. POEGMA hydrogels provide a suitable environment for cells and can be expanded to multi-layer, multi-cellular networks with tunable micro-architectures to better mimic more complex aligned (e.g. muscle) and/or multi-layer (e.g. smooth muscle vasculature, esophageal) tissues.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Successful regeneration of diseased tissues relies first on understanding the healthy tissue structures and functions that currently exist within the body, and second, how to synthetically replicate those structures using biomaterials. Re-creating the natural networks that cells use to attach and grow has many challenges, including the challenge of creating nano-scale structures, controlling any immune response to the biomaterial(s) used, and ensuring the correct response of cells to the fabricated structures. One method of generating suitable nano-scale structures is through a process called electrospinning, specifically when it is used to produce hydrogel-based nanofibers which can bind large amounts of water. When implanted, hydrogels swell to form a hydrated environment suitable for cells. These nanofibers are generated on a scale that is smaller than the encapsulated cells to allow for guided cell responses to the material. Furthermore, the use of cell-friendly polymer solutions allows for cells to be in contact with the biomaterial without resulting in high cell death. In this thesis, aligned and/or multi-layered nanofiber structures are generated to replicate the naturally existing support structures seen in the body. These fibers are also loaded with cells to create semi-functional body tissues that in the future can serve to replace non-functional tissues or used to better understand cell interactions with their environment.


title: The application of metabolomics in assessment of nutrition, sources of variation in food-related metabolites, and identification of -omics features of childhood obesity

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject: Metabolomics Nutrition Biomarkers Obesity Microbiome Multi-omics Variability Epidemiology Food

abstract: Ideally, a nutritional biomarker serves as an objective measure of the intake of a particular food or nutrient, may provide a reflection of health and disease processes, and can aid in the development of personalized nutritional recommendations. However, few food biomarkers have been validated and most have yet to be critically appraised in the literature. With the increased use of metabolomics in population-based studies, it is important to identify the sources of variability in nutritional biomarkers that may be attributed to intrinsic physiologic characteristics and extrinsic factors so that exposure-outcome associations can be examined more accurately. Additionally, circulating metabolites are associated with obesity-related changes in gut microbiome but there has been limited integration of metabolomics with microbiome in childhood obesity, and even less is known in non-white populations. This dissertation presents a series of studies that provide direct support for utility of nutritional biomarkers in population-based studies. The first study, presented in Chapter 2, contributes to the growing literature on food-based biomarkers by generating a comprehensive list of metabolites associated with a comprehensive list of all individual foods and food groups, and rated the evidence based on interstudy repeatability and study design. Chapter 3 identifies sources of variability in serum metabolite concentrations in White Europeans and South Asian pregnant women, thereby guiding appropriate statistical modeling when utilizing metabolomics in nutritional epidemiological studies. Chapter 4 provides results from a multi-omics integration analysis of serum metabolites and amplicon sequence variants of 16S ribosomal RNA genes to identify biomarkers that discriminate children with and without obesity. Collectively, the results showed that a specific food/food group may give rise to many metabolites, however in several cases, a single metabolite can be a good indicator of food intake. Dietary factors explained the highest proportion of variability in exogenous food-based biomarkers relative to non-dietary factors, whereas the contribution of non-dietary factors was either similar or lower for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from more than one food source. Most of the circulating metabolites differed by ethnicity (South Asian and White Europeans). Biomarkers with good evidence can be considered direct surrogates for food intake, however, they can be influenced by several non-dietary factors, which require appropriate consideration during the statistical analyses of the data. Finally, the results showed notable differences in serum metabolome and specific gut bacterial species, and between specific metabolites and bacterial species related to childhood obesity. Obesity related metabolic pathways such as glutamate and carnitine metabolism may provide insight into the metabolic processes related to early onset of obesity in childhood.

abstract: Dissertation

abstract: Doctor of Philosophy (Medical Science)


title: Polaris and TRACE/PARCS Code Development for CANDU Analysis

contributor:
Novog, David
Engineering Physics

subject:
CANDU
analysis
software
SCALE
Polaris
PARCS
TRACE
reactor physics
thermalhydraulics
reactor control
uncertainty analysis
BEPU
simulation
safety analysis
nuclear

abstract:
McMaster University DOCTOR OF PHILOSOPHY (2022) Hamilton, Ontario (Engineering
Physics)
TITLE: Development and Evaluation of Polaris CANDU Geometry Modelling and of
TRACE_Mac/PARCS_Mac Coupling with RRS for CANDU Analysis
AUTHOR: Simon Younan, M.A.Sc. (McMaster University), B.Eng. (McMaster University)
SUPERVISOR: Dr. David Novog
NUMBER OF PAGES: xiv, 163

abstract:
In the field of nuclear safety analysis, as computers have become more powerful,
there has been a trend away from low-fidelity models using conservative assumptions, to
high-fidelity best-estimate models combined with uncertainty analysis. A number of these
tools have been developed in the United States, due to the popularity of light water
reactors. These include the SCALE analysis suite developed by ORNL, as well as the PARCS
and TRACE tools backed by the USNRC. This work explores adapting the capabilities of
these tools to the analysis of CANDU reactors.
The Polaris sequence, introduced in SCALE 6.2, was extended in this work to support
CANDU geometries and compared to existing SCALE sequences such as TRITON. Emphasis
was placed on the Embedded Self-Shielding Method (ESSM), introduced with Polaris. Both
Polaris and ESSM were evaluated and found to perform adequately for CANDU
geometries. The accuracy of ESSM was found to improve when the precomputed selfshielding
factors were updated using a CANDU representation.
The PARCS diffusion code and the TRACE system thermalhydraulics code were
coupled, using the built-in coupling capability between the two codes. In addition, the
Exterior Communications Interface (ECI), used for coupling with TRACE, was utilized. A
Python interface to the ECI library was developed in this work and used to couple an RRS
model written in Python to the coupled PARCS/TRACE model. A number of code
modifications were made to accommodate the required coupling and correct code
deficiencies, with the modified versions named PARCS_Mac and TRACE_Mac. The
coupled codes were able to simulate multiple transients based on prior studies as well as
operational events. The code updates performed in this work may be used for many
future studies, particularly for uncertainty propagation through a full set of calculations,
from the lattice model to a full coupled system model.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Modern nuclear safety analysis tools offer more accurate predictions for the safety
and operation of nuclear reactors, including CANDU reactors. These codes take advantage
of modern computer hardware, and also a shift in philosophy from conservative analysis
to best estimate plus uncertainty analysis. The goal of this thesis was to adapt a number
of modern tools to support CANDU analysis and uncertainty propagation, with a particular
emphasis on coupling of multiple interacting models. These tools were then
demonstrated, and results analyzed.
The simulations performed in this work were successful in producing results
comparable to prior studies along with experimental and operational data. This included
the simulation of four weeks of reactor operation including “shim mode” operation.
Sensitivity and uncertainty analyses were performed over the course of the work to
quantify the precision and significance of the results as well as to identify areas of interest
for future research.


title: The Role of an Accessory Protein Family in Type VI Secretion

contributor:
Whitney, John
Biochemistry and Biomedical Sciences

abstract:
The type VI secretion system (T6SS) is a widely distributed protein nano-machinery found in
Gram-negative bacteria. T6SSs are a harpoon-like apparatus that delivers toxic effector proteins
directly into target cells in a contact-dependent manner. These effectors are associated with a
diverse range of functions such as cytoskeletal modification, biofilm formation, and bacterial
competition. Effectors are loaded onto the T6SS by interacting with its structural components.
Often, additional accessory proteins are needed for the secretion of these effector proteins.
Despite their importance, the direct role of these accessory proteins in the assembly of the T6SS
warhead or its subsequent ‘firing’ is unclear. One such example is the putative DUF2169 family
of proteins. These proteins are required for effector secretion, however, the molecular function of DUF2169 proteins remains unknown.
I have shown that DUF2169-encoding genes co-occur with the structural components of T6SS,
such as VgrG and effectors that possess a specialized N-terminal PAAR-like domain. Using a
Pseudomonas aeruginosa T6SS-associated gene cluster, I show the network of protein
interactions with DUF2169 and these T6SS structural components. Furthermore, I was able to
show that these gene clusters form a conserved synteny. Multiple proteins encoded within
DUF2169 syntenies are predicted to mimic previously characterized proteins associated with
T6SS function. Lastly, using X-ray crystallography I was able to solve the structure of DUF2169
from Vibrio xiamenensis as the first representative of the DUF2169 protein family. Additionally,
using structural predictions I show the molecular interaction between DUF2169 and PAAR-like
domains of effectors as a potential chaperone. Gaining structural insight into the role of this
protein will not only enhance our understanding of T6SS function but also highlight the
mechanistic differences between different T6SS warheads. Since T6SSs can deliver a variety of
proteins into both prokaryotic and eukaryotic cells, understanding how this delivery mechanism
works expands our knowledge of how bacteria interact with diverse cell types. Furthermore,
uncovering a new mechanism for directly delivering proteins into different cell types has
valuable potential for medical and industrial applications.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Gram-negative bacteria can use a pathway called the type VI secretion system or T6SS to kill
these competitor bacterial species. T6SS is a protein complex that facilitates the injection of
toxic proteins, from attacking cells directly into target cells. The secretion of these toxic proteins
requires additional accessory proteins, which recruit and stabilize the toxic proteins before
secretion. In this work, I characterize an accessory protein family that functions as a chaperone
for these toxic proteins. First, I showed that these accessory protein family genes are linked to
genes that encode for the core T6SS apparatus proteins. Secondly, I was able to capture the first snapshot of this accessory protein family. This snapshot gives molecular details into the role of this accessory protein in T6SS secretion. Collectively, these results expand our knowledge of
how bacteria use the T6SS to secrete toxic proteins. Uncovering a new mechanism for directly
delivering proteins into different cell types has valuable potential for medical and industrial
applications.