title: Cigarette smoke exposure and impaired endoplasmic reticulum stress responses underlie altered pulmonary macrophage composition and function during lung injury, fibrosis, and repair.

title: Investigating macrophage dysfunction in pulmonary fibrosis

contributor:
Ask, Kjetil
Medical Sciences

abstract:
RATIONALE. Fibrotic interstitial lung diseases (ILDs) comprise a wide array of heterogeneous disorders of known and unknown etiology. Pulmonary fibrosis constitutes the late phase of ILDs. A variety of extrinsic and intrinsic risk factors are implicated in fibrotic ILD development and pathogenesis, with macrophages considered central
orchestrators of disease pathogenesis. Particularly, cigarette smoking, protein misfolding, endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR), have been associated with impaired macrophage activation and function. However, a comprehensive understanding of the impact of these processes on the composition and function of pulmonary macrophage subpopulations and subsequently on tissue remodelling in pulmonary fibrosis is yet to be elucidated. In this Ph.D. thesis, we assessed the impact of cigarette smoke (CS) exposure and the myeloid-specific deletion of Atf6α, one of the UPR mediators, on pulmonary macrophage subpopulation composition and function during lung injury, tissue remodelling, and fibrogenesis.
METHODS. Current literature to date demonstrates conflicting evidence regarding the impact of smoking status on long-term outcomes in the setting of fibrotic ILDs. Therefore, to further understand the impact of smoking status on fibrotic ILD patients’ survival, we began by assessing a prospective observational cohort, the Canadian Registry for Pulmonary Fibrosis (CARE-PF). This included 3062 patients with fibrotic ILD who were considered smokers or never smokers. Next, we used a preclinical experimental mouse model of concurrent bleomycin-induced lung injury and CS exposure to investigate the effect of CS on macrophage subpopulation composition and function during tissue remodelling processes. Lastly, given that CS is known to stimulate the UPR and that an
impaired UPR is a potential mechanism for macrophage dysfunction, we specifically addressed the impact of altered UPR on pulmonary macrophage composition and function during bleomycin-induced lung injury. To achieve that, we utilized the myeloid-specific deletion of Atf6α, one of the UPR mediators, experimental approach.
MAIN RESULTS. Findings from subgroup analysis of CARE-PF patient cohort demonstrated that overall, there was a significant interaction between smoking and fibrotic ILD diagnosis (p-value for interaction is 0.039), with respect to mortality. Specifically, the subgroup analysis has shown that smoking was an effect modifier and significantly increased mortality in connective tissue disease-associated ILD and unclassifiable ILD
patients, but did not have a significant effect on mortality in idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis patients. Furthermore, preclinical findings demonstrated that cigarette smoke exposure impaired the composition of pulmonary macrophages increasing CD11b+ subpopulations including monocyte-derived alveolar macrophages (Mo-AM) as well as interstitial macrophage (IM)1, -2 and -3, at multiple CS exposure timepoints. The expansion of Mo-AM and IM3 was dependent on IL-1α and likely reflective of increased cell recruitment. Compositional changes in macrophage subpopulations were associated with impaired induction of fibrogenesis including decreased α-smooth muscle actin positive myofibroblast following intratracheal bleomycin treatment. Mechanistically, in vivo and ex vivo assays demonstrated predominant macrophage M1 functional status and reduced matrix metallopeptidase 9 activity in cigarette smoke-exposed mice. Lastly, following bleomycin administration, the myeloid-specific deletion of Atf6α altered pulmonary macrophage composition, expanding CD11b+ populations with dual polarized CD38+CD206+ expressing macrophages. Compositional changes were associated with an aggravation of fibrogenesis including increased myofibroblast and collagen deposition. Further mechanistic ex vivo investigation revealed that ATF6α was required for CHOP induction and for the apoptotic death of bone marrow-derived CD11b+ macrophages during chronic ER stress, a process we speculate to be crucial for the attenuation of fibrogenesis.
CONCLUSION. CS and aberrant ER stress/UPR disturbed pulmonary macrophage subpopulation composition and function, expanding CD11b+ macrophages, and resulted in alterations in wound healing and repair processes. Further investigation of CD11b+ macrophages in clinical samples obtained from fibrotic ILD patients enrolled in CARE-PF is required. Targeting these populations through the UPR might offer a potential therapeutic approach to halt fibrotic ILD progression. We believe that a better understanding of the complex interplay of CS, UPR, and macrophage will identify potential intervention strategies to restore conventional macrophage and UPR functions
and mitigate disease exacerbation.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Fibrotic interstitial lung diseases (ILDs) comprise a wide array of devastating, irreversible,
and ultimately fatal heterogeneous disorders of known and unknown etiology. Pulmonary
fibrosis constitutes the late phase of ILDs. Pulmonary fibrosis is characterized by
progressive lung scarring due to excessive wound healing. The exact triggers which initiate
fibrotic processes remain unknown. Nevertheless, it is currently believed that in the
genetically pre-disposed lung, cigarette smoke exposure contributes to the development of
pathogenic fibrosis. Notably, central to the pathogenesis of cigarette smoke-associated
pulmonary fibrosis is the macrophage. In addition to smoking, intrinsic processes mediated
by protein misfolding, prolonged endoplasmic reticulum (ER) stress, and chronic unfolded
protein response (UPR) perform vital roles in macrophage activation in pulmonary fibrosis.
To date, the mechanisms by which continuous smoking and altered ER stress/UPR affect
pulmonary macrophage composition, function and consequently pulmonary fibrosis
development, progression, and immunopathogenesis are yet to be elucidated. This Ph.D.
thesis begins by assessing the impact of smoking on the survival and pulmonary function
outcomes of patients diagnosed with fibrotic ILDs. Subsequently, the thesis investigates
the effects of smoking and aberrant ER stress/UPR on pulmonary macrophage composition
and function in the setting of lung injury, tissue remodelling, and fibrogenesis using
preclinical experimental mouse models.


title: Universal Position-Sensorless Control for Switched Reluctance Motor Drives

contributor:
Emadi, Ali
Electrical and Computer Engineering

subject:
Switched reluctance motor
position-sensorless control

abstract:
Switched reluctance motors (SRMs) are promising candidates for electric vehicles due to lower manufacturing costs, higher efficiency, and robustness operation in a harsh envi-ronment. For accurate control of the SRM, the real-time rotor position is needed for phase computation. To obtain position information, position-sensorless control techniques have been developed to take the role of position sensors in commercial SRM drives for cost reduction or sensor-fault tolerance capability. Nowadays, the position-sensorless control of SRMs still suffers from a technical problem: the dependence on magnetic characteris-tics. Existing position estimation algorithms often require time-consuming offline meas-urement of magnetic parameters, limiting the broad applications due to the low generality. It is therefore of great significance to develop universal position-sensorless control tech-niques with less magnetic parameter dependence.
Zero- and low-speed position-sensorless control of the SRM needs high-frequency in-jection into the idle phase to measure the stator inductance. Rotor position is often esti-mated from the prestored inductance lookup table but is replaced by a new regional phase-locked loop (RPLL) with a self-commissioning process in this thesis. The modeling of the unsaturated stator inductance can be established automatically via the pulse voltage injection at the initial stage without offline testing. The RPLL embedded with a three-phase heterodyne design can estimate the full-cycle rotor position from the idle-phase in-ductance based on the unsaturated inductance model. The proposed low-speed position estimator can also realize robust sensorless control in four-quadrant operation and magnet-ic saturation conditions without complicated magnetic characteristics. Besides, local sta-bility of the position estimator is proved, and an optimized parameter design scheme is given.
Although pulse voltage injection offers accurate position estimation in low-speed op-eration, the induced pulse current results in additional copper loss and torque ripples. This problem is overcome in the thesis by regulating the magnitude of induced current at a minimal level. The induced current regulator is designed as a terminal sliding-mode con-troller that adjusts the injection voltage online over the whole idle-phase period. Proper control parameter selection based on the convergence analysis and stability proof ensures robust control performance against parameter uncertainties. The proposed pulse injection scheme combined with the RPLL can guarantee accurate position estimation while reduc-ing copper losses and torque ripples significantly.
Due to the shortened idle-phase duration when the rotor speed increases, pulse injec-tion methods are infeasible for high-speed position estimation. To solve the problem, this thesis proposes a nonlinear observer based on feature position estimation in conduction phases for high-speed sensorless control. A self-commissioning method is adopted to cap-ture a two-dimensional flux linkage curve at a feature position, which avoids offline measurement of the complete three-dimensional characteristics. However, the estimated feature position has low resolution, and its estimation accuracy is degraded by nonideal flux linkage errors. To improve the sensorless control performance, a nonlinear state ob-server using online Fourier series is then designed to eliminate disturbances in position es-timation. Parameter design based on a small-signal analysis is also given to guarantee ac-curate position and speed estimation.
High-speed position-sensorless control is further simplified using a new quadrature flux estimator without using any flux linkage characteristics. The method requires neither offline measurement nor online self-commissioning. This advantage is realized by adopt-ing a speed-adaptive bandpass filter to extract the fundamental flux linkage. A three-phase phase-locked loop is then used to estimate the rotor position from the orthogonal flux linkage signals without a priori knowledge of the SRM magnetic characteristics. The magnetic-parameter-free position estimation can facilitate the application of sensorless control in a general-purpose SRM converter.
A wide-speed range position estimation scheme is realized by combining both the low-speed and high-speed position estimation approaches. Consequently, a universal posi-tion-sensorless control scheme is proposed in the thesis, covering the full-speed range and not requiring offline measurement effort.
The proposed position estimation schemes are verified on a 5.5 kW 12/8 SRM test bench.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Investigating the impact of cigarette smoke on the immunopathogenesis of chronic respiratory disease

title: CIGARETTE SMOKE IMPACT ON RESPIRATORY DISEASE IMMUNOPATHOLOGY

contributor:
Stampfli, Martin
Medical Sciences

subject:
Cigarette smoke
Respiratory disease
COPD
Autoantibodies
Macrophage
Immunology
Immune system
Tissue remodelling

abstract: Overall, the work presented in this thesis explored the impact of cigarette smoke on the immunopathogenesis of respiratory disease. This thesis highlighted the determinantal impact of cigarette smoke on (auto)antibody levels and pulmonary macrophage composition. Work completed by Steven P Cass 2016-2021.

abstract:
Cigarette smoke is an insidious insult that is associated with a spectrum of respiratory diseases that range from cancer to obstructive diseases such as chronic obstructive pulmonary disease (COPD), to restrictive diseases such as idiopathic pulmonary fibrosis (IPF). In this thesis, we explore how cigarette smoke impacts immune components that contribute to respiratory disease.
To begin, we assessed the impact of cigarette smoke on airway antibody and autoantibody levels. We assessed sputum, a non-invasive method to sample the lower airways, to directly assess the presence of antibodies and autoantibodies in COPD. Total immunoglobulin M (IgM), IgG and IgA were detectable in the sputum of subjects. Notably, in patients with mild to moderate COPD, current smoking status was associated with decreased IgM and IgG. Next, using a comprehensive autoantigen array, we measured matched sputum and serum autoantibodies in 224 individuals. Serum autoantibodies were more abundant than sputum autoantibodies and correlated strongly between two independent COPD cohorts. Overall, the autoantibody profile of a patient with COPD was the same as a control subject. A proportion of autoantibody specificities were differentially expressed in patients with COPD with anti-tissue autoantibodies weakly associated with measures of emphysema. Taken together, these data suggested chronic cigarette smoke exposure was associated with limited differential expression of autoantibodies, but these changes were not a reliable method to identify COPD status.
In our third study, we assessed the impact of cigarette smoke exposure on the composition and function of pulmonary macrophage subpopulations.  Macrophages perform a central role in respiratory host defence and are implicated in the pathobiology of several respiratory diseases. Using a mouse model of cigarette smoke exposure, we reported cigarette smoke-induced expansion of CD11b+ macrophage subpopulations including monocyte-derived alveolar macrophages and interstitial macrophages. The altered pulmonary macrophage composition following cigarette smoke exposure contributed to attenuated fibrogenesis in a model of bleomycin-induced lung injury. This study offered insight to pulmonary macrophage composition and function following cigarette smoke exposure.
	This thesis summarises the original contributions and work completed during the course of this Ph.D., aimed at understanding the impact of cigarette smoke exposure on immune components central to respiratory disease. In conclusion, these findings shed light on the presence of (auto)antibodies in patients with COPD and the composition of macrophage subpopulations following cigarette smoke exposure.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Currently there are 1.3 billion people who use tobacco across the world. The most common method to consume tobacco is by smoking cigarettes. Cigarette smoking is well-known to cause disease; however, smoking rates are still increasing with more daily cigarette smokers in 2012 than there were in 1980. In this thesis, we explore the impact of cigarette smoke upon the immune system. We first assessed whether cigarette smoking impacts the levels of antibodies, proteins that are produced by the immune system to protect against foreign bodies, in healthy individuals, cigarette smokers without disease and patients with chronic obstructive pulmonary disease (COPD). We found that current smokers had decreased antibodies in the airways, thus predisposing cigarette smokers to increased damage. In our second study, we measured the presence of airway and blood autoantibodies. These are antibodies that target self and have the potential to inflict damage. We discovered that patients with COPD had minor changes in autoantibodies and these changes were weakly associated with emphysema. In our third study, we evaluated the impact of cigarette smoke on lung macrophages, cells that eat and destroy foreign bodies, in a mouse model of cigarette smoke exposure. Cigarette smoke increased the number of bone marrow-derived macrophages and this change in macrophage populations was associated with a reduced wound healing ability. Overall, these studies offer insight into how cigarette smoke impairs the function of the immune system and contributes to lung disease.


title: The Impact of Homophily and Herd Size on Decision Confidence in the E-commerce Context: A Social Identity Approach

contributor:
Hassenien, Khaled
Head, Milena
Business

subject:
E-COMMERCE
HERD SIZE
HOMOPHILY
UNCERTAINTY
DECISION CONFIDENCE

abstract:
As online shopping continues to grow rapidly, research indicates its massive uptake can be the result of the integration of social media technologies within the e-commerce interface. This has been further exacerbated by the COVID-19 pandemic which has led to an acceleration in the use of e-commerce. However, despite the growing popularity of e-commerce, shopping online is characterized by high levels of uncertainty given the spatial and temporal separation between consumer and vendor. This presents a dire impact on a consumer’s decision-making process and can specifically impact a consumer’s decision confidence. Decision confidence is an important construct that has been shown to be central in influencing a consumer’s behaviour, specifically in regards to purchase-related activities. Few studies have shed light on the factors influencing a consumer’s decision confidence in the e-commerce context.
Online shopping platforms fitted with social data markers are able to gauge and track the activities and attributes of online consumers, providing convenient heuristics on various measures such as the total number of recommendations for a product, or the degree of similarity between consumers. These markers may facilitate group identification through the development of herd behaviour. Herd behaviour arises in situations of uncertainty and motivates individuals to identify with a group (herd), and conform to its actions. Various aspects of a herd can influence group identification. This research focuses on two aspects of herd behaviour in e-commerce environments: homophily and herd size. Homophily is the degree to which individuals are similar, and in this study, we examine homophily from the perspective of an individual and the herd to which they may be exposed to.  Herd size is the number of individuals in a group taking a specific action such as an online purchase decision.
Drawing on the social identity approach and uncertainty identity theory, this investigation hones in on how homophily and herd size arise in the e-commerce context, and examines how group identification through homophily and herd size may reduce uncertainty and build decision confidence through the formation of trust, entitativity, sense of community and information helpfulness. A research model is developed along with a set of supported hypotheses. An online experiment utilizing a hypothetical e-commerce website was conducted with 400 participants. The results were analyzed using structural equation modeling and choice-based conjoint analysis. The results suggest that while homophily significantly impacts trust, sense of community, entitativity and information helpfulness, herd size does not. The results also suggest that whereas trust, sense of community and information helpfulness positively impact decision confidence, entitativity does not. It was also empirically demonstrated that participants preferred measures of homophily in the e-commerce interface more than measures of herd size. Furthermore, it was demonstrated that participants preferred measures indicating homophily in interests and demographics more than information on either alone, and that information on homophily in interests was more preferred than information on homophily in demographics.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Despite the rapid uptake in e-commerce, shopping online continues to be characterized by high levels of uncertainty given the spatial and temporal separation between consumer and vendor. This uncertainty negatively impacts a consumer’s decision confidence, which is a key driver in influencing consumer behaviour.
Drawing on the social identity approach and uncertainty identity theory, this study investigates how elements of the e-commerce interface can facilitate group identification, a process which has been empirically demonstrated to reduce uncertainty and thereby increase decision confidence. Findings of this study suggest that measures of homophily embedded within an e-commerce platform can work through various mediators to facilitate group membership which can positively impact a consumer’s decision confidence.
Theoretical and practical contributions of this study are discussed for researchers, academics, and practitioners wishing to explore those aspects of online shopping that an aid the decision-making process through group-related processes.


title: The Implications of Delta-9-tetrahydrocannabinol on Localized Immune and Hormonal Responses Mediated by Trophoblasts of the Human Placenta

contributor:
Raha, Sandeep
Medical Sciences

subject:
Placenta
Pregnancy
Trophoblast
Th1/Th2 cytokines
Delta-9-tetrahydrocannabinol

abstract: Over the approximate nine months of its intrauterine existence, the development of the fetus is supported by the human placenta. This transient organ is central to pregnancy success as it facilitates maternal-fetal exchange, immunological tolerance, and hormone production. Villous trophoblasts mediate placental formation by engaging in a continuous turnover process of proliferation, differentiation, fusion, and apoptosis. In doing so, cytotrophoblasts and syncytiotrophoblasts maintain the integrity of the outer placental lining known as the syncytium. Exposure to drugs, however, can compromise placental establishment, which can in turn adversely impact pregnancy and fetal health. Specifically, cannabis is widely used by women of reproductive age and during pregnancy. While maternal cannabis use is linked to poor outcomes such as preterm birth and neurodevelopmental delays in exposed children, the underlying mechanisms are not well-defined. First, we characterized a functionally relevant cell line to model differentiation and fusion. In a comparison of the BeWo and BeWo b30 cell lines, our findings demonstrated that both models similarly undergo fusion. We then explored the implications of exposure to delta-9- tetrahydrocannabinol (∆9-THC) on the immunological roles of villous trophoblasts. We observed that cytotrophoblast differentiation and fusion were associated with localized inflammation due to elevated interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α) but inhibited interleukin-4 (IL-4) and interleukin-10 (IL-10) production. ∆9-THC exposure impaired this T helper 1/2 cytokine balance through decreased IL-2 and TNF-α as well as increased IL-4 and IL-10 levels. Subsequently, we investigated the effects of ∆9-THC in TNF-α- and IL-10-dominant environments, to represent inflammatory and immunomodulatory microenvironments, respectively. Coincident with inflammation, ∆9-THC attenuated trophoblast fusion and the biosynthesis of steroid hormones, progesterone and cortisol, through perturbed cytochrome P450 regulation. This thesis ultimately lays a foundation for understanding how cannabis use during pregnancy may compromise the fusogenic, immune and endocrine functions of villous trophoblasts in the placenta.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The human placenta is a pregnancy-specific organ that supports the health of the mother- to-be and fetus. Stem cells known as cytotrophoblasts undergo differentiation and fusion to support the establishment of the syncytium, which creates a boundary that separates the maternal and fetal circulations. In the case of cannabis consumption during pregnancy, its biologically active components can travel to the placenta, cross the syncytium, and enter fetal blood. Our primary objective was to determine how cannabis exposure can impact the formation and maintenance of the syncytium. While maternal use has been linked to short- and long-term consequences for child health, existing research lacks a complete understanding of the underlying mechanisms. We demonstrate that cannabis exposure alters the production of important immune and hormonal factors during cytotrophoblast fusion, which may play a role in mediating poor placental development. Ultimately, it is critical to explore the implications of cannabis use for female reproductive health due to a rising trend in its use.


title: Investigation into mechanisms for antifungal resistance in Aspergillus fumigatus

contributor:
Xu, Jianping
Biology

subject:
Aspergillus fumigatus
Antifungal resistance
Triazoles
Amphotericin B
Comparative genomics

abstract: Aspergillus fumigatus is a filamentous saprophytic mold that is found abundantly in the biosphere. A. fumigatus is also an airborne human pathogen and is considered the major cause of aspergillosis, infections caused by inhalation of conidia. In immunocompetent individuals, the spores rarely cause any harm as they are cleared by innate pulmonary defences; however, in immunocompromised patients, the host immune system can fail to clear the inhaled conidia and aspergillosis may develop. Indeed, aspergillosis represents a major cause of morbidity and mortality in these populations. Aspergillosis is commonly treated using triazole and amphotericin B (AMB) antifungal agents. However, the increasing prevalence of triazole resistant strains and emergence of AMB resistance has become a challenge in treatment. To further expand our knowledge on the mechanisms of antifungal resistance in the species, we tested previously known or associated genes for antifungal resistance as well as investigated novel mechanisms via multiple genome-wide association studies (GWAS), which used a total of 211 genomes from A. fumigatus strains in 12 countries. Our results identified many novel mutations related to triazole and AMB resistance. Specifically, using stepwise GWAS analyses, we identified 6 and 18 missense variants to be significantly associated with itraconazole and voriconazole resistance, respectively. A linkage disequilibrium analysis identified six additional missense variants associated with triazole resistance, with two of these six being consistently associated with pan-azole resistance across subsets of samples. Furthermore, examination of known mutation sites and genes overexpressed with triazole exposure found a total of 65 SNPs implicated in triazole resistance. For the AMB study, we identified a total of 34 mutations associated with AMB tolerance using a GWAS. Subsequent analysis with 143 progeny strains, generated from a laboratory cross and genotyped with PCR-RFLP, identified epistatic interactions between five of these SNP sites that impacted growth in different concentrations of AMB. With the expanding immunocompromised population and increasing frequency of antifungal resistance, our results will help in investigating novel resistance mechanisms in A. fumigatus and in expanding the molecular diagnostic toolset in resistance screening, to enable rapid and accurate diagnosis and treatment decision-making.

abstract: Thesis

abstract: Master of Science (MSc)


title: Scalable Human Intestine Model with Accessible Lumen and Perfusable Branched Vasculature

contributor:
Zhang, Boyang
Chemical Engineering

subject:
in vitro intestine model
organoids
organ-on-a-chip
perfusable vasculature

abstract: Two-dimensional cell culture and animal models inadequately represent human pharmacokinetics and diseases like inflammatory bowel disease and colorectal cancer. This means missed diagnostic and therapeutic opportunities, high drug attrition rates, and a portfolio of approved drugs that underdeliver the desired benefits to patient outcomes. This encourages the development of a more physiologically relevant intestine model. The objective of this work was to develop a 384-well plate organ-on-a-chip platform, IFlowPlateTM, that can accommodate up to 128 human intestine models with accessible lumens and perfusable branched vasculature in an ECM environment. Fibrin-Matrigel® was used a structurally supportive and biologically instructive substrate that enabled: (1) prolonged cell culture (at least 15 days) with routine refreshment of aprotinin-supplemented medium, (2) formation of a confluent Caco-2 monolayer with barrier function, and (3) de novo assembly of a vascular network with barrier function. A fluorescent dextran permeability assay was used for in situ real-time measurements of epithelial barrier function in a high-throughput manner. Mixed co-culture of endothelial cells and fibroblasts in fibrin-Matrigel® resulted in the formation of an interconnected network of patent vessels that retained an albumin surrogate tracer within the luminal space indicating endothelial barrier function. To improve the success rate of anastomoses between living vessels and fluidic channels, the modification of inherently hydrophobic PDMS and polystyrene culture surfaces with ECM protein was explored. To address the limitations of a cancer cell line-derived intestine model, the replacement of Caco-2 cells with biopsied-derived colon organoid cells was investigated. Different gel formulations were assessed for their ability to induce colon organoid fragments to form monolayers. Finally, the incorporation of multiscale intestinal topography and luminal flow was considered through a modified approach to plate fabrication, whereby moulded alginate is embedded in ECM and sacrificed to generate a scaffold. Work to make the moulded alginate more robust is presented.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Two-dimensional cell culture and animal models inadequately represent human drug metabolism and diseases like inflammatory bowel disease and colorectal cancer. The objective of this work is to develop a more physiologically relevant human intestine model. Using fabrication techniques pioneered by the semiconductor industry, a custom organ-on- a-chip platform in the format of a 384-well plate was developed. This platform is compatible with standard laboratory equipment and practices and can accommodate up to 128 human intestine models comprised of the intestinal epithelium and associated network of blood vessels. In this platform, the cells of the intestinal epithelium and vasculature are supported by a network of natural proteins. This allows processes like vessel growth to be modelled in this platform. Vessel growth plays a key role in the progression of inflammatory bowel disease and cancer, and this model could help scientists better understand these diseases.


title: Corrosion Inhibition of Magnesium Alloy by Dissolved Lithium Carbonate

contributor:
Kish, Joseph R.
Materials Science and Engineering

subject: ZEK100, AZ31B-H24, Mg alloys, Inhibitors

subject: Cathodic activation, SVET,

abstract:
The extent to which dissolved Li2CO3 can inhibit corrosion of lightweight Mg alloy sheet metal in contact with aqueous NaCl solutions was determined. Two Mg alloy sheet metal alloys were studied, which include: AZ31B (3% Al, 1% Zn, 0.5% Mn, balance Mg) and ZEK100 (1.3% Zn, 0.2% Nd, 0.25% Zr, balance Mg).
Corrosion inhibition was first determined for each alloy separately when immersed in 0.1 M NaCl (aq), with and without dissolved Li2CO3 added. The addition of 100 mM Li2CO3 (aq) reduces the corrosion rate of AZ31B by a factor of ~10 and ZEK100 by a factor of ~12.  Inhibition involves a reduction in both global anodic dissolution and cathode (H2 gas evolution) kinetics. It also involves suppression of localized filament-like corrosion and associated anode/cathode activation. Site specific cross-sectional analysis of the surface film formed during forced anode activation (polarization) revealed the formation of a Li-doped MgO film, akin to what forms, and provides protection to, Mg alloys with Li added as an alloying element. Such film formation was used to explain all corrosion inhibition aspects.
Corrosion inhibition was then determined for ZEK100 when immersed in 0.1 M NaCl (aq) with and without a spray-deposited Li2CO3 surface coatings added. A commercial hexafluoro-titanate/zirconate-polymer conversion coating (Bonderite® MNT 5200) also served as the comparative basis. The Li2CO3-coated surface exhibits the lowest relative corrosion, whereas the conversion-coated surface exhibits the highest. Improved corrosion control is attributed to the formation of a compact coating (physical contribution) and the ability of dissolved Li2CO3 to inhibit both the anode and cathode kinetics (electrochemical) contribution. The findings are of interest to automotive industry as a possible means to effectively control corrosion of Mg alloy sheet metal using Li2CO3 as a surface pre-treatment or the inclusion of Li2CO3 to a polymer as an inhibitor additive.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The objective of this research was to determine the extent to which dissolved lithium carbonate (Li2CO3) can inhibit corrosion of lightweight magnesium (Mg) alloy sheet metal in contact with aqueous NaCl solutions. Corrosion inhibition by dissolved Li2CO3 in 0.1 M NaCl (aq) was demonstrated for two Mg alloy sheet metal alloys: AZ31B (3% Al, 1% Zn, 0.5% Mn, balance Mg) and ZEK100 (1.3% Zn, 0.2% Nd, 0.25% Zr, balance Mg). As a next step towards the development of a protective coating scheme, corrosion inhibition of ZEK100 by Li2CO3, as a surface coating applied, is achieved through a reduction of both the anodic dissolution and the cathode (H2 gas evolution) kinetics in large part by the formation of a Li-doped MgO film at anodic dissolution sites.


title: Pandemic Deaths: Media Representations of Long-Term Care in Ontario as a Sociological Case Study

contributor:
Kapiriri, Dr. Lydia
Health and Aging

subject: Long-Term Care Facilities; Institutions; Medicalization; Iatrogenesis; Pandemicization

abstract: The mass media influences our worldviews and perceptions, especially of social problems and potential solutions. Importantly, media messages, especially when repeated over time and during a crisis (real or perceived), tend to influence future public policy. Consistent with other periods of crisis and uncertainty, the COVID-19 pandemicization has led to an increased consumption of and reliance on news for accurate information and guidance on what to do and how to act amidst changing public health regulations and social norms. While the aging demographic has made media headlines before the COVID-19 pandemic was declared, the death of nearly 4,000 long-term care facility patients in Ontario alone since March 2020, most of them older adults, has increased the salience of Long-Term Care in the news (television, radio, newspapers, and digital news platforms). In this regard, many claims have been made in the media regarding older adults and their care and safety. But how are the problems leading to mass deaths in LTCFs defined and subsequent solutions presented in the mass media? In order to answer this question, this research asks: how are aging, care, and safety constructed or portrayed in newspaper coverage of LTC in Ontario during the first eight months of the COVID-19 pandemicization? Moreover, what are the implications of these portrayals for an aging population whereby nearly all of us will either need assistance at some point in our lives, provide this assistance to others, or both? Newspaper articles in the National Post on the topic of LTC from March to November 2020 were reviewed using Critical Discourse Analysis. Findings indicate event bias in reporting, journalistic ignorance on the issues in LTC and for those confined therein, dehumanization of older adult subjects, and highly medicalized notions of care and safety.

abstract: Thesis

abstract: Master of Arts (MA)

abstract: The mass media influences our perceptions, especially of societal problems and potential solutions. Consistent with other periods of uncertainty, since the declaration of the COVID-19 pandemic, consumption of and reliance on news has increased among the public. Importantly, media messaging during a crisis often influences future public policy with the potential to further exacerbate the crisis. The death of nearly 4,000 long-term care facility patients in Ontario alone since March 2020, most of them older adults, has increased the salience of Long-Term Care in the news, but toward what end? In order to deconstruct media messages during this time of tremendous upheaval, this research asks: how are age(ing), care, and safety portrayed in newspaper coverage of LTC in Ontario during the first eight months of the COVID-19 pandemic? What are the consequences of these portrayals for an aging population whereby nearly all of us will either need assistance at some point in our lives, provide this assistance to others, or both?


title: A Two-branch Neural Network for Non-homogeneous Dehazing via Ensemble Learning

contributor:
Chen, Jun
Electrical and Computer Engineering

abstract: Recently, there has been rapid and significant progress on image dehazing. Many deep learning based methods have shown their superb performance in handling homogeneous dehazing problems. However, we observe that even if a carefully designed convolutional neural network (CNN) can perform well on large-scaled dehazing benchmarks, the network usually fails on the non-homogeneous dehazing datasets introduced by NTIRE challenges. The reasons are mainly in two folds. Firstly, due to its non-homogeneous nature, the non-uniformly distributed haze is harder to be removed than the homogeneous haze. Secondly, the research challenge only provides limited data (there are only 25 training pairs in NH-Haze 2021 dataset). Thus, learning the mapping from the domain of hazy images to that of clear ones based on very limited data is extremely hard. To this end, we propose a simple but effective approach for non-homogeneous dehazing via ensemble learning. To be specific, we introduce a two-branch neural network to separately deal with the aforementioned problems and then map their distinct features by a learnable fusion tail. We show extensive experimental results to illustrate the effectiveness of our proposed method.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Using the CRISPR/Cas9 system to understand the biology of natural killer cells and unleash their function in the tumour microenvironment

contributor: Medical Sciences (Molecular Virology and Immunology Program)

subject: NK cell

subject: CRISPR/Cas9

subject: CD56

subject: Cbl-b

subject: Cancer immunotherapy

abstract:
NK cell based anti-tumour therapies demonstrate high efficacy in targeting hematological malignancies, however, treatments for advanced solid tumours face challenges. The immunosuppressive environment produced by tumours prevents NK cells from maintaining cytotoxic activity and reducing tumour burden. Enhancing NK cell activation is essential to improve their function against solid tumours. Genetic manipulation of primary NK cells with viral and non-viral methods has seen a drastic improvement in recent years. Lentiviral vectors are being used to generate CAR-NK cells ex vivo, while refinement of electroporation protocols has allowed for the generation of stable gene knockouts in primary NK cells. To establish and validate the generation of a stable knockout in primary human NK cells we focused on targeting the NCAM-1 (CD56) surface adhesion molecule. The high surface expression of CD56 in NK cells makes it a suitable target to establish the knockout protocol. Furthermore, despite its levels of expression being correlated to different functional phenotypes, the role of CD56 in NK cell function is not understood.
Here we have shown that current lentiviral transduction protocols are not viable methods to deliver the sgRNA/Cas9 system into primary NK cells. However, we found that nucleofection of the sgRNA/Cas9 complex into NK cells is an efficient method to generate gene knockouts. Using newly generated CD56KO NK cells we have shown that the expression of CD56 has no effect on NK cell cytotoxicity, cytokine production, proliferation, and in vivo tissue trafficking.
In parallel, we have also identified an intracellular pathway that is active in the tumour microenvironment and could inhibit NK cell function. Recent studies on the intracellular signaling of the E3 ubiquitin-protein ligase Cbl-b have highlighted its role in inhibiting NK cell tumour lytic and anti-metastatic activity. Immunosuppressive factors produced by tumours activate the Cbl-b pathway, leading to the targeted degradation of signaling proteins required for NK cell activation. We have shown that Cbl-b is upregulated in ex vivo expanded NK cells cultured with GAS6 or ovarian cancer ascites. Therefore, the generation of human primary Cbl-bKO NK cells could be a beneficial asset to enhance NK cell cancer immunotherapy.

abstract: Thesis

abstract: Master of Science (MSc)


title: Radiation Shielding Concrete for Spent Nuclear Fuel Interim Dry Storage

contributor:
Chidiac, Samir E
Civil Engineering

abstract:
The demand for nuclear energy, which is marketed as zero-emission clean energy and a secure source of electricity, is continuously rising globally. However, associated radioactive waste such as spent nuclear fuel (SNF) presents a serious health and waste management hurdle. Interim dry storage methods have emerged as a remedial measure for the nuclear industry. This includes the concrete-based dry storage cask which is the focus of this study.
The evolution and design requirements of SNF dry storage casks and interim storage facilities were first reviewed, and the existing design and operation challenges were identified. Accordingly, four comprehensive studies were undertaken: 1) quantify the effects of minerals and other additives added to enhance radiation shielding concrete on the concrete physical and mechanical properties; 2) develop a user-friendly computational software, named MRCsC, for estimating fast neutron macroscopic removal cross-section, ΣR (in cm-1), for shielding materials; 3) investigate experimentally and analytically the effects of adding powder boron carbide on Portland cement hydration kinetics and concrete compressive strength and radiation shielding properties; 4) study analytically the effectiveness of aggregates such as barite and celestite on concrete radiation shielding properties, and model the feasibility of developed concrete mixes as an overpack in a sandwich-design storage cask using the software OpenMC.
Overall, the results reveal that sandwich-design concrete cask meets all the requirements for SNF dry storage. The addition of powder boron carbide, up to 50% by weight of cement, delayed the cement initial setting time by approximately 6 h, yielded a 15% increase in cumulative heat of hydration and a 28% increase in concrete compressive strength after 3 days, and increased the thermal neutron absorption (Σabs) close to 62000%. Concrete mixes with barite and celestite, as coarse aggregates replacement, significantly improve concrete radiation shielding efficiency and feasibility of sandwich-design storage cask. The OpenMC model results revealed over 60% decrease in the total dose rate.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
The dire need for radioactive wastes disposal, especially spent nuclear fuel (SNF) being the most hazardous, has increased with the ever-increasing accumulated amount worldwide. This disposal must be safe, efficient, and long-term. Therefore, different techniques have been employed to provide secure storage for these harmful wastes. However, one technique has lately gained notable importance in the absence of a permanent repository until now; which is the interim dry storage technique. This technique guarantees secured long-term storage, with relatively low costs, for all kinds of radioactive wastes.
Concrete, a reasonably cheap construction material, is one of the main components existing in multiple faces of interim dry storage. As a result, continuous research aims to develop concrete mixes with enhanced properties, especially radiation shielding properties. This would lead to a reduction in the needed thickness/area, simplifying the overall design requirements, and saving materials, thus decreasing the total costs.
Accordingly, developing concrete mixes with improved properties, specifically radiation shielding properties, is the pivot of this research.


title: Defining the role of Xin and associated proteins in skeletal muscle health

contributor: Medical Sciences (Cell Biology and Metabolism)

abstract:
Xin is a F-actin cytoskeletal remodelling adaptor protein important for skeletal muscle health,
including functionality and regeneration. Previous studies from our lab have proposed new roles for Xin based on Xin -/- studies in murine skeletal muscle and satellite cells (SCs). We discovered that Xin also maintained mitochondrial morphology and function and facilitated extracellular Ca2+ entry by stabilizing membrane protein channel components. However, these observations lacked a molecular basis, as many of Xin’s protein binding partners remain unknown. The main objective of this study was to utilize a Xin overexpression (OE) model to aid in discovering the function of Xin within skeletal muscle and identify new Xin binding partners. While Xin OE had a no discernible effect on myoblast morphological features and F-actin distribution, it significantly hindered differentiation into multi-nucleated myotubes. Time based differentiation assays from Xin OE myoblasts showed myotube lengths were decreased at day 5 (20%; P<.001) and further decreased at day 7 (60%; P<.0001). Xin OE cells displayed an abnormal increase mitochondrial enzyme content (~2.94 fold) and a reduction in myoblast motility (~45%, P <0.05), both which likely contributed to deficits in differentiation. Tracking Xin’s subcellular localization, Xin colocalized with mitochondria markers (~71 % Overlap; R2 0.68) and was present in mitochondria fractionations. Xin co-immunoprecipitated with mitochondrial-associated membrane (MAM) tether proteins: VDAC, Mitofusin 1, and Mitofusin 2. Furthermore, Xin interacted with extracellular calcium entry channels and related proteins such as: Orai1, Stim-1, Junctin, Triadin, and Homer. These results provide further evidence that Xin is a multi-functional protein which regulates mitochondria and cellular calcium entry by directly interacting with MAM tethers and calcium channels. Based on our Xin overexpression and knockout experiments, these molecular interactions ultimately play a role in myoblast differentiation and maintain contractile and metabolic function within skeletal muscle fibers.

abstract: Dissertation

abstract: Master of Science in Medical Sciences (MSMS)


title: Advanced Pre-processing Techniques for cloud-based Degradation Detection using Artificial Intelligence (AI)

contributor:
Habibi, Saeid
Mechanical Engineering

subject:
Artificial Intelligence
Pre-processing techniques
Automotive

abstract:
Predictive maintenance is extremely important to fleet owners. On-duty automobile engine failures add cost of extra towing, gas and labor expenses which can add up to millions of dollars every year. Early knowledge of upcoming failures helps reduce these expenses. Thus, companies invest considerably in fault detection and diagnosis (FDD) systems to reduce unnecessary costs. Artificial Intelligence (AI) is getting increasingly used in the data driven signal based FDD industry because it requires less labor and equipment. It also results in higher productivity since it can operate continuously. This research offers Artificial Intelligence based solutions to detect and diagnose the degradation of three Internal Combustion Engine (ICE) parts which may cause on-duty failures: lead-acid accessory battery, spark plugs, and Exhaust Gas Recirculation (EGR) valve. Since the goal behind most FDD systems is cost
reduction, it is important to reduce the cost of the FDD test. Therefore, all the FDD solutions proposed in this research are based on three types of built-in sensors: battery voltage sensor, knock sensors and speed sensor. Furthermore, the engine database, the Machine Learning (ML) and Deep Learning (DL) models, and the virtual operating machines were all stored and operated in the cloud.
In this research, eight Machine Learning (ML) and Deep Learning (DL) models are proposed to detect degradations in three vehicle parts mentioned above. Additionally, novel advanced pre-processing approaches were designed to enhance the performance of the models. All the developed models showed excellent detection accuracies while classifying engine data obtained under artificially and physically induced fault conditions. Since some variant data samples could not be detected due to experimental flaws, defective sensors and changes in temperature and humidity, novel pre-processing methods were proposed for Long Short-Term Memory Networks (LSTM-RNN) and Convolutional Neural Networks (CNN) which solved the data variability problem and outperformed the previous ML/DL models.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The Portraits of the Roman Empress Sabina: A Numismatic and Sculptural Study

contributor:
Beckmann, Martin
Classics

subject:
portraiture
numismatics
Rome
Roman women
sculpture
Roman provinces

abstract:
The Roman Empress Sabina is a pivotal figure in the representation of imperial women.  She appears with more portrait types and on a higher proportion of the coinage produced both at Rome and in the provinces than any of her predecessors.  While her sculpted likenesses do not compare in number to Livia’s, they do exceed those of most of the intervening women.  This variety and quantity of representation created a new paradigm that was followed in subsequent reigns.  All of this is contrasted with the lack of attention paid to Sabina in ancient historical writing, making the portraits of Sabina the best source on her life.
My study differs from previous examinations of Sabina’s portraits in its methodological approach.  I begin with a study of the coinage produced at Rome.  I establish a concrete chronology of these coins through the use of die studies of both the aurei and dupondii/asses in order to resolve unanswered questions about the sequence and dating of Sabina’s portrait types.  Through this new chronology, I interpret the significance of each portrait type.  I then conduct the first detailed study of the provincial coin portraits of Sabina.  The differences between the distribution of portrait types in quantity, chronology, and geography between the imperial and provincial coins reveals some of the mechanisms behind the two media and the reception of Sabina throughout the Empire.  Comparing these data with the sculpture helps illuminate the distinctions in production and dissemination between media.  Through this study, I create the most complete picture of Sabina’s portraiture to date and challenge previously held assumptions concerning the mechanisms of portrait creation.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The Empress Sabina was married to the Emperor Hadrian for his entire reign of over twenty years (117-138).  Although she is almost completely absent from the ancient historical record, her portraits are more plentiful and varied than those of any imperial woman before her, making these our best source of information about her.  This study covers the portraits of Sabina which appear on coins produced in Rome, coins produced in the Roman provinces, and sculpture produced throughout the Empire.  The analysis of the coins produced at Rome establishes the chronology of the different representations of Sabina.  This chronology facilitates the interpretation of why these changes in the Empress’s appearance were made.  Comparison between the portraits in different media and from different areas of the Empire reveals the impact of context on the production, dissemination, and style of imperial portraits.


title: Complementary, Alternative, and Integrative Medicine, Natural Health Products, and Medical Cannabis: Patient Preference and Prevalence of Use, Quality of Patient Health Information, and Safety and Effectiveness Concerns

contributor:
Busse, Jason Walter
Health Research Methodology

subject:
complementary and alternative medicine
integrative medicine
natural health products
medical cannabis
patient preference
quality of information
safety and effectiveness

abstract: The thesis is comprised of three separate studies that each relate to one of the aforementioned therapy types: complementary, alternative, and integrative medicine (CAIM), natural health products (NHPs), and medical cannabis. Parallels can be drawn across these therapy types in general including patient preference and prevalence of use, quality of patient health information, and safety and effectiveness concerns. Knowledge of these parallels both informed the development of these three studies and emerged across findings. Chapter 1 provides a comprehensive introduction to these parallels in the context of CAIM, NHPs, and medical cannabis. Chapter 2 comprises a cross-sectional survey determining NHP use disclosure to primary care physicians among patients attending a Canadian naturopathic clinic. Chapter 3 comprises a qualitative interview study identifying attitudes towards medical cannabis among family physicians practicing in Ontario, Canada. Chapter 4 comprises a sentiment analysis of Twitter data to understand how CAIM is mentioned during the COVID-19 pandemic. Lastly, chapter 5 serves as the conclusion of this thesis, and summarizes the most important findings, addresses study strengths and limitations, and discusses future directions from this work.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: AN INVESTIGATION INTO THE ROLE OF MMP9 IN REGULATING CYTOSKELETAL REMODELLING DURING TGF-β INDUCED EMT IN THE LENS

contributor:
West-Mays, Judith
Medical Sciences

abstract:
Fibrotic cataracts are attributed to transforming growth factor-beta (TGF-β)-induced epithelial-to-mesenchymal transition (EMT) (Eldred et al., 2011). Using in vivo and ex vivo mouse knockout (KO) models, our laboratory has identified matrix metalloproteinase-9 (MMP9) as an essential protein in the EMT process. However, alternations to the cytoskeleton were observed in MMP9KO mouse lens epithelial cells (LECs) (Korol et al., 2014). In addition, alpha-smooth muscle actin and filamentous actin stress fibres were absent in TGF-β2 treated MMP9KO mouse LECs, and a NanoString analysis revealed no marked differences in ACTA2 and ACTB expression between the lenses of TGF-β-overexpressing mice (TGF-βtg) and TGF-βtg mice on a MMP9KO background. Our laboratory subsequently conducted a cytoskeletal protein array, which revealed the differential regulation of numerous proteins in MMP9KO mouse LECs.
	The purpose of this thesis is to validate select proteins from the protein array, and reveal pathways that are regulated by MMP9 during TGF-β2-induced EMT. In order to improve the efficiency of experiments, the novel MMP9-specific inhibitor, JNJ0966, was confirmed to be able to prevent TGF-β2-induced EMT in rat LEC explants. Cortactin, focal adhesion kinase (FAK), lim-domain kinase 1 (LIMK1) and myosin light chain 2 were selected from the array and analyzed via western blot and immunofluorescence analyses. Results from the protein array and validation studies agree for all selected proteins except for FAK. Although FAK was upregulated in rat LECs that were co-treated with JNJ0966 and TGF-β2 (TG:JNJ), it was not activated to exert its effects. Interestingly, LIMK1 was also observed to be localized to the nucleus in JNJ0966-treated LECs. The localization of MRTF-A was also analyzed via immunohistochemistry, and we observed reduced MRTF-A nuclear translocation in TG:JNJ LECs. Results from this thesis revealed that MMP9 deficiency differentially regulated proteins involved in actin polymerization and cell migration, and these alterations conferred resistance against TGF-β2-induced EMT.

abstract: Thesis

abstract: Master of Science (MSc)


title: Evaluation of Point of Care Ultrasound Training for Midwives

contributor:
Murray-Davis, Beth
Health Science Education

subject:
Midwifery
Midwifery Education
Point of Care Ultrasound
Point of Care Ultrasound Training
Continuing Health Professions Education
Health Professions Education

abstract: MSc. Thesis

abstract:
Introduction: In 2018, the College of Midwives of Ontario expanded the scope of practice for registered midwives to include performing point of care ultrasound (POCUS) to aid their obstetrical clinical assessments. This project evaluated learner sonography knowledge, skill acquisitions, and integration of this technology following an innovative POCUS curriculum developed for midwives to understand the impacts of this training.

Methods: Concurrent triangulation with mixed methods was used in this study through surveys and interviews. First, the surveys were used to collect data across four time points including before and after the intervention. Five- and seven-point Likert scale questions were analyzed through descriptive statistics. Open-ended questions were qualitatively analyzed using thematic analyses. Second, the semi-structured interviews were conducted to better understand participants’ attitudes and clinical behaviours. Interviews were coded and analyzed using a combination of Corbin and Strauss as well as Charmaz approaches to grounded theory.

Results: The findings demonstrated how there was a positive growth in learner comfort with POCUS and a desire to continue using it during clinical practice. The frequency of POCUS use within antenatal care increased with common applications including fetal presentation and assessment of pregnancy viability. The interviews highlighted five themes: facilitating learning, improving care, refining the role of the midwife, serving community, and maintaining competency. Access to clinical placements and the cost of a device were identified as barriers to promoting POCUS skill sets. Participants who had access to a device and completed the clinical practicum are continuing to use sonography within their clinics to provide more comprehensive client care.

Conclusions: This project demonstrates how POCUS training can positively impact midwives particularly with aiding clinical decision making such as those regarding fetal viability and presentation. However, the challenges with obtaining a clinical practicum to ensure competency and the cost and access to a device, are significant barriers that unless they are addressed, may result in minimal integration within community practices.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract: The ability to conduct ultrasounds has recently been included in Ontario midwives’ scope of practice. This project evaluated a newly developed Point of Care Ultrasound (POCUS) curriculum for practicing midwives to understand how midwives can learn and apply POCUS into their clinical work. Learners completed surveys at four time points from pre-course to one-year post-course to share their experiences of knowledge and skill acquisition and applying this training to their clinical work. Five midwives also participated in an interview to share their perspectives about the course more in-depth. It was found that Ontario midwives were very interested to learn POCUS to improve client care. Unfortunately, they struggled finding time and opportunities to refine their sonography skills such as securing a clinical practicum or the funds to purchase a device. However overall, POCUS in midwifery was well received, this technology and its respective education should continue to be supported in Ontario.


title: A Discrete Wavelet Transform GAN for NonHomogeneous Dehazing

subject:
NonHomogeneous Dehazing
Discrete Wavelet Transform
Generative Adversarial Network
Deep Learning

abstract: Hazy images are often subject to color distortion, blurring and other visible quality degradation. Some existing CNN-based methods have shown great performance on removing the homogeneous haze, but they are not robust in the non-homogeneous case. The reason is twofold. Firstly, due to the complicated haze distribution, texture details are easy to get lost during the dehazing process. Secondly, since the training pairs are hard to be collected, training on limited data can easily lead to the over-fitting problem. To tackle these two issues, we introduce a novel dehazing network using the 2D discrete wavelet transform, namely DW-GAN. Specifically, we propose a two-branch network to deal with the aforementioned problems. By utilizing the wavelet transform in the DWT branch, our proposed method can retain more high-frequency information in feature maps. To prevent over-fitting, ImageNet pre-trained Res2Net is adopted in the knowledge adaptation branch. Owing to the robust feature representations of ImageNet pre-training, the generalization ability of our network is improved dramatically. Finally, a patch-based discriminator is used to reduce artifacts of the restored images. Extensive experimental results demonstrate that the proposed method outperforms the state-of-the-art quantitatively and qualitatively.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Origin of RNA on Biogenic Worlds

contributor:
Pudritz, Ralph E.
Physics and Astronomy

subject:
Astrobiology
Atmospheric Chemistry
Origins of Life
Planetary Astrophysics

abstract:
Given the role of HCN as a reactant in RNA building block production (e.g. nucleobases, ribose, and 2-aminooxazole), we propose that an atmosphere rich in hydrogen cyanide (HCN) is a distinguishing feature of what we term biogenic worlds. These are worlds that can produce key biomolecules for the emergence of life in situ rather than requiring they be delivered, e.g., by meteorites. To attack the question of whether early Earth was biogenic, we develop a series of new capabilities including the calculation of missing/unknown HCN reaction rate coefficients, the simulation of HCN chemistry in planetary atmospheres, and the coupling of atmospheric HCN chemistry and rain-out to the production and evolution of RNA building blocks in warm little ponds (WLPs). We make a major leap in understanding the origin of RNA on a biogenic early Earth by building a comprehensive model that couples terrestrial geochemistry, radiative transfer, atmospheric photochemistry, lightning chemistry, and aqueous pond chemistry.

             We begin by developing an accurate and feasible method to calculate missing reaction rate coefficients related to HCN chemistry in planetary atmospheres. We use density functional theory simulations to solve the transition states for various reactions, and use the simulated energies and partition functions to calculate the corresponding rate coefficients using the principles of statistical mechanics. We initially explore and calculate rate coefficients for a total of 110 reactions present in reducing atmospheres dominated by N2, CH4, and H2, including 48 reactions that were previously unknown in the literature. Our rate coefficients are most commonly within a factor of two of experimental values, and generally always within an order of magnitude of these values. This accuracy is consistent with the typical uncertainties assigned in large-scale kinetic data evaluations.

             Next, we develop a consistent reduced atmospheric hybrid chemical network (CRAHCN) containing experimental values when available (32%) and our calculated rate coefficients otherwise (68%). To validate our chemistry, we couple CRAHCN to a 1D disequilibrium chemical kinetic model (ChemKM) to compute HCN production in the reducing atmosphere of Saturn's moon Titan. Our calculated atmospheric HCN profile agrees very well with the measurements performed by instruments aboard the Cassini spacecraft, suggesting our chemical network is accurate for modeling HCN production in reducing environments. We also perform sensitivity analyses on this chemistry and find HCN production and destruction on Titan can be understood in terms of only 19 dominant reactions. The process begins with UV photodissociation of N2 and CH4 in the upper atmosphere, and galactic cosmic ray dissociation of these species in the lower atmosphere. The dissociation radicals then proceed to react along four main channels to produce HCN. It is of particular excitement that one of these channels was newly discovered in this work.

Moving forward to modeling early Earth, we expand upon CRAHCN by exploring and calculating rate coefficients related to HCN and H2CO chemistry in atmospheres with oxidizing conditions. We calculate the rate coefficients for 126 new reactions, including 45 reactions that were first discovered in this work. We find the accuracy of our method continues to produce most commonly factor of two agreement with respect to experimental values. Next, we develop the oxygen extension to CRAHCN (CRAHCN-O), containing a total of 259 reactions for computing HCN and H2CO production in atmospheres dominated by N2, CO2, H2, CH4, and H2O. Again, experimental rate coefficients are used when available (43%), and our calculated values are used otherwise (57%).

We then build a comprehensive model with a unique coupling of early Earth geochemistry, radiative transfer, atmospheric UV and lightning chemistry, and aqueous chemistry in WLPs. We calculate self-consistent pressure-temperature profiles using a 1D radiative transfer code called petitRADTRANS, and couple these to CRAHCN-O and ChemKM to simulate HCN and H2CO production on early Earth. We model two epochs, at 4.4 and 4.0 billion years ago (bya), which differ in atmospheric composition, luminosity, UV intensity, radical production from lightning, and impact bombardment rate. The respective reducing and oxidizing atmospheric compositions of the 4.4 and 4.0 bya epochs are mainly driven by the balance of H2 impact degassing and CO2 outgassing from volcanoes. We then couple the rain-out of HCN with a comprehensive WLP model to compute the in situ production of RNA building blocks for each epoch. HCN pond concentrations are multiplied by experimental yields to calculate biomolecule production, and there are various biomolecule sinks present including UV photodissociation, hydrolysis and seepage.

At 4.4 bya, we find that HCN rain-out leads to peak adenine production of 2.8μM (378 ppb) for maximum lightning conditions. These concentrations are comparable to the peak adenine concentrations delivered by carbon-rich meteorites (10.6μM); however, the concentrations from in situ production persist for > 100 million years in contrast to ~days for meteoritic concentrations. Guanine, cytosine, uracil and thymine concentrations from in situ production at this time peak in the 0.19–3.2μM range, and ribose and 2-aminooxazole peak in the nM range. We note that cytosine and thymine are not present in meteorites, suggesting this biogenic pathway may be one of the only plausible origins of these RNA and DNA building blocks. We find that the high mixing ratio of HCN near the surface of our 4.4 bya model is mainly driven by lightning chemistry rather than UV chemistry. Our results show that HCN production at the surface is linearly dependent on lightning flash density. This result supports a lightning-based Miller-Urey scenario for the origin of RNA building blocks. At 4.0 bya, HCN production and rain-out is 2–3 orders of magnitude less abundant than it is at 4.4 bya, leading to negligible concentrations of RNA building blocks in WLPs during this late oxidizing phase. Similar to HCN production in Titan's atmosphere, HCN production in early Earth's atmosphere is strongly correlated with CH4 content. Reducing (H2-dominant) conditions sustain CH4 levels at a roughly constant ppm-level over 100 million years, which is favourable for HCN production. In oxidizing conditions, CH4 is readily oxidized into CO2, leading to less HCN. These results suggest that early Earth was biogenic at 4.4 bya, and remained so for at least ~100 million years, but was over by 4.0 bya due to oxidation of the atmosphere.

This thesis provides a firm theoretical foundation for an origin of RNA in WLPs on a biogenic early Earth within about 200 million years after the Moon-forming impact and the cooling of the magma ocean.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A CULTURAL ADAPTATION OF WESTERN PSYCHOLOGY: EVALUATING THE ROLE OF COLLABORATIVE CARE IN A SCHOOL BASED MENTAL HEALTH PROGRAM IN THE EASTERN MEDITERRANEAN REGION

contributor:
Savelli, Mat
Global Health

subject:
school mental health
transcultural psychiatry
collaborative care
child health
implementation science

abstract:
Globally, children and youth are more vulnerable to experiencing mental health
challenges; early intervention is key to preventing ongoing mental health difficulties into
adolescence and adulthood. School-based mental health interventions have proven to be
effective but require a significant amount of collaboration between teachers, parents,
mental health specialists and other important stakeholders. Equally noteworthy are the
significant treatment, resource and capacity gaps between high and low to middle income
countries when it comes to child mental health; the SHINE research group seeks to
implement a school-based mental health program in countries in the Eastern
Mediterranean region. They also intend to scale-up the prevention and intervention
capabilities of said countries to improve overall child mental health. This study
investigated the role of collaborative care in SHINE’s program development and
implementation processes, while examining the cultural and societal challenges
associated with implementing a school mental health program developed primarily in
high-income countries to specific non-Western contexts. Individual and small-group indepth interviews were conducted with ten key stakeholders from the SHINE team and
partner countries (specifically Iran, Jordan and Egypt). Findings identified the potential
for the collaborative care approach within the SHINE school mental health program to
greatly ameliorate child mental health outcomes. Additionally, participants noted the
necessity for clearer stakeholder role definition and differentiation of general vs specific
program elements between countries. Challenges associated with implementing the
intervention in the Eastern Mediterranean region included the dominant role of the
family, challenging societal norms and stigmatization and structural barriers to applying
SHINE’s specific program resources. In summary, the role of collaborative care is
increasingly important to SHINE’s current efforts in improving child mental health,
however, individual cultural and country characteristics should be an area of emphasis
moving forward.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
The SHINE research group are implementing a school-based mental health intervention
in the Eastern Mediterranean region, alongside a facilitated collaborative learning group
involving key local and global stakeholders. This study focuses on the collaborative care
element of the school-based mental health program and its impact on the overall
functioning of the intervention, in different country contexts. Collaborative care involves
the interactions between parents, teachers, mental health professionals and researchers to
ensure the sustainability of the program as well as its scalability to different country
contexts. This is an exploratory qualitative study with a case study design; data has been
collected with ten participants through individual and small group in-depth interviews.
Interviews were transcribed, coded and then cross-compared using thematic analysis to
identify overarching patterns. The primary goals of the study are to examine the role of
collaboration as well as to consider some of the challenges of applying Western
psychological interventions to diverse country and cultural contexts.


title: Bioengineered Liver Assembloids with Zonation

contributor:
Zhang, Boyang
Biomedical Engineering

subject: tissue spheroids, hPSC, assembloid, vasculature, liver

abstract: There are a number of pressing issues that the creation of a biomimetic liver culture may be able to solve including catching hepatic mal interactions that are currently missed in preclinical drug screening and offering an alternative solution in the shortage of organs for liver transplant. There are multiple hepatic models that have been created to overcome these issues. However, of the many considerations that need to be taken in the creation of a biomimetic liver model, many fail to capture the functional zone-patterning that is found in vivo. Here is detailed the creation of a hepatic assembloid model that incorporates zone-specific human pluripotent stem cell derived hepatocytes for the recapitulation of zone-patterning in the liver tissues. Use of our lab’s z-wire plate and PGS z-wire scaffold allows for the formation of elongated 3D tissues that resembles the overall morphology of the liver acinus and facilitate the spontaneous development of an aligned vascular-like network. Sustained hepatocyte-specific function in these tissues are promising indicators for application of the hepatic models in drug screening, disease modelling, and regenerative medicine.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Soil-Structure Interaction of Deeply Embedded Structures

contributor:
Guo, Peijun
Civil Engineering

subject: Soil-Structure Interaction

subject: Seismic Waves

subject: Rayleigh Waves

subject: Seismic Lateral Earth Pressure

subject: Three-dimensional Wave Propagation Theory

subject: Spectral Element Method

abstract:
In recent years, the desperate need for reliable clean and relatively small power demand has emerged for edge-of-grid or off-grid regions to keep pace with development demands. A salient technology that has gained much attention for this purpose is the Small Modular Reactors, i.e., SMRs. SMRs differ from conventional Nuclear Power Plants (NPPs) in many aspects, specifically the enclosing structure of the reactor. The burial depth of the SMR structure is expected to reach great depths. For example, the substructure depth reaches 30 m in the SMR design proposed by NuScale (NuScale Power, 2020). Consequently, seismic analysis of deeply embedded structures with a relatively small footprint has been identified as one of the challenges to the safe implementation of SMR technology (DIS-16-04, 2016). Such structures are expected to be more sensitive to surface wave propagation and the seismic interaction with nearby substructures and nonstructural elements such as pipelines.
This dissertation develops analytical and numerical methods to analyze the seismic earth pressure exerted on the SMR substructure by considering the effects of seismic surface waves, structure-soil-structure interaction (SSSI), and the interaction with nearby pipelines. The three-dimensional wave propagation theory is employed in the analysis. Solutions for the earth pressure induced by Rayleigh waves are obtained for substructures deeply embedded into homogeneous or multilayered soil profiles. In addition, the effect of thin soil layer (stiff or soft) soils in a soil profile is investigated in the presence of Rayleigh waves. Furthermore, additional earth pressure due to SSSI is examined, and a simplified procedure is proposed based on the three-dimensional wave propagation theory and a guided flow chart to track seismic wave interference. The SSSI analysis yields solutions for the optimal distance between substructures corresponding to the minimum SSSI in new designs. The interaction between substructures and nearby pipelines is explored numerically using the Spectral Element Method. SPECFEM2D software is adopted to perform the analysis, where the three-dimensional wave propagation is successfully implemented. Based on the analysis for pipelines with different configurations, general conclusions are drawn regarding the additional earth pressure on substructures and pipelines based on a comprehensive parametric study of various parameters. In addition, this research also provides an approach to determine the backfill configuration and the selection of backfill materials, which could minimize the seismic amplitudes transmitted to substructures.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Small Modular Reactors (SMRs) are the cornerstone of recent developments in the nuclear industry. However, the SMRs technology faces several safety-related challenges, which includes the earthquake hazards related to the large embedment depth of the enclosing structure. In particular, the major concerns are about the risks related to seismic surface waves as well as the seismic interaction between nearby structural and non-structural elements (e.g., pipelines). The thesis addressed these major concerns by developing analytical and numerical methods to complement the analysis for the integrity of SMRs with sufficient seismic resistance. The solutions are verified and benchmarked using data in the literature. Future researches are suggested to further improve seismic analysis of SMRs.


title: Inherent Acts of Self-determination: Administrative Control of Elementary Education at Six Nations, 1960-2005

contributor:
Bouchier, Nancy
History

subject: First Nations Education

subject: Administrative Control

subject: Self-determination

subject: Sovereignty

subject: Haudenosaunee

abstract: I collaborate with Elders of the Six Nations of the Grand River Territory – mainly former vice-principals and principals – to share their stories about elementary school administration of the community’s day schools of the 1960s, 70s, and 80s, and of the larger consolidated schools thereafter. By engaging in storywork with them, their stories reveal that as Indigenous organizations like the National Indian Brotherhood/Assembly of First Nations (NIB/AFN) warned First Nations about mistaking administrative control, or delegated authority as it framed it, as real, local control over their children’s education, vice-principals and principals in Six Nations reframed it as inherent acts of self-determination and sovereignty over education. Drawing on Audra Simpson’s nested sovereignty, and Glen Sean Coulthard’s self-recognition to produce a more accurate representation of administrative control in the community, the author argues that vice-principals and principals in Six Nations did not mistake their practice as delegated authority but instead – as inherently sovereign actors – went through a process of negotiating self-determination and sovereignty within the Department of Indian Affairs and Northern Development Canada’s (DIAND) educational framework to upset its status quo of First Nations only managing educational programs and services. If sovereignty is understood to be a process, rather than a destination as Robert Allen Warrior suggests, then vice-principals and principals exercising administrative control on a daily basis in their schools should be recognized as inherently self-determining and sovereign. By sharing their stories, they reveal that they possess the authority to determine the definition and character of administrative control at the local level. The argument’s implication being that there are alternative ways of knowing and understanding administrative control in First Nations schools, rather than the national discourse that evolved in the decades following the NIB’s Indian Control of Indian Education.

abstract: Thesis

abstract: Master of Arts (MA)

abstract: I collaborate with Elders of the Six Nations of the Grand River Territory – mainly former vice-principals and principals – to share their stories about elementary school administration of the community’s day schools of the 1960s, 70s, and 80s, and of the larger consolidated schools of the 1990s and early 2000s. By engaging in storywork with the Elders, their stories reveal that as Indigenous organizations like the National Indian Brotherhood/Assembly of First Nations (NIB/AFN) warned First Nations communities about mistaking administrative control, or delegated authority as it framed it, as real, local control over their children’s education, vice-principals and principals in Six Nations reframed it as inherent acts of self-determination and sovereignty over education. Their stories provide an alternative way of knowing and understanding administrative control in First Nations schools.


title: Membrane Filtration of Microplastic Fibers: Assessment of Membrane, Microplastic, and Solution Properties

contributor:
Latulippe, David
Hoare, Todd
Chemical Engineering

abstract: Microplastics (MPs), plastic particles less than 5 mm in size, have become ubiquitous in the environment due to increasing plastic production and pollution. MPs pose a significant threat to both aquatic life and human health due to their small size and heterogeneity in shape (e.g. fragments, fibers, films etc.) and chemistry (e.g. polyethylene, polystyrene, polypropylene etc.) A significant source from which MPs can enter the environment is the effluents of wastewater treatment plants (WWTPs). Membrane filtration systems, used in some WWTPs, have been shown to be effective at removing MPs, as most MPs are larger than the membrane pores. Understanding the impacts MPs have on membrane filtration is a growing area of interest due to their potential adverse effects, though all studies to date have been focused specifically on MP fragments. As MP fibers (MPFs) are common in both the influents and effluents of membrane systems in WWTPs, it is important to understand their impact on membranes and how they can be removed. In this work, polystyrene was electrospun into a fiber mat, which was cut using a cryostat to yield MPFs. Fluorescent MPFs were created by doping the electrospinning solution with meso-tetraphenylporphyrin, enabling the detection of MPFs in suspension. These MPFs were used to investigate the impacts of membrane pore size, solution chemistry, and MPF length on the removal of MPFs and membrane fouling. MPFs were found in the permeate of a 5 µm membrane, with some MPFs exceeding the nominal membrane pore size. Feed suspensions with shorter MPFs were found to result in more MPFs passing through the membranes compared to feed suspensions with wider variation in MPF lengths. When MPFs were suspended in real WW, both 0.22 µm and 5 µm membranes experienced more fouling compared to when MPFs were suspended in Milli-Q water. This work highlights the importance of working with solutions and particles realistic to those found in WWTPs and the environment to better understand the impact MPFs can have on membrane filtration.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Microplastics, plastic particles that are less than 5 mm in size, have been found throughout the environment due to increasing plastic production and use. Microplastics pose a significant threat to aquatic life as when ingested, microplastics can have negative impacts on the development, behaviour, and mortality of aquatic organisms.  Wastewater treatment plants have been found to be a significant source through which microplastics enter the environment as microbeads from personal care products and microplastic fibers from the laundering of synthetic textiles are discharged into municipal sewage systems. Membrane filtration systems used in some wastewater treatment plants have been shown to be effective for microplastic removal but few studies exist examining the filtration of microplastics in depth. In this work, microplastic fibers were manufactured, mimicking those found in wastewater treatment plants, to use in membrane filtration experiments. The impact of membrane properties, solution chemistries, and microplastic fiber properties on membrane filtration were examined.


title: Advanced Multilevel Topologies and Control for EV Ultra-Fast Charging Applications

contributor:
Narimani, Mehdi
Electrical and Computer Engineering

subject:
EV Charging
Multilevel Converters

abstract:
The inevitable choice for the automotive industry to suppress greenhouse gas
emissions is zero-emission vehicles such as battery electric vehicles. Some of the
main barriers regarding the adoption of electric vehicles are range anxiety, and lack
of charging infrastructure, which can be addressed by ultra-fast chargers or charging
stations. The conventional ultra-fast chargers are low-voltage (LV) connected
through line-frequency transformers, which pose disadvantages such as low
efficiency, high cost, and large footprints. The medium-voltage (MV) connected
charging station is proposed by the researchers to overcome the challenges regarding
the conventional chargers by eliminating the line-frequency transformer and direct
connection to the medium voltage.
The most challenging part of the medium-voltage ultra-fast chargers is the
AC/DC stage connection to the medium voltage. Different medium-voltage
multilevel converters have been proposed to facilitate the direct connection to the
medium-voltage grid. However, disadvantages such as a high number of components
and control complexity weaken the strength of medium-voltage connected stations.
The main focus of this thesis is on novel advanced medium-voltage multilevel
topologies and control techniques for medium-voltage connected ultra-fast EV
charging applications. First, a novel controller based on SPWM is proposed to
control the flying capacitor voltages of a four-level T-type Nested Neutral Point
Clamped (NNPC) topology. Second, a new five-level T-type NNPC topology is
proposed that has a minimum number of components in comparison to other
existing five-level topologies. To extend the voltage and power rating, a novel seven-level
topology is proposed that has the lowest number of components in comparison
to other existing topologies. Moreover, three different controllers are developed to
control the voltages of the seven-level topology based on Model Predictive Control,
where the challenges regarding significant computational burden and weighting
factor elimination are addressed.
Finally, an MV-connected ultra-fast charging station architecture is proposed,
where the proposed seven-level topology is considered as the AC/DC stage.
Comparison of the proposed topology to the LV-connected stations shows that the
efficiency, cost, and power quality of the charging stations can be improved
significantly.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Prediction of Antimicrobial Resistance Phenotypes from Genotype

contributor:
McArthur, Andrew G.
Biochemistry and Biomedical Sciences

subject:
antimicrobial resistance
phenotype
genomics
genotype
microbiology
bacteria
bioinformatics

abstract:
Antimicrobial resistance (AMR) is a threat to global health, food security, and economic productivity. Infections caused by drug resistant Gram-negative pathogens, such as Escherichia coli, Pseudomonas aeruginosa, and Neisseria gonorrhoeae, are continuously becoming harder to treat due to limited treatment options and long turnaround times for culture-based phenotypic diagnosis. Alternatively, genotypic approaches that exploit whole genome sequencing have the potential to be faster and more accurate. Genotypic approaches rely on using bacterial genomes to predict AMR phenotypes.

I generated a rules-based algorithm and machine learning models using known resistance determinants from bacterial genomes to predict resistance or susceptibility.
I showed that machine learning was superior to a rules-based algorithm and achieved an average accuracy of 94% and 89% for E. coli and P. aeruginosa, respectively. These machine learning models identified novel AMR genotype-phenotype relationships between known resistance determinants and resistance phenotypes, which were experimentally validated.

To identify the parameters that can improve machine learning models, I tested a variety of genetic features, algorithms, and evaluation metrics. I observed an intricate dependency between parameters for AMR prediction performance, illustrating that careful selection of parameters is required to generate accurate AMR prediction models.

A limitation of this work was its prediction of resistance and susceptibility categories, as these are interpretations of minimum inhibitory concentrations defined by clinical breakpoint guidelines. Since multiple guidelines exist, these prediction models are not generalizable, so prediction of MIC values was explored. The average accuracy of my MIC prediction models was 86%, 41%, and 98% for E. coli, P. aeruginosa, and N. gonorrhoea, respectively.

Despite the multifactorial and intricate nature of the resistome, I was able to accurately predict AMR phenotypes for many antibiotics for these pathogens. This is a step towards advanced diagnostic microbiology methods driven by genomics.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Many surgeries, chemotherapy, and transplantation will be impossible if antibiotic resistance is not addressed. Antibiotic misuse, overuse, and time to definitive therapy exacerbate this global health problem. Phenotypic testing determines definitive therapy, but bacterial culturing is slow. A potentially faster and more accurate approach relies on sequencing the pathogen’s genome.

I used machine learning to generate antibiotic resistance prediction models that achieved average accuracies of 94% and 89% for Escherichia coli and Pseudomonas aeruginosa, respectively. These models identified novel relationships between known resistance genes and resistance phenotypes, which were experimentally validated.

Resistance and susceptibility are interpretations of a minimum inhibitory concentration (MIC) using a clinical breakpoint guideline. Since there are different guidelines, I generated MIC prediction models with average accuracies of 86%, 41%, and 98% for E. coli, P. aeruginosa, and Neisseria gonorrhoea, respectively.

My findings work towards a world where clinical sequencing and genomics-based diagnostics are the gold standard.


title: Performance Improvement of Switched Reluctance Motor (SRM) Drives Through Online Optimization Based Reference Current Identification and Digital Sliding-Mode Control

contributor:
Emadi, Ali
Nahid-Mobarakeh, Babak
Electrical and Computer Engineering

subject:
Switched Reluctance Machines
Digital Sliding-Mode Control
Nonlinear Optimization

abstract:
This thesis presents a torque control mechanism for switched reluctance machine
(SRM) drives. The proposed mechanism is capable of maintaining ripple free torque
control while minimizing the copper loss or mode-0 radial force or both at a fixed
switching frequency.
In the proposed approach, the torque control problem is addressed by splitting
it into two parts. The first part consists of identification of optimum phase current
references while the second part incorporates the design of an efficient current controller.
For the identification of optimum phase current references, three algorithms
are presented in the form of a developmental process. The nature of the online optimization
problem is demonstrated using a simple 2-dimensional gradient descent
method. Subsequently, a parametric form gradient descent algorithm is presented
which transforms the original optimization problem into two 1-dimensional problems,
viz. torque error minimization and identification of optimum search direction. This
method yields improved computational efficiency and accuracy. The third algorithm
incorporates projection using equality constraint on the phase torque contributions to
achieve a 1-dimensional solution process. Although this algorithm takes more iteration
as compared to the parametric form gradient descent algorithm, it demonstrates greater accuracy and computational efficiency. A comparative analysis of these algorithms
is performed in at different operating conditions in terms of the torque ripple
magnitude and computational effort.
The thesis also presents a comprehensive analysis of well known control techniques
for application in SRM current control in discrete-time domain. This analysis also
presents a comparative evaluation of these control techniques under different operating
conditions. On account of this analysis, several recommendations pertaining to
the performance improvement are presented.
Finally, a digital sliding-mode based model-free current controller suitable for fixed
switching frequency operation is presented. The proposed controller is capable of
providing a consistent dynamic response over wide operating range without utilizing
any model information. The reference current tracking performance of this controller
is verified through simulation studies in MATLAB/Simulink® environment and over
a 1.2kW, 100V, 2500RPM, 12/8 experimental SRM drive.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Multiscale Electron Microscopy Imaging and Spectroscopy of Atomically Thin Layers at Heteroepitaxial Interfaces

contributor:
Bassim, Nabil
Materials Science and Engineering

subject: heteroepitaxy

subject: 2D gallium

subject: cadmium telluride

subject: confinement heteroepitaxy

subject: scanning transmission electron microscopy

subject: electron energy loss spectroscopy

abstract:
Two-dimensional (2D) materials have properties that are often different from their three-dimensional (3D) bulk form. Many of these materials are stable at ambient conditions, which allows them to be integrated with other 2D- or 3D-materials to form heterostructures. Integration of various dimensional materials attains unique electrical and optical properties that aid in developing novel electronic devices. The interface of the heterogeneous integration of these films can exhibit a weak van der Waals-like bonding.
In this thesis, an advanced characterization (from atomic to millimeter resolution) of various dimensional materials with weakly bonded interfaces is developed and employed to understand their behavior at scale. First, a large-area single-crystal cadmium telluride thin film is grown incommensurately and strain-free to a sapphire substrate despite a significant 3.7% lattice mismatch. The film remarkably delaminates as a bulk single crystal film due to an atomically thin tellurium that spontaneously forms at the interface. Aberration-corrected electron microscopy and spectroscopy reveal both the van der Waals-like structure and bonding at the film/substrate interface. Second, a large-area atomically thin gallium is intercalated at the interface of epitaxial graphene. Correlative microscopy workflows are applied to understand the thickness uniformity and area coverage of the 2D–gallium over few millimeters of the sample. Utilizing multiple correlative methods, SEM image contrast is found to be directly related to the presence of the intercalated gallium. The origin of the SEM contrast is investigated as a function of the surface potential. Then, the heterostructure characterization is scaled up over a few square millimeter areas by segmenting SEM images, each acquired with nanometer-scale resolution. Additionally, transmission electron microscopy is applied to investigate the interface of gallium–SiC, the gallium air–stability, and the role of the substrate on the heteroepitaxial growth of 2D–gallium, which charts a path for further development of these materials.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Intelligent Energy Management Strategy for Eco-driving in Connected and Autonomous Hybrid Electric Vehicles

contributor:
Emadi, Ali
Mechanical Engineering

subject: Connected Vehicles, Eco-driving, Energy Management Strategy, Hybrid Electric Vehicles, Reinforcement Learning

abstract:
This thesis focuses on developing an intelligent energy management strategy for eco-driving in Connected and Autonomous Hybrid Electric Vehicles (CA-HEV's), which can be implemented in real-time. The strategy is divided into two layers, i.e. the upper level controller and the lower level controller. The upper level controller can be executed on the remote server. It is responsible for extracting the information from the driver about the trip and the vehicle information using the communication capabilities of the CA-HEV. The gathered information is then utilized by dynamic programming (DP), which is implemented in a bi-layer fashion to reduce the computation burden on the server. The outer layer of the DP algorithm  and the optimal velocity trajectory and the inner layer optimizes the power distribution in the powertrain to minimize fuel consumption alongside maintaining charge balance conditions. These global optimal results are evaluated for an ideal environment without any traffic information. The lower level controller is responsible for real-time implementation on vehicles in the real world environment and is based on a well-accredited reinforcement learning (RL) strategy, i.e., Q-learning. The RL-based controller optimally distributes the power in a CA-HEV and maintains charge balance conditions. Furthermore, the RL-based controller is also trained on the remote server based on global optimal results obtained from the DP algorithm. The optimal parameter information is then resent to the vehicle's embedded controller for real-time implementation. Simulations are performed for Toyata Prius (2010) on MATLAB and Simulink, and road information is gathered from SUMO. Simulation results provide a comparative study between the global optimal and the RL-based controller. To validate the adaptiveness of the RL-based controller, it is also tested on two approximate real-world
drivecycles and its performance is compared against global optimal results evaluated using DP.

abstract: Thesis

abstract: Master of Applied Science (MASc)