title: Trauma-informed care within and across systems of care

contributor:
Hanna, Steven
Health Policy

subject: trauma, trauma-informed care, child welfare, education, justice, health, social services

abstract:
Trauma has been described as a pressing public health concern and research evidence demonstrates how unresolved trauma can lead to multiple co-morbidities including chronic medical conditions such as cardiovascular disease. Furthermore, epidemiological evidence demonstrates the high prevalence of trauma histories amongst service users seeking care across a range of systems including child welfare, education, health, social services and the criminal justice system. In response, the concept of trauma-informed care (TIC) has emerged, but how TIC can be conceptually defined and utilized remains unclear in the scholarly literature.
This dissertation utilizes a variety of methodological approaches to explore how and under what conditions TIC can be utilized within and across systems of care to address the prevalence of trauma-affected individuals seeking care. First, a critical interpretive synthesis of the TIC literature provides an overview of how TIC can be defined and utilized through the development of a conceptual framework situating TIC within and across systems of care. A theoretical framework outlines important contextual factors, such as system arrangements as well as the political system, that can act as either barriers or facilitators to the operationalization of TIC. Second, a document analysis examines how and under what conditions TIC is utilized in adult mental health policy documents in Ontario, Canada. Finally, a case study explores what factors led to the exclusion of TIC from Ontario’s first province-wide strategy on mental health and addictions. Collectively, these three studies add several substantive, methodological and theoretical contributions regarding a cohesive understanding of what is trauma, how TIC can be defined and operationalized and the role of TIC at various levels within and across systems of care.  Mobilizing sustainable and effective TIC has been demonstrated to improve the overall health and well-being of both service users and services providers, leading to stronger systems of care and healthier communities and societies at large.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: The concept of trauma-informed care (TIC) has emerged in response to increased awareness regarding the prevalence and impact of trauma. A growing body of empirical literature has demonstrated the effectiveness of TIC within specific programs and services as well as at the organizational and system levels. What constitutes trauma, however, and how TIC can be defined and operationalized at various levels remains unclear. This thesis aims to address these gaps in the literature by: (1) developing a conceptual framework on TIC and a theoretical framework outlining the barriers and facilitators of TIC (2) examining how and under what conditions can TIC be utilized in mental health policy documents (3) exploring what are the political factors that can lead governments to decide against utilizing TIC.


title: Examination of Mitochondrial Bioenergetics in Skeletal Muscle Biopsies from Adults with Type 1 Diabetes

contributor:
Hawke, Thomas
Medical Sciences

subject:
Mitochondria
Type 1 Diabetes
Mitochondrial Bioenergetics
T1D
Diabetic myopathy
Muscle biopsy
High-resolution respirometry
Mitochondrial respiration
ROS
Sex differences
Sexual dimorphism
Mitochondrial density
OXPHOS
Mitochondrial ultrastructure

abstract: The overall objective of this thesis was to examine mitochondrial bioenergetics in muscle biopsies from humans with type 1 diabetes (T1D) to gain a deeper understanding of the cellular mechanism(s) underlying changes to skeletal muscle health reported in T1D, a phenotype we have referred to as ‘diabetic myopathy’. It was hypothesized that humans with T1D, compared to their matched counterparts without diabetes (control), would demonstrate significant deficiencies in muscle mitochondrial function and ultrastructure/content as determined by the gold-standard in vitro methodology: high-resolution respirometry and transmission electron microscopy, respectively. It was further hypothesized that sex differences would not exist in mitochondrial function with T1D, and mitochondrial deficiencies would be more dramatic at an earlier age with T1D. Adults with uncomplicated T1D and strictly matched controls (age, sex, BMI, self-reported physical activity levels) were recruited from surrounding university-dwelling communities. Site-specific deficiencies in mitochondrial respiration, H2O2 emission, and calcium retention capacity were found in young, physically active adults with T1D despite normal mitochondrial content. Further experiments revealed that muscle mitochondrial respiration in women and men differentially adapt to the T1D environment where men with T1D have lower complex II but higher complex I respiration compared to women with T1D, while women (irrespective of T1D) have lower ADP sensitivity. Women with T1D also demonstrated lower H2O2 emission compared to men with T1D. In contrast, despite a lower mitochondrial content in middle- to older-aged adults with T1D, mitochondrial respiration (normalized to content) was either normal or increased in adults with T1D compared to control, with observable differences between sexes. Overall, this research has demonstrated that despite being recreationally to physically active, adults with uncomplicated T1D with moderately well-managed glycemia demonstrate alterations in skeletal muscle mitochondrial function and ultrastructure, including differences between sexes.

abstract: Dissertation

abstract: Doctor of Science  (PhD)

abstract: Type 1 diabetes (T1D) is a complex disease that still has no known cure. Current treatment focuses on managing blood sugar levels with exogenous insulin injections and frequent blood sugar checks. However, over time, people with T1D still develop serious complications that inevitably impact their quality of life and lifespan. A potential adjuvant therapy to prevent complications in T1D is improving the health of skeletal muscle through exercise given its role in stabilizing blood sugar/lipid levels and whole-body insulin sensitivity. However, this area continues to be severely understudied in the T1D population. Thus, this thesis examined skeletal muscle metabolic ‘health’ from adults with T1D who do not have major diabetes complications and manage their blood glucose moderately-well. Through a series of novel experiments, we found that young and middle- to older-aged adults with T1D have alterations in the metabolic engines of their muscles, and depending on biological sex, the alterations manifest as either heightened or degraded cellular function. These findings are the first to provide a comprehensive cellular investigation of the impact of T1D on the metabolic health of skeletal muscle in people with T1D and provide the foundation for future research examining skeletal muscle as an essential and early adjuvant therapy in this population.


title: Design and Analysis of a 70KW 3-Level Active Neutral Point Clamped (ANPC) Inverter for Traction Applications

contributor:
Narimani, Mehdi
Emadi, Ali
Electrical and Computer Engineering

subject:
Active Neutral Point Clamped
Traction Inverter

abstract:
For an Electrical Vehicle, the power is delivered from the battery pack to the electric
motor through the use of power converter. Many research projects have been conducted
in improving the efficiency of traction inverters. Inverter topologies are categorized
based on the number of voltage levels of the inverter output phase voltage. The
conventional 2-level Voltage Source Inverter (VSI) is commonly used as a traction
inverter due to its simple structure. Due to the recent trend in utilizing higher DClink
voltage in traction motor drives to achieve a higher power rating, multi-level
inverters are gaining attention to replace the conventional VSI in EV powertrain.
Multi-level voltage source inverters (MLVSI) have been widely adopted in high-power
converters and medium-voltage drives. There are four major categories of
MLVSI: the Flying Capacitor (FC), Neutral Point Clamped (NPC), Cascaded and
Hybrid. The power rating of the MLVSI increases with the increase of inverter levels,
but the size, number of switching devices, cost and control difficulty also increases.
Due to the above reasons, 3-level NPC can be a good solution for traction inverters.
Due to the structure and control limitation, Diode Clamp NPC suffers from uneven
loss distribution and neutral point voltage balancing issues. This issue can be resolved
with Active Clamped NPC (ANPC). In this thesis, the design, simulation, prototyping
and testing of a 70kw 3-level ANPC traction is introduced.

abstract: Thesis

abstract: Master of Science (MSc)


title: Acoustic Noise Reduction in an 8/6 Switched Reluctance Machine using Structural Design

contributor:
Emadi, Ali
Bilgin, Berker
Mechanical Engineering

subject:
Acoustic noise
SRM
Vibration
Radial force
Structural design
Noise reduction

abstract:
Switched reluctance motors (SRMs) possess many desirable qualities for the long-term sustainability of electrified transportation such as cheap production costs and simple, robust configurations. However, high acoustic noise and torque ripple are two performance imperfections that have prevented the widespread implementation of SRMs. This thesis investigates design techniques to reduce the acoustic noise produced by an 8/6 SRM while also analyzing the impact each design has on the motor’s performance.
    The fundamentals of  SRMs are discussed  including the operating principles, modelling and control strategies. The multiphysics finite element analysis (FEA) toolchain used to accurately model acoustic noise and vibrations of SRMs is described. Using the network of FEA tools, nodal forces and natural frequencies of a four phase 8/6 SRM are analyzed to study the acoustic noise and vibration behaviours. The FEA process is validated experimentally by matching measured vibration modes and acoustic noise sound pressure level (SPL) with FEA numerical results.
    Through inspiration from an extensive literature review, various design techniques are applied to a baseline four phase 8/6 SRM and compared for both acoustic noise reduction and EM performance criteria. The investigated designs were split into two categories, stator-housing modifications that aim to increase the stiffness of the assembly and rotor modifications that aim to reduce the magnitude of radial forces while preserving performance.
    The best design strategies as determined by the comparative analysis were then further optimized to combine the best techniques together for the 8/6 SRM. The proposed structural improvements included the modifications of the stator yoke shape along with increasing the number of fastening components involved in the assembly. Additionally, an iterative procedure for the parametric modelling of windows introduced to the rotor poles is outlined. The best design considerations are combined to create the design of a novel 8/6 SRM which significantly reduces the acoustic noise produced by the motor with little impact to performance.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Mechanisms of type VI secretion system effector transport and toxicity

contributor:
Whitney, John
Biochemistry and Biomedical Sciences

subject:
Interbacterial competition
Type VI secretion system
Membrane protein toxins
Chaperone proteins
Bacterial alarmones
(p)ppApp synthetases

abstract: The type VI secretion system (T6SS) is a protein export pathway that mediates competition between Gram-negative bacteria by facilitating the injection of toxic effector proteins from attacking cells into target cells. To function properly, many T6SSs require at least one protein that possesses a proline-alanine-alanine-arginine (PAAR) domain. These PAAR domains are often found within large, multi-domain effectors that possess additional N- and C-terminal extension domains whose function in type VI secretion is not well understood. The work described herein uncovers the function of these accessory domains across multiple PAAR-containing effectors. First, I demonstrated that thousands of PAAR effectors possess N-terminal transmembrane domains (TMDs) and that these effectors require a family of molecular chaperones for stability in the cell prior to their export by the T6SS. Our findings are corroborated by co-crystal structures of chaperones in complex with the TMDs of their cognate effectors, capturing the first high-resolution structural snapshots of T6SS chaperone-effector interactions. Second, I characterize a previously undescribed prePAAR effector named Tas1. My work shows that the C-terminus of Tas1 possesses a toxin domain that pyrophosphorylates ADP and ATP to synthesize the nucleotides adenosine penta- and tetraphosphate (hereafter referred to as (p)ppApp). Delivery of Tas1 into competitor cells drives the rapid accumulation of (p)ppApp, depletion of ADP and ATP, and widespread dysregulation of essential metabolic pathways, resulting in target cell death. These findings reveal a new mechanism of interbacterial antagonism, the first characterization of a (p)ppApp synthetase and the first demonstration of a role for (p)ppApp in bacterial physiology. TMD- and toxin-containing PAAR proteins constitute a large family of over 6,000 T6SS effectors found in Gram-negative bacteria. My work on these proteins has uncovered that different regions found within effectors have distinct roles in trafficking between bacterial cells and in the growth inhibition of the target cell.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Bacteria constantly compete with their neighbours for resources and space. The type VI secretion system is a protein complex that facilitates competition between Gram-negative bacteria by facilitating the injection of protein toxins, also known as effectors, from attacking cells into target cells. In this work, I characterize several members of a large family of membrane protein effectors. First, I showed that these effectors require a novel family of chaperone proteins for stability and recruitment to the type VI secretion system apparatus. Second, I characterized the growth-inhibitory properties of one of these effectors in-depth and showed that it possesses a toxin domain that depletes the essential nucleotides ATP and ADP in target cells by synthesizing the nucleotides adenosine penta- and tetraphosphate, (p)ppApp. Together, these studies revealed a new mechanism for the intercellular delivery of membrane protein toxins and uncovered the first known physiological role of a (p)ppApp-synthesizing enzyme in bacteria.


title: THE EFFECTS OF AGING AND ALZHEIMER’S DISEASE ON RETROGRADE NEUROTROPHIN TRANSPORT IN BASAL FOREBRAIN CHOLINERGIC NEURONS

title: RETROGRADE NEUROTROPHIN TRANSPORT IN BASAL FOREBRIAN NEURONS

contributor:
Fahnestock, Margaret
Neuroscience

subject:
Basal forebrain
Neurotrophin
proNGF
BDNF
TrkA
TrkB
Axonal Transport
Retrograde Transport
Aging
Alzheimer's Disease
p75
Oxidative Stress
PTP1B
Rab proteins
Rab5
Rab7
3xTg-AD

abstract:
Basal forebrain cholinergic neurons (BFCNs) are critical for learning and memory. Profound and early BFCN degeneration is a hallmark of aging and Alzheimer’s disease (AD). BFCNs depend for their survival on the retrograde axonal transport of neurotrophins, proteins critical for neuronal function. Neurotrophins like brain derived neurotrophic factor (BDNF) and pro-nerve growth factor (proNGF) are retrogradely transported to BFCNs from their synaptic targets. In AD, neurotrophin levels are increased within BFCN target areas and reduced in the basal forebrain, implicating dysfunctional neurotrophin transport in AD pathogenesis. However, neurotrophin transport within this highly susceptible neuronal population is currently poorly understood.

We began by establishing protocols for the accurate quantification of axonal transport in BFCNs using microfluidic culture. We then determined the effect of age on neurotrophin transport. BFCNs were left in culture for up to 3 weeks to model aging in vitro. BFCNs initially displayed robust neurotrophin transport, which diminished with in vitro age. We observed that the levels of proNGF receptor tropomyosin-related kinase-A (TrkA) were reduced in aged neurons. Additionally, neurotrophin transport in BFCNs derived from 3xTg-AD mice, an AD model, was also impaired.

Next, we sought to determine a mechanism for these transport deficits. First, we determined that proNGF transport was solely contingent upon the levels of TrkA. We then found that elevation of oxidative stress, an established AD contributor, significantly reduced both TrkA levels and proNGF retrograde transport. TrkA levels are partially regulated by protein tyrosine phosphatase-1B (PTP1B), an enzyme whose activity is reduced by oxidation. PTP1B antagonism significantly reduced TrkA levels and proNGF retrograde transport in BFCNs. Treatment of BFCNs with PTP1B-activating antioxidants rescued TrkA levels, proNGF transport, and proNGF-mediated axonal degeneration.

Our results suggest that oxidative stress contributes to BFCN degeneration in aging and AD by impairing retrograde neurotrophin transport via oxidative PTP1B-mediated TrkA loss.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: During aging and Alzheimer’s disease (AD), the connections between neurons, a type of brain cell, break down, causing memory loss. This breakdown begins in a brain area called the basal forebrain. Basal forebrain neurons rely upon the transport of nutrients along their connections with other neurons, called axons, for proper function. This transport process becomes impaired in AD. Our goal was to understand why this happens. First, we determined that axonal transport was impaired with age and in basal forebrain neurons of mice genetically predisposed to develop AD. We recreated these impairments by increasing the levels of harmful molecules called reactive oxidative species (ROS). ROS levels increase with age and become abnormally high during AD. We found that increased ROS impair axonal transport and contribute to the breakdown of basal forebrain neurons. Our work suggests that reducing ROS will help prevent the breakdown of basal forebrain neurons in AD.


title: Investigating the in vivo effects of cannabis smoke exposure on lung innate immunity

contributor:
Hirota, Jeremy
Medical Sciences

subject: cannabis lung immunity influenza

abstract:
Cannabis is widely used for recreational and medicinal purposes. Inhalation of cannabis smoke is the predominant method of drug consumption, exposing the lungs to THC and CBD, as well as a plethora of toxic combustion products. Clinical observations suggest that cannabis smoking contributes to the development of respiratory symptoms and may play a role in the pathogenesis of inflammatory lung disease. However, the association between cannabis smoke, dysregulated pulmonary immunity, and the development of lung disease is inconclusive. To improve our understanding of this relationship, we developed novel mouse models to investigate the effect of cannabis smoke exposure on lung immunity.
Using compositionally relevant cannabis strains, we established a mouse model of cannabis smoke exposure and validated that it delivers cannabis smoke by measuring cannabis smoke-associated metabolites in the blood. In our initial lung immune characterization, we demonstrated that acute cannabis smoke exposure induces modest changes to innate immune cellularity in the airways and lung tissue. Specifically, lung macrophage subpopulations were proportionally altered following smoke exposure. As well, we demonstrated that lung disease-associated mediators, including MDC, TARC, and VEGF, were dysregulated in cannabis smoke-exposed lung tissue.
In addition to our initial characterization, we established a first-of-its-kind concurrent cannabis smoke exposure and influenza infection model. Using this model, we demonstrated that cannabis smoke exposure exacerbates weight loss following influenza infection. These increases in weight loss corresponded with dysregulated cellular responses and immune mediator expression. Cell types involved in early innate immune signaling, such as macrophages and dendritic cells, were significantly affected by concurrent exposure and infection. Additionally, anti-viral mediators. including IFNγ, IP-10, RANTES, and TNFα, were decreased in cannabis smoke-exposed, infected lung tissue.
Collectively, we defined two novel models of cannabis smoke exposure that can be leveraged in future investigations on the inflammatory effects and associated health outcomes of cannabis smoke.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Cannabis is widely used for recreational and medical purposes. Smoking is the most popular method to consume the drug among users. However, little is understood about the effects of cannabis smoke on lung health, despite evidence suggesting that it may lead to negative health outcomes. To address this gap in knowledge, we developed two unique mouse models of cannabis smoke exposure. Using these models, we explored the effects of cannabis smoke on lung immune responses in healthy and influenza infected mice. Our findings suggested that lung immunity is altered following cannabis smoke exposure. Additionally, we found that overall health was worsened during influenza infection in cannabis smoke-exposed mice. This effect was associated with weakened viral immunity in the lungs. The models we developed and the findings using it thus far create the foundation for future studies on cannabis smoke and lung health.


title: Monitoring-Camera-Assisted SLAM for Indoor Positioning and Navigation

contributor:
Chen, Jun
Electrical and Computer Engineering

subject: Monocular SLAM

abstract:
In the information age, intelligent indoor positioning and navigation services are required in many application scenarios. However, most current visual positioning systems cannot function alone and have to rely on additional information from other modules. Nowadays, public places are usually equipped with monitoring cameras, which can be exploited as anchors for positioning, thus enabling the vision module to work independently.

In this thesis, a high-precision indoor positioning and navigation system is proposed, which integrates monitoring cameras and smartphone cameras. Firstly, based on feature matching and geometric relationships, the system obtains the transformation scale from relative lengths in the cameras’ perspective to actual distances in the floor plan. Secondly, by scale transformation, projection, rotation and translation, the user's initial position in the real environment can be determined. Then, as the user moves forward, the system continues to track and provide correct navigation prompts.

The designed system is implemented and tested in different application scenarios. It is proved that our system achieves a positioning accuracy of 0.46m and a successful navigation rate of 90.6%, which outperforms the state-of-the-art schemes by 13% and 3% respectively. Moreover, the system latency is only 0.2s, which meets the real-time demands.

In summary, assisted by widely deployed monitoring cameras, our system can provide users with accurate and reliable indoor positioning and navigation services.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Characterizing the Role of Extracellular Vesicles in Bacteria-Host Communication

contributor:
Bienenstock, John
Neuroscience

abstract: The gastrointestinal tract contains trillions of symbiotic microorganisms (microbiota) that are critical for normal immunity, physiology, and development. Yet the extent to which these microbes influence neurodevelopment, and the mechanisms they use to do so, are poorly characterized. Using a mouse model, we show that perturbations of the maternal microbiota by treatment with low-dose penicillin during the last week of pregnancy alters behaviour and microbiota composition in adult offspring. These changes were sex-specific; female offspring had reduced anxiety-like behaviours, while males showed abnormal social behaviours, which correlated with altered hippocampal gene expression and reduced regulatory T cells. Microbiota composition was distinct between sexes and from untreated controls, suggesting that antibiotic exposure altered microbiota, which may have mediated other changes seen. To investigate a mechanism by which gut microbes may influence distal organ systems, we focused on the bacterium Lacticaseibacillus rhamnosus JB-1. We found that membrane vesicles (MV) produced by JB-1 contain lipoteichoic acid, which activates Toll-like receptor 2 (TLR2) and induces interleukin-10 production by dendritic cells. We further showed that JB-1 MV are internalized by human and mouse intestinal epithelial cell lines in a clathrin-dependent manner in culture, and by mouse intestinal epithelial cells in vivo. We then fed JB-1 bacteria to mice and showed that within 2.5 hours there are functional nanoparticles in their blood that reproduce effects associated with the fed bacteria. Plasma nanoparticles from fed mice had a size distribution distinct from that of saline-fed mice. They also activated TLR2 and induced interleukin-10 production by dendritic cells via lipoteichoic acid. These nanoparticles are likely bacterial MV as they contained bacterial protein and DNA from a novel bacteriophage in the original fed bacteria. Altogether these experiments support a role for microbiota in neurodevelopment and demonstrate novel nanoparticulate mechanisms of bacteria-host communication that may underlie their systemic influence.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Recent research shows that the trillions of microorganisms residing in our gut influence our development, brain function, and immunity, through mostly unknown mechanisms. To learn more, we gave pregnant mice penicillin to kill bacteria in their gut and found that this altered the brain and behaviour of their adult offspring. However, it is unclear how these bacteria could influence fetal mice in the womb. To test a potential mechanism, we investigated one type of bacteria and found that it naturally produces nanoparticles that contain immune-modulating cargo and are internalized by cells of the gut lining. When we fed these bacteria to mice, we discovered that the same nanoparticles were present in their bloodstream within 2.5 hours. This suggests that gut bacteria can produce nanoparticles that traverse the gut lining into the circulatory system, which may be one mechanism by which bacteria influence the organism they inhabit.


title: Targeting Tumour Antigen Heterogeneity with Dual-Specific Adoptive Cell Transfer

contributor:
Wan, Yonghong
Medical Sciences

subject:
Cancer
Immunotherapy
Adoptive Cell Therapy
Oncolytic Virus
Oncolytic Viral Vaccine
T Cell
Chimeric Antigen Receptor

abstract: Through the years, cancer therapies have progressed rapidly, pouring out novel treatments such as gene therapy, small molecule therapies and immunotherapy. One such immunotherapy, adoptive cell transfer (ACT), augmented through the addition of a chimeric antigen receptor (CAR), has proven success in treatment of hematological malignancies. Additionally, oncolytic viruses (OV) and OV-based (OVV) therapies, have shown promising results in both clinical and pre-clinical studies. In most instances, when applied as a monotherapy, the aforementioned treatment methods are incapable of inducing complete tumour remission. The Wan lab has developed an approach combining ACT with OVV therapies that dramatically increase therapeutic benefit resulting in complete regression of well-established solid tumours. Despite promising results, certain tumours can still escape this combination therapy through antigen loss resulting in antigen negative relapse (ANR). To further augment the therapy, the addition of a secondary receptor (CAR) provides the ACT multiple avenues of attack to prevent ANR. In this dissertation, we define culture conditions that promote strong expression of the CAR alongside confirmation of function in an in vitro setting. Following, it is demonstrated that OVV boosted dual-targeting T cells carry strong T cell activity by measure of cytokine release in vivo. Despite promising T cell activity data, dual-specific T cells are unable to improve tumour control and survival once relapse occurs. The failure to control relapse remains unclear however evidence points towards lack of T cell persistence, poor CAR function in vivo and a lack of endogenous T cell response leading to compounding effects that prevent dual-targeting T cells from preventing ANR. Although dual specific therapies have shown poor efficacy in preventing ANR, further study must be completed to identify areas of improvement – such as persistence, as the potential for success in using dual-targeting T cells coupled with OVVs still lies untapped.

abstract: Thesis

abstract: Master of Science (MSc)


title: Local sustained delivery of antibody therapeutics from injectable hydrogels for the treatment of glioblastoma

contributor:
Wylie, Ryan
Chemical Biology

abstract:
Modern production techniques and new therapeutic targets have resulted in the development of different antibody-based treatment modalities, increasing the repertoire of viable drug candidates. The clinical success of immune checkpoint inhibitors (ICIs) has generated great interest in antibody-based drugs as cancer immunotherapeutics.
The lack of treatment options for glioblastoma, the most malignant glioma, has expedited the investigation of antibody immunotherapeutics for glioblastoma. However, glioblastoma’s low tumor mutational burden (TMB) and immunosuppressive tumor immune microenvironment (TIME) render ICI monotherapies ineffective. Furthermore, physiological barriers (blood-brain barrier) impede drug localization, requiring high systemic doses that result in severe immunological side effects. To address these limitations, we demonstrate the benefit of: (1) local sustained release of antibody immunotherapeutics to increase the duration and magnitude of anti-cancer response and, (2) combination therapies to further promote immune cell mediated killing of glioblastoma.
With the goal of creating an implant for the local infusion of immunotherapeutics (LIIT), herein, I describe the development of an injectable hydrogel that incorporates an affinity based drug delivery system (DDS). Using well known affinity interactions, a three component DDS referred to as competitive affinity release (CAR) released a bioactive antibody for >100d. CAR was then modified to a new system called displacement affinity release (DAR), for the delivery of minimally modified antibody. An in situ gelling, injectable, low-fouling poly(carboxybetaine) hydrogel was fabricated for the localization of the DDS.
The DDS hydrogel combination was used to deliver a dual antigen T cell engager (DATE) targeting CD133 positive glioblastoma cells in 3D embedded spheroid cultures and a patient derived xenograft model. Controlled release of CD133 targeting DATE increased survival benefit within the xenograft model. Within the 3D embedded spheroid model, the combination therapy of DATE with an αPD-1 ICI increased and sustained cytotoxic effects.
Here I developed a platform technology for the local infusion of immunotherapeutics (LIIT), amenable to any antibody cancer immunotherapeutics. This project demonstrates how local infusion with immunostimulatory drugs can increase the magnitude and duration of anti-cancer immunotherapy in glioblastoma where physiological barriers impede drug accumulation.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Drugs that enable the immune system to recognize cancer have the potential to produce numerous anti-cancer treatments, revolutionizing the field cancer research. However, many of these drugs are clinically ineffective because of toxic side effects from high doses required to achieve therapeutic concentrations. Additionally, physiological transport barriers in cancers, especially brain cancer, impede drug distribution, and make it more difficult to reach therapeutic levels.
Delivering drugs to the correct location and for an optimal amount of time will improve drug efficacy. Drug loaded implants mostly composed of water, known as hydrogels, can be injected at the disease site for the slow infusion of drug into the area. This would simultaneously decrease the need for frequent drug administrations and decrease toxic side effects.
	Here, we present the development and testing of a medical implant that delivers drugs that redirect the immune system to recognize and kill brain tumors. The chemical properties of the implant were optimized for safe injection into the brain and for long term drug infusion. By extending the time of drug exposure using the implant, drug effectiveness was increased in mice bearing human brain cancer. Additionally, we showed the development of an in vitro model for brain cancer where anti-cancer effects of the drug loaded implant can be easily observed for applications in drug screening. This thesis, therefore, demonstrates how implantable materials can increase the effectiveness of anti-cancer drugs through efficient drug delivery.


title: Understanding NICU-to-Home Transitions for Adolescent Mothers: Theory, Methods and Research

contributor:
Jack, Susan
Nursing

subject: Nursing; Qualitative Research; Nursing Theory; Neonatal Intensive Care; Adolescent Mother

abstract:
Each year in Canada there are nearly 13,000 infants born to women under the age of 20 years (Statistics Canada, 2016). Infants born to adolescent mothers are at an increased risk for preterm birth, low birth weight, and congenital anomalies, making these infants more likely to require hospitalization in a neonatal intensive care unit (NICU) shortly after birth (DeMarco et al., 2021; Fleming et al., 2013; Shrim et al., 2011). Admission of their infant to the NICU creates an increasingly complex situation, as adolescent mothers and their children often already experience multiple social, psychological, and economic difficulties (Fleming et al., 2015). Additionally, adolescents are still developing important cognitive functions, such as advanced reasoning and decision-making, thus making their ability to navigate complex systems such as the NICU particularly challenging (Blakemore & Choudhury, 2006). However, the unique experience of the adolescent mother within the context of the NICU and their transition-home following discharge is poorly understood. Therefore, the overall purpose of this thesis was to explore the issue of transition-home from NICU for adolescent mothers with infants admitted to the NICU.
Three overarching goals guided this thesis work, these goals were to: (a) understand the transition experiences of adolescent mothers with infants in the NICU from a theoretical perspective; (b) understand how to best collect rich qualitative data among study participants experiencing marginalization or stigma; and (c) conduct research to further understand the phenomena and how to begin to address transition-related issues. Findings related to each of these goals are presented in four manuscripts that make up this sandwich thesis, including a critical review of theory, an exploration of methods, and an interpretive description study exploring NICU-to-Home transitions. The work presented in this thesis emphasizes the complexity of the NICU-to-home transition for adolescent mothers. Findings highlight the need for strategies within the NICU to mitigate the negative influence of this experience and opportunities for more integrated models of care within the NICU and extending into the community. Implications for research, policy, and nursing education and practice are discussed.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Pregnancy and parenting during adolescence and care transitions from neonatal intensive care unit (NICU) to home are relatively complex experiences. While each have been explored separately, very little is known about when these experiences intersect. This thesis examines theory and methods related to this complex intersection and describes findings of research exploring NICU-to-home care transitions for adolescent parents.


title: Towards "A New History of Man": Anticolonial Liberation and the Anti-Nationalist Possibilities of Friendship in South Asian Literature

contributor:
Attewell, Nadine
English and Cultural Studies

subject: South Asian Literature; Friendship; Anticolonial Liberation; Nationalism

abstract:
This dissertation argues that friendship can enliven the revolutionary humanist politics of twentieth century anticolonial movements. Twenty-first century nationalism, including that of former colonies, extends the violence of empire and breaks from the visions of anticolonial revolutionaries, such as Frantz Fanon, who sought to overthrow imperial domination by also progressing beyond the nation-state. Through a study of friendships that emerge in the context of anticolonial struggle and form across racial, class, caste, national, gendered, and religious differences, I argue that friendship is crucial to the development of a politics rooted in the wellbeing of the global collective and oppositional to both colonialism and nationalism.
	The main focus of this project is South Asia. Taking the fortification of Hindu nationalism in postcolonial India as a departure point, I read a set of literary texts situated in the South Asian anticolonial context that depict friendships formed across racial, class, caste, national, gendered, and religious difference. I demonstrate how many of these friendships contest strict divisions between self and Other and the colonial, class, and nationalist structures that keep these divisions intact. I organize each chapter according to three spaces that recur in South Asian literature as crucial to the creation and mobilization of friendship across difference: the ship, the home, and the ashram. Moving between these three spaces, I argue that in the emotional bonds of friendship, we can trace the emergence of a collective politics—one that refuses the divisions of self and Other central to the projects of empire and the basis upon which contemporary nationalisms thrive.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: This project explores the anti-nationalist possibilities of friendship. Anticolonial revolutionaries of the twentieth century, such as Frantz Fanon, envisioned a humanist politics that refused the violence of both empire and the nation-state. Such a politics, rooted in the wellbeing of the global collective, has been lost in the proliferation of nationalisms in both former empires and colonies; however, I argue that the study of friendship can help enliven these collective politics. This project focuses on the political possibilities of friendships formed in the specific context of South Asian Independence movements. I read a set of South Asian literary texts that depict friendships established across racial, class, caste, religious, gendered, and national difference. Tracing these friendships as they take shape on the ship, in the home, and in the ashram, I ask: how might these depictions of friendships help reinvigorate a revolutionary, anticolonial politics that seeks to progress beyond the violence of the nation-state?


title: Geometric Magnetic Frustration in Crystal Lattices: Synthesis and Magnetic Characterization of Breathing Pyrochlore Candidates CuAlCr4S8 and CuAlCr4Se8

subject:
Condensed Matter Physics
Solid State Physics
Experimental Physics
Frustrated Magnetism

abstract: The breathing pyrochlore lattice is a relatively recently discovered variant of the extensively studied pyrochlore. Materials exhibiting this structure possess the chemical formula AA’B4X8 and form a lattice of interpenetrating corner-sharing tetrahedra of alternating sizes due to the differences in atomic radii of the A and A’ atoms that occupy the neighbouring sites. The difference in tetrahedra size can be quantified by the breathing factor B_f≡d'/d  . This lattice exhibits magnetic frustration as a result of its geometry, as the tetrahedral structure prevents all nearest neighbour interactions from being satisfied, and the introduction of the breathing factor breaks the symmetry of the nearest neighbour Hamiltonian, providing an arena for studying interesting magnetic interactions. Here, I present an experimental study of the breathing pyrochlore candidates CuAlCr4S8 and CuAlCr4Se8. I provide the procedure for synthesis using solid state techniques, as well as a structural analysis using X-ray diffraction and Rietveld refinement. I also perform a magnetic characterization of the samples using SQUID magnetometry, where M(H) and M(T) measurements are conducted. Through analysis of these measurements, I conclude CuAlCr4S8 forms a nearly pure breathing pyrochlore with no magnetic impurities and B_f=1.087. This is the first reporting of this material. The sample undergoes a significant transition at T_c≈26K which appears to be first order in nature and possibly antiferromagnetic. This material has a Curie-Weiss temperature θ_CW=-61.93K. Analysis of CuAlCr4Se8 shows it forms a mixed site pyrochlore structure, with a small paramagnetic impurity Cr0.68Se ≈2.5%. This material exhibits multiple characteristic temperatures and spin glass-like behaviour with θ_CW=17.14K.


title: The Impact of Punishment and Reward Feedback on Sequence Learning

contributor:
Carter, Michael
Kinesiology

subject:
Serial reaction time task
Training
Retention
Preregistered
Online collection

abstract: Next to practice itself, feedback provided to a learner from an external source such as a coach or therapist is considered the most important factor facilitating skill acquisition. Past research has suggested that punishment and reward feedback have dissociable effects on learning and retention, respectively. However, other studies have suggested a more reliable effect of punishment feedback while failing to replicate the benefit of reward on retention. This discrepancy across experiments may be the result of seemingly innocuous methodological differences. Here, I ran a pre-registered online experiment to test the replicability of the supposed dissociable effects of punishment and reward on learning during training and retention, respectively. Participants were randomly assigned to receive either punishment feedback (n = 34) or reward feedback (n = 34) during the training period as they learned a repeating 12-element sequence in a serial reaction time task. Feedback consisted of participants either seeing a red (Punishment group) or green (Reward group) box flash on their computer screen and, unbeknownst to them, either a corresponding loss (Punishment group) or gain (Reward group) of points from their starting total. Participants were informed that a good final point score (i.e., the higher the better) could earn them extra entries into a gift card lottery. Contrary to what much of the literature has found, our results revealed no statistically significant differences between groups in either the training or retention phases of the experiment. In conclusion, the findings of this experiment failed to replicate the previously found dissociable effects of punishment and reward feedback on learning and retention, respectively. The data instead suggests that providing participants with punishment or reward feedback may affect learning and retention in a similar manner.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The information that you get from your senses, along with the comments and criticisms given to you by others, are all forms of feedback that may or may not be available in your environment. Feedback can often be given to you in the form of a punishment or a reward in an effort to facilitate your performance of a motor skill, such as learning to juggle a soccer ball. In this thesis, I explored whether punishment and reward feedback have dissociable effects on the way people learn and retain a new motor skill. Some individuals received punishment feedback by seeing a red box flash on their screen and losing points, while others received reward feedback by seeing a green box flash on their screen and gaining points. Although the participants learned the new motor skill in the experiment, the results showed that reward and punishment feedback did not differentially impact motor learning. These results suggest that either reward or punishment feedback may be a useful feedback strategy for promoting motor learning.


title: Combined Punishment and Reward Feedback During Sequence Learning

subject:
Serial reaction time task
Transition schedules
Training
Retention
Preregistered
Online collection

abstract: Punishment and reward feedback during motor learning tasks appear to have some beneficial impact on learning and retention, respectively. Therefore, it is possible that combining punishment and reward feedback would benefit both learning and retention. Within the sports coaching domain, a combination of punishment and reward feedback schedule has been suggested to improve performance. According to the coaching literature, the most effective approach is providing reward-to-punishment feedback. However, transitioning from punishment-to-reward feedback may be more effective based on the motor learning literature. The present study examined the utility of combining punishment and reward feedback through a transition schedule approach during a serial reaction time task. To test the competing predictions about feedback order, half the participants received punishment-to-reward feedback and the other half received the reverse order. Our results revealed that training response time significantly improved with no significant difference between the order of feedback. However, both types of feedback order did not improve retention during the same-day and delayed post-tests. Yet, the non-significant equivalence test indicates that these findings remain inconclusive. Finally, within-subjects analysis of the punishment and reward conditions found that training significantly improved response time with no difference between them. In this case, the equivalence test was significant, revealing that the estimated effect was surprisingly small. Overall, the current study failed to find conclusive evidence that the order of a transition feedback schedule matters for learning and retention. However, the difference between punishment and reward conditions may be smaller than previously assumed by motor learning studies.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: An important part of learning any skill is receiving information that helps us recognize mistakes and improve our performance, known as feedback. In fact, feedback presented as a punishment or reward has been shown to improve an individual's ability to learn and retain skills, respectively. Therefore, can combining punishment and reward feedback benefit both learning and retention? One way to deliver both types of feedback is using a transition schedule. Some have recommended that transitioning from punishment to reward feedback would be most effective, while others have suggested the reverse order. The current study examined whether the order of receiving punishment and reward feedback affected learning and retention. To test this, subjects either received punishment-to-reward feedback or reward-to-punishment feedback during a key-pressing task. Our results did not find conclusive evidence that the order mattered for learning and retention. Furthermore, the difference between punishment and reward feedback overall was smaller than previously thought. These findings highlight that more studies may need to be conducted to get a better understanding of whether the order of punishment and reward feedback can benefit both learning and retention.


title: Learning Curves in Minimally Invasive Thoracic Surgery

contributor:
Hanna, Waël
Health Research Methodology

subject: Learning Curve, Minimally Invasive Surgery, Thoracic Surgery, Non-Small Cell Lung Cancer, Robotic Surgery, Video-assisted Surgery, CUSUM, Physician Education

abstract:
Introduction: As the number of minimally invasive technologies increases in the field of thoracic surgery, so have the number of learning curve analyses performed for these innovations. Variation in learning curve methodology makes between-study comparisons and evidence syntheses difficult. Furthermore, poorly described and reported learning curve analyses make the results difficult to apply to different clinical settings. The objective of this systematic review is to characterize the variability in the methods used to construct and describe learning curves, with the goal of identifying shortcomings and potential areas for improvement in this line of research.
Methods: A search of Ovid Medline, Ovid Embase, EBSCO CINAHL, and Web of Science was performed. Studies of learning curves of anatomical lung resection operations in adult patients published in the English language were eligible for inclusion. Two reviewers independently assessed studies for eligibility, and extracted relevant data.
Results: The search yielded 56 articles eligible for inclusion in the present review. A variety of methods were used to construct the learning curve, with chronological grouping of cases being the most commonly used technique in 22 (39.29%) studies, followed by the cumulative sum method, employed in 21 (37.50%) studies. A total of 15 unique metrics were used for learning curve analyses; operative time was the most common metric, used in 39 (69.64%) studies. A large proportion of studies failed to provide details on learning curve parameters such as competency thresholds, surgeon’s prior experience, case complexity, and learning curve definition. Considerable heterogeneity was found in the methods and reporting standards of learning curve evaluations in minimally invasive thoracic surgery.
Conflicts of Interest: None.
Funding Source: Boris Family Centre for Robotic Surgery.

abstract: Thesis

abstract: Master of Science (MSc)


title: Refinement and testing of CTF for annular flow regime and incorporation of fluid properties

contributor: Engineering Physics and Nuclear Engineering

subject:
Annular Flow
COBRA-TF
Enthalpy imbalance factor
Fluid properties
CHF
Pressure drop

abstract:
The current study focuses on improving and testing the CTF thermalhydraulics computer code. CTF is a thermalhydraulic code used for subchannel analysis of nuclear power reactors developed as part of the US DOE CASL program and distributed by North Carolina State University. Subchannel analyses are used to predict the local fuel temperatures and coolant conditions inside a complex nuclear fuel assembly. Such calculations are used to improve designs of nuclear fuel, improve operating margins, or perform safety analysis. An important part of the code development process is the verification and validation for its intended use. In this work validation activities are performed using the RISO experiments are modeled in CTF for adiabatic and diabatic cases in annular flow regimes and a limited set of tests in CANDU geometries. The CTF predictions significantly overpredicted the pressure drop for cases involving annular flow conditions. Depending on the application, such overprediction can result in significant errors in the computation of fuel element dryout and other figures of merit. For example, an analysis using fixed pressure boundary conditions CTF predicts much lower subchannel flows and hence fuel element temperatures may be overestimated. On the other hand, for a scenario with mass flux and inlet pressure as boundary conditions, the impact of pressure drop discrepancies on dryout predictions may be lower. Therefore, there is a particular focus in this thesis on the two-phase pressure drop models and the RISO experiment specifically, since the RISO tests involve a range of annular flow conditions which is prototypical of many CANDU accident analysis conditions.
In addition to the RISO experiments, 28-element CANDU full scale rod bundle experiments are modeled in CTF for single-phase and two-phase flow conditions. Cases are modeled for crept and uncrept conditions with different bearing pad heights i.e., 1.17 mm and 1.35mm. Pressure drop predictions are compared with the experimental results where single-phase comparisons are in good agreement while an overprediction of ~25% is observed for two-phase conditions. The effect of bearing pads on the subchannel local parameters, like mass flow rate, are also studied. Furthermore, the effect of turbulent mixing rate on subchannel enthalpy distribution in the bundle and CHF in different subchannels is also analyzed.
Based on the comparison to the RISO and CANDU 28 element test databases, the overprediction of pressure drop in the annular flow regime needs improvement in the current version of CTF. This overprediction of the frictional pressure drop results from either wall drag or interfacial shear stress phenomena. In this study, it is demonstrated that the issue occurs mostly as a result of interfacial friction factor modelling this work examines several alternative approaches. The results show the Ju’s and Sun’s interfacial friction factor better predicts the results among all the other six correlations implemented in CTF.
The major impediment in further testing of CTF is that it lacks the capability to simulate R-134a fluids. Given there is a large database of R-134a two-phase tests, another aspect of this thesis is to extend CTF for application and validation using refrigerants. The current CTF version only supports fluid properties for water and FLiBe salts. By adding R-134a fluid properties the testing and validation range of CTF is broadened for different experiments performed using R-134a fluids. CHF experiments are modeled in CTF and results are compared with experimental data. For local conditions correlation, 2006 water LUT are used to predict CHF and DNBR. The fluid-to-fluid scaling method is applied in CTF when using CTF with R-134a fluid properties for CHF and DNBR predictions to account for the difference in fluid properties between R-134a and the CHF look-up table.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
COBRA-TF (CTF) is a thermalhydraulic code, based on the historical code COBRA-TF, used for subchannel analysis of nuclear power reactors. Subchannel analysis can be used to predict the local fuel temperatures and coolant conditions inside a complex nuclear fuel assembly.  CTF is a transient code that simultaneously solves conservation equations for mass, momentum, and energy for the three coolant phases present, i.e. vapor, continuous liquid, and entrained liquid droplet phases.
The scope of the current study includes 1) testing the code for conditions relevant to CANDU accident analysis, 2) refinement of the models that are used in two-phase interfacial friction calculations, and 3) inclusion of alternate fluid properties. The testing of CTF is performed with different experimental databases covering CANDU thermalhydraulic conditions. The refinement is done by improving the pressure drop prediction in the annular flow regime by using different interfacial friction factor correlations from earlier studies in the literature. The current CTF version includes water and liquid salt properties (FLiBe) for coolant fluids. Freon (R-134a) fluid properties have been added in CTF in order to broaden the testing range of CTF for different experimental database using R-134a as working fluid.


title: Defining Pediatric Chronic Critical Illness

contributor:
Choong, Karen
Rochwerg, Bram
Obeid, Joyce
McNally, James Dayre
Health Research Methodology

subject:
pediatrics
critical care
chronic critical illness
scoping review

abstract: Introduction: Improvements in the delivery of intensive care have led to a growing number of children with chronic medical conditions at significant risk of recurrent and prolonged critical illness. These patients are increasingly described as having pediatric chronic critical illness (CCI). To date, pediatric CCI is without an accepted consensus case definition. Objective: To evaluate how pediatric CCI has been defined in the current literature, including the concept of prolonged PICU admission, and describe the methodologies used to develop any existing definitions. Secondary aims included describing patient characteristics and outcomes evaluated in included studies. Methods: We searched four electronic databases for studies evaluating children identified with “CCI.” We also searched for studies describing prolonged PICU admission, as this concept is related to pediatric CCI. We developed a hybrid crowdsourcing and machine-learning (ML) methodology to complete citation screening. Screening and data abstraction were performed by two reviewers, independently and in duplicate. We completed data abstraction including details of population definitions, demographic and clinical characteristics of children with CCI, and outcomes evaluated. Results: Twenty-eight reviewers from 11 countries performed citation screening, with a mean sensitivity of 92%. Of 24,729 unique citations assessed for eligibility, 453 full-texts were reviewed and 67 studies were included. Of these, 12 studies (18%) defined CCI, most commonly by a prolonged PICU length of stay (LOS), either in isolation or in addition related to medical complexity patient characteristics and/or readmissions rate. The concept of prolonged PICU admission was defined in an additional 55 (82%) studies by a median of 14 days (range, 1 day-6 weeks). Conclusion: To our knowledge, this scoping review provides the most comprehensive epidemiologic evidence addressing pediatric CCI. Our results suggest a uniform consensus definition is needed in order to advance this emerging and important area of pediatric critical care research.

abstract: Thesis

abstract: Master of Science (MSc)


title: Evaluating the effects of exercise on Natural Killer cell cytotoxicity in pre- and post-pubertal boys and girls

title: Exercise and Natural Killer cell cytotoxicity in youth

contributor:
Obeid, Joyce
Medical Sciences

subject: Pediatric Exercise Immunology

abstract: Natural killer (NK) cells are a type of lymphocyte involved in innate and adaptive immunity. In adults, exercise can increase NK cell cytotoxicity both as a total percent of target cell lysis and an increase in the function of each NK cell. Much less is known about this response in children. Thus, the objectives of this study were to examine: 1) the effects of exercise intensity and structure on NK specific lysis and NKCA per cell in youth, and 2) differences in baseline and post-exercise specific lysis and NKCA per cell by pubertal status and sex. We also examined the NK cell and NK subset response to these exercise protocols by pubertal status and sex to help contextualize the NK functional response. We recruited healthy, recreationally active pre-pubertal (8-11 years, N=5) and late/post-pubertal (15-18 years, N=6) children from the Hamilton community. Participants completed 4 experimental cycling sessions in a randomized order including: high intensity intermittent (HI-INT) or continuous (HI-CONT), and moderate intensity intermittent (MOD-INT) or continuous (MOD-CONT) cycling. Blood was collected at baseline (PRE), immediately post-exercise (POST), and at 30- and 60-minutes recovery (REC1 and REC2, respectively). Peripheral Blood Mononuclear Cells (PBMC) were isolated from each timepoint and used in a cytotoxic assay with K562 targets. Flow cytometry was used to quantify target cell death (reported as specific lysis and NKCA per cell), and to determine NK cells and subsets as a proportion of lymphocytes. Exercise significantly increased specific lysis from PRE (25.1± 6.7%) to POST (30.6±11.0%), while NKCA per cell increased from PRE (0.69±0.76) to REC2 (1.3±1.3); p<0.05 for both. These responses were seen irrespective of exercise intensity and structure, pubertal status, and sex. The % total NK cells increased from PRE to POST (6.8±2.8% vs. 13.6±7.2%), and was greater in post-pubertal children vs. pre-pubertal children (20.9±6.2% vs. 9.1±4.3%), and after HI-INT (15.5±8.1%) and MOD-INT (16.2±9.5%) vs. HI-CONT (12.0 ± 5.0%) and MOD-CONT exercises (10.6 ± 4.5%; p<0.05 for all). Acute exercise can enhance NK cell cytotoxicity in youth regardless of exercise intensity, structure, pubertal status, or sex. NK function and mobilization responses to exercise did not always align, which suggests that unique post-exercise processes contribute to changes in NK cell proportions, specific lysis, and NKCA per cell. Our study has enhanced the understanding of exercise-induced changes NK cell cytotoxicity in the growing years. Future research will focus on explaining these effects, and exploring the clinical application of exercise programs in youth.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The purpose of this study was to determine if exercise can increase the function of Natural Killer cells (NK cells) in children. These cells are a very important part of our immune system that work to protect us from harmful infections and cancers. We also wanted to see if puberty or sex influence how NK cells respond to exercise. We asked boys and girls who were 8-11 years old or 15-18 years old to visit our lab 5 times. During their first visit, we measured their fitness level. In the next 4 visits, they completed one of four different types of exercise including: 1) 30 minutes of hard cycling, 2) 5 minutes of stop-and-start hard cycling, 3) 30 minutes of less hard cycling, and 4) 5 minutes of stop-and-start less hard cycling. We collected blood at four times during each session, including: 1) before the exercise, 2) immediately after the exercise, 3) 30-minutes after exercise, and 4) 60-minutes after exercise. We took NK cells from this blood and added them to cancer cells. We measured how many cancer cells were killed by the NK cells. We were interested in learning if exercise changed the percent of cancer cells killed by NK cells. We also wanted to know if exercise helped make each NK cell a better killer. We found that immediately after exercise, NK cells were able to kill a greater percent of cancer cells than they could before exercise. We also found that at 60-minutes after exercise, each NK cell killed a greater number of cancer cells than they were able to before exercise. There were no differences in NK cell cancer killing capacity between boys and girls, or between pre-pubertal or post-pubertal children. Our study helps us understand how we can increase important immune functions with exercise in children.


title: Detection and quantification of Legionella pneumophila using latex agglutination test

contributor:
Puri, Ishwar
Biomedical Engineering

abstract: Legionella pneumophila (L. pneumophila) are ubiquitous in environmental water sources that are responsible for causing sporadic and epidemic cases of atypical pneumonia, called Legionnaires’ disease (LD), after inhalation of contaminated water droplets. There is a need for a rapid detection method for Legionella pneumophila fluid samples without the need for complex instrumentation. Agglutination assays are widely used in biology and medicine for their simplicity and specificity.  However, conventional agglutination tests only provide presumptive results. Here I describe and perform a latex agglutination test (LAT) that can detect and quantify L. pneumophila in a sample by determining the degree of agglutination. The latex microbeads (beads) are coated with polyclonal antibodies using established methods. The optimal ratio of the beads to the antibody for the best performance of LAT was found to be 20:3. L. pneumophila serogroup 1 is chosen as the target bacteria and Escherichia coli K12 as the negative control. Strains of L. pneumophila serogroup 1 were cultured and inactivated by heat treatment for safety. The target bacteria displaying the antigenic epitopes were mixed with the antibody-coated beads and have been shown to facilitate agglutination. Micro-channels fabricated using adhesive tapes are used to entrap the fluid sample, where an image analysis algorithm quantifies the degree of agglutination using images obtained by a microscope, thereby, resolving issues with complex techniques. Specific binding between antibody and L. pneumophila serogroup 1 is investigated by tracking the motion of the beads and bacteria in the images. The number of beads involved in agglutination compared to the total number of beads present in an image determines the degree of agglutination. The sample volume used for detection is 3 µL and the detection limit of the method is 106 cells/ml. Compared to expensive and complex PCR techniques and time-consuming culture methods, this LAT is simple, affordable, and can produce results within hours using only a microscope.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Supporting the Development of Ethics Tools for Innovation in Humanitarian Contexts

title: Ethical Innovation in Humanitarian Contexts

contributor:
Schwartz, Lisa
Health Policy

subject: Humanitarian Ethics Innovation

abstract:
In humanitarian settings (such as natural disasters, conflicts, famines, etc), innovation can be as important as regular programmatic activities or research, and can sometimes be difficult to distinguish from either of these. At once experimental and responsive, innovation can be a welcome response to an unresolved problem, but also lack the oversight of research and the reliability of established practices. To help address the unique ethical tensions that arise in humanitarian innovation, the research presented in this dissertation was conducted as part of a consultancy-grant with the Humanitarian Innovation Fund (HIF). The aim of this partnership was to support the development of evidence-based ethics tools for innovation in humanitarian contexts. In this dissertation I present three unique contributions to the body of knowledge surrounding humanitarian ethics research.
The first article presents the overarching research architecture that was employed in partnership with the HIF, highlighting strengths and weaknesses of this approach to the development of ethics tools. The second article presents the findings from a scoping review of academic and grey literature focusing on ethics and humanitarian innovation, identifying ethical tensions across innovation stages as well as a common thread of solutionism. The final article presents a qualitative description of key stakeholder interviews, which highlighted the need for micro (tools for reflection), meso (funding structures), and macro (sectoral learning and transparency) level shifts to foster ethical humanitarian innovation. Taken together, these contributions point to a humanitarian innovation ecosystem that is very much still in its nascency, potentially vulnerable to exploitation by market interests, and has not established effective mechanisms to facilitate learning and collaboration between funders, innovators, and affected populations.
This research and the associated toolkit begin to respond to the immediate need for resources, and provide empirical support for larger sectoral change. Further research and the establishment of a community of practice surrounding these tools will be critical to the continued pursuit of humanitarian innovation in an accountable, ethical, and impactful manner.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Over the past decade there has been an intense proliferation of innovation activities in the humanitarian sector (challenges, labs, accelerators), but a lack of practitioner-oriented resources to facilitate ethical decision making and reflection when pursuing these activities. This research was conducted through a consultancy-grant between the Humanitarian Innovation Fund & the Humanitarian Health Ethics Research Group, with the aim of supporting the development of evidence-based resources to foster ethical innovation in humanitarian contexts. Qualitative interviews and literature reviews were used to explore the landscape of what is known and to identify gaps and needs, which informed the series of iterative tool workshops. This research ultimately produced five unique tools and a series of case studies, as well as greater understanding of the ethical dimensions of humanitarian innovation. Further research and the establishment of a community of practice surrounding these tools will be critical to the continued pursuit of humanitarian innovation in an accountable, ethical, and impactful manner.


title: Solutions and limits of the Thomas-Fermi-Dirac-Von Weizsacker energy with background potential

contributor:
Bronsard, Lia
Alama, Stanley
Mathematics and Statistics

subject:
calculus of variations
partial differential equations
pattern formation
nonlocal

abstract:
We study energy-driven nonlocal pattern forming systems with opposing interactions. Selections are drawn from the area of Quantum Physics, and nonlocalities are present via Coulombian type interactions. More precisely, we study Thomas-Fermi-Dirac-Von Weizsacker (TFDW) type models, which are mass-constrained variational problems. The TFDW model is a physical model describing ground state electron configurations of many-body systems.

First, we consider minimization problems of the TFDW type, both for general external potentials and for perturbations of the Newtonian potential satisfying mild conditions. We describe the structure of minimizing sequences, and obtain a more precise characterization of patterns in minimizing sequences for the TFDW functionals regularized by long-range perturbations.

Second, we consider the TFDW model and the Liquid Drop Model with external potential, a model proposed by Gamow in the context of nuclear structure.  It has been observed that the TFDW model and the Liquid Drop Model exhibit many of the same properties, especially in regard to the existence and nonexistence of minimizers.  We show that, under a "sharp interface'' scaling of the coefficients, the TFDW energy with constrained mass Gamma-converges to the Liquid Drop model, for a general class of external potentials.  Finally, we present some consequences for global minimizers of each model.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Efficiency Measures of Superabsorbent Polymers as Internal Curing of Cement Paste

contributor:
Chidiac, Samir
Civil Engineering

subject:
Internal curing
Superabsorbent polymers
Heat of hydration
Nuclear magnetic resonance
Internal curing efficiency
Degree of hydration
Diffusion coefficient
Agglomeration

abstract:
Mixes with lower water to cement (w/c) ratio and supplementary cementing materials produce strong and durable concrete. The consequence of lowering w/c is an increase in autogenous shrinkage (AS), which contributes to concrete cracking. Internal curing (IC) is shown to mitigate AS, however improper dosing of IC material can negatively affect the concrete properties. The effectiveness of IC material, such as superabsorbent polymer (SAP), depends on the 1) amount of water stored, 2) particle distribution, and 3) ability to deliver water. The objective of this research is to quantify the in-situ efficiency of SAP by investigating its effect on the cement chemical reaction using non-destructive testing methods, specifically isothermal calorimetry and nuclear magnetic resonance (NMR).

IC was tested with varying quantities of SAP in plain cement paste using white Portland cement and three w/c (0.30, 0.32, 0.35). Overdosing of the SAP material was found to significantly affect the hydration reaction and reduce the efficiency of the material. The initial porosity of the paste influences the ability of IC to provide water. However, the extra porosity provided by SAP needs to be considered when calculating the degree of hydration. Particle agglomeration occurs when the mass of SAP to IC water is greater than 5% and is the main factor causing loss of efficiency. A new geometric model was developed to estimate the SAP distribution within the cement paste. The model employs the SAP absorption determined by NMR and assumes that the SAP particles are spherical, of equal diameter, and individual particles absorb the same amount of pore solution. The results reveal that particle spacing increases with agglomeration and reduces the IC efficiency.

A hybrid 1-D finite element transient flow model was developed to reverse engineer the effective diffusion coefficient from the NMR water distribution. The gel solid volume fraction and its impedance to water transfer were accounted for through the cement degree of hydration and tortuosity factor, respectively. Model results reveal that the effective water diffusion coefficient depends on w/c, gel volume fraction, and tortuosity once the cement gel fractions start to connect, i.e., after 20% cement degree of hydration. The diffusion length quantifies the distance water can transfer from the SAP to the cement paste.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: An Exploratory Descriptive Study Evaluating Divergence in the Judgment of Clinical and Public Health Recommendations for the Management of the Novel Coronavirus Disease (COVID-19)

title: DESCRIBING DIVERGENCE IN COMPARABLE COVID-19 RECOMMENDATIONS

contributor:
Schunemann, Holger
Health Research Methodology

subject: Public Health

abstract:
Background: The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has unravelled a global demand for rapid and reliable guidance at the clinical, systems, and policy levels. Therefore, to equip decision-makers with the appropriate knowledge and tools, organizations have published evidence-informed guidance for its prevention and treatment.
Objectives: Various organizations may produce comparable but diverging recommendations for the same intervention or health scope. Diverging recommendations are those that contain varying judgements in their strength, direction, or subgroup consideration associated with the intervention. Nonetheless, the extent of divergence between COVID-19 recommendations remains unknown. Consequently, the primary objectives of this study are to 1) describe the frequency and types of divergence between COVID-19 recommendations for the same intervention and 2) investigate differences in the guideline development process for a selected sample of diverging recommendations.
Methods: We screened guidelines for divergence using the digital COVID-19 Recommendations Catalogue (covid19.recmap.org). Diverging recommendations for the same intervention were grouped into clusters, and differences in their formal judgment of strength and direction were appraised. Additionally, we compared any differences between PICO criteria for comparable recommendations addressing the same health scope. Descriptive statistics were performed to assess the frequency and types of divergence. Finally, we applied deductive content analysis to evaluate differences in the methods for a sample of 12 recommendation clusters.
Results: Two-hundred twenty-three diverging recommendations resulted in the categorization of 66 clusters. Twenty-nine clusters contained clinical also stated as therapeutic recommendations, and 37 clusters contained public health recommendations. Each cluster had a range of 2-8 individual recommendations in divergence with at least one recommendation for the same intervention. Clinical recommendations were more likely to diverge in formal judgment than public health recommendations (P < 0.001). We identified differences in the date of publication, the interpretation of evidence, and in the judgments of the Evidence-to-Decision framework between comparable recommendations. Consequently, results from our study may have important implications for comparing duplicate recommendations and for making clinical practice decisions.
Conclusions: From our study, we have identified diverging recommendations for a range of COVID-19 related interventions. These recommendations may have important implications for clinical practice and public health decisions.

abstract: Thesis

abstract: Master of Public Health (MPH)


title: Indigenous Reunification In Child Welfare: A Scoping Review

contributor:
Freeman, Bonnie
Social Work

subject:
Indigenous
Reunification
Child Welfare
Aboriginal
Child Protection
First Nations
Reintegration
Scoping Review

abstract: This thesis looks at the process of reunification for Indigenous children following a time in the care of the child welfare system.  To understand what has been studied in the area of reunification of Indigenous children back to their families, a scoping review process is undertaken to gathering and mapping the available research.  The initial search produced a total of 1823 abstracts.  After applying an inclusion and exclusion reviewing process, the scoping review resulted in a total of 44 literature sources for this study.  This study uses Cindy Blackstock’s Breath of Life Theory as the theoretical framework to understand and reimagine the process of reunification from the perspective of the child, the family, the worker, and substitute caregiver.  The review found support for the idea that research and programs relating to reunification for Indigenous children needs to use Indigenous methods and ways of thinking.  Five themes emerged from this review, the use of Indigenous ways of knowing, this theme is central throughout the literature and informs the other four themes: structural vs. individual assessment/intervention, trauma/reconciliation, connections/relationships, and Indigenous research.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Mechanistic Understanding of Tau Alternative Splicing in Neurons Using Proteomics

contributor:
Lu, Yu
Biochemistry and Biomedical Sciences

subject:
Tau
Alternative splicing
Proteomics

abstract: Tauopathies refer to a group of neurodegenerative diseases that are characterized by pathological aggregations of the microtubule-associated protein Tau (MAPT). Aberrant alternative splicing of Tau exon 10 leads to the imbalanced expression of Tau isoforms that contain either 3 or 4 microtubule binding repeats (3R-Tau or 4R-Tau) and this is sufficient to cause the formation of Tau inclusions. Nonetheless, the exact molecular mechanisms that regulate aberrant Tau exon 10 splicing regulation and subsequent Tau aggregation in tauopathies remain elusive. In my thesis research, I used RNA Antisense Purification by Mass Spectrometry (RAP-MS) to identify upstream regulators of Tau splicing events. Among the 15 identified novel protein candidates, I validated that hnRNPA2B1 and hnRNPC are required to promote 4R-Tau expression, whereas hnRNPH1 supports 3R-Tau expression. Separately, to elucidate the functional difference between 3R- and 4R-Tau isoforms, I performed proximity-dependent biotin identification (BioID2) for all six human central nervous system Tau isoforms in mouse primary neurons. Followed by tandem mass tag (TMT)-labeling proteomics and data analysis, I observed that 4R-Tau proximal proteins are highly enriched in endocytosis, whereas 3R-Tau proximal proteins show top enrichment in fatty acid metabolism. Through further biochemical validations, I found that MAT2A, a S-adenosylmethionine synthase, has higher binding affinity with 3R-Tau versus 4R-Tau. Overall, using novel proteomics methods, I discovered novel Tau splicing regulators and characterized the neuronal Tau isoform-specific proximity proteome networks. These proteins, once validated through future functional studies in cellular and animal models, can represent therapeutic and diagnostic targets for neurodegenerative tauopathies.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Biological Embedding of Child Maltreatment: A Systematic Review of Biomarkers and Resilience in Children and Youth

contributor:
Gonzalez, Andrea
Neuroscience

subject:
child maltreatment
methylation
epigenetics
telomere length
resilience
biological embedding

abstract: Objective: Child maltreatment (CM) is a widespread problem associated with poor mental and physical health outcomes. The underlying mechanisms of this link are not always well understood, however certain biological changes observed in maltreated individuals may play a role in connecting experience and outcome. This review specifically focuses on two markers of biological embedding, DNA methylation (DNAm) and telomere length (TL) in maltreated children and youth. As biomarker changes are not uniform among maltreated children, we additionally discuss biological and environmental resilience factors that may contribute to variability. Methods: We conducted a systematic review of Medline, Embase and PsycInfo databases for studies examining DNAm and/or TL in maltreated children and youth. Methodological quality of the included articles was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) checklists for cohort studies and randomized control trials. Data extraction focused on various factors including population and CM (type, chronicity, severity, and duration) characteristics. Results: The initial search returned 1,688 non-duplicate results, with 417 full text articles reviewed. Twenty-six articles from 16 studies were ultimately included of which 8 examined telomere length and 18 examined DNA methylation. Conclusions: While some heterogeneity of findings was found, evidence supports differential changes in both biomarkers associated with CM. This review enhances understanding of the constellation of biological changes related to CM and consideration of the important role of resilience factors in mitigating risk. Elucidating these factors may highlight targets for future study and intervention development.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Child maltreatment is a serious problem linked to poor mental and physical health outcomes. The mechanisms of these links are not always clear, however biological changes observed in some maltreated individuals may play a role. Here, we systematically review literature related to two biomarkers of interest in maltreated children, telomere length and DNA methylation. Findings are varied; however, overall, they support an association between child maltreatment and changes in both biomarkers. We additionally discuss factors that may confer resilience related to these changes to highlight potential targets for future study and interventions.


title: Analysis of Four and Five-Way Data and Other Topics in Clustering

contributor:
McNicholas, Paul D.
Statistics

subject:
Mixture models
Tensors
Skewed probability distributions
EM algorithm
Multidimensional arrays

abstract:
Clustering is the process of finding underlying group structure in data. As the scale of
data collection continues to grow, this “big data” phenomenon results in more complex data structures. These data structures are not always compatible with traditional
clustering methods, making their use problematic. This thesis presents methodology
for analyzing samples of four-way and higher data, examples of these more complex
data types. These data structures consist of samples of continuous data arranged in
multidimensional arrays. A large emphasis is placed on clustering this data using
mixture models that leverage tensor-variate distributions to model the data. Parameter estimation for all these methods are based on the expectation-maximization
algorithm. Both simulated and real data are used for illustration.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: Probabilistic Ensemble-based Streamflow Forecasting Framework

contributor:
Coulibaly, Paulin
Civil Engineering

subject:
Water resources
Hydrology
Streamflow
Forecasting
Streamflow forecasting
Uncertainty
Uncertainty quantification
Bayesian Model Averaging
BMA
Precipitation forecasting
Flood
Flood forecasting
Streamflow simulation
Hydrologic modeling
Conceptual rainfall-runoff modeling
Hydrologic Uncertainty Processor
Entropy theory

abstract:
Streamflow forecasting is a fundamental component of various water resources management systems, ranging from flood control and mitigation to long-term planning of irrigation and hydropower systems. In the context of floods, a probabilistic forecasting system is required for proper and effective decision-making. Therefore, the primary goal of this research is the development of an advanced ensemble-based streamflow forecasting framework to better quantify the predictive uncertainty and generate enhanced probabilistic forecasts. This research started by comprehensively evaluating the performances of various lumped conceptual models in data-poor watersheds and comparing various Bayesian Model Averaging (BMA) modifications for probabilistic streamflow simulation. Then, using the concept of BMA, two novel probabilistic post-processing approaches were developed to enhance streamflow forecasting performance. The combination of the entropy theory and the BMA method leads to an entropy-based Bayesian Model Averaging (En-BMA) approach for enhanced probabilistic streamflow and precipitation forecasting. Also, the integration of the Hydrologic Uncertainty Processor (HUP) and the BMA methods is proposed for probabilistic post-processing of multi-model streamflow forecasts.
Results indicated that the MACHBV and GR4J models are highly competent in simulating hydrological processes within data-scarce watersheds, however, the presence of the lower skill hydrologic models is still beneficial for ensemble-based streamflow forecasting. The comprehensive verification of the BMA approach in terms of streamflow predictions has identified the merits of implementing some of the previously recommended modifications and showed the importance of possessing a mutually exclusive and collectively exhaustive ensemble. By targeting the remaining limitation of the BMA approach, the proposed En-BMA method can improve probabilistic streamflow forecasting, especially under high flow conditions. Also, the proposed HUP-BMA approach has taken advantage of both HUP and BMA methods to better quantify the hydrologic uncertainty. Moreover, the applicability of the modified En-BMA as a more robust post-processing approach for precipitation forecasting, compared to BMA, has been demonstrated.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Possessing a reliable streamflow forecasting framework is of special importance in various fields of operational water resources management, non-structural flood mitigation in particular. Accurate and reliable streamflow forecasts lead to the best possible in-advanced flood control decisions which can significantly reduce its consequent loss of lives and properties. The main objective of this research is to develop an enhanced ensemble-based probabilistic streamflow forecasting approach through proper quantification of predictive uncertainty using an ensemble of streamflow forecasts. The key contributions are: (1) implementing multiple diverse forecasts with full coverage of future possibilities in the Bayesian ensemble-based forecasting method to produce more accurate and reliable forecasts; and (2) developing an ensemble-based Bayesian post-processing approach to enhance the hydrologic uncertainty quantification by taking the advantages of multiple forecasts and initial flow observation. The findings of this study are expected to benefit streamflow forecasting, flood control and mitigation, and water resources management and planning.


title: Mental Health of Children & Youth in Canada

contributor:
Gillett, James
Sociology

subject:
mental health
youth
children
educational discrepancy
ethnicity

abstract: Do the experiences that children and youth face early in life impact their mental health differently across immigrant generations? And do these associations vary by ethnicity and gender? My thesis addresses these significant and critical questions, as immigrants have been a large contributor to Canada’s population and are expected to grow in the next couple of decades. Research on the complexities of the social environments that shape and contribute to a child and youth’s mental health has been well documented in literature throughout the years. However, current research on immigrant children and youth that have examined the healthy immigrant effect across immigrant generations (immigrants versus. Native-born) in Canada have been sparse as there have been relatively few studies on this topic. Moreover, the studies on the healthy immigrant effect of children and youth immigrants in Canada have been inconclusive if immigrant children and youth have this initial health advantage. My study contributes to the understanding of how children and youth can experience similar life events (e.g., having parent-child educational aspiration discrepancies and sense of community belonging) but can impact their mental health differently based on immigrant status as well as ethnicity and gender. I use data from the Hamilton Youth Study (HYS) (2013) that has a representative sample of first-, second-, and native-born children of children and youth living in Hamilton, Ontario, Canada to examine parent-child educational aspirations and mental health across immigrant generations along with gender. I also use data of the Canadian Community Health Survey-Mental Health (2012) along with the Census data to examine the association of how South Asian and Chinese youth living in similar ethnic neighborhoods contributes to their sense of belonging and impacts their mental health across generations. To test out these associations, I conducted Ordinary Least Squares regression for chapters 2 and 4 and Hierarchal Linear Modelling (HLM) techniques for chapter 3. These three papers contribute to the discussion of the healthy immigrant effect of children and youth by suggesting that children and youth that experience the same events earlier in life can impact their life to a greater extent more than others based on immigrant status, as well as ethnicity and gender.

abstract: Thesis

abstract: Candidate in Philosophy


title: Power Allocation for Spatial Optical-OFDM With Dimming

contributor:
Steve, Hranilovic
Electrical and Computer Engineering

subject: VLC SO-OFDM

abstract:
Light-emitting diode (LED) luminaires are ubiquitous and widely used in our daily life. Because of energy efficiency and illumination requirements,  LED lamps are required to dim. In addition to the lighting function, visible light communication (VLC) is being considered as a potential technology beyond 5G.  Orthogonal frequency-division multiplexing (OFDM) is a  popular modulation choice and most recently spatial optical OFDM (SO-OFDM) has been used with multiple LEDs. SO-OFDM is a low complexity way of constructing OFDM signals by sending a series of narrow-band emissions from different LEDs and allowing them to sum in space. The integration of dimming within an SO-OFDM framework remains an open area of research.  In this thesis, an optimal dimming strategy for optical power allocation is
proposed based on SO-OFDM in visible light communication systems under different
illumination requirements, i.e., dimming. Firstly,  a non-convex problem is formulated to maximize the capacity of SO-OFDM under a specified dimming target. Furthermore, this non-convex problem is broken into a group of convex problems through approximations and constraint relaxation.

The proposed scheme can optimize the power allocation in SO-OFDM and achieve the dimming target at the same time. According to the proposed power allocation scheme, more of the power is allocated to subcarriers with low noise variance. This phenomenon makes sense to take advantage of good channels when power is limited and is similar to the conventional water-filling method. When the dimming target and signal-to-noise ratio (SNR) is sufficiently high,
the optimal distribution approaches a uniform distribution that agrees well with conventional water filling in a high SNR regime.
Compared with traditional digital dimming, the proposed spatial dimming method can not only use spatial domain for dimming but also allocates power to different subcarriers according to channel conditions which is more efficient.
Analytical and numerical results imply that the proposed scheme converges quickly and performs well compared with traditional power allocation methods.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Sensitivity to Model Structure in a Stochastic Rosenzweig-MacArthur Model Driven by a Compound Poisson Process

contributor:
Wolkowicz, Gail
Mathematics

subject: Probability, Analysis

abstract:
In this thesis we study the matter of hypersensitivity to model structure in the Rosenzweig-
MacArthur predator-prey model, and in particular whether the introduction of stochasticity
reduces the sensitivity of the !-limit sets to small changes in the underlying vector
field. To do this, we study the steady-state probability distributions of stochastic differential
equations driven by a compound Poisson process on a bounded subset of Rn, as
steady-state distributions are analogous to !-limit sets for stochastic differential equations.
We take a primarily analytic approach, showing that the steady-state distributions
are equivalent to weak measure-valued solutions to a certain partial differential equation.
We then analyze perturbations of the underlying vector field using tools from the theory
of compact operators. Finally, we numerically simulate and compare solutions to both
the deterministic and stochastic versions of the Rosenzweig-MacArthur model.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Stringent Response of Salmonella Typhimurium

contributor:
Coombes, Brian K.
Biochemistry and Biomedical Sciences

subject: Salmonella Typhimurium, stringent response, host-pathogen interactions, innate immunity

abstract: Bacteria inhabit diverse environmental niches and consequently, must modulate their metabolism to adapt to stress. The nucleotide second messengers guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) (collectively referred to as (p)ppGpp) are essential for survival during nutrient starvation. (p)ppGpp is synthesized by the RelA-SpoT homologue (RSH) protein family and coordinates the control of cellular metabolism through its combined effect on over 50 proteins. While the role of (p)ppGpp has largely been associated with nutrient limitation, recent studies have shown that (p)ppGpp and related nucleotides have a previously underappreciated effect on different aspects of bacterial physiology, such as regulating bacterial interactions with its host. This thesis focuses on the coordination of virulence gene expression and evasion of host immunity by (p)ppGpp in Salmonella enterica serovar Typhimurium. In the first data chapter, I describe the role of (p)ppGpp in mediating bacterial resistance to killing by the human complement system. I identified that (p)ppGpp activates ppnN, a nucleotide metabolism associated enzyme, and the biosynthesis of lipopolysaccharide O-antigen to protect Salmonella from cell lysis by complement. The second data chapter compares and contrasts the stringent response of an invasive clinical isolate of Salmonella Typhimurium to a strain of Salmonella Typhimurium that causes acute gastroenteritis using RNA-sequencing. Critical analysis of our transcriptomics dataset showed that flagellar-based motility is differentially regulated by (p)ppGpp in the two strains of Salmonella. Together, these findings demonstrate that (p)ppGpp has significant functional roles beyond mediating adaptation to nutrient limitation.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)