VictorJuiz/thesis huggingface dataset:
Assessment of Cardiovascular Adaptation, Organ Perfusion, and Tissue Hypoxia in an Antibody Mediated Model of Moderate Anemia

Anemia is associated with increased brain and kidney injury, and mortality in surgical patients by undefined mechanisms. We hypothesize that anemia-induced tissue hypoxia is a potential unifying mechanism. A transgenic mouse model(HIF-ODD Luciferase) was utilized to assess the impact of antibody-mediated anemia on adaptive cardiovascular responses, tissue PO2(PtO2), and hypoxia-inducible factor(HIF)-expression. Red blood cell(RBC)-specific antibody(TER119) induced anemia via intravascular hemolysis, and splenic and hepatic RBC sequestration. Anemia-induced cardiovascular adaptations included increased: 1)peripheral arterial oxygen saturation, 2)cardiac output, 3)internal carotid blood flow, and 4)cerebrovascular reactivity. These mechanisms contributed to maintain brain PtO2. By contrast, renal perfusion was not increased, leading to a reduced renal PtO2. Also, increased HIF-1Îą expression was observed in renal, hepatic, and gut regions. These findings demonstrate that anemia-induced tissue hypoxia occurs in an organ specific manner. These data support the hypothesis that renal and splanchnic hypoxia may contribute to increased organ injury and mortality in anemic patients.

Keywords: Anemia
Cardiovascular
Organ Perfusion
Tissue Hypoxia
Advisor: Mazer, C David
Hare, Gregory MT
Transduction of Human Alpha Synuclein in the Subcoeruleus Region causes Symptoms of REM Sleep Behaviour Disorder in Mice

During rapid-eye-movement (REM) sleep, dreams and wake-like cortical activity accompany muscle paralysis (atonia) interspersed with phasic twitches, motor characteristics controlled by the pontine subcoeruleus (SubC) region. REM sleep behaviour disorder (RBD) is a disruption of motor control during REM sleep, manifesting as loss of atonia, increased twitches, and overt movements. Over 90% of RBD patients develop synucleinopathy, a neurodegenerative disorder associated with aggregates of the protein alpha-synuclein (αSyn). While brains of RBD patients show αsyn aggregates within the SubC region, there is currently no direct evidence of the effects SubC αSyn-related pathology will have on REM sleep. Using targeted overexpression of human αSyn in the SubC, I demonstrated αSyn-aggregation, excessive muscle twitches during REM sleep, and slowing of cortical activity in wild type mice. This project links RBD symptoms and αSyn in the SubC region, and has produced an RBD model that is clinically-relevant to the pathology of human synucleinopathy.

Keywords: adeno-associated virus
alpha-synuclein
REM sleep
REM sleep behaviour disorder
synucleinopathy
twitches
Advisor: Peever, John
Cell-based IL-12 Immunotherapy In A Transgenic Murine Breast Cancer Model

Interleukin-12 (IL-12) is a pro-inflammatory cytokine that plays a major role in immune responses. IL-12 causes increases in T and NK cell proliferation, interferon-Îł (IFN- Îł) production and leads to a TH1 differentiation bias and cell-mediated immunity. Due to the many potent pro-inflammatory effects, the use of IL-12 for cancer immunotherapy has been a constant topic of debate. A promising approach to cancer immunotherapy has been studied by our lab where a small number of transduced tumour cells expressing IL-12 are injected to initiate an immune response. Upon injection, these IL-12 transduced host tumour cells cause sustained rejection, even to challenges with the original parent tumour. The effectiveness of this model has thus far been demonstrated in murine leukaemias and various solid tumour models. In this thesis, I have developed a novel breast cancer cell line model derived from the MMTV-PyMT transgenic breast cancer model to expand the cell-based IL-12 cancer immunotherapy into a more clinically relevant solid tumour model.

Keywords: Breast Cancer
Immunotherapy
Interleukin 12
MMTV-PyMT
Transgenic
Advisor: Paige, Christopher J
Evaluating Sit-to-stand Across Various Armrest Configurations in Older Adults with Limited Mobility

This study investigated the differences in kinematics and kinetics of the lower limbs and load applications of the upper limbs across various armrest configurations. Configurations tested include nine combinations through three anterior-posterior (AP) positions (close, middle, far) and three height positions (low, middle, high). A linked-segment model was used to calculate kinetics and kinematics of the lower limbs using an inverse dynamic analysis. Forces were recorded from two force plates below the feet and two load cells embedded in the armrests. Farther armrest AP positions yielded higher pulling forces and were encountered with greater moments about the knees and hips. Higher armrest positions yielded greater pulling forces and were encountered with reduced moments about the hips and ankles. Stability was best in far and high positions. Potential applications for this research include an armrest design guideline for use by seating companies, rehab therapists, and for potential armrest products.

Keywords: aging
armrest
mobility
sit-to-stand
Advisor: Dutta, Tilak
Don't Get Caught in the Cold, Warm-up Your JVM: Understand and Eliminate JVM Warm-up Overhead in Data-parallel Systems

Many widely used, latency sensitive, data-parallel distributed systems, such as HDFS, Hive, and Spark choose to use the Java Virtual Machine (JVM), despite debate on the overhead of doing so. This thesis analyzes the extent and causes of the JVM performance overhead in the above mentioned systems. Surprisingly, we find that the warm-up overhead is frequently the bottleneck, taking 33% of execution time for a 1GB HDFS read, and an average of 21 seconds for Spark queries. The findings on JVM warm-up overhead reveal a contradiction between the principle of parallelization, i.e., speeding up long running jobs by parallelizing them into short tasks, and amortizing JVM warm-up overhead through long tasks. We solve this problem by designing HotTub, a modified JVM that amortizes the warm-up overhead over the lifetime of a cluster node instead of over a single job.

Keywords: Big Data
Distributed Systems
Java Virtual Machine
Performance
Advisor: Yuan, Ding
Wholesale Broadband Access and Regulatory Appeals in the Canadian Telecommunications Industry: An Institutional Analysis

This thesis focuses on Canada’s federal regulatory appeal procedure, the “Petition to the Governor in Council” (GiC), and questions how it integrates with other institutional actors in the country’s telecommunications policymaking apparatus. The research applies the Institutional Analysis and Development framework methodology to a recent GiC appeal decision in favour of mandated wholesale broadband access to fibre-to-the-premises facilities. This appeal decision, the thesis suggests, helps to illustrate how Canada’s telecommunications regulator, the CRTC, has maintained its ability to shape the specifics of policy outcomes. Despite GiC jurisdiction over the direction to telecommunications regulation, as well as obstructions to CRTC policy development that can transpire as a byproduct of GiC appeal decisions, the findings show that the CRTC has nevertheless defended its status as the lead actor in the regime. The thesis also points to areas where the GiC procedure would benefit from improved transparency and strengthened conduits for regional representation.

Keywords: Broadband
Communications
Institutional Economics
Internet Law
Regulatory Law
Telecommunications Policy
Advisor: McEwen, Rhonda
Estimating a Toronto Pedestrian Route Choice Model using Smartphone GPS Data: It's Not the Destination, but the Journey, that Matters

City planning has an emphasis on working towards creating walkable cities with boulevards, wide sidewalks, and social spaces. This study uses revealed preference GPS data collected through a smartphone-based travel survey and discrete choice modelling techniques to determine pedestriansâ preferences towards street infrastructure, built environment, and land use. A path size logit model with stochastic route choice generation choice set was used for this model. The results of the model showed that distance, the number of turns, the number of signalized intersections, and distance along links with sidewalks on both sides of the street were significant variables in the route choice model. Turns are found to be equivalent to an additional 32m, signalized intersections are equivalent to a reduction of 34m, and travel along streets with sidewalks on both sides of the road is perceived as 33% shorter than streets with other sidewalk conditions.

Keywords: Path Size Logit
Pedestrian
Route Choice
Smartphone Data
Stochastic
Advisor: Miller, Eric J
Evaluation of a Real-time Buying Power Engine for Wealth and Asset Management

Large banks provide wealth management services to their clients, through which investors can use cash and borrowed funds to invest in securities. The implementations of technologies for these services are long-term, capital projects which require rigorous assessment before selection and implementation. An evaluation framework was developed by incorporating individual frameworks and assessing capabilities. The goal of this framework is to provide a standardized approach for the evaluation of various technology vendors. One potential vendor was evaluated using the developed framework, outlining performance and capability metrics, gaps and action items for compliance to the Bankâ s needs. Using the results of the evaluation framework, a recommendation was provided to the Bank for further steps towards implementation of the vendorâ s solution.

Advisor: Paradi, Joseph C
Objective Vision-based Assessment of Parkinsonism and Levodopa-induced Dyskinesia in Persons with Parkinsonâ s Disease

Parkinsonâ s disease (PD) is the second most common neurodegenerative disease, with the incidence rate climbing rapidly as the global population ages. While levodopa is effective at treating PD symptoms, prolonged usage can introduce additional motor complications called levodopa-induced dyskinesias (LID). Assessment of PD/LID requires regular visits to a clinic; however, the intermittent nature of assessments can fail to capture changes in a personâ s condition. With computational power becoming increasingly more affordable, computer vision is an accessible means of performing more frequent and objective PD assessments. A study of deep learning for human pose estimation was conducted to examine the feasibility of extracting body movements from videos of PD assessments. Machine learning was applied to detect and estimate the severity of PD/LID using movement features. Results indicate computer vision is a promising candidate for objective PD assessment, thus laying the foundation for an automated system for evaluation of PD motor symptoms.

Keywords: Computer vision
Deep learning
Disease management
Health monitoring
Parkinson's disease
Advisor: Taati, Babak
Fernie, Geoff
Exploration of Essential Biological Processes by Construction of Conditional Alleles of Non-essential Genes in S. cerevisiae

Conditional mutants in S. cerevisiae have been useful tools in studying essential gene functions. In this study, I describe a new method that makes use of yeast deletion collections with a marker swap system to generate conditional temperature sensitive (TS) mutations in non-essential genes. I created TS mutants of BNI1, a non-essential formin gene, in various genetic backgrounds that BNI1 is essential for viability. I also constructed reciprocal TS alleles in five genes that are synthetic lethal with bni1 deletion. I screened for dosage suppressors in various synthetic lethal backgrounds of BNI1, covering different biological processes. I identified process-specific as well as common suppressors for each synthetic lethal pair. I also constructed morphological marker strains that are compatible with my system. My studies demonstrate the feasibility of construction TS mutant alleles of non-essential genes, and their utility for exploring synthetic lethal phenotypes.

Keywords: Budding yeast
Dosage suppression
Genetic interactions
Mutagenesis
Synthetic lethality
Advisor: Andrews, Brenda
Boone, Charlie
Genetic Adaptation Contributing to Increased Gonococcal Fitness during Vaginal Infection of CEACAM-humanized Mice

Neisseria gonorrhoeae (Gc), the obligate human pathogen responsible for gonorrhea, has drastic consequences on reproductive health, if left untreated. Although, vaginal infection in wild-type mice can simulate asymptomatic colonization, important host-specific factors essential for human infection are overlooked. I utilize mice expressing human CEACAM3, CEACAM5, and CEACAM6, to reveal factors promoting mucosal colonization. By serial passaging Gc in the lower genital tract of these mice, I demonstrate a higher proportion of mice colonized in subsequent infections, suggesting selection for bacteria better capable of colonization. No changes in susceptibility of bacteria to low pH, complement-mediated killing or antimicrobial peptides, mCRAMP and mBD-1, were observed. Finally, a genome-wide analysis identified mutations acquired by in vivo adapted isolates. One mutation has previously been investigated as a promising vaccine target, validating the infection model and screening process. Further examination of other identified changes may provide insight into the Gc lifestyle within the genital mucosa.

Keywords: bacterial fitness
carcinoembryonic antigen-related cell adhesion molecule
Neisseria gonorrhoeae
transgenic mice
vaginal infection
whole genome sequencing
Advisor: Gray-Owen, Scott D.
Balance and Knee Joint Kinematics after Total Knee Arthroplasty: Comparing Cruciate-retaining and Posterior-stabilized Designs

Total knee arthroplasty (TKA) is a common surgical procedure for osteoarthritis and other degenerative conditions of the knee. Posterior stabilization may be achieved using a cam and post mechanism (PS), or by retention of the posterior cruciate ligament (CR). Little evidence exists to indicate superiority of either PS or CR designs. Further, few studies have examined balance in TKA patients, despite an established link to falls risk. Patients with PS- and CR-TKA were compared to healthy, age-matched controls. A methodology was established for assessment of balance and knee kinematics in TKA patients. Data collection included demographics, participant-reported outcomes, objective functional measures, and balance and kinematic assessment during postural perturbations. While all groups displayed similar balance performance, we identified important functional and kinematic differences between TKA groups. Further study is required to identify the mechanisms by which TKA impacts falls risk, and to further define biomechanical differences between these implants.

Keywords: Balance
Biomechanics
Knee
Posterior Cruciate Ligament
Total Knee Arthroplasty
Advisor: Fernie, Geoff
Examining Civil Society Participation in the Health Sector: The Case of Brazil's Health Councils

This thesis focuses on Brazil's Health Councils (Conselhos de Saude) to explore challenges in institutionalizing civil society participation. By conducting interviews with Health Council members at the municipal, state and national levels, this thesis examines how Health Councils operate and identifies some of the challenges evident in institutionalizing civil society participation. The thesis reports that Health Councils lack autonomy from the government to fulfill their mandate, membership guidelines limit the level of inclusion of civil society members, government representatives manipulate other members and provide limited support for Health Councils. In addition, it also reports that there is a lack of resources necessary to run Health Councils, there is an inadequate level of training of Health Council members, and there is a reported strong sense of individualism amongst members. These issues appear to have an impact on Health Councilsâ ability to successfully fulfill their mandate.

Keywords: Brazil
civil society participation
good governance
health councils
health policy
Advisor: Kohler, Jillian C
Investigating Molecular Differences related to T-bet-Positive Tumor-infiltrating Lymphocytes in Axillary Node-negative Breast Cancer

The clinical outcomes of axillary node-negative (ANN) breast cancer (BC) patients were previously shown to be positively associated with T-bet+ tumor-infiltrating lymphocytes (TILs). This study identified differences in miRNA and gene expression, and in PD-L1 expression between T-bet+/high and T-bet-/low tumors that provided insights into how T-bet+ TIL- mediated immunesurveillance may relate to tumor characteristics and disease outcome in ANN BC. The differentially expressed (DE) miRNAs were associated with intrinsic cancer-related pathways and immune-modulatory activities. miR-135a, in particular, was downregulated in T- bet+/high tumors, and was shown to be a direct suppressor of CXCL10, a T lymphocyte-recruiting chemokine. Among the DE genes, BRD4, a co-activator of NF-kB, was upregulated in T-bet+/high tumors at both mRNA and protein levels, suggesting a link between BRD4 expression and T-bet+-TIL-mediated inflammatory activities. The mRNA expression of PD-L1, a T-cell inhibitory marker, was associated with T-bet+ TILs, and basal subtype.

Keywords: BRD4
Breast Cancer
miRNA
PD-L1
T-bet
TIL
Advisor: Andrulis, Irene L
Transit User Mode Choice Behaviour in Response to TTC Rapid Transit Service Disruption

Disruption of transit service is a common occurrence in many cities around the world, and these incidents may have serious impacts on the transit userâ s journey. The purpose of this study is to investigate transit user commuting mode choice in response to rapid transit service disruption in the City of Toronto. A joint Revealed Preference and Stated Preference survey is designed to gather information on the respondentâ s actual response to the most recent service disruption and also responses under a set of hypothetical service disruption scenarios. A transit trip planner tool is developed to generate alternative transit options to avoid the disrupted segment. Econometric models are presented, including a joint RP-SP model, showing that the following factors, in addition to travel time and cost, are significant at 95% confidence: frequency of subway trip, trip purpose, subway delay, shuttle bus delay, weather, age, and income. Policy implications are also discussed.

Keywords: Mode Choice
Public Transit
RP-SP survey
Subway Service Disruption
Toronto Transit Commission
Travel Behaviour
Advisor: Shalaby, Amer S
Miller, Eric J
Understanding the Travel Behaviour of Families with Dependent Children Within the Context of Activity Based Modelling

This thesis presents in investigation into several inter-related travel decisions made by families with children, a topic which has been generally overlooked by major travel demand models. The primary goal of this investigation was to develop an empirical understanding of these decisions which would allow the behaviour of families with children to be accurately represented in an activity scheduling model. The first of these decisions is the joint choice of whether a family will use a out-of-home childcare service, and the location of that service, and the thesis proposes an econometric model for this nested choice. A novel method for generating the daycare location choice set using a stochastic frontier model is proposed and tested. Finally, the effect of needing to drop off a child at daycare or school in the morning on an adultâ s choice of travel mode and departure time is analyzed.

Advisor: Habib, Khandker N
Autonomous Ground Target Tracking, Testing, Commissioning and Operations for Greenhouse Gas Satellite Demonstrator (GHGSat-D)

Greenhouse gas satellite demonstrator (GHGSat-D) is a microsatellite designed, built, tested and operated by Space Flight Laboratory (SFL) on behalf of GHGSat Inc. that demonstrates the payload technology needed to monitor carbon dioxide and methane gas emissions, which directly contribute to the epidemic that is global warming, using an infrared spectrometer and a hyperspectral imager. Mission background and satellite overview are presented, followed by a deeper look into various methods of ground and environmental testing involving the author in preparation for satellite integration and operations. A more efficient method of downloading data while maximizing use of pass time is established through the implementation of an autonomous ground target tracking algorithm. Finally, results of a successful commissioning phase and daily operations are revealed.

Advisor: Zee, Robert Zee
Modelling H3.3-G34R mutation in vitro and in vivo

Brain tumours are the most common solid tumours in children, with pediatric high-grade gliomas (PHGG) displaying clinically aggressive behaviour and dire survival outcomes. Previous evidence points toward a histone 3 variant H3F3A mutation (H3.3-G34R) in pediatric glioblastomas, which results in redistribution of the histone mark H3K36me3. It has been shown that H3K36me3 is necessary for recruitment of the mismatch repair (MMR) protein complex hMutSalpha (hMSH2-hMSH6). In vitro, Western blot and immunofluorescence analysis was performed on immortalized normal human astrocytes (iNHAs) to establish decreased H3K36me3 levels in S phase synchronized H3.3-G34R mutant cells. MSH6 foci formation was unaffected in the absence of a DNA damage inducing agent. In vivo, immunohistochemical analysis on H3.3-G34R xenograft tumour showed decreased levels of H3K36me3. Therefore, the H3.3-G34R mutation leads to loss of H3K36me3 levels, highlighting another impact of epigenetic disruption in PHGG.

Keywords: Cancer
H3.3-G34R
H3K36me3
High Grade Glioma
Histone Mutation
Pediatric
Advisor: Hawkins, Cynthia
Functional Analysis of Short Linear Motifs in Intrinsically Disordered Regions

Short linear motifs (SLiMs) are regulatory binding sites that are involved in signalling and protein regulation. SLiMs are often found in intrinsically disordered regions (IDRs) which are rapidly evolving and lack stable tertiary conformations. Despite their prevalence throughout the proteome, many SLiMs still remain unknown and understanding how they cooperate and evolved are ongoing endeavours. The goal of this thesis is to address the properties of SLiMs and how they evolved, using bioinformatics methods and evolutionary models. To further examine the role of SLiMs in signal transduction, I show that deletion of predicted SLiMs (pSLiMs) has a broad range of quantitative effects on signalling pathway output. Next, to explore what properties are important in substrate recognition, I show that the combination and order of motifs can predict target specificity. Lastly, using a comparative phylogenetic approach to investigate the evolution of motifs, I provide evidence that phosphorylation and docking sites coevolved.

Keywords: coevolution
comparative phylogenetics
computational biology
intrinsically disordered regions
short linear motifs
SLiM combinations
Advisor: Moses, Alan M
Temperature-dependent Patterns of Gene Expression in Caenorhabditis briggsae

Discerning the genetic basis of adaptive phenotypes is a fundamental problem in biology that remains an open question. Studies using high-throughput sequencing methods of gene expression have contributed greatly to our understanding of how genotype becomes phenotype by treating gene expression as an intermediary phenotype, especially under variable environmental conditions. Using whole genome high-throughput RNAseq data, I characterized the responses of Temperate and Tropical genotypes of Caenorhabditis briggsae to chronic temperature stress. These genotypes show evidence of local adaptation, suggesting that differences in their responses to temperature may underlie adaptive phenotypes. I discovered that a large proportion of genes show genotype-specific changes in gene expression in response to temperature (genotype-by-temperature interactions), and that most of these genotype-specific responses occur under heat stress. These results suggest that responses to cold stress and heat stress are qualitatively different, and identify sets of genes that suggest further study into temperature-adapted phenotypes.

Advisor: Cutter, Asher D