VictorJuiz/thesis huggingface dataset:
CHARACTERIZING AQP9: A REGULATOR OF EPIPHYSEAL PLATE CHONDROCYTE PROLIFERATION, HYPERTROPHY, AND LONG BONE GROWTH

Aquaporin-9 (AQP9) is a membrane channel protein suspected to regulate growth in the epiphyseal plate. As long bone defects often possess limited non-surgical options, novel factors underlying bone growth must be continuously explored to advance effective treatments. I hypothesized that Aqp9 is an important epiphyseal plate chondrocyte channel regulating the process of endochondral ossification. In this study, Aqp9 -/- mouse long bones compared to wildtype mouse long bones showed a neonatal hindlimb-specific acceleration of growth followed by reduced length in the juvenile age. Analysis of Aqp9 -/- epiphyseal plates and chondrocytes showed an early disposition for proliferation and aversion from hypertrophy, suggesting that Aqp9 may function similarly to genes such as Col10a1 and Mmp13. This study provides insight into chondrocyte membrane channel proteins and their regulation of the growing epiphyseal plate, demonstrating that Aqp9 may be a novel therapeutic target for the non-invasive intervention of leg length discrepancies.

Keywords: aquaporin
bone
channelome
chondrocyte
endochondral ossification
epiphyseal plate
Advisor: Kannu, Peter
Resveratrol Effect on Oral Inflammatory Load in Chronic Periodontitis: A Pilot Study

Chronic periodontitis is an inflammatory disease that diminishes tooth-supporting structures and is dependent on neutrophil recruitment and oxidative stress. An anti-oxidant, resveratrol (3, 4’, 5-trihydroxystilbene) blocks neutrophil recruitment and oxidative bursts. Thus, resveratrol can help lessen oral inflammatory load (OIL), thereby reducing clinical manifestations of periodontitis. It was hypothesized that OIL will be further reduced in periodontitis patients treated with SRP plus resveratrol, compared to SRP alone. A randomized triple-blind clinical trial was conducted. By measuring clinical parameters, oral neutrophil numbers, and neutrophil phenotypes, it was demonstrated that, while not statistically significant, resveratrol treatment further reduced OIL. Importantly, patients treated with resveratrol demonstrated earlier responses to treatment compared to those on placebo. This pilot study demonstrated the potential benefits of resveratrol, as an adjunctive treatment to SRP. Further research should be conducted with larger cohorts to examine the benefits of resveratrol in patients with periodontal diseases, particularly those with co-morbidities.

Keywords: Periodontitis
Resveratrol
Advisor: Tenenbaum, Howard
Evaluating the Glycogenic Activity and Therapeutic Capacity of PPP1R3D in a Mouse Model of Lafora Disease

Lafora disease (LD) is an intractable, neurodegenerative epilepsy caused by loss-of-function mutations in the EPM2A or EPM2B genes. Central to LD is the accumulation of malstructured glycogen (Lafora bodies; LB) in neurons, a consequence of dysregulated glycogen synthesis. Glycogen synthase catalyzes glycogen formation and is activated by dephosphorylation. The latter is mediated by glycogen-targeting subunits of protein phosphatase 1, including PTG (R5) and R6, known formally as PPP1R3D, both abundantly expressed in brain. PTG knockout in LD mice rescues LD, including near-complete disappearance of LB and neurodegeneration. I examined whether the same could be achieved with R6 knockout. Despite significant brain glycogen and LB reductions in R6-deficient-Epm2a-/- mice, substantial amounts of LB remained and neurodegeneration was not rescued. This partial effect remains unexplained. Future experiments to resolve the difference with PTG will shed important light on both LB formation and Lafora disease, and brain glycogen metabolism.

Keywords: glycogen
glycogen targeting subunit
lafora bodies
Lafora disease
neurology
PPP1R3D
Advisor: Minassian, Berge A
Scherer, Stephen W
A Reverse Genetics Approach to Examining Drosophila Social Interaction Networks (SINs)

Social network analysis is a powerful tool for understanding the underlying mechanisms that regulate the evolution of sociality. The social behaviour of individuals manifests in non-random inter-individual social interactions, including cooperation in foraging, mating, and competition. These interactions comprise the social network of the population, affecting group-level processes such as information flow and disease transmission. Social network structure is quantifiable; therefore, understanding the reciprocal relationship between these processes and network structure could provide insight into the fitness consequences of various social behaviour strategies, and why they persist within the population. Most studies which utilize the network approach rely on observational data of animal populations. These studies are limited because researchers are unable to manipulate the genetic and social environment. Therefore, the objective of my thesis is to provide insight into how social interaction network (SIN) structure is affected by genetic mechanisms and social context using the model organism Drosophila melanogaster.

Keywords: DIP‑B
Drosophila melanogaster
Group size
Olfactory sensilla
Social context
Social network
Advisor: Levine, Joel D
Applying Stable Carbon Isotopic Analysis at the Natural Abundance Level to Determine the Origin of Docosahexaenoic Acid in the Brain of the Fat-1 Mouse

Current methods applied to study the origin and metabolism of brain fatty acids involve the administration of synthesized fatty acid tracers. The high cost of these tracers makes it infeasible to conduct chronic studies through this approach, limiting study durations to acute time points that may not reflect the chronic, steady-state, metabolism of fatty acids. Here, we provide the proof-of-concept of a cost-efficient alternative method: natural abundance compound specific isotope analysis by isotope ratio mass spectrometry. Through the application of this method, we differentiated between tissue docosahexaenoic acid (DHA) originating directly from diet or DHA biochemically synthesized in a complex transgenic model: the fat-1 mouse. We further determined pre-formed dietary DHA to be the main source of brain DHA in fat-1 mice fed a diet rich in n-6 and/or n-3 PUFA. Future studies could utilize this approach to answer complex question pertaining to brain fatty acids origin and metabolism.

Keywords: Brain
compound specific isotope analysis
docosahexaenoic acid
Fat-1 mouse
isotope ratio mass spectrometry
Advisor: Bazinet, Richard P
The Neurostructural Phenotypes of CACNA1C rs1006737 in Adolescents with Bipolar Disorder and Healthy Controls of Caucasian Race

Background: CACNA1C rs1006737 has been implicated in structural brain differences in adults with bipolar disorder (BD) and/or healthy controls (HCs). No prior study has examined associations between rs1006737 and brain structure in adolescents. Methods: Seventy-one adolescents (14-20 years; 38BD, 33HC) underwent 3-Tesla Magnetic Resonance Imaging (MRI). ROI and whole-brain vertex-wise analyses examined cortical and subcortical volume, surface area (SA), and/or thickness. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and total intracranial volume. Results: Vertex-wise analysis found significant diagnosis-by-rs1006737 interactions for prefrontal and occipital brain structure Main effects of rs1006737 were found on anterior cingulate cortex SA from ROI analysis, and occipital SA from vertex-wise analysis. Conclusion: The current study identified neurostructural intermediate phenotypes relevant to the impact of CACNA1C rs1006737 on adolescent BD. Further investigation is warranted into the relevance of rs1006737 associations with BD-specific elevations in regional SA.

Keywords: Adolescent
Bipolar Disorder
brain structure
CACNA1C
Neuroimaging
rs1006737
Advisor: Goldstein, Benjamin I
Genotyping and Phenotypic Analysis of Streptococcus mutans Isolates From Children With and Without Dental Caries

Within dental plaque, Streptococcus mutans produces acids from fermentable carbohydrates, decreasing the biofilm pH, causing enamel demineralization. S. mutans produces persisters, dormant variants of cells that survive lethal antibiotic concentrations without developing antibiotic resistance. Persisters have been associated with infection chronicity. We hypothesized that phenotypic heterogeneity of S. mutans is directly associated with cariogenicity. S. mutans were isolated from plaque collected from caries-free (CF) children and children with Severe Early Childhood Caries (S-ECC). For each identified genotype, an acid tolerance analysis was performed and persisters were quantified. In S-ECC patients with >1 strain, the dominant strain exhibited higher cell survival following exposure to pH 3.2, whereas in CF patients, survival was similar. S. mutans isolates from S-ECC patients produced ~15x more persisters than isolates from CF patients. S. mutans exhibits phenotypic diversity. The ability of S. mutans to produce high levels of persisters may be a hallmark of cariogenicity.

Keywords: Acidurance
Caries
Early Childhood Caries
Persistence
S mutans
Streptococcus mutans
Advisor: Levesque, Celine
The Sooting Propensities of Ethanol, Ethylene, Propylene, and Butylene at Elevated Pressures

Laminar co-flow diffusion flames of ethanol-doped methane flames with 10% of carbon from ethanol up to 6 bar and nitrogen-diluted alkene flames of ethylene and propylene up to 8 bar and 1-butylene up to 2.5 bar were investigated. Line-of-sight spectral emission measurements were inverted with an Abel-type algorithm to obtain radially resolved soot volume fraction and temperature measurements. Ethanol-doped methane flames displayed consistently higher soot yields than neat methane flames, but only a slightly higher pressure dependence. Comparing the nitrogen-diluted alkene flames, 1-butylene produced the most soot, followed by propylene and ethylene. Propylene and 1-butylene displayed similar sooting propensity pressure dependencies, but ethylene was found to have a significantly stronger pressure dependence. This was attributed to the greater concentration of aromatics in the pyrolysis products of propylene and 1-butylene as aromatics have been found to have a weaker sooting propensity pressure dependence.

Keywords: combustion
flame
pressure
soot
Advisor: Gülder, Ömer L
Adversarial Attacks on Face Detectors using Neural Net based Constrained Optimization

Adversarial attacks involve adding, small, often imperceptible, perturbations to inputs with the goal of getting a machine learning model to misclassifying them. While many different adversarial attack strategies have been proposed on image classification models, object detection pipelines have been much harder to break. In this thesis, we propose a novel strategy to craft adversarial examples by solving a constrained optimization problem using an adversarial generator network. Our approach is fast and scalable, requiring only a forward pass through our trained generator network to craft an adversarial sample. Unlike in many attack strategies we show that the same trained generator is capable of attacking new images without explicitly optimizing on them. We evaluate our attack on a trained Faster R-CNN face detector on the cropped 300-W face dataset where we manage to reduce the number of detected faces to 0.5% of all originally detected faces.

Keywords: Adversarial Attacks
Computer Vision
Face Detection
Faster R-CNN
Machine Learning
Neural Networks
Advisor: Aarabi, Parham
Quantification of Mutans Streptococci and Persister Cells in Orthodontic Patients: A Pilot Investigation

Orthodontic patients have higher risk for dental caries. Within plaque biofilm, mutans streptococci (MS) are present together with persister cells (PC), a microbial subset that confers disease chronicity and relapse potential. PC levels are elevated by environmental stresses, e.g., orthodontic treatment. Our purpose was to quantify, for the first time, MS and PC in orthodontic patients. Plaque samples were collected in 17 patients at 0, 1 and 6 months after fixed appliance bonding. Percentage of MS and PC were determined by microbiological assays. Overall, treatment did not affect %MS and %PC (P>0.05). However, %PC response to treatment appeared to be dependent on baseline %MS values. Patients with low %MS at baseline had an increase in %PC during treatment, while %PC decreased in those with high baseline %MS. Orthodontic treatment may provide a way for MS to persist in individual orthodontic patients with specific subtypes and contribute to higher caries incidence.

Keywords: Biofilm
Dental Caries
Dental Plaque
Mutans Streptococci
Orthodontics
Persisters
Advisor: Gong, Siew-Ging
Levesque, Celine M
The Role of Synaptic Inhibition in the Primary Motor Cortex of an ALS Mouse Model

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease resulting from the degeneration of motor neurons in the cortex and spinal cord. ALS is the most common neurodegenerative disorder of the motor system and involves progressive muscle weakness and atrophy. Cortical hyperexcitability is a hallmark feature of ALS, and recent studies report reductions in synaptic inhibition in the primary motor cortex (M1) presymptomatically. Rescuing interneuron-mediated inhibition is a promising strategy for reducing hyperexcitability and slowing the onset of ALS. This study aimed to determine whether chemogenetic or pharmacological tools could decrease pyramidal neuron hyperexcitability in Layer 5 of the M1 (L5-M1) in the SOD1G93A ALS mouse model. The principle novel findings of my work are: (i) increasing GABAergic interneuron-mediated inhibition onto L5-M1 pyramidal neurons rescues hyperexcitability of M1 pyramidal neurons and (ii) riluzole reduces hyperexcitability and affects intrinsic membrane properties of M1 pyramidal neurons.

Keywords: Amyotrophic Lateral Sclerosis
Chemogenetics
Electrophysiology
Primary Motor Cortex
Riluzole
Synaptic Inhibition
Advisor: Woodin, Melanie A
The Role of ATP and P2X Purinoceptor 7 in the Development of Cerebral Tau

ATP release and signalling via the P2X7 receptor have been implicated in numerous pathological processes including neurodegeneration and may play a role in the development of tauopathies. We injected ATP analogue bzATP intraventricularly into C57BL/6 mice, pre-treated with either intraperitoneal P2X7R antagonist Brilliant Blue G (BBG) or vehicle. Behavioural outcomes, levels of phosphorylated tau, and immunohistochemical changes in astrocytes and microglia were assessed at 2 weeks and 3 months after treatment. We observed increased immobile time in the tail suspension test and poor performance on rotarod for bzATP-treated mice at 3 months post-treatment, which were diminished by BBG pre-treatment. Western blot revealed increased levels of phosphorylated tau in bzATP-treated mice compared to controls. Astrocytic marker GFAP showed increased periventricular staining at both 2 weeks and 3 months for bzATP-treated mice but microglial marker IBA1 showed no changes. In summary, ATP-P2X7R-mediated mechanisms lead to development of behavioural deficits and increased phosphorylated tau.

Keywords: ATP
Neurodegeneration
P2X7R
Tau
Tauopathy
Advisor: Hazrati, Lili-Naz
Survival of Class III Amalgam and Composite Restorations in Primary Cuspid Teeth

OBJECTIVE: The aim of this retrospective cohort study was to determine the survival of class III amalgam and composite restorations in primary canines. METHODS: A chart review was done on patients seen at the University of Toronto’s pediatric dental clinic between 1999 and 2017. RESULTS: The median survival time of amalgam and composite was approximately 4.5 years and 3.8 years respectively. There was no significant difference between the clinical survival of amalgam and composite (log-rank test: p=0.09, Wilcoxon: p=0.31). Amalgam was significantly less likely to fail due to recurrent caries versus composite (p

Keywords: Amalgam
Caries
Composite
Dentistry
Restorations
Survival
Advisor: Andrews, Paul
Cultivating an American Worldview: A Comparative Analysis of Perspectives of the Middle East, Arabs, and Muslims in US Public High School “World History” Curricula

The institution of public education in democratic societies has been used as an effective tool for regulating national identity. In the last four decades, “World History” courses have become a fundamental part of mainstream American social studies. These courses offer a standardized narrative regarding the histories of non-Western regions. This study explores high school social studies curricula in Texas, New York, California,Virginia, and North Dakota focusing on how the frameworks address Islamic, Middle Eastern, and North African history. The analysis addresses the state frameworks’ ability to effectively present Islamic and Arab history within proper context and critiques various problematic paradigms rooted in modernization theory and orientalism. In critiquing the content of these frameworks and contextualizing policy in American public education, this paper intends to scrutinize the challenges of teaching the Middle East in the United States public high schools.

Keywords: Islamic History
Middle Eastern History
Middle East Studies
Secondary Education
Social Studies
United States
Advisor: Reilly, James A.
Enhancing FPGA Architecture for Efficient Deep Learning Inference

Deep Learning (DL) has become best-in-class for numerous applications but at a high computational cost that necessitates high-performance energy-efficient acceleration. FPGAs offer an appealing DL inference acceleration platform due to their flexibility and energy-efficiency. This thesis explores FPGA architectural changes to enhance the efficiency of a class of DL models, convolutional neural networks (CNNs), on FPGAs. We first build three state-of-the-art CNN computing architectures (CAs) as benchmarks representative of the DL domain and quantify the FPGA vs. ASIC efficiency gaps for these CAs to highlight the bottlenecks of current FPGA architectures. Then, we enhance the flexibility of digital signal processing (DSP) blocks on current FPGAs for low-precision DL. Our DSP block increases the performance of 8-bit and 4-bit CNN inference by 1.3x and 1.6x respectively with minimal block area overhead. Finally, we present a preliminary evaluation of logic block architectural changes, leaving their detailed evaluation for future work.

Keywords: Convolutional Neural Networks
Deep Learning
FPGA Architecture
Hardware Acceleration
Advisor: Betz, Vaughn
Identification of E3 Ubiquitin Ligase, UBR5, as a Potential Interactor of TTC7A and PI4KIIIα

Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) results in severe intestinal and immune disease phenotypes, one of them being Very Early Onset Inflammatory Bowel Disease (VEO-IBD). TTC7A is part of an evolutionarily conserved pathway and acts as a scaffolding protein recruiting Phosphatidylinositol 4-kinase Type III Alpha (PI4KIIIα) to the plasma membrane (PM). This conserved pathway helps PI4KIIIA phosphorylate phosphatidylinositol (PI) to PI 4-phosphate (PI4P) at the PM. The PIPs downstream of PI4P have been implicated in maintaining cell polarity and survival. Previously, mass spectrometry was performed to identify potential TTC7A binding partners. Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) was identified as one of the top TTC7A binding proteins. Results show co-immunoprecipitation of UBR5 with TTC7A along with mutants (E71K, Q526X, A832T) identified at The Hospital for Sick Children. Results also suggest that UBR5 may be part of the PI4KIIIA-FAM126A-TTC7A complex (and therefore implicate UBR5 in PM PI4P synthesis).

Keywords: FAM126A
PI4KIIIα
PI4P
TTC7A
UBR5
VEO-IBD
Advisor: Muise, Aleixo
Development of a Low-Cost Diagnostic Tool to Assess the Sufficiency of Food Drying Processes in Developing Countries

Food drying reduces moisture content supporting microbial growth that contributes to food spoilage in developing countries. However, there is a lack of efficient low-cost tools to assess the sufficiency of food drying in small-scale operations in developing countries. Thus, a model was developed using a thermal imaging process to determine the moisture content of dried Royal Gala apples based on their cooling rate. Fitted regression curves showing absolute temperature versus cooling time were plotted for different wet basis moisture contents. The regression curve obtained for a safe range of moisture (9-11%) produced an equation with a higher constant and exponent than the curve for a potentially unsafe range (15-17%), showing the potential of this method. Further analysis is needed to evaluate the applicability of this method in other types of dried foods and conditions, as well as to explore the possibility to use the developed model in a mobile application.

Keywords: Co-operatives
Developing countries
Dried food
Moisture content
Moisture measurement
Small-scale operations
Advisor: Touchie, Marianne
MacLean, Heather L
Exploring the Role of Somatostatin in the Pathogenesis of Alzheimer’s disease

The amyloid-β (Aβ) peptide is understood to be a critical factor in the pathogenesis of Alzheimer’s disease (AD), with soluble Aβ oligomers (oAβ) observed to be particularly toxic to neurons. For this reason, we undertook an in-depth search for oAβ binders in human brain, taking advantage of advanced mass spectrometry workflows. This analysis revealed the peptide somatostatin (SST) to be the most selective binder to oAβ in affinity capture experiments. Furthermore, SST was observed to interfere with Aβ aggregation kinetics and promote the formation of distinct 50-60 kDa Aβ assemblies. In a follow-up investigation of the SST interactome, it was revealed that SST predominantly binds to several members of the family of P-type ATPases, particularly the Na+/K+-ATPase. Subsequent validation experiments confirmed this interaction and identified a tryptophan residue within SST as critical for binding. These findings bring to light potentially new mechanisms for SST action in normal physiology and AD.

Keywords: Alzheimer's disease
Amyloid-β
Neurodegeneration
Neuroscience
P-type ATPase
Somatostatin
Advisor: Schmitt-Ulms, Gerold
On Establishing PPG Biometrics for Human Recognition: Feasibility and Variability

This thesis presents a new biometric modality called Photoplethysmograph (PPG) for biometric authentication. PPG records the blood volume change from any part of the body with a combination of a light emitting diode and a photo diode. Therefore, it is the easiest to acquire amongst all medical biometric traits. Although PPG is a time-dependent physiological signal and alters with physical and psychological stress, most of the prior art has neglected these factors. This work presents the ‘BioSec.Lab PPG Database’ and establishes the PPG as biometrics through a comprehensive analysis on its distinctiveness and robustness under exercise, emotions, time-lapse, and noisy conditions. Performances under all variations mentioned above are assessed using various methodologies. Encouraging Equal Error Rates (EER) between 0.00%-36.09% were achieved with relaxed states and under different variations from the three databases.

Keywords: Authentication
Biometric Recognition
BioSec.Lab PPG database
Machine Learning
Pattern Recognition
Photoplethysmograph (PPG)
Advisor: Hatzinakos, Dimitrios