VictorJuiz/thesis huggingface dataset:
Construction and Characterization of a Nano-shuttle for the Delivery of Meitner-Auger Electron-emitting Radionuclides to Human Breast Cancer Cells

Meitner-Auger electrons (MAE) are low energy electrons ( < 25 keV) emitted by certain radionuclides. These MAEs precisely irradiate cancerous cells due to their subcellular range (nm to um). One approach to deliver MAE-emittting radionuclides into cancer cells is construction of a nano-shuttle. A nano-shuttle is composed of gold nanoparticles (AuNPs) modified with peptides (RDG) that would target cell surface αVβ3 integrins on MDA-MB-231 and MDA-MB-468 human breast cancer cells, and a nuclear localization sequence (NLS) that would import the nano-shuttle into the cell nucleus. This research was focused on the construction and characterization of a nano-shuttle for the delivery of Meitner-Auger electron emitting 111In and 99mTc into human breast cancer cells. A peptide vector that is composed of sequences of RGD (arginine-glycine-aspartic acid), a NLS (nuclear localization sequence), a terminal cysteine for foming a Au-thiol bond and tyrosine for radioiodination was linked to AuNPs and labelled 111In through DOTA chelators. This peptide further included a hexahistidine sequence for labeling with the 99mTc(I) tricarbonyl complex. Cell binding of 99mTc was mediated by both the RGD and NLS determined by competition binding assays using an excess of RGD and NLS peptides or peptide vectors. Similar cell binding results were found for 111In-labeled AuNPs. The result of these experiments demonstrated more blocking by excess peptide vector and NLS compared to excess RGD. This suggests that NLS functions as a cell-penetrating peptide and cell uptake was mediated by both RGD and NLS sequences.

Advisor: Reilly, Raymond
The Effect of the HIV-antiretroviral Dolutegravir on Glucose Homeostasis in Healthy Mice and its Implication on Fetal Toxicity

Dolutegravir (DTG)-containing antiretroviral therapy is a preferred regimen for all people living with HIV. However, DTG use has been associated with weight gain and rare events of hyperglycemia, as well as an increased risk for neural tube defects (NTDs) in pregnancy. As pre-pregnancy obesity and hyperglycemia contribute to an increased risk for congenital defects, we aimed to characterize the effects of DTG on glucose homeostasis and its impact on the emergence of congenital anomalies. The first study assessed metabolic changes in female mice over 9 weeks of DTG treatment. We found transient blood glucose elevations, and changes to insulin and lipid metabolism in the DTG-treated animals. In the second study, length of DTG treatment on maternal glucose homeostasis and rates of fetal anomalies were investigated. Increased rates of NTDs were observed in dams starting DTG-based treatment at conception, suggesting that DTG-associated changes to maternal metabolism are likely responsible for NTDs.

Advisor: Serghides, Lena LS
Diabetes, Perivascular Spaces, and Cerebral Small Vessel Disease in Cerebrovascular Disease and Across the Neurodegenerations

Type 2 diabetes mellitus (T2DM) and hypertension are established risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). Patients with neurodegenerative diseases were stratified by presence or absence of T2DM, and MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH) and lacunes (LACN), and PVS in the white matter (wmPVS) or basal ganglia (bgPVS). Patients with T2DM had greater wmPVS volume, but not other SVD volumes, with greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found total natural indirect effects of T2DM on all other SVD volumes that were mediated by wmPVS: pWMH, dWMH, pLACN, and dLACN, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal targets to mitigate the impact of T2DM on cerebral small vessels.

Advisor: Swardfager, Walter
A Contrastive Learning framework for Self-supervised Pre-training of 3D Point Cloud Networks with Visual Data

Reducing the quantity of annotations required during supervised training is vital when labels are scarce and costly. This reduction is especially important for segmentation tasks involving 3D datasets, which are often significantly smaller, and more challenging to annotate, than their image-based counterparts. Self-supervised pre-training on large unlabeled datasets is one way to reduce the amount of manual annotations needed. Previous work has focused on pre-training with point cloud data exclusively; this approach often requires two or more registered views. In this thesis, we combine image and pointmodalities, by first learning self-supervised image features and then using these features to train a 3D model. By incorporating visual data, which is often included in many 3D datasets, our pre-training method requires a single scan of a scene only. We demonstrate that our pre-training approach, despite using single scans, achieves comparable performance to other multi-scan, point cloud-only methods.

Keywords: Contrastive Learning
Point Clouds
Self-Supervised
Advisor: Kelly, Jonathan
Multi-UAV Cooperative Hunting in Three-dimensional Environment with Obstacles

The primary objective of this thesis is to solve the cooperative hunting problem with multiple unmanned aerial vehicles (UAVs) in scenarios where obstacles of various sizes are in a three-dimensional (3D) static or dynamic environment while avoiding the downwash impact. This solution combines a Hungarian Vertices Assignment strategy, a 3D encirclement strategy, a novel revised particle swarm optimization (PSO) path planning algorithm, an obstacle avoidance algorithm, and a controller. Varied from the standard PSO path planning, which draws particles at random locations in random directions around the hunter agents, this revised particle swarm optimization path planning algorithm increases the computational efficiency in finding the trajectory and next position for each hunter agent by initializing the particle swarm along the direction toward the goal position. Simulation results show that the solution successfully hunts and encircles a moving or stationary target simultaneously in a dynamic or static obstacle-rich cluttered environment.

Keywords: Control System
Cooperative Hunting
Downwash Impact
Drone
Path Planning
UAV
Advisor: Liu, Hugh H.T.
A Hopeful Research of a Necessary Revolution: Influences of Turkish Political Theatre

As a Turkish artist who grew up influenced by the works of left-wing figures, the author sets out to research how Turkish political theatre from 1960 to 1980 impacted the period as well as future generations. Through autoethnographic methods, this paper aims to examine the chain of artistic and political influence between Nâzım Hikmet, Genco Erkal, and the author. By referring to existing scholarship and privileging materialist analysis, the depoliticization of post-1980 is observed as the result of capitalist development, oppressive propaganda, and active dismantling of socialist movements and organizations. The paper ends with two original artistic creations by the author, presented as the inspired results of the research, to move forward the chain of influence. The writing of the paper itself is offered as a political performance that calls for collective action. Yazar, solcu figürlerin eserlerinden etkilenerek büyüyen bir Türk sanatçı olarak 1960'tan 1980'e kadar Türk politik tiyatrosunun dönemi ve gelecek nesilleri nasıl etkilediğini araştırmaya koyulur. Bu makale, Nâzım Hikmet, Genco Erkal ve yazar arasındaki sanatsal ve politik etki zincirini otoetnografik yöntemlerle incelemeyi amaçlamaktadır. 1980 sonrasının depolitizasyonu mevcut bilime atıfta bulunularak ve materyalist analize öncelik verilerek, kapitalist gelişmenin, baskıcı propagandanın ve sosyalist hareketlerin ve örgütlerin kasıtlı olarak dağıtılmasının bir sonucu olarak gözlemlenir. Makale, etki zincirini ilerletmek için araştırmanın ilham verici sonuçları olarak sunulan yazarın iki orijinal sanatsal yaratımıyla sona ermektedir. Makalenin yazılışı da, kolektif eylem çağrısı yapan politik bir performans olarak sunuluyor.

Keywords: 1960-1980
autoethnography
capitalism
political theatre
socialism
Turkish theatre
Advisor: Carter, Jill
Evaluating Stream Fish Community Responses to Environmental Change through Biological Indices

Freshwater fish species require, and compete for, suitable habitats to maximize various physiological and behavioral processes. Yet, the habitats on which they rely are being modified by localized human activities and global climate change, resulting in increased temperatures and decreased health. Monitoring fish communities in areas affected by these modifications (i.e., urban areas) allows for responses to be tracked and trends identified. Biological indices are often used in these areas as they can succinctly communicate community responses to resource managers and the public, but are also criticized based on the metrics and scoring used and their lack of consideration for sampling variability. Here, long-term stream fish community monitoring data, different indices, and their responses in both urbanized and less impacted areas are evaluated, contributing to the confidence with which monitoring programs can interpret sampling results and identify areas for improvement when using or developing new indices.

Keywords: fish
freshwater
health
index
temperature
Advisor: Jackson, Donald
Open-source Implementation and Clinical Acceptability Assessment of Organ-at-risk auto-segmentation in Head Neck Cancers

Auto-segmentation of organs at risk (OAR) in cancer patients holds the potential to improve efficacy and reduce inter-observer variability in radiotherapy planning. While studies have shown that deep learning auto-segmentation models can reach high accuracy, they often fail to reach the level of transparency and reproducibility required to assess the models’ generalizability and clinical acceptability, hindering the adoption of auto-segmentation systems in clinical environments. In this study, we leverage the recent advances in deep learning and open science platforms to reimplement and compare the performance of eleven published OAR auto-segmentation models on the largest compendium of head and neck cancer imaging datasets to date. We further provide examples as to how clinical acceptability assessment could accelerate the adoption of auto-segmentation systems in the clinic by establishing ‘baseline’ clinical acceptability threshold(s) for nineteen organs-at-risk in the head and neck region. Our data, open-source models and computational framework are providing a strong foundation for benchmarking segmentation tools, a key challenge for accelerated clinical adoption of these methods.

Keywords: auto segmentation
deep learning
head and neck cancer
oar
organs at risk
unet
Advisor: Haibe-Kains, Benjamin
Further Investigating the Transformation of Benzene Derivatives in Acidic Conditions by the Fungus Hormoconis Resinae

Different strains of H. resinae have been found to use several pathways to transform a number of benzene derivatives. Further study of the transformation of toluene, benzaldehyde, and benzyl alcohol by H. resinae ATCC 34066 was carried out in acidic solutions, with different fungus culturing media, both with and without glucose. It was found that H. resinae ATCC 34066 is not able to transform toluene at all, though it is tolerant to concentrations up to 50 ppm. The fungus was able to reduce benzaldehyde to benzyl alcohol up to concentrations of 500 ppm, both in the presence of glucose and without it. Glucose was found to be a preferred culturing media to PDA with smaller observed transformation lag times. Benzaldehyde to benzyl alcohol conversion ratios by the fungus were found to be higher in the presence of glucose. Further study is needed to better understand the benzene derivative transformation pathways.

Keywords: Benzene derivatives
Bioremediation
Groundwater
Hormoconis resinae
Advisor: Sleep, Brent E
Constructing Points Systems in Accumulative and Independent Sports via Bayesian Regression

The goal of ranking systems is to objectively evaluate multiple performances over a certain period of time. Concerns with current points ranking systems stem from reward imbalance across tiers and selective participation. This has implications on athlete funding through national team selections and Olympic qualifications. We propose a Bayesian framework for designing and evaluating an accumulative points system that can be applied to any multi-competitor sport. In a case study for slopestyle snowboarding, we used data from world, continental, and national events between 2016 and 2019. We demonstrate through Monte Carlo simulation experiments that our Bayesian points system is both more accurate at calculating athlete ranks and more consistent when athletes attempt to game the system.

Keywords: Bayesian Regression
Ranking System
Simulations
Sports Analytics
Advisor: Chan, Timothy C.Y.
Environmentally Induced Changes to Neuron Connectivity and Morphology in the Brain of the C. elegans dauer

An organism’s survival relies on the ability of the nervous system to convert a vast array of sensory information into appropriate motor responses. Processing conducted by the nervous system is complex, even in simple animals. In the nematode C. elegans, sensory neurons connect to an intricate, layered network of interneurons and motor neurons. Many neuron-to-neuron connections are stable from birth to adulthood, but recent developments show that even some of the most stable connections in the nervous system can change in response to environmental stress. In this thesis, I describe the significant changes to network connectivity and neurite morphology in a C. elegans model of environmental stress, the dauer stage. I show that one of the most prominent dauer-specific changes, the loss of the RIC-to-AVA connection, correlates with behavioural responses. The dauer is not simply a paused developmental state, but has active remodeling of neuron connectivity.

Keywords: Behavior
C. elegans
Connectomics
Development
Electron Microscopy
Advisor: Zhen, Mei
Common Genetic Variants in CHRNA5 Alter β-amyloid Neuropathology and Highlight Chandelier Cells in Human Aging and Alzheimer’s Disease

Changes in high-affinity nicotinic acetylcholine receptors are connected to cognitive impairment in Alzheimer’s Disease (AD). The nicotinic α5 subunit (coded by CHRNA5) is important for attention and cognition, however its role in the context of aging and neuropathology is unknown. Here, we investigate, in an aged human cohort, the impact two common CHRNA5 polymorphisms: the function-compromising rs16969968 and the expression-altering rs1979905. We observed a significant negative association between the high CHRNA5-expression rs1979905A2 genotype and β-amyloid load. Furthermore, we found that the greatest abundance of CHRNA5 expression was in chandelier cells, a specialized set of interneurons enriched for β-amyloid-binding genes. Finally, we found that in subjects homozygous for the minor allele of the CHRNA5 function-compromising polymorphism rs16969968, chandelier cell proportions in the prefrontal cortex are significantly decreased at high levels β-amyloid levels. Taken together, these findings urge further investigation into the role of CHRNA5 and chandelier cells in AD neuroprotection.

Advisor: Lambe, Evelyn EKL
Identifying Susceptibility Factors of Psoriatic Disease using Single-cell RNA Sequencing

Psoriatic arthritis (PsA) is an immune mediated musculoskeletal inflammatory disease that manifests itself in approximately a third of psoriasis patients – an immune mediated disease characterized by hyperproliferative keratinocytes and T-cell infiltration. An accurate and timely diagnosis is essential to prevent irreversible joint and bone damage, yet there are currently no validated biomarkers for PsA. To identify possible biomarkers, we employed single-cell RNA sequencing on peripheral blood mononuclear cells of PsA, psoriasis, and healthy controls. We focused on two proteins A20 and IkBα that were dysregulated in PsA cell subsets in addition to numerous interferon stimulated genes that were differentially expressed. Confirming interferon-mediated influence on immune activity serum IFNα levels were higher among PsA patients with four or more swollen joints than patients with less than two. Future studies should explore the predictive value of IFNα serum levels as a biomarker of PsA patients that will develop more severe disease.

Keywords: Biomarkers
Psoriasis
Psoriatic Arthritis
scRNA-seq
Single-cell RNA sequencing
TCR
Advisor: Gladman, Dafna D
A Scheduling-based Constraint Programming Approach to Solving a Complex Two-dimensional Two-stage Cutting Stock Problem

We investigate the novel Two-Dimensional Two-stage Cutting Stock Problem with Flexible Length, Flexible Demand, Order-to-Order Marriageability, and Scheduling Costs (2SCSP-FFMS): orders for rectangular items must be cut from treated rectangular stocks using guillotine cuts with the objective to minimize waste, inventory cost, and tardiness cost. Different from problems in the literature, the 2SCSP-FFMS allows the item length and total order demands to vary within customer-specified intervals. We first investigate a variation of the problem that ignores marriageability (pairwise conflicts between orders) and scheduling costs, proposing constraint programming models, mixed-integer programming models, and heuristics. Then, we study a second variation that adds the marriageability requirement before examining the full 2SCSP-FFMS problem. Accordingly, we extend the approaches that performed best in the first variation to the second one and the full 2SCSP-FFMS. For each of these problems, we perform empirical analysis on both generated and real-life industrial instances. Notably, our scheduling-based constraint programming model has orders-of-magnitude smaller memory requirements over other exact methods and can be competitive with a customized multi-phase heuristic.

Keywords: Constraint Programming
Cutting Stock Problem
Guillotine Cuts
Heuristics
Mixed-Integer Linear Programming
Optimization
Advisor: Beck, Christopher
Investigating the Establishment of the Developmental Transitions of Cortical Neural Precursors at the Transcriptional Level

Adult neural stem cells (NSCs) arise from radial precursor cells (RPs) in the embryo that build the brain by generating different neural cell types in a temporally and regionally defined manner. An emerging model proposes that adult NSCs transition from RPs which can generate different neural cell types in response to signals in the environment. In Chapter 3 of this thesis, I have tested the hypothesis that developing cortical neural precursors are multipotent and show that they may have the potential to generate both excitatory and inhibitory neurons. In Chapter 4, I hypothesize that the time around birth is an important developmental period for neural precursors as they transition gradually from RPs to adult NSCs. I show that perinatal neural precursors take on a unique transition state, undergoing transcriptional changes within the first few days after birth.

Keywords: Cortex
Development
Neural stem cells
Neurogenesis
Advisor: Kaplan, David R.
Intercultural Bilingual Education (IBE) and the Image of Indigenous People and Quechua Speakers in the Peruvian Andes

In Peru, there are currently more than 27,000 government-funded IBE schools located mostly in rural areas. These schools were created to redress the historical marginalization of indigenous languages like Quechua and to narrow the achievement gap between indigenous and non-­indigenous students linked with the privileging of Spanish linguistic and cultural practices. While Quechua is recognized in the Peruvian constitution as an official language and is spoken by roughly 4 million Peruvians, parents continue to equate education with Spanish language education. They do not encourage their children to learn Quechua due to its low status. This linguistic bias is related to many factors including the social stigma attached to Quechua as the language of illiterate indigenous. This study examines how discourse in various IBE policies imagines Indigenous people and Quechua speakers to be. I also include my voice through my own personal experience as the daughter of Quechua speakers.

Keywords: Churcampa
Education
Intercultural Bilingual Education
Language
Peruvian Andes
Quechua
Advisor: Bale, Jeff
An Optimal Control Approach to Model-based Stimulation of Phase-reduced Networks of Spiking Neurons

As the dynamics of artificial neural networks are increasingly more influenced by their biological roots, important insight lies at the intersection of neuroscience and control theory. The high-dimensionality of these networks and the nonlinearity of microscopic neuronal dynamics often preclude direct applications of conventional control. Mean-field models offer alternative low-order descriptions of the collective macroscopic behaviour of neurons. These orders may be bridged through the study of neuronal synchronization, which is believed to underlie several brain disorders. We propose a model-based control framework to regulate neuronal spiking activity based on a synchronization observable. It is inspired by the neurosurgical procedure of deep brain stimulation, whereby an implanted open-loop neurostimulator injects high-frequency current pulses into the affected brain region. While the desynchronization of neuronal activity is a leading hypothesis behind its effectiveness, the mechanism remains poorly understood. We turn to optimal control to tailor the stimulation to the observed pathophysiology.

Keywords: deep brain stimulation
neuronal dynamics
optimal control
Advisor: D'Eleuterio, Gabriele M. T.
Lake Ice in a Rainfall Dominated Southern and Central Ontario

Winter precipitation long-term (1900 - 2019), short-term (1990 - 2019) and projected (2015 - 2099) trends were studied over central and southern Ontario. Precipitation trends, especially rainfall, increased over the long-term and projections. The increase in winter rainfall motivated the development of a new version of the Canadian Lake Ice Model (CLIMo), CLIMo - Temperate Rain, which incorporates the heat fluxes and mass contributions of rainfall. CLIMo-TR improved simulations of lake ice thicknesses during thaw and rainfall events, however break-up tended to be overestimated. Rainfall primarily affected lake ice through its mass contribution to the lake ice surface, which led to a thicker snow layer and white ice formation. Few short-term lake ice trends were seen, while projected trends expect significantly shorter ice cover durations and decreases in maximum, mean and SD of thickness. As winter seasons become warmer and winter rainfall increases, understanding rainfall effects on lake ice will be of importance.

Keywords: lake ice
limnology
modelling
Ontario
precipitation
winter rain
Advisor: Brown, Laura