VictorJuiz/thesis huggingface dataset:
Age- and Sex-dependent Changes in Fear Memory Expression

Fear learning is essential to survival, and is differentially expressed across our lifetime. Fear memories, while long-lasting and robust, can be attenuated by extinction, which is considerably less effective and can lead to relapse. While extinction in young animals leads to permanent fear erasure, in adult rodents extinction is inefficient, and fear memories tend to resurface. Two key brain areas, prefrontal cortex (PFC) and amygdala, are necessary for extinction learning. We investigated spontaneous recovery of auditory fear memory nine days after training in P15, P18, P21, P25 and P30 mice. We found that females exhibit this extinction switch between P21 and P25, whereas males may display an earlier switch between P18 and P21. Our future work will use optogenetics to precisely manipulate the mPFC-BLA circuit involved in fear extinction to determine the exact contribution of this circuit to the switch in extinction learning taking place in early life.

Keywords: amygdala
development
early life
fear
memory
Advisor: Arruda Carvalho, Maithe
The Potential for Genotype-by-environment Interactions to Maintain Genetic Variation in a Model Legume-rhizobia Mutualism

The maintenance of genetic variation in mutualism-related traits is key for understanding mutualism evolution, yet the mechanisms maintaining variation remain unclear. We asked whether genotype-by-environment (GxE) interaction is a potential mechanism maintaining variation in the model legume-rhizobia system, Medicago truncatula-Ensifer meliloti. We planted 50 legume genotypes in a greenhouse under ambient light, and shade to reflect reduced carbon availability for plants. We found an expected reduction under shaded conditions for plant performance traits such as leaf number, aboveground, and belowground biomass, and a mutualism-related trait, nodule number. We also found GxE for nodule number, with ~83% of this interaction due to shifts in genotype fitness rank order across light environments, coupled with strong positive directional selection on nodule number regardless of light environment. Our results suggest that GxE can maintain genetic variation in a mutualism-related trait that is under consistent positive directional selection across light environments.

Keywords: genetic variation
genotype-by-environment
legume-rhizobia
mutualism
Advisor: Stinchcombe, John R
The Adaptive Potential of Lifetime Fitness Increases under a Future Climate Change Scenario in a Population of Brassica rapa

The persistence of any declining population in the face of an environmental perturbation may depend on how fast natural selection restores fitness, a process called “evolutionary rescue”. Evolutionary rescue depends on the adaptive potential for fitness: the additive genetic variance for fitness (VA(W)) divided by mean fitness (W ̅). I conducted an outdoor warming experiment to estimate the change in VA(W) and W ̅ in the annual Brassica rapa using a predicted 2100 temperature regime. Surprisingly, plants exposed to a warmer climate exhibited greater W ̅, suggesting plasticity may enable population persistence to climate change, but could also hinder the adaptive potential by increasing denominator W ̅. Nevertheless, the magnitude of VA(W) expressed under heated conditions was considerably higher, thereby a greater adaptive potential was observed. My findings suggest that standing genetic variation in B. rapa may be sufficient to buffer and facilitate rapid adaptive evolution to warmer temperatures imposed by climate change.

Keywords: adaptive potential
Brassica rapa
climate change
fitness
Fundamental Theorem of Natural Selection
population genetics
Advisor: Weis, Arthur E
Tracking Nanoparticle Uptake in a Spontaneous and Immunocompetent Liver Tumor Model

There is a tremendous focus on the application of nanomaterials for the treatment of cancer. Non-primate models are conventionally used to assess the biomedical utility of nanomaterials. We introduce a pre-clinical woodchuck hepatitis virus (WHV) induced liver cancer model as a platform for nanoparticle (NP)-based in vivo experiments. Persistent WHV infection causes liver cancer development in woodchucks, mimicking human hepatitis B virus (HBV)-induced liver cancer development. We found that the liver and spleen were the primary sites of NP accumulation. Subcellular analyses revealed NPs in the lysosomes of macrophages. Through transcriptome profiling, we uncovered that NPs are taken up primarily by immunosuppressive macrophages within the woodchuck liver. Lastly, we identified that immune and non-immune cells in the woodchuck liver play a role in NP uptake using single-cell RNA-sequencing. The woodchuck-HCC model has the potential to be an invaluable tool to examine NP-based immune modifiers that promote host anti-tumor immunity.

Keywords: Hepatocellular carcinoma
Liver
Macrophages
Marmota monax
Nanoparticles
Woodchuck Hepatitis Virus
Advisor: MacParland, Sonya
Photodynamic Therapy Dose Planning for Peripheral Lung Cancer

Lung cancer is still responsible for approximately one fifth of cancer deaths worldwide and there is a rising trend in the number of cases that present themselves more diffusely in peripheral regions. Newer techniques, like photodynamic therapy (PDT) can help combat this disease. PDT dose planning requires knowledge of the optical properties of the tissue (TOP), the effect of internal structures (airways, blood) on the light distribution and the threshold value required to trigger cell death. In pig models with STEEN: mu_eff525=2.580 ± 0.275, mu_eff665=1.233 ± 0.072 and mu_eff808=0.756 ± 0.047; with blood: mu_eff525=2.664 ± 0.198, mu_eff665=1.820 ± 0.067 and mu_eff808=0.779 ± 0.066; in human with blood: mu_eff525=2.487 ± 0.233, mu_eff665=1.178 ± 0.197 and mu_eff808=1.057 ± 0.070. Using a Monte Carlo simulator: FullMonte, threshold values for healthy porcine lung tissue could be calculated: T= 3.53x10^17 ± 1.12x10^19 and T=1.46x10^17 ± 8.34x10^17.

Keywords: dose planning
lung cancer
optical properties
peripheral
Photodynamic therapy
threshold value
Advisor: Lilge, Lothar
Neurogenesis-mediated Forgetting in Morris Water Maze

Neurogenesis, the generation of new neurons in the hippocampus, has been identified as an underlying mechanism for forgetting of hippocampus-dependent memories in adult and infant mice. However, a recent study failed to replicate neurogenesis-mediated forgetting in rats using multiple measures of spatial memory in the Morris water maze paradigm. Thus, the current study aims to explore explanations for this discrepancy by investigating neurogenesis-mediated forgetting in mice using the Morris water maze paradigm. I analyzed behavioral changes associated with increased neurogenesis in the Morris water maze with multiple quantitative measures in both adult and infant mice. My results showed that neurogenesis-mediated forgetting is reflected in behavioral measures that capture the loss of memory precision, but not measures that only capture the memory gist. I also found evidence that neurogenesis-associated loss of memory precision results in memory generalization.

Keywords: animal behavior
forgetting
hippocampus
memory
neurogenesis
water maze
Advisor: Frankland, Paul W
The Role of the Ventral Hippocampal-accumbens Shell Circuit in Cued Approach-avoidance Decision Making

Approach-avoidance conflict resolution is a form of decision making that is critical for survival and requires the effective evaluation of stimuli with mixed outcomes. Recent evidence has implicated the ventral hippocampus (vHPC) and nucleus accumbens (NAc) in the regulation of approach-avoidance conflict resolution. This thesis aimed to extend this finding by investigating the functional connectivity between the vHPC and NAc shell in learned approach-avoidance decision making. To achieve this, rats were surgically injected with inhibitory DREADDs into the vCA1 and implanted with guide cannulae over the shell. Rats were trained to associate visual-tactile cues with three different outcomes: reward, shock or no outcome, in a Y-maze. Following successful learning, rodents underwent a test in which aversive and appetitive cues were superimposed to elicit approach-avoidance conflict. In the presence of this motivational conflict, chemogenic inhibition of the vCA1-NAc circuit resulted in an increased time spent decision making.

Keywords: Approach-Avoidance Conflict
Decision-Making
Hippocampus
Nucleus Accumbens
Advisor: Ito, Rutsuko
Visual Working Memory Resets to a Loss of Stimulus-representation Correspondence in an Object-based Manner

Visual working memory (VWM) is a theoretical mental space to represent visual information for a task. To date, attempts to characterize VWM have primarily utilized static visual information. However, our visual experience during real-life tasks is rarely static. How do people represent dynamically-changing visual information in mind for a task at hand? In Experiment 1, we demonstrated two ways that VWM can represent a dynamically changing stimulus. When the stimulus changes continuously, VWM amends its existing representation to accommodate the change (i.e., updates). However, when the stimulus changes discretely, VWM discards its existing representation, and re-encodes a new representation of the changed stimulus (i.e., resets). In Experiment 2, we found that VWM resets to a discrete featural change regardless of its task-relevance. This finding suggests that VWM resets its representations in an object-based manner, and thus supporting the object-based theory of VWM representations.

Keywords: CDA
Continuous
Object-based
Reset
Visual Working Memory
VWM
Advisor: Fukuda, Keisuke
Bernhardt-Walther, Dirk
High-speed Motion Generation for Mobile Manipulators

Mobile manipulators consist of a mobile platform equipped with one or more robot arms and are of interest for a wide array of challenging tasks because of their extended workspace and dexterity. Typically, mobile manipulators are deployed in slow-motion collaborative robot scenarios, but they are capable of more challenging tasks. In this thesis, we consider scenarios where accurate high-speed motions are required. We proposed two different frameworks for this regime of tasks: (i) a modular framework that includes a bi-level motion planner and a learning-based controller; and (ii) an end-to-end framework that is based on deep reinforcement learning and simulation-to-reality transfer techniques. We evaluate our frameworks with a mobile manipulator platform through numerous high-speed ball catching experiments, where we show a success rate of 85.33% for real robots and 85.60% for simulated robots.

Keywords: Mobile manipulator
Motion planning
Neural network
Reinforcement learning
Advisor: Schoellig, Angela
Shkurti, Florian
Ca2+ Influx Through TRPV4 Regulates DDR1-dependent Collagen Remodeling

Tissue fibrosis involves excessive deposition of disorganized collagen fibrils, which interferes with organ structure and function. The Discoidin Domain Receptor 1 (DDR1), a fibrillar collagen receptor tyrosine kinase strongly linked to fibrosis, promotes collagen remodeling by increased non-muscle myosin IIA (NMIIA)-dependent cell contraction. While the regulation of the DDR1-NMIIA interaction is not understood, Ca2+ signaling is known to control cell contraction and indirectly regulates NMIIA activity. Transient Receptor Potential Vanilloid Type 4 (TRPV4) is a Ca2+-permeable ion channel, of which expression is associated with fibrosis and may contribute to the regulation of collagen remodeling. Here we investigated how TRPV4 and DDR1 act collectively to regulate collagen remodeling. We found that TRPV4-mediated Ca2+ signaling in fura-2/AM-loaded, β1 integrin-null cells regulated DDR1-dependent remodeling. DDR1 activation increased co-localization of DDR1, TRPV4 and NMIIA. An improved understanding of how these proteins interact could suggest a regulatory mechanism for DDR1-dependent collagen contraction in fibrosis.

Keywords: Adhesion receptor
Calcium
Collagen remodeling
Fibrosis
Focal adhesions
Myosin
Advisor: McCulloch, Christopher A
An Eye Tracking System for a Virtual Reality Headset

This research describes a head-mounted eye tracking system for a commercial virtual reality (VR) system. The system uses infrared LEDs that illuminate the eyes and cameras to capture eye images and a 3D gaze estimation model that uses the locations pupil center and corneal reflections in the eye images. It generates gaze estimates that are insensitive to headset slippage. A key contribution of the work is a novel method to determine the correspondence between the corneal reflections and the LEDs. This is done using a fully convolutional neural network (CNN) based on the UNET architecture, which correctly identies and matches 91% of reflections in tests. The eye tracking system has an average gaze accuracy of 1.1°, which is at least 100% better than current VR eye tracking systems. The high accuracy of the system was maintained with up to 10 mm of headset slippage.

Keywords: Computer Vision
Deep Learning
Eye Tracking
Human Computer Interaction
Semantic Segmentation
Virtual Reality
Advisor: Rose, Jonathan
Eizenman, Moshe
The Relationship Between Number of Medicines Prescribed, Free Medicines, and Adherence

Introduction: The number of medicines prescribed to a patient can be an obstacle to medicine adherence. CLEAN Meds randomized clinical trial aimed to determine the provision of essential medicines at no charge. Providing free medicines improved adherence. However, free medicine provision, might have different effects depending on the number of medicines prescribed to a patient.Objective: To determine whether the number of prescribed medicines modifies the beneficial effect of free medicine distribution. Methods: Using binary logistic regression, the analysis determines whether the number of medications modified the intervention of free medicine distribution while correcting for confounders. Results: While providing medicines free of charge improves adherence (P= 0.02), this effect was not modified by the number of medicines prescribed (p = 0.52). Conclusion: The beneficial effect of free medicine distribution does not depend on the number of medicines prescribed. These findings can help inform changes to medicine access policies in Canada.

Keywords: Health Policy
Health Services Research
Medicine Access
Patient Health
Pharmacare
Public Health
Advisor: Persaud, Nav
Computational Analysis of the AC Stark Effect on the Elelctonic and Single Photon Excitation of Bacteriorhodopsin

Time-resolved serial femtosecond crystallography at X-ray free-electron lasers have provided unprecedented insight into the mechanistic natures of Bacteriorhodopsin, however, the use of high power densities to excite the protein to obtain appreciable signal raises concerns due to the influence of nonlinear optical effects. In this work, one effect is addressed, namely the Stark effect by utility of a bacteriorhodopsin model described at the CPCM-B3LYP-D3/def2-SVP and TD-B3LYP-D3/def2-SVP levels of theory using Born-Oppenheimer molecular dynamics. The results demonstrate the Stark effect at these high peak powers on the electronic transitions causes states that are originally low in oscillator strength to increase to the extent in which population transfer to them becomes highly probable and even greater than that of to the biologically-relevant S0→S1 transition. Population transfer to these electronic surfaces would dictate a different set of photoinduced dynamics and mandate consideration when such high peak powers are used for initial-state preparation.

Keywords: Bacteriorhodopsin
Biochemistry
Born-Oppenheimer Molecular Dynamics
Computational Chemistry
Physical Chemistry
Stark Effect
Advisor: Miller, Robert J. D.
Diet Quality in Relation to Income, Education, and Food Insecurity among Canadian Adults

Given the social gradient in nutrition-related conditions in Canada, we investigated the relationships between Canadian adults’ socioeconomic characteristics and diet quality. Using the Canadian Community Health Survey 2015: Nutrition, we compared one-day mean intakes foradults aged 25-64 (n=8,109) by income quintile, education, and food insecurity status. While few differences were identified based on income quintile, post-secondary education and food security benefitted Canadians’ intake of micronutrients, fibre, fruits/vegetables, percent of energy from ultra-processed foods and/or Healthy Eating Index scores. High income/education in women was also associated with higher diet quality in most indicators analyzed. However, sodium and saturated fat intakes did not differ by socioeconomic characteristics. Our results indicate that higher socioeconomic status, particularly in women, is associated with higher diet quality. Moving forward, nutrition policy should consider the relationships between socioeconomic status and diet quality to optimize interventions and reduce the likelihood of exacerbating the nutrition disparities observed.

Keywords: Canada
Diet quality
Nutrition disparities
Socioeconomic status
Advisor: Tarasuk, Valerie
Diethylenetriamine (DETA) Mitigation at Strathcona Mill: Adsorption Isotherms and Geochemical Modelling

Diethylenetriamine (DETA) is an effective reagent for pyrrhotite depression in the flotation of copper-nickel sulphide ores. The rejection of pyrrhotite can increase the concentrate grade and decrease smelter SO2 emissions. DETA can form soluble and stable complexes with nickel and copper at alkaline pH. Thus, the use of DETA in mineral processing can result in soluble metal complexes in the effluent that cannot be removed by conventional wastewater treatment facilities. The objective of this thesis is to understand how DETA behaves in the tailings management area using geochemical modelling and sorption tests. The geochemical modelling showed that Cu and Ni form stable complexes with DETA through pH range 2 to 14 and 4 to 14, respectively. The adsorption tests indicated warm temperature and acidic pH promote the adsorption. Upon dilution, DETA desorbs off from the solids. These results can provide guidance for the development and assessment of DETA mitigation plan.

Advisor: Bobicki, Erin
Widening the Lens of Actionability: Primary Care Providers’ Experiences and Needs in Managing Incidental Genomic Results

Aim: To explore primary care providers’ (PCPs) experiences and needs in managing incidental genomic results. Methods: Qualitative interpretive descriptive study consisting of semi-structured telephone interviews with PCPs based on incidental genomic results from either a patient in their practice or a hypothetical patient. Results: 15 PCPs in Ontario, Canada were interviewed. PCPs approached management of incidental genomic results through the lens of actionability: their ability to take actions to impact a patient’s current or future health. PCPs had a wider concept of actionability than defined in medical genetics but that aligned with primary care theory. Actionability mitigated the harms of learning incidental genomic results, namely patient anxiety and unnecessary investigations. Conclusions: PCPs considered a wide range of actions to make incidental genomic results relevant for patients. An optimized results report providing resources and a summary of recommended follow-up actions could facilitate integration of incidental genomic results into primary care.

Keywords: Genetics
Genomics
Health services research
Incidental results
Primary care
Qualitative research
Advisor: Bombard, Yvonne
Carroll, June C
Comparing the Magnitude of Oral Health Inequality in Canada, United States and United Kingdom

Objectives: To compare the magnitude of oral health inequality over time in Canada and United States (US), and at a single point in time between Canada, US and United Kingdom (UK). Methodology: Data was obtained from five national surveys; two Canadian, two American and one from the UK. The slope index and relative index of inequality were used to estimate absolute and relative inequality, respectively. Results: In both Canada and the US, absolute inequality in oral disease declined while relative inequality increased; however, inequality for filled teeth declined significantly. Inequality in untreated decay was highest in the US, and in Canada for edentulism. Inequality was lowest in the UK for both untreated decay and filled teeth. Conclusion: Despite what appears to be greater utilization of restorative care among the poor over time, inequality in oral disease prevailed in all three countries and was consistently higher in the US, followed by Canada and lowest in the UK.

Keywords: oral health
Socioeconomic inequality
Advisor: Quiñonez, Carlos
Examining the Link between Social Class and Lay Beliefs

Researchers propose that social class can be studied as its own distinct form of culture. As such, we propose that similar to past findings on how there are cultural differences in lay beliefs, social class should also have an influence on our lay beliefs. We also propose a theoretical model in which social class may influence our lay beliefs through SDO and PRD. In Study 1, we examine the influence of social class on lay beliefs. We found support for our model and we were able to replicate these results in a large-scale pre-registered study. In Study 2 and 3 we aim to establish the causal direction of the relationship between social class and lay beliefs. We discuss the importance of our findings and future studies that we would be running.

Keywords: Lay Beliefs
Social Class
Advisor: Lee, Spike W.S.
Neel, Rebecca
Development of a Protocol for Awake 2-photon Fluorescence Microscopy Vascular Imaging in a Rat Model

Functional imaging refers to the study of brain physiology through changes in brain metabolism, blood flow, and neuronal activity. Most functional imaging studies to date have examined vascular response to neuronal activation in anesthetized animals to keep the animal still while imaging. Anesthesia is a major confound as different anesthetics have variable effects on vascular function. The aim of my project was to develop the protocol for non-anesthetized 2-photon fluorescence imaging in a rat. Using Fischer344 rats, I optimized a cranial window combined with prism implants to achieve optical access into the whisker barrel cortex – an unexplored region in rats. My protocol enabled visualization of diving vessel branching points for the first time. A custom-designed flat treadmill was built to facilitate acclimatization to the awake imaging setup. This study showcases a novel method representing a platform for future studies investigating vascular function and dysfunction in the absence of anesthesia.

Keywords: 2-Photon Microscopy
Awake Imaging
Cerebrovascular Network
Rat
Vascular Compromise
Whisker Barrel Cortex
Advisor: McLaurin, JoAnne
Individual Variability and Sex Differences in Conditioned Pain Modulation and the Impact of Resilience, and Conditioning Stimulus Pain Unpleasantness and Salience

This thesis determined how individual variability in conditioned pain modulation (CPM) relates to sex and resilience (personal attributes), and pain unpleasantness and salience (attributes of conditioning stimuli (CS)). Healthy participants (51 females, 55 males) underwent CPM testing with painful heat test stimuli (TS) and CS. The CS reduced TS pain ratings in half of participants (CPM subgroup) but had no effect or increased TS pain in the others (no-CPM subgroup). A whole group regression model explained CPM after accounting for all variables. In the CPM subgroup model, CPM correlated with CS pain unpleasantness. Correlation analyses showed that in the 1) CPM subgroup: CPM correlated with CS pain unpleasantness in males, 2) no-CPM subgroup: CPM and resilience were negatively correlated in males; CPM and CS pain unpleasantness were correlated in females, 3) whole group: CPM correlated with CS salience and pain unpleasantness. Therefore, personal attributes and CS attributes contribute to CPM.

Keywords: Conditioning stimulus
Pain modulation
Resilience
Salience
Sex differences
Unpleasantness
Advisor: Davis, Karen D