VictorJuiz/thesis huggingface dataset:
Museums and Human-nature Relationships in Japan: A Case Study Analysis of Echigo-Tsumari Art Field

Echigo-Tsumari Art Field (ETAF) presents an expanded type of museum overlooked in the museological literature. Embarking from ETAF’s own assertions—that “all of satoyama is an art museum” and that “human beings are part of nature”—I conduct an autoethnography and content analysis on materials gathered during participation in the 2018 Echigo-Tsumari Art Triennale. I demonstrate how ETAF enacts and interprets heritage in mediating between state and grassroots interests. ETAF’s practice of regionalism—its adoption of the satoyama concept of encultured nature, mapping and thematization—results in both normative and strategically diversified representations of collective identity. ETAF’s narrative draws from a selective history to depict historically marginalized agricultural lifeways, becoming an expressive metaphor for ongoing regional regeneration. When placed within salient socio-historical contexts, these findings illustrate how ETAF both departs from and leverages traditional top-down museological approaches towards social cohesion, pointing to the mediating potential of cultural institutions in declining communities.

Keywords: art festivals
contemporary art
Japanese culture
museums
nature
regional development
Advisor: Brower, Matthew
Functional Contributions of TGFB2 Signaling to Metanephric Progenitors and Stromal Cells

Recent analyses using spatial and temporal targeted genetic deletions of Hh signaling components revealed lineage-specific requirements within the metanephric progenitor pool and their stromal derivatives. Stage-specific activation of Hedgehog signaling through a Ptch1-deficiency in metanephric progenitors leads to intrinsic ureteropelvic junction (UPJ) obstruction and hydronephrosis in mice. Ptch1-deficient metanephric progenitors give rise to ectopically located stromal cells which occlude the presumptive ureteropelvic junction and block proper urinary outflow. Preliminary evidence implicates transformation growth factor beta 2 (TGFB2) as a downstream effector of Hedgehog signaling. Here, we show that, while TGFB signaling is dispensable within the metanephric progenitors during normal kidney development, it acts downstream of Hh signaling to contribute to the pathogenesis of UPJ obstruction. A lack of TGFB signaling in a Ptch1-deficient background partially rescues the frequency and severity of hydronephrosis. Further, single-cell RNA sequencing investigates novel targets of Hedgehog-TGFB signaling in the stromal and nephrogenic lineages.

Keywords: Hedgehog
Stroma
Transformation Growth Factor Beta
Ureteropelvic Junction Obstruction
Advisor: Rosenblum, Norman D
Sleep-dependent Consolidation Enhances Naturalistic Episodic Memory Recall

Compared to wakefulness, sleep can enhance episodic memory through consolidation. Yet, sleep may not boost all aspects of memory given that it has been shown to favour memory for spatiotemporal over item details. Previous work has tested memory for lab-based stimuli in one experimental session, making it unclear whether these findings generalize to memory for real-life events over a longer period of time. To address this question, we assessed participants’ memory after they experienced the same staged event with online recognition memory tests across four timepoints. Participants made true/ false judgments about the items and sequences they encountered during the event, allowing us to dissociate between these two memory measures. These data suggest that sleep, relative to wakefulness, confers a widespread – but short-lived –mnemonic advantage since both elements of episodic memory were equally retained. This investigation yields insights into the mnemonic benefit of sleep-dependent consolidation for our real-world experiences.

Keywords: consolidation
episodic memory
item memory
naturalistic design
sequence memory
sleep
Advisor: Levine, Brian
Characterizing the Basis of Strigolactone Perception by HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2

The HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2 (HTL/KAI2) α/β hydrolases likely play a critical role in the life cycle of parasitic plants of the genus Striga. Several of these hydrolases serve as receptors for strigolactones (SLs), a class of compounds exuded by the roots of some plants, including many economically significant crops. Upon perception of minute levels of SLs, Striga seeds germinate and parasitize the nearby host, often leading to massive losses in crop yields in affected regions. We have produced a series of mutant variants of the Arabidopsis thaliana homolog of HTL/KAI2, which is only weakly responsive to SL. By substituting certain key amino acids in the protein’s active site, we have created a receptor conferring increased Arabidopsis germination under inhibitory conditions in the presence of SL. Additional study of this mutant receptor may offer insight into the biochemical basis of Striga’s SL sensitivity.

Keywords: hormone receptor
karrikin
strigolactone
synthetic biology
Advisor: Lumba, Shelley
Towards Humanizing Online Discourse - Exploring Linguistic and Emotional Tones in Online Learning

Online learning has seen tremendous growth over the last few years, but there is limited research in understanding the role of tones in an online learning environment. The goal of this thesis is to explore the presence of both emotional and linguistic tones in threaded discourse to understand their role in online conversations. This study presents evidence of the presence of emotions in online discussions using a sequential mixed-methods design by analyzing text using machine learning techniques based on the theory of psycholinguistics to predict both linguistic and emotional tones in discourse. It further explores participants’ experiences and insights using semi-structured interviews with learners and instructors. The analysis uncovered significant differences in tone across different courses, users and notes. This research is a first step to acknowledge, identify and understand tones in text written by the user; thereby humanizing text discourse online.

Keywords: Affective learning
Emotions
Online learner
Online learning
Advisor: Hewitt, Jim
Investigation of a Potential Slam-dependent Secreted Protein in Vibrio harveyi

Vibrio harveyi is a Gram-negative bacterium predominantly existing in marine environments. It has a wide host range infecting various marine animals. A Slam-containing gene cluster was identified in V. harveyi. Slam and Slam substrates are bacterial proteins usually associated with bacterial virulence. My project was to determine the Slam-dependency, structure and ligand of a V. harveyi Slam substrate named PUF1. In this study, I successfully reconstituted Slam- dependent secretion of PUF1 in E.coli cells. Using X-ray crystallography, I determined the structure of PUF1, illustrating it has a comparable tertiary structure to those of previously identified Slam substrates consisting of a b-handle domain and a b-barrel domain. The structure of PUF1 and spectroscopic analysis disclosed the role of PUF1 as hemophore. Interestingly, unlike previously identified Slam substrates that are surface lipoproteins, PUF1 is not attached to the cell surface. Rather, PUF1 is a secreted protein reporting a new type of Slam substrate.

Keywords: hemophore
secretion
Slam
Vibrio harveyi
Advisor: Moraes, Trevor
Development and Evaluation of a Prototype Camera System for Intraoperative Video Recording of Open Surgery

Intraoperative video enables better surgical training, continued performance enhancement and quality improvement initiatives; however, there exists a lack of technology to reliably and routinely capture high-quality video of open surgical procedures. Using the limitations of previously identified capture systems as innovation targets, we developed a prototype camera system and benchmarked it against existing capture technology using objective and subjective evaluation frameworks. In a simulated OR environment, there was less movement of the prototype camera measured by a physical sensor, and algorithmic video analysis demonstrated more stable, sharper, higher contrast images but with more surgical field obstruction. In the real OR environment, surgeons rated the usability of the prototype more favourably for ‘weight’ and ‘would recommend to a colleague’, and rated the video product higher for ‘camera stability’ but lower for ‘unobstructed view of the surgical field’. This work demonstrates a novel and effective method for intraoperative video capture of open surgery.

Keywords: camera technology
computer vision
innovation
machine learning
open surgery
surgical video
Advisor: Grantcharov, Teodor P
Human Milk-based Protein Concentrate Supports Growth of Weanling Rats

This study explores the feasibility of using donor human milk to produce a protein concentrate and evaluates whether its use can support normal growth in weanling rats. A human milk-based protein (HMP) concentrate was produced from defatted milk, followed by membrane filtration and high hydrostatic pressure (HHP) processing. Thirty rats were randomized and fed AIN-93G diets containing casein, the HMP concentrate, or a bovine whey protein isolate for four weeks. No significant differences in body weight, feed consumption, fat mass, or plasma amino acid profiles were observed between rats fed the HMP concentrate and those fed the control diet. Full cecum weights were higher in rats fed the HMP concentrate (mean difference, 5.6; 95%CI, 4.5-6.7 g; p

Keywords: donor human milk
human milk protein
preclinical assessment
rat bioassay
very low birth weight infant
Advisor: O'Connor, Deborah L
Unger, Sharon
The Effect of Prolonged Nitrate Administration on Ocular Disease Phenotypes in a Transgenic Rat Model of Chronic Hypertension

Nitrate-based vasodilators (NBVs), a source of nitric oxide, are used to treat multiple cardiovascular diseases, including hypertension. However, epidemiological studies suggest that chronic nitrate intake (from NBVs/dietary nitrates) is a risk factor for retinal diseases, including age-related macular degeneration (AMD). Additionally, we previously demonstrated that combining NBVs with oxidative stress increased outer retinal atrophy in a rat model of dry AMD. We therefore hypothesized that prolonged administration of isosorbide dinitrate (ISDN), a NBV, may reduce hypertension, but aggravate ocular disease phenotypes in the (mREN2)27 transgenic rat model of chronic hypertension. Using in vivo ophthalmic imaging and systolic blood pressure (SBP) measurements, we established the (mREN2)27 model to mimic features of retinovascular disease in patients. In summary, following a five-week treatment period, ISDN did not reduce SBP compared to hypertensive (mREN2)27 rodents but exacerbated ocular disease phenotypes in male (mREN2)27 rats. Investigations into the role of nitrates and inflammation are ongoing.

Keywords: age-related macular degeneration
confocal scanning laser ophthalmoscope
hypertension
hypertensive retinopathy
nitric oxide
organic nitrates
Advisor: Boyd, Shelley R
FOXO1: A Novel Metabolic Target in the Reversal of Radiation Fibrosis

Radiation fibrosis (RF) is a long-term consequence of cancer radiotherapy with complex pathophysiology leading to tissue dysfunction and patient morbidity. Our laboratory has demonstrated that suppression of fatty acid oxidation (FAO) is a predominant alteration in RF, and that adipose-derived stromal cell (ADSC) transplantation restores metabolism while reducing fibrosis severity. We hypothesized that epigenetic regulation of metabolism may be central to RF pathogenesis and treatment. Genome-wide methylation profiling of ADSC-treated fibrotic murine tissue revealed that hypermethylation of FOXO1 binding sites may be therapeutically favourable. Pharmacological inhibition of FOXO1 restored the expression of FAO genes, decreased fibrotic protein expression, and reduced murine skin fibrosis severity. Moreover, a convergence of the FOXO1 and prostaglandin E2 pathways was identified as a novel mechanism through which FOXO1 may regulate RF. This work will lead to a deeper understanding of RF pathogenesis while proceeding toward a novel therapeutic strategy for the treatment of this condition.

Keywords: Fibrosis
Metabolism
Radiotherapy
Advisor: Liu, Fei-Fei
Characterizing Trends in the Dietary Patterns of Canadians: Evidence from Two Cycles of the Canadian Community Health Survey—Nutrition

Healthy dietary patterns have been associated with reduced risk of non-communicable diseases. The overall goals of this thesis were to examine adherence to healthy dietary patterns using nationally-representative Canadian data and to determine the association between these trends and obesity among Canadian adults. In the first study, the likelihood of being obese was compared between samples from the Canadian Community Health Survey-Nutrition (CCHS) 2004 and CCHS 2015; results suggested that Canadian adults who did not adhere to a healthy dietary pattern had over 2x greater odds of obesity than those who did adhere. In the second study, an energy-dense, low-fiber and high fat dietary pattern was identified in CCHS 2015; results suggest key foods to focus on in policy which contribute to an “obesogenic” dietary pattern. The findings presented in this thesis highlight the importance of examining healthy dietary patterns and their association with health outcomes among the Canadian population.

Keywords: Canadian Community Health Survey
CCHS
dietary patterns
obesity
Advisor: L'Abbe, Mary R
The Effects of Viral Mimics on P-glycoprotein Function in the Developing Blood-brain Barrier

The blood-brain barrier (BBB) is formed by brain endothelial cells (BECs) which are supported by astrocytes. BEC expression of the drug transporter P-glycoprotein (P-gp) acts to protect the brain from xenobiotics. Astrocytes increase P-gp function in BECs in fetuses and neonates. Astrocytes are also an immune regulator in the brain, releasing cytokines after infection. Cytokines inhibit P-gp function in BECs. We investigated the effects of viral infection in developing astrocytes and BECs in the context of P-gp activity. Results indicate that although there is a modest inflammatory response within neonatal astrocytes initiated by viral mimics, this is insufficient to decrease P-gp activity within BECs. These findings suggest there is some resistance to the acute effects of viral infection at the level of P-gp function, in the developing brain. Future research will investigate whether this resistance to viral mimics persists within an in vivo system.

Advisor: Matthews, Stephen G
hCF-chip: A Model for Human Cardiac Fibrosis

Cardiac fibrosis is a strong contributor to heart failure, but a lack of suitable human models limits our understanding of disease progression. We engineered a human cardiac-fibrosis-on-a-chip (hCF-chip) model that allows for real-time assessment of cardiomyocyte function and aims to provide an accessible platform for studying human cardiac fibrosis in vitro. The hCF-chip is a microfabricated device with co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes that uses transforming growth factor-β1 as a trigger for fibrosis. The hCF-chip shows increased expression of BNP and reproduces key hallmarks of cardiac fibrosis including decreased force of contraction, increased excitation threshold, increased extracellular matrix deposition, increased tissue stiffness, and an transcriptomic profile consistent with human cardiac fibrosis. Treatment with the standard of care drugs losartan and carvedilol decreased BNP secretion, the anti-fibrotic drug pirfenidone decreased tissue stiffness and BNP secretion, and the senolytics dasatinib and quercetin showed improved tissue functional parameters.

Keywords: heart-on-a-chip
organ-on-chip
Advisor: Vasconcelos, Sara N
The Effect of Remyelination on Behavioural Recovery following Mild Traumatic Brain Injury in Mice

Mild traumatic brain injury (TBI) is a serious public health concern, representing 80-90% of all TBI cases. While symptoms are often transient, 10-15% of patients with mild TBI experience persistent symptoms. We investigated the role that white matter damage and repair may play in the etiology of symptom generation and recovery. Results indicate that mice with mild TBI experience working memory impairment at 3 days post-impact but recover to sham levels by 6 weeks post-impact. The optic tract, corticospinal tract, and anterior commissure were white matter regions found to be particularly vulnerable to damage following mild TBI. Results also indicate that preventing the formation of new myelin after mild TBI may prolong working memory impairment, suggesting that myelin repair may be necessary for functional recovery.

Keywords: behaviour
concussion
magnetic resonance imaging
myelin
traumatic brain injury
Advisor: Wheeler, Anne L
Prediction of Local Control in Brain Metastases following Stereotactic Radiosurgery Treatment

Radiomics shows promise for predicting local failure (LF) in brain metastases (BM) treated with stereotactic radiosurgery (SRS). This investigation sought to determine if radiomic features provide complementary information to routinely available clinical variables. We trained a Random Forest (RF) classifier for LF prediction on a dataset of 408 BMs from 87 patients in a cross-fold validation manner, to observe the change in predictive power from including radiomic features alongside clinical features. The addition of any one of the top nine radiomic features to the set of clinical variables resulted in a significant (p

Keywords: Brain Metastasis
Local Control
Neuro-oncology
Radiomics
Response Prediction
Advisor: Martel, Anne L
Effects of Sex and Ethanol on Approach-Avoidance Conflict Resolution: Including Female Subjects in a Preclinical Model of Alcohol Use Disorder

Preclinical research into alcohol use disorder (AUD) has advanced rapidly over the past decade with the popularization of the intermittent access two-bottle choice drinking paradigm. A major gap in the current literature stems from the widespread failure to incorporate female subjects into preclinical AUD models. Evidence suggests that females actually progress to abuse faster than males and suffer worse from negative health consequences associated with excessive ethanol intake. The current study utilized Long-Evans rats of both sexes to explore approach-avoidance conflict resolution and a potential preclinical AUD model. Female versus male and ethanol-exposed versus ethanol-naïve rats displayed reduced approach of conflict. Females self-administered higher levels of ethanol than males. In subsequent challenges, high-drinking animals compared to moderate- and low- drinking animals reached higher breakpoints on a progressive ratio test, but showed neither higher levels of ethanol seeking during extinction, nor increased resistance to footshock punishment paired with the ethanol reward.

Advisor: Ito, Rutsuko
Investigating the Mechanistic Basis of T-cell Functional Regulation Mediated by PTPN2-WAVE2 interaction

PTPN2 is implicated in risk for various autoimmune diseases; however, the mechanistic interactions involved in PTPN2-mediated T-cell regulation remain elusive. The Siminovitch lab has identified actin regulatory protein WAVE2 as a PTPN2 interacting partner from T-cells. To assess the mechanism whereby this interaction influences T-cell function, we investigated the possibility that PTPN2-WAVE2 binding enables PTPN2 to shuttle nucleocytoplasmically to modulate regulators of T-cell responses. Here, we show that WAVE2 and PTPN2 translocate to the nucleus after IL-4 treatment, together with increased WAVE2 binding to PTPN2 C-terminus, thereby giving PTPN2 access to its nuclear substrates. PTPN2 nuclear translocation is impaired in WAVE2-deficient T-cells and pSTATs levels are significantly altered in WAVE2-deficient and overexpressing T-cells compared to wild-type after γc cytokine treatment. These findings show that WAVE2 may regulate PTPN2 nuclear translocation, consequently, regulating PTPN2-mediated dephosphorylation of nuclear pSTATs. Together, these results reveal a significant role for PTPN2-WAVE2 interaction in T-cell regulation.

Keywords: Autoimmune Disease
Cytokine receptor signaling pathway
Phosphatase
Protein-protein interaction
T-cell receptor signaling pathway
T-cells
Advisor: Siminovitch, Katherine
Multi-scale Design of a Lithium Ion Battery Pack for Electric Vehicles

Lithium-ion batteries have emerged as the most affordable and convenient energy storage solution to power electric vehicles (EV). However, further advances are still needed to improve their performance, lifespan, and safety, which requires better control of their tightly coupled electrical and thermal responses. This thesis project designed, simulated, built, and tested a lithium-ion battery module with a focus on battery thermal management. The core component of this design is a state-of-the-art heat-exchanger made of a network of low-cost extruded microchannel tubes for parallel liquid-cooling of pouch cells, a lightweight aluminum structure that accounts for only 10\% of the total module’s weight and also provides structural support for the cells. The parallel cooling approach yields a superior cooling performance because it minimizes temperature gradients across the pack. This thesis also demonstrates the scalability of this modular battery design by building a functional battery pack that will be deployed in a concept EV.

Keywords: Battery Heat Exchanger
EV Battery Pack Design
EV thermal management
Lithium ion battery module
Parallel liquid battery cooling
Pouch cell cooling
Advisor: Amon, Cristina
Trescases, Olivier
Ketamine Prevents a Persistent Increase in α5 GABAA Receptor Activity Induced by General Anesthetic Drugs

GABAA receptors mediate two distinct forms of inhibition: phasic inhibition and tonic inhibition. In the hippocampus, tonic inhibition is mainly mediated by extrasynaptic α5 subunit-containing GABAA receptors, and sustained overexpression of these receptors contributes to cognitive deficits and mood disorders. Recently, ketamine, a NMDA receptor antagonist, was shown to prevent postoperative cognitive deficits and exert long-lasting antidepressant effects in patients. Given this relationship, we hypothesize that ketamine prevents a persistent increase in α5 subunit-containing GABAA receptor activity. Using whole-cell patch-clamp recordings, we show for the first time that ketamine prevents this overactivity in mouse hippocampal neurons in vitro. Furthermore, this effect is mediated by key proteins implicated in ketamine’s antidepressant actions including BDNF and GSK3β, but not by inhibition of NMDA receptors. Interestingly, ketamine acts through both neurons and astrocytes to prevent this overactivity. Our study provides a novel mechanism for the cognition-sparing and antidepressant properties of ketamine.

Keywords: Anesthetic drugs
Cognitive deficits
Ketamine
Persistent effects
Tonic inhibition
α5GABAARs
Advisor: Orser, Beverley A