VictorJuiz/thesis huggingface dataset:
'So what are you going to eat?': Insights from a Simple Foods and Intuitive Eating workshop Series
Keywords: Critical food education
Embodied literacy
Food literacy
Intuitive eating
Nutrition education
Ultra-processed foods

This qualitative study is situated at the intersection of nutrition education, food literacy (Vidgen & Gallegos, 2014), intuitive eating (Tribole & Resch, 2012), and understandings of the health implications of regularly consuming ultra-processed foods (Monteiro, 2009). In this thesis I explore the perspectives and experiences of seven parents and caregivers from a vulnerable population who participated in a 12-part workshop series (held in a kitchen-equipped community facility in a large Ontarian city). The workshops, which focused on a novel healthy eating framework called ‘Simple Intuitive Eating’ (SIE), revolved around discussing SIE, practicing cooking techniques, tasting resultant foods, and collectively sharing challenges and strategies related to living healthily in a contemporary urban environment. I co-facilitated these workshops alongside a registered dietitian (with whom I also co-created SIE and the workshop curriculum). In this critical case study (Flyvbjerg, 2011), I asked: 1) How do workshop participants make sense of SIE?; and 2) What supports and barriers are operative for participants with regards to eating simply and intuitively? Data sources included pre-, post-, and three-month-post-workshop interviews with participants; video of workshop sessions; participants’ journals; and my field notes and post-workshop audio debriefs. Significant themes were identified in the data using theoretical sampling and constant comparative methods (Lincoln & Guba, 1985). Velardo’s (2015) model of food literacy was useful in interpreting participants’ views on SIE. SIE also interfaced with participants’ preferences for ‘real’ foods, and underscored the roles of trust and ethical sensibility in food literacy. I adapted Castro et al.’s (2016) articulation of patient-centredness, participation and empowerment to a workshop context so as to interpret participants’ experiences with regards to SIE and the workshops themselves. Some participants employed a strategy of ‘muddling through’ (Lindblom, 1959) in navigating complexities of SIE, changing old habits, and home-cooking. Supports and barriers identified in terms of practicing SIE included: economic, temporal, sociocultural-familial and culinary dimensions; awareness, sensation and hunger; habit and addiction; stress, exhaustion and convenience; acquiring food; and exercise, mobility and other coincident health challenges. Findings supported embodied dimensions of food literacy. Implications from this research are provided for food researchers, health practitioners, pedagogues and policymakers.
Music Performance Anxiety on the Classical Guitar: Expert Strategies from Psychology and Pedagogy
Keywords: classical guitar
guitar
music performance anxiety
pedagogy
performance
stage fright

Music performance anxiety (MPA) seriously affects nearly all musicians at some point in their lives and may cause musicians to abandon their careers or develop maladaptive coping mechanisms to manage their symptoms. While peer-reviewed studies have explored a broad array of psychological treatments for MPA, a paucity of research exists regarding expert classical guitarists’ recommendations for MPA symptom management. Since all post-secondary guitar instructors at the expert level interact with MPA in themselves and their students, and each instrumental discipline has idiosyncratic presentations of MPA, this dissertation seeks to understand common approaches and MPA management strategies from the perspective of classical guitar instructors at the post-secondary level—a cohort which includes the researcher. The project compares guitar experts’ recommendations with existing treatment protocols from psychology to understand MPA from a deeper scientific and heuristic perspective while providing pathways for novel research in this topic. This research concluded that guitarists’ approaches prioritized performance excellence and complete mental and physical preparation to manage MPA, while psychological treatments prioritized cognitive components of MPA, musician’s well-being, and symptom reduction. An impressive convergence of approaches appeared in the guitar and psychology literature, particularly regarding the use of mindfulness strategies and strategies from sports psychology.
Testing Immune Mechanisms and Other Hypotheses of Idiosyncratic Drug-Induced Liver Injury (IDILI)
Keywords: Adverse drug reactions
Animal models
Idiosyncratic drug reactions
Idiosyncratic drug-induced liver injury
Nevirapine
PD-1

Idiosyncratic drug reactions (IDRs) are adverse drug reactions that do not occur in most patients treated with a drug but remain a major concern in the pharmaceutical industry due to the high risk of uncertainty in its incidence, which may also lead to significant patient morbidity and mortality. As idiosyncratic as they are in humans, IDRs are also as rare in animals, and few valid animal models can simulate the clinical picture seen in humans. The current understanding of how IDRs occur is superficial, but there is compelling evidence that most IDRs are mediated by the immune system. We have developed a valid animal model using a Pd-1-/- mouse with the administration of anti-CTLA-4 to impair immune tolerance in order to unmask the potential of different drugs to cause idiosyncratic drug-induced liver injury (IDILI). As observed with green tea extract, the Pd-1-/- model was able to unmask its ability to cause liver injury similar to the clinical picture in patients. In addition to the modulation of the immune system, other factors such as inhibition of the mitochondrial electron transport chain or the presence of risk factors may contribute to the increased severity of IDILI. The presence of danger-associated molecular patterns (DAMPs) may add to the severity of liver injury; however, complex tolerogenic mechanisms may prevent the progression towards liver failure. Moreover, inhibition of the mitochondrial electron transport chain with rotenone in the Pd-1-/- model did not increase isoniazid-induced liver injury. Although we have developed a validated mouse model, mice are not the best model to study all drugs and IDRs as there are interspecies differences. To address this limitation, we successfully developed a Pd-1 mutant rat using CRISPR/Cas9 technology to study drugs, such as nevirapine, that cannot be studied in mice due to the lack of the required enzyme to create the reactive metabolite. The presence of a drug-mediated skin rash was not observed in the Pd-1 mutant rat, although moderate-to-severe liver injury was observed, which further adds to the complexity of IDILI and IDRs in general.
Religion and Police Legitimacy: the Case of Israel’s Haredi Community
Keywords: Haredim
Israel
Police Legitimacy
Policing
Religion
Social Capital

This dissertation analyzes police legitimacy within a Jewish religious minority community in Israel, the Haredim. Informed by theories of procedural justice, social capital, integrative enclave, and community-society, the study explores the overarching theme of religion in police legitimacy. The chapters are organized into three distinct yet inter-related case studies and implement various research designs. In these chapters, I discuss possible mechanisms that have contributed to the surprising improvement in police legitimacy within this community. In the first article, I describe the Israeli-Haredi societal situation over the last twenty years and identify forces of modernization that have contributed to higher acceptance and Haredi participation with the police, namely increased trust and cooperation. I suggest that police legitimacy has gradually developed in a dialogical manner between the community and the police. The second article discusses brokerage with the police and demonstrates how, during the first wave of COVID-19, the community shifted its communication channels with the police, leaning more heavily on professional knowledge brokers rather than traditional religious brokers. This article discusses the potential for long-term improvement of police legitimacy within the community as a result of this shift in social capital. The third article focuses on organizations as socialization mechanisms that provide a safe space for Haredim to explore the Israeli public sphere and vice versa. Organizations that assist the police in various matters, and include Haredi volunteers, provide this religious minority with the opportunity to enhance communication with the police while keeping intact religious observance. In conclusion, the dissertation provides insight into the role of religion in policing and police legitimacy, offering an important view of religion as a unique factor. Theoretically, the dissertation contributes to the understanding of (1) how police legitimacy develops over time and how religion interacts with this process; (2) how social capital access, and hence communication channels with the police, may shift under certain circumstances within religious communities; and (3) how religious organizations with ties to the police working with integrative enclaves serve as agents of socialization. Limitations and future directions for research are discussed in all three articles, as well as in the conclusion.
The Pathogenesis of CKD: Studies of FSTL1 and ACE2
Keywords: CKD
FSTL1
Kidney

Mechanism(s) responsible for the progression of chronic kidney disease (CKD) to end stage renal disease have not been fully elucidated. During my Ph.D. studies I completed bioinformatic, in vitro, in-silico, and in vivo studies to address this gap in current knowledge.In a first series of experiments, microarray analysis of kidneys from Col4a3-/- mice, an experimental model of CKD, revealed an early increase in follistatin-like-1 (FSTL1) expression. Little is known about FSTL1 in experimental or human CKD. FSTL1 localized to interstitial cells by RNAscope® and single cell transcriptomic data from human CKD showed that FSTL1 was confined to fibroblasts/myofibroblasts. In vitro, FSTL1 activated AP1 and NFκB, increased collagen I and interleukin-6 expression, and induced apoptosis in kidney cells. FSTL1 expression in kidneys from humans with CKD associated with age, eGFR, and proteinuria and was also related to interstitial fibrosis and tubular atrophy. Remarkably, CKD progression in participants with FSGS from the Nephrotic Syndrome Study Network (NEPTUNE) study was greater in patients with high baseline FSTL1 mRNA levels. Angiotensin-converting enzyme 2 (ACE2) catalyzes conversion of angiotensin (Ang) II to Ang-(1–7). It is decreased in kidneys from Col4a3–/– mice and recombinant ACE2 (rACE2) administration lessens kidney injury in these mice. Interestingly, ACE2 is a receptor for SARS-CoV-2 but little is known about renal ACE2 expression in human CKD. I accessed renal tubulointerstitial (TI) and glomerular microarray expression data and clinical variables from healthy living donors and patients with CKD from the European Renal cDNA Bank. ACE2 expression was greater in males than females and lower in the glomeruli. Genes involved in inflammation and fibrosis correlated inversely with ACE2 expression. I then studied ACE2 expression in participants with FSGS from NEPTUNE. ACE2 expression was related to both sex and eGFR in this cohort. ACE2 expression was inversely related to kidney interstitial fibrosis, and tubular atrophy, in males but not in females. In summary, my studies support the hypotheses that intrarenal FSTL1 and low ACE2 contribute to the progression of CKD, suggesting that they may be important targets for the development of new treatment approaches to CKD.
Elucidating the Role of Tankyrase Inhibition during Pancreatic Specification and β Cell Lineage Commitment using hPSCs
Keywords: Beta cells
Diabetes
Insulin
Stem cells
Tankyrase

Human pluripotent stem cells (hPSCs) differentiation into pancreatic endocrine cells has been proposed as a strategy to generate surrogate islets to treat type 1 diabetes (T1D), which is caused by the autoimmune destruction of pancreatic β cells. Current hPSC differentiation methods attempt to recapitulate pancreas organogenesis in a 6-stage protocol using a series of growth factor-enriched media to modulate developmental pathways. However, these protocols generate low yield of β-like cells that are metabolically immature. Proper endoderm patterning at early differentiation stages can dramatically impact the terminal culture and understanding the pathways controlling pancreatic progenitor (PP) formation could improve the endocrine cell differentiation. We previously directed efficient PP differentiation using nicotinamide (NA), EGF and Noggin. However, the role of NA during pancreas commitment remains unclear due to its role in multiple cellular pathways. Using a screening assay, we demonstrated that NA induces PP specification by targeting tankyrases (TNKS), which are central regulators of several signaling networks, including the canonical Wnt signaling. In Chapter 3, we showed that canonical Wnt signaling prevents pancreatic differentiation and promotes gastrointestinal development, whereas TNKS inhibition induces pancreas commitment. We further identified that a highly selective TNKSi, WIKI4, predisposed PPs to β-like cell commitment, improving β-like cell purity and yield compared to the NA counterpart. In Chapter 4, we performed transcriptomic analysis to explore possible mechanisms by which WIKI4 predisposes PPs to β-like cell commitment. We showed that WIKI4 treatment reduced the proliferation of the non-PP population and activated integrin signaling, which is the mediator between cytoskeleton and extracellular matrix. In Chapter 5, we demonstrated that WIKI4 treatment during PP commitment profoundly affects β-like cell function in vitro and in vivo. We showed that WIKI4-derived PP gave rise to glucose responsive β-like cells in vitro and upon transplantation, WIKI4-derived grafts normalized glycemia in diabetic mice. In contrast, NA-derived PPs gave rise to β-like cells that failed to respond to glucose challenges in vitro and in vivo. Altogether, we showed that TNKS inhibition during PP formation enhances β-like cell commitment. Our work reinforces the notion that improving early lineage commitment is a valuable strategy to enhance β-like cell differentiation.
Quantitative Fast FLIM-FRET (qF3) to Study BCL-2 Family Protein-protein Interactions in Live Cells
Keywords: Apoptosis
BCL-2 family
BH3 mimetics
Fluorescence lifetime imaging microscopy
Forster Resonance Energy Transfer
Quantitative Fast FLIM-FRET (qF3)

The BCL-2 family proteins can promote or prevent cell death (pro- and anti-apoptotic proteins respectively). They function via an intricate network of intra-family interactions, the balance of which regulates the point of no return in apoptosis: mitochondrial outer membrane permeabilization (MOMP). Cancer cells may become ’addicted to‘ the expression of one or more anti-apoptotic proteins to evade death, so several compounds (called BH3 mimetics) have been developed that inhibit anti-apoptotic proteins, BCL-2, BCL-XL, or MCL-1 to initiate cell death. However, most BCL-2 family proteins have yet to be purified in full-length, and most BH3 mimetics have only been validated using peptides and truncated anti-apoptotic proteins in solution. To more reliably predict how these inhibitors will work in the clinic, we used Fluorescence Lifetime Imaging Microscopy (FLIM) to detect Fӧrster resonance energy transfer (FRET), or FLIM-FRET microscopy, to measure interactions between full-length BCL-2 family proteins in live cells. To measure FRET we fuse a donor fluorophore to one protein and an acceptor fluorophore to another, expressing both in the cell. If the two fusion proteins interact they bring the donor in close enough proximity with the acceptor for FRET to occur, resulting in a decrease in donor lifetime. However, traditional FLIM-FRET is low throughput and generates binding curves that vary between experiments due to the X-axis being measured in arbitrary units of intensity; not suitable for screening. This thesis highlights our contributions to the FLIM-FRET method, culminating in the introduction of our quantitative Fast FLIM-FRET (qF3) technique. We used qF3 to screen 15 promising BH3 mimetics to displace interactions of 24 full-length BCL-2 family protein-protein complexes in live cells and find that some compounds are highly functional, yet many exhibited unsuspected cross-reactivities and/or poor function. Finally, we used FLIM-FRET to closely study the interactions of BCL-2 Interacting Killer (BIK) protein in live cells. BIK is a membrane-anchored protein well-known for its localization to the endoplasmic reticulum(ER). In order to investigate BIK function in cells, we swapped the targeting sequences of BCL-XL and BCL-2 for localization to mitochondria or ER and surprisingly BIK interacted with BCL-XL/BCL-2-targeted to mitochondria. Finally, we propose a possible model and discuss the implications regarding BIK function.
Migrant Youth, Islandness, and Belonging on Prince Edward Island
Keywords: belonging
immigration
international education
island studies
islandness
Prince Edward Island

The small Canadian province of Prince Edward Island has recently experienced a population boom, driven largely by international immigration. As a sub-national jurisdiction with considerable leverage over immigration and education policy, PEI has targeted young migrating international students in immigration and education marketing, positioning such migrants as ideal future Islanders whose arrival will reverse population loss. This qualitative study considers the lived experiences of nine such migrants, all of whom arrived on PEI on international student visas within the last six years and all of whom have expressed a desire, however nominal, to remain in the province following graduation. Using narrative and arts-informed research—in particular, photo elicitation and photovoice—this multi-modal, multi-stage study explores how migrating students experience various forms of belonging and exclusion in Island material and symbolic space. Hall’s (2017) theory of ethnos as an organizing and disciplinary practice for establishing and maintaining group identity is extended into the realm of Island space, to consider how the conditions and practices of islandness as a key vector of Island identity exclude migrating students from Island society in various ways. Findings suggest that historical discourses focused on maintaining a homogenized Island identity, constructed through operationalizing and policing a strict insider/outsider binary, punishes racialized subjects in particular. While a vibrant and diverse younger population suggests the Island may be reaching a demographic inflection point, in which migrating students benefit from parallel economies of affect and capital, data suggest that social and political networks continue to privilege and elevate white Islanders within material and symbolic Island spaces. Further, findings demonstrate how the Island imaginary continues to be produced within Island and transnational space in strategic and disciplinary ways as traditional, rural, past-centric, and culturally homogenous, despite ample evidence to the contrary. The research makes an important contribution to critical international education studies by considering the influential role sub-national policy and branding play in shaping how migrating students experience settlement and place. Further, the research offers an important case study to island studies scholars considering how island place, identity, and social relations shape (and are in turn shaped by) the conditions of international migration.
Discount Factor Estimation in Inverse Reinforcement Learning
Keywords: discount factor
inverse reinforcement learning
maximum entropy

In reinforcement learning, the reward that guides the learning process of a decision-maker acting in an environment to achieve a goal can be non-trivial to specify. As such, inverse reinforcement learning (IRL) seeks to observe an expert and explain behaviour in terms of a reward. However, behaviour of humans is linked to the choice of discount factor and arbitrary choices of discount factor in IRL can lead to different rewards and optimal behaviours. Thus, discount factor estimation as part of the IRL framework is crucial to mitigate such bias in the learning process. This thesis evolves a utility-based objective within the maximum entropy IRL algorithmic framework to simultaneously estimate the discount factor and reward in a gradient-based manner via explicit computations of derivatives. The case of a single expert is first investigated prior to extension to multiple experts, in which Expectation-Maximization procedure is employed to learn each expert's cluster of trajectories and obtain maximum likelihood estimates of interest. Experimental and numerical studies on MDP environments, e.g., Grid-World are carried out with evaluative performance measures. Furthermore, an application to real-world traffic data is presented. Driving behaviour of humans may react sub-optimally to congestion leading to loss in traffic capacity. Therefore, a comparison of the observed traffic flow with theoretical maximum flow gives a quantified loss. Recommendations are also made on how a human driver should be nudged to minimize the loss. This is possible by solving three optimization problems: IRL given traffic data to learn actual reward and discount factor, forward reinforcement learning using a flow-based reward to generate ideal driving behaviour leading to theoretical maximum traffic flow, and a least-square fitting procedure to compute ideal rewards. Empirical evaluations on highway 401 in Greater Toronto Area are carried out to validate the approach.