VictorJuiz/thesis huggingface dataset:
Fatty Acid and NOD1-mediated Macrophage Polarization: Implications for Metabolic Inflammation and Insulin Resistance

Insulin resistance is a major contributor to the pathogenesis of obesity-linked type 2 diabetes (T2D). Over the last 15 years, T2D has become increasingly recognized as a chronic inflammatory disease, with immune cells, most notably macrophages, representing an important link between lipid intake and insulin resistance. During high fat diets (HFD), macrophages infiltrate tissues that regulate glucose metabolism, including adipose tissue, liver, and skeletal muscle. Concomitantly, HFD disrupts the intestinal barrier, permitting translocation of gut bacterial compounds into circulation. It has been hypothesized that these compounds, along with certain lipids, activate macrophages to a pro-inflammatory polarized phenotype, resulting in production of pro-inflammatory cytokines that directly interfere with insulin signalling in parenchymal cells of metabolism-defining tissues. However, the identity of the lipids and gut-derived factors that influence macrophage polarization, along with the underlying mechanisms, remain to be elucidated. In contrast to saturated fats, consumption of certain unsaturated fatty acids has beneficial effects on glucose homeostasis. Using isolated bone marrow-derived macrophages cultured ex vivo, we find that the monounsaturated fatty acid cis-palmitoleate promotes anti-inflammatory macrophage polarization. Specifically, cis-palmitoleate counteracts pro-inflammatory polarization induced by long-term HFD in vivo or by acute exposure to the saturated fatty acid palmitate in vitro. Further, we show that these anti-inflammatory effects are partially mediated by AMPK. When characterizing other diet-linked factors with immunoregulatory activity, we identify that activators of NOD1, a receptor for bacterial peptidoglycan, increase in circulation of HFD-fed mice. Moreover depleting NOD1 specifically in hematopoietic cells limits pro-inflammatory macrophage polarization within adipose tissue, and simultaneously improves whole-body insulin responsiveness without affecting body weight or adiposity. Collectively, our findings highlight that specific fatty acids and innate immune receptors have critical involvement in macrophage polarization under obesogenic conditions. These results suggest that cell-targeted anti-inflammatory strategies may have therapeutic promise in the alleviation of insulin resistance preceding T2D.

Keywords: Immunology
Inflammation
Insulin Resistance
Obesity
Type 2 Diabetes
Advisor: Klip, Amira
Philpott, Dana J
Creation and Evolution of a Community of Practice Focused on Critical Action Research in an Ecuadorian University

This research examines the learning experiences of a group of university language professors within their Landscape of Practice (Wenger, 2010; Wenger-Trayner Wenger-Trayner, 2015b) and how these learning experiences are shaped after partaking in a Community of Practice (CoP) (Wenger, 1998; Wenger-Trayner Wenger-Trayner, 2015b) that focuses on critical action research (CAR). The study is an action research informed case study that draws from the communities of practice conceptual framework considered within the social learning systems (Wenger, 2000; Blackmore, 2012). Qualitative data was collected from 16 members of the community, including eight focal participants, through observations, questionnaires, document review, conversational interviews and focus groups. Findings suggest that participants perceive the initiative of creating a community of practice as a positive and worthwhile endeavor because it allows them to learn about critical action research within a group that shares interests and expectations. Furthermore, the participants explain how this space for interaction has opened opportunities to understand the link between teaching and research, move beyond academic egoism, and share experiences as well as knowledge. Themes emerging from the analysis suggest that, although perceptions and understandings of critical action research and social justice have shifted after participating in the community and two CAR projects have since been proposed, there is still a need to encourage the use of this research approach within universities in Ecuador where inequity among professors seems to be the rule. In addition, the data highlights factors that have enabled or constrained the commitment of participants to community activities as well as their own academic and professional development.

Keywords: Communities of practice
Critical action research
Social justice
University professors
Advisor: GagnĂŠ, Antoinette
Regulating Traditional Medicine Professionals in the Public Interest: A Case Study of Chinese Medicine and Acupuncture Regulation in Ontario, Canada

Many complementary and alternative medicine (CAM) interventions, such as acupuncture and herbal medicines, are rooted in traditional medicine (TM) systems indigenous to particular cultures and lands. The World Health Organization has recommended that nations take steps to regulate both TM and CAM practitioners worldwide, with the aim of enhancing their ‘safety, quality and effectiveness’. Several United Nations bodies have moreover recommended that nations take steps to protect TM knowledge, and prevent further misappropriation of TM practices. However, to date, very few studies have investigated or discussed how regulators may address the unique complexities of regulating TM practitioners and TM-rooted practices. This PhD dissertation – a qualitative case study of traditional Chinese medicine and acupuncture regulation in the province of Ontario, Canada: a) explores the range of factors that distinguish the regulation of traditional medicine practices and professionals from biomedical professionals; and b) considers how the ‘public interest’ may be conceptualized to appropriately address these distinguishing factors in regulatory context. Data for the study was generated from several sources, including mixed methods survey, documentary review, and 32 key informant interviews. Analytic approaches included thematic and critical discourse analyses using the principle of ‘regulatory equity’ as a guiding concept. Postcolonial, multiculturalism, and boundary work theories, as well as legal principles of disparate impact discrimination and reasonable accommodation, were applied across the study. This body of work points to ways in which regulatory structures in Western liberal democracies may systemically privilege biomedical and non-immigrant practitioners by examining state risk discourses and the construction of regulatory boundaries for acupuncture; the issue of English-language fluency for immigrant practitioners; and the negotiation of safety, quality and epistemology in acupuncture standard-setting across professions. In this light, a series of strategies is proposed to assist regulators in negotiating equitable approaches to CAM and TM regulation. Emphasizing a broad conception of the ‘public interest,’ these strategies prioritize protection of traditional knowledge frameworks, while seeking to accommodate biomedical practitioners’ safe and skilled adoption of TM-rooted health care approaches.

Keywords: acupuncture
Chinese medicine
complementary medicine
public interest
statutory regulation
traditional medicine
Advisor: Boon, Heather
The Urge to Vary: Schubert's Variation Practice from Schubertiades to Sonata Forms

The Urge to Vary: Schubert’s Variation Practice from Schubertiades to Sonata Forms Caitlin G. Martinkus Doctor of Philosophy, Music Theory Faculty of Music University of Toronto 2017 Abstract Repetition has long been a focal point of both critiques and scholarly inquiries of Schubert’s instrumental music. Casting repetition as redundant, critics condemned his instrumental music—especially those works in sonata forms—throughout the majority of the nineteenth- and twentieth-centuries. Recently, variation has emerged as a fruitful lens for the analysis of repetition in Schubert’s sonata forms. Building upon this notion, I further illuminate the role of variation (as a set of techniques, musical processes, and form) in Schubert’s idiom. To develop an analytical framework tailored to the analysis of variation, I establish why variation would be so prominent in Schubert’s oeuvre, and how it is employed. I lay the conceptual and analytical framework of the dissertation in Chapters 1 and 2. Chapter 1 establishes the centrality of repetition to discourse on Schubert and, through a thorough consideration of Schubert’s musical-social life, establishes the relevance of variation beyond composition. I also consider current tools of Formenlehre analysis, and situate my use of William Caplin’s theory of formal functions as a supplement to analyses of variation. Chapter 2 investigates idiomatic variation techniques. These techniques, set against the backdrop of Schubert’s musical training and practice, form the variation perspective that guides my analyses of sonata forms. In Chapters 3 and 4 I analyze the interaction between elements of variation and sonata form. I create my own analytical tools, including the concepts of embedded versus distributed variations, and tight-knit versus loose variation procedures, to demonstrate the presence of variation within and across large-scale units of musical form. Three full-movement case studies highlight Schubert’s use of variation (techniques and form) across expositions, developments, and recapitulations. Most pronounced in these analyses is Schubert’s use of variation in development sections. I thus close my analytical chapters by problematizing the binary opposition between thematic development and variation, for it is a distinction that lies at the heart of many critiques of Schubert’s sonata forms. Ultimately, this study reveals the many and nuanced ways in which elements of variation permeate Schubert’s oeuvre through a unique analytical framework, and situates Schubert’s sonata forms within the ever-evolving historical trajectory of the genre.

Keywords: Formal Functions
Franz Schubert
Musical Form
Sonata Form
Theme and Variation
Advisor: Vande Moortele, Steven
Properties and Paradigms of Robust Optimization

Robust optimization is a methodology for dealing with uncertainty in optimization problems. In this thesis, we provide a deeper understanding of the properties and paradigms of robust optimization. We examine the continuity properties of robust optimization problems with respect to their uncertainty sets, and the paradigms of implementation error under a robust optimization framework, both of which arose from questions asked during the application of robust optimization to healthcare problems. We begin with an overview of the robust optimization methodology, starting with a general standard formulation of a robust optimization problem, following with a discussion of a variety of specific well-known robust optimization formulations, and ending with a presentation of some generalizations and extensions of robust optimization. We then present a computational study verifying the effectiveness of an adaptive and robust radiation therapy (ARRT) methodology for treating lung cancer for a class of physically motivated breathing patterns, adding to the results of the original paper which proposed the methodology. Inspired by the convergence properties of the ARRT method, we establish a more general result regarding the continuity of robust optimization with respect to the uncertainty set. In particular, we prove quantitative stability of the optimal value and approximate optimal solution set and the qualitative stability of the optimal solution set, by way of a transformation that links robust linear optimization and linear semi-infinite optimization. Finally, we study the application of robust optimization to network flow problems under implementation error, with applications to manufacturing process flexibility problems. In classical process flexibility literature, it is implicitly assumed that the underlying network flow problem is always implemented perfectly, with most focus being placed on network design in order to ensure responsiveness to demand variation. In contrast, we study the underlying network flow problem, and how feasibility-preserving implementation error on the network flow solutions can be detrimental to performance of certain network designs. We formulate a robust optimization problem with an endogenous uncertainty set to model the system, but ultimately use an auxiliary linear programming problem to generate solutions which, though not provably optimal, are nonetheless generally more robust than standard solutions.

Keywords: Linear semi infinite optimization
Process flexibility
Radiation therapy
Robust optimization
Sensitivity analysis
Advisor: Chan, Timothy CY
The Sources and Transport of Organic Contaminants in Urban Watersheds: Unraveling the Effects of Land Use, Hydrology, and Chemical Properties

The goal of this thesis was to expand the limited body of knowledge surrounding chemodynamics of organic contaminants in urban streams during runoff events. Specifically, this work assessed effects of urbanization, hydrology, and chemical properties on sources and transport of organic contaminants. To fulfill this objective, high frequency sampling was conducted in paired urban and rural watersheds during rainfall and snowmelt. The analytes included both classic (polycyclic aromatic hydrocarbons) and emerging organic contaminants (benzotriazole ultraviolet stabilizers, benzotriazole corrosion inhibitors) covering a range of properties. Area-normalized fluxes for the three chemical groups averaged across the sampling events were 8 to 24 times higher in the urban watershed, likely due to a combination of greater in-watershed emissions and reduced retention. Temporal patterns in contaminant concentrations were relatively homogeneous across chemical groups in the urban watershed. During rainfall, concentrations of more hydrophilic chemicals with a longer history of emissions leading to relatively contaminated groundwater were consistently diluted at higher stream discharges. Hydrophobic chemicals instead showed increasing concentrations with increasing discharge, due to their affinity for suspended sediment (SS) and effective mobilization of different sediment caches during the event. Differences in modes of emission and transport pathways controlled patterns in hydrophobic contaminant concentrations that were normalized to SS weight. Contaminants travelling from watershed surfaces to the stream network showed early flushes, while those emitted directly to stream banks and stream channels were diluted with relatively clean surface inputs. During snowmelt, the urban landscape was the major driver of patterns in contaminant concentrations. Early maxima occurred for all contaminant groups due to quick transport of meltwater, including particles, over impervious surfaces and via sewer networks. This also applied to SS-weighted concentrations of hydrophobic chemicals. In general, this work has contributed knowledge required to develop suitable strategies for monitoring and mitigating organic contamination in urban streams.

Keywords: benzotriazoles
polycyclic aromatic hydrocarbons
rainfall chemodynamics
snowmelt chemodynamics
urban watersheds
Advisor: Wania, Frank
Injured Workersâ Moral Engagement in the Compensation System: The Social Production of Problematic Claiming Experience

A small proportion of compensation claims in Ontario are complex, prolonged, and often adversarial. These claims are associated with chronic disability, unemployment, and financial and emotional suffering for injured workers, and significant financial and administrative burden for the compensation system. This thesis employed a critical interpretive qualitative design to better understand sociologically the issue of ‘problematic claiming’ from the standpoint of injured workers. A key finding is that injured workers engage with the compensation system morally, framing their experience of claiming in terms of right and wrong, just and unjust, good and bad. Their experience is characterized by mistrust, confrontation with system players, feelings of dehumanization and judgement. Injured workers in this study responded to their moral experience of claiming through the performance of ‘identity work’: attempts at reputation repair that involved displaying their status as ‘good workers’ and ‘good claimants’. This thesis elaborates on this central finding and explores what might produce injured workers’ moral engagement in compensation by considering three social discursive contexts that may play a role in shaping the system and the understandings and practices of those within it: the injured worker movement’s ‘justice discourse’, and the broader societal-level discourses of sick role and neoliberalism. This analysis contributes to both the substantive field of work and health and the theoretical field of social theory. The findings illuminate the tensions and related consequences that arise from the differing conceptions of claiming between injured workers and the compensation board. Highlighting the value of applying concepts from the social sciences to the study of the relationship between work and health, the research underscores the continued and expanded usefulness of sick role theory in contemporary studies of health and illness behavior, and provides empirical substance for understanding the notion of moral in sociological terms.

Keywords: Discourse
Injured workers
Neoliberalism
Occupational health
Sick role
Workers' compensation
Advisor: Eakin, Joan
Guilt in Childhood: Intersections with Regulatory Functioning and Implications for Aggression

We know that guilt plays an important role in managing social behavior across development, particularly in reducing the likelihood of aggression against others. However, this is to a large extent where developmental research on the adaptive nature of guilt stands, as few studies have ventured deeper into the underlying mechanisms of guilt and beyond its direct corresponding action tendencies. This dissertation aimed to address these overarching gaps and thereby achieve deeper theoretical and clinical understandings of guilt in childhood. Study 1 considered the current state of the literature as an endpoint and asked: How does children’s guilt emerge in the first place? It investigated the regulatory building blocks of guilt responses in real time and found that changes in physiology leading up to and during transgressions were uniquely associated with the intensity of children’s guilt following such transgressions. Next, the existing literature was considered a starting point from which the aggression-reducing properties of guilt were examined beyond mere direct effects. Studies 2 and 3 tested whether high guilt offset the aggravating links between underarousal and overarousal, respectively, and aggression at different points in childhood. Study 2 found that lower resting heart rate was significantly associated with higher physical aggression for children who reported low—but not medium and high—levels of guilt. Study 3 found that within-child spikes in daily anger that were higher than such children’s typical anger levels were significantly associated with higher aggression, but less so for those with high levels of guilt. In sum, this dissertation focused on the intersections of guilt and regulatory functioning to understand the underlying mechanisms of guilt and its links to aggressive behavior in childhood. In doing so, it significantly contributed to our knowledge of the momentary formation of children’s guilt and its multifaceted role in mitigating aggression in the face of regulatory deficits.

Keywords: aggression
childhood
development
emotion regulation
guilt
psychophysiology
Advisor: Malti, Tina
A Role for Glycosylphosphatidylinositol Anchored Proteins in T Lymphocyte Homeostasis

The glycosylphosphatidylinositol (GPI) anchorage of proteins to the outer leaflet of the plasma membrane imparts unique properties and controversial functionality. While all GPI-anchored proteins (GPI-AP) contain a conserved GPI core structure, they represent a large class of functionally diverse proteins with known capacities for intracellular signalling, protein trafficking, and localization within membrane microdomains, termed lipid rafts (LR). Many studies have implicated GPI-AP as regulators of T cell receptor (TCR)-mediated cellular activation, however, as they are not transmembrane molecules, mechanisms underpinning their signalling capacity remain elusive. We have isolated a mutant clonal variant devoid of GPI-AP. This T cell clone produced 10-100-fold more TCR-induced interleukin (IL)-2 than the GPI-AP+ parent clone. As GPI-AP reside exclusively within LR, we hypothesized that within this signalling scaffold, they may function as essential regulators of TCR/CD3-mediated “on” and “off” signals. Model systems utilizing GPI-AP+ and GPI-AP- variants of the antigen specific, IL-2-dependent T cell clone, and primary GPI-AP- T cells were generated towards directly testing this hypothesis. In the clonal system, GPI-AP deficiency was shown to impart a prolonged TCR/CD3-induced clonal expansion, which correlated with both enhanced IL-2 messenger RNA (mRNA) and protein production. The re-expression of GPI-AP abrogated the prolonged growth/survival phenotype, consistent with a GPI-AP-dependent attenuation of TCR/CD3 signalling. The phenotype was recapitulated in primary GPI-AP- CD4+ T cells. Hypersensitive TCR/CD3 signalling in the primary model correlated with an enhanced basal kinase activity of the Src-family protein tyrosine kinase Fyn, essential for TCR/CD3 induced IL-2 production. The role of the GPI-anchor, as opposed to that of one or more GPI-anchored proteins in supporting this phenotype was assessed using GPI-anchor sufficient, GPI-AP deficient primary T cells. Preliminary results demonstrated that the TCR/CD3-induced IL-2 phenotype of GPI+/GPI-AP- closely resembles that of GPI-AP+, wild-type T cells. While a mixed genetic background in these GPI+/GPI-AP- T cells precludes formal proof of this conclusion, results thus far attribute a potentially novel role for GPI in regulating homeostatic T cell physiology. The biological significance of the results may provide insight into the mechanism underpinning the human disease paroxysmal nocturnal hemoglobinuria, the maintenance of cellular homeostasis and proliferative disease states writ large.

Keywords: glycosylphosphatidylinositol anchored proteins
GPI-AP
Homeostasis
IL-2
Immunology
T lymphocyte
Advisor: Julius, Michael H