VictorJuiz/thesis huggingface dataset:
The Role of Circular RNAs in Cardiac Remodeling
Keywords: actin polymerize
circRNA
circular RNAs
mitochondria
Splicing factor
translation

Circular RNAs (circRNAs) are RNAs with a unique circular structure that generated from back splicing processes. These circular molecules were discovered more than 40 years ago but failed to raise scientific interests until lately. Increasing studies have found that these circular RNAs might not be just by-products of splicing process but possess important regulatory functions through different cellular event. It is true that most circular RNAs are currently being studied in the field of cancer and many of them have been confirmed to be involved in the process of tumorigenesis, circular RNAs are also involved in other non-cancer disease fields. Significant progress has been made in recent period shown that circular RNAs play important physiological and pathological roles in cardiovascular diseases. Fibrotic cardiac remodeling is a maladaptive response to acute or chronic injury that leads to arrythmia and progressive heart failure. The underlying mechanisms remain unclear. I validated novel methods and built mature platform for circular RNA function studies. These include an improved model for circular RNA overexpression, a protocol for specific and efficient pulldown circular RNA-binding partners, and development of circular RNA transgenic mice. Such techniques could be conducted into the circular RNA field and facilitate the research. By using such techniques, I characterized the role of two circRNAs chosen from high-throughput RNA sequencing analysis, circITGα9 and circSLC8A1, in the pathological process of cardiac remodeling. While circITGα9 generates functions through a direct binding with Tropomyosin 3, circSLC8A1 regulates cardiac remodeling by synthesizing a novel peptide which further interact with mitochondria proteins. This thesis outlined the regulatory roles of these circular RNAs and explored their potential in serving as therapeutic targets in fibrotic cardiac remodeling process. On one hand, my study contributes to circular RNA field by providing new platforms to support functional studies and characterizing the specific roles of two circular RNAs, circITGα9 and circSLC8A1. On the other hand, my study contributes to cardiovascular field by providing new regulatory mechanisms and potential therapeutic possibilities to achieve better understanding of physiological and pathological developments of the heart.
“Why Doing Good is So Hard”: Examining Community Efforts to Help Criminalized Individuals in Canada
Keywords: community corrections
criminalized women
penal voluntary sector
prisoner reentry
punishment
voluntary sector studies

In the Canadian context, the efforts of charitable and non-profit organizations have long been considered key to understanding both the historical trajectory and contemporary shape of punishment. Recently, scholars have suggested that economic and political developments such as neoliberalism and welfare state retrenchment have meant that these organizations, as well as their broader communities, have taken on larger roles in criminal justice processes. In response, there has been a flurry of research examining the penal voluntary sector. Some scholars have suggested that this sector is part of the archipelago of social control, responsible for widening carceral nets and diversifying penal power, while others have envisioned this sector as agitating for social change, improving public safety, facilitating personal growth, and even saving lives. Few studies, however, have explored questions about the size, scope, structure, and boundaries of these diverse organizations and adjacent community efforts collectively. As a result, although valuable analyses have examined parts of the penal voluntary sector and their practices, little guidance is available with regard to conceptualizing the overall texture of this domain. This dissertation is one step toward clarifying the overarching logic that structures practice among the wide range of organizations, associations, and individuals seeking to help criminalized individuals in Canada. In particular, this research draws from the theoretical work of Pierre Bourdieu and the American pragmatist philosophical tradition to advance a view of this domain as structured around the struggle over who and what are legitimately helping criminalized individuals. It explores how diverse efforts to help criminalized individuals fit together—and where, when, and why they sometimes conflict. In doing so, this dissertation furthers understandings of: (i) the diversity of actors working to help criminalized individuals; (ii) the normative assumptions underpinning this work; (iii) the relationships between individuals, organizations, and groups in this domain; and (iv) the impact of various helping efforts on criminalized individuals. Throughout this research, I mobilize four types of qualitative data as evidence: fieldnotes from ethnographic participant observation in penal voluntary sector organizations; semi-structured interviews with volunteers and staff at these organizations; organizational documents obtained through fieldwork; and publicly archived materials.
Epigenetic Regulation Controls Intrinsic and Extrinsic Drivers of Gastrointestinal Development
Keywords: Chromatin Accessibility
Epigenetics
Gastrointestinal Development
Intercellular Communincation
Lineage Fate Decisions
Transcription Factors

Gastrointestinal development begins with the formation of a featureless tube known as the primitive gut tube. Endodermal cells lining the inside of the gut tube differentiate into the functional epithelial units of the gastrointestinal system. Mesodermal cells surround the endodermal layer and eventually develop into an array of mesenchymal cells which support epithelial function. Development and maturation of the primitive gut tube into the structurally and functionally unique organs of the gastrointestinal system requires highly specific spatial and temporal patterns of gene expression. However, it remains unclear what forces regulate spatiotemporal gene expression patterns in the early gut. Epigenetic control of gene expression offers a possible mechanism for orchestrating the necessary gene expression patterns, but very little is known about how epigenetic forces regulate gut development. In this thesis, I first investigated how intrinsic epigenetic mechanisms influence gut development by mapping the genome-wide chromatin accessibility profile of the developing gut tube at a single-cell resolution, revealing that at the level of chromatin, individual cells are primed to acquire specific lineage fates. I further mapped epigenetic changes throughout gut development, demonstrating how each organ leverages a unique suite of chromatin accessibility patterns and transcription factors (TFs) to reinforce lineage fate decisions. I further showed that loss of the foregut and hindgut lineage-specific TFs, Sox2 and Cdx2, leads to fate shifts in chromatin accessibility patterns, linking TFs, accessibility, and lineage fate decisions in gut development. Finally, I demonstrated that Sox2 overexpression in early development induces pancreatic transformation into foregut precursors. Further, I investigated how epigenetic forces control extrinsic regulators of lineage fate decisions, specifically intercellular communication. Here, I show that mesenchymal cells control epithelial fate and function through Polycomb Repressive Complex 2 (PRC2)-mediated chromatin bivalency. While key lineage-determining genes possess tissue-specific patterns of chromatin accessibility, PRC2 controls WNT ligand expression in mesenchymal cells without altering accessibility. Reduction of mesenchymal WNT secretion rescues organ fate and proliferation defects caused by PRC2 loss. Collectively, my work highlights how epigenetic mechanisms are critical regulators of gastrointestinal development, functioning intrinsically and extrinsically to regulate gene expression patterns required for lineage fate decisions.
Monstrosity on the Southwest Frontier: Grotesque Terrain, Body, and Voice in the Works of Henry Clay Lewis and George Washington Harris
Keywords: George Washington Harris
Grotesque
Henry Clay Lewis
Southwest Frontier

Deploying ideas derived from Wolfgang Kayser, Mikhail Bakhtin, and others, this analysis brings to bear paradigms of grotesque theory to explore causal relationships and models of connectivity among terrain, body, and voice in selected work from the literature of the Southwest Frontier. In so doing, it recontextualizes received conceptions of the function of the grotesque in this literary corpus and in the aesthetic of two of its most gifted practitioners, Henry Clay Lewis and George Washington Harris, writers who are the most radical and experimental with the subversive power of this material.At the narrative centre of these tall-tales are frontier “roarers”—therianthropic rhetorical monsters in the liminal space posited by Frederick Turner’s “Theory of the Frontier.” Critical work on Southwest Frontier literature has represented grotesque characters and effects. Signalling the presence of the grotesque in this corpus, this scholarship has predominantly focused on grotesque character or activity as evidence of the monstrous in a normative world and of monstrum as portent. This study, however, looks at this literature, and in particular the works of Lewis and Harris, as a “way of seeing,” and shows how models of terrain, body, and voice are mobilized to convey that vision. In these two authors, the grotesque moves from dislocating effects created by shocking incongruities or monstrous character sketches recorded by urbane literary narrators to an aesthetic structure and strategy. Lewis creates a hoaxingly autobiographical Swamp Doctor as oral centre, while Harris produces the quintessential American freak Sut Lovingood, a monster who engineers monstrous tableaux to violently assail and ultimately reorient the perceptions of his auditors. The product of conscious design rather than psychotic excesses, I argue, these structures and strategies put into new perspective the arcs of these authors’ work and of their central voices. What other critics see as perverse and obscene aesthetic failure, I see as coherent and purposive aesthetic accomplishment. These arcs are strategic and aesthetic tours de force, emblems of the instability at the heart of their creators’ transgressive grotesquerie.
Welcome to the Oasis of The Real: The Aesthetics of Convergence in Augmented Reality
Keywords: Augmented Reality
Cultural Heritage
Digital Art
Digital Heritage
Locative Media
Museum Apps

While Augmented Reality (AR) becomes a ubiquitous technology through applications like Snapchat and Pokémon Go, this study is pioneering in that it offers an in-depth analysis of AR’s cultural production and perceptual paradigms. The thesis maps and outlines twelve categories of AR apps, which are indicative of twelve different ways to experience social space and (re)construct cultural narratives through AR. Focusing on AR apps in cultural settings such as art, museum apps, and cultural heritage projects, this research provides the first overarching, medium-specific framework for both the analysis and production of AR apps in cultural settings.This study begins by synthesizing three common approaches to the technology, in order to reconceptualize AR as a relational, creative, and immersive medium. It further argues that Augmented Reality produces a Convergent Reality (CR): an environment in which material and virtual aspects of bodies, technologies, and landscapes are united through the interactive experiences constructed by such apparatuses. By studying the diverse relationships AR facilitates between digital data and actual environments and by analyzing AR’s unique and complex modes of interactivity, this study identifies six categories of AR as a spatial medium and six categories of AR as a temporal medium. These categories are organized into two diagrammatic models, which expand the common approach to AR as a primarily spatial technology. Analyzing over 40 AR apps, Welcome to the Oasis of the Real shows how AR interfaces can function as effective tools to affirm, contest, or reorganize power structures and cultural narratives, thus demonstrating the technology’s potential to make new spaces for historically underrepresented populations. Accordingly, this research also explains why AR is an effective tool for social activism and how AR can be creatively utilized by GLAM institutions to facilitate innovative experiences and engage visitors in a meaningful – rather than in a gimmicky – interaction.
Essays on Immigrant Mental Health: A Look at Health Reporting, Model Identification, and Policy Changes
Keywords: Administrative health data
Healthy immigrant effect
Immigrant
Language proficiency
Mental health
Self-report data

Upon arrival to the host country, immigrants are, on average, physically healthier than the native-born population; however, it is unclear whether this health benefit extends to mental health or whether it applies to recent immigrant cohorts. This thesis seeks to understand the healthy immigrant effect with regards to mental health, by examining aspects of mental health reporting and immigrant mental health using both survey and administrative health data. The first chapter explores the potential role of stigma in mental health reporting by combining survey data, which may be subject to reporting biases, and administrative health data, an alternative source of data, which may be more objective. Results suggest that underreporting may be highest for the most stigmatizing conditions, such as schizophrenia and self-harm, followed by mood disorders, and lowest for physical health conditions, such as cancer and diabetes. The second chapter attempts to disentangle the role of length of stay, period, and cohort in explaining the healthy immigrant effect in mental health as measured by poor mental health and the presence of mood and/or anxiety disorders. Accounting for length of stay, period, and cohort effects is necessary to avoid biased results. Using orthogonal polynomial parameterization in the model, results suggest that period effects are insignificant and thus do not play a role in explaining immigrant mental health. Furthermore, mental health appears to decline the longer immigrants remain in Canada in the survey data, but not in the administrative data. These data sources may be measuring different aspects of health and health care utilization. The third chapter explores the presence of cohort effects in immigrant mental health by evaluating the impact of three policy changes associated with increasingly strict language requirements and applied differentially to cohorts of recent immigrants in each visa class. Results show that mental health care utilization decreased for immigrants who were most impacted by the policy compared to long-term residents, particularly following policies that coincided with periods of increased English proficiency as an entry requirement. This suggests that language proficiency may be associated with one’s own mental health and/or ability to access health care.
Methacrylic Acid Based Hydrogels for Enhanced Skeletal Muscle Regeneration
Keywords: Hydrogel
Macrophage Polarization
Methacrylic Acid
Regenerative Medicine
Skeletal Muscle
Tissue Enginering

Skeletal muscles make up 40-50% of the human body’s mass and are used in most daily activities. While muscles have a remarkable ability to regenerate following small injuries, massive loss of muscle tissue, termed volumetric muscle loss (VML), results in the formation of scar tissue and persistent loss of function. The current treatment for these injuries, autologous tissues grafts, suffers from limited availability, donor site morbidity, infection, and necrosis. A novel method of enhancing skeletal muscle regeneration is through regenerative biomaterials, such as those containing methacrylic-acid (MAA). MAA-based materials have been found to promote wound healing, new vessel formation, and macrophage polarization; however, MAA has yet to be studied outside the skin. The goal of this thesis was to expand the applications of MAA-based materials from beyond the skin into skeletal muscle. In the first aim, the effects of MAA-poly(ethylene glycol) (MAA-PEG) hydrogels on immune cell recruitment and macrophage polarization were examined. Non-degradable hydrogels were found to damage muscle. Thus, degradable hydrogels with degradation rates of either 2 (fast-degrading) or 7 days (slow-degrading) were synthesized. When injected into the tibialis anterior muscle of mice, both slow and fast degrading hydrogels increased the expression of Tnfα, Il10, and pro-regenerative M2 macrophage markers. Moreover, the slow degrading hydrogel decreased the number of pro-inflammatory MHCII+ macrophages. An unbiased t-distributed stochastic neighbor embedding (tSNE) analysis suggested the involvement of additional immune cells (e.g., dendritic cells) in the effect of MAA on skeletal muscle. In the last aim, the ability of MAA-PEG and MAA-collagen hydrogels to promote functional regeneration after a VML injury was evaluated. The MAA-collagen hydrogel increased muscle regeneration both morphologically and functionally. Treatment with this hydrogel also enhanced vascularization and innervation of the injured muscle. These effects were attributed to the hydrogel’s immunomodulatory function as it reduced the recruitment of pro-inflammatory M1 macrophages (MHCII+CD206-). Moreover, the regenerative ability of MAA depended on the carrier material: the MAA-PEG hydrogel did not show the same regenerative potential in this context. It is hoped that the MAA-collagen hydrogel could be a simple treatment to restore muscle function to patients who would not otherwise recover.
The Kusamala Program for Primary Caregivers of Children with Severe Acute Malnutrition in Malawi
Keywords: child development
nurturing care framework
nutrition
psychosocial stimulation
SAM
severe acute malnutrition

Children with severe acute malnutrition (SAM) with clinical co-morbidities who require nutritional rehabilitation unit (NRU) treatment are prone to poor long-term developmental and nutritional outcomes. The Kusamala Program is a four-day hospital-based counselling program for caregivers of children with SAM that integrates nutrition, water, sanitation and hygiene, and psychosocial stimulation, aimed at improving these outcomes. The objective of this research was to evaluate the effects of the Kusamala Program on child development and nutritional status in children with SAM six months after NRU discharge. Furthermore, we aimed to qualitatively understand perceptions and experiences of caregivers of children with SAM who participated in the intervention. We conducted a cluster-randomized controlled trial with caregivers and their children 6-59 months of age with SAM admitted to the Moyo NRU in Blantyre, Malawi. The primary outcome of the trial was child development according to Malawi Developmental Assessment Tool (MDAT) composite z-scores of gross motor, fine motor, language, and social domains. A qualitative component with focus group discussions and in-depth interviews was also completed with a subset of caregivers who participated in the trial. Sixty-eight caregivers and children were enrolled to clusters by week and randomized to the comparison arm and 104 to the intervention arm. There were no differences in child development, with mean MDAT composite z-scores in the comparison arm of -1.2 (95% CI: -2.1, -0.22) and in the intervention arm of -1.1 (95% CI: -1.9, -0.40) (p=0.93). The qualitative evaluation with 20 caregivers indicated that the three modules of the Kusamala Program were appropriate and that caregivers applied many of the lessons learned at home. In conclusion, the Kusamala Program did not result in improved developmental or nutritional outcomes, yet it was viewed positively by caregivers according to qualitative results. Future research should evaluate more intensive interventions for caregivers and children with SAM.
The Glial Response to Focused Ultrasound-mediated Permeabilization of the Blood-brain Barrier: Evaluating the Potential Contribution of Microglia and Astrocytes to Pathology and Regeneration
Keywords: Astrocytes
Blood-brain barrier
Brain Regeneration
Focused Ultrasound
Machine Learning
Microglia

Focused ultrasound in the presence of intravenous microbubbles (FUS) facilitates the non-invasive temporary permeabilization of the blood-brain barrier (BBB) for delivering therapeutics to the brain. FUS-mediated BBB modulation is known to activate microglia and astrocytes, which can exacerbate pathology or promote neuroprotection. I hypothesized that FUS induced a transient activation of microglia and astrocyte that is consistent with pro-regenerative functions. Firstly, I developed a method, MORPHological assessment of Outlier clusters (MORPHIOUS), to quantify microglial and astrocytic activation. MORPHIOUS is a machine learning tool that detects clusters of activated glia in histological sections by referencing control sample cell morphologies. As validation, identified clusters of activated microglia and astrocytes exhibited hallmark morphological and marker changes. Indeed, activated microglia were deramified and upregulated transforming growth factor beta 1 (Tgfβ1), and activated astrocytes were hypertrophic and expressed nestin. MORPHIOUS can therefore sensitively detect activated glia. Secondly, I used MORPHIOUS to characterize microglial and astrocytic activation from 1 to 30 days (D) post-FUS. Microglial activation peaked at 1D and was progressively attenuated between 4D and 30D post-FUS. Activated microglia predominantly colocalized with Tgfβ1, indicative of anti-inflammatory and neuroprotective functions; but not with the inflammation-associated cluster of differentiation 68. Astrocytic activation peaked at 4D and was significantly attenuated by 30D post-FUS. Activated astrocytes did not significantly proliferate or upregulate glial scar components. Thus, post-FUS glial activation was transient, and not indicative of pathology. Thirdly, to evaluate the regenerative potential of the brain environment post-FUS, I characterized neural progenitor cell (NPC) proliferation and oligodendrogenesis. NPC proliferation increased between 4D and 7D post-FUS and coincided with the activated astrocytic upregulation of insulin-like growth factor 2. Moreover, an increased proliferation of oligodendrocyte progenitors increased between 1D and 4D, promoted the number of newly developed oligodendrocytes at 30D. Therefore, post-FUS glial activation is permissive of broader brain regenerative programs. Collectively, this data supports my hypothesis by demonstrating that the FUS-mediated activation of microglia and astrocytes is transient, upregulates regenerative factors, and occurs alongside enhanced neurogenesis and oligodendrogenesis. This work positions FUS-mediated BBB permeabilization as a promising component of multimodal therapies, with potential to aid in the treatment of neurodegenerative disorders.