VictorJuiz/thesis huggingface dataset:
Investigating the Neurobiologic Function of Tubby - Identification of a novel role for Tubby in RNA Biology

Tubby and Tubby-like proteins play important roles in neuronal function and maintenance. Mutations in the Tubby (Tub) gene lead to maturity-onset obesity, insulin resistance, and progressive vision and hearing loss in mice and humans. The Tubby family of proteins contain a highly conserved Tubby domain. Structure-function analyses of the Tubby domain suggests that it contains a negatively-charged groove that has appropriate dimensions for binding nucleic acids. Furthermore, Tubby has also been implicated in endocytosis, vesicular transport and ciliary transport. tubby mice display dysregulation of many neuropeptides in the hypothalamus and mislocalization of certain G-protein coupled receptors (GPCRs) in neuronal cilia. In this thesis, I have provided evidence that Tubby regulates the expression of Neuropeptide Y (Npy) post-transcriptionally, an orexigenic peptide that is misregulated in the hypothalamus of tubby mice. Furthermore, using affinity purification-mass spectrometry (AP-MS), I show that Tubby interacts with RNA-binding proteins that are involved in RNA processing, small RNA ribonucleoprotein complexes and translation regulation. Moreover, using individual nucleotide resolution crosslink and immunoprecipitate RNA sequencing (iCLIP-seq), I have provided evidence that Tubby associates with RNA. iCLIP-seq data shows that Tubby targets transcripts of protein-coding and small nucleolar RNA (snoRNA) genes. snoRNAs are the most enriched class of RNAs that are bound by Tubby. Intriguingly, iCLIP-seq data also shows that Tubby interacts with mRNAs of several GPCRs. Here, I have shown that Tubby associates with the Rhodopsin (Rho) mRNA in vitro, suggesting that the mislocalization of Rhodopsin (a retinal GPCR) observed in the retina of tubby mice might be due to an RNA-based function of Tubby. In summary, the data presented in this thesis uncovers a previously unknown RNA-based cellular role for Tubby and shows that Tubby associates with snoRNAs and mRNAs of GPCRs. Currently, on-going work in the laboratory aims to dissect the snoRNA-based function of Tubby and the Tubby-dependent RNA-based mechanism that regulates the appropriate localization of certain GPCRs in neuronal cilia.

Keywords: Diabates
Hypothalamus
Metabolism
Obesity
RNA
Advisor: Cordes, Sabine P
Dynamic Multiscale Modeling of Crystal Structures with Applications to Polymorphic and Ultra-high Temperature Ceramics

Certain materials exhibit complex behavior explained by nanoscale kinetics of reconstructive polymorphic nature. The scales of such materials are inherently multiscale from atomistic to continuum domains. Concurrent multiscale approaches provide a feasible solution to the taxing power demand of conventional atomistic-based models. The recent work of the Bridging Cell Method (BCM) has shown great acumen in addressing current limitations that plague such classes of multiscale models. However, BCM relies on the Atomic-scale Finite Element (AFE) framework, which is a static-based formulation. Also, a lack of statistical thermodynamic consistency makes comparison to molecular dynamics (MD) results challenging. The BCM relies on temperature-based potential to enforce thermal effect in the simulation instead of thermostats. In parallel, atomic description of its embedded structure has always relied on simplified parameterization that cannot extract atomic features (e.g. dislocations, crack tips, crystal phases, etc.) for complex, non-monoatomic materials with varying space groups under the same crystal group. The objective of this work comes into two main folds: to develop of set of parameter capable of extracting atomic features of interest for complex crystalline systems and formulate a generalized dynamic model of the BCM for mechanical characterization of arbitrary atomic-continuum structures. To achieve those objectives, a set of parameters based on the Common Neighborhood Parameter (CNP) has been introduced with a focus to complex, non-monoatomic crystalline structures. Also, a dynamic formulation to the finite-element based BCM has been developed for those structures under a microcanonical ensemble consistency with a new set of representative elements, dubbed the Dynamic Atomic-scale Finite Element (DAFE) framework. Case studies are then presented first for the characterization parameters to show their efficiency for fine atomic feature extraction. Also, the new dynamic model is portrayed in simulations with a tensile and a fracture around a void. Next, the set of formulations is applied to phase transformation of Anatase to Rutile along the critical transformation planes to characterize the mechanics of transformation and mechanical property of the polymorphic ceramic. This has allowed an investigation of the temperature effect on Anatase’s stability from nanoscale while obtaining the product’s elastic modulus upon the plane of transformation.

Keywords: Anatase
Bridging Cell Method
common neighborhood
concurrent
Multiscale
Titania
Advisor: Behdinan, Kamran
Directed Differentiation of Mouse and Human Pluripotent Stem Cells to Renal Progenitors and Kidney Organoids

Pluripotent stem cells (PSC) hold great promise in regenerative medicine. In order to harness their potential, we need to understand how to differentiate PSC to the cell types of interest. Here, we differentiated mouse embryonic stem cells (ESC) to renal progenitors and kidney organoids in a controlled and step-wise manner. We used microarray to explore whole genome transcriptional changes that occurred at each stage of differentiation and found that as the cells differentiated, genes associated with metanephros, ureteric bud and blood vessel development, and cell-matrix adhesion were significantly upregulated. Over-expression of Pax2, Six1, Eya1 and Hox11 paralogues during differentiation did not improve differentiation efficiency. We were able to aggregate the renal progenitors to form kidney organoids consisting of LTL+/E cadherin+ mature proximal tubules and extracellular matrix proteins secreted by the cells themselves. We showed how we can use ESC-derived organoids to study cisplatin-induced kidney injury and as a platform for nephrotoxicity screening. Next, we used a mouse secondary reprogramming system to generate induced pluripotent stem cells (iPSC) from proximal tubule cells (PTC) and tail tip fibroblasts (TTF). We showed that there were no significant differences in the expression of pluripotency-associated markers and renal progenitor markers between the undifferentiated PTC iPSC and TTF iPSC, but after differentiation to renal progenitors, the expression of renal progenitor markers was significantly higher in PTC iPSC-derived progenitors compared to TTF iPSC-derived progenitors. Lastly, we adapted our mouse ESC differentiation protocol to human iPSC and found that the protocol could yield approximately 40% SIX2+ cells. In summary, we demonstrated a novel method of differentiating mouse ESC to renal progenitors and kidney organoids, showed how we can modify this system to investigate the influence of gene dosage and epigenetic memory on renal differentiation, and lastly, showed how we can use this organoid system as a semi-high throughput platform for nephrotoxicity screening.

Advisor: Rogers, Ian
Nagy, Andras
Teacher experience and teacher identity: A case study of three math teachers learning to teach in a Canada-China Reciprocal Learning Project

We can improve the quality of learning for teachers by studying the experiences of teacher learning. Through my facilitation of a group of three Math teachers in a Canada-China Reciprocal Learning Project over two years, I investigated teachers' experiences of learning in depth. I used a qualitative research approach to engage teachers in reflecting actively on their process of learning. Evidence of their learning was gathered by conducting interviews, observing lessons that they taught, visiting their workplaces, and reviewing documentary data of their teaching and learning. A couple of theoretical foundations-Kolb's Experiential Learning Theory and Ying's Social Constructive Learning Theory guided the research in examining how authentic teacher learning develops, as well as how social, community, and personal factors interactively influence a teacher's learning experience. Additionally, I examined the relationships between teacher's experiences of learning and their perceptions of teacher identity. The findings indicated that the experiences of teachers contributed to and continued to modify their perspectives of identifying themselves professionally, while teachers' perceptions of their professional identity influenced their ways of learning and teaching practices. The findings showed: (1) teachers achieved effective learning through interactive dialogues and active reflections; (2) through the partnered activities in the project, teachers built their sustained community of learning; (3) teachers achieved effective learning through engaging other stakeholders in their process of learning, such as students, principals and parents; (4) teachers' experiences of learning in the partnership were impacted by social factors in their school contexts as well as their personal factors; (5) teachers were self-guided/motivated learners as they sought resources to assist their teaching and other professional work at school; and (6) their partnership learning experiences potentially influenced teachers' school practices. Implications from this study suggested that authentic teacher learning is personal as well as socially constructed. Teacher educators need to respect teachers' voices regarding what they need to learn, and how they want to learn. Centering teachers in the learning process is essential for effective teacher learning. Obstacles for learning were discussed in the last chapter, and suggestions for future research were also included in the thesis.

Keywords: case studies
collaborative learning
cross-cultural learning
teacher experience
teacher identity
teacher learning
Advisor: Mcdougall, Douglas
Booth, David
Investigation of Psychological Trauma in Journalists and the Development of the Toronto Moral Injury Scale for Journalists

Journalists fulfill an important civic function by keeping society informed of events that can have a direct impact on their citizens' well-being. By doing so, they risk exposing themselves to dangers associated with their profession. While the physical risks are well documented, the psychological risks are harder to quantify. This thesis investigates the psychological impact on journalists of exposure to potentially traumatic events and transgressions of deeply held moral beliefs. Six studies are presented with the first four focusing on the fear- and anxiety-based aspects of trauma and the remaining two focusing on moral injury. The first study, a mapping review of the trauma literature, concludes that journalists are at an elevated risk for exposure to potentially traumatic events, and that rates of trauma-related psychopathology are higher than in the general population. Study two and three reveal that posttraumatic stress disorder (PTSD) phenomenology is dominated by reexperiencing symptoms in a sample of journalists with well over a decade of frontline experience and that print reporters in the same sample are at a higher risk for PTSD and depression than photographers. An investigation of Afghan journalists in study four highlights the extreme stressors confronted by them, their correspondingly high levels of psychopathology and the relative ineffectiveness of mental health therapy given to a minority of those in distress. The mapping review of the moral injury literature in study five finds that journalists may be at an elevated risk for moral injury and that more research is needed to determine the nature and effects of moral injury and how it pertains to journalists. The most salient finding to emerge from this literature review is the need for the development and validation of a journalist-specific moral injury scale. The sixth study details the development of such a scale. The Toronto Moral Injury Scale for Journalists is theoretically and statistically robust and gives the profession, for the first time, a content relevant psychometric measure to inform clinical care and future research.

Keywords: Depression
Journalism
Mental health
Moral injury
Posttraumatic stress disorder
Scale development
Advisor: Feinstein, Anthony
Film as Intervention: Raising the Bar for Teacher’s Engagement with Indigenous Content

This dissertation aims to ask numerous interrelated research questions. Of most importance and enveloping all of them is: does Indigenous-produced drama, in particular Jeff Barnaby’s Rhymes for Young Ghouls (Barnaby, 2013), create a transformative environment for teachers to engage with issues affecting Indigenous people and the lived history of colonial violence? To find the answer to this question I facilitated 4 discussions with 3 educators where I incorporated Grounded theory with a Cultural studies mode of inquiry. This would also be informed by various theoretical touchstones from the history of Indigenous film and from some of the existing literature on Indigenous education; in particular Susan Dion’s Braiding Histories (2010) read in conjunction with scholar/activist Ariel Smith’s theorization of Indigenous ‘horror’ film (2015). I hypothesized that the teachers participating in the study would have their positionalities disrupted as a result of viewing Rhymes for Young Ghouls (2013) and would then be able to engage their classes in awareness of Indigenous/Canadian issues. Though the participants agreed that it was an emotionally gripping and powerful film the results did not suggest that the research participants changed their views and conceptions of themselves in relation to colonialism as a result of viewing Rhymes for Young Ghouls (2013). The findings demonstrated the potential for a critical intervention to take place when teachers incorporate a film like Rhymes for Young Ghouls (2013) into their curriculum. Evidence of the affective power of Rhymes is represented in the research participants’ responses in addition to the strategies discussed to enable an exhibition of the film to a classroom of young adults. The concluding results will leave one hopeful that there is still a will and a way to incorporate such a gritty film into secondary-school curriculum to challenge ongoing manifestations of colonial violence against Indigenous peoples.

Keywords: Curriculum
Indigenous Film
Advisor: Restoule, Jean-Paul
The Coordination of Health and Social Care in the Community for Seniors with Complex Needs

The aim of this thesis was to understand the conditions for coordinating health care and social care by examining the micro-level processes and practices of policy implementation in home and community care services. A qualitative single case study was conducted with two embedded units of analysis: 1) home care (HC) services care coordination of first-dollar, publicly financed extended health care services, and 2) community support services (CSS) care coordination of publicly subsidized services, outside of the extended health care basket of services. Qualitative data were collected from publicly available governmental and organizational documents. Semi-structured qualitative interviews were conducted with 33 home and community care case managers (15 HC managers, 18 CSS case managers). Data were analyzed using an abductive approach to thematic analysis. Drawing on street-level bureaucracy theory, this thesis assumes that examining how discretion is exercised by case managers in their efforts with arranging services for individual clients will illuminate how health and social care coordination policies are implemented. This thesis found public entitlements for the assessment of eligibility for home and community care services focuses on mostly medically oriented care and excludes necessary services for the most vulnerable of older adults, namely those with lower financial means and with social care needs. Given this, the thesis illustrates the importance of discretion in policy implementation. HC case managers were subject to more extensive rules and practice guidelines than CSS case managers. Despite this difference in formal expectations across sub-sectors, both sets of case managers were able to exercise discretion and deliver care outside of formal rules and guidelines. In other words, the case managers provided “extra care” to vulnerable clients who would otherwise not be served if formal policies were strictly adhered to, serving as something of a relief valve in a context of systemic under-funding. Overall, this thesis demonstrates how the practice of health and social care coordination is a complex endeavor, one that relies on the discretion of front-line health care and social care professionals in addition to being influenced by policy strategies and managerial models for care delivery.

Keywords: Care coordination
Health and social care
Health policy
Home care
Older adults
Street-level bureaucracy
Advisor: Kuluski, Kerry
Miller, Fiona A
World History in the Tumultuous 1330s: A Study of Nicholas Trevet’s Anglo-Norman Cronicles

The following study comprises a sustained reading of the Cronicles (c. 1328-1334), a universal history written by the English Dominican Nicholas Trevet. Trevet’s history is known primarily as the source for Geoffrey Chaucer’s Man of Law’s Tale; this dissertation reads the Cronicles as a text in its own right, with its own strategies of language and form, and its own historical context. Chapter 1 places the Cronicles into the framework of “universal history,” a heuristic grouping of texts in which space and time function as prominent vectors for the conveyance of meaning. The manipulation of universal-historical form allows Vincent of Beauvais, one of Trevet’s closest sources, to place the Dominican Order at the providential end of history; the Cronicles’ form, by contrast, suggests divine interest in England and its kings. Chapter 2 offers a close reading of the Cronicles’ treatment of the biblical Maccabees. Sustained attention to this material belies the supposed singularity of the work’s central narrative, the Tale of Constance. The masculine, heroic ethos of the Maccabees story complements the work’s pervasive engagement with women’s history. Trevet alters his sources, moreover, to bring Maccabean history, and biblical history more broadly, into alignment with the Anglo-British past. Chapter 3 reads the Cronicles’ other major narrative, the Tale of Constance, within the context of Trevet’s historical project. The Tale functions to slow down the pace of history and to surface its latent processes; crucially, however, Trevet also encourages us to read the Tale itself as history. Understood in this way, the Constance story functions as an origin-point, both for English Christianity and for conflict between Muslims and Christians in the Holy Land. England’s past is thus yoked to the latter, with crusade emerging as another vector for the nation’s providential significance. The final chapter places the Cronicles into the context of several fourteenth-century developments. Trevet’s genealogical program updates previous Plantagenet efforts in response to contemporary political uncertainty. The work’s oft-noted investment in Christian history, and its imbricated focus on England, reflect contemporary methods of conceptualizing and articulating the nation in religious terms.

Keywords: Chaucer
form
historiography
literature
medieval
Trevet
Advisor: Akbari, Suzanne C
Hierarchical Discrete-event Supervisory Control of AC Multi-microgrid Systems

This thesis reports the Research, Development, and Demonstration (RD) of a Supervisory Control (SC) system, based on Supervisory Control Theory (SCT), to provide discrete-state power management functions as part of the control of an AC multi-microgrid system. The SC system includes a two-layer hierarchical structure and synthesized as a decentralized system, using the Discrete-Event-System (DES) model of the multi-microgrid system (plant) and the proposed SC strategy. The SC system enables a logically optimal decision-making process, i.e., guarantees to i) make operational decisions subsequent to all possible discrete-event scenarios that are represented in the DES model of the plant, ii) remain non-blocking and non-conflicting, and iii) provide scalability. The main differences and features of the proposed SC system, as compared with the conventional SCADA-based Energy Management System (EMS), are: * The SC system, subsequent to a discrete event, e.g., a circuit-breaker opening or state-of-charge of a battery storage reaching a limit, makes a decision on a new i) operational mode, e.g., grid-connected or islanded, and/or ii) control state, e.g., grid-following or grid-forming control functions. The SCADA-based EMS, based on power flow studies, optimizes the steady-state operation in the time-frame between two consecutive discrete events. * The SC system should respond to an event within a few to tens of milliseconds, since the SC system's decision determines viability of the system operation condition. The SCADA-based EMS assumes a viable steady-state operating condition and its response is not time-critical. A multi-microgrid study system, composed of four single microgrids, is developed to evaluate the performance of the proposed SC system in an off-line hybrid PSCAD-MATLAB environment, where the multi-microgrid and local controllers are represented in the PSCAD platform and the SC system is modeled in the MATLAB-Stateflow toolbox. The study results are verified in a RTDS-PLCnext Hardware-In-the-Loop (HIL) platform, where the multi-microgrid and local controllers are represented in the RTDS real-time simulator and the SC system is implemented in the PLCnext control platform.

Keywords: Energy-Storage-Systems
Multi-microgrid Systems
Power Distribution Systems
Power Management Systems
Renewable Energies
Supervisory-Control-Theory
Advisor: Iravani, Reza