VictorJuiz/thesis huggingface dataset:
Unsupervised and Supervised Methods for Analysis of Human Multimodal Transcriptome Data

Studying the RNAs expressed in cells has enabled the discovery of different types of RNA with different functions. Many RNAs, however, have no associated function. Therefore, we need to develop novel methods to facilitate and accelerate the elucidation of these RNAs. In this thesis, I developed two machine learning methods allowing summarization and visualization of large collections of transcriptomic datasets. I also show that these methods allow generating biological hypotheses for known RNAs with unknown functions. I describe these methods in three chapters. Chapter 2 describes our SegRNA method for unsupervised annotation of multi-experiment transcriptome datasets. SegRNA annotations enabled the visualization of the most common patterns of transcriptomic signal from multiple assays: GRO-seq, CAGE, and RNA-seq. The most common patterns not only indicated the differences between these assays, but they also identified RNAs with different sizes and from different subcellular localization. SegRNA annotations are cell-type–specific. To date, the annotation that we generated for the K562 cell line is the first cell-type annotation that integrates RNA sizes, localization, and different assays. We show in this chapter that this annotation allows identifying novel short RNAs. Chapter 3 describes my collaboration with the FANTOM6 consortium. I show the experiments that led to the decision of using SegRNA with manual parameters to annotate the transcriptional changes that follow the knockdown of long non-coding RNAs, at 2 bp resolution. We used our method to generate 99 annotations that summarize 510 CAGE datasets. These SegRNA annotations successfully identified 92% of the knocked down long non-coding RNAs as downregulated, while SegRNA annotated on average 7% of the genes as downregulated. Chapter 4 describes our supervised cell lineage analysis (CLA) method for the identification of cell-type–specific, and lineage-specific RNAs. Identifying these RNAs requires running tools that generate a large number of results which makes the results hard to interpret. CLA automates these steps by identifying RNAs that discriminate cell types and summarizing the RNAs with a lineage score. We show that this approach enabled the identification of novel cell-type–specific alternative promoters. This thesis introduces tools that allow researchers to better understand the transcriptome by facilitating its interpretation.

Keywords: Cell Lineage
Computational Biology
DBN
Ontology
SegRNA
Transcriptomics
Advisor: Hoffman, Michael M
Hardware Checkpointing and Productive Debugging Flows for FPGAs

As FPGAs become larger and more complex, productive debugging is becoming more challenging. In this work, we detail a new debugging flow based on hardware checkpointing that provides full visibility and controllability while maintaining reasonable execution speed. Hardware checkpointing is useful not only for debugging but also enables several other capabilities such as live migration, fault recovery, and context switching; however, it has been difficult to achieve for FPGA applications. In this thesis, we overcome the challenges of checkpointing FPGA designs and realize the proposed checkpoint-based debugging flow. First, we propose techniques and wrappers that can safely interrupt a running design to create a consistent (restartable) checkpoint while avoiding hazards such as data loss or deadlock. We also develop approaches and tools that can access buried on-chip state that cannot be directly captured to create complete checkpoints. We next propose a checkpoint-based debugging framework, StateMover, that can seamlessly move the design state back and forth between an FPGA and a simulator, achieving the best of both worlds: speed and observability. Finally, we build a transaction-based co-simulation framework, StateLink, to extend the functionality of the proposed debugging flow to systems that cannot be entirely moved to a simulator such as CPU+FPGA accelerators or datacenter-scale applications. The combination of these tools enables new and productive debugging flows. StateMover allows designs to run at full hardware speed until a region of interest is approached. Then, a checkpoint can be loaded and its execution observed and controlled in a simulator. StateLink allows a designer-selected portion of the system to be moved into a simulation, enabling simulation speedups of up to 25x versus simulating the entire design. We demonstrate on several designs that StateMover and StateLink support can be added to a design with low resource and timing overhead, and illustrate the utility of the flow by debugging a complete Memcached system.

Keywords: Checkpointing
Debugging
FPGA
Advisor: Betz, Vaughn
Negation in Cree

This thesis investigates the negative particles used in two varieties of Cree: Muskeg Cree (a.k.a. Swampy Cree) and Plains Cree. Previous literature on Plains Cree has implicated a variety of factors potentially relevant to the choice of negative particle, including: inflectional order, clause type, clausal versus constituent negation, reality status, and veridicality (Cook 2014; Reinholtz and Wolfart 1996; Déchaine and Wolfart 2017). Discussion of Muskeg Cree has broadly claimed that inflectional order alone determines the negative particle used (Ellis 2000; MacKenzie 1992). This thesis investigates these attested patterns of negation in Plains Cree and Muskeg Cree, using a variety of methods from variationist sociolinguistics, statistical analyses, and semantic fieldwork. Corpus analysis of published literary materials was performed, as well as interviews with speakers that included translation, grammaticality judgment tasks, and storyboards. The results indicate that Plains Cree negation broadly reinforce the claim that inflectional order and reality status are relevant factors affecting negator use. It also appears that there may be additional unidentified factors at play in negation in this variety. In contrast, Muskeg Cree negation does not appear to be consistent with the previously identified pattern. The negator mwāc, previously considered marginal, is the overwhelmingly preferred negator for non-imperative negation across the modern speakers interviewed. Mwāc is used across a variety of contexts, regardless of inflectional order, while other non-imperative negators, ēkā and mōna, are dispreferred, rare, or even non-existent for many speakers. Substantial variation in negator use was observed for Muskeg Cree, both between literary and elicited materials, as well as between speakers being interviewed. This indicates that the hetereogeneity within the Muskeg variety of Cree has been underestimated, with greater variation in how speakers are able to express themselves through negation. These findings have implications for the teaching of negation in Muskeg Cree, and support the use of varied methodologies in the examination of language. They provide new insights into the pattern of use of negation in Muskeg Cree, an understudied language.

Keywords: algonquian
cree
muskeg cree
negation
plains cree
swampy cree
Advisor: Lima, Suzi
Performing Technology: Mapping Interface Metaphors and Interactive Dramaturgies

Digital technologies are not dramaturgically neutral. Rather, when we make the choice to use a piece of technology in performance practice, the technology has already made a series of choices for us. These choices manifest in the interface metaphors that define how we interact with digital technology and are deeply embedded in the developmental ancestry of each device.Given the profound impact of computational systems on performance, it is critically important to question when those choices are made, by whom, and to what extent, if any, computer systems make or define users’ dramaturgical choices. This process is rooted in digital dramaturgy, an interdisciplinary approach that combines intermedial-performance study, media theory, history of technology, and hands-on experimentation to establish a hybrid critical framework with a practice-based methodology which directly engages with computer hardware, software, and wetware. Through a series of case studies presented over five chapters, this dissertation examines several prominent contemporary technologies used in performance, including digital projection systems, media servers purpose-built for performance use such as TroikaTronix’s Isadora, Figure 53’s Qlab, and livestreaming studio Open Broadcaster, as well as playful appropriations of the Xbox 360 Kinect motion tracking camera and videoconferencing platform Zoom. These digital technologies use non-linguistic metaphors, including images, sounds, gestures, sensors, and other techniques which relate the logic and structure of prior (often analog) systems within the current (digital) technology. As such, this research draws on George Lakoff and Mark Johnson’s notion of conceptual metaphors, which recognizes that metaphors are not merely linguistic devices, but systemic cultural expressions which humans use to communicate ideas and concepts on a structural level. In each case study, this research aims to identify what metaphors are present, how they are constructed, and most importantly, assess how they drive what is created using that technology. This thesis finds that modern digital technologies embedded technical or creative dramaturgy. When used within a performance, these technologies complicate power dynamics, foster specific ways of doing and thinking, and even enforce rigid modes of production. By mapping and revealing how these technological systems operate, this research hopes to encourage exploring and building new alternatives.

Keywords: digital
dramaturgy
performance
technology
Advisor: Budde, Antje
Identifying Sources of Missing Heritability and Translating Genomic Variation in Nicotine Metabolism

Cigarette smoking continues to be a leading cause of preventable death. The rate of nicotine’s metabolic inactivation is mediated predominately by CYP2A6 enzyme activity, phenotyped by the nicotine metabolite ratio (NMR). The NMR is associated with several smoking behaviours, including differences in cessation outcomes and disease risk. The NMR is limited in that it requires specialized assays to run and cannot be quantified in non-regular smokers. These limitations prevent prediction of metabolizer status to evaluate disease-risk within these groups, or response to clinical drugs metabolized by CYP2A6. In contrast, genetic data is increasingly available in clinical studies and settings. Twin studies yield high heritability estimates for the NMR, indicating a genetic underpinning, yet known genetic variants explain only a fraction of the variation in the NMR. In this thesis, we explored potential sources of this missing heritability. With the rise of genome-wide association studies, novel variants associated with the NMR have been identified, but approaches to integrate these variants with known CYP2A6 variants have not been described. We developed weighted genetic risk scores (wGRSs) in both African- and in European-ancestral populations and contrasted these wGRSs to earlier genetic scoring and cross-ancestry approaches. Overall, we highlighted the ability of ancestry-specific wGRSs to replicate NMR-associated smoking cessation outcomes, such as demonstrating unique metabolizer by treatment interactions. Rare variants (minor allele frequency <1%) have been proposed to explain another portion of missing heritability. We used targeted sequencing to identify 38 novel CYP2A6 rare variants; novel variants were functionally characterized through in vivo, in silico, and in vitro approaches, and integrated into the wGRSs. On a population level, there is a minor contribution of CYP2A6 rare variants to NMR heritability; however, they provide an important contribution to the resulting prediction of metabolizer status for individuals genotyped with rare variants. Together these findings capture up to 33% and 34% of the genetic variation in the NMR in African and European populations, respectively. Overall, the research presented expands our knowledge of genetic variation in nicotine metabolism, providing insight into CYP2A6 genetic differences between ancestral populations, and enhancing our ability to use genetics to predict CYP2A6 activity.

Keywords: Ancestry
CYP2A6
Genetic Risk Score
Nicotine
Pharmacogenetics
Rare Variants
Advisor: Tyndale, Rachel F.
An Examination of the Socio-political Forces Shaping End-of-life Conversations in Interprofessional Primary Care with Medically Frail Older Adults

Scholarship in the field of end-of-life (EOL) conversations has grown over the last three decades. However, despite a large body of work, there remain theoretical, methodological, and substantive gaps to inform an understanding of the issue of delayed or avoided EOL conversations in primary care. This critical ethnography informed by biomedicalization attempts to build an understanding, rooted in empirical data, of how EOL conversations happen and also why they might not happen in the primary care of medically frail older adults. Data includes observations of 25 clinical appointments involving clinicians and medically frail older patients and/or their care partners at an urban Family Health Team in Ontario, Canada as well as 94.5 hours of structured observations of clinicians’ day-to-day activities excluding direct patient care, and 27 interviews with participants. Key findings highlight the multiple and competing discourses circulating in primary care that constrain EOL conversations. In appointments with patients’ ‘most responsible providers’ (MRPs), the more life discourse constrains talk of decline and dying, making EOL conversations less possible. More life is aligned with the culture of biomedicine and clinical practice guidelines as well as the culture of life extension in the West, giving this discourse influence. Interprofessional collaboration (IPC) in EOL conversations is also limited, with nurses and allied health clinicians rarely being involved in EOL conversations. Neoliberal-biomedical discourse shapes factors at the structural, organizational, and practice levels, encouraging efficiency and biomedical dominance in ways that limit opportunities for IPC in EOL conversations. I recommend primary care as a specialty reflects on its entrenchment in a culture of care that valorizes more life and (re)create clinical practice guidelines and measures to align with person-centredness more meaningfully. Additionally, for nurses and allied health clinicians to become involved in EOL conversations with frail older adults, they need to share in clinical decision-making. Structurally, improving IPC must address constraints from neoliberal and biomedical ideologies. Clinicians can also collectively work at the practice level to create change. Future research should take a participator approach with patients, care partners, and interprofessional clinicians to develop ways of supporting holistic relational care & communication in primary care.

Keywords: Advance care planning
Biomedicalization
Critical Ethnography
Discourse
End-of-life conversations
Primary care
Advisor: Kontos, Pia
Exploring Waiting for Child Transplant Candidates and Families

Suffering is embodied, deeply personal, and yet connects people across time and space; that is, suffering can be socially relational. Relational suffering is potentially no more evident than in the context of children awaiting organ and bone marrow transplants. As the child with a life-threatening condition suffers, so do many others around them. In addition, a spate of professionals devote their lives to alleviating patient and family suffering. Currently, the social aspects of such suffering continue to be poorly understood by health researchers attending to organ and bone marrow transplantation processes. Specifically, evidence from the extant literature on organ and bone marrow transplantation hints to the waiting process as an important form of, patient and family, relational suffering. Yet very little is known about: how children and families wait; what happens physically, socially, emotionally, psychologically, spiritually, and existentially to children and their families while waiting; and, what resources and supports children and their families could use to relationally cope while/with waiting. Utilizing a narrative ethnographic approach (Gubrium & Holstein, 2009), I conducted a 17 month in-depth, field-based exploration through in situ interactions with four child organ and bone marrow transplant recipients, their families, and 20 HCPs both working with families or with experience in transplantations. I developed a theoretical, conceptual, and practical understanding of waiting/suffering by exploring families’ stories about waiting in uncertainty for a transplant over time. I explored what happened in and to relationships within families, between parents and friends, other parents of children with a life-threatening condition, and work colleagues. From the findings, I propose a working 'narrative roadmap' of children's and families’ experiences of waiting for a transplant to help guide families through the process of waiting, and to support HCPs in caring for them. Further, I propose a conceptual 'Relational Web of Suffering' as a heuristic tool for HCPs and bioethicists caring for families to illustrate how families’ social support networks operate while suffering, and people’s multi-dimensional (e.g., social, emotional, physical, spiritual) roles during waiting.

Keywords: Families
Healing
Illness
Relational Suffering
Suffering
Waiting
Advisor: Atkinson, Michael
An Exploratory Descriptive Study of Implicit Bias in Police Recruits and Applicants at the RCMP

Abstract An Exploratory Descriptive Study of Implicit Bias in Police Recruits and Applicants at the RCMP Philip Elias Semple Doctor of Philosophy Department of Leadership, Higher and Adult Education, Ontario Institute for Studies in Education University of Toronto 2022 This study sought to explore the nature, degree and impact of implicit bias in police recruits and their instructors attending the Royal Canadian Mounted Police (RCMP) training facility in Regina, Saskatchewan. The bias explored was in relation to Black men and women. Findings were generated using a mixed methods form of research. Quantitative data were obtained using an implicit bias measuring tool and qualitative data were gleaned from key experts external to the police services. The rationale behind choosing the implicit bias test called Implicitly as the main data collection instrument, its characteristics, and established validity are discussed. The issues of bias and racism are explored from a police and social perspective. Implications, ways to mitigate implicit bias and prevent unsuitable candidates from being hired into positions of power such as policing are also discussed. Significant limitations were encountered in the implementation of the initial research protocol. At the original intended test site, the Ontario Police College (OPC), none of the instructors and only two recruits attempted to complete the Implicitly test. Furthermore, at the second site, the RCMP Depot, none of the instructors chose to participate and only 61 out of 800 invited recruits completed the Implicitly test. However, the Implicitly tests were subsequently offered by the RCMP to recruit applicants and a robust sample of 5,282 tests were completed and the aggregated results made available to me for this study as de-identified secondary data. These secondary data provided the focus of the discussions with five key external experts who shared their perceptions stressing the need for the testing to be a mandatory part of the hiring process for policing because of the potential impact of bias in officer’s position of power. They also thought that the implicit bias testing could be useful in helping to determine the efficacy of recruit training. Key findings identified some significant limitations. These overall test results showed low ranges of implicit bias for both RCMP recruits who completed the tests and recruit applicant participants. Exploring the reason(s) for the lack of participation by the instructors and recruits urgently warrants further investigation.

Keywords: adult education
bias
college education
higher education
implicit bias
police
Advisor: Janzen, Katharine
Thank You for Being a Friend: Social Integration and Psychological Well-being in Lesbian Older Adults

A growing body of research has identified the relationship between loneliness and numerous adverse health outcomes in adults over the age of 55. Lesbian, gay, and bisexual (LGB) older adults have been flagged as an especially high-risk group, and while social networks have been shown to protect against loneliness in LGBT youth, this has yet to be investigated in older adults. A growing arena for social connection in older adults is the Internet, with over 45% of seniors reporting regular use of social media sites; however, disagreement persists regarding the influence of these sites on mental health, particularly in LGB older adults. This study examined associations between social integration and psychological well-being among lesbian older adults and a demographically similar sample of heterosexual women. Additionally, the study explored the mediating roles of mental health status (loneliness, depression, anxiety) and social media (use and attitudes) on this relationship, as well as the influence of the COVID-19 pandemic on social communication. Lesbian (n = 201) and heterosexual women (n = 245) between the ages of 55 and 85 completed online questionnaires assessing social integration, psychological well-being, mental health status, social media, and changes in communication patterns during COVID-19. In each sample, social integration was significantly correlated with psychological well-being; however, lesbian and heterosexual older women did not significantly differ in levels of social integration or well-being, and neither sexual orientation nor age moderated this relationship. Loneliness, depression, and anxiety were found to significantly mediate the relationship between social integration and psychological well-being, particularly regarding the more objective dimensions of social integration. Conversely, social media use and attitudes were not found to be significant mediators, and no notable changes in communication patterns during the COVID-19 pandemic were found. These results suggest that social integration is importantly linked to psychological well-being in both lesbian and heterosexual older adult women, and that this relationship is indirectly affected by mental health status. While the limited representativeness of the study sample may restrict the generalizability of these findings, they generally strengthen support for considering social factors when addressing the mental health needs of lesbian older adults.

Keywords: LGB
Mental health
Older adults
Psychological well-being
Social media
Social networks
Advisor: Schneider, Margaret