VictorJuiz/thesis huggingface dataset:
Programmable Self-Regenerating Bioelectronic Devices

The rise of nanoscience has revolutionized biomedical research, resulting in bio-nanotechnologies that are radically improving our health and wellness. These unprecedented advancements can be attributed to the new tools and techniques that are used to effectively and reliably investigate and interact with biological systems. Enabling conversion between biological and electronic signals would provide a way to construct powerful and affordable bioelectronic technologies. However, currently, there is no general way to do that primarily because the solid-state digital and the soft and wet biological worlds are disconnected in the modern electronics industry. By converging the principles and toolkits of molecular biology with digital electronics, herein, I present the development and application of a new type of bioelectric signal transduction method, modeled as a ‘molecular pendulum’ (MP). The resulting devices utilizing the MP mechanism are reagent-free, i.e., they are self-contained and function autonomously without needing any external reagents, and self-regenerating, i.e., they adaptively change their response to report on the dynamic changes in their host environment. These properties make the MP strategy ideal for developing new biosensing devices including innovative wearable and implantable medical technologies that have not yet been possible. First, I describe the device architecture and working principle of the MP sensing strategy and highlight their unique key properties. Then, I present several applications of the MP method including the development of a direct, reagent-free detection system for emerging pathogens, a synthetic bioreceptor-based MP system for monitoring cardiac abnormalities, and easily programmable, field-deployable MP devices for body-interfaced biosensing systems. The clinical significance of these new bioelectronic technologies has been demonstrated by validating them in analyzing different types of human samples including saliva, sweat, and whole blood, and comparing them with existing gold-standard methods such as PCR and ELISA tests. The pursuit of interfacing electronics with the wondrous biological world presented in this thesis will hopefully inspire and guide excellence and innovation in future bioelectronic technologies for human health.

Keywords: Bioelectronics
Biomolecular Sensing
DNA Nanotechnology
Electrochemistry
Nanomaterials
Advisor: Sargent, Edward
Investigating Sex and Gender Influences on the Use and Effects of Cannabis

Sex and gender differences have been demonstrated in the use, harms, and effects of cannabis and in cannabis use disorder. However, research investigating these differences is limited, particularly as the cannabis landscape continues to rapidly shift and grow following the legalization of non-medical cannabis. Study 1 examined sex differences in the acute pharmacological effects of an intoxicating dose of alcohol combined with a moderate dose of cannabis (12.5%/94 mg ∆9-tetrahydrocannabinol; THC) smoked ad libitum in 28 adults (12 females, 16 males) who used cannabis at least once per week. Limited sex differences were found across all outcomes; however, in the alcohol-cannabis combined condition, females smoked significantly less cannabis, though no sex differences were uncovered in any acute effects. Study 2 investigated sex differences in the acute pharmacological effects of a range of cannabis doses (0%/0 mg, 6.25%/47 mg, 12.5%94 mg, 22.0%/165 mg THC) smoked ad libitum in 35 adults (18 females, 17 males) who used cannabis 1-5 days per week. Minimal sex differences were revealed in smoking topography, blood cannabinoid concentrations, vitals, subjective effects, pharmacokinetic-pharmacodynamic relationships, mood, and cognition. Study 3 explored gender influences on cannabis use and treatment trajectories through qualitative interviews with 23 adults (10 cisgender women, 12 cisgender men, 1 non-binary person) who had received treatment for cannabis-related problems. Four major themes were identified including: 1) a lack of perceived relationship between gender and cannabis use trajectories; 2) influences of masculinity and recreational motivations for cannabis use among men; 3) influences of social factors, stigma, and coping with mental health symptoms on cannabis use trajectories among women; and 4) influences of concurrent substance use and a lack of awareness of cannabis harms and treatment options on cannabis use trajectories, regardless of gender. Additionally, Study 3 unexpectedly uncovered fraudulent and deceptive practices in some virtual participants, providing the opportunity to generate awareness of this growing issue in online studies and offer potential strategies to detect and prevent fraud and deception in future research. These findings provide insights into the influences of sex on the acute effects of cannabis and the influences of gender on cannabis use and treatment trajectories, highlighting the importance of considering sex and gender when examining the use, harms, and effects of cannabis to better inform education, prevention, and treatment.

Keywords: Cannabis
Cannabis Use Disorder
Gender
Sex
THC
Advisor: Brands, Bruna
BIONIC: Biological Network Integration using Convolutions

Biological networks constructed from varied data can be used to map cellular function, but each data type has limitations. Network integration promises to address these limitations by combining and automatically weighting input information to obtain a more accurate and comprehensive representation of the underlying biology. I developed a deep learning-based network integration algorithm that incorporates a graph neural network (GNN) framework. My method, BIONIC (Biological Network Integration using Convolutions), learns features which contain substantially more functional information compared to existing approaches. BIONIC has unsupervised and semi-supervised learning modes, making use of available gene function annotations. BIONIC is scalable in both size and quantity of the input networks, making it feasible to integrate numerous networks on the scale of the human genome. To demonstrate the utility of BIONIC in identifying novel biology, I predicted essential gene chemical-genetic interactions from non-essential gene profiles in yeast, which were then experimentally validated by other members of the lab.

Keywords: Biological
BIONIC
Functional
Integration
Network
Systems
Advisor: Boone, Charlie
Bader, Gary
Unions, Moral Economies, and Inequality: An Empirical Investigation into Cultural Pathways Linking Union Density to Income Inequality, 1970s-2010s

Union decline is a major contributor to rising income inequality among both unionized and non-unionized workers, which has increased by more than 40 percent since the 1980s. The moral economy perspective argues that unions foster egalitarian wage norms that are materialized in redistributive policies, wage regulations, and employers’ compensation practices. While plausible, the moral economy perspective is largely speculative. Drawing on large-scale survey data between the 1970s and 2010s, I perform a step-by-step mediation analysis of the moral economy perspective. Results show that higher union density is associated with higher support for reducing income inequality, lending support for the cultural role of unions. Results also show that wage norms explain a small portion of union density effects on voting Democratic in presidential elections and wage variance increases. Findings lend limited support for the moral economy perspective and lay an empirical foundation for evaluating unions’ normative effects on income inequality.

Keywords: Income Inequality
Moral Economy
Norms
Politics
Unions
Advisor: Silver, Daniel
Collective Creativity in Jazz and Creative Music: Preparing Original Compositions for “Togetherness”

This dissertation examines collaborative musical creativity through the idea of “togetherness” at a multi-week music intensive educational program for composer-performer-improvisers (or simply musicians) in jazz and creative music. At this summer program, musicians from different musical backgrounds and nation-states come together and collaborate in creativity in the preparing and playing of their original compositions. The story told through this project focuses on how musicians facilitated the inclusion of diverse creativities and identities throughout original improvisational compositions together, not just in solos. Three weeks of ethnographic fieldwork in 2016 and 2017, as well as auto-ethnographic observations of the same program in 2012, are here focused on participants’ experiences during their time in this program. These observations provide the basis for understanding how these musicians view their music as creative specifically because it was made together. Drawing on theories of community and the idea of “art worlds” (Becker 2008), and in examining how groups facilitated togetherness, this project reveals how particular notions of creativity were negotiated and what these negotiations mean for practices of jazz and creative music.

Keywords: Collaboration
Community
Creative Music
Creativity
Improvisation
Jazz Music
Advisor: Packman, Jeff
Investigating Equitable Access to Evidence-Based Literacy in French Immersion

This dissertation uses convergent mixed methods to investigate literacy development in French Immersion (FI). Overall, the research in this dissertation aims to enable equitable access to high-quality literacy instruction in Ontario FI programs. The first study shone a light on the experiences of children with special education needs (SEN) and/or coming from low socioeconomic status (SES) backgrounds. Scholars have raised concerns about the accessibility of FI for students with SEN (Selvachandran, 2022; Kay-Raining Bird et al., 2021). However, little research has been conducted in partnership with low SES families. I conducted semi-structured interviews with eight families from various SES backgrounds who had children, with or without SEN, enrolled in FI. Families valued FI for its benefits but found it challenging to support their child’s school success. The results furthermore showed that families faced significant systemic barriers if they were from low SES communities, had children with SEN, or both. The second study explored the contribution of orthographic specificity to word reading accuracy and fluency among students enrolled in FI schools. According to the lexical quality hypothesis, word reading consists of phonology, orthography, and meaning (Perfetti & Hart, 2002). Following the paradigm used in Van Goch et al. (2014), I investigated whether orthographic specificity (i.e., distinguishing between orthographically similar words like leek-leak) significantly contributed to word reading ability in English and French. 130 Canadian children were assessed in grades 1-3 (ages 6-9; Time 1, T1), and one year later in grades 2-4 at Time 2 (T2). Analyses found that orthographic specificity explained unique variance in word reading fluency and accuracy across both languages in concurrent analyses. Furthermore, longitudinal analyses showed a significant indirect effect of T1 orthographic specificity on T2 word reading accuracy and fluency in both languages. These results support the specificity of orthographic knowledge as an essential constituent of the Lexical Quality Hypothesis (LQH; Perfetti & Hart, 2002). Taken together, this dissertation demonstrates that more equitable policies are necessary to support the literacy development of diverse students in FI. This dissertation shows that equitable and accessible early assessment and intervention is possible, and crucial to diverse children’s success in FI.

Keywords: Accessibility
Dynamic Assessment
French Immersion
Literacy
Multilingualism
Orthographic Specificity
Advisor: Chen, Xi
In vivo CRISPR Screens Identify Dual Function of MEN1 in Regulating Tumor-microenvironment Interactions

Functional genomic screens in 2D cell culture are of limited use for identifying therapeutic targets that modulate tumor cell-microenvironment cell interactions. By comparing targeted CRISPR-Cas9 screens in 2D culture of A549 lung cancer cells versus xenografts derived from the same cell line, this project has identified MEN1 as the top hit that confers differential effects in vitro and in vivo. Knockout of MEN1 in multiple solid cancer types does not impact cell proliferation in vitro, but significantly promotes or inhibits tumor growth in immunodeficient or immunocompetent mice, respectively. Mechanistically, knockout of MEN1 leads to increased chromatin interaction of its interaction partner MLL1 (KMT2A), a histone methyltransferase, to repetitive genomic regions, where it activates expression of double-stranded RNA and presence of cytosolic DNA. This results in MAVS and cGAS-STING dependent activation of viral mimicry response, which induces infiltration of neutrophils and CD8+ T cells in immunodeficient and immunocompetent mice respectively. Consistently, multiple immune cell infiltrations are negatively correlated with MEN1 abundance and positively correlated with that of MLL1 in patient tumors of a broad range of cancer types. Pharmacological disturbance of MEN1-MLL interaction reduces tumor growth in CD8+ T cell dependent manner, with enhanced activity in combination with anti-PD-1 treatment. These findings reveal tumor microenvironment-dependent oncogenic and tumor suppressive functions of MEN1 and provide rationale for therapeutic targeting of MEN1 alone or in combination with immunotherapy in multiple solid cancer types.

Keywords: immune cell infiltration
in vivo CRISPR screen
MEN1 duel function
novel drug development
tumor microenvironment
viral mimicry
Advisor: Tsao, Ming-Sound
He, Housheng
Autobiographical Writing for Adult Newcomer English Language Learners

Motivated by the Language Instruction for Newcomers to Canada (LINC) program’s autobiography component, which asked newcomer learners to share their life stories, this study investigates the impact of practicing autobiographical writing on adult newcomer learners’ English learning and their identities and self-reflections. Using a multi-staged action research design, this study involved a six-week autobiographical writing class I taught to eight volunteer learners, using lesson plans informed by interviews I had conducted with experienced English language instructors. This study includes the following data: instructor participant interviews (n=8), lesson plans and revision documents, learner pre- (n=8) and post-course interviews (n=4), learners’ written work produced in the course, and my reflections as the researcher, designer of the curriculum, and instructor of the course. Qualitative analysis of the data and the case studies of the focal learners reveal that autobiographical writing can support adult newcomers’ English learning and positively influence their identities and self-reflections. The findings in this dissertation call into question the LINC program’s decision to eliminate autobiography as a required component since it can help amplify learner voices and support their self-expression. As such, this study advocates for complementary research to engage more participants and various stakeholders to further examine the impact of autobiographical writing on language learners.

Keywords: autobiographical writing
English as an additional language education
English writing instruction
immigrant education
lived experiences
newcomer settlement
Advisor: Kerekes, Julie JK
Encoding the Underlying Dynamics of Complex Time Series With a Focus on Healthcare Applications

Time series data captures temporal patterns and provides invaluable insights into various dynamic phenomena. In healthcare, time series plays a crucial role in understanding the temporal dynamics of individuals' health, enabling early detection of medical conditions, personalized treatment plans, and proactive healthcare management. This thesis addresses some of the challenges associated with modelling real-world time series data and provides novel solutions for encoding generalizable knowledge from the data that is applicable to multitude of tasks. This study presents a self-supervised framework for learning representations tailored to non-stationary time series. This framework captures transferable insights from the data that can be effectively applied across a range of tasks. The results demonstrate the potential of this approach for downstream prediction, clustering as well as in tracking health state trajectories for early detection. To improve the interpretability of the underlying representations, a solution is presented that decouples different factors of variability into independent encodings with generative models and through counterfactual regularization. The proposed approach enables multitude of tasks including counterfactual sample generation with control over different underlying factors which is a powerful tool for applications such as modelling drug responses in individuals. This thesis also explores explainability in time series models and its impact on adoption of these models in clinical practice. It introduces an information-theoretic approach for explaining the output of time series models by taking into account the temporal correlations in the data. The overarching objective of this thesis is to design solutions that bring machine learning models closer to adoption in clinical practice. In the concluding chapter, this is demonstrated through a case study that illustrates the pathway from design to deployment of a risk estimator model, highlighting the challenges in this journey and introducing protocols for comprehensive evaluation of its performance, usability, and safety in practice. In conclusion, this thesis contributes novel machine learning solutions to tackle the challenges associated with modelling real-world time series and deployment. The proposed solutions have the potential to unlock the rich information embedded in time series, enabling their adoption in various applications, particularly in healthcare.

Advisor: Goldenberg, Anna
Research on Competition in the Health Care Industry

Although the role of competition in the health care sector has been extensively explored in developed countries, evidence from China is limited. This dissertation comprised three research projects that examined the health consequences of competition in the health care industry in China: 1) to explore the impacts of pharmacy competition on drug expenditures by individuals who purchased drugs for influenza at pharmacies from 2015 to 2019 in Changde city, Hunan province, China; 2) to assess the impacts of hospital competition on the quality of outpatient care for individuals who had outpatient visits at hospitals for influenza from 2015 to 2019 in Changde city, Hunan province, China; and 3) to compare the impacts of hospital competition by hospital-type on the quality of inpatient care for individuals who were admitted for chronic obstructive pulmonary disease at hospitals in the fourth quarter of 2017 and 2019 in Sichuan province, China. This dissertation demonstrated that: 1) pharmacy competition was associated with a decline in annual average influenza-specific drug expenditures by individuals with influenza; 2) hospital competition contributed to an increase in the quality of outpatient care for outpatients with influenza; and 3) the impacts of hospital competition on the quality of inpatient care for those with chronic obstructive pulmonary disease depended on the quality measure used and on hospital-type. These findings jointly have implications for the design of health policies and efforts to both enhance the quality of healthcare services and to control healthcare expenditures.

Advisor: Coyte, Peter C
Multiparametric and Multivariate Analysis of White Matter Microstructure and its Relationship with Psychosexuality

Neuroimaging research on psychosexuality, including gender identity and sexual orientation, often focuses on Western adults and lacks adolescent and non-Western populations. Here, the dissertation addresses these absences by investigating white matter (WM) microstructure, which characterizes the structural connectivity of the brain. WM microstructure has been associated with differences in pubertal development, sex steroid hormones, and psychosexuality. Three multiparametric and multivariate studies investigated developmental, hormonal, and psychosexual associations with WM microstructure in sexually and gender diverse Canadian adolescents and Thai adults. Metrics of WM tissue organization, density, and myelination were derived from diffusion tensor imaging using fractional anisotropy (FA), axial (AD), and radial diffusivity (RD). T1 relaxometry, an additional proxy of myelination was included in Study 1. The studies used whole-brain, mass-univariate tract-based spatial statistics and multivariate partial least squares analyses. Study 1 investigated WM microstructural associations in cisgender and transgender adolescents with age, estradiol, physical development, and sexual attractions. Study 2 compared the WM microstructure of sexually and gender diverse adults, including a group of transfeminine individuals using gender-affirming hormones (GAH). In the same adults, Study 3 explored associations between WM microstructure, psychosexuality, and performance on a mental rotation task (MRT). The findings indicated that pubertal development, hormones, and psychosexuality were related to WM microstructure. Study 1 revealed strong relationships between AD and T1 relaxometry and pubertal development in most WM tracts in cisgender boys. Weaker and less consistent associations were found in cisgender girls and transgender boys. Study 2 replicated Western findings of FA, AD, and RD differences in straight cisgender men and women in the fornix, corpus callosum, and several association tracts, but the indices were not differentiated by androphilic and gynephilic sexual attractions. GAH-use was related to lower organization and faster diffusion in the forceps minor of transfeminine adults. In Study 3, a multiplicity of brain patterns illustrated the relationship between MRT score and WM microstructure and appeared to depend on group membership, suggesting that brain-behaviour associations may vary with psychosexual identity. Together, the studies reveal the complexity of characterizing psychosexual-neural phenotypes. The dissertation concludes with a discussion of potential underlying mechanisms, including culture, genetics, and hormones.

Keywords: diffusion tensor imaging
neuroendocrinology
neuroimaging
Sex/gender
transgender
white matter microstructure
Advisor: VanderLaan, Doug P
Lai, Meng-Chuan