VictorJuiz/thesis huggingface dataset:
Getting Down to Brass & Wax: The Material Culture of Physics at Canadian Universities, 1890-1939

This thesis explores the scientific apparatus of physics at Canadian universities from 1890 to the onset of World War Two. It is divided into two complementary sections. The first section adopts a collections and material culture approach to analyze the accumulations of historical apparatus that emerged at departments of physics. Through considering how artifacts in these environments avoid destruction, how they come to form collections, and the implications of these processes for the surviving artifacts as evidence of the scientific past, it complicates existing accounts of these narratives. It examines the close and definitive relationship these collections have to their home department and how they are shaped over time, most notably by technical members of staff. This dissertation concludes that collected sets of surviving artifacts at university departments form a particularly rich historical source due to their shared history, while simultaneously noting the importance of fully considering these collections’ formations and evolution through to the present day. The second section of the dissertation offers a materially-focused history of experimental and practical physics as it emerged and matured in Canada. Informed directly by the material remnants of each university’s physics programme and the discussion in the first section, it traces shifts in thinking about teaching and research in physics relevant to both Canadian and international contexts. This includes the use of imported instruments to establish legitimacy away from scientific centres, the early influence of engineering and technical programmes, the rapid developments in research and teaching in the period following the First World War, and the central importance of department workshops, technical skills, and makers throughout this period. Together, these themes contribute a history of physics in Canada in which materiality, in the form of equipment and laboratory spaces, played a definitive role. This dissertation demonstrates the ability of large sets of seemingly mundane scientific artifacts to contribute a useful narrative history, and reveal new details about less-well recorded elements of the history of science, such as the role of technical staff. As such, it represents a model for future work examining the large quantity of historic scientific material at university departments.

Keywords: Canada
collections
material culture
physics
science
university
Advisor: Yeang, Chen-Pang
Woods, Rebecca
Three Essays in Industrial Organization

This thesis includes three chapters studying various topics related to industrial organization. My first chapter develops a novel procurement auction model with endogenous public information acquisition and ex-post cost uncertainty to study the effect of information policy on procurement cost. Bidders can exert costly effort to learn about the project and update their beliefs about the ex-post cost before participating in the auction. First, it allows risk-averse bidders to reduce their ex-post cost uncertainty and, thus, their risk premium on bids. Second, the acquired information generates additional information rent, which increases their bids. I estimate the model using unique administrative data from the Indiana Department of Transportation, which publishes all observable outcomes of bidders’ information acquisition on its Question and Answer platform. I find that not allowing bidders to acquire information increases the average procurement cost by 1.62%. Second, changing the endogenous model of public information acquisition to a private one generates higher expected procurement costs when competition is high. My second chapter develops a simultaneous multiple-procurement auction model under the presence of capacity constraints. In this environment, winning multiple auctions induces additional complementarity payoffs coming from synergies between auctions. But winning also increases the capacity constraints of the winner. I investigate the marginal effect of participating in an additional auction. I find that increasing an additional small auction will decrease the total average procurement cost by 2.8% or 70,000. The second counterfactual analysis looks at the effect of joint bidding on bids. Allowing bidders to submit a joint bid can potentially decrease the bids by 8% for the median auction. My third chapter studies the bidding capacity mechanism in procurement auctions. The bidding capacity mechanism restricts bidders' eligibility to submit a bid in an auction based on their available bidding capacity. I use a fixed effects model to test the linear relationship of bidding capacity with bidders' bid and bid submission decisions. I find that bidders with a higher bidding capacity will have a higher chance of submitting a bid to an auction, participating in more auctions in a period and submitting a more competitive bid.

Advisor: Luo, Yao
The Cello Exercise Index: Considering Technique Resources for Cello Teachers and Students

This dissertation is an analysis and codification of technical exercises written for the cello. The research aims to investigate this repertoire, understand its value, and consider the relevance of exercises for contemporary cellists. Technical exercises have been a mainstay of cello pedagogy but are rarely indexed in detail. This lack of indexing prevents cellists from effectively and efficiently using exercises for teaching, learning, and practicing cello technique. To address this issue, I created a traditional “back of the book” index not just for one book, but for a representative majority of the exercise repertoire. To build this “Cello Exercise Index,” I individually analyzed, tagged, and entered data for the contents of exercise books, ultimately creating a resource that allows users to search for, browse, and filter exercises according to their needs. This document serves as a guide to the Cello Exercise Index. Interested musicians could simply use the Index, but those who wish to learn about the methodology behind its creation, the potential benefits of this resource, and consider the general value of exercises will find discussions of these topics in this dissertation. After an introduction to the project in Chapter 1, Chapter 2 is a review of existing literature, including both historical information about the cello’s development and precedents in the form of analyses of pedagogical material. Chapter 3 details the methodology for the creation of the Index, including selection of sources and organization. Chapter 4 is a guide to using the Index, along with a summary of some difficulties encountered during its creation and their solutions. Telling a more complete story about the cello technical exercise meant discovering how and why contemporary cellists use exercises in their performing and teaching. To get a snapshot of the role of exercises in today’s cello studios, I conducted a series of semi-structured interviews to hear perspectives and opinions from four prominent cello teachers. Chapter 5 is a description of the interview component, including methodology and emergent themes. To conclude, Chapter 6 summarizes the project and considers directions for future research.

Keywords: Cello
Cello Exercises
Cello Pedagogy
Index
Technique
Advisor: Tan, Daphne
Remodeling of Peptidoglycan Biosynthesis in Staphylococcus aureus for Enhanced Antimicrobial Activity and Novel Drug Discovery

Multidrug resistant Staphylococcus aureus is a prevalent opportunistic pathogen with limited treatments available. The development of antibiotic resistance in S. aureus requires new therapeutics and a clearer understanding of its drug-resistant properties at the cellular level. In this work, I have discovered a novel class of antibiotics known as the lasso peptides that targets lipid II, the main precursor molecule for building bacterial peptidoglycan. I show that WalKR, an essential two-component system that regulates peptidoglycan remodeling, is key to understanding antibiotic susceptibility and resistance in multidrug-resistant S. aureus. Mutations in walR confer a hypersensitive reaction to tunicamycin, albeit resistance to all other cell wall targeting antibiotics. I have conducted a comprehensive biochemical and transcriptional profile of this phenomenon whereby a downregulation of peptidoglycan recycling is the indirect cause of the wal mutant phenotype. I show that in vivo studies of tunicamycin treatment can restrict the growth and dissemination of wal-mediated S. aureus infections while clinical antibiotics available cannot. This study highlights the important need for new antimicrobial matter and a new indirect mechanism wal mutations confer on S. aureus.

Keywords: antibiotic
cell wall
infectious disease
peptidoglycan
Staphylococcus aureus
Advisor: Nodwell, Justin R
The Orchestral Symphonies of Charles-Marie Widor: Context, Form and Performances

This dissertation studies the five orchestral symphonies of Charles-Marie Widor (1844–1937), who was an organist and composer highly regarded in his own time. These works have been severely neglected by major studies of French Romantic symphonies, by symphony orchestras, and by the organ world (three of the orchestral symphonies also include organ), even though his solo organ works have remained popular in the repertory. Following an introduction that surveys the relevant extant literature, Chapter 1 situates the symphonies in the context of Widor’s long and successful professional career and within the context of symphonies by other composers in the French Romantic symphonic tradition, such as Gounod, Saint-Saëns, and Franck. In Chapter 2, I study Widor’s orchestration manual and its relation to orchestration in the five orchestral symphonies and his Symphony for organ and orchestra, Op. 42bis, a transcription of three movements from his symphonies for solo organ (Nos. 2 and 6). Chapter 3 provides a substantial study of form, addressing thematic layout and key scheme, both within and across movements, as well as the borrowing of pre-existing musical material from sacred sources (Gregorian chant and Lutheran chorale). The chapter chronicles two trends from early symphonies to late: the increasing complexity of inter-movement (cyclic) thematic relationships and the increasing sense that the final movement is the culmination of a formal trajectory that spans the entire symphony. I make a case that in the later symphonies Widor is experimenting with two-dimensional sonata form (Vande Moortele 2009), in which a multi-movement work has sonata forms within one or more individual movements and a large-scale, overarching, sonata-like trajectory that encompasses the whole piece. Chapter 4 addresses performance issues. It surveys Widor’s own comments on performance practice, provides practical considerations for performing symphonies with organ, and studies tempi choices in Widor’s recorded performance of his famous organ Toccata. The chapter concludes with a case study of Symphony No. 1, which relates form to performance, compares tempi strategies in extant recordings of the work, and communicates some personal performance ideas based on my experience performing the work with the University of Toronto Symphony Orchestra. Chapter 5 is a brief epilogue that reviews the main conclusions of the thesis and points to ideas for future research.

Keywords: orchestra
organ
performance
sonata form
symphonies
Widor
Advisor: Sallmen, Mark
The Coloniality of Data Work: Power and Inequality in Outsourced Data Production for Machine Learning

Many research and industry organizations outsource labour-intensive processes of data generation, annotation, and algorithmic verification—what this dissertation refers to as data work—to workers worldwide through digital platforms. A subset of the gig economy, these platforms consider workers independent users with no employment rights, pay them per task, and control them with automated algorithmic managers. This dissertation focuses its study on the data worker population in Venezuela—a Latin American country experiencing a socioeconomic crisis exacerbated by the COVID-19 pandemic and where a significant number of data workers in the Global South are located—to understand the coloniality of data work, or the historical patterns of power that define contemporary data production. This dissertation looks at how power imbalances are reproduced in outsourced data work through a configuration of actions, discourses, and objects—the “data production dispositif”—by which platform companies profit from marginalized workers in a socioeconomic condition characterized by high disembeddedness, or a lack of regulations and protections on the population. Social inequalities are reproduced through the data production process and local worker communities mitigate these power imbalances by relying on the support of family members, neighbours, and colleagues online. Furthermore, the data production dispositif ensures that workers’ voices are suppressed in the data annotation process through algorithmic management and surveillance, resulting in datasets generated exclusively by clients, with their worldviews encoded in algorithms through training. The coloniality of data work is thus characterized by an extractivist method of generating data that privileges profit and the epistemic dominance of those in power. This dissertation argues that data production is a process and that the quality of data and artificial intelligence algorithms depend on incorporating a plurality of workers’ voices and the decommodification of their labour away from market dependency. This process is multifaceted and requires the responsibility of the computing industry, policy centred on worker communities, and support of local worker-led initiatives.

Keywords: coloniality
crowdsourcing
data
machine learning
platforms
Advisor: Delfanti, Alessandro
Identifying Novel Vulnerabilities of KRAS using the MaMTH and SIMPL Assays

KRAS is a plasma membrane anchored small GTPase that serves as an ON/OFF switch in many cell signalling pathways. When mutated, KRAS assumes a conformation that is constitutively active, resulting in unchecked signalling that promotes tumorigenic phenotypes such as uncontrolled cell proliferation. Oncogenic KRAS is detectable in approximately 20% of human cancers. Yet, only one KRAS variant, KRAS G12C, has been identified as a therapeutic target, whereas other more prevalent or lethal isotypes, such as KRAS G12D or G12V, remain undruggable. Consequently, the objective of this study was to identify novel vulnerabilities of KRAS using two approaches that could be therapeutically exploited. Using MaMTH-HTS, I screened the human ORFeome collection (13,000 human ORFs) for protein-protein interactions (PPIs) of KRAS and identified 113 interactors of KRAS WT, 109 interactors of KRAS G12R, a mutant found in pancreatic cancers, and 42 overlapping interactors. Further investigation revealed KRAS variant-specific sub-networks of interactors with distinct pathogenicity, function, or subcellular localization. Orthogonal validation of PPIs revealed that SLC26A2, a multifunctionalanion exchanger, showed a strong interaction signal with KRAS WT rather than KRAS G12R, which may have biological implications. Parallel to this strategy, I collaborated with two pharmaceutical partners to identify KRAS G12V inhibitors. In collaboration with Evotec AG, a large-scale drug screen of 200,000 compounds using the MaMTH-DS (MaMTH Drug Screening) assay was conducted, and 39 molecules were identified for further study. Second, in collaboration with Cyclica Inc., an AI-augmented virtual screen of the Enamine REAL space of 1.3B compounds was performed to select molecules with a high probability of specifically binding KRAS G12V. Sixty-three AI-selected molecules were synthesized de novo, and their activity against the KRAS G12V-CRAF PPI was evaluated using MaMTH-DS. I identified four molecules that disrupted this interaction, one of which reduced the viability of cancer cell line moles. Overall, this study has uncovered several biological and chemical vulnerabilities of KRAS that may become therapeutically exploitable for the treatment of KRAS-driven cancers.

Advisor: Stagljar, Igor
Work-based Learning in the Ugandan Secondary School Curriculum

Beginning in 1997, the Ugandan government introduced different initiatives that have had the primary goal of updating and expanding the country’s secondary school system. This was aimed at improving the performance of students and developing a curriculum able to cultivate the skills and competences of students. Work-based learning (WBL) was situated as an alternative form of learning able to serve as the foundation of national development. This study delved into the value of WBL by carrying out an investigation in 10 secondary schools in northern Uganda, with 10 learners and 10 teachers. It also concentrated on the relationship that is found between anti-colonial education and WBL. Through the usage of a mixed research methodology, data was collected between January 2019 and June 2019. The objectives of the study were to investigate the experiences of Ugandan secondary teachers and learners participating in WBL. Attention was given to the study of the implementation of WBL and its role in the skills development of learners, its potential benefits, and the potential barriers to its implementation. The target population was secondary school students and teachers in northern Uganda and the study used stratified random sampling. The study showed that there is an absence of a strong WBL infrastructure, and that there is a need to work on the areas of job shadowing, apprenticeship, and internships. Recommendations include a need for policy changes, development of diverse pedagogical tools, career interests, fostering of business community partnership, professional development, and the need to cultivate indigenous knowledge. In conclusion, there is a need for an overhaul of the secondary school curriculum in Uganda.

Keywords: Experiential learning
Work Based Learning
Advisor: Wane, Njoki
The Development of Persona as a Tool for Online Learning

The purpose of this thesis was to explore if learner personas could be used as a tool for learner-centred online learning. Personas can be a powerful design tool when applied to online learning design and could assist instructors in envisioning and planning for distinct “archetypes” of online learners and is one way that can be used to characterize the needs, goals, experience and accessibility requirements of learners (Lilley et al., 2012; Pyper et al., 2011; Rogers et al., 2011; Ward & Parr, 2010). The study intended to create a compelling and approachable representation of data based on representative data from observations made while doing a comprehensive case study. Personas can be tools or a broader lens that instructors can use to extend or complement their teaching, adding to the constructivist and collective knowledge of the group, ideally interrogating ideas within the online environment (Dalley-Hewer et al., 2012; Garrison et al., 2001; Scardamalia & Bereiter, 2005). Accordingly, a course developed as part of a COI should provide a space for “meaningful discourse and [to] develop personal and lasting understandings of course topics” (Garrison et al., 1999; Oztok et al., 2014; Rourke & Kanuka, 2009). This study found that using distinct personas––as a way to envision the learner’s individual journeys and engagement patterns––can guide the instructor’s thoughts about how the learners’ themselves add to their own personal understanding. The personas also offered a way for instructors to dialogue with colleagues in context about similar learners across other course offerings, providing a practical way for instructors and designers to look at their courses from the perspective of the learner (Jonassen et al., 1995; Swan et al., 2009a; Ward, 2010). The study used log-file data from threaded conversations, student participatory behaviours, and student reflective journals, along with instructor interviews and insight from a comprehensive literature review. This contributed to the development of five specific personas, created from specific facts as general archetypes. The next steps in this study included how these findings about one course offering can be translated into future studies and tool development.

Keywords: constructivism
design
learner-centered
pedagogy
persona
professional development
Advisor: Brett, Clare Dr.
Sex and Estrous Cycle Differences on CYP2D in the Brain (vs Liver); Impact on Oxycodone Metabolism and Resulting Analgesia

Sex and estrous cycle differences in opioid analgesia occur in rodents and humans; differences in drug metabolism and resulting drug and metabolite concentrations could contribute. Since numerous opioids are cytochrome P450 2D (CYP2D) enzyme substrates and variation in CYP2D alters opioid drug concentrations and responses, we investigated the sex and cycle differences in oxycodone and metabolite concentrations and resulting analgesia (nociception) in rats. We also explored the impact of CYP2D in the brain (versus liver) on these differences and explored the potential mechanism of hormonal regulation. This was investigated through selective inhibition of CYP2D in the brain using a mechanism-based inhibitor, propranolol (or vehicle), given by intracerebroventricular (ICV) injection 24 hours before testing with oral oxycodone in male and female (in estrus and in diestrus) rats. To explore hormonal regulation, ovariectomized (or sham-operated) females were treated systemically with estradiol, progesterone, or vehicle, followed by ICV propranolol (or vehicle) pre-treatment and oral oxycodone. Analgesia was measured using tail-flick latency, while brain drug and metabolite concentrations were measured in vivo by microdialysis. Across oxycodone doses, females in diestrus had greater analgesia compared to males and females in estrus. Analgesia correlated with brain oxycodone, but not brain oxymorphone or noroxycodone concentrations, or plasma drug or metabolite concentrations. ICV propranolol (versus vehicle) pre-treatments increased brain oxycodone concentrations, and decreased brain oxymorphone/oxycodone drug ratios (an in vivo CYP2D activity phenotype in the brain) in males and females in estrus, but not in females in diestrus. Brain oxymorphone/oxycodone drug ratio was inversely correlated with analgesia. Together, sex and cycle differences were observed in oxycodone analgesia and brain oxycodone concentrations; CYP2D in the brain is a major contributor to these observed differences. Following ovariectomy there was little to no impact of brain CYP2D inhibition on brain oxycodone concentration or analgesia, similar to females in diestrus. The impact of selective inhibition of CYP2D in the brain, on brain oxycodone concentration and analgesia was restored following acute estradiol, but not progesterone, treatment. Sex, cycle and hormone regulation of CYP2D in brain may contribute to the large inter-individual variation in response to numerous centrally acting CYP2D substrate drugs, including opioids.

Keywords: Analgesia
Central drug metabolism
CYP2D
Cytochrome P450
Estrous cycle differences
Oxycodone
Advisor: Tyndale, Rachel