VictorJuiz/thesis huggingface dataset:
Identifying Novel Genes and Pathways Correlated with Group 3 and Group 4 Medulloblastoma Metastasis to the Spine

Medulloblastoma (MB) is a cancer of the cerebellum and the most common childhood brain malignancy. For children with high-risk MB, mortality is nearly always the result of the primary tumour having metastasized to the leptomeninges. This is due to the fact that current therapy for metastatic MB is less effective than that for primary disease. This is a product of the fact that most MB research has focused on primary tumours rather than metastases, due to the low availability of metastatic MB tissues for research, and, until recently, the absence of mouse models of metastatic MB. With greater understanding of primary MB has come a more rounded foundation upon which to build a better therapy. Thus, it is exciting to note that mouse models of MB dissemination now exist, and with these models has come first glimpses of mechanisms that may be driving MB metastasis. In an effort to build upon this new body of knowledge our lab engaged in a process of repeated selection for increased metastasis propensity among spine metastases from mouse patient-derived xenograft (PDX) models of human Group 3 and Group 4 MB. By phenotypically selecting for increased metastasis propensity, we would necessarily also select for increased activity of the genes and pathways necessary and sufficient for increased metastasis propensity, some of which might represent valuable new therapeutic targets. In this manner, we have identified several long non-coding RNAs (lncRNAs) and Cancer Testis Antigen (CTA) genes increasingly transcribed in correlation with metastasis. Further, we have found that their increased transcription is followed closely by the activation of several well- known metastasis pathways. So lncRNAs and CTA genes may represent novel new components of the complex systems regulating MB metastasis.

Keywords: medulloblastoma
metastasis
CTA genes
lncRNA
Advisor: Taylor, Michael D.
Bader, Gary
Biochemical and Genomic Insights into the Translocation of Large Clostridial Toxins across Host Cell Membranes

Large Clostridial Toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells and tissues. Members of the LCT family include C. difficile toxins TcdA and TcdB, P. sordellii toxins TcsL and TcsH, C. novyi toxin TcnA and C. perfringens toxin TpeL. From the 19th century to present day, LCT-secreting bacteria have been isolated from the wounds, blood and organs of diseased individuals, and LCTs have been implicated as the primary virulence factors in a variety of infections, including C. difficile infection and wound-associated gas gangrene. To invade cells and cause infection, LCTs utilize their multi-domain architecture – containing a glycosyltransferase domain (GTD), a cysteine protease domain (CPD) and a receptor-binding and translocation domain (T-domain) – to bind host cell receptors, triggering internalization into acidified vesicles and translocation of the cytotoxic GTD across the endosomal membrane and into the cytosol. The focus of this thesis is on the translocation of LCTs across the endosomal membrane, a process that is essential for intoxication yet remains poorly understood. Using biochemical and genomic approaches, we have determined the membrane-inserting regions within the LCT T-domain that form the putative translocation pore, and have uncovered an evolutionarily conserved translocase that is present in the T-domain of LCTs and distant homologues. We also have shown that LCT homologues are functional translocases of novel, cytotoxic proteins, and may function as plant pathogens in the environment. In summary, this thesis provides new insights into the elusive process of LCT translocation and future perspectives for understanding LCT translocation and LCT homologue function.

Keywords: Clostridia
Toxins
Translocation
Advisor: Melnyk, Roman A
The Effects of Aging on Sensory Feedback Utilization During the Planning of Upper Limb Movements

Previous work on sensorimotor integration for movement planning has mainly focused on visual environments and targets. Further, age-related adaptations to sensorimotor integration for movement planning are seldom explored. In the current dissertation, four experiments were conducted to investigate sensorimotor processes occurring during movement planning to targets of varying sensory modality, in both younger and older adults. They were asked to perform upper limb reaching movements to various target cues in the absence of visual feedback, and reaction time was evaluated as the main outcome variable. The goal of the first experiment was to investigate if target modality modulated movement planning time, and if these effects were different across age groups. The results showed longer reaction times for movements planned to somatosensory targets versus visual or bimodal targets, and these longer reaction times were significantly longer for older adults than for younger adults. The goals of the second and third experiments were to test for any contributing effects known to be affected by aging, such as sensory acuity or movement planning strategy. The results showed that older adults did not appear to have acuity deficits, nor did they plan their movements differently than younger adults to the various sensory cues. The goal of the fourth experiment was to implement a somatosensory perturbation to further investigate sensorimotor processes when planning movements to somatosensory targets. The results showed that somatosensory perturbations to the effector limb caused even further elongation of reaction times, and this effect was greater in older than younger adults. Overall, the current work provides a further look into the age-related differences in somatomotor integration processes, when planning movements to somatosensory targets. It was hypothesized that sensorimotor transformations may be responsible for the delays in movement planning time, as older adults may be mapping all cues into a visual reference frame, regardless of the presence of visual inputs.

Keywords: aging
motor planning
sensory transformation
somatosensory
vision
Advisor: Tremblay, Luc
Essays in Industrial Organization and Banking

This thesis contains three chapters exploring topics related to industrial organization and banking. The first chapter studies how banks compete through interest rates and credit rationing in the U.S. mortgage market. I estimate a structural model of bank competition in interest rates and credit rationing using U.S. mortgage data. I use the estimated model to show how banks optimally trade-off interest rates and credit rationing, and illustrate its policy relevance by examining the magnitude and the form of banks' pass through -- to clients -- of a cut in funding costs. I find that banks pass through their lower funding cost by not only cutting interest rates but also relaxing credit rationing. There is substantial heterogeneity in the pass through in both margins and this is mainly explained by heterogeneity in two different types of banks' costs: funding cost of originating mortgages and cost of processing applications. The second chapter surveys recent papers using structural models to study lending markets from an industrial organization perspective. I show that the papers can be divided into two modeling and estimation frameworks: the discrete choice, differentiated product model framework and the search model framework. The discrete choice model framework is based on seminal work by Einav, Jenkins, and Levin (2012) and is used to study how issues related to adverse selection, moral hazard, and market structure affect lending market outcomes. The search model framework, on the other hand, encompasses a variety of approaches focusing on how search frictions affect lending outcomes. I compare and contrast the two different frameworks and also suggest areas for future research. The third chapter studies the factors that drive mortgage securitization in the U.S. I combine a multinomial probit model of mortgage securitization with unique application-level mortgage data to study how loan- and bank-level characteristics affect bank securitization incentives. Overall, I find that lower mortgage quality and higher bank resource constraints lead to higher mortgage securitization by banks.

Advisor: Aguirregabiria, Victor
I Too Know Why The Caged Bird Sings: Rapping and Spoken Word as Activism and Education

ABSTRACT I have often witnessed how racialized children, youths, and young people have mobilized these practices through their cultural production. Such actions have served to (re)imagine what constitutes literacy, thus making space for more complex, fluid, and robust understandings of the literacy practices of Black youth (Fisher, 2003; Kinloch, 2010; Kirkland, 2013; Rowsell, 2011). The project is a collection of four narrative case studies that examined how four young Black men in the Greater Toronto Area employ spoken word poetry and rapping in their education and activism work. Drawing on New Literacy Studies (e.g., Street, 2003), the rhetoric of cultural production (Gaztambide-Fernández, 2013), and Critical Race Theory (e.g., Ladson-Billings Tate, 1995), I explore how they each created out-of-school educational workshops as a respond to the low self-esteem, depression, and marginalization as well as the creative potential of the racialized youth and children they support in the schools and communities they work within. As such, the two key questions that guided this research are: (a) How do these four Black young men explain their choice to use spoken word poetry and rapping to express their lived realities, including the systemic racism they continue to live with? (b) How do these four Black young men use spoken word poetry and rapping to educate themselves and their communities? Three key themes emerged from the narrative case study data. First, these Black young men engage in the cultural production of rapping and spoken word poetry as a method of expressing and theorizing their emotional lives and lived realities. Their cultural production helped them make sense of and cope with the pain and difficulties they have experienced. Second, the cultural production of these young men counters problematic, monolithic conceptualizations of Black people in Canada. Participants’ critical and creative labour provide counter-narratives to the stereotypical ways that Black youth are regarded. Third, findings highlight how Ebele, Kofi, TD, and Efe created a “new” form of education that supports the healing of racialized children and youths in urban communities, as alternatives to formal educational institutions that often marginalize Black children and youths.

Keywords: Blackness
Gender
Hip-Hop
Masculinity
Poetry
Youth
Advisor: Simon, Dr. Rob
Modeling of Carbon Nanoparticle Formation in Combustion and Pyrolysis Environments and Its Application in the Carbon Black Industry

Carbonaceous nanoparticles such as soot and carbon black (CB) are formed during the incomplete combustion or pyrolysis of hydrocarbons. Soot is a threat to human health and climate change, while CB has diverse applications that depend on the particle morphology, e.g., aggregate structure. Predictive numerical tools capable of estimating the mean particle properties such as the primary particle size, mobility diameter, and particle number density help to prevent the unwanted formation of soot and assist the CB manufacturers to fine-tune their products. This thesis seeks the implementation of an aerosol dynamics model into a plug flow code to simulate the CB synthesis in flow reactors. Inception, surface growth, and coagulation control process yield and agglomerate morphology. New particles are formed by the reversible clustering of polycyclic aromatic hydrocarbons (PAHs) followed by chemical bond formation, i.e., chemical dimerization, and grow with Hydrogen Abstraction Carbon Addition and chemical adsorption of PAHs on the surface of particles. Irreversible PAH clustering and surface adsorption continuously convert more than 90% of the PAH precursors to new particles even in the low temperature (T

Keywords: Carbon Black
Modeling
Morphology Prediction
Oxidation
Soot
TEM
Advisor: Thomson, Murray J
The Latin Past and the Poetry of Catullus

This dissertation examines the relationship of the Latin poet Catullus to the preceding Latin poetic tradition, particularly to the pre-eminent figure of that tradition, pater Ennius. Classical scholarship has long thought the nature of this relationship settled: in a surge of revolutionary force (so goes the story), Catullus and his poetic peers (the “neoterics”) broke violently away from Ennius and the dominant Ennian tradition, turning instead to the recherché Greek poetry of the Hellenistic period for their inspiration. My study complicates this dominant narrative: Ennius, I argue, had a foundational, positive influence on Catullus; Catullan poetry was evolutionary, not revolutionary at Rome. Chapter 1 sets the stage by redefining neotericism: this was a broad poetic movement that included, not just Catullus and his friends (“the neoteric school”), but a majority of the Latin poets writing c. 90-40 BCE. Neotericism, moreover, was an evolutionary phenomenon, an elaboration of second-century Latin poetry. Chapters 2-4 attend to specific Catullan poems that engage closely and allusively with Ennius. Chapter 2 shows how, in poem 64, Catullus reinvents Roman epic on the model left to him by Ennius. Chapter 3 takes up poem 116, which I read as a programmatic statement of its author’s Ennian-Callimachean poetics. Chapter 4 turns to poems 1 and 68: here I demonstrate how Catullus draws on Ennius qua complex cultural authority in order to defend, question, and think through his own identity as a Transpadane-Roman.

Keywords: Catullus
Ennius
Latin poetry
Neoterics
Roman Republic
Advisor: Dewar, Michael
Studies of Stratospheric and Tropospheric Ozone, NO2, and BrO Using UV-Visible Spectroscopy in the Arctic and at Mid-latitudes

This thesis utilizes UV-visible spectroscopy to develop new datasets, study Arctic and urban atmospheric composition, and validate satellite data products. The primary instruments used here (the Ground-Based Spectrometers, or GBSs) have been taking measurements at the Polar Environment Atmospheric Research Laboratory (PEARL, 80.05°N, 86.42°W) since 1999 and 2006, respectively.The GBS dataset, combined with other measurements at PEARL, was used to validate ozone and NO2 measurements from the Atmospheric Chemistry Experiment (ACE) and Optical Spectrograph and InfraRed Imaging System (OSIRIS) satellite instruments. Ozone from all instruments agrees to within 12.0%, while NO2 measurements agree to within 33.2%. There are no apparent systematic changes in the observed differences between the satellite and the ground-based instruments over time. In the winter/spring of 2020, the unusually strong and cold polar vortex led to unprecedented Arctic ozone depletion. Total column ozone was at an all-time low in the 20-year GBS dataset. Chlorine activation inside the vortex was ongoing until the end of March, resulting in mean chemical ozone loss of 111-127 DU (27-31%) over Eureka, which represents similar absolute loss and greater relative loss compared to that in spring 2011. GBS BrO partial columns were used to investigate Arctic tropospheric ozone depletion during four bromine activation seasons. BrO enhancements show two modes differentiated by air mass history. Contact with the snowpack on sea ice corresponds to increased BrO for one of these modes only, while the other mode is related to storms that almost always bring bromine-enriched air to Eureka. The presence of coarse mode aerosols (likely sea salt aerosol) is a necessary and sufficient condition for observing BrO at Eureka, indicating that sea salt aerosols play an active role in bromine activation. A tropospheric NO2 profile dataset was retrieved from 2018-2020 Pandora spectrometer measurements to investigate NO2 pollution in Toronto. Retrievals using optimal estimation and parametric algorithms show good agreement. Seasonal and diurnal variability is apparent in both the NO2 partial column and surface concentration datasets. During the spring 2020 COVID-19 lockdown in Toronto, daily maximum NO2 values showed substantial reductions.

Keywords: Arctic
NO2
PEARL
stratospheric ozone
tropospheric bromine activation
UV-vis spectroscopy
Advisor: Strong, Kimberly
Identification and Characterization of the Role of REEP5 in Sarco-Endoplasmic Reticulum Formation, Maintenance, and Function in Cardiac Muscle

Heart failure (HF) remains the most rapidly rising cardiovascular disease and the leading cause of inpatient hospitalization worldwide, with costs exceeding $30 billion dollars annually in North America. While many key regulators of heart function have been identified, yet effective therapies aimed at healing or reversing the progression of HF remain restricted due to the complex nature of the disease and a lack of understanding of the functional membrane proteome of the heart. Here, we created a blueprint of all critical membrane and membrane-associated proteins in the heart by mapping several transcriptomic- and proteomic-based datasets against our mass spectrometry dataset of membrane-enriched protein clusters from human fetal and mouse neonatal cardiomyocytes. We identified 173 membrane-associated proteins that are conserved among eukaryotic species, cardiac-enriched, and have not been previously linked to a cardiac phenotype. These poorly annotated cardiac-enriched membrane proteins represent excellent candidates in follow-up studies aimed at elucidating the underlying molecular mechanisms of cardiomyopathies and HF. One of the highly ranked, poorly annotated, and cardiac-enriched membrane proteins was REEP5, a sarco-endoplasmic reticulum (SR/ER) membrane protein. In a follow-up study we tested the hypothesis that physiological REEP5 expression is important for cardiac SR/ER organization and heart function. In vitro REEP5 depletion in isolated functional adult mouse cardiomyocytes resulted in SR/ER membrane vacuolization and impaired cellular processes including activated cardiac ER stress pathways and dysregulated Ca2+ cycles. Subsequent in vivo CRISPR/Cas9-mediated REEP5 loss-of-function zebrafish mutants showed sensitized cardiac dysfunction upon pharmacological HF induction. Similarly, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse resulted in lethal diastolic cardiac dysfunction with dilated cardiac chambers and reduced ejection fraction. Altogether, these results demonstrated 1. Our cardiomyocyte membrane proteome dataset proves instrumental to studies aimed at characterizing novel regulators of heart function and identifying potential heart disease markers and/or therapeutic targets, 2. The critical role of REEP5 in cardiac SR/ER organization, embryonic heart development, and heart function.

Advisor: Gramolini, Anthony O
Early Theravāda Place-making in the Shadow of Mount Meru: Negotiating the Architecture, Space, and Landscape of “Buddhist Terraces”/Praḥ Vihār at Angkor Thom, Cambodia c. 13th-16th Centuries

This Dissertation explores the material remains of the religious transition from Brahmano-Buddhist practice to Theravāda Buddhism of the Angkorian Empire (802-1431 CE) which occurred within and surrounding the urban citadel of Angkor Thom between the 14th-16th centuries. The study of this major social and political transformation is based on an analysis of the remains of wooden prayer halls, called “Buddhist Terraces” or praḥ vihār, emblems of less centralized religious practices and the institutionalization of a Theravāda-aligned saṅgha in Cambodia. In the absence of inscriptions following the end of the 13th century, anthropological approaches to landscape, memory, ritual, and place-making provide the analytical framework for the interpretation of Angkor Thom’s Theravāda Buddhist constructions and the resulting politico-religious changes across the urban landscape. Two seasons of survey and one of excavation revealed an architecturally diverse array of over seventy praḥ vihār within Angkor Thom alone, built in reference to previously constructed urban infrastructure such as roads, canals, city blocks, and earlier ritual complexes of unidentified affiliation. In turn, my analysis identified that certain architectural forms and the functions they afforded directly correlated with pre-Theravāda ritual practices and building technologies. Significant Brahmano-Buddhist temples such as the Bayon and Western Prasat Top were also architecturally and ritualistically transformed by the founding of praḥ vihār in the immediate vicinity of these monuments, as well as by the carving of new iconography reflective of growing Ayutthayan geopolitical influence. This reformation of the landscape created new ritual centers within the old and endowed earlier structures with new religious purpose, establishing “foci of memory” across the landscape. Such strategies of place-making maintained the sacrality of Angkor Thom as an integraed cosmographic urban center. The remaking of Angkor Thom’s Theravāda religious landscape, however, was the negotiated outcome of competing factions such as centralizing state institutions and quasi-independent monastic communities. My thesis posits that regardless of the societal and material changes that accompanied Theravāda Buddhism, the “temple” tradition which materialized Angkor’s religious pre-eminence witnessed considerable continuity through time. This tradition is believed to have transcended key epochal breaks including the gradual dissolution of Brahmano-Buddhism as an imperial institution. Ultimately, this Dissertation provides the first systematic investigation of a distinctive Theravāda Buddhist landscape that reinvented Angkor Thom beginning in the late-13th century.

Keywords: Angkor
Archaeology
Cambodia
GIS
Landscape
Theravada Buddhism
Advisor: Swenson, Edward R
Miller, Heather M.L.