VictorJuiz/thesis huggingface dataset:
Recording the Work of a World: Anne Charlotte Robertson’s Diary Film and the Domestication of Cinema

Anne Charlotte Robertson’s Five Year Diary is a multi-modal project that comprises cinematic, written, audio and food diaries that span forty years of the artist’s life. Robertson would come to understand the work in different ways: as a weight loss diary; as a “trousseau” for her “one true love,” to present to him when they meet; and, in periods of psychic breakdown, as a film that would encompass the history of the entire world. This dissertation takes up these three ways of framing the project to describe and make sense of Five Year Diary. In doing so it positions Robertson more prominently in terms of two scholarly histories: the history of feminist art in the United States, and the history of experimental film, particularly in the form of personal or diary filmmaking. When Robertson begins her multi-modal Five Year Diary in 1981, she is doing so at the tail-end of the women’s liberation movements that coursed through the United States in the 1960s and 1970s. The diary project takes up many of the concerns of second wave feminism, including gendered labour, women’s time, and feminist desire. Robertson thus uses the diary, which historically has often been one of the only forms easily accessible to women, for the project of feminist world-making that Five Year Diary engages in. Her intervention here lies on two fronts. First, as an artist that makes of the most extensive and conceptually rich use of the diary within feminist art and filmmaking; and second, in her veneration of domesticity and heterosexual marriage, as forming part of an alternative history of second-wave feminism. It is Robertson’s treatment of the domestic that forms one axis of her intervention in the history of experimental film: by collapsing the labour of the home and the labour of the filmmaker, hers is, I argue, the true “domestication of cinema” that David E James attributes to Stan Brakhage. The second axis relates to form and how the diary film has traditionally been sketched in experimental scholarship, as fragmented, often formless, an assertion Robertson’s rigorous formalism and carefully pieced together aesthetic vision undermines.

Keywords: Anne Charlotte Robertson
diary
labour
mental illness
multi-modal
world-making
Advisor: Price, Brian
Ontario’s Graduate Certificate Programs: An Exploration into Colleges’ Perspectives and Students’ Decision-making Processes

This mixed methods study explored the nature and role of one of the credentials offered by the Colleges of Applied Arts and Technology (CAATs) – graduate certificates – in school to work transition of Ontarians and it explored students’ decision-making processes when enrolling in these programs. The role of education in human capital theory underpins specific ways qualifications can be used for economic progress; however, in liberal market economies where an education logic dominates, such a role is not clearly defined. The conceptual frameworks that grounded my study included Iannelli and Raffe’s (2007) concept of transition systems, differentiation (cited in Parsons Platt, 1973, Rhoades, 1983), Perna’s (2006) model of student choice, and Reverse Transfer (cited in Clark, 1960; Hossler et. al, 2012). These were used to analyze data from: 335 program websites; statistical data from the Ontario government and Colleges Ontario documents; and, interviews with six institutional leaders, five program coordinators from five selected CAATs (out of 24), four third-party professionals and 17 students. The quantitative data included all graduate certificates offered by 22 English language Ontario CAATs in fall 2017. The conclusions drawn from this study suggest that graduate certificate programs are the only post-diploma credential offered by the CAATs where degrees are one of the key entry requirements. Due to the government’s policies and market pressures, these programs are relatively homogenous which contributes to isomorphism in Ontario CAATs. These programs produce highly positive labour-market outcomes and this study’s participants considered these program curricula to be closely linked with the job market. However, the system-wide data show that more than half of the graduates get jobs outside their fields of study. Participants perceived the level of these programs to be higher than baccalaureate programs and students enrolled in these programs to gain applied skills which were not offered by their previous education. This study contributes to the existing literature on role of qualifications in liberal market economies and may inform policy, improve program design and delivery, and help increase the understanding of role of these credentials in Ontario’s transition and higher education systems.

Keywords: Differentiation Framework
Graduate Certificates
Human Capital Theory
Reverse Transfer
Student Decision-making
Transition Systems
Advisor: Wheelahan, Leesa
New Methodologies for the Synthesis of Aminoboronic Acids and Tetrahydroquinolines

There has been a rising interest in aminoboronic acids since their medicinal properties have been realized. Thus, new strategies for the synthesis of α- and β-aminoboronic acids would enable the discovery of bioactive molecules. Tetrahydroquinolines are also privileged scaffolds that are commonly found in natural products and therapeutically relevant molecules. This thesis reports the use of amphoteric boron carbonyl reagents in the synthesis of α- and β-aminoboronic acids. Following the introduction, Chapter 2 discusses the development of the Ugi four-component reaction with α-boryl isocyanide to furnish peptidomimetic α-aminoboronic acids. These molecules were shown to be bioactive against human caseinolytic protease P. In Chapter 3, the preparation of various β-aminoboronic acids from α-boryl aldehydes is described such as boryl enamide synthesis, boryl-Strecker reaction and an Ugi/aza-Wittig multicomponent reaction. The boryl enamides were highly useful synthetic intermediates and enabled the construction of tetracyclic lactams. The β-aminocyano(MIDA)boronates generated from the boryl-Strecker reaction were found to be potent and selective inhibitors of serine hydrolase α/β-hydrolase domain 3. Lastly, Chapter 4 presents a novel strategy for the synthesis of Povarov-type products using photocatalysis.

Keywords: boron
caseinolytic protease P
inhibitors
multicomponent reactions
photochemistry
serine hydrolases
Advisor: Yudin, Andrei K.
Latent-variable models for drug response prediction and genetic testing

High-throughput DNA sequencing and related biotechnologies revolutionized our understanding of human genomics and diseases with genetic component, particularly of cancer -- one of the leading causes of death world-wide. Despite the progress in cancer research and availability of over 150 FDA-approved anti-cancer drugs, the cancer treatment is often unsuccessful. Identifying the best cancer treatment using computational models to personalize drug response prediction holds great promise to improve patient’s chances of successful recovery. Unfortunately, the computational task of predicting drug response remains very challenging. In this thesis I develop a deep latent-variable machine learning model with amortized variational inference that improves accuracy of drug response prediction over the currently used models. Besides increased expressiveness of this model thanks to parameterization by neural networks, the achieved improvement stems from integration of drug-induced perturbation profiles, a resource not fully utilized before. Clinical trial datasets of cancer treatments which also include genomic characterization of the tumours are small and scarce, therefore for the vast majority of drugs only responses in pre-clinical biological models are available. To this end, I assess applicability of popular domain adaptation approach, based on domain-invariant representation learning, to the drug response prediction task. I conclude that necessary conditions of successful domain adaptation are often not satisfied in the available datasets and as such many current methods are misguided. Last but not least, in this thesis I also contribute to the area of non-invasive prenatal testing. Using a hidden Markov model I propose a method for analysis of cell-free DNA fragments isolated from maternal plasma that also contain admixture of DNA fragments derived from the fetal genome. Here presented method is a first proof-of-concept for non-invasive sub-chromosomal CNV detection.

Keywords: domain adaptation
drug response prediction
hidden markov model
machine learning
non-invasive prenatal testing
variational autoencoder
Advisor: Goldenberg, Anna
Brudno, Michael
Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression

Cell-based therapies hold great promise for the future of modern medicine. A large number of injuries and diseases that are currently not possible to cure or effectively treat could benefit from therapeutic approaches where healthy cells are transplanted into the disease/injury sites. However, before stem cell-based therapies can become a reality, several major obstacles need to be overcome. One of the most pressing is the rejection of allogeneic transplants. Although patient-derived induced Pluripotent Stem Cells (iPSCs) may offer an appealing solution, the derivation, expansion and quality control needed for application in clinical settings is prohibitively expensive and time-consuming. This thesis describes the creation of pluripotent stem cell lines that are accepted as allografts without the need for systemic immune suppression. We genetically altered murine Embryonic Stem Cells (mESCs) to express a set of eight immune-modulatory genes at high levels. Transplantation of these cells into allogeneic hosts resulted in the successful formation of teratomas. Most importantly, this immunologic acceptance was achieved without the administration of immune-suppressive drugs. We envision that this approach will allow the same cell line to be used for transplantation into any individual. Rigorous testing and quality control would be cost-effective and cells could be made available as “off the shelf” products.

Keywords: allograft tolerance
immune evasion
stem cells
tolerance
transplantation
Advisor: Lye, Stephen
Wheeler, Michael
Interneuron Specific (Dis)Inhibitory Control in the CA1 Hippocampus: A Single-cell Computational Study Spanning In Vitro and In Vivo Virtual Network Contexts

The hippocampus, an area of the brain responsible for memory formation, has a large diversity of different inhibitory neuron types. Because inhibitory neurons are fewer than excitatory neurons, they are relatively less studied. In this thesis, I study one such neuron type, the interneuron specific 3 (IS3) cell. IS3 cells belong to a neuronal class that specializes in the inhibition of other inhibitory neurons, including oriens lacunosum moleculare (OLM) cells, which suggests a primary role in disinhibitory control of excitatory neurons. In vivo, it is unknown when IS3 cells become activated and how they contribute to circuit function. I use computational modelling techniques to create in vivo-like scenarios for IS3 cell models, to predict their activation under various patterns of behaviourally-relevant spiking inputs. Specifically, I find that IS3 cells require approximately balanced inhibition and excitation to generate in vivo-like states that remain sensitive to additional inputs. During these states, their inputs dictate that they become activated during the rising to peak phases of theta rhythms as well as during sharp wave- associated ripples, though inclusion of inhibition dampens their recruitment during the latter. Analysis of experimental data confirms their activation during the rising to peak phases of theta rhythms, however only towards the end of theta-run epochs. As well, IS3 cells are not active during sharp wave-associated ripples, suggesting the presence of additional inhibitory mechanisms. Further computational modelling predicts that IS3 cell activation primarily lengthens the interspike intervals of OLM cells rather than elicits post-inhibitory rebound spiking. This suggests that IS3 cell control over OLM cell spiking is mainly facilitated through disinhibition of pyramidal cells and not direct connections from IS3 cells to OLM cells. Lastly, the excitability of IS3 cells is altered during aging. Using computational modelling I predict that the electrical changes are due to alterations in fast delayed rectifier potassium channel expression. While experimental recordings of these currents does not confirm significant changes during aging, considerable conductance variability suggests more expression modulation of these channels. Altogether, this work provides insights into the biophysical mechanisms through which IS3 cells are active and contribute to circuit function in vivo.

Keywords: Computational Neuroscience
Disinhibition
Hippocampus
Interneurons
Advisor: Skinner, Frances K
Physiological Stress Reactivity in Childhood Leukemia and Lymphoma Patients and an Exploration of Neurological and Behavioural Characteristics Associated with Stress Regulation

Significant stress during childhood is associated with health and functional consequences related to dysfunctional physiological stress regulation. Childhood cancer is a stressful experience with indirect evidence of altered regulation of the many systems integrated for appropriate stress regulation. No studies have investigated stress reactivity in this population, however evidence of altered i) physiological stress signalling, ii) neurological structure and function, and iii) coping characteristics, including physical activity and fitness, and psychosocial function, have been reported. To investigate this, 15 childhood cancer patients ages 8-18 who had completed treatment in the previous 6-36 months, and 16 age and sex matched healthy controls were recruited to participate in the study. Participants completed psychological stress testing (TSST- C), resting structural brain scans (DTI), a submaximal aerobic test, in-magnet exercise using 31P MRS, as well as questionnaires relating to physical activity habits, psychological resilience, quality of life, and stress experiences. Salivary samples for cortisol, sAA, and cytokines, as well as, HR, and ratings of perceived stress were collected at 3 time-points prior to (home, -15 minutes, -0 minutes) and 3 time-points following (+0 minutes, +15 minutes, +45 minutes) the TSST-C. No group or interaction effects were observed for HPA reactivity, but patients exhibited lower sAA and HR responses, as well as higher overall IL-8 and TNFa concentrations. Resting DTI showed significant differences between groups for mean FA, MD, RD, and AD of corticolimbic regions analysed. Regional FA differences were also found in the bilateral amygdalae, hippocampi, and interhemispheric limbic lobe. Lower estimated relative VO2peak and HR responses to exercise, as well as ATP regeneration by oxidative phosphorylation and anaerobic glycolysis, and physical activity were found in the patient group, with moderate to large effect sizes. No significant differences were found between groups for psychological wellbeing. These findings indicate that childhood leukemia and lymphoma patients have evidence of blunted SAM reactivity to psychological stress, and neurological and behavioural characteristics that may increase their risk of stress dysregulation and associated adverse health and functional outcomes.

Keywords: 31P MRS
Diffusion Tensor Imaging
Late-effects of childrens cancer
Physical activity
Stress reactivity
Advisor: Wells, Greg D
Apollo in Thebes: Using a Genetically Encoded Family of Sensors to Study NADP+ Dynamics using Deep Learning

Accumulation of reactive oxygen species (ROS) lies at the core of many diseases including cardiovascular disease, neurological disorders and type 2 diabetes (T2D). In turn, ROS is scavenged through antioxidant pathways powered via intracellular NADPH/NADP+ redox. The relationship between NADPH/NADP+ redox and ROS accumulation is particularly important to T2D as there is evidence that both ROS and NADPH/NADP+ are under looser regulatory control due to their roles as signaling molecules in the pancreatic beta-cell. Understanding how these dual roles contribute to beta-cell dysfunction under metabolic stress is therefore critical to an etiological understanding of the disease. Unfortunately, a lack of suitable NADPH/NADP+ redox sensors have left this field understudied. To that end, we use a novel application of fluorescence polarization (Apollo) to develop the NADPH/NADP+ redox sensor Apollo-NADP+ and adapt it for various subcellular compartments including the mitochondria and the nucleus. Using this sensor, we were able to show that significant NADPH/NADP+ depletion precedes ROS accumulation, which highlights the importance of NADPH/NADP+ as a tool to study the mechanisms behind ROS accumulation. Using mitochondrial-targeted Apollo-NADP+, we were also able to identify the mitochondria as a root of NADPH/NADP+ dysfunction under lipotoxicity. Further investigation of these results in the context of beta-cell heterogeneity requires both a high-throughput imaging and a high-throughput analysis platform. High-throughput imaging was accomplished through the creation of a custom, three-colour, widefield polarization microscope, while high-throughput analysis was accomplished through the Thebes analysis pipeline, which used deep learning in order to split the tasks into: cell boxing, cell masking, and subcellular segmentation. Although performing widefield imaging for Apollo sensors requires additional optimization, we were able to demonstrate some key results including apparent cell heterogeneity in the beta-cells in dispersed islets. Overall, this project furthers the field of sensor design through the Apollo family of sensors as well as providing a set of tools that can be used towards the study of NADPH/NADP+ redox beyond the context of T2D.

Keywords: Deep Learning
Fluorescence Anisotropy
Microscopy
NADPH/NADP+ Redox
Type 2 Diabetes
Advisor: Rocheleau, Jonathan V
Aeroacoustics of Shallow Cylindrical Cavities with Specific Application to the Inter-wheel Region of Aircraft Nose Landing Gears

Cylindrical cavities located on the interior sidewalls of aircraft nose landing gear wheels generate high amplitude tones when subject to grazing flow at aircraft approach speeds. These geometries consist of two, closely spaced shallow cavities, with depth-to-diameter ratios typically less than h/d

Keywords: Aeroacoustics
Aerodynamics
Cavity
Landing Gear
Advisor: Ekmekci, Alis
Rhodium-Catalyzed Enantioselective Desymmetrizations of Oxabicyclic Alkenes and Alkene Difunctionalization via Nickel-Catalyzed Arylcyanation

The synthesis of heterocycles using transition metal catalysis is a topic of broad interest in the field of organic chemistry. Transition metal catalysts allow many diverse bond disconnections to be realized, allowing for many ways to assemble heterocycles. Many of the transformations developed in the Lautens group are aimed at atom economical bond construction processes that streamline synthesis and minimize waste. The arylcyanation reaction and the asymmetric ring opening (ARO) reaction are two examples of methods developed in our group that embody this design principle. Chapter 1 of this thesis describes the development of a nickel-catalyzed arylcyanation reaction for the synthesis of 3,3-disubstituted oxindoles. This method was inspired by our work on the palladium-catalyzed arylcyanation reaction, originally developed to address challenges in the formal synthesis of (+)-corynoline. This nickel-catalyzed reaction uses an air-stable catalyst precursor to achieve a highly practical synthesis of a nitrile-containing oxindole via a domino Heck-cyanide capture cascade. Derivatizations of the nitrile group affords a series of novel heterocyclic scaffolds. Chapter 2 details the discovery and development of a novel enantioselective cycloisomerization reaction of oxabicyclic alkenes. Our work on developing the intramolecular asymmetric ring opening reaction led to the discovery of a novel epoxide synthesis. Specifically, when bridgehead substituted oxabicyclic alkenes with non-nucleophilic side chains are reacted with the [Rh(cod)2]OTf/PPF-PtBu2 catalyst in the absence of an external nucleophile, chiral epoxides are obtained. The synthesis of epoxides through cycloisomerization reactions possesses 100% atom economy and avoids the use of external oxidant. Chapter 3 describes an asymmetric ring opening reaction, specifically to address gaps in the methodology concerning amine nucleophiles. We were inspired by our group’s previous attempts to use amino acid derived nucleophiles in the ARO reaction. We developed a way to incorporate amino acids into the ARO reaction by employing their 2-nitrobenzenesulfonamide (nosyl) derivatives as pronucleophiles. Intriguingly, we observed a divergence in reactivity between the diastereomeric hydroxyester products, in that one diastereomer was capable of lactonization and the other was not. This led to the enantioselective synthesis of chiral oxazinones, which are similar to the naphthoxazine class of compounds which possess dopaminergic activity.

Keywords: Catalysis
Enantioselective
Heterocycles
Nickel
Rhodium
Ring Opening
Advisor: Lautens, Mark
Tracing the Distribution of Pb and Trace Elements in the Canadian Arctic from the Atmosphere to the Ocean

Trace elements (TEs) play important roles in biogeochemical processes in the Arctic and understanding their cycling along with their isotopes will help us understand better the warming induced changes in the Arctic. This dissertation measured Pb, its isotopes and other TEs in aerosols and seawater samples collected in the Canadian Arctic. Lead and its isotopes are useful particulate source tracers and can be used to understand particulate contaminant inputs and oceanic circulation. Iron is also evaluated because it is an important micronutrient for primary production in the ocean. This study shows that anthropogenic aerosols from Europe and Russia (Eurasia) still dominate during the Arctic Haze period (winter–spring) and particulate pollution levels are relatively stable in the Arctic since the 2000s. This study also traced the anthropogenic Pb from aerosols to the Canadian Arctic seawater using Pb isotope measurements. Historic Eurasian Pb with distinctively low 206Pb/207Pb (

Keywords: aerosols
Arctic Ocean
Baffin Bay
Canadian Arctic Archipelago
trace elements
trace metal isotopes
Advisor: Bergquist, Bridget