VictorJuiz/thesis huggingface dataset:
Synthesis and Reactivity of Electron-deficient Boron Species

The reactivity of boron-containing molecules of extreme electrophilicity has been minimally explored in comparison with other aspects of fundamental boron chemistry. This dissertation describes research into the fundamental reactivity and bonding of the electron-deficient boron compounds of different molecular charges (0 or +1) and electronic multiplicities (1 or 2). Depending upon their substitution pattern, highly Lewis acidic boron reagents can participate in unusual reactivity. Borocyclic radicals and diamagnetic heterocyclic boroles were prepared in hydroboration and frustrated Lewis pair hydrogenation reactions of redox-active o-iminoquinone and α-diimine ligands and highly electrophilic boron reagents. Hydride-substituted boranes were found to stoichiometrically react with strong aliphatic carbon–fluorine bonds. The net transformation was found to depend on the natures of both the fluorinated substrate and the hydridoborane. For highly electrophilic boranes, a dehydrofluorination or boryldefluorination reaction was observed, whereas hydrodefluorination was found for less electron-deficient boranes. The use of an auxiliary Lewis acid initiator was also briefly explored in carbon–fluorine bond reduction. The synthesis and reactivity of uncommon, two-coordinate borocations was systematically explored. A rare carbon-substituted borinium cation was prepared or generated as the salt of various anions and used in reactivity studies. The reactivity of organo(amino)borinium cations was found to preferentially involve boron–carbon bond insertion over boron–nitrogen bond insertion. A diorganoborinium cation was investigated in frustrated Lewis pair as well as frustrated radical pair chemistry. The formation of an unprecedented diboranium cation in reactions of the borinium cation with reducing agents was observed. Reactivity of the diboranium cation with small molecules indicated both boronium- and borinium-like reactivity. Extension of the diboranium cation synthesis to other boron reagents furnished an unusual triboron(8) cation. Investigations of boron–boron bonded reagents in diboranium synthesis unexpectedly produced an isolable and highly-substituted pentaborane(9) compound, likely via boron(I) intermediates. Reactions of hydridoborane compounds were generally found to undergo redox chemistry in reactions of tetraaryldiborane(4) reagent. Analysis of related reactions involving dihydrogen show previously undocumented similarities. Collectively, these findings show new modes of reactivity for well-known boron reagents and provide strong motivation for further studies of electron-deficient boron compounds.

Keywords: Boron
Cations
Frustrated Lewis Pair
Lewis acid
Main group chemistry
Radicals
Advisor: Stephan, Douglas W
Elucidating the Mechanism(s) of Action of Anti-Erythrocyte Antibodies in a Murine Model of Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder that causes thrombocytopenia (decreased platelet numbers in the blood) primarily due to the presence of antiplatelet autoantibodies. Anti-D therapy (treatment with an antibody against the Rhesus-D factor on erythrocytes) has been proven to ameliorate ITP but as a human-derived product, it is limited in quantity and carries the potential risk of transferring emerging pathogens. Additionally, the US Food and Drug Administration has issued a black box warning for potentially serious adverse effects in ITP patients, including anemia, fever and/or chills. Therefore, there is incentive present for developing a safe and effective recombinant replacement that mimics the therapeutic activity of anti-D. Thus far, monoclonal anti-D antibodies have only had limited clinical success and better knowledge of its mechanism is required to accelerate the development of anti-D alternatives. This thesis documents studies that evaluated multiple anti-erythrocyte antibodies (as surrogates for anti-D) in murine models of ITP in order to provide insight regarding their mechanism(s) of action. Results indicate that adverse events such as anemia and temperature flux, which can be indicative of inflammatory activity, are not required for ITP amelioration; thus demonstrating that certain toxicities associated with anti-D therapy are independent of therapeutic activity and have the potential to be minimized when developing and/or screening synthetic alternatives. Additionally, it was also shown that the ability of the anti-erythrocyte antibodies to ameliorate murine ITP in vivo is correlated with, and therefore can be predicted by, their ability to mediate erythrocyte phagocytosis and inhibit platelet phagocytosis in vitro. The data suggests that the inhibition of in vitro platelet phagocytosis may prove to be a valuable tool for testing the functionality of erythrocyte-specific antibodies and screening likely candidates for clinical use in ITP. Mechanistically, evidence is provided demonstrating that anti-erythrocyte antibodies do not lead to a decrease in the expression level of the activating receptor FcγRIIIA on splenic macrophages, but instead are likely exerting their therapeutic activity through a direct competitive blocking mechanism. The results provide substantial support for the mononuclear phagocytic system (MPS) blockade hypothesis as the primary mechanism of action in anti-erythrocyte antibody-mediated ITP amelioration.

Advisor: Lazarus, Alan H
Individual and Statistical Characterization of the Giant Exoplanet Population

The field of observational exoplanet astronomy has seen tremendous progress over the span of only a few decades. Now, we find ourselves at the dawn of a new era: the characterization of distant worlds. Novel observational methods and statistical techniques allow us to explore not only the trends in bulk properties within the exoplanet population, but the atmospheric properties of individual planets as well. In this thesis, we aim to produce a more comprehensive view of the giant exoplanet population across a range of orbital distances, from the chemical inventory, thermal structure, and orbital characteristics of hot Jupiters, to the occurrence rate of cold giants and their correlation with inner planets. We begin by characterizing the orbital parameters of a single hot Jupiter, reporting on the spin-orbit misalignment and precession of the planetary system based on gravity-darkened transit observations. We then investigate the composition and thermal structure of an ultra hot Jupiter atmosphere, searching for water vapor and TiO in its optical transmission and emission spectra. We also provide confirmation of neutral atomic iron in the day-side atmosphere of an ultra hot Jupiter, and introduce a new likelihood mapping technique to constrain a planet's day-night contrast and peak phase offset using high-resolution Doppler spectroscopy alone for the first time. Lastly, we turn out attention to characterizing the population of outer planets. We perform an automated search for and statistical study of transiting cold giant planets orbiting Sun-like stars, discussing their occurrence rate, radius distribution, and correlation with inner planets. These works will have implications for theories of planet formation at both the inner and outer edges of planetary systems, allowing us to develop a clearer understanding of planet formation and evolution. The breadth of these studies is also a testament to the advancing capabilities of observational exoplanet science, and we anticipate that the future of the field lies in the study of Earth-like planets and the statistical trends in atmospheric properties across the exoplanet population.

Keywords: Atmospheres
Exoplanet Characterization
Exoplanets
Observational Astronomy
Population Statistics
Advisor: Jayawardhana, Ray
Wu, Yanqin
Fetal Blood Flow Mapping with Magnetic Resonance Imaging

Phase contrast magnetic resonance imaging (MRI) has the potential to assess fetal blood flow. However, it faces challenges such as the small size of fetal vessels, the high fetal heart rate, uncontrolled fetal motion, limited methods to measure the fetal heart rate and the considerable complexity of the fetal circulatory system. In this thesis, methods allowing rapid fetal flow measurement are developed with retrospective motion correction and derivation of the fetal heart rate which allow generating dynamic volumetric fetal flow networks providing novel ways for comprehensive evaluation of the normal circulation and its disruption by pathologies. The thesis first presents the healthy fetal circulatory system and how it is altered by intrauterine growth restriction and congenital heart diseases in Chapter 1. Assessment and management of fetal pathologies with ultrasound are presented along with a discussion of associated limitations. Applications of MRI for fetal blood flow quantification along with an overview of the relevant acquisition, acceleration and reconstruction techniques are discussed. The achievements in this work are then discussed in three incremental stages. First, a pipeline for rapid single slice phase contrast MRI for fetal blood flow measurement with retrospective motion correction is demonstrated in Chapter 2. Second, motion corrected and conventional phase contrast MRI are compared in Chapter 3 to show the effects of motion correction on fetal blood flow measurement. Third, rapid multislice phase contrast MRI measurements from multiple stacks are combined with motion correction to reconstruct dynamic volumetric fetal blood flow networks. Finally, Chapter 5 presents the scope of the contributions from this thesis in the contemporary scientific literature along with further applications of and improvements in the developed tools.

Advisor: Macgowan , Christopher
A Public Matter? : An Ethical Analysis of the Canadian Pharmacare Public Policy Debate, 1997-2019

Background: Canada lacks universal pharmaceutical coverage (pharmacare). Calls for the implementation of national pharmacare date back to the introduction of Canadian Medicare and have recently resurfaced on the federal health policy agenda. Although public policies raise ethical and political questions, to date there has been limited analysis of the normative rationales that underpin arguments in the Canadian pharmacare debate. Accordingly, the objective of this study was to examine how bioethics—as a practically-oriented, normative inquiry—could contribute to understanding and informing the contemporary pharmacare policy debate. Methods: I conducted a qualitative, empirical bioethics case study of the Canadian pharmacare public policy debate from 1997 to 2019. I used an adapted thematic analysis to characterize the main policy arguments in 72 policy documents and transcripts in terms of their underlying normative rationales. To inform my analysis and interpretation of the data, I drew on a theoretical framework of four philosophical accounts of the division of public and private responsibility in the organization, financing, and delivery of health insurance. Findings: The contemporary pharmacare policy debate has shifted from considering whether to determining how universal pharmaceutical coverage ought to be realized; three main forms of universal coverage have been considered: public single-payer, a ‘fill-in-the-gaps,’ multi-payer program that builds on the existing mix of public and private insurance, and catastrophic coverage. The three proposals appeal to distinct normative rationales and accounts of political responsibility vis-à-vis health and health insurance. In turn, they frame and justify the problems of access, costs, and appropriateness and their attendant policy solutions differently. Growing support for public single-payer pharmacare in the contemporary debate is justified in reference to more explicit appeals to its efficiency-promoting features in addition to its equity- and community-promoting ones. Conclusion: This study provides an understanding of how arguments in the Canadian pharmacare policy debate are justified normatively. It suggests that the pharmacare debate is a politically normative debate that will require adjudicating between distinct policy objectives. The analysis illustrates how normative policy analysis can help discern and reframe underlying normative disputes in public policy debates.

Keywords: Justice
Pharmaceutical insurance
Public health ethics
Qualitative research
Solidarity
Universal health coverage
Advisor: Thompson, Alison K
Development of Hybrid Fire Simulation Methods and Their Applications to Column Fire Tests

The design philosophy in structural fire design has been shifting from prescriptive design toward performance-based design. The hybrid fire simulation method, where a physical element and a numerical model are integrated, can be used to combine the benefits of the element-level fire test and system-level fire analysis. Although the development of the hybrid fire simulation method started in the late 1990s, a fully automated robust method for large-scale numerical-experimental hybrid fire simulation has not been developed yet. In this study, two hybrid fire simulation methods are proposed and validated through full-scale column tests. The simulation schemes, substructuring methods, and stability issues are discussed in detail in this thesis. A steel moment frame was selected as a reference structure for the validation tests. The proposed methods were applied for parametric studies of steel columns and reinforced concrete columns to investigate the effect of load ratio and the axial constraint ratio on the performance of columns at elevated temperatures. The proposed method is also applied to a scaled steel braced frame that was subjected to fire following an earthquake. A set of temperature- and constraint-dependent demand-capacity curves was proposed for steel columns. The proposed curves were validated through hybrid fire simulations of steel columns. The results of the fire tests in this study demonstrate the importance of considering a realistic boundary condition for evaluating the fire performance of columns. The proposed methods provide a novel way to investigate structural fire performance through large-scale numerical-experimental hybrid fire simulations.

Keywords: Fire performance
Fire simulation
Hybrid simulation
Large-scale fire test
Structural fire design
Advisor: Kwon, Oh-Sung
Extracellular Contractile Injection Systems (eCIS) - Characterization of Conserved Phage Tail-like Structures in Streptomyces

Extracellular contractile injection systems (eCIS) are bacteriophage tail-like structures produced by bacteria that have been implicated in diverse interactions with eukaryotic cells. Despite their distribution across many bacteria and archaea they have been relatively understudied and are often misclassified as other secretion systems or tailocins. In this work I performed a comprehensive analysis of eCIS across bacterial genomes. I show that all eCIS are comprised of nine core protein families and are closely related to contractile phage tails, a relationship emphasized by the discovery of rare eCIS-like prophages that are the likely evolutionary link between the two. I classify eCIS into six distinct groups and show that group 1 eCIS are ubiquitous in the Streptomyces genus, where their production is linked to the developmental program of these complex filamentous bacteria. The eCIS of Streptomyces coelicolor are natively produced as intracellular phage tail-like structures. Mutations that abrogate eCIS formation cause developmental defects and reduced levels of hyphal cell death at specific times during differentiation that correlate with maximal eCIS production, suggesting a potential role in programmed cell death.

Keywords: phage
programmed cell death
secretion system
Streptomyces
tape measure protein
Advisor: Davidson, Alan AD
Interactions of Early-life Temperature Exposure, Offspring Genotype and Maternal Care on Later-life Maternal Care Provisioning in Female Rats

The early-life maternal environment has a profound effect on offspring behaviour, including the transmission of maternal care across generations. Variations in rat maternal care provisioning are associated with alterations in the oxytocinergic and dopaminergic systems in the maternal brain and, in turn, maternal care received by pups can alter oxytocinergic and dopaminergic systems in the rat pup brain. Though there has been progress in elucidating the biological mechanisms underlying the developmental programming of maternal care, the mechanisms that link maternal care received to alterations in the dopaminergic and oxytocinergic systems in the offspring remains to be an active area of research. Previous work has studied the transmission of pup licking across generations, but there are other relevant factors that could interact with pup licking on later-life maternal care provisioning. In this thesis, I review early-life temperature exposure and offspring genotype as important factors also involved in the developmental programming of maternal care. One project directly manipulated early-life temperature exposure and levels of supplemental licking-like tactile stimulation. The second project investigated the main effects of observed early-life inter-individual maternal licking received and interactions with naturally occurring genetic variants in dopamine-related genes. I hypothesized that early-life temperature exposure and offspring genotype would interact with licking-like tactile stimulation or pup licking to alter the oxytocinergic and dopaminergic systems in the offspring and also influence their later-life maternal care provisioning. I found that 1) early-life temperature exposure influenced the epigenetic regulation of the oxytocin gene in week-old female pups with changes in oxytocin transcript abundance and 2) that both early-life temperature exposure and supplemental tactile stimulation affected later-life maternal care provisioning. In addition, I found that a single nucleotide polymorphism in the dopamine receptor 2 gene interacted with inter-individual maternal licking received on 3) later-life performance on dopamine-related tasks and 4) maternal licking provisioning. Moreover, the association between maternal licking received and maternal licking provisioning was mediated by dopamine levels in the nucleus accumbens of the maternal brain. These findings suggest novel biological mechanisms of the developmental programming of maternal care that could be involved with the transmission of maternal care across generations.

Advisor: McGowan, Patrick O
Tactical Dramaturgies: Media, the State, and the Performance of Place-Based Activism

This dissertation seeks to develop a theory of protest as it relates to the tactics and mobilizations of specific groups and the performance of their ethical, aesthetic, and philosophical responses to the contested relationships between state and space. In doing so, I make use of theoretical frameworks provided by performance, the social production of space, and media theories in order to develop a theoretical analysis of resistant practices of Idle No More, Occupy Wall Street, and the Zapatista Army of National Liberation (EZLN). In these sites I explore moments of performative resistance that challenge the supremacy of state power, dominion over language and voice, control of the body, and agency over space. Primarily informed by Marxist spatial theory, supplemented by additional postcolonial and feminist theory and Indigenous knowledges, I examine digitally-enabled networks of solidarity and place-based activism that take up a critical stance towards digital networks, technologies, and cultures. My theoretical fusion of Henri Lefebvre, Brechtian performance traditions, and Glen Coulthard’s challenge to recognition politics, generates for me a form of critique that makes the case for an inclusive and empowering spatial ethics. I have, therefore, sought to highlight the threads that connect these different philosophies and to seek out some of those places where such ethics can be put into practice through radical performances of political resistance. These mobilized performances which enact the tensions between margins and centres, ephemerality and materiality, localism and international solidarity, become the elements of a tactical dramaturgy that reveals the precarity of those ideologies and mechanisms of oppressive power. Drawing on examples from these acts of political resistance, the sites and theory come together in my analysis under three broad themes: the voice as a challenge to the universal, the occupation of space as a challenge to state spatial supremacy, and the invocation of the mortified body as a rejection of the biopolitical state.

Keywords: Media
Performance
Protest
Space
Advisor: Freeman, Barry
Biomechanical and Ecological Insights on Evolutionary Transitions from Animal to Wind Pollination in Flowering Plants

Wind pollination (anemophily) has evolved from animal pollination (zoophily) at least 65 times among angiosperm lineages and is associated with a characteristic syndrome of floral traits, probably reflecting convergent adaptation to aerodynamically driven processes. In this thesis, I investigated the floral trait modifications promoting wind pollination, their fitness effects in contrasting environments, and the evolutionary significance of ambophily, in which both wind and insect pollination occur. I focused on traits promoting pollen release in air because it is the critical first stage of wind pollination and is constrained in most zoophilous taxa. I begin by reviewing the aerodynamic principles governing pollen release to identify likely targets of selection for anemophily. I then performed a comparative biomechanical analysis of pollen release using Thalictrum (Ranunculaceae), an herbaceous genus with multiple independent transitions between pollen vectors. I demonstrated that turbulence-induced vibration of stamens is the primary mechanism of pollen release, and is more likely to occur in species with lower natural frequencies, an intrinsic property of materials in which length and mass vary inversely. I also investigated intraspecific variation in natural frequency and its effects on fitness in dioecious ambophilous T. pubescens. I detected heritable population differences in natural frequency and thus pollen release, and demonstrated using field experiments that selection favours lower natural frequencies when pollinators limit seed set. I then investigated the evolutionary stability of ambophily in T. pubescens by evaluating how variation in density and sex ratio affects pollination success through animal versus wind pollination. I demonstrated that fitness losses resulting from declining pollinator service are offset by wind pollination suggesting that the reproductive flexibility provided by ambophily may be adaptive in populations facing demographic uncertainty. Finally, I examined factors causing male-biased sex ratios in T. pubescens. Several lines of evidence indicated that the bias is likely established early in the life cycle, perhaps at the seed stage, perhaps reflecting an adaptive bias of the primary sex ratio. My thesis provides novel results and insights on the biomechanics of wind pollination and the microevolutionary processes operating during the early stages in the transition from animal to wind pollination.

Keywords: ambophily
evolutionary transitions
plant biomechanics
pollen dispersal
pollination syndromes
wind pollination
Advisor: Barrett, Spencer C.H.