VictorJuiz/thesis huggingface dataset:
The Choral-Orchestral Works of Stephen Chatman
Keywords: Choral Conducting

Canadian composer Stephen Chatman has composed noteworthy works within multiple musical genres, thus achieving international stature. Included among his compositions are several choral-orchestral works, which comprise the focus of this study. In my research, I determined the musical characteristics of Chatman’s choral-orchestral works, described how those works may be effectively prepared for performance by conductors, and assessed Chatman’s contributions to the choral-orchestral genre in Canada. A review of a wide assortment of literature and resources concerning Stephen Chatman’s works in the context of Canadian choral-orchestral repertoire produced fruitful results. I examined numerous and varied accomplishments of the composer using information found in dissertations and writings devoted specifically to Chatman and his music. Further research using materials located in the Chatman fonds at Library and Archives Canada yielded a comprehensive documentation of Chatman’s professional career and musical output. In addition, I achieved substantial insight through personal interviews with Chatman and seven other associated individuals who provided unique and informative data about his music. In this thesis, I discuss distinctive musical and textual characteristics of seven of Chatman’s choral-orchestral works: four major works composed for symphonic choir and full orchestra, and three shorter, single-movement works. I completed detailed analyses for two of these major works, Proud Music of the Storm (2001) and A Song of Joys (2013-14). During the analysis process, I discovered common threads, as well as advancements in Chatman’s compositional style over time. In order to facilitate successful performances of Chatman’s music, I prepared a conductor’s guide with detailed rehearsal suggestions for these two works specifically. To assist with score preparation, conductors will find informative data in the appendices: facts and features for all seven Chatman works studied and charts comprising bar-by-bar flow chart analyses for Proud Music of the Storm and A Song of Joys. It is my hope that this research will help promote these fine contributions within the contemporary choral-orchestral genre of music in Canada.
Estimating Psychosis Risk in Individuals at Clinical High Risk using Event–related Brain Potential Indices of Cognitive Processing
Keywords: Clinically High Risk
Electroencephalogram
Event Related Potentials
Gamma Auditory Steady State
N400
Psychosis

Background: The N400 event-related brain potential waveform occurs in response to potentially meaningful stimuli and this effect is thought to reflect greater activation of related versus unrelated concepts in long-term semantic memory. In normal participants, related targets elicit smaller (less negative) N400 amplitudes than do unrelated items. These N400 semantic priming effects are found to be attenuated in schizophrenia patients, suggesting impaired activation of related concepts. Individuals at clinical high risk (CHR) for schizophrenia experience subthreshold symptoms of the disorder, including decreased functioning. The event-related potential Mismatch Negativity (MMN), P3a and gamma ASSR measures have been found to be abnormal in CHR patients compared to controls.Aim: We aimed to examine whether N400 semantic priming deficits are a biomarker of the CHR state, whether decreased N400 semantic priming predicts conversion to psychosis in this population over two years, and whether N400 effects predict high-risk symptomatology and impaired functioning over time. Methods: We examined the N400 ERP semantic priming effect, the MMN, P3a and gamma ASSR in a sample of CHR participants and healthy controls. We then re-assessed the CHR group at one and two years to measure global functioning, positive psychotic symptoms, and conversion status. Results: We found a deficient N400 effect in the CHR group compared to controls. In this group, the N400 was related to role functioning and cognitive defects at baseline, social functioning at one-year follow-up, and improvement of positive symptoms and functioning over two years’ follow-up. Conclusion: This study indicates that the N400 priming effect is deficient at the CHR state and may contribute to the worsening of positive symptoms and functioning over time. Given that only a minority of CHR individuals will go on to develop schizophrenia, efforts to refine our ability to identify those at highest risk are critical. These findings may help to target limited resources to those individuals at risk who need it the most and minimize unnecessary treatment and side effects.
Greenhouse Gas Emission Mitigation Pathways for Light-duty Vehicle Fleets under Ambitious Climate Targets
Keywords: Biofuel
Climate Change Mitigation
Electric Vehicle
Life Cycle Assessment
Light-duty Vehicle
Lightweighting

Mitigating greenhouse gas (GHG) emissions from light-duty passenger vehicles (LDVs) will be necessary to maintain global warming below 2 °C, and ideally below 1.5 °C. In this dissertation, methods to estimate the life cycle GHG emission implications of LDV-focused mitigation strategies and to outline mitigation pathways under ambitious climate targets are developed at national and urban scales. First, a fleet-based life cycle model, the FLAME (Fleet Life cycle Assessment and Material-flow Estimation) is developed to examine the life cycle GHG emission implications of mitigation strategies, such as lightweighting the U.S. LDV fleet or deploying mid-level ethanol blends (15-30% ethanol by volume) in Canada's LDV fleet. The model combines the high technological resolution of life cycle assessment (LCA) with the temporal and dynamic perspectives of LDV fleet models. Recommendations are provided on the most effective timing of the mitigation strategies, and on their contributions to national GHG emission reduction pledges. Then, the FLAME model is augmented with a backcasting procedure to outline GHG emission mitigation pathways for LDV fleets to maintain global warming below 2 °C, and the electrification of the U.S. LDV fleet is used as a case study. The backcasting procedure relies on an innovative approach based on Integrated Assessment Models (IAMs) to quantify national and sectoral GHG emission budgets. Finally, the CURTAIL model (Climate change constrained URban passenger TrAnsport Integrated Life cycle assessment) is developed and applied in Singapore to integrate all passenger land transport modes at an urban level and to seek associated combinations of mitigation strategies that are consistent with maintaining global warming below 2 °C or 1.5 °C. The methods developed in this dissertation bridge gaps between the refined perspectives of LCA and the global perspectives of IAMs to support the development of national and urban policies for LDVs to respect ambitious climate targets. The findings suggest that there is no technological silver-bullet, there is an urgency to act, and all mitigation efforts should be pursued.
Adaptive myelination and its synchronous dynamics in the Kuramoto network model with state-dependent delays
Keywords: Delay differential equations
Kuramoto model
Synchronization
White matter plasticity

White matter pathways form a complex network of myelinated axons that play a critical role in brain function by facilitating the timely transmission of neural signals. Recent evidence reveals that white matter networks are adaptive and that myelin undergoes continuous reformation through behaviour and learning during both developmental stages and adulthood in the mammalian life cycle. Consequently, this allows axonal conduction delays to adjust in order to regulate the timing of neuron signals propagating between different brain regions. Despite its newly founded relevance, the network distribution of conduction delays have yet to be widely incorporated in computational models, as the delays are typically assumed to be either constant or ignored altogether. From its clear influence towards temporal dynamics, we are interested in how adaptive myelination affects oscillatory synchrony in the brain. We introduce a plasticity rule into the delays of a weakly coupled oscillator network, whose positions relative to its natural limit cycle oscillations is described through a coupled phase model. From this, the addition of slowly adaptive network delays can potentially lead coupled oscillators to a more phase synchronous limit cycle. To see how adaptive white matter remodelling can shape synchronous dynamics, we modify the canonical Kuramoto model by enabling all connections with phase-dependent delays that change over time. We directly compare the synchronous behaviours of the Kuramoto model equipped with static delays and adaptive delays by analyzing the synchronized equilibria and stability of the system's phases. Our mathematical analysis of the model with Dirac and exponentially distributed connection delays, supported by numerical simulations, demonstrates that larger, more widely varying distributions of delays generally impede synchronization in the Kuramoto network. Adaptive delays act as a stabilizing mechanism for the synchrony of the network by adjusting towards a more optimal distribution of delays. Adaptive delays also make global synchronization more resilient to perturbations and injury towards network architecture. Our results provide insights about the potential significance of activity-dependent myelination. We hope that these results lay out the groundwork to computationally study the influence of adaptative myelination towards large-scale brain synchrony.
Towards Biologically Plausible Gradient Descent
Keywords: Credit assignment
Deep learning
Gradient descent
Neural networks
Pyramidal neurons

Synaptic plasticity is the primary physiological mechanism underlying learning in the brain. It is dependent on pre- and post-synaptic neuronal activities, and can be mediated by neuromodulatory signals. However, to date, computational models of learning that are based on pre- and post-synaptic activity and/or global neuromodulatory reward signals for plasticity have not been able to learn complex tasks that animals are capable of. In the machine learning field, neural network models with many layers of computations trained using gradient descent have been highly successful in learning difficult tasks with near-human level performance. To date, it remains unclear how gradient descent could be implemented in neural circuits with many layers of synaptic connections. The overarching goal of this thesis is to develop theories for how the unique properties of neurons can be leveraged to enable gradient descent in deep circuits and allow them to learn complex tasks. The work in this thesis is divided into three projects. The first project demonstrates that networks of cortical pyramidal neurons, which have segregated apical dendrites and exhibit bursting behavior driven by dendritic plateau potentials, can in theory leverage these physiological properties to approximate gradient descent through multiple layers of synaptic connections. The second project presents a theory for how ensembles of pyramidal neurons can multiplex sensory and learning signals using bursting and short-term plasticity, in order to approximate gradient descent and learn complex visual recognition tasks that previous biologically inspired models have struggled with. The final project focuses on the fact that machine learning models implementing gradient descent assume symmetric feedforward and feedback weights, and presents a theory for how the spiking properties of neurons can enable them to align feedforward and feedback weights in a network. As a whole, this work aims to bridge the gap between powerful algorithms developed in the machine learning field and our current understanding of learning in the brain. To this end, we develop novel theories into how neuronal circuits in the brain can coordinate the learning of complex tasks, and present a number of experimental predictions that are fruitful avenues for future experimental research.
Investigating the Involvement of the Sulfotransferase Pathway in Drug-induced Skin Rash
Keywords: covalent binding
idiosyncratic drug reactions
reactive metabolite
skin rash
sulfotransferase

Circumstantial evidence suggests that most idiosyncratic drug reactions are caused by chemically reactive metabolites of the drug that covalently binds to proteins. The skin is a major target of idiosyncratic reactions; however, drug metabolism in the skin is limited. One exception is the presence of relatively high sulfotransferase activity in human skin. For example, nevirapine-induced skin rash is caused by a reactive benzylic sulfate formed in the skin. The working hypothesis is that the serious skin rashes caused by other drugs involve reactive sulfate metabolites formed in the skin. Trimethoprim, lamotrigine, valdecoxib, and sertraline have the potential to produce reactive sulfate metabolites that may be responsible for drug-induced skin rash. Anti-drug antibodies against trimethoprim, lamotrigine, and valdecoxib were made to study covalent binding of the drug to proteins. Brown Norway rats were treated with these drugs, and their liver and skin proteins were immunoblotted to look for covalent binding. No covalent binding of any of these drugs was detected in the skin, but covalent binding of trimethoprim was detected in the liver. The immunoassay may not be sufficiently sensitive to detect covalent binding in the skin, or binding may be limited to human skin. The sulfates of hydroxy-trimethoprim and lamotrigine-N-oxide, which are metabolites of these drugs, were chemically synthesized, and both were found to be chemically reactive. Surprisingly, even hydroxy-trimethoprim itself had sufficient reactivity to covalently bind to proteins in vitro. Dr. Liu, our collaborator at the University of Toledo, tested whether hydroxy-trimethoprim, lamotrigine-N-oxide, hydroxy-valdecoxib or hydroxy-sertraline were substrates of human sulfotransferases. He found that lamotrigine-N-oxide was a substrate for several human sulfotransferases, while hydroxy-trimethoprim was only a substrate for the fetal sulfotransferase SULT1C4, and hydroxy-valdecoxib and hydroxy-sertraline were not substrates for human sulfotransferases. That implies that the rashes caused by valdecoxib and sertraline are not due to a sulfate metabolite. Given that hydroxy-trimethoprim is only a substrate for a fetal sulfotransferase but is weakly reactive, it may be responsible for trimethoprim rashes. The rash caused by lamotrigine is likely due to the N-O-sulfate; however, detection of covalent binding in skin would have strengthened the evidence for this hypothesis.
Being as a Kind in Plato's Sophist
Keywords: Being
Kind
metaphysics
ontology
Plato
Sophist

What is being for Plato? While in several dialogues ‘being’ (to on, ousia) typically designates the intelligible domain in general, in the Sophist Plato was led, through his engagement with the paradox of falsehood and the problem of not-being, to single out being as just one among the kinds (or forms) – notably, one of the so-called ‘greatest kinds’. Surprisingly little effort has been devoted by scholars to working out the motivations and implications of this move. I shall argue that the kind being, just like any other kind (or form), is first and foremost conceived of by Plato as a robust causal principle. It is not a most generic genus encompassing all other genera, but the entity metaphysically responsible for the property named after it, viz. being (simpliciter). Against the current orthodoxy, I therefore think that the famous slogan ‘to be is to be something’, often taken to capture a fundamental truth of Plato’s conception of being, does not fit the Sophist. Further, this also means that, unlike many modern philosophers, Plato conceives of being as a real property. What property? Although the Sophist is not fully explicit on this point, Plato probably suggests that it is the property of having ‘the power to act or to be acted upon’, which can be interpreted as the power to take part in a causal relation. Finally, I argue that the isolation of a kind being is a necessary condition for Plato’s account of not-being. Were there no kind being, Plato could not bring his ambitious project about not-being to completion.
The Bidirectional Acquisition of Oral and Nasal Gestural Timing in L2 Brazilian Portuguese and Rioplatense Spanish Nasal Structures
Keywords: Articulatory Phonology
L2 Acquisition
Nasal structures
Phonetics
Portuguese
Spanish

Brazilian Portuguese (BP) nasal vowels (Ṽᴺ) and Rioplatense Spanish (RS) vowel + nasal sequences (VN) are realized with two oral (vowel and consonant) gestures and a nasal (velum) gesture, but they differ in the way these gestures are sequenced. Adult native speakers of RS and BP who aim to acquire the opposite language will thus need to learn this cross-linguistic difference. On the one hand, non-native speakers of BP will have to realize a longer overlap of the vowel and velum gestures and a shorter nasal coda. On the other hand, non-native speakers of RS will need to produce a shorter gestural overlap and a longer nasal coda. The main purpose of this dissertation is to investigate the relative difficulties that RS and BP speakers encounter at the phonetic and phonological levels when acquiring the gestural pattern of the other language’s nasal structure. To accomplish this goal, four studies were conducted. The findings from the studies on monolingual and bilingual production suggest that nasal structures in RS and BP are similar but differ in terms of their gestural timing and that their phonetic implementation and phonological representation may be affected by the dominant language of heritage speakers. Moreover, the studies on naïve and L2 perception and production indicate that, with experience in the L2, the timing of the oral-nasal gestural overlap can be acquired by non-native speakers. However, the gestural timing of a longer nasal coda seems more difficult to realize than that of a shorter nasal coda, not only at first exposure but also with more experience in the L2. This suggests that nasal coda weakening, a common phonological process in language variation and change, poses less articulatory difficulties to L2 learners than nasal coda strengthening. We propose that a gestural timing constraint on nasal coda strengthening should be integrated into L2 models of phonological acquisition to better predict and explain relative difficulties encountered by L2 learners.
Nonlinear Nanobubble Behaviour for Vascular and Extravascular Applications
Keywords: Contrast Agent
Imaging
Microbubbles and Nanobubbles
Nanomedicine
Therapy
Ultrasound

Nanomedicines exhibit novel properties with structural versatility, improved pharmacokinetic profiles, and multifunctionality for advanced delivery strategies targeting infiltrative tumours while sparing surrounding normal tissue. Consolidating the abilities of traditional nanoparticles with conventional ultrasound agents by shrinking microbubbles to the nanoscale can have profound effects on bubble behaviour, bringing new possibilities as well as challenges. This dissertation aims to address current limitations of nanobubbles, laying the groundwork for their utility within and beyond the vasculature. Insights on nanobubble behaviour in vessel- and tissue-mimicking surroundings through theoretical and experimental approaches are presented. The first observation that nanobubbles can initiate sustained pressure threshold-dependent nonlinear scattering is shown, and found to be highly sensitive to nonlinear shell rheology. Novel direct acoustic evidence that nanobubbles can extravasate intact is then demonstrated upon different delivery avenues with real-time acoustic and visual observations in tumour-affected functional circulation at the microscale. An ultrasound-stimulated in situ conversion of microbubbles to nanobubbles is studied and compared to passive and ultrasound-mediated delivery of injected nanobubbles, with acute vascular events from ultrasound-stimulation of nanobubbles being visualized for the first time. Developing a tool for further examination of nanobubbles, their scattering is then systematically investigated at high frequencies with a view to establishing imaging schemes based on their physical behaviour. Pressure-calibrated amplitude modulation is employed on a commercial pre-clinical array system, resulting in enhanced contrast-to-tissue ratios onthe order of 10 dB in a phantom and in vivo. Collectively, the developments achieved in this thesis aim to extend bubble-mediated approaches through the integration of nanomedicine and ultrasound.
Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in Schizophrenia
Keywords: Cannabis
Cannabis Use Disorder
Comorbidity
Repetitive Transcranial Magnetic Stimulation
rTMS
Schizophrenia

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in Schizophrenia Karolina Bidzinski nee KozakDoctor of Philosophy 2021 Institute of Medical Science University of Toronto ABSTRACTRationale: Schizophrenia is a debilitating psychiatric disorder, with poor functional outcomes. Problematic cannabis use among the schizophrenia population is high, with 26% diagnosed with comorbid cannabis use disorder (CUD), which negatively impacts psychosocial functioning. These patients also have greater difficulty quitting cannabis, which may reflect putative deficits in the prefrontal cortex. To date, there are still no established evidence-based treatments for this comorbidity. Aims: Primary: Determine effects of high frequency (20 Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use outcomes in outpatients with schizophrenia and CUD. Secondary: Examine effects of active vs. sham rTMS on cannabis craving/withdrawal, psychiatric symptoms, and cognitive functioning. Hypotheses: Primary: Active vs. sham rTMS will result in significantly greater reductions of cannabis use and cannabis abstinences rates. Secondary: Active vs. sham rTMS will result in significantly greater reductions in cannabis craving/withdrawal symptoms, and positive and negative symptoms of schizophrenia, and greater improvements in cognition. Methods: A preliminary double-blind, sham-controlled randomized trial. A total of N=24 subjects were enrolled, and n=19 participants were randomized to receive either active (n=9) or sham (n=10) high frequency rTMS 5x/week for 4 weeks, combined with weekly behavioural support sessions. Cannabis use and symptomatology were monitored weekly through self-report and urine toxicology. A cognitive/neurophysiological battery was administered at pre (Baseline) and post (Day 28). Results: Although no significant differences in cannabis use from Baseline to Day 28 between active and sham treatment were found, contrast estimates indicated greater reductions in cannabis use in the active group (GPD: Estimate=0.33, p=0.207). A trend toward significantly greater reduction in craving score (MCQ Factor 3) over time was found in active vs. sham (Estimate=3.92, p=0.064). Significant reductions in PANSS positive (Estimate=2.42, p=0.018) and total (Estimate=5.03, p=0.019) symptoms over time were found in active vs. sham groups. Significant improvement in Continuous Performance Test (e.g., sustained attention) over time was found in active vs. sham groups (Estimate=6.58, p=0.048). rTMS was safe and well-tolerated, with a high retention rate of 17/19 (90%) outpatients completing the study. Conclusions: Our preliminary findings support the notion that rTMS is a safe and potentially effective treatment for comorbid CUD and schizophrenia.