VictorJuiz/thesis huggingface dataset:
Acquiring Information from Bayesian Surprise in Cognitive Linear Gaussian Dynamic Systems

The development of autonomous systems (AS) requires cognitive entities capable of acquiring information, learning, planning, and reasoning that eventually adapt to environmental uncertainties. Since surprising events encourage learning and information-seeking in biological agents, this research suggests surprise as the intrinsic motivator to design cognitive dynamic systems undergoing autonomous behavior. Amongst several definitions of surprise, this thesis proposes the Bayesian surprise to express information utility and to guide novelty acquisition from uncertain measurements by considering the impact of new data on changing prior beliefs. By adopting Gaussian noise-driven linear dynamic models to represent the environment, the Bayesian surprise drives the system to estimate future environmental states from noisy measurements and execute a decision to minimize the estimation error over time. This research implements a novel planning algorithm, where the system computes the contribution of prospective actions---which are available from a library---to state estimation and selects the one that maximizes the expectation of Bayesian surprise. Theoretical analysis shows that the action corresponding to the highest expectation of Bayesian surprise conveys the maximum information and reduces the state estimation error. Furthermore, a learning and planning algorithm is derived by intrinsically assigning novel rewards which are developed based on the expectation of Bayesian surprise. This thesis proposes reward functions inspired by credibility measures in estimation/control theory to evaluate the consequences of past actions. The performances of the proposed algorithms are compared to the state-of-the-art for numerous experiments. For a cognitive linear Gaussian dynamic application (i.e., cognitive radar), results show that the proposed planning algorithm outperforms its competitors with respect to the mean square relative error when one-step and multiple-step planning are considered. In comparison to alternative methods, the learning and planning algorithm implemented by the proposed surprise-based rewards significantly improves the state estimation performance. Also, results indicate that multiple-step planning does not necessarily lead to lower error, mainly when the environment changes abruptly.

Keywords: Autonomous systems
Bayesian surprise
Cognitive linear Gaussian dynamic systems
Cognitive radar
Expectation of Bayesian surprise
Surprise-based internal rewards
Advisor: Plataniotis, Konstantinos N
Essays in Econometrics, Industrial Organization, and Technology

Recent developments in machine learning (ML) have facilitated the development of new methodologies to estimate structural economic models. This thesis contributes to the existing literature by developing new methodologies that combine Bayesian statistics with ML for structural model estimation and inference. In Chapter 1, I develop a model of the short-term accommodations market in Austin, Texas on Airbnb using Bayesian Neural Networks and simulate the effect of allowing platform fees to vary with consumer demand. I find that scaling fees with demand could have earned Airbnb an additional 10% in revenue over the period 2015-2019. In Chapter 2, I develop a method to estimate a first price sealed bid auction model using less observable data than what has conventionally been considered necessary. By combining a Bernstein polynomial with a Metropolis-Hastings sampler, I obtain point estimates and credible intervals on all primitives. Chapter 3 is joint work with my supervisor Martin Burda. We develop a statistical method to impose functional shape constraints on functions modeled by a flexible neural network that incorporates uncertainty inherent in the network structure. Further, we develop a method of architectural learning which enables simultaneous estimation via MCMC of both the network parameters and architecture.

Advisor: Burda, Martin
Luo, Yao
Structural and Mechanistic Characterization of Type II-C Anti-CRISPR Proteins

The CRISPR-Cas adaptive immune system provides bacteria with defence against phage predation.CRISPR-Cas systems use protein-RNA complexes to cleave and eliminate invading phage genomes in a sequence specific manner. Phages have evolved a countermeasure through the expression of small protein inhibitors against CRISPR-Cas called “anti-CRISPRs”. Anti-CRISPR proteins use incredibly diverse mechanisms to either bind directly to or enzymatically modify Cas proteins to prevent cleavage mediated by CRISPR-Cas. CRISPR-Cas enzymes, especially Cas9, have been repurposed in many biotechnologies including genome editing. Anti-CRISPRs have potential to be utilized as “off-switches” for CRISPRCas9 gene editing, addressing safety and ethical concerns for the technology. Since their discovery in 2013, over 90 protein families of anti-CRISPRs have been reported, with 37 being inhibitors of Cas9 specifically. However, much of the mechanistic details of the anti-CRISPR proteins are left incomplete. In this thesis work, I characterize the inhibitory mechanisms of two CRISPR-Cas9 inhibitors, AcrIIC4 and AcrIIC5, using structural biology and biochemical and biophysical assays. I demonstrate that AcrIIC4 inhibits the DNA cleavage activity of Cas9 by binding to the REC2 domain of Cas9 and preventing the conformational changes required for Cas9 to switch into the active state, while AcrIIC5 inhibits Cas9 from binding to target DNA using DNA mimicry. The inhibitory mechanisms elucidated in my thesis work can be applied to the potential development of AcrIIC4 and AcrIIC5 for biotechnological purposes. This work also expands our knowledge of the vast arsenal phages have evolved to circumvent CRISPRCas defence.

Keywords: anti-CRISPR
Cas9
CRISPR-Cas
Advisor: Maxwell, Karen L
Evidence for Somatosensory Facilitation during Object Reception and Action Observation

Previous research on somatosensory and tactile processing related to movement has focused on somatosensory and tactile suppression as well as the modulating factors that contribute to this suppression. However, there is a large discrepancy between the understanding of the factors that influence somatosensory and tactile suppression vs. the factors that influence somatosensory and tactile facilitation. Therefore, the aim of the dissertation was to unravel some of the factors related to the facilitation of somatosensory and tactile processing. Study 1 specifically addressed whether the expectation of tactile feedback utilization would lead to tactile facilitation during an object reception task. The results showed that tactile perception was improved as the object approached an individual’s hand and even when the individual only had the expectation of contact (i.e., when the object unexpectedly stopped short of the hand). Study 2 specifically addressed whether observed moment speed influenced tactile processing during action observation. The results showed that tactile perception was improved when observing slow reaching and grasping movements but not when observing higher movement speeds. Study 3 specifically addressed whether somatosensory processing was influenced by the speed of observed social touch interactions. The results showed that the difference in the speed of the interaction led to a greater change in somatosensory processing when observing ball-to-hand vs. ball-to-leaf-contact. Overall, the dissertation provides novel evidence for the facilitation of somatosensory and tactile processing in anticipation of tactile feedback utilization, with kinematics as a modulating factor when observing action and social touch interactions.

Keywords: Action
Action Observation
Social Touch
Somatosensory
Touch
Advisor: Tremblay, Luc
Talking Back: An Exploration of Negative Self-Talk in Undergraduate Voice Majors

This research centers on the experience of negative self-talk in undergraduate voice majors. The research questions are (1) How prevalent is negative self-talk in individual singers? (2) Why do students experience negative self-talk? (3) How does negative self-talk impact the wellbeing of this population? And (4) Can mindfulness-based meditation serve as an effective intervention in reducing the effects of negative self-talk? To answer these questions, a multiple case study was designed alongside an eight-week mindfulness-based intervention. Five undergraduate student participants were sent an email once a week for eight weeks, which included introductions to mindfulness concepts and audio files of guided meditations, which they were to practice daily. During these eight weeks, each student participated in a series of three interviews and completed questionnaires relating to music performance anxiety, self-efficacy, and mindfulness following “high stakes” performances of their choosing. In Chapter 1 of this dissertation, I present my own experience with negative self-talk in performance, and in Chapter 2, I review the current literature on Music Performance Anxiety (MPA), self-talk, and wellbeing. I present my research design and intervention in Chapter 3 and describe the five participant case studies in Chapter 4. I provide within-case and cross-case analyses in Chapter 5. In the cross-case analysis, four themes emerged: 1) Cognitive manifestations of performance anxiety; 2) Comparison; 3) Over-analyzing; and 4) Increased mindfulness. Following the eight-week intervention, overall awareness around performance and performance process increased, a deeper connection to breath was developed, and greater overall acceptance was gained. Chapter 6 contains a discussion of limitations and future directions for this research. Given the results of this and similar studies, I suggest that music educators consider adding mindfulness practices into their curriculum to enhance both the performance experience and overall wellbeing of student musicians. This intervention took place during the COVID-19 pandemic, which is discussed throughout.

Keywords: Meditation
Mindfulness
MPA
Music
Performance
Self-Talk
Advisor: Tan, Daphne
Synthesis and Characterization Of Cellulose Nanocrystal Based Rod-Like Nanoparticles For Investigation Of Surface Chemistry Effects On Cellular Internalization of Nanoparticles

Cellulose nanocrystals (CNCs) are biocompatible, non-toxic nanoparticles with many surface hydroxyl functionalities available for chemical modification. In this thesis, I describe the modification of CNCs for applications in the investigation of how nanoparticles interact with cancer cells. I modify CNCs with benzaldehyde functionalities as reactive handles for conjugation with hydrazinonicotinamide-modified polymers via a bisarylhydrazone. I first describe the sequential epoxidation and amination of pristine CNCs and carry out analysis of the effects of the reaction conditions. I then describe the synthesis of mPEG-PGlu(DOTA)-HyNic polymers using three different lengths of mPEG. The final polymer modification I describe is that of Folate-PEG-HyNic. In a final synthetic step, I conjugate the HyNic polymers to the CNC-aldehyde in a UV-Vis quantifiable reaction generating four CNC-polymer conjugates: CNC-PEG2K, CNC-PEG3K, CNC-PEG11K, and CNC-Folate. In this thesis, I describe careful and systemic study of the many synthetic steps. My interest in synthesizing these CNC-polymer conjugates was as potential drug delivery vehicles and for a systematic investigation of the effects of nanoparticle surface chemistry on cellular internalization. Surface chemistry effects were analyzed by measuring the median fluorescent intensity by flow cytometry of cell populations incubated with fluorescein-labelled CNC-polymer conjugates. The effects of PEG length were investigated using the CNC-PEG2K, CNC-PEG3K, and CNC-PEG11K conjugates upon incubation with two ovarian cancer cell lines, SKOV3 and HeyA8. I found that cellular internalization decreased with increased PEG block length for each of the cell lines. Additionally, I was able to use the same two cell lines to investigate active vs passive targeting of nanoparticles to cells as HeyA8 has low folate receptor expression whereas SKOV3 has high folate receptor expression. I found that the amount of nanoparticles internalized by and adhered to SKOV3 was higher for the actively targeted conjugate (CNC-Folate) than for the passively targeted conjugate (CNC-PEG2K). Finally, I used trypan blue incubation experiments to distinguish CNC conjugates adhered to the cell surface from those that were internalized. The results described in this thesis add to the conversations about CNC modification and characterization as well as the requirements for effective nanomedicines.

Keywords: cellulose
CNC
nanoparticles
ovarian cancer
polymers
Advisor: Winnik, Mitchell A
Canada's Hot Little Prophet?: Walt Whitman, Richard Bucke, Psychiatry, and Metaphysical Religions in Nineteenth-Century Ontario

My dissertation focuses on the friendship between the Canadian psychiatrist and superintendent for the London Asylum for the Insane, Dr. Richard Maurice Bucke and the American poet, Walt Whitman. I situate their adaptation and reimagining of a Christian ideology to suit their psychiatric and poetic needs within nineteenth-century interrelatedness of Christian, medical, psychiatric, and new metaphysical religions. The physical body is known through observation and experimentation, which then creates a “neutral” body from which other bodies can be adjudicated. This “neutral body” becomes an unnecessarily complex or impractical mechanical device that is often poorly constructed and even dangerous. In other words, both Bucke and Whitman embed a sense of Christian ideology into the physical bodies of those they are either diagnosing or writing about. The first chapter of my dissertation provides a literature review including relevant literature from the study of religion in regard to new metaphysical religions, science, and the relationship between religion and the secular. I also provide an overview of the literature regarding nineteenth-century asylums as well as the relevant literature on Bucke and Whitman. My second chapter provides an overview of the relationship between the history of new metaphysical religions and psychiatry. The bulk of my analysis comes in chapters three and four where I go in-depth regarding the relationship between Bucke and Whitman, how their ideas of religion impacted each other and their own works respectively. Finally, I examine their conceptions of religion and the body through the framework of the Cosmos. Ultimately, I argue that both Whitman and Bucke create distinct (but complementary in their consequences) conceptions of Cosmos due to a shared, Christian centred, ideological framework. Further, imagining bodies as having cosmic potential like Whitman and Bucke do, allows them to maintain their positions of authority as the science and discourse revolving around gendered and racialized bodies changes.

Keywords: Cosmos
History of Medicine
History of Psychiatry
Metaphysical Religion
Study of Religion
Advisor: Derry, Ken KD
Harris, Jennifer JH
Security Enhancement of Power Transformer Differential Protection

The growing use of information and communication technologies information and communication technologies (ICTs) in power grid operational environments has been essential for operators to improve the monitoring, maintenance and control of power generation, transmission and distribution, however, at the expense of an increased grid exposure to cyber threats. Information technology (IT) and operational technology (OT) convergence has incentivized hackers to trigger more attacks on cyber-physical systems in recent years. This has resulted in more global investment on cybersecurity. Moreover, the amount of data flow in such systems is beyond human supervision capabilities. Hence, data driven methods provide a wealth of opportunities to enhance cybersecurity. Of specific interest, we focus on the use of machine learning in an IT/OT converged environment for the purpose of intrusion detection, an essential step in cyber-physical grid security due to the complex nature of emerging power systems. We focus on the IEC 61850 substation environment, which lies at the heart of IT/OT convergence. This thesis first searches for the optimized models using applicable neural network architectures and compares their performances. The results of hyperparameter tuning are used to propose universal models for all types of faults for each architecture for IEC 61850 transformer protection relays. Next, an adversarial training method is proposed to enhance the security of the models. The performance of the models before and after adversarial training is compared. The results are used to propose the best model for enhancing the security of the transformer protective relays. Then, a black-box attack framework is proposed to study the capability of the attacker to conduct a successful attack without knowing the model parameters.

Keywords: adversarial training
anomaly detection
cyber-physical security
machine learning
smart grid
trustworthy machine learning
Advisor: Kundur, Deepa
Modeling Congenital Heart Disease in Mice and Assessing its Effects on Fetal Brain Development

In congenital heart disease (CHD), defined as structural defects of the heart that arise in-utero, neurocognitive deficits are common and are associated with brain dysmaturation in the perinatal period. Clinical studies involving CHD cohorts have shown an association between fetal brain abnormalities and hypoxemia, which is thought to result from altered cardiovascular physiology due to CHD. However, despite this association, it is not known whether the cardiac lesion in CHD causes cerebral hypoxia. Furthermore, given that factors such as shared genetic defects in heart and brain development and underlying placental disease may independently contribute to brain abnormalities, the extent to which hypoxemia/decreased substrate delivery is responsible for fetal brain dysmaturation in CHD is unknown. In this thesis, I examine whether fetal brain abnormalities can be directly caused by altered hemodynamics due to CHD. To investigate this question, I developed a surgically-induced, cardiac-specific mouse model of a CHD known as hypoplastic left heart syndrome (HLHS), which is clinically associated with hypoxemia and brain abnormalities. Next, I interrogated brain development in HLHS fetal mice using high-resolution magnetic resonance imaging (MRI) and immunohistochemistry. At a structural level, HLHS mice had volumetric reductions in compartments responsible for neurogenesis and white matter development, as observed clinically, and the size of these brain structures was partly determined by the size of the cardiac vessels. Furthermore, HLHS mice had volume loss in midbrain structures, which has not been previously observed. At a cellular level, HLHS mice had increased cerebral hypoxia and a decreased number of mature neurons globally. Given these results, I make the case that during development, altered cardiovascular physiology due to a severe cardiac lesion can directly cause brain dysmaturation at a structural and cellular level, independent of genetic factors. Furthermore, given that HLHS mice show evidence of cerebral hypoxia, therapies aimed at improving cerebral substrate delivery should be explored for improving neurological outcomes in the CHD population.

Keywords: Brain
Congenital heart disease
Imaging
Immunohistochemistry
Mouse
Neurodevelopment
Advisor: Sled, John G
Investigation of a Heme Uptake System in Acinetobacter baumannii

Iron is an essential micronutrient required for bacterial growth and survival. Heme is the largest source of iron in humans, but is inaccessible as it is tightly bound by proteins like hemoglobin. Bacteria rely on specialized protein machinery to capture host heme. Therefore, these pathways are attractive therapeutic targets which necessitates an in depth understanding of how they function. Two gene clusters predicted to function in heme acquisition in the opportunistic pathogen, Acinetobacter baumannii, are examples of such pathways requiring further characterization. This is especially important as A. baumannii is an increasing threat to global health due to its extensive antibiotic resistance. In this thesis, I show that one of the predicted gene clusters functions to support growth in hemoprotein scarce conditions. This gene cluster encodes an outer membrane translocon that secretes a hemophore called HphA into the environment. HphA binds to Hb and passively scavenges its heme, which is then shuttled to the outer membrane hemophore receptor, HphR, for subsequent uptake. The HphR-heme uptake pathway plays a crucial role in A. baumannii virulence and thus, has potential for future therapeutic interventions.

Advisor: Moraes, Trevor F
Alterations in NMDARs and STEP in the Hippocampus of a Fragile X Syndrome Mouse Model

Fragile X Syndrome (FXS) is one of the most prevalent developmental disorders causing intellectual disability. The disorder has a high burden on society and no efficient treatment options exist. FXS typically stems from mutations that silence the Fragile X messenger ribonucleoprotein 1 (Fmr1) gene hindering the production of the protein, Fragile X Messenger Ribonucleoprotein (FMRP). According to a long-held theory, based on results from animal Fmr1 knock-out (KO) models, the absence of FMRP causes exaggerated metabotropic glutamate receptor (mGluR) signaling which in turn leads to impairments in the KO. Drugs blocking mGluRs are known to normalize synaptic deficits and reverse traits in the animal models, but in clinical trials the approach has failed to translate to FXS patients. The failure of clinical trials has led to a search for new protein and signaling pathway targets that may offer a treatment for FXS. In this thesis, the role of the glutamatergic N-methyl-D-aspartate receptor (NMDAR), and the synaptic protein, Striatal-Enriched Protein Tyrosine Phosphatase (STEP)61, were examined in the hippocampus of Fmr1 KOs. NMDARs are required for some excitatory synaptic functions and are comprised of several subunits that change in expression with development. The Fmr1 KO mouse showed an age-dependent decrease of the NMDAR subunit GluN2A expression compared to wild-type (WT) littermates. The decreased GluN2A resulted in a delayed developmental switch in the GluN2A/GluN2B ratio, a switch that is important for the optimal development of synapses. Furthermore, the KO expression differences were accompanied by a developmental-dependent deficit in long-term potentiation (LTP). However, the developmental impact was only found in the CA1 area of the hippocampus, since the dentate gyrus (DG) showed a consistent decline in GluN2A expression and LTP impairment throughout development. Additionally, this thesis reports a contribution of an increased STEP61 activity accompanied by a decreased activity of the tyrosine kinase Src to the NMDAR-related deficits in the Fmr1 KO in both hippocampal areas. Taken together, this work shows the importance for developmental studies and distinguishing between hippocampal subregions in cellular, synaptic, and behavioural functions in the FXS model. Furthermore, it highlights STEP61 as a target for further investigation into FXS therapeutics.

Advisor: Collingridge, Graham GLC