VictorJuiz/thesis huggingface dataset:
Investigating the Mechanisms of Perinatal Neuron Degeneration, Survival, and their Differentiation from Neural Precursor Cells of the V-SVZ
Keywords: Degeneration
Neurodevelopment
Neurons and glia
Neuroprotectant
Stem cells and neural precursors
Translation and translational repression

For the formation and maintenance of functional neuronal networks, the generation of neurons from their progenitors developmentally as well as their continued survival once the circuitry has been established are both crucial for nervous system homeostasis and plasticity, with disruptions resulting in neuropathologies. For the integrity of this process, first, cellular mechanisms need to temporally orchestrate the correct neuronal fate delineation from multipotent precursors and second, transduced pro-life signals need to suppress degeneration-promoting transcriptional programs to ensure continued survival. In this thesis, I describe a novel 4E-T-based translational regulation mechanism that “fine-tunes” the timing of neurogenesis, coordinating the correct emergence ofinterneurons from transcriptionally pre-fated early postnatal precursors (Chapter 5), in addition to characterizing a novel neuroprotectant promoting survival by suppressing the degeneration of peripheral neurons and potently protecting axonal mitochondria (Chapter 4). Postnatal precursors which possess multi-lineage potency and the ability to renew long-term, are a continuous source of neuronal progeny for tissue formation and repair, and must balance their maintenance through self-renewal, expansion of their pools through proliferation, and the need to generate progeny through differentiation. In Chapter 5 of this thesis, I demonstrate that postnatal precursors are “pre-fated”, expressing neuronal differentiation instructing specifier transcripts, and that a 4E-T-based regulatory mechanism involving translational repression modulates protein synthesis levels of these mRNA targets, controlling timely neurogenesis. Established peripheral neurons and their axonal projections need to then be preserved for the lifetime of the organism to ensure proper circuit function. One goal of the work presented in this thesis is to identify safe-in-man drugs that can block or delay axon degeneration, and to use these drugs to characterize new degeneration pathways. To this end, the work described in Chapter 4 describes and identifies the multikinase inhibitor Foretinib as being protective in sympathetic, sensory and motor neurons across multiple degeneration paradigms. Thus, my thesis traces the trajectory of neurons in two main aspects of neurobiology: from onset of fate commitment and appropriate neuronal lineage acquisition, to maintenance and protection in maturity once neurons integrate into circuits, highlighting the consequences to the organism in the case of aberration in either process.
Characterization and Design of Nickel-binding Proteins towards Metal Recovery Applications
Keywords: ABC transporters
biomining
high-throughput screening
metal binding
metal recovery
solute-binding proteins

Nickel is an important metal in the adoption of greener technologies needed to transition to cleaner economies, and mines face pressure to source it more sustainably. Nature has evolved nickel-specific ATP-binding cassette (ABC) importers that can transport nickel across a cell’s membrane from the environment into the cytoplasm. Specifically, their solute-binding component known as the nickel-binding protein (NiBP) scavenges the cell’s periplasmic space to deliver metals to the cognate permease complex for transport. Existing methods for metal-binding characterization are not amenable to protein engineering efforts that rely on screening libraries of variants with different substrates. Using natural changes in protein fluorescence during a metal-binding event, we first optimized an assay previously reported in literature to measure the binding affinity (K¬D) of NiBP complexes with nickel and other metals. This assay was validated by determining the KD of the well-characterized NiBP CjNikZ from Campylobacter jejuni, which was comparable to reported values, so it was then used to demonstrate the presence of Ni(II)-binding activity in the uncharacterized NiBP called CcNikZ-II from Clostridium carboxidivorans. Next, we determined the crystal structure of CcNikZ-II, which revealed the potential Ni(II)-binding site located close to a short variable loop. Mutagenesis identified the CcNikZ-II residues involved in Ni(II) binding, but the role of the variable (v-)loop of this protein (TEDKYT) remained unclear. We purified nine CcNikZ-II homologues and determined the nickel-binding affinity of these proteins using an intrinsic fluorescence quenching assay, which showed all these proteins have higher KD for Ni(II) than CcNikZ-II. Furthermore, we replaced the CcNikZ-II v-loop sequence (TEDKYT) with those from the other homologues with higher affinity and found that the engineered CcNikZ-II variants have a higher binding affinity to Ni(II). Metal promiscuity screening further demonstrated the importance of the secondary coordination sphere in controlling affinity and specificity. Finally, an engineered E. coli strain (Ni_v.1) was created and tested in 10 ppm NiCl2 solution matching environmental conditions and demonstrated 7-fold improvement in nickel bioaccumulation performance compared to controls. Thus, both wildtype and engineering microbial NiBPs can be engineered for improved metal binding and selectivity and used for developing bio-based technologies for metal recovery applications.
Excellence and Access for Ontario’s Higher Education System: How Universities Commit to Both
Keywords: academic excellence
access
differentiation
equity diversity inclusion
strategic mandate agreement
widening participation

This thesis describes two phases that together investigate how the 20 Ontario universities commit to the values of widening participation and academic excellence, which are often viewed as competing. This research employs theories and concepts at the intersection of sociology and politics of education, namely, maximally maintained inequality, effectively maintained inequality, isomorphism, and legitimacy to compare Ontario to international trends of social stratification and inequality within the higher education sector. Phase 1 provides a landscape analysis of Ontario’s higher education system and a classification of Ontario’s universities as recruiting or selecting. The universities were classified using three sources of data. The first was the entering grade-point averages across universities and programs from Common University Data Ontario (CUDO), the second was a discourse analysis of websites for five programs (Arts, Science, Business, Engineering, and Nursing) at each university, and third was Maclean’s (a Canadian current affairs magazine) rankings of university reputation. Phase 1 found that certain Ontario universities were distinctively selecting across most programs, while others were recruiting across most programs, and that the majority of Ontario universities had both selecting and recruiting programs. In phase 2, I conducted a discourse analysis of guiding documents (Strategic Mandate Agreements and Strategic Plans), and discourse analysis of publicly facing websites and viewbooks to explore how two of Ontario’s selecting universities and two recruiting universities commit to both widening participation and academic excellence. The findings reveal that Ontario’s selecting universities and programs prioritize being perceived as academically excellent (e.g., rigorous training, prestigious learning opportunities, leading innovation, and impact) on a global stage. Recruiting universities prioritize widening participation for local communities through strong recruiting and retention discourse and local community building through research. Recruiting and selecting universities use the discourse of academic excellence and widening participation to establish cognitive, moral, and pragmatic legitimacy. Selecting universities commit to widening participation to the extent that it does not challenge perceptions of global academic excellence. The findings of Phases 1 and 2 are relevant for policymakers, researchers, university leaders, and the public, as Ontario’s differentiated higher education system is not removed from the debate around equality of opportunity.
Optimizing Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder
Keywords: Brain stimulation
Neuromodulation
Neurostimulation
rTMS
TMS
Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a well-established and effective intervention in MDD, with an advantageous side-effect profile over medication. Unfortunately, widespread adoption of rTMS has been impeded by several obstacles limiting clinical accessibility, including high costs of acquisition and operation, technical challenges because of the current complexity of the procedure, and the lack of validated and scalable biomarkers to help predict treatment outcome. To address these issues, we explored novel rTMS delivery methods, including parabolic coils with broad stimulation areas allowing easy targeting, safe and well-tolerated low-frequency 1 Hz stimulation delivered on the most affordable FDA-approved rTMS devices, an open-room setting allowing a single technician to attend to multiple patients, custom-made equipment reducing costs, and performed schedule optimization using treatment acceleration. We subsequently attempted to maximize effects by optimizing stimulation parameters. Lastly, we researched heart rate variability (HRV) as a potential biomarker to predict treatment outcomes. Our initial chart review studies helped us determine that the use of parabolic coils combined with 1 Hz rTMS was safe and well-tolerated in the treatment of MDD. Our second study showed that accelerated 1 Hz rTMS with parabolic coils was also safe, well-tolerated. We also showed that an open-room setting was feasible and that our custom-made rTMS equipment was reliable. Given the limited clinical effects observed in those studies, we researched an even more intensive accelerated 1 Hz rTMS protocol in our third study and found evidence of increased effectiveness. Lastly, we did not observe any significant association between baseline pre-treatment resting-state HRV and clinical outcomes. In the final part of this thesis, we summarize our findings and discuss their implications for the treatment of MDD. We conclude by discuss the various limitations inherent to this preliminary work and potential future directions. Given its established efficacy in MDD and its lower side-effect profile compared to medication, efforts should be made to make rTMS more accessible. Our work proposes several ways to improve rTMS by simplifying procedures to reduce costs and therefore potentially increasing accessibility at the community level, increase clinical effects and help with patient selection.
Unlocking Dynamic Cameras for Visual Navigation
Keywords: Calibration
Drones
Dynamic Cameras
Gimbal cameras
State Estimation
Visual SLAM

The ability of a mobile robot to navigate reliably in an unknown environment depends on the information perceived from its surroundings, usually available in the form of measurements from sensors. However, most of the current sensor configurations assume a static rigid transformation between the sensors, placing many limitations on its performance, especially when undergoing high dynamic motion profiles. A Dynamic Camera consists of a camera mounted to an actuated mechanism such as a gimbal and offers several advantages compared to the static case. However, In order to accurately relate information across these cameras and other sensors, a precise time-varying extrinsic calibration needs to be determined. In this dissertation, I present novel methods to calibrate a Dynamic Camera to other sensors such as static cameras and IMUs. First, I analyze a Dynamic Camera Cluster system, and present an information theoretic Next-Best-View formulation that directly minimizes the uncertainty on the calibration parameters and test the resulting calibration in a visual-inertial odometry application. Second, I present a novel analysis of the redundant parameters in the calibration system when joint angle values to the actuated mechanism are unavailable and propose a novel minimal parameterization to resolve the degeneracies. Third, I present the online calibration between a Dynamic Camera and an IMU, and analyze the observability properties of the calibration parameters. I perform extensive tests in simulation and in the real world, consisting of a 3-DOF gimbal and a 5-DOF manipulator, demonstrating our ability to recover an accurate calibration, thereby allowing Dynamic Cameras to be used in visual navigation applications.
Point-of-care Detection Platforms for Metabolic Biomarker and Infectious Disease
Keywords: COVID-19
Electrochemical biosensing
Flexible electronics
Point-of-care diagnosis

The metabolic and protein biomarkers are the most significant detection targets for the point-of-care disease diagnosis and healthcare. The chronic diseases are among the world’s leading causes of mortality, and the COVID-19 pandemic is continuously burdening the global health, especially impacting the low-income, resource-limited regions. Accurate point-of-care detection of biomarkers is an important monitoring strategy for chronic disease development. Early detection of infectious disease outbreaks can reduce the ultimate size of the outbreak and the overall morbidity and mortality due to the disease, in which diagnosis plays an important role. As available diagnostic technologies require well-trained personnel, expensive equipment and complex assay procedure and consume a large amount of time in medical laboratories, there is an urgent need for low-cost portable platforms that can provide fast, accurate, and ideally multiplexed diagnosis of infectious diseases at the point of care. This thesis reports on the design, fabrication, and demonstration of electrochemical point-of-care detection systems for metabolic and protein biomarkers. Rapid results have been achieved by employing electrochemical enzymatic reactions on devices with simple fabrication and preparation. The systems have demonstrated high sensitivity and specificity comparable to state-of-the-art laboratory tests. The works reported in this thesis show strong potential to lead to portable systems for point-of-care diagnosis.
How Gospel Pianists Learn Black Gospel Music: Developing Gospel Music Education in Postsecondary Institutions Beyond Choral Music
Keywords: anti-Black racism
aural musicianship skills
critical race theory
gospel piano pedagogy
narratives of learning gospel piano
university gospel music curriculum

The purpose of this study was to create a foundation for the inclusion of gospel piano instruction in the curriculum of postsecondary institutions. Critical Race Theory (Bell, 1987, 1995; Dumas, 2013, 2016; Ladson-Billings, 1998; Yosso, 2005) was used as a theoretical underpinning to interrogate the existence of anti-Black racism in music education and the ways in which Black music, history, culture and voices have been historically silenced in music curriculum. Narrative Inquiry (Clandinin, 2020; Connelly & Clandinin, 1990; Creswell & Guetterman, 2019; Downey & Clandinin, 2020) was used to explore the lived experiences and perspectives of eight professional Black gospel pianists. In conjunction, autoethnography (Davis & Ellis, 2010; Reed-Danahay, 1997) was used to explore the lived experience and perspective of the researcher while engaging in private gospel piano lessons. The study was guided by the question, ‘How can the traditions and practices of learning to play piano in the Black gospel style be used to enrich the curriculum of music in postsecondary institutions?’ The data was gathered through semi-structured interviews and autoethnography experience tracking forms. Findings revealed five broad themes suggesting how postsecondary music institutions can be enriched by including gospel piano in the curriculum: (1) Developing Aural Musicianship and Improvisational Skills; (2) Developing Well-Rounded Musicians; (3) Embracing Diversity; (4) Developing Community Partnerships; and (5) Expanding Gospel Music Programs. These findings provide valuable insights into the practices of learning Black gospel piano and may be used to inform the inclusion of gospel piano in the curriculum of postsecondary music institutions. This integration into the postsecondary curriculum may expand existing gospel music programs or introduce new gospel music courses with the purpose of diversifying music curricula and dismantling anti-Black racism in music education.
The Utility of Second-Tier Genomic Sequencing for Hereditary Cancer Syndromes: A Mixed-Methods Study
Keywords: Clinical utility
Genome sequencing
Health services research
Health technology assessment
Hereditary cancers
Mixed-methods research

Background: Identification of patients with hereditary cancer syndromes (HCS) is important to detect high-risk patients who become eligible for surveillance and preventive surgeries that reduce cancer risk or detect it earlier, reducing morbidity and mortality. Standard panels only identify 10-20% of HCS patients. Genomic sequencing (GS) may identify more high-risk patients; however, evidence demonstrating utility of GS in HCS is lacking. Methods: This mixed-methods thesis aimed to explore the utility of second-tier GS for HCS. The first study explored clinician-reported utility of GS for HCS and other indications through a qualitative study using semi-structured interviews with Canadian clinicians with GS experience. Transcripts were thematically analyzed using constant comparison. The second study evaluated clinical utility of second-tier GS for HCS through chart review and survey conducted for cancer patients undergoing GS in an RCT. Charts were reviewed to extract diagnostic yield and management changes data. The final study explored patient-reported utility of cancer GS results by conducting a qualitative study using semi-structured interviews with patients who received second-tier GS as part of the aforementioned RCT. Transcripts were analyzed using constant comparison, similar to aim 1. Finally, a narrative approach was used to integrate quantitative and qualitative data. Results: All three studies suggest that GS provides limited utility above standard panels in HCS patients. The first qualitative study found that cancer clinicians attributed minimal utility from second-tier GS, who emphasized that the additional low/moderate penetrance results identified would not change management. The second study revealed that second-tier GS identified pathogenic results in 10% of patients, most in low/moderate penetrance genes with minimal actionability and at the cost of a high VUS rate of 90%. Findings from the third study indicated that patients centered their perceptions of utility of GS results on whether they changed management. Consequently, patients without management changes perceived anxiety and became hypervigilant, experiencing harms. Conclusions: As a second-tier test, GS provided limited utility for cancer patients and may be triggering harms. Our findings call for practice interventions to support patients receiving uninformative results from cancer genetic testing and for research to establish the utility of first-tier GS in HCS.
Yoga in the Mokṣopāya
Keywords: advaita
Buddhism
emptiness
Hinduism
Rāma
Yoga

This thesis aims to elucidate the Yoga of the Mokṣopāya, a philosophical story-text from tenth century Kashmir in which the sage Vasistha imparts teachings to the young Lord Rama on the illusory nature of the world and the path to liberation. In the Mokṣopāya we find a unique nondual idealist philosophy that teaches that the entire world is a dream of the cosmic mind—nothing is fundamentally real—and professes to convey the ultimate truth of all established philosophies while adhering to none in particular. The Mokṣopāya is most popularly known in its later recension as the Yogavāsiṣṭha—a well-known and important text of nondual Vedānta which has been transmitted, translated, and commented upon over the centuries––however, the Yogavāsiṣṭha has significant textual corruption which took place during the transmission of the Mokṣopāya sometime after it was composed. This dissertation draws upon the work of the Mokṣopāya project and the nearly complete critical edition of the Mokṣopāya which presents scholars with a unique opportunity to study this unknown nondual pre-Advaita Vedānta tradition. I suggest that the Mokṣopāya is a Yoga text grounded in a unique and idiosyncratic nondual Sāṃkhya system of knowledge with a strong Yogācāra Buddhist influence and similarities to early Haṭha Yoga. In fact, I suggest that a similar historical context could have led to the development of both Haṭha Yoga and the Mokṣopāya since many common elements are found between the two traditions. Specifically, the Mokṣopāya shares elements with Haṭha Yoga that include the raising of kuṇḍalinī, the intonation of the syllable OṂ, the central focus on prāṇa and kumbhaka, a doctrine of siddhis, a goal of jīvanmukti or embodied liberation, a notion of immortality in the body, a practice of conscious Yogic dying, a doctrine of the prāṇa-sun which is fire that consumes the apāna-moon which is water in a centre in the core of the body, and descriptions of yogins retreating to clean and beautiful but simple Yogic huts or caves to practice nirvikalpa samādhi on animal skin seats in the lotus posture with the openings of the body closed off to keep the flow of prāṇa inside.