VictorJuiz/thesis huggingface dataset:
The Clustered Protocadherins in the Form and Function of Cerebellar Purkinje Cells

The cerebellum is a brain region that regulates the control of movement. It also participates in non-motor functions, such as social and repetitive behaviours. At the heart of the cerebellar circuitry are the Purkinje cells (PCs). These neurons provide the sole exit of neural information from the cerebellar cortex. PCs possess distinguishing features: 1) their exuberant dendrites are uniformly distributed with minimal self-overlap through a process called dendrite self-avoidance; 2) they fire intrinsically at regular and high-frequency intervals even without synaptic input. PCs prominently express the clustered Protocadherins (cPCDHS), a group of cell surface recognition molecules. They are encoded by 58 genes, divided into three clusters: α-Pcdh (Pcdha), β-Pcdh (Pcdhb), and γ-Pcdh (Pcdhg). Previously, we showed that PCDHGs regulate PC dendrite self-avoidance (Lefebvre et al., 2012). However, the roles of the other clusters in PC self-avoidance and overall, the cPCDHs’ roles in PC function have not been elucidated. Here, I investigated the functional interactions between the Pcdha and Pcdhg clusters in PC dendrite self-avoidance, as well as their roles in PC firing and behavioural output. My PC self-avoidance analysis demonstrated that the loss of Pcdhas leads to defects of similar severity to loss of Pcdhgs, suggesting that both clusters are equally required. Dendrite self-crossing defects were exacerbated in Pcdha; Pcdhg double mutant PCs compared to single mutants, revealing partial redundancy. Developmental PCs lacking Pcdhgs displayed increased dendrite density and malformed filopodia, suggesting deficits in filopodia retraction lead to self-avoidance defects. The cPcdhs also influenced PC functions. Mouse mutants harboring a PC-specific deletion of Pcdhgs, with or without an additional global Pcdha heterozygous deletion, displayed motor impairments on the rotarod and in their gait. Non-motor functions were spared. Motor deficits were accompanied by dysfunctional PC firing properties. Mutant PCs exhibited lower intrinsic firing rates and excitability with elevated potassium currents, possibly resulting from Kv3.3 channel disinhibition. In CHO cells, a PCDHG isoform physically interacted with Kv3.3 channels, revealing a potential mechanism for cPCDH inhibition of Kv3.3 channels. My work is the first to show that the cPCDH clusters cooperate in PC dendrite self-avoidance, and that the cPCDHs can regulate the firing properties of a neuron, as well as PC-specific behavioural output.

Keywords: cerebellum
clustered Protocadherins
intrinsic firing
Kcnc3 Kv3.3 channels potassium voltage-gated channel subfamily C member 3
Purkinje neurons
Advisor: Lefebvre, Julie
Cultural Socialization Among Chinese Parents in Canada and the United States: Role of Racism, Co-ethnic Social Capital, and Regional-level Characteristics

Cultural socialization refers to the parenting practices that promote children’s ethnic pride and transmit cultural messages, customs, and traditions. It has been found to be beneficial to cultural minority children and adolescents in terms of their mental health, cognitive development, and identity development. Understanding the factors associated with parental cultural socialization can inform direct services and tailor program designs. However, there is a lack of literature about cultural socialization among Chinese parents who live in Canada and the United States, particularly the relationship between broader social factors and their behaviours. Using an ecological approach, supplemented by social dominance theory and theories of social capital, this dissertation studies the role of social factors, namely experiences with racism, co-ethnic social capital, and regional-level characteristics, in Chinese Canadian and Chinese American parents’ cultural socialization. This dissertation consists of an introduction, three distinct research papers, and a conclusion. All three papers present the findings of an online cross-sectional survey study with Chinese Canadian and Chinese American parents (n=478). Paper one explores the interconnection among parents’ experiences with acute, everyday, and internalized racism and their cultural socialization practices. Paper two examines the role of offline and online co-ethnic social capital (i.e., cultural resources from co-ethnic networks) in cultural socialization. Paper three investigates the interrelationship between three regional-level factors, including ethnic density, ethnic diversity, and regional socioeconomic status, and individual-level factors, namely internalized racism and cultural socialization. This dissertation fills the knowledge gap by providing insight into how social environments may affect cultural socialization through parents’ appraisal and sense-making of their social experiences. The significant role of internalized racism found in this study, along with the unique nature of anti-Asian racism, demonstrate the need for social workers and parenting services to address racial and cultural hierarchies, internalized social scripts, and the subtle and chronic forms of racism experienced by Chinese in Canada and the United States. The dissertation also points out the need to encourage co-ethnic bonds and the development of local ethnic communities. Implications for social work practices and future research are discussed.

Keywords: Chinese
Cultural socialization
Ecological
Neighbourhood
Racism
Social capital
Advisor: Fang, Lin
Concussion Public Policy for Elementary and High Schools in Ontario: Assessment of Content, Implementation, and Impact of PPM158

Background and Objective: Concussions are a rising public health problem and have particular impact on the well-being of children and youth aged eighteen and under, having increased in rate 4.4-fold from 2003 to 2013 in Ontario.1 Concussion public policies have been developed across the United States and in Ontario, Canada, to address this issue, and further knowledge about them would help inform evidence-based policies. The objectives of the three studies in this thesis are to 1) develop consensus-based concussion public policy recommendations, 2) identify barriers to and facilitators of Policy/Program Memorandum 158 (PPM158) implementation, and 3) assess whether there has been a change in the rate of concussion-related visits associated with the establishment of PPM158.Methods: To address the first objective, we employed a modified Delphi method with a multi-disciplinary expert group. To address the second objective, we developed a survey and analyzed data with both quantitative and qualitative methods. To address the third objective, we used segmented regression in an interrupted time series design. We hypothesized that PPM158 was associated with a rise in concussion-related visit rates. Results: The results of the first study yielded 30 concussion public policy recommendations categorized into 6 categories: 1) Concussion Education, 2) Return-to-Learn, 3) Removal and Return-to-Play, 4) Communication, 5) Prevention of Concussion, and 6) General. The findings of the second study included specific barriers to PPM158 implementation in Ontario, such as poor parent/guardian concussion education and low access to physician/nurse practitioner notes for return-to-activity. Facilitators of PPM158 implementation included consistency in implementation and use of resources such as relationships with healthcare professionals. The findings of the third study were an immediate increase in concussion-related visits after the effective date of PPM158 in 2015, followed by a decrease in the trend of concussion-related visits by Ontarians aged 4-18. The high-income group and the oldest age-group (13-18) both had differentially greater response to implementation of PPM158.Conclusions: Together, these three studies make novel contributions to the concussion public policy content, implementation, and impact literature. These findings provide the context and recommendations for changes to improve existing concussion public policies and directions for future research.

Advisor: Tator, Charles
Essays on the Economics of Education and Crime

This thesis contains three papers examining the effects of various policy choices, related to policing crime and providing schooling options for children, on the education outcomes of children in primary school. In Chapter 1, I examine the effects of a geographically targeted proactive policing strategy in Los Angeles on the education outcomes of young students. I document substantial heterogeneity in the effects of the policy, which enhanced police authority to arrest suspected gang members inside `safety zones'. Although the targeted policing strategy was effective in reducing crime and improving academic progress for many, the analysis draws attention to collateral damage inflicted on some at-risk children that ongoing and future policing initiatives could seek to mitigate. In Chapter 2, I investigate how the consolidations of public schools in an underperforming system impacted students and teachers who were displaced by closures, as well as those who were indirectly affected. Using a matched event study design that controls for students’ enrollment histories, we observe no persistent negative effects on students’ achievement in standardized tests, consistent with the existing literature. Moreover, students displaced from underperforming schools experience large achievement gains relative to their non-displaced peers. Altogether, the results indicate that cost-saving consolidations can be made without harm to achievement when schools are closed in the vicinity of adequate alternatives, and under ideal circumstances can be advantageous. Chapter 3 assesses whether expansion of school choice through the open enrollment provision of `No Child Left Behind' (NCLB) was effective in shifting students away from low performing schools in California. Using the discontinuous assignment to open enrollment under NCLB, I identify the causal effect of being sanctioned with open enrollment on subsequent enrollment growth. I uncover small and statistically insignificant enrollment declines for schools that marginally failed to make AYP and were sanctioned with school choice for one year, and statistically significant declines in enrolment growth of 2.7 percentage points for schools that had school choice for a second year. Heterogeneity analysis suggest that school supply constrains hinder the ability of school choices policies to improve education quality.

Advisor: McMillan, Robert
Broadband Field Enhancement in Plasmonic Nanostructures and Associated Molecular Sensing Applications in the Visible and Infrared Regimes

Broadband plasmonic light trapping enables the development of versatile platforms for enhanced light-matter interaction with applications in many fields including high-sensitivity molecular detection. Specifically, enhanced vibrational spectroscopy is a promising modality for point-of-care testing, which can enable rapid disease detection and improve patient outcomes. In this dissertation we explore the design, fabrication and implementation of devices for broadband electromagnetic field enhancement in both the visible and infrared regimes, and demonstrate their potential as platforms for point-of-care disease detection. We present a versatile, analytical and highly accurate design paradigm for rainbow trapping in sub-wavelength cavity arrays by utilizing both groove-width and groove-length as tuning parameters. To produce devices capable of visible field enhancement, we couple this design technique with fabrication through multilayer thin-film deposition and focused ion beam milling, enabling the realization of unprecedented feature sizes down to 5 nm and corresponding extreme field enhancements. We additionally develop devices for broadband infrared enhancement using nanoskiving as a rapid, high-throughput alternative to ion milling, maintaining ultrathin groove widths and facilitating ultra-high aspect ratios up to 500. We demonstrate high-sensitivity molecular sensing in width-graded cavity arrays using both surface enhanced Raman spectroscopy and surface enhanced infrared absorption. Using concentric 'bullseye’ cavity arrays and enhanced Raman spectroscopy we detect dilute rhodamine 6G in water at two excitation wavelengths, and by varying the cavity geometry show that enhanced surface area is a key parameter in maximizing measurement sensitivity. To realize enhanced infrared absorption, we measure the absorption spectra of the polymer PMMA on a width-graded multilayer structure, demonstrating broadband infrared field enhancement across the fingerprint region. To illustrate the utility of broadband plasmonic devices as platforms for disease detection we develop an animal model for the detection of biomarkers for cardiovascular disease using multi-wavelength enhanced Raman spectroscopy and machine learning classification. Through this label-free method we obtain classification accuracies over 90%, and show that multi-wavelength classification consistently produces greater accuracies than single-wavelength models. We further explore the impact of key experimental design factors on the robustness of ML models and provide a guideline for the advancement of vibrational spectroscopy towards clinical point-of-care testing.

Advisor: Kherani, Nazir P
Matsuura, Naomi
A New Perspective on the Wetting of a Surface by the Drops of an Emulsion

Spinodal wetting theory of a drop on a solid substrate requires that a bridge be formed, which connects the drop and the substrate, and that this bridge grows laterally to complete the spreading process. Here, we show that due to trace solubility, dissolved drop phase can diffuse to the solid surface, and then nucleate and grow in the form of islands. Coalescence between the drop and the islands completes the wetting process. In this work, experiments involving buoyancy-driven motion of glycerol drops in viscous suspending media, towards a flat substrate such as mica or SU-8 were conducted. The film drainage dynamics and wetting behavior were captured using reflection interference contrast microscopy (RICM). When glycerol drops settled in silicone oil , towards a mica substrate, the film drainage ceased due to polymer confinement at film thicknesses of about 10 nm. Further, glycerol islands were found to emerge at the silicone oil/mica interface. Eventually, coalescence between the glycerol drop and the glycerol islands completed the wetting process. The experiments were then extended to small-molecule media such as castor oil, and in the presence of a non-ionic surfactant called Span 80. When glycerol drops settled in castor oil towards a plasma-treated SU-8 substrate, glycerol islands were found to nucleate and grow. The addition of Span 80 to castor oil caused dramatic nucleation of islands with a foam-like cellular structure owing to a reduction in the nucleation barrier. The stability of high curvature islands in the presence of a low curvature drop was addressed by considering an extended Kelvin equation that accounts for disjoining pressures near the contact line. This equation predicts that while the solubility associated with a curved surface is higher than that of a flat surface, the solubility is significantly decreased near the contact line, provided the surface forces are attractive between the substrate and the drop phase. Using this hypothesis, we developed mathematical models corresponding to influx at the contact line and outflux over the curved surface of an island. Our stability analysis showed that during the approach of a drop towards an attractive substrate, islands can continuously grow.

Keywords: Film instability
Heterogeneous nucleation
Interference contrast microscopy
Polymer confinement
Thin film drainage
Wetting
Advisor: Ramachandran, Arun
High-throughput Biomedical Devices for Clinical Applications

Microfluidic systems have shown tremendous promise in biomedical applications; however, their clinical adoption has been slow. Particularly in fertility and pharmaceutical applications, the limited throughput of microfluidics is a barrier to translation. This thesis seeks to address barriers to scaling microfluidics throughput to meet the clinical application requirements. In many cases this involves the development of new architectures that extend interaction areas – of cells and structures, of cells and imaging area, and of fluid reactants for cell-free therapeutics. The first work demonstrates a 3D-structured device that processes a high volume of raw semen and selects the highest quality sperm with a sufficient quantity for downstream assisted reproduction treatments (Chapter 3). This work is further advanced toward the clinical adoption with a successful pilot test at a Toronto fertility center. Focusing on the male infertility diagnosis, an automated sperm DNA integrity assessment method is developed that quantifies DNA quality of thousands of sperm cells at the single-cell and population levels (Chapter 4). Building on the developed automated technique, a new method is developed that uniquely enables spatial mapping of the DNA quality of sperm inside microfluidic devices with a single-cell resolution (Chapter 5). In the last work, an exchange-membrane system is developed for therapeutic proteins synthesis at a clinically relevant throughput (Chapter 6).

Advisor: Sinton, David DS
Elucidating and Harnessing Atomistic Processes to Design Nanoparticles

Crystals are known to grow nonclassically or via four classical modes (the layer-by-layer, dislocation-driven, dendritic, and normal modes). While the field of nanoscience considers this framework to interpret inorganic nanoparticle (NP) growth, how many NPs grow remains enigmatic, suggesting that this framework may be incomplete. This thesis develops approaches to investigate NP growth, expands this framework, and applies these insights to design NPs. Supersaturation is the fundamental parameter driving crystal formation but generally cannot be measured during colloidal NP growth. We develop a methodology that relates the optical properties of growing NPs to the supersaturation dynamics underlying their growth. Using this approach, we investigate the seed-mediated growth of Au nanocubes, revealing a triphasic sequence of supersaturation dynamics, which is more complex than previously imagined. Our approach can be used to predict NP growth profiles and identify supersaturation-associated shape evolutions, providing insight towards rational design. We next studied the solution-phase growth of pentatwinned Au nanorods without Br, Ag, or ammonium surfactants. Lower supersaturation conditions favored anisotropic growth, which appeared at variance with the known modes. The vicinal facets of these nanorods (situated inbetween {100} side-facets and {111} end-facets) facilitated {100}-to-vicinal-to-{111} adatom funneling. Our results were consistent with nanorods growing via two modes simultaneously: radial growth occurred via the layer-by-layer mode on {100} side-facets, whereas asymmetric interfacet adatom migration to {111} end-facets mediated longitudinal growth. The latter supports a fundamental growth mode in which monomer deposition and integration occur on different facets. To expand the design capabilities for colloidal NPs, we developed the transitory synthesis pathway, which uses transitory ligands to spatiotemporally separate synthesis from capping. Transitory synthesis uses simple benchtop chemistry to enable for the efficient, modular design of NPs and their final surface features. We experimentally demonstrated >100 distinct NPs, including heterostructured multimetallic compositions and many previously unattainable designs. Lastly, we conducted proof-of-concept studies towards the development of NP timers integrated within contact lenses. Based on NP colloidal stability, these indicators passively use discrete, programmable color transitions to prompt patients to dispose of their lenses after the recommended lifetime. Moreover, this approach is compatible with industry standard sterilization and manufacturing practices.

Keywords: capping agent
classical crystal growth theory
nanorod
supersaturation
surface diffusion
vicinal facet
Advisor: Gu, Frank X
Energy Transfer in Emerging Triplet Fusion Platforms: Towards Functional Photon Upconversion Technologies

While the concept of converting low-energy photons to higher energy photons may sound fictional from a thermodynamic view, triplet fusion upconversion achieves this in a trade of photon number for photon energy. This incoherent photon upconversion process is a spectral management strategy that yields higher energy photons from the energetic input of two or more low-energy photons. Using the process of triplet fusion, energy is stored in the long-lived triplet excited states of molecules until a suitable energy outlet is found. Combing the energy from these two triplet-excited chromophores yields an emissive singlet with more energy than the original input photons. In this thesis, I explore the development of triplet fusion upconversion platforms, using spectroscopic insight to inform key application targets.I introduce the concepts fundamental to understanding triplet fusion upconversion—outlining how triplet excited states are prepared, how energy is transferred between them, and how the energy from these triplets may be combined in a useful way. I provide the theoretical background required for understanding spectroscopic observables and highlight focal points of the quantum mechanical principles controlling triplet exciton interactions. Then, I report my proof-of-concept demonstration of nanocrystal-sensitized upconversion photochemistry. I focus on the process of endothermic triplet sensitization using a novel class of ultrasmall lead sulfide nanocrystals. Spectroscopy of this system reveals the quantitative benefits of using nanocrystal sensitizers with long excited-state lifetimes. Additionally, I improve the performance of these vulnerable nanocrystal sensitizers by installing a monolayer, self-limiting shell. Mitigating non-radiative losses in these nanocrystals pays immediate dividends for triplet sensitization and upconversion, highlighting the need for top-to-bottom design. Finally, I focus on the process of triplet fusion itself, investigating the triplet fusion kinetics of a structurally rigid tetracene dimer. Comparing this novel emitter with monomer controls reveals incisive differences in the usage of triplet excitations after sensitization, hinting at a key concentration dependence. Using spectroscopy as a tool to understand the key photophysical targets for nanocrystal-sensitized triplet fusion upconversion applications, I provide an outlook for future work in this domain. I especially focus on systems that would benefit from the synergistic design rules identified in this thesis.

Keywords: nanocrystal
photophysics
spectroscopy
upconversion
Advisor: Wilson, Mark W B