VictorJuiz/thesis huggingface dataset:
Comparative Analysis of CaV1 and CaV2 Voltage-gated Calcium Channels from Trichoplax adhaerens Reveals Early Divergence of Channel Types and Biophysical Properties

To translate electrical signals into chemical signals at the synapse, cells employ voltage-gated calcium (CaV) channels. Most animals have three types of CaV channels, CaV1-CaV3, and of these, CaV1 and CaV2 channels have distinct roles at the synapse that are conserved across many animal phyla, from invertebrates to humans. CaV2 channels are involved in exocytosis of vesicles from the presynaptic cell, and CaV1 channels are typically involved in triggering gene transcription or contraction at the postsynaptic cell. CaV1 and CaV2 channels from nematodes to mammals have conserved features that are important for their post-/presynaptic functions, and it is possible that these features are conserved in more early-diverging animals as well. The most early-diverging animal phylum to have all three CaV channel homologues is the Placozoa. Placozoans are microscopic, marine animals that lack true tissues and synapses but still exhibit complex behaviours. Because they lack synapses but have all three types of CaV channels, they can be used as an evolutionary outgroup to examine the properties of CaV1 and CaV2 channels. The work presented in this thesis describes the characterization of the CaV1 and CaV2 channel homologues cloned from the placozoan Trichoplax adhaerens. The T. adhaerens CaV1 (TCaV1) and CaV2 (TCaV2) channels share structural and functional features that differentiate them from the TCaV3 channel. The biophysical properties of the TCaV channels were found to be more similar to their mammalian homologues than each other. However, differences in modulation by cytosolic proteins such as G-proteins and calmodulin, which are defining features of these channels in mammals, are lacking in TCaV1 and TCaV2 channels. Thus, ancestral CaV1 and CaV2 channels likely diverged in their biophysical properties before gaining the ability to be modulated by different cytosolic proteins. Finally, TCaV1 and TCaV2 channel expression was examined in vivo, revealing that these channels are expressed in cell types that are known to be contractile and neuroendocrine-like. The differences in TCaV1 and TCaV2 expression suggests that they have different functions in vivo. Overall, this work provides invaluable insight into the properties of T. adhaerens CaV channels and contributes to our understanding of metazoan CaV channel evolution.

Keywords: calcium
early-diverging
evolution
invertebrate
Trichoplax adhaerens
voltage gated calcium channels
Advisor: Senatore, Adriano
Development of Main Group Systems for Small Molecules Activation

Frustrated Lewis pairs (FLP) have been introduced as an alternative to transition metal catalyst. Since the first discovery in 2006, FLP has found diverse applications in areas such as small molecules activation and catalysis. The present thesis has two major directions: 1) find new types of FLP; 2) demonstrate their unusual reactivity. Alkali metal species are shown to mimic FLP behavior. The combinations of Lewis acidic alkali metal cations with hydride (H-), carbanions (R3C-), amides (R2N-) or phosphides (R2P-) are shown to activate H2 reversibly and hydrogenate unsaturated molecules. In addition, the reaction of alkali metal species with CO affords the transient anionic carbene intermediate, which can either undergo CO polymerization or react with H2 to form the Fischer-Tropsch type of products. In a different approach, we showed compounds contain covalently bonded group 13 and 15 elements remain reactive towards CO2 activation. For example, indium amide systems (R2In-NR’2) are shown to readily activate CO2 and has been developed as catalysts for the synthesis of 1,3-disubstituted ureas.

Advisor: Stephan, Douglas Wade
Machine Learning-aided High-throughput Synthesis and Development of Optoelectronic Materials

In recent years, researchers have increasingly turned to machine learning (ML) techniques to help accelerate research spanning disparate fields. This has largely been motivated by the advent of readily accessible high-performance computing techniques; and equally by the need to decrease the time in which lab-scale products reach the market. The development of metal-halide perovskites (MHPs) in particular can benefit from accelerated techniques: MHPs have emerged as excellent optoelectronic materials, but despite seeing unprecedented research intensity in the last decade, only a small fraction of the available chemical space has been explored. In this thesis I present workflows to accelerate the discovery and understanding of new optoelectronic materials.I begin by developing a ML-accelerated workflow for the synthesis and characterization of perovskite single crystals. I demonstrate that a Protein Crystallization Robot can be modified to prepare autonomously 288 independent perovskite single crystal growths. The robot acquires iii images as the crystal growth proceeds, allowing for direct measurement and classification of each experiment. I then use this method, aided by ML, to discover the growth conditions for a new Cl-based MHP. I characterize this perovskite and find that it emits light in the deep-blue region. Next, I use Quasi-Elastic Neutron Scattering (QENS) to identify the dynamics of the multiple cations in state-of-art perovskite solar cell compositions as a function of bromine incorporation. I find that the suppression of one of the cations, FA, correlates with an increased carrier lifetime. I find that when the fraction of bromine that is incorporated reaches 0.15 – a composition used extensively in literature for single-junction solar cells – the FA rotation is suppressed by more than 25% compared to the pure iodine composition. Lastly, I demonstrate how the high-throughput method I developed can be applied to discover new EO modulating materials. I use the robotic workflow to synthesize high quality perovskite single crystals. I train an ML model to classify the space group of a material from its pXRD spectra, which allows for the rapid evaluation of non-centrosymmetry, a key consideration in EO modulating materials. With this workflow I screen > 30 different ligands for new perovskite single crystals and discover three new noncentrosymmetric perovskites.

Keywords: High Throughput Experimentation
Machine Leaning
Optoelectronics
Advisor: Sargent, Edward
Unthinkability and the Self

According to one familiar story, when ordered to retract and renounce his anti-Catholic views, Martin Luther’s response was “Here I stand, I can do no other”. Like Luther, we each have our own personal limits, lines that our conscience won’t allow us to cross. These lim-its of unthinkability are where we find the self. Crossing these limits undermines one’s in-tegrity as a person. But what is it for something to be unthinkable for someone? Roughly speaking, I argue that an action is unthinkable if and only if the agent judges that she should never treat any consideration as a reason in favor of performing this action.Any plausible view of unthinkability must meet three main challenges. First, there is the challenge of “failure”. A plausible view of unthinkable must allow room for failure, that is, for the possibility of doing the unthinkable. Moreover, such a view must also explain what is special about the failure implicated in doing the unthinkable (as opposed, for instance, to the failure implicated in acting akratically). On my view, failure is possible since it is possi-ble to judge one way and act another. In addition, my view captures the special, self-undermining nature of the failure implicated in doing the unthinkable, as doing the un-thinkable consists in judging against one’s better judgment. Second, a view of unthinkability must meet the “incapacity” challenge. A view of unthinka-bility must allow us to distinguish between cases of like Luther’s – i.e. cases in which one cannot do something because it is unthinkable – and cases of mere psychological incapaci-ty – i.e. cases in which one cannot do something because it is especially disgusting or frightening. My view meets this challenge by spelling out unthinkability in terms of one’s reasoning rather than in terms of one’s motivation. Third and finally, my view of unthinkability meets the “stability” challenge: it explains that those judgments about reasoning in which one’s unthinkability consists, are more stable than other judgments (like those implicated in belief and intention), because these “un-thinkability judgments” are resistant to any incentive for reconsidering or getting oneself to change them.

Advisor: Clark, Philip
Holistic Curriculum for the Technology-mediated Post-secondary Course

This case study research examines the adaptation, design, and enactment of John P. Miller’s Holistic Curriculum (2019) in a technology-mediated post-secondary course consisting of 90 students. The research is grounded in the field of curriculum studies through a social constructivist perspective and is informed through the framework of 21st century competencies which value active learning, metacognition, and digital literacy over specific disciplinary knowledge. The course directs students toward developing these competencies as they critically identify and reflect on relationships between technology and culture, economy and power, and industry and media. A primary learning outcome is for students to contemplate their technology usage through Ursula M. Franklin’s lens of holistic and prescriptive technologies (1990). Holistic technologies create potentials for innovation, communication, and collaboration, while prescriptive technologies pose perils of conformity, inactivity, and complacency. This research occurred amid social distancing measures that were necessitated by the COVID-19 pandemic, and thus was conducted entirely online. Data indicated that students were highly engaged in the course, as it fostered a sense of connection and community, and was seen as relevant across personal, professional, academic, and creative contexts. Findings also indicated promotion of critical thinking, metacognition, and the transfer of knowledge across subject domains and disciplinary boundaries. Considerations for future enactments of Holistic Curriculum in post-secondary courses and other the technology-mediated educational contexts are recommended. These include a synthesis of holistic perspectives to inform the design of technology-mediated curriculum and the pedagogical significance of a passionate and compassionate teacher presence.

Keywords: Digital Media
Higher Education
Holistic Curriculum
Holistic Education
Technology
Advisor: Brett, Clare
The Impact of Psychosocial Factors on the Outcome of Surgical Repair for Rotator Cuff Tears – A Prospective Cohort (IMPROVE Study)

Rotator cuff tears are a common cause of pain and reduced function in the shoulder. The impact of psychosocial factors on patient outcomes following rotator cuff repair (RCR) surgery is unclear. The main goal of this thesis was to determine the association of psychosocial factors and outcomes in patients undergoing RCR surgery. Objectives: (1) To determine if psychosocial factors are associated with post-operative outcomes one-year after RCR surgery. (2) To determine if psychosocial factors are associated with disease severity at baseline. (3) To determine if psychosocial measures improve in patients one-year after RCR surgery. (4) To determine if treating surgeons are able to accurately assess patient’s mental health status at the baseline visit. Methods: A multi-centre, prospective, cohort study was performed where patients with a full-thickness rotator cuff tear were enrolled prior to RCR surgery. Patients completed multiple validated questionnaires to measure psychosocial functioning (symptoms of depression, anxiety, pain catastrophizing, treatment expectations and social support) at the pre-operative visit. Patients were followed for one year after their surgery. The primary outcome was the patient-reported Western Ontario Rotator Cuff Index (WORC) completed at one-year. The secondary outcomes were the Constant Murley Score (Constant) and the EQ-5D-5L. A multivariable regression analysis was performed. Results: 244 patients were enrolled, and 137 patients have completed a one-year follow-up. When controlling for other key variables, a multiple linear regression analysis did not demonstrate an independent association between any of the psychosocial factors and WORC scores at one year. Patients with higher levels of pain catastrophizing prior to surgery presented with worse WORC scores, Constant scores, and EQ-5D-5L health index scores at baseline and worse Constant scores at one-year. The remaining psychosocial factors were not associated with worse WORC scores at baseline. Scores on all of the psychosocial questionnaires improved between baseline and the one-year follow-up visit. The surgeons’ rating of patient’s mental health did not agree with the scores from the questionnaires. Conclusion: In this patient population, we found a low rate of clinically significant psychological symptoms and when controlling for other variables, psychosocial factors did not have a significant impact on outcomes after RCR.

Keywords: Psychosocial factors
Rotator cuff tears
Surgical outcomes
Advisor: Nauth, Aaron
The Effect of Hemodynamics on Endothelial Cell Gene Expression: The Interaction between Cis-DNA Elements and Chromatin-based Pathways

Endothelial cells (ECs) are professional sensors of shear stress (SS), the frictional force of blood flow. Endothelial nitric oxide synthase (eNOS) is an EC-specific gene predominantly expressed in arterial regions of atheroprotective laminar flow with high SS. This prototypic arterial EC gene contains two distinct flow-responsive cis-DNA elements in the promoter, the Shear Stress Response Element (SSRE) and the Krüppel-Like Factor (KLF) element. To investigate the in vivo function of these cis-DNA elements, insertional transgenic mice with a mutation at each element were generated using a murine eNOS promoter-β-galactosidase reporter. Surprisingly, the SSRE mutation abolished eNOS transcription and was associated with aberrant hypermethylation at the eNOS proximal promoter. The KLF mutation demonstrated an integration site-specific decrease in eNOS transcription, again with marked promoter methylation. Together, this indicated that both elements are necessary for a transcriptionally permissive, hypomethylated eNOS promoter and neither element alone is sufficient for eNOS transcription in vivo. We also examined the genome-wide DNA methylation profiles in arterial ECs exposed to different flow conditions. Global methylation and hydroxymethylation levels showed no changes in vivo between the aortic arch and the descending thoracic aorta in mice, as well as in human ECs in vitro under distinct arterial flow patterns, suggesting that flow-mediated changes in DNA methylation are gene-specific. Two arterial EC genes, namely eNOS and C-X-C motif chemokine receptor 4 (CXCR4), showed differential endothelial responses to SS that were associated with changes in proximal promoter DNA methylation. Laminar flow induced eNOS expression but repressed CXCR4 expression. Conversely, disturbed flow repressed eNOS expression but induced CXCR4 expression. Methylation levels at the proximal promoter region of each gene were significantly correlated with its repressed gene expression in a flow-dependent manner, indicating a mechanistic role of promoter DNA methylation in flow-mediated endothelial gene regulation. In conclusion, we describe the in vivo function of flow-responsive cis-DNA elements for the first time and present evidence for biological interplay between these elements and chromatin-based pathways, particularly DNA methylation. Moreover, we demonstrate that the expression of arterial EC genes, eNOS and CXCR4, is regulated by flow-dependent epigenetic mechanisms, offering new mechanism-based therapeutic strategies for cardiovascular diseases.

Keywords: Atherosclerosis
DNA methylation
Endothelial cells
Epigenetics
Hemodynamics
Shear stress
Advisor: Marsden, Philip
Synthesis and Surface Modification of NaLnF4 Nanoparticles Toward Applications in Mass Cytometry

This thesis describes the synthesis, surface modification and characterization of lanthanide nanoparticles (NaLnF4 NPs) designed to be used as high sensitivity reagents in mass cytometry. In the first part of my thesis, I describe my work preparing a library of single-lanthanide NaLnF4 NPs (Ln = Pr, Nd, Sm, Eu, Tb, Ho) and NaLuF4:Gd,Yb,Er upconversion nanoparticles (UCNPs) of varying diameters. From these studies, I found that identical reaction conditions led to different cubic-to-hexagonal phase change behaviors for different NaLnF4 NPs. I also observed a correlation between the phase transformation, average diameter, and size distribution of the resulting NPs. For NaLuF4:Gd.Yb,Er UCNPs, I found that in the absence of Lu, Gd promotes direct nucleation of NPs in the hexagonal phase, while the presence of Lu promotes initial nucleation in the cubic phase. I also discuss the batch-to-batch reproducibility of several reactions. Here, I found that some reactions (eg. 4 and 12 nm NaLuF4:Gd,Yb,Er UCNPs) were more reproducible than others (eg. 13 nm NaTbF4 NPs). I also present a method to troubleshoot a particular problem encountered with the NaLnF4 NP reaction, whose signature was the colour of the reaction mixture becoming brown. In the second part of this thesis, I describe my work on the surface modification NaLnF4 NPs. First, I present the work on silica coating NaLnF4 NPs (SiO2@NaLnF4 NPs) using the reverse microemulsion method. I found that by adjusting the purification method used to isolate NaLnF4 NPs from the original reaction mixture, NaLnF4 NPs of a variety of compositions, and prepared using different reaction conditions, can be coated with a thin silica shell. Dynamic light scattering experiments were carried out to better understand the silica coating process, however these results were difficult to interpret. Finally, I functionalized SiO2@NaTbF4 NPs with azide-functionalized PEG polymers. Considerable effort was spent trying to characterize the grafting density of the PEG polymers. Unfortunately, I found that these NPs had limited long-term colloidal stability in PBS buffer, and further work is required to improve the colloidal stability and to test these NPs in MC experiments.

Keywords: lanthanide nanoparticles
silica coating
surface modification
upconversion nanoparticles
Advisor: Winnik, Mitchell A
Real-time Delay Prediction and Quality of Service Assurance for Traffic Management in Service Systems

Ensuring quality of service (QoS) is one of the important challenges facing service providers. A key metric of the QoS is the experienced delay by the customers, which can depend on various factors such as the demand patterns, service capacity and the scheduling discipline. In this thesis, we study delay distribution prediction in service networks and propose novel QoS assurance methods which target the mentioned factors. In particular, the proposed methods require no knowledge of the system model or parameters, which is an important feature for real-world applications. We first consider the delay distribution prediction problem in tandem and acyclic queueing networks. Our analytical results suggest that the Gaussian mixture model can be a good candidate for estimating the end-to-end delay distribution in these systems. Motivated by this result, we use mixture density networks to propose a delay distribution predictor based on queue length information, which requires no knowledge of the system model or parameters. As the next step, we take a reinforcement learning (RL) approach and propose an admission controller with the goal of providing probabilistic upper-bounds on the end-to-end delay of the accepted jobs, while minimizing the probability of unnecessary rejections. Since admission control might not be a viable solution in some applications, we propose a deep RL-based service-rate controller as an alternative, which is capable of providing probabilistic upper-bounds on the end-to-end delay of the system by dynamic adjustment of the service rates. In the last part of this thesis, we study urban traffic management, as another important example of service systems. Specifically, we introduce two notions of fairness in this context, which are concerned with the delay of the vehicles and throughput of the traffic flows at an intersection. This is particularly important asneglecting fairness can lead to situations where some vehicles experience unacceptable long delays, or where the throughput of a particular traffic flow is highly impacted by the fluctuations of another conflicting flow. Finally, we propose two traffic signal control methods for implementing these fairness notions, which also consider the efficiency of the system at the same time.

Keywords: Quality of service
queueing
Reinforcement learning
service systems
Advisor: Leon-Garcia, Alberto
The Effects of Intelligence, Personality Traits, L1 Fluency, and L2 proficiency on L2 Spoken Fluency

This dissertation explores the underlying structure of second language (L2) fluency by investigating inter-learner variability via a comparison of the relative contributions of two understudied variables, intelligence and personality traits (extraversion, neuroticism, openness to experience, conscientiousness, agreeableness) versus known L2 fluency predictors, namely, first language (L1) fluency, and L2 lexical and grammatical proficiency. Previous research has rarely considered the effects of intelligence and personality on L2 fluency, despite their omnipresence in psychology studies. Two exceptions are Dewaele (1999) and Dewaele Furnham (2000) who found positive correlations between extraversion and L2 fluency measures, suggesting that personality may contribute to L2 fluency variation. However, this previous research failed to control for L1 fluency and L2 proficiency, known corelates of L2 fluency (e.g., Hilton, 2008; Riazantseva, 2001), lacked comprehensive fluency analyses, and relied on univariate analyses that cannot compare the effect sizes of multiple fluency predictors.In the present study, L1 and L2 speech data were elicited from 73 advanced Anglophone learners of French via a picture description task and analyzed for seven standard fluency measures. The Big Five Aspect Scales test (DeYoung, Quilty, Peterson, 2007) and a short form of Raven’s Standard Progressive Matrices (Bilker, Hansen, Brensinger, Richard, Gur Gur, 2012) evaluated personality and intelligence. A Vocabulary Levels Test and a sentence scramble test (Department of French Studies, 2020) measured lexical and grammatical proficiency. Correlational analyses demonstrated significant relationships between L2 fluency and L1 fluency, L2 lexical and grammatical proficiency, and openness to experience. Sequential regressions revealed that L1 fluency explained more L2 fluency variance than proficiency. Openness to experience was not a significant predictor after accounting for L1 fluency. This dissertation contributes to our understanding of the relative importance of L2 fluency predictors including personality and intelligence and makes a methodological contribution via its use of multivariate statistics.

Keywords: English
French
intelligence
language learning
personality
second language
Advisor: Steele, Jeffrey