VictorJuiz/thesis huggingface dataset:
Chemistry and Reactivity of Lone Pair Bearing Electron Deficient Main Group Compounds
Keywords: Frustrated Lewis Pairs
Hydrosilylation
Lewis Acid Catalysis
Main Group
Polycationic Lewis Acids
Radical Chemistry

Due to concerns around the cost, abundance, and toxicity of precious metal systems used for various chemical transformations, substantial research has targeted cleaner and cheaper catalysts. Motivated by the discovery of frustrated Lewis pairs (FLPs) and their ability to reversibly activate H2, main group compounds have become attractive alternatives. Consequently, metal-free advancements have recently been reported for nitrogen fixation and the Fischer-Tropsch process. To continually develop these new advancements, new and robust Lewis acid compounds are of significant fundamental interest. This work explores the synthesis and reactivity of various electrophilic compounds based on carbon, phosphorus, and sulfur. The reactivity of electron-deficient N,N’-diamidocarbenes (DAC) was explored with various common main group Lewis acids with results showcasing their ability to stabilize unpaired electrons. These carbenes were shown to undergo nucleophilic substitution to the C6F5 rings of B(C6F5)3 leading to the stabilization of analogues of the B(C6F5)3•- radical anion. Furthermore, with other Lewis acids, such as Ph3C+, spontaneous radical formation was observed, a rare observation from the combination of a Lewis acid and a Lewis base. New base-stabilized phosphorus(III) polycationic species were prepared through the use of various ligands based on nitrogen and phosphorus. An air-stable P(III)2+ example bearing a terpyridine ligand was shown to be an effective catalyst towards the hydrosilylation or reductive hydrodeoxygenation of aldehydes, ketones, and olefins. Similarly, new P(III)3+ species stabilized by transannular interactions showed unusual ambiphilicity by these highly charged species. Finally, this strategy was used in the synthesis of new and robust base-stabilized thionylium dicationic (SO2+) species. Computational and experimental studies show that these compounds are moderate Lewis acids through S-N σ* orbitals, with comparable Lewis acidity to BF3 and PF5. These compounds were shown to be able to enact the C-F bond activations, with the loss of SOF2; and O2- abstraction reactions of phosphine oxides and CuO, with the loss of SO2. Furthermore, due to a high s-character of the lone pair of these SO2+ species, they were highly resistant towards the direct oxidation of the sulfur centre.
Development of High-temperature Thermoplastic Foams: Investigation on Foaming Behaviors of Sulfone Polymers
Keywords: Foam injection molding
High temperature thermoplastics
Microcellular foams
Nanocomposite
One-step batch foaming
Solubility

One of global efforts to address the growing environmental concerns pertaining to energy consumption in automotive and aerospace industries is to replace conventional materials with lightweight alternatives. In this regard, development of industrially viable high-temperature polymeric foams is of significant interest. Generating microcellular structures with lightweight thermoplastics would not only provide weight reduction but also tailorable properties based on the cell architecture. Furthermore, utilizing environmentally benign physical blowing agents, for instance CO2 and N2, to develop such structures would additionally reduce the environmental footprint of manufacturing processes. Despite the economic and the environmental advantages of high temperature polymeric foams, the development is still at its inception. There is a limited number of studies on the foaming of high temperature polymers and the majority are based on the two-step batch foaming process, in which cell nucleation was induced thermally through rapid heating. Although the results may be meaningful, it is not applicable to continuous foaming processes that utilize pressure quench as a means of inducing thermal instability. In this regard, the present dissertation is dedicated to investigating various aspects of processing high-temperature sulfone polymer foams and making a transition from small scale batch to continuous processes. The study commenced with fundamental research on the solution properties of sulfone polymers and CO2. Empirical as well as theoretical determination of gas solubility and observation on plasticizing effects of CO2 on the thermal behaviors of polysulfone (PSU) and polyethersulfone (PES) were conducted and discussed in relations to foaming. The one-step batch foaming process was employed to discern the effects of processing parameters on the foaming behaviors of PSU and PES. Uniform cellular structures exhibiting high cell densities ranging up to 1010 cells/cm3 were developed affirming that the pressure quench method was effective in producing high density foams. Subsequently, foam injection molding techniques were implemented for the continuous production of PSU foams. Impact and tensile properties of the foams were characterized and analyzed based on the parameters of cellular structures. Lastly, graphene nanoplatelet (GnP) was introduced in the processing of PES foams. The effectiveness of GnP as a cell nucleating agent, and the effects of cell structures on the electrical performance of the nanocomposites were investigated. Overall, the dissertation provides a comprehensive framework of high-temperature foam processing that focuses on process-structure-property relationships of sulfone polymer foams.
Data Fusion Methods to Support Travel Demand Modelling in Emerging Contexts
Keywords: Choice modelling
Data fusion
Econometrics
Emerging transportation services
Travel demand modelling

In the face of growing incomprehensiveness of traditional data sources, lack of behavioural information of emerging sources, and changing data requirements of advanced models, the dissertation investigates the feasibility of fusing data from multiple sources to generate richer, more comprehensive, and more representative information to support disaggregate travel demand modelling. It presents an econometric data fusion framework that is based on four dimensions: purpose of fusion, characteristics of input data, feature of fusion methods, and nature of outputs. It proposes a conceptual framework to integrate econometric data fusion with activity-travel model to create a consistent simulation system. The thesis presents four empirical investigations that implement parts of the proposed conceptual framework. The first two studies demonstrate the feasibility of fusing traditional data with emerging data to infer the missing semantic information of the latter. The first exercise proposes an econometric fusion method to infer trip purposes from GPS trajectories of ride-hailing services in Toronto by combining with travel survey and land use data. The inferred trip purpose pattern extends our understanding about ride-hailing demand and helps account for trip underreporting in travel surveys. The second investigation infers origin and destination zones of transit trips from smart card data by fusing with survey data, land use information, and network characteristics. This helps generate up-to-date demand data necessary for public transport planning and operations. The dissertation also demonstrates the feasibility of fusing multiple survey data to capture travel attitudes and preferences. The third analysis focuses on enriching a “core” travel diary survey with attitudinal information from “satellite” surveys via implicit fusion to evaluate the impacts of COVID-19 on passenger travel demand. The results highlight the ability of the imputed variables to support the estimation of an advanced econometric model. The fourth investigation proposes a model-based method to fuse repeated cross-sectional travel survey data based on the theory of rational inattention to capture travel preference evolution and enhance the forecasting robustness of discrete choice models. Taken together, the components of this dissertation lay the framework for producing rich and accurate input data for evidence-based transportation planning in the emerging context.
Art for whose sake? Occupational Identity, Commercialization, and Innovation in the “Porcelain Capital” of China
Keywords: Art
China
Identity
Innovation
Occupations and professions

When and how could experts translate the growing power of the audiences of their work (e.g., clients and customers), which existing research often characterizes as an occupational identity threat, into an opportunity for product innovation and identity reconstruction? I answer this question using a qualitative ethnography and a quantitative audit study of porcelain artists in China who have been forced to cater to market audience demands due to a market shift. I found that when facing challenging feedback from market audiences on their work, artists who distilled the core material element(s) of their work products that signify their occupational identity, and successfully experimented novel work products integrating their distilled material element(s) with audience feedback, innovated new artistic products and reconstructed their occupational identity. I further found that artists who did not go through the distilling and/or experimenting processes either quit the market or built strong segmentation between the work products that they created catering to audience feedback from their occupational identity through work product self-categorization, which helped protect their existing work and occupational identity. These findings contribute to a richer understanding of the role audience feedback, material objects, and innovation play in occupational identity processes, as well as the market implications of holding an unwavering occupational identity.
Evaluation of Strategies for Managing Anemia and Transfusion in Cardiac Surgery and Risk Factors for Cardiovascular Health
Keywords: Anemia
Cardiac Surgery
Cardiovascular Disease
Transfusion

Patients with high cardiovascular risk may develop coronary artery disease requiring surgical intervention. The primary focus of this thesis was to evaluate strategies for reducing the potential risks associated with anemia in cardiac surgical patients. A secondary focus of this thesis was to explore the potential cardiovascular risks associated with cannabis in young adults. The first study was a subset analysis of the Transfusion Thresholds in Cardiac Surgery (TRICS-III) trial evaluating transfusion thresholds in patients with acute myocardial infarction on long-term cardiovascular outcomes, and a synthesis of the results with all available evidence through a systematic review and meta-analysis. We identified that liberal transfusion strategies may reduce the risk for long-term major adverse cardiovascular events. The second study was a subgroup analysis of the TRICS-III trial evaluating transfusion thresholds in patients with diabetes undergoing cardiac surgery. Despite patients with diabetes having increased cardiovascular risk, restrictive transfusion did not increase the risk for clinical outcomes and was more effective at reducing transfusion. The third study was a translational study of the TRICS-III trial evaluating the role of plasma methemoglobin as a marker for anemia-induced tissue hypoxia. Reductions in hemoglobin were associated with increases in methemoglobin, and elevated post-surgical methemoglobin was associated with an increased risk for neurological outcomes. The fourth study was a cross-sectional analysis of the nationally representative Behavioral Risk Factor Surveillance System survey to evaluate the association between recent cannabis use and myocardial infarction in young adults. Recent cannabis use was associated with a 2-fold increase in the risk for myocardial infarction. This risk was elevated in more frequent users of cannabis, and was sustained across all methods of consumption. We demonstrated that there may be differences in the susceptibility of anemia and tolerance to transfusion in specific subgroups of patients with high cardiovascular risk undergoing cardiac surgery, and incorporation of a biological marker of anemic stress may better inform clinical decision making for personalizing transfusion therapy for improving postoperative clinical outcomes and reducing unnecessary exposure to banked blood. Additionally, insights from our cross-sectional study may inform individual decision making regarding an underappreciated cardiovascular risk associated with cannabis use.
Improving Precision of Vancomycin Dosing in Neonatal Sepsis based on Clinical Outcome Evaluation and Population Pharmacokinetics
Keywords: neonatal intensive care unit
neonates
population pharmacokinetics
therapeutic drug monitoring
vancomycin

Background: Neonatal sepsis is commonly treated with vancomycin in the neonatal intensive care unit (NICU). Vancomycin dosing remains a challenge in neonates due to significant pharmacokinetic variability and unclear vancomycin target range.Objectives: This research aims to determine vancomycin target range associated with clinical outcomes and develop a better dosing strategy using population pharmacokinetics (popPK) to maximize probability to reach study-derived target range in neonates. Methods: A systematic review was conducted to summarize vancomycin popPK models in neonatal and paediatric patients. A retrospective cohort study included NICU patients receiving intravenous vancomycin. The associations between vancomycin trough concentrations and persistent/recurrent infections and mortality or acute kidney injury were assessed using logistic regression and classification and regression tree (CART) analyses. A popPK model was derived and validated using nonlinear mixed effects modelling. The predictive performance of the derived popPK model was compared against published popPK models. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens. Results: A one-compartment model incorporating weight, postmenstrual age (PMA), and serum creatinine (SCR) best described the observed data from 655 vancomycin courses in 448 neonates with highest accuracy and precision compared to other published models. A strong association between time to reach target range and composite outcomes was demonstrated (p=0.005). A vancomycin trough concentration >10 mg/L was associated with lower odds of persistent/recurrent infections (adjusted odds ratio: 0.3, 95% confidence interval (CI): 0.09-0.86, p=0.023) and >15 mg/L was associated with increased risk of acute kidney injury (adjusted hazard ratio of 2.94, 95% CI: 1.10-7.90, p=0.003). CART-derived area under the concentration-time curve over 24 hours (AUC24h) of 420-650 mg*h/L appeared to be associated with lowest risk of persistent/recurrent infections or mortality (p=0.025). MCS-derived vancomycin doses achieved >90% target attainment for trough target range of 10-15 mg/L in majority of PMA and SCR categories (78%). Conclusion: A vancomycin trough target range of 10-15 mg/L was associated with most optimal outcomes in treating neonatal sepsis, which supports using vancomycin trough concentrations for therapeutic drug monitoring in neonates. A vancomycin dosing guideline using loading dose was derived to increase probability of target attainment and time at target in neonates.
Investigating WDR12 as a Therapeutic Target in Breast Cancer
Keywords: breast cancer
drug target
ribosome biogenesis
senescence
WD40 repeat
WDR12

Breast cancer is the most diagnosed and lethal cancer globally in women. Presently, there is a need for novel targets for the development of improved therapeutics. Data mining through genetic screens suggests that the ribosome biogenesis protein WDR12 is essential for breast cancer cell proliferation. In this study, we characterize the effects of WDR12 knockdown in a panel of breast cancer cells. We show that WDR12 knockdown induces ribosomal RNA (rRNA) processing defects resulting in strong growth inhibition in all breast cancer cells tested, however only a subset of lines displayed short-term cell cycle defects. To further understand the cellular consequences of WDR12 suppression, we investigated the global proteomic landscape and found that WDR12 knockdown results in a perturbation of translational and ribosome biogenesis-related networks. Furthermore, we performed RNA-sequencing to assess the global transcriptional changes upon WDR12 knockdown and found dysregulation of the endoplasmic reticulum (ER) stress response pathway. Finally, we characterized the effect of long-term WDR12 suppression and found that growth inhibition was in part due to cellular senescence. Our results demonstrate that WDR12 is implicated in breast cancer cell growth and senescence, and its suppression may represent a viable therapeutic target for breast cancer.
Meeting in the Middle: Teacher-Facilitation of Play and Math Learning in Contemporary Kindergarten
Keywords: kindergarten
mathematics
play

Early math ability is a powerful predictor of future academic learning and opportunity (Duncan et al., 2007). To teach early math skills, many kindergarten programs world-wide endorse (Tafa, 2008), or mandate, play-based pedagogy (Ontario Ministry of Education, 2016), yet all play is not equal when it comes to math learning. Experimental evidence shows that a specific type of teacher-facilitated play, called guided play, leads to greater math learning gains than traditional approaches like direct instruction or free play (Fisher et al., 2013; Skene et al., 2022), however, classroom-based research shows that guided play is uncommon in practice (Wickstrom et al., 2019). Further work is needed to understand how teachers are successfully translating theory into practice by optimizing the middle ground of guided play to support early math learning.This study used qualitative inquiry and thematic analysis to respond to this central challenge. It began by collecting survey data to understand kindergarten educators’ perspectives regarding play, math, and the integration of play and math. Participants who described guiding play to support math were purposefully selected for follow up interviews. Results identified three key findings. First, the majority of educators described more indirect approaches to play and math learning in kindergarten, where children learn math through opportunities for free play without adult intervention. Conversely, only a minority of educators described more direct, or teacher-facilitated, approaches to math learning in kindergarten through various approaches to play and direct instruction. Second, educators who described these teacher-facilitated approaches also described evolving their conceptualizations of play and math learning into a singular and unified construct, that young children learn math through play. Third, this evolved perspective helped educators to then implement various approaches to guided play in practice. Implications of these findings point to a larger conversation about the need to move away from child-led approaches to early math learning and towards teacher-facilitated approaches instead. Importantly, this discussion will identify the key factors that educators leveraged to help them successfully transition towards teacher-facilitated approaches to math and will discuss what can be done to support more educators in also successfully making this transition.
Elucidating the Role of Lipid Binding Domains in V-ATPase a-subunits
Keywords: membrane protein
phosphoinositides
V-ATPase

V-ATPases are H+ pumps essential for housekeeping functions such as acidifying Golgi, lysosomes, and endosomes. V-ATPases on the plasma membrane (PM) of osteoclasts pump acid onto the surface of bone to demineralize bone, while V-ATPases on the PM of tumour cells acidify the extracellular space required for metastasis. A drug design towards inhibiting V-ATPase activity to prevent bone loss or metastasis must develop a strategy for targeting only V-ATPases on the PM of tumour cells or osteoclasts without affecting V-ATPases involved in housekeeping roles. In mammalian cells, the V-ATPase a subunit has four isoforms, a1-4, that are responsible for targeting V-ATPases to specific cellular locations. Human mutations in the four isoforms have been linked to different diseases. Among the four isoforms, a2 is found in the Golgi membrane while a3 and a4 are primarily expressed on the PM of osteoclast, and kidney cells, respectively. In invasive cancer, both a3 and a4 at the PM of tumour cells are required for tissue invasion and metastasis. Protein primary structures reveal a putative phosphoinositide (PIP) binding domains, containing a highly conserved basic motifs within all a isoforms. Using site-directed mutagenesis, I showed that the basic motifs to affect PIPs interaction and that disruption of the interaction impaired membrane targeting of the N-terminal domains of both a2 and a4 isoforms. In addition, altered levels of membrane PIPs mislocalized both proteins. Mutations in a1, a2, a3 and a4 are associated with epileptic encephalopathy, cutis laxa, osteopetrosis and renal tubular acidosis (dRTA), respectively. To understand the role of a subunit-PIPs interaction in human diseases, disease-causing mutations occurring within the putative binding domains, specifically: a2.K237_V238del (cutis laxa), and a4.K237del (dRTA) demonstrated defective PIP binding in vitro and impaired membrane retention/targeting in HEK293 cells. This data suggests that the a2-PI(4)P interaction is required for Golgi retention/targeting, and a4¬-PI(4,5)P2 interaction is required plasma membrane retention/targeting. This work enhances our understanding of a subunit functional domains, and informs potential targeted therapeutic treatment for metastatic cancer and bone loss pathologies.