VictorJuiz/thesis huggingface dataset:
Item Response Theory and Measurement Invariance Investigations of the Youth Level of Service/Case Management Inventory (YLS/CMI)

Derived from the Risk-Need-Responsivity framework, the Youth Level of Service/Case Management Inventory (YLS/CMI) is a widely implemented instrument used to assess risk of recidivism in justice-involved youth. Its results inform risk classification, sentencing decisions, and treatment planning. Given the impact of the YLS/CMI on the lives of justice-involved youth, its validity needs to be thoroughly investigated. This dissertation is comprised of three studies examining the psychometric properties of the YLS/CMI based on samples of community-sentenced youth in Ontario, Canada. Study 1 examined the YLS/CMI items and its internal structure using item response theory (IRT) analyses and confirmatory factor analysis. The YLS/CMI items loaded onto their respective domains and the domains in turn converged onto a single factor as theorized in the RNR framework. The IRT analyses demonstrated that the instrument was most informative for youth with average risk levels, with items from the Personality, Attitude, and Criminal History domains especially adept at discriminating between individuals with varying risk levels. Study 2 explored the measurement invariance of the YLS/CMI across gender (male vs. female) and race (Black vs. White) using differential item functioning (DIF) analyses within an IRT framework. Most of the items demonstrated similar discrimination across subgroups, with the exception of verbally aggressive across gender, and poor relations with father across race. Several items demonstrated differential likelihood of endorsement across gender and race. Study 3 examined the measurement invariance of the YLS/CMI across a sample of Indigenous and non-Indigenous justice-involved youth using DIF. Results demonstrated similar discrimination of the items across groups, with the exception of poor frustration tolerance. Items from the Education domain were more likely to be endorsed for non-Indigenous youth, while items from the Substance Abuse domain were more likely to be endorsed for Indigenous youth. Results also indicated that the total scores were not predictive of recidivism for Indigenous youth. Findings from this dissertation highlight the importance of investigating the psychometric properties of risk assessment instruments in order to establish its validity and understand its implications for justice-involved individuals.

Keywords: Differential Item Functioning
Item Responsive Theory
Risk Assessment
Risk Need Responsivity
Youth Justice
Advisor: Peterson-Badali, Michele
Skilling, Tracey
Indium Oxide Photocatalysis Doping, Defects and CO2 Reduction

Heterogeneous catalysis, in which the reaction of gaseous or liquid chemicals is facilitated at the surface of a solid material, is responsible for the majority of chemicals and fuels production on the industrial scale. The energy required to drive these reactions is typically derived from the combustion of non-renewable fossil resources and carries with it a significant and unavoidable carbon footprint. In the pursuit of an environmentally responsible and sustainable chemical industry, being increasingly motivated by concerns regarding climate change caused by excessive CO2 emissions, green chemistry approaches to heterogeneous catalysis are being actively sought. Such methodologies include the electrification of chemical- and fuel-production processes using renewable forms of energy, the replacement of fossil feedstock chemicals by CO2 and the substitution of heterogeneous thermocatalysis by photocatalysis. To realize this utopian vision of a sustainable future, the discovery and optimization of highly active, selective and stable CO2 catalysts is imperative. Catalytic metal oxides in particular are renowned ‘chameleons’ in the materials world, being capable of filling diverse roles in solid-state chemistry, physics and engineering, as well as being employed in the production of many industrial products, processes and devices. This prevalence of metal oxides is traceable to their myriad compositions, structures and forms, variations of which bestow upon them diverse properties, functionality and utility. Herein, we utilized two photocatalyst engineering methods to tune the surface and electronic properties of indium oxide nanomaterials that could enable solar powered gas-phase heterogeneous catalytic CO2 hydrogenation reactions. More specifically, detailed investigation on the synthesis, structure, property relations of bismuth substituted defect-laden indium oxide and reduced black indium oxide materials were established through comprehensive characterizations that include HRTEM, XAFS, XPS and PXRD. An understanding of the photochemistry and photophysics that underpins the excited state surface chemistry of gaseous H2 and CO2 has also been explored through a combination of computational modeling and advanced surface characterization methods such as Near Ambient Pressure XPS, and DRIFTS. Together these studies have demonstrated how rational and systematic variations in the structure-property relations of indium oxide enlighten our understanding of gas-phase heterogeneous CO2 photocatalysis and provide a platform for photocatalyst engineering.

Keywords: Carbon Dioxide
Defect Engineering
Indium Oxide
Photocatalyst
Advisor: Ozin, Geoffrey
Environmental Reactions of Novel and Legacy Fluorosurfactants

Per- and polyfluoroalkyl substances (PFAS) are a class of environmental contaminants grouped together by the presence of a perfluoroalkyl moiety. PFAS have a range of applications depending on their specific chemical structure including as direct-use surfactants. Due to concerns about persistence, bioaccumulation potential, and toxicity, some PFAS have been phased-out and replaced with new PFAS. This thesis explores the environmental fate of one phased-out fluorosurfactant, and one novel fluorosurfactant and its synthetic intermediate. Perfluoroalkyl phosphinic acids (PFPiAs) are fluorosurfactants that were used as wetting and levelling agents and as defoaming additives to pesticide formulations. Male Sprague-Dawley rats were dosed with C6/C8 PFPiA or C8/C8 PFPiA, which were metabolized to form persistent perfluoroalkyl phosphonic acids (PFPAs), and 1H-perfluoroalkanes (1H-PFAs), which contain one labile hydrogen that may undergo further metabolism. This was the first reported cleavage of a C-P bond in mammals, and the first attempt to characterize the degradation of any perfluoroalkyl acid. A new fluorosurfactant on the market was designed with the intention that it would degrade in the environment to non-bioaccumulative components. The surfactant diFESOS, and its semi-volatile synthetic intermediate FESOH were investigated. Atmospheric oxidation experiments of FESOH reported a short lifetime with respect to reaction with OH radicals. FESOH undergoes multiple defluorination steps to form products with fewer fluorine atoms, including perfluoropropanoic acid (PFPrA) as the terminal aqueous phase product. The surfactant diFESOS, FESOH, and another major degradation product were incubated with activated sludge from a wastewater treatment plant to assess aerobic microbial degradation. Ultimately, diFESOS degraded to lower fluorinated acidic PFAS, including small amounts of PFPrA. The formation of the metabolite 2H-3:2 PFECA is hypothesized to occur via defluorination on a carbon adjacent to the sulfur atom, which we believe has not been previously reported. Overall, major metabolites have lower bioaccumulation potential than the parent diFESOS surfactant. These laboratory studies enable understanding of environmental fate of these specific PFAS, and also contribute to fundamentally understanding the reactivity of highly fluorinated molecules, which may allow for the design of chemicals that can harness the functionality of organofluorine without persisting in the environment.

Keywords: atmospheric chemistry
biodegradation
biotransformation
contaminant
environmental chemistry
PFAS
Advisor: Mabury, Scott A
Methacrylic Acid-based Biomaterials and their Applications in Diabetes and Soft Tissue Repair

Regenerative medicine holds the promise to restore the functionality of damaged tissue through the use of medical devices that can enhance mechanical performance or deliver therapeutic cells. Clinical implementation of these devices has been limited by challenges associated with fibrosis and/or poor vascularization. Improved device design and materials are required to accelerate healing and reduce inflammation post-implantation. Methacrylic acid (MAA)-based materials are promising candidates for improving the functionality of medical devices due to their ability to enhance vascularization and tissue healing. The present work explores this proposition by evaluating the performance of two MAA-coated implants and a MAA-collagen gel: a polypropylene surgical mesh, a pancreatic islet transplantation device and a wound dressing. The first two devices were coated with MAA-co-isodecyl acrylate and implanted in mice subcutaneously; the last was produced by immobilizing polyMAA to collagen using carbodiimide chemistry. The coating lowered the inflammation around the polypropylene mesh and generated constructive remodeling by biasing the tissue response towards vascularization instead of fibrosis. To assess the effect of the coating on therapeutic cell survival, coated and uncoated devices were implanted in diabetic mice. Pancreatic islets were transplanted into implanted devices and the glucose levels were compared across both groups. Animals with MAA coated devices had the highest islet survival rate and became normoglycemic within 3 weeks of transplantation. Islet survival rate for animals with uncoated devices was low, and they remained diabetic. For wound healing polyMAA was used in a regenerative medicine application that did not require a permanent implant by utilizing a bio-degradable delivery vehicle. The topical application of this gel on hard-to-heal diabetic wounds increased vascularization, and hastened closure. Overall, the ability of MAA-based materials to overcome challenges associated with fibrosis and poor vascularization has been demonstrated in three different areas of regenerative medicine. Future work should explore the use of polyMAA-collagen gels for other tissue engineering applications

Advisor: Sefton, Michael V
Capture and Electrochemical Reduction of Carbon Dioxide to Value-added Material

The atmospheric concentration of anthropogenic greenhouse gases (GHGs) has increased substantially in the past 50 years, particularly in recent years. In response, interest in CO2 capture technologies and methodologies to reduce it to valuable synthetic building blocks, such as carbon monoxide (CO), methanol (CH3OH) and methane (CH4), has increased. Although proposing to tackle the climate issue with current carbon capture and storage (CCS) technologies is unrealistic, chemical utilization of CO2 has great potential. Controlled and selective electrochemical CO2 reduction to fuel from renewable energy, such as electricity, is a promising approach to remove and utilize CO2 from air. Electrochemical CO2 reduction reactions (CO2RRs) are among the most promising techniques for this purpose due to their simple operation and environmental economy. To achieve a system viable for industrial implementation, thoughtful design of the electrochemical cell and the molecular catalysts are both important. This body of work demonstrates a wide range of potential applications for CO2 capture and utilization. Strategies involving CO2 capture and its reduction are described and systematically evaluated in different electrolyzer setups, and a series of new catalysts sporting tunable features fit for both homogeneous and heterogeneous applications are reported herein. Successful reduction of CO2 to several gaseous products, including CO, CH4 and a CH3OH liquid product, were achieved using metallated and non-metallated porphyrin electrocatalysts as well as cost-effective and commercially available linear amines. In sum, electrochemical reduction of CO2 using homogeneous porphyrin catalysts in non-aqueous environment as well as heterogeneous immobilized porphyrin catalysts in an aqueous environment was investigated using H-Cell and Flow-Cell technologies for potential industrial applications. We have also introduced new and cost-effective primary amine catalysts for CO2RR, which is a unique approach for industrial applications. The work herein demonstrates the potential of facile porphyrin-based systems and reports on their remarkable performance as CO2 reductive electrocatalysts. Moreover, it serves as an example of an adaptive synthetic design that can demonstrate the value of reductive CO2 technology for industrial large-scale applications to fight climate change issues.

Keywords: CO2 Conversion
CO2 Reduction
CO2RR
Heterogeneous electrocatalysts
Homogeneous electrocatalysts
Porphyrin Catalysts
Advisor: Kraatz, Bernie
Zhang, Xiao-an
Intrinsic and Interfacial Fatigue of Graphene

The booming applications of graphene in flexible electronics, mechanical structures, and biomedical sensors require robust mechanical and structural properties as a premise. With the ever-increasing demand for the long-term reliability of graphene-based devices and structures, the fatigue behavior of graphene necessitates careful investigation, especially its intrinsic and interfacial fatigue behavior. The fatigue concern of graphene is more stringent under extreme loading conditions in more complicated designs, such as at severe stress concentrations and abundant interfaces in flexible devices. Here we enabled the intrinsic fatigue study of suspended two-dimensional (2D) materials based on a modified atomic force microscopy technique. We discovered that monolayer and few-layer graphene also suffered fatigue, but they exhibited remarkable fatigue life of more than one billion cycles at large stress levels (e.g., at σ_mean=71 GPa and ∆σ=5.6 GPa), which is higher than any materials reported to date. Surprisingly, monolayer graphene did not reveal any obvious progressive damage during cyclic loading as manifested by its non-changing morphology and non-degraded mechanical properties. Molecular dynamics simulations further revealed bond reconfiguration near the defective site only immediately prior to fracture. Such non-progressive fatigue nature indicates the inapplicability of macroscopic fatigue mechanisms and challenges the fatigue definition at the atomic scale. A kinetic theory was proposed to explain the fatigue behavior of graphene and highlight the strong cyclic effect on reducing its lifetime. Graphene oxide, meanwhile, also exhibited ultrahigh fatigue resistance, but revealed clear progressive damage, similar to conventional fatigue mechanisms. Despite the record-high intrinsic fatigue life of graphene, we observed significant interfacial fatigue damage when introducing graphene-polymer contact. The significant elastic mismatch and weak van der Waals (vdW) interactions at the interface not only cause graphene buckling but also propagate the buckles under cyclic loading. The buckle propagation was revealed to follow an inverse Paris’ law. Moreover, cyclic loading through the vdW interfaces could also induce significant fracture of graphene even in tens of cycles, with the main fracture modes identified as in-plane shear and tear. These studies provide fundamental insights on the dynamic reliability of graphene and call for further fatigue studies of other 2D materials and their interfaces.

Keywords: fatigue
fracture
graphene
interface
kinetics
Advisor: Filleter, Tobin
Sun, Yu
Regulation of necroptotic-apoptotic signaling in vitro and in vivo

Programmed cell death (PCD) is an evolutionarily conserved process observable in all metazoans. In mammals this process is requisite for organ and structural development of the fetus, pathogen clearance, tissue remodeling and homeostasis, responses to cellular stress, and suppression of oncogenesis. Several major forms of PCD have been characterized to date, including apoptosis, necroptosis and autophagy-dependent cell death (ADCD). Each of these forms of PCD demonstrate their own morphologic and molecular features. In particular, apoptotic and necroptotic cell death have been identified in many circumstances to be competitive in nature, often displaying a ‘winner take all’ dynamic where necroptosis provides a backup role in many tissues upon failure of apoptosis. To better understand the regulation of PCD and more specifically the interactions between apoptosis and necroptosis, I have examined these forms of cell death in two models: (1) cisplatin-mediated cell death of homogeneous populations of embryonic stem (ES) cells in vitro and (2) endothelin-1 mediated ischemic/reperfusion injury in the murine cortex in vivo. In addition to homologous gene recombination, I have also utilized pharmacologic inhibitors to interrogate the interaction of these pathways in detail for both models. Using these methods, I demonstrate that ES cells exposed to cisplatin demonstrate a hitherto uncharacterized novel form of cooperative PCD between apoptotic caspase-3 and necroptotic RIPK1 and RIPK3. Further analyses suggest that RIPK1 and RIPK3 signaling lie upstream of caspase-3 in this cooperative pathway and that the resulting cell morphology and molecular details of dead/dying cells reflect neither traditional apoptosis nor necroptosis, instead demonstrating a hybrid of both. Characterization of the neuronal cell death involved in endothelin-1-mediated cortical ischemic/reperfusion injury in vivo was similarly observed to be protected through inhibition of either RIPK1 or caspase-3. Interestingly, protection induced by inhibition of RIPK1 seem to occur upstream of caspase-3-mediated apoptosis similar to features observed in ES cells. This identification of a novel co-operative apoptotic/necroptotic signaling in turn have important implications for cell death regulation in primary tissues – in terms of both pathologic processes and pharmacologic interventions.

Keywords: apoptosis
CRISPR
necroptosis
programmed cell death
stem cells
stroke
Advisor: Henderson, Jeffrey
Gastrointestinal Transcription Factors drive Lineage-specific Developmental Programs in Organ Specification and Cancer

The adult gut houses a series of organs derived from a naïve, embryonic population, called the endoderm. During embryonic development, the endoderm specifies into unique gastrointestinal identities through the temporal and spatial control of master transcription factors. Expressed in a tissue-specific manner, master transcription factors bind to DNA regulatory elements of multiple target genes to activate organ-specific transcriptional programs. During gut development, these programs drive organ specification, its growth, and lastly, lineage determination and maintenance. Although accumulating evidence shows global enhancer activation and aberrant expression of developmental transcription factors in gut cancers, little is known about how these factors drive gastric development and cancer. In this thesis, I first defined gastrointestinal organ-specific chromatin accessibility and gene expression during development using high-throughput sequencing technologies: cumulative analysis revealed dynamic epigenetic regulation of SOX family of transcription factors during gastric determination. Furthermore, I revealed that Sox2 is not only essential for gastric specification, by maintaining chromatin accessibility at forestomach lineage loci, but it is also sufficient to promote gastric/squamous transformation upon Cdx2 deletion in the embryonic intestine. To assess if organ specific developmental programs are activated in adult gut cancers, I compared our gastrointestinal lineage-specific transcriptomes to the publicly available human gastrointestinal cancer data. Here, I found that stomach and intestinal lineage-specific programs are reactivated in Sox2-high/Sox9-high and Cdx2-high cancers, respectively, emphasizing tissue ontogeny as a mechanism for cancer initiation. By analyzing mice deleted for both Sox2 and Sox9, we revealed their potentially redundant roles in both gastric development and cancer, highlighting the significance of developmental lineage programs reactivated by gastrointestinal transcription factors in cancer.

Keywords: Epigenetics
Gastric Cancer
Organ Specification
Sox2
Sox9
Transcription Factors
Advisor: Kim, Tae-Hee
Rapid and Direct Enumeration of Hematopoietic Stem Cells in Unenriched Cell Populations

Hematopoietic stem cells (HSCs) are rare cells that sustain life-long blood cell production and can be transplanted to treat various hematological disorders. HSC enumeration is important for gauging potential therapeutic efficacy, and the current gold standard relies on months-long xenotransplantation assays, which are challenging and impractical for routine screening. It was hypothesized that rare cell populations such as HSCs can be more readily identified and enumerated based on their specific transcriptional signature and an ultrahigh throughput single-cell RT-PCR platform was pioneered. Using this platform, simultaneous detection of three targets at single-molecule level and one-step RT-PCR that integrated all the processing steps from cell lysis to the generation of fluorescent amplification products in nanolitre droplets were demonstrated. A probabilistic deconvolution algorithm was developed to decouple the confounding effects of ambient RNA and cell doublets, allowing the construction of single-cell gene signature profiles as well as the decomposition of heterogeneous populations. Furthermore, a simulation model of the droplet RT-PCR experiment was constructed to explore the limits of the platform and guide experimental design. By mixing cell lines at predetermined ratios and enumerating them instantaneously, the assay’s capability to distinguish between, and provide frequency readouts of, various cell populations based on their gene signatures was illustrated. Potential candidate markers for HSC enumeration were identified by analyzing existing microarray data collected from highly purified populations of hematopoietic stem and progenitor cells. The droplet RT-PCR platform was evaluated against other single-cell gene expression profiling technologies using an analytic hierarchy process-based framework that took into consideration their technical capabilities, logistics, accessibility, and cost. This methodological approach allows the ranking of technologies based on the requirements of specific applications, established the droplet RT-PCR platform as the most appropriate solution to routine HSC enumeration, and revealed technological gaps for further development. In summary, this work provides a suite of novel tools for ultrahigh throughput single-cell gene expression profiling and rare cell detection. It lays the technological foundations for identifying and implementing a unique RNA signature for robust and rapid enumeration of HSCs, which will accelerate stem cell research and facilitate clinical management to provide more effective HSC transplantation treatments.

Keywords: Hematopoietic Stem Cells
Microdroplet
Microfluidics
Rare cell detection
RT-PCR
Single-cell
Advisor: Zandstra, Peter W