Surface Sensitive Studies of Interfacial Water Structure in Saturated Aqueous Solution of NaClO4

Over the past years, it has been found that understanding the metal/water interaction plays a vital role in multidisciplinary fields ranging from heterogeneous catalysis and electrocatalysis to water in salt systems for advancing commercial battery technologies. It is also believed that the main properties of the WiS (water in salt) electrolytes are mainly linked to the chemical and physical properties of the interfaces between the water molecules in the WiS system and the metal electrode. This research focuses on conducting surface-sensitive studies on interfacial water in WiS systems, and the main approach of these experiments is to investigate water interaction and orientation as a function of the surface charge and NaClO4 concentration at the water/Gold electrode interface. In pursuit of this objective, ATR (attenuated total reflectance) was utilized to gain knowledge about the structure of water molecules in the solution as the concentration of NaClO4 increasing Additionally, ATR technique can provide an insight into the hydrogen bonding in the water in salt system. Utilizing ATR-SEIRAS (Attenuated Total Reflectance Surface-Enhanced Infrared Absorption Spectroscopy) in the subsequent phase of the project could potentially demonstrate valuable data about potential-dependent water adsorption as well as changes in hydrogen network strength in the double layer region as a function of the applied potential. The outcomes from the ATRSEIRAS technique provided a representation of the possible orientation of water molecules in different potentials. The hydrogen-oriented upward arrangement for water molecules is proposed in positive potentials, while in negative potentials, the hydrogen atoms of water are closer to the surface. Subsequently, the hydrogen network is stronger on the positively charged surface

Host Choice Selection in The Aster Yellows Pathosystem

The abstract of this item is unavailable due to an embargo

Voices for Change: Qualitative Content Analysis of Environmental Activists with Autism in the News

Peer ReviewedThree activists have played key roles in recent climate activism in the UK: Greta Thunberg, Dara McAnulty, and Chris Packham. Through qualitative content analysis of popular news coverage, this study explores the messages conveyed about these activists and the social inequities prevalent in media portrayals of activism more broadly. The analysis revealed that while there was content explaining and defining the causes championed by these activists, it was often overshadowed by subject-centric portrayals. The news coverage tended to emphasize the agency and influence of these individuals, while also placing undue focus on their various identity constructs. The coverage also adopted personalized and sensationalized writing strategies. Although this news coverage offered a more inclusive representation of activists in terms of disability, age, and gender, it simultaneously reinforced stereotypes, prejudice, and the authority of White, middle- to upper-class activists from the global North. These findings highlight tensions between reinforcing and challenging the privileged few who are typically allowed to represent and capture public attention and action on pressing issues

Exploring the Stability of Self-Compassion, Self-Criticism, and Grit in Professional Triathletes Within Training

Professional triathletes need to navigate a fine line of training for three sports along with the mental and physical challenges of trying to meet standards of performance in order to be successful. The purpose of my research was to observe, through an exploratory through a single case design (SCD) study, whether self-criticism, self-compassion, and grit fluctuate for professional triathletes over a 3-week training period in which they are trying to achieve performance standards. Two professional long distance triathletes completed pre- and post-test measures of self-compassion, along with daily reports of these same measures. A visual analysis of daily measures was performed, recealing a general lack of stability in the variables examined both within and across participants. While one of the two athletes did not meet standards on two consecutive days as a naturally occurring intervention point, differences in stability before and after not meeting standards were challenging to interpret and demonstrate the complexity in athletes’ experiences related to trying to achieve performance standards. It remains for future research to determine whether the daily fluctuations I observed are representative of “true” daily changes in the constructs themselves or a result of measurement error associated with using single-time measures (or a combination of both)

IMMUNOHISTOCHEMISTRY AS A TOOL FOR MECHANISTIC STUDIES OF RADIOIMMUNOTHERAPY OF OSTEOSARCOMA

Osteosarcoma (OS), characterised by the direct formation of immature bone or osteoid tissue by tumor cells, is a primary malignant bone cancer affecting humans and canines. This study explores the potential of Targeted Radionuclide Therapy (TRT), specifically Radioimmunotherapy (RIT), as a novel treatment approach for OS. RIT utilises antibody molecules to deliver radiation to tumor cells, with promising applications in treating metastatic disorders. Notably, the cation-independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) has been identified as a viable therapeutic target for RIT in OS due to its high expression in tumor cells. To investigate the impact of RIT on the OS tumor microenvironment (TME), we conducted Immunohistochemistry (IHC) analyses. The results revealed a reduction in IGF2R-positive cells, OS stem cells, and pro-tumorigenic M2 macrophages following RIT. Notably, RIT showed diverse effects on natural killer (NK) cells and M1 macrophages. Specifically, RIT employed two radioisotopes with different decay schemes: the alpha-emitting Actinium-225 (225Ac) and the betaemitting Lutetium-177 (177Lu). The alpha-emitting 225Ac led to a decrease in NK cell numbers; at the same time, the beta-emitting 177Lu increased NK cell populations, potentially indicating a stimulating effect. Likewise, the increase in M1 macrophages numbers in Gracie (canine OS cell line) and the decrease in M1 macrophages numbers in OS33 (human OS cell line) post-RIT suggests the highly dynamic and variable behaviour of TME. This research underscores the potential of RIT in modulating the TME and offers new insights into its efficacy against OS. Understanding the intricate relationship between RIT, the choice of a radioisotope, and TME is essential for refining treatment strategies and harnessing the immune system's capabilities. This study paves the way for more personalised and effective therapeutic approaches, which could benefit patients facing this challenging cancer

INFLUENCE OF MICROBIAL SULFATE REDUCTION ON PORE-WATER CHEMISTRY IN OIL SANDS FROTH TREATMENT TAILINGS

Oxidative weathering of froth treatment tailings (FTT) at oil sands mines in Northern Alberta has the potential to generate acidic and metalliferous porewater. Residual bitumen and light hydrocarbons in FTT support growth of a diverse range of microbes, including those capable of dissimilatory sulfate reduction (DSR). This biogeochemical process can be effective in removing sulfide-mineral oxidation products such as Fe, SO4, and trace elements including As, Co, Cu, Ni, Se, and Zn through sulfate reduction and sulfide mineral precipitation under anoxic conditions. While previous experiments that have stimulated sulfidogenesis through organic carbon amendments effectively decreased the mass flux of sulfide-mineral oxidation products in mining environments, the extent of this process and its ability to attenuate sulfide-mineral oxidation products in FTT supported by residual hydrocarbons is unknown. The objective of this thesis is to assess the impact of microbial sulfate reduction on FTT pore-water geochemistry and to determine the potential extent to which this process may be supported by residual hydrocarbons within the tailings deposit. Laboratory experiments were designed to examine the influence of sulfidogenesis on pore-water chemistry and to constrain rates of sulfate reduction, while assessing the capacity for metal(loid) removal due to this process. Through batch and column experiments sulfate reduction was found to contribute to metal(loid) and sulfate removal, as well as pH buffering and H2S generation. Removal of As, Co, Ni, and Se exceeded 90% in simulated porewater over a pH range of 5 – 8. Removal of Fe was minimal below pH 7, but exceeded 95% in solutions above pH 7 with long residence times. Zn removal was influenced by ∑S(-II)(aq) concentrations, with increased Zn removal seen at lower ∑S(-II)(aq) concentrations. Sulfur isotope samples taken during the batch experiment show an increase in 34S-SO4 with decreasing SO4(aq) concentrations over time, showing ongoing microbial sulfate reduction during the experiment. A mass-based approach to determine sulfate removal found sulfur removal rates remained constant around 1.5 μmol d-1 g-1 when solutions were not saturated with respect to gypsum. Residence time and pH were major influences on the effectiveness of sulfate reduction, with enhanced metal(loid) removal occurring with longer residence times at circumneutral pH. These results show the pool of organic carbon in FTT deposits is capable of supporting dissimilatory sulfate reduction and this process can decrease mass fluxes of sulfide-mineral oxidation products in FTT porewater

BALANCING OTIPEMISIWAK AND WAHKOHTOWIN: MÉTIS WOMEN AT ST. FRANÇOIS XAVIER, MANITOBA, 1790-1840

Centering the principles of otipemisiwak and wahkohtowin, this thesis examines the role of Métis women in the development of the community of St. François Xavier. While recent historiographical shifts have emphasized community-engaged histories and women’s voices, the role of Métis women within the Red River region during the first half of the nineteenth century remains largely underexplored. This research addresses this gap by highlighting how women were instrumental in shaping the community’s identity during the period of 1790-1840. Utilizing the worldviews of otipemisiwak and wahkohtowin offers a nuanced understanding of how Métis women embedded these concepts into the collective identity, asserting their independence whilst nurturing kinship. Ultimately, this thesis sheds light on the enduring significance of Métis women’s leadership and their vital role in shaping Métis identity, offering a deeper understanding of the community of St. François Xavier as a whole

Microbial Pretreatment of Camelina Straw and Switchgrass for the Production of Solid Biofuel Pellets and Bioethanol

The abstract of this item is unavailable due to an embargo

Towards High Throughput Determination of Biotransformation Rates of Chemical Mixtures Using Isolated Perfused Trout Livers

In the field of environmental risk assessment, aquatic contaminants are typically characterized by their persistence, bioaccumulation potential, and toxicity (PBT). Bioconcentration factor (BCF) is the most common metric for evaluating bioaccumulation potential and is frequently estimated using Quantitative-Structure-Activity-Relationships (QSARs) and other in silico tools. These methods can estimate BCF based upon the physicochemical characteristics of a chemical and the toxicokinetic parameters of a model organism for chemicals which do not undergo biotransformation. For chemicals which are actively biotransformed, whole animal in vivo exposures have classically been required to determine BCF for regulatory acceptance. Recently, in vitro substrate depletion assays have been adopted as an alternative to in vivo testing due to concerns of cost and ethics. The results of these assays have been met with doubt due to uncertainties involved with in vitro-in vivo extrapolation (IVIVE) methods required to bridge the gap between target organs of biotransformation such as the liver, and whole-organism outcomes. The overall objective of this thesis was to validate an IVIVE approach for estimating biotransformation in rainbow trout (Oncorhynchus mykiss) by using the isolated perfused liver method, which represents an intermediate between in vitro and in vivo. The first study (Chapter 2) involved comparing direct measurements of hepatic clearance in the isolated perfused liver with in vitro determinations of clearance which were previously published as part of a collaborative international trial for the regulatory adoption of in vitro substrate depletion assays. This comparison was performed for the model biotransformation substrate chemicals pyrene, phenanthrene, 4-n-nonylphenol, deltamethrin, and methoxychlor. The hepatic clearance rate of these chemicals was determined in isolated perfused livers by measuring the difference between chemical concentration as it entered and exited the liver, giving a measure of chemical elimination due to biotransformation. Experiments were performed over a period of several hours to validate physiological performance, and measurements of glucose efflux and pH were used to confirm aerobic respiration and thus metabolic activity. In addition, the influence of protein binding on hepatic clearance was investigated by varying the concentration of bovine serum albumin (BSA) in perfusates spiked with chemical. Measured clearances were in good agreement with in vitro substrate depletion models coupled with an IVIVE approach which takes protein binding into account. Overall, this study indicated that uncertainty associated with current IVIVE models is likely due to extrahepatic biotransformation, variability in BCF test designs, and inaccuracies in partitioning estimates or other kinetic processes such as uptake across the gills, rather than the reliability of in vitro test methodologies. The second study (Chapter 3) focused on expanding the domain of applicability of the isolated perfused liver method following validation in Chapter 2 as well as concurrent research investigating mixture experiments in ionizable organic compounds (IOCs). One of the primary concerns about bioaccumulation assessment methods regardless of in silico, in vitro, or in vivo approaches is the limited number of chemicals which have been successfully tested. To achieve the throughput needed by modern chemical risk assessment frameworks, a mixture experiment was performed using the isolated perfused liver model. This study used a chemical mixture obtained from the United States Environmental Protection Agency (EPA) as part of the EPA’s non-targeted analysis collaborative trial (ENTACT). This mixture contained over 500 chemicals, and the study utilized advanced high-resolution-mass-spectrometry (HRMS) methods to detect individual compounds in mixture at the very low concentrations required for mixture experiments. Hepatic clearance was determined for 20 substances in this mixture simultaneously, representing diverse classes of chemicals including pharmaceuticals, pesticides, and industrial chemicals. This study demonstrated that the isolated perfused liver method can be a valuable tool for bioaccumulation screening, and validated the performance of this model for diverse groups of chemicals. Chapter 4 discusses the present state of bioaccumulation assessment with regard to biotransformed chemicals, focusing on the role of the isolated perfused liver method and the goals of validation and demonstration set out by this thesis. Many studies have focused on which factors involved in IVIVE drive the discrepancies between BCFs determined by in vivo exposures with those predicted by IVIVE approaches. The difference between chemical freely available for biotransformation in the systemic circulation in vivo versus in vitro has been identified as a source of uncertainty. This ratio has typically been assumed to be identical, as this assumption whilst mechanistically impossible leads to a more reliable prediction of BCF. In Chapter 2, it was demonstrated that the influence of protein binding on hepatic clearance can be incorporated into an IVIVE model to increase reliability, indicating that prior assumptions were inappropriate. Concerns over limited domain of applicability were addressed in Chapter 3 as well as in concurrent work involving IOCs, focusing on the high-throughput nature of these experiments in which six fish were used to screen 20 chemicals. In summary, the isolated perfused liver model advanced in this thesis work has contributed to the field of bioaccumulation assessment by validating presently adopted in vitro assays. Furthermore, this work has expanded the chemical scope of methods developed to achieve high-throughput predictions of biotransformation, serving as the basis for incorporation into reliable IVIVE models

NUCLEAR FACTOR ERYTHROID 2 RELATED FACTOR-1 (NRF1) MEDIATES CELASTROL-INDUCED GENE REGULATION, DEPENDING ON ITS HETERODIMERIC INTERACTIONS

Oxidative stress has been recognized as critical in human aging and the progression of many chronic diseases, including cancer. Cells undergo oxidative stress when the overproduction of reactive oxygen species (ROS) within the cell outweighs its antioxidant defenses. As a defense mechanism, a series of cytoprotective genes is initiated and regulated by various transcription factors in order to minimize oxidative damage to the cell. NF-E2-related factor 1 (NRF1) is a Cap'N'Collar (CNC) transcription factor family member that plays a major role in regulating genes involved in defense against cell stress and damage. For example, NRF1 is a vital regulator of antioxidant and proteasome genes to counteract ROS and impaired protein homeostasis. Upon stress caused by impaired protein turnover, NRF1 undergoes endoplasmic reticulum to nuclear translocation and binds antioxidant response elements (ARE) located in close proximity to stress defense genes throughout the genome. The result is altered transcription of the associated gene. While this general concept has been established, the mechanism by which NRF1 is processed, selected for nuclear translocation rather than degradation, and the role of post-translational modifications is not understood. Moreover, previous studies show NRF1 must form a heterodimer with other transcription factors such as small musculoaponeurotic fibrosarcoma oncogene homolog (MAF) proteins to bind AREs and regulate gene transcription. The mechanism underlying NRF1 heterodimer formation and ARE binding and whether distinct heterodimers regulate distinct genes is unclear. I hypothesize NRF1 regulates proteasome and oxidative stress defense via specific heterodimer interactions. In this thesis, I describe our identification of the nutraceutical celastrol as a stimulant for NRF1’s transcriptional activity. For centuries, celastrol has been used to treat inflammatory and chronic diseases and more recently found to influence a multitude of stress pathways and suppress chymotrypsin-like activity of the proteasome. I then proceeded to use celastrol to investigate my hypothesis. Using cultured Hep3B cells, I show celastrol elicits dose-dependent inhibition of the proteasome and this increases the level of a cleaved NRF1 protein product known to regulate transcription. Using clustered regularly interspaced short palindromic repeats (CRISPR)/cas9 based technology to produce NRF1 loss-of-function cells, I show celastrol induces transcription of proteasome and oxidative stress defense genes in an NRF1-dependent manner. Likewise, quantitative polymerase chain reaction measurement of immunoprecipitated chromatin revealed that NRF1 binds to AREs in stress defense genes GCLC, GCLM, HO1, NQO1A in a manner that corresponds with transcription regulatory profiles. Moreover, ablation of NRF1 heterodimers MAFG, MAFK, or MAFF resulted in refractory responses to celastrol that partially and nonredundantly matched NRF1 deficiency. Collectively, results of my research support a model whereby NRF1 heterodimerization with MAFK regulates one gene sub-set or program, whereas heterodimerization with MAFG or MAFF regulates another one. In other words, specific heterodimeric interactions coordinately stimulate or repress the transcription of a group of target genes