VictorJuiz/thesis huggingface dataset:
Standardizing Injustice in Transition-related Medicine?: An Institutional Ethnography of How Assessment Protocols Coordinate Inequitable Access to Hormones and Surgeries in Canada
Keywords: health professions education
hormone therapy
mental health
transgender studies
transition-related surgery

Transgender (trans) people experience barriers to transition medicine such as cross-sex hormones and sex reassignment surgeries. In response, standardized care protocols, such as the World Professional Association of Transgender Health standards of care (WPATH-SOC), are recommended to improve gaps in care. To better understand how standardized care protocols shape access to transition medicine in Canada, I draw on institutional ethnography as a critical research strategy. In this dissertation I thus explicate how the main protocols used to assess trans people’s psychosocial readiness for hormones or surgeries serve a powerful coordinating function. Although significant advocacy targets the Diagnostic and Statistical Manual for Mental Disorders for pathologizing trans identity through the gender dysphoria diagnosis, my research demonstrates that the WPATH-SOC standardizes an entire model of care based in pathologization. This research project uses data obtained through talking with twenty-two trans people, clinicians, clinician-educators, and hospital administrators, observing clinician-education workshops, and analyzing pertinent assessment protocols and healthcare policy texts. My dissertation makes three substantive contributions to the areas of public health, trans studies, and health professions education research. First, I show that standardized readiness assessments previously understood as innocuous instead contribute to inequities and further pathologize trans people. Second, I argue that in the absence of trans health in the formal health professions education curricula, standardized assessment protocols serve as a form of curriculum, coordinating how health professionals learn and teach this clinical sub-specialty. Third, the results of this research hold the potential to bolster trans health advocacy efforts by identifying how assessment protocols rule health professionals’ and trans people’s resistance practices. In the spirit of activist institutional ethnography this dissertation concludes with a discussion on recommended future advocacy and systems change in the areas of policy, education, and practice.
Shape-specific Patterning of Polymer-functionalized Nanoparticles
Keywords: Gold
Nanoparticles
Patches
Polymer
Shape

It has been shown that polymers end-tethered to a two-dimensional substrate will collapse into so-called “pinned micelles” upon exposure to poor solvency conditions. These structures consist of polymer-dense cores surrounded by stretched polymer “legs” as a result of constrained de-wetting. This thesis transfers this known phenomenon to a three-dimensional system: nanoparticles end-grafted with polymer ligands, as a unique strategy to surface pattern nanoparticles with polymer patches. Using spherical gold nanoparticles functionalized with thiol-terminated ligands (mainly polystyrene), the quality of the solvent was reduced and as a response, the uniformly thick polymer brush layer collapsed. In this process, polymer patches are formed to reduce unfavorable interactions at the polymer-solvent interface. The size, distribution, and number of pinned micelles were controlled by three factors: (i) polymer molecular weight, (ii) polymer grafting density, and (iii) nanoparticle diameter. Each factor played a role in the resulting surface free-energy of the system, based on the gain in energy from the polymer-polymer interaction within the micelle core and the energetic cost of stretching the polymer tethers required to form the pinned micelles. The nanoparticle shape played a role in controlling or directing the patches onto specific regions of the nanoparticle surface. For nanoparticles which have various regions of local curvature (e.g. nanocubes, triangular prisms, nanodumbbells, and nanorods), the patches were found to be more stable in regions of higher curvature such as edges, vertices, and tips of various nanoparticle geometries (i.e. predicable localization of polymer patches). Interestingly for nanorods, which exhibit different curvatures along their longitudinal and transverse axes, there is an asymmetric polymer stretching, yielding a unique helicoidal wrapping of the polymer patches. Finally, the stability of the polymer patches was studied for various temperature conditions. The patches are stable over several days at 23 and 40 degrees Celsius, however at 80 degrees Celsius, the patches merge and as a result, the number of patches per nanoparticle decreases. Eventually, the thiol-terminated polymer detaches from the nanoparticle surface. These effects emphasize the lability of the thiol-terminated polymer ligands, given that sufficient energy is applied to the system.
Hippocampal Contributions to Structuring and Segmenting Experience
Keywords: Hippocampus
Memory
Spatial navigation
Virtual reality

The hippocampus plays a key role in establishing spatial and event boundaries, crucial for constructing and maintaining cognitive maps in spatial and non-spatial domains. The present set of studies investigated these processes in the context of navigating large-scale, virtual spaces (Google Street View) and viewing visual narratives (film). The first study is composed of two behavioural experiments that highlight the representational priority of turns along travelled routes. Locations associated with turns were recollected better and produced a temporal overestimation bias, compared with locations following turns. The second study presents an fMRI investigation of the interactions between hippocampal representations of decision points and navigational goals along familiar routes. The relationship between decision points and goal representations was modulated by goal proximity, and developed with experience in the virtual environment. This experience-related development suggests that hippocampal representations are reconfigured to represent the most relevant aspects of the environment. The third study presents an fMRI investigation of a large cross-sectional adult lifespan sample in which participants watched a movie. The hippocampus was the only region that consistently represented within-event details as unrelated or dissimilar, in a manner that was distinct from the neocortex. While most neocortical representations remained stable with age, the pattern overlap in the hippocampus, the anterior temporal lobe, and the orbitofrontal cortex increased significantly, suggesting a loss of precision and a potential susceptibility to interference. Together, these studies provide evidence that the representation and segmentation of the temporal flow of experience are key organizational features of episodic memory and navigation. These dimensions are captured in moment-to-moment hippocampal dynamics and malleable by different contexts.
Nursing Professionalization, Gender Equality, and the Welfare State: Identifying Macro-level Factors that Advance Nursing Professionalization
Keywords: gender equality policies
nursing human resources
nursing professionalization
structural political and economic factors
time-series cross-sectional design
welfare state regimes and policy

Nursing professionalization has important benefits for the nursing workforce, patients, and health systems. Given the large number of associated goals, the process is ongoing and of continuous relevance to all countries where nursing is practiced. Although the body of research focusing on this topic is vast, the macro-level structural determinants of this process are currently less understood. The objectives of this thesis were to examine the effects of (a) welfare state and gender regimes and (b) measures of education, health, family, labour market, and gender policies on nursing professionalization in high-income countries. The literature review conducted synthesised health and socio-political studies, bringing attention to key links between nursing professionalization and welfare state policies. The empirical analysis consisted of two studies, the first one focused on the welfare state and the second one on gender equality, both using a time-series, cross-sectional design and fixed-effects linear regression models. The analysis covered 16 years and 22 countries. The findings suggest that both the average regulated nurse and the nurse graduate ratios differ among welfare state and gender regimes. In addition, the following policy measures were found to be predictive of (a) the regulated nurse ratio: total government expenditure on education, total and public health care spending, length of paid paternity leave, female share of tertiary education graduates, female share of employment in managerial positions, gender wage gap, and female share of seats in national parliaments; and of (b) the nurse graduate ratio: total government expenditure on education, total health care spending, length of both paid maternity and paid paternity leaves, female share of employment in managerial positions, gender wage gap, female share of seats in national parliaments, and female labour force participation rate. This study’s findings could add to existing upstream advocacy efforts to strengthen nursing and the nursing workforce through healthy public policy.
Detail and Temporal Structure in Memory for Real-world Experiences: Age- and Time-related Changes
Keywords: aging
context
memory
recollection

Episodic memory was initially defined as our ability to relive event-specific details and to remember the temporal context in which those details occurred. A rich tradition of laboratory studies has focused on memory organization, but the to-be-remembered stimuli bore little resemblance to real-world experiences. Conversely, autobiographical memory studies provide greater ecological validity but are limited in their measurement of recall organization. In this dissertation, I report three behavioural experiments that examine temporal structure in memory for real-world episodes, its relation to memory detail, and how these dimensions change with increasing age and remoteness. Chapter 2 describes an experiment probing remote temporal order and item recognition memory for objects encountered in a museum exhibit, using photographs of the exhibit and similar lures. Lure discrimination declined more than temporal order memory across a lifespan sample, although aging was associated with decreased flexibility in reconstructing order. Chapter 3 investigated how memory for the details and temporal structure of a single extended event change over time, using verbal true/false tests and a within-subjects delay manipulation. Memory for specific details declined rapidly whereas memory for temporal order was stable from 1 hour to 1 month and increased significantly overnight. Aging was associated with a marked decline in order memory at all delays, in contrast to a subtler and time-dependent decline in detail memory. Chapter 4 describes a study examining spontaneous temporal organization in free recall of extended real-world episodes. Younger and older adults tended to cluster their recall according to temporal proximity with a forward-going bias, extending principles of recall dynamics in laboratory studies to autobiographical-like memory. Moreover, more temporally organized memories were also denser in episodic detail, suggesting a relationship between structure and phenomenology within single recall narratives. Overall, these studies bridge a gap between laboratory memory and autobiographical memory literatures and methods, and provide a richer picture both of how we remember past episodes, and how we fail to do so. More specifically, they suggest that temporal organization is a critical determinant of memory success and quality over long timescales and is particularly vulnerable to age-related decline.
Performance and Stability of Electron-Accepting Boron Subphthalocyanines in Organic Photovoltaics
Keywords: organic
photovoltaic
solar
stability
subphthalocyanine

Boron subphthalocyanine (BsubPc) is a promising organic material with favourable optical and electronic properties for application in organic photovoltaics (OPVs). These properties can be tuned by chemically modifying the peripheral and axial substituents of the BsubPc. In this thesis, the influence of different substituents on the OPV performance of BsubPc as an electron acceptor was assessed using a standardized OPV configuration. Substitution of the BsubPc peripheral hydrogens with chlorines is used to adjust the voltage output of OPVs, but the ability to tune the voltage output using pure BsubPc is quantized based on the number of peripheral positions. Mixtures of compounds with different degrees of peripheral chlorination were found to behave as electronic alloys, providing infinite degrees of material tunability. The effects of axial substitution with phenyl and phenoxy groups were also explored and showed promising time-zero OPV performances. Phenoxy-BsubPcs provided a unique platform to study halogen bonding within OPVs, which were observed to influence molecular orientation and significantly impact OPV performance. The stability of the most promising BsubPcs was assessed and compared in OPVs. Outdoor testing revealed that peripheral chlorination and the addition of benzene rings (boron subnaphthalocyanine) have minimal impact on stability, but axial phenylation and phenoxylation dramatically reduce stability. Given the freedom to peripherally halogenate a BsubPc without impacting stability, these conclusions lay the foundation for the development of new BsubPcs and BsubPc alloys. Through strategic halogen placement, energy levels and molecular orientation can be controlled simultaneously to achieve the ideal materials for OPVs.
Investigation of Escherichia coli [NiFe]-Hydrogenase Maturation
Keywords: Escherichia coli
Hydrogenase
Metal Homeostasis
Metallochaperones
Nickel

[NiFe]-hydrogenases catalyze the reversible oxidation of hydrogen gas at a bimetallic active site and are important enzymes in bacteria and archaea for anaerobic growth and pathogenesis. The maturation of [NiFe]-hydrogenase requires at least seven dedicated accessory proteins to assemble and insert the components of the NiFe(CN)2CO catalytic site. The penultimate maturation step is the delivery of nickel to a primed hydrogenase precursor protein, a process that is accomplished by the metallochaperone proteins HypA, HypB, and SlyD. This delivery process is supported by proteins that import, export, regulate, and store nickel to ensure a sufficient supply while also mitigating the innate toxicity of this transition metal. In this work, nickel delivery to the [NiFe]-hydrogenase in Escherichia coli was examined using microbiological, biochemical, spectroscopic, and computational methods. The results demonstrate that protein-protein interactions between the metallochaperones afford layers of nickel selectivity. The protein complexes HypA-HypB and SlyD-HypB are modulated by the GTPase cycle of HypB and mediate the selective release of nickel over zinc. In addition, characterization of the metal-binding sites of HypA and HypB revealed different binding modalities, suggesting distinct acquisition and release mechanisms for these metallochaperones. This thesis also describes the development and employment of a high-throughput whole-cell [NiFe]-hydrogenase assay. The assay was used to screen the Keio collection of single gene deletion strains of E. coli and uncovered, for the first time, eutK as a component of the nickel delivery pathway and nickel homeostasis. The assay was also used to determine extracellular nickel concentrations required to bypass the nickel uptake and delivery processes to validate those systems as potential therapeutic targets, setting the stage for the search for small molecules that inhibit the biosynthesis of [NiFe]-hydrogenase. Together, this work gives insight into several aspects of the crucial nickel delivery process that bacteria use to produce [NiFe]-hydrogenase.
An Integrative Modelling Approach for Disordered Proteins using Single-molecule Fluorescence Spectroscopy
Keywords: Ensemble modelling
Integrative structural biology
Intrinsically disordered proteins
Multiparameter fluorescence detection
Polymer physics
Single molecule biophysics

The primary sequences of Intrinsically Disordered Proteins (IDPs) encode for relatively flat, but not featureless, energy landscapes. Consequently, characterizing their conformational properties is non-trivial due to their heterogeneity and interconversion of conformations. I developed experimental protocols and data analysis tools to study IDPs using single-molecule Förster Resonance Energy Transfer (smFRET) with Multiparameter Fluorescence Detection (MFD). Using multiple parameters of fluorescence is necessary to make accurate and unambiguous distance measurements using the mean transfer efficiency
The Role of Actin Polymerization in the Regulation of the Superficial Zone Chondrocyte Phenotype
Keywords: Actin Cytoskeleton
Cell division control protein 42 homolog (CDC42)
Myocardin-Related Transcription Factor-A (MRTF-A)
Superficial Zone Chondrocyte Phenotype
Transcriptional Co-Activator with PDZ-Binding Motif (TAZ)
Yes-Associated Protein (YAP)

The superficial zone (SZ) plays a multifaceted role in maintaining cartilage tissue homeostasis, in part through expression of the chondroprotective molecules proteoglycan 4 (PRG4) and tenascin C (TNC). Although studies have investigated the pathways regulating the primary chondrocyte phenotype, these studies use full-thickness chondrocytes (FTC), which are primarily comprised of chondrocytes exhibiting a round morphology. However, SZ chondrocytes (SZC) have an elongated morphology, accounting for up to 10-20% of the cells of native tissue. Thus, the results obtained using FTC may not be applicable to the SZC population. We observed that the elongated shape of SZC is maintained in vitro at 48 hours and used this feature to facilitate characterization studies and evaluation of signaling pathways that regulate the SZC phenotype. SZC had a lower G-/F-actin ratio, compared to deep zone chondrocytes (DZC), indicating the presence of more polymerized actin. Additionally, SZC expressed the actin-regulated transcription factors myocardin-related transcription factor-A (MRTF-A), yes-associated protein (YAP), and transcriptional co-activator with PDZ-binding motif (TAZ). However, TAZ was more highly expressed in DZC. In this study, we investigated the role of MRTF-A and YAP/TAZ in the regulation of the SZC phenotype downstream of the Rho GTPase CDC42 and actin polymerization. While PRG4 and TNC were regulated by CDC42 and actin polymerization, the pathways downstream of actin diverged. Firstly, treatment with actin depolymerizing agents latrunculin B and cytochalasin D had differential effects on PRG4 and TNC mRNA and protein levels. Secondly, siRNA-mediated knockdown of MRTF-A decreased TNC mRNA and protein levels with no effect on PRG4 accumulation. Thirdly, while PRG4 mRNA and protein levels decreased with siRNA-mediated knockdown of YAP/TAZ, TNC decreased only with TAZ knockdown. YAP/TAZ did not have synergistic effects in regulating expression of PRG4 and TNC in SZC. Importantly, TAZ knockdown did not affect YAP levels and vice versa. However, decreased nuclear TAZ was observed with MRTF-A knockdown (day 5), suggesting crosstalk between these two signaling pathways. While CDC42 may contribute to the SZC phenotype through multiple actin-dependent and independent pathways, this work identifies a novel finding demonstrating the role of MRTF-A and YAP/TAZ in the regulation of the SZC phenotype.
MicroRNA-34a-5p Promotes Joint Destruction During Obesity and Osteoarthritis
Keywords: Antisense oligonucleotide
MicroRNA
Obesity
Osteoarthritis
Preclinical study
Therapeutic

Osteoarthritis (OA) is a chronic degenerative joint disease and the most common cause of disability among older individuals. We previously found that levels of microRNA-34a-5p (miR-34a-5p) in synovial fluid increase during late-stage (grade III/IV) compared to grade I/II radiographic knee OA; however, the role of miR-34a-5p in OA pathophysiology and its potential as a therapeutic target is largely unknown. In the current study, I found that miR-34a-5p expression was increased in the plasma, knee articular cartilage and synovial tissue of total knee replacement (TKR) patients compared to healthy controls and early OA synovial tissue. Similarly, miR-34a-5p expression was increased in knee joint tissues of a surgically-induced (destabilization of medial meniscus (DMM)) mouse model of OA. Since obesity is a significant risk factor for OA development, I first showed that plasma miR-34a-5p expression was further elevated in obese versus non obese OA patients. In addition, miR-34a-5p expression was highly elevated in plasma and knee joints of obese mice subjected to high fat diet. My in vitro studies revealed that miR-34a-5p mimic promoted critical mediators involved in catabolic processes in human chondrocytes and increased expression of synovitis-associated markers in human fibroblast-like synoviocytes (FLS). Conversely, miR-34a-5p antisense oligonucleotide (ASO) treatment promoted anabolic effects in chondrocytes and reduced the expression of pro-fibrotic and pro-inflammatory markers in FLS. In conjunction with my in vitro findings, intra-articular injection of miR-34a-5p mimic in mice induced OA pathological changes such as cartilage degeneration and synovitis. Notably, my preclinical studies conclusively demonstrated the therapeutic potential of intra-articular injections of miR-34a-5p ASO, which imparted cartilage-protective effects in both normal weight and high-fat diet-fed mice subjected to OA surgery. To investigate the regulatory mechanisms of miR-34a-5p in articular cartilage, chondrocytes obtained from miR-34a knock out (KO) mice or wild-types (WT) were subjected to RNA Sequencing and putative signaling pathways regulated by miR-34a-5p were determined. This is the first study to propose a link between obesity and OA via dysregulated miR-34a-5p expression and provides first preclinical evidence for OA therapeutic intervention using a miR-34a-5p ASO.