VictorJuiz/thesis huggingface dataset:
Probing the Molecular Mechanisms Underlying Familial Amyotrophic Lateral Sclerosis: New Insight into Unfolding and Misfolding Mechanisms of the Cu, Zn Superoxide Dismutase
Keywords: amyotrophic lateral sclerosis
protein folding
neurodegeneration
conformational disease
inverse Laplace transform
superoxide dismutase
protein misfolding
metalloproteins
kinetics
protein aggregation

While great strides have been made in treating many classes of human disease, the late-onset neurodegenerative diseases continue to elude modern medicine. These diseases, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), the transmissible spongiform encephalopathies (TSEs), and amyotrophic lateral sclerosis (ALS), involve accumulation of insoluble aggregates of one or more causative proteins, leading to progressive loss of central nervous system neurons, progressively worsening neurological symptoms, and eventual patient death. All of these diseases are currently incurable and fatal. In the case of ALS, progressive death of upper and lower motor neurons leads to full-body paralysis, respiratory difficulty, and patient death. Of the subset of ALS cases showing familial inheritance, approximately 20% are caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). These mutations do not have the common property of impairing SOD1's normal function as a free radical scavenger. Instead, they are thought to increase the protein's likelihood of misfolding and aggregating via a poorly-understood aggregation cascade. It is believed that species populated along the misfolding and aggregation pathway may prove to be good targets for therapies designed to block accumulation of downstream toxic species, or to prevent aberrant protein-protein interactions responsible for neurotoxicity. In this thesis, several new techniques are developed to enable detailed elucidation of the SOD1 unfolding and misfolding pathways. Time-resolved measurements collected during SOD1 unfolding or misfolding of release of bound Cu and Zn, of changes in intrinsic fluorescence, of exposure of hydrophobic surface area, and of alterations in the chemical environment of histidine residues, are presented. A new mathematical analysis technique named the Analytical Laplace Inversion Algorithm is developed for rapid extraction of mechanistic information from these time-resolved signals. These tools are applied to the construction of the most detailed models to date of the unfolding and misfolding mechanisms of WT and ALS-causing mutant SOD1. The models presented identify several well-populated unfolding and misfolding intermediates that could serve as good targets for therapies designed to address the fundamental molecular mechanisms underlying SOD1-associated ALS, and to treat what is currently a devastating and incurable disease.
Virus and Virus-sized Particle Transport in Variable-aperture Dolomite Rock Fractures
Keywords: Variable-aperture rock fracture
Dolomite rock
Virus transport
Colloid transport
Rock matrix diffusion
Fracture surface roughness

In this thesis a study of the factors affecting virus and virus-sized particle transport in discrete fractured dolomite rocks is presented. Physical and chemical characteristics of two fractured rocks were determined, including fracture aperture distribution, rock matrix porosity, mineral composition, and surface charge. Hydraulic and transport tests were conducted in the fractures with a conservative solute (bromide) and carboxylate-modified latex (CML) microspheres of three sizes (20, 200, and 500 nm in diameter). The earlier arrival of larger microspheres as compared to bromide indicated the effects of pore-size exclusion and preferential flow paths in the fractures. The tailing of the bromide and the smaller microsphere (20 nm) in the breakthrough curves (BTC) indicated the diffusive mass transfer between the mobile water (flowing) and immobile water (stagnant water in the low aperture areas and porous rock matrix). The effects of ionic strength and cation type on the transport of viruses (bacteriophages MS2 and PR772) and virus-sized microspheres (20 and 200 nm) were determined from the transport tests in a fracture at three levels of ionic strength (3, 5, and 12 mM) and composition (containing Na+ and/or Ca2+ ions). Retention of the microspheres and bacteriophages increased with increasing ionic strength. The addition of divalent ions (Ca2+) influenced the retention to a greater extent than monovalent ions (Na+). The effects of the aperture distribution variability, matrix diffusion, and specific discharge on the solute and microsphere transport were determined from the transport tests conducted in two fractures. The higher variability in the aperture distribution contributed to higher solute dispersion, and flow channeling as evident from the breakthrough curves for individual spatially distributed outlets. A three-dimensional model simulation of the bromide transport with varying matrix porosity identified that the porous matrix influenced the solute transport. In the transport tests, retention of the microspheres decreased with increasing specific discharge in both fractures. The results of this research have helped in identifying the important factors and their effects on solute, virus, and virus-sized colloid transport in fractured dolomite rocks, which can be useful in determining the risk of pathogen contamination of water supplies in fractured dolomite rock aquifers.
Resilient Women: Resisting the Pressure to Be Thin
Keywords: Eating disorders
Pressures for thinness
Qualitative
Protective factors

The purpose of this study was to explore protective factors that help women resist societal pressures for thinness. The present study used a qualitative life history methodology to examine the experiences of women who identified themselves as resilient to pressures to be thin and as liking their bodies regardless of size. In-depth semi-structured interviews were conducted with 14 women, ages 18 to 25, representing diverse social and ethno-cultural backgrounds and body physiques. In the interviews, the participants were inquired about their experiences related to anything they felt was helpful for them in developing a positive body image from childhood, adolescence, and to present day. The interviews were transcribed and analyzed for themes using constructivist grounded theory methodology. Data analysis was informed by the feminist theoretical approach, with attention paid to social and contextual factors. Three core categories emerged from the analysis, which included protective factors associated with participants’ experiences of identity, ways of inhabiting their bodies, and the nature of social influences in their lives. This research highlighted the women’s active role in maintaining a resilient stance in the face of pressures for thinness as well as the importance of social factors that assist them in this process.
Beginning and Intermediate Piano Students' Experiences Participating in Evaluative Performances
Keywords: music examination
music competition
piano instruction
motivation
performance anxiety
parents
piano teachers
beginning piano student
intermediate piano students
adjudication

Abstract Evaluative performances, such as festivals and conservatory examinations, frequently play a large role in formal piano study. Many teachers and parents assume that requiring students to participate in these evaluations will result in several benefits, including increased discipline and motivation, exposure to a balanced and rigorous music curriculum, and access to helpful feedback from expert adjudicators and examiners. However, not all students experience positive outcomes as a result of their participation in evaluative performances. Using a multi-method approach that incorporates grounded theory and narrative inquiry, this research provides insight into how beginning and intermediate piano students experience participating in festivals and examinations and what factors contribute to the quality of students’ experiences. Positive experiences with evaluative performances are characterized by positive emotional outcomes, meaningful music learning, and the development of a strong musical identity. The theoretical model developed through this research presents several important contributors to students’ positive experiences with evaluative performances, including students’ understandings, values, and goals related to music learning, and their abilities and inclinations as performers. The entire learning process must take place within a supportive relational context. When students have positive experiences with evaluative performances, their self-efficacy is heightened. They also experience self-determination regarding their music studies and their involvement in evaluative performances. The self-efficacy and self-determination that follow students’ success and positive experiences motivate further involvement in music study.
Engineering Synthetic Control over Rho GTPases using Ca2+ and Calmodulin Signaling
Keywords: Ca2+ signaling
Rho GTPases

Engineered protein systems have been created to impart new functions, or “re-program” mammalian cells for applications including cancer and HIV/AIDS therapies. The successful development of mammalian cells for re-programming will depend on having well-defined, modular systems. Migration is a particularly important cell function that will determine the efficiency and efficacy of many re-programming applications in vivo, and Rho proteins are responsible for regulation of cell migration natively. While there have been several reports of photo-activated Rho proteins, no strategy has been developed such that Rho proteins and cell migration can be controlled by a variety of extracellular stimuli that may be compatible with signaling in large organisms. Here, several methods are described for engineering Ca2+-sensitive Rho proteins so that the large, natural toolbox of Ca2+-mobilizing proteins can use the Ca2+ intermediate to activate Rho proteins in response to a variety of exogenous stimuli, including chemicals, growth factors, and light. First, an unreported calmodulin binding site was identified in RhoA. This knowledge was used to create a tandem fusion of RhoA and calmodulin that mediated Ca2+-sensitive bleb retraction in response to a variety of Ca2+-elevating chemicals. Ca2+-mobilizing modules including channelrhodopsin-2 and nicotinic acetylcholine receptor α4 were used for light- and acetylcholine-dependent bleb retraction. Second, a more robust morphology switch was created by embedding a calmodulin binding site into RhoA to enable Ca2+-responsive bleb formation. A wider range of Ca2+-mobilizing modules were also used here including LOVS1K/Orai1 and vascular endothelial growth factor 2. Combining Ca2+-mobilizing and Ca2+-responsive modules increased amoeboid-like cell migration in wound closure and transwell assays. Finally, the embedded peptide design was applied to Rac1 and Cdc42 to enable control of new morphologies and migration modes. The modular Ca2+ control over Rho proteins developed here is an important contribution to cell re-programming because it shows that control over cell migration can be rewired in a way that is flexible and tunable.
The Role of the PTPN22 (Lyp/Pep) Phosphatase and its Disease-associated Variant in T-cell Signalling
Keywords: Immunology
Cell Signalling

The PTPN22 gene encoding the Lyp/Pep protein tyrosine phosphatase has recently been described as a negative regulator of T-cell receptor signalling. Little biological information is available on this protein, but a variant allele in this gene conferring a R620W change has been associated with rheumatoid arthritis and other autoimmune disease states. To gain further understanding into the roles of Lyp, this work is aimed at identifying and characterizing Lyp interactions, and elucidating the effect of the variant Lyp in immunological disease. Specifically, the interaction of Lyp with the ubiquitin ligase Cbl was further examined and characterized to uncover its role in T-cells. Furthermore, the biochemical and functional differences of the variant Lyp were examined by utilizing a murine model of the variant, Pep R619W. This work led to novel findings on the stability of the protein and its resulting dysfunction, leading to cell hyperresponsiveness. Finally, a new role for Lyp in controlling cell migration was uncovered through its interaction with GRK2. The inhibitory properties of Lyp on cell migration are disrupted in the presence of the Lyp R620W variant, leading to dysregulation of GRK2 function and altered migratory properties of cells, particularly in the collagen-antibody induced arthritis model. Understanding the normal function of Lyp, as well as dysfunction of the variant, will provide new insights into normal T-cell signalling and aid in the understanding of the processes of autoimmunity.
How Genes and the Environment Shape what Mothers Say, Think, and Do
Keywords: Behavioural genetics
Mothering

Human maternal responsiveness is a complex repertoire of infant-related behaviours and attitudes, which vary between and within mothers. Environmental and socioeconomic factors undoubtedly influence maternal care, but less is known about how genetic variation associates with maternal responsiveness. Where genetic variation has been examined in relation to mothering, the moderating effects of early life experiences in the mother have not been explored. Additionally, studies tend to focus on maternal sensitivity, neglecting to explore other dimensions of maternal responsiveness. The purpose of the present thesis was to explore genetic variation in three gene families – dopamine (DA), serotonin (5-HT), and oxytocin (OXT) – in relation to differences in maternal care in a Caucasian sample of new mothers recruited in early pregnancy from Hamilton, Ontario (N=187). Furthermore, interactions between early experiences in the mothers’ lives and their genetic polymorphic variants were examined. Early experience was a combined measure of the Parental Bonding Instrument and the Childhood Trauma Questionnaire. Maternal behaviour during mother-infant interaction was assessed at 6 months postpartum and derived from a video-recorded 30-minute mother-infant interaction. The behavioural outcomes of interest maternal sensitivity (assessed using the Ainsworth Maternal Care Scales) and maternal behaviors (vocalizing, orienting away from infant, instrumental caregiving). We also assessed maternal attitudes about parenting the infant at 6 months postpartum. Multiple polymorphisms on DA receptors D1 (rs686, rs4532, rs265981, rs265976, rs5326) and D2 (rs6277, rs1799732, rs1799978, rs1800497) associated with maternal vocalizing and orienting away from the infant, respectively. The OXT polymorphisms rs2740210 and rs4813627 associated with infant-directed vocalizing. A major polymorphism on the 5-HT transporter (5HTTLPR and a related rs25531 polymorphism) associated significantly with maternal sensitivity. There were gene-environment interactions between this 5-HT polymorphism and early adversity in association with maternal orienting away and maternal attitudes. Gene-environment interactions were also found between the OXT polymorphisms rs2740210 and rs4813627 and instrumental care of the infant. These results suggest that variations in genes encoding major brain neurotransmitters and neurohormones are related to observed maternal behaviour and self-reported maternal attitudes. These results showcase the importance of exploring multiple dimensions of complex behavioural phenotypes like mothering.
Beyond the ‘Bedrooms of the Nation’: An Interpretative Phenomenological Analysis of Canadian Adolescents with Lesbian, Gay, or Bisexual-identified Parents
Keywords: lesbian
gay
parenting
family
adolescent
identity
narrative
interpretative phenomenological analysis
IPA
bisexual
GSA
QSA
school
education
personality

Although parenting by lesbian, gay, and bisexual-identified (LGB) individuals has attracted increasing research attention over the past few decades, relatively little focus has been given to the personal identity development of adolescents raised in such families. There is scant qualitative data that describes the phenomenon from the viewpoint of Canadian adolescents; this study aims to give voice to those with parents that identify as non-heterosexual. In semi- structured interviews, participants were asked to explain how they made sense of being from an LGB-led family, particularly within the contexts of school and Canadian society, and of what unique needs they perceived families like theirs to have. For inclusion in the study, each participant needed to have at least one LGB-identified parent. Additionally, they needed to be a current or recent student in an Ontario secondary school. A convenience sampling method was used to locate nine (N=9) participants. Three of the participants were male, and six were female. All participants were Canadian-born English speakers who ranged in age from 13 to 19 years old, with a mean age of 17.5. The interview schedule was constructed with input from existing narrative psychology literature, consultation with fellow students and faculty, and inspiration from other semi- structured protocols such as The Life Story Interview (McAdams, 2008). Interpretative Phenomenological Analysis (IPA) was employed to organize and evaluate responses. Thematic findings were organized within three domains. First, family-related themes were considered, such as interviewees’ responses to parental disclosures of an LGB identity, responses of extended family members, and perceived advantages of having LGB-identified parents. Second, school-related themes were found, such as how children choose to disclose their parents’ sexual identity to peers. Finally, themes related to queer identity were considered, since many participants revealed their parents’ sexual identity intersected with other narratives (e.g., being Canadian, being heterosexual, the master narrative of heteronormativity, etc.) to create multiple layers to their own sense of self. The study endeavours to add a qualitative approach to the literature so that Canadian adolescents’ narratives are represented in the overall understanding of the phenomenon of LGB- led families. It also has potential to impact the development of school policies and curricula and to enrich the quality of life for LGB-led families.
On C^1 Rigidity for Circle Maps with a Break Point
Keywords: circle maps with a break point
rigidity

The thesis consists of two main results. The first main result is a proof that C^1 rigidity holds for circle maps with a break point for almost all rotation numbers. The second main result is a proof that C^1 robust rigidity holds for circle maps in the fractional linear transformation (FLT) pair family. That is, for this family, C^1 rigidity holds for all irrational rotation numbers. The approach taken here of proving a more general theorem that C^1 rigidity holds for circle maps with a break point satisfying a `derivatives close condition', allows us to obtain both of our main results as corollaries of this more general theorem.
Sympotic and Rhapsodic Discourse in the Homeric Epics
Keywords: Ancient Greek Epic
Homer
Symposium

This dissertation examines the relationship between sympotic and rhapsodic discourses and the Homeric epics and specifically considers how an understanding of sympotic discourse can affect an external audience’s perception of events within the narrative. Heroic feasting is examined and defined as an activity which signifies different attitudes and aesthetics than the symposium. Yet a case is made for the possibility that Greek people are practicing symposia at a time when rhapsodes – the creative composers-in-performance of the epics – would have been freely incorporating material from the contemporary world into their performances. This is a period of time extending over much of the 7th century, and perhaps even into some time before and after. I analyze both the symposium and rhapsodic performances as discourses, using literary, archaeological, epigraphic, and iconographic evidence to define markers – certain signs, gestures, attitudes, accoutrement, and behavior specific to each – of each discourse. By treating the symposium and rhapsodic performances as discourses with their own markers, I establish a methodology with which to examine certain passages of the epics and the implicit meanings conveyed in them. Odysseus is thus shown to be manipulating sympotic discourse in the Phaeacian episodes of the Odyssey in order to win a favorable return home – at least as the contemporary external audience familiar with sympotic conventions of speaking and behaving would have understood it. Achilles too is treated, with specific reference to his behavior in the embassy scene of the Iliad. The sympotic discourse conveyed by the actions and attitudes of Achilles and Patroclus can be shown to communicate additional layers of meaning to the external audience and perhaps reference extra-Iliadic motifs concerning Achilles’ behavior at symposia. A proper understanding of rhapsodic and sympotic discourses within the epics not only contributes to a more nuanced understanding of character behavior within the epics and audiences’ perception of such behavior, but also challenges our understanding of the role of archaic social institutions such as the symposium within the epics.
Internationally Trained Immigrants and Ontario Colleges
Keywords: Internationally Trained Immigrants
Ontario Colleges

This study explored the responsiveness of two Ontario Colleges (called Eastern and Western for the purposes of this study) in the Greater Toronto Area (GTA) to internationally trained immigrant (ITI) students accessing college education for retraining purposes. Many highly educated immigrants are unable to have their credentials recognized because professional regulatory bodies and employers are reluctant to accept their previous education and work experience. Therefore, many ITIs access Ontario college education in the hope that, upon graduation, they will find skill-related employment that will contribute to their settlement in Canada. The purpose of this research was to examine how the two participating colleges address the ITI students’ occupation-specific needs in their current institutional policies and practices. Qualitative research methods, interviews and document analysis, were utilized to examine the admission and program delivery practices at each of the study colleges. Interviews were conducted with 13 ITI student participants and 14 college personnel to provide an opportunity for them to voice their opinions about their college experiences. To provide direction for interpreting and analyzing the research findings, the single- and double-loop organizational learning framework developed by Argyris and Schon (1974, 1978) was used. The findings suggest that Eastern and Western Colleges have different approaches in valuing and placing importance in responding to ITI students’ retraining needs. The data indicated that ITI students at Eastern College were not perceived by college personnel as a unique group of students having specific retraining needs; rather, they were seen as part of the larger student constituency. On the other hand, Western College recognized the ITI students’ distinctive occupation-specific needs and made commitments towards improving its policies and practices to increase the College’s effectiveness in meeting the ITIs needs. Although limited to only two Ontario colleges, the study findings have some important implications for theory and practice. The findings have contributed to increased awareness and a better understanding of challenges ITI students face in accessing Ontario college education, and it has offered recommendations for college efforts to respond to ITI students’ educational needs.