VictorJuiz/thesis huggingface dataset:
Structural and Functional Characterization of the RING-like Protein RTF2
Keywords: dimer
E3 ligase
RING domain
splicing

RING and RING-like domains represent the functional component on the vast majority of E3 ligases. With over 600 known members, the family of RING E3 ligases promote the direct transfer of ubiquitin from an E2 onto a substrate, acting as the key mediators of specificity during the reaction. However, beyond acting as a simple scaffold for E2-binding, many RING and RING-like domains have been found to play a more active role by inducing conformational selectivity in the otherwise flexible E2~ubiquitin conjugate. With their central role in the ubiquitination reaction, it is no surprise that RING and RING-like domains exhibit a wide array of regulatory mechanisms that govern their activity, including the ability to function in different oligomeric states. Specifically, while some function as monomers, many RING and RING-like E3 ligases are dependent on dimerization for their activity. This thesis explores the structure and function of a poorly characterized, evolutionarily conserved RING-like protein RTF2. In the first chapter, I examine the crystal structure of human RTF2 revealing two conserved RING-like domains: an N-terminal U-box-like domain associated with a SP-RING domain in an arrangement I describe as an intra-chain heterodimer. I then move on to describe a role for RTF2 in pre-mRNA splicing and begin to explore its interactome using proximity-dependent biotin identification (BioID). In the third chapter, I identify conserved functional elements on both RING-like domains and demonstrate the importance of these residues for RTF2-dependent splicing, possibly by facilitating E2 recruitment. Together, these results reveal a novel RING-like structural mode and provide a foundation for further work examining the mechanism underlying RTF2 function and its role in pre-mRNA splicing.
The Role of the E-protein HEBAlt in T-Cell Development
Keywords: bHLH
E protein
Immunity
T cell
Transcription factor
Tyrosine Phosphorylation

Developing T-cells require the coordinated function of various transcription factors to promote T-lineage progression, among which is the E-protein HeLa E-box Binding (HEB) factor involved in promoting T-lineage specification and commitment. HEB-deficient mice have altered gene expression, changes in proliferation in the early double-negative (DN) stages, and blocks in T-cell development at the CD8+ Immature Single Positive (ISP8) stage. Although previous studies highlighted the importance of HEB in T-cell development, they failed to distinguish between the HEB isoforms HEBCan (Canonical) and HEBAlt (Alternative) which are produced by different transcription start sites. I set out to identify the functional differences between the HEB factors by investigating specifically the function of HEBAlt in the context of T-cell development. I began by investigating whether the Alt-domain, the defining feature of HEBAlt, is required for HEBAlt transcriptional activity. My findings demonstrated that phosphorylation of a tyrosine (Y)-rich YYY motif is required to activate HEBAlt, and that this phosphorylation may be dependent on Janus kinases, as a result of interleukin-7-receptor signaling within the thymus. Phosphorylation of HEBAlt does not affect subcellular localization and the activity of other E-proteins, however it reduces protein degradation. HEBAlt phosphorylation at the YYY-motif results in greater resistance to Inhibitor of DNA-binding protein-mediated inhibition and comparable transcriptional activity to other E-proteins involved in T-cell development. Phosphorylated HEBAlt also appears to be required for the regulation of a pre-T Cell Receptor- enhancer. In addition, we generated HEBAlt-transgenic and HEBAlt-deficient mice. Our analyses showed that HEBAlt-transgenic mice have reduced proportions of ISP8 cells, opposite to HEB-deficient mice, suggesting HEBAlt may promote developmental progression at the ISP8-to-CD4+CD8+ Double Positive (DP) stages. In vitro T-cell differentiation of HEBAlt-transgenic progenitors have reduced ISP8 cell and greater DP cell proportions, further supporting the role for HEBAlt promoting faster ISP8-to-DP transition. Interestingly, HEBAlt-deficient mice appeared to have no altered proportions in their ISP8 compartments, possibly due to the presence of HEBCan and other E-proteins that may compensate for HEBAlt absence. Overall, our results suggest that HEBAlt function requires phosphorylation at the YYY-motif to be activated, and that HEBAlt may promote the transition of ISP8-to-DP cells in T-cell development.
Application of Cerebral Hemodynamic Imaging in Neurodegenerative Diseases
Keywords: Alzheimer's disease
Arterial spin labelled MRI
Cerebral hemodynamics
Cognitive and motor impairment
functional MRI
Neurodegeneration

Cerebrovascular dysfunction is a pathological change that occurs in neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Whether cerebrovascular dysfunction is a cause, consequence, or co-pathology of neurodegeneration remains a topic of research debate. There is, however, an agreement on the important role of cerebrovascular measures in neurodegeneration progression. This thesis investigated arterial spin-labeled (ASL) and blood oxygenation level-dependent (BOLD) MRI to characterize cerebral hemodynamics in adults with a range of clinical symptoms related to neurodegeneration. The first study of this thesis developed an ASL postprocessing quality enhancement algorithm. My proposed algorithm resulted in higher quality blood flow images, i.e. higher similarity with nuclear medicine-based blood flow imaging. I conclude that there is an opportunity to implement this algorithm to improve clinical ASL. The second study investigated whether a single ASL summary measure can distinguish cognitively unimpaired, mild cognitive impairment, and Alzheimer’s disease groups. I found that spatial variability of blood flow images is increased in the cognitively impaired groups. Moreover, spatial variability of blood flow contributed to cognitive group classification after adjusting for established neuroimaging markers of Alzheimer’s, e.g. structural changes and protein markers. The third study investigated the temporal variability of BOLD signal among adults with Parkinson’s disease. I found that temporal variability of blood flow alongside with dopamine deficiency explain between-subject variability in clinical symptoms. The findings of this thesis 1) help to establish best practices in postprocessing of ASL and BOLD images in cohorts with neurodegenerative diseases, and 2) reveal that non-invasive MRI-based hemodynamic features can be used to explain clinical symptoms in the spectrum of neurodegeneration. In conclusion, this thesis capitalized on the versatility of MRI to produce cerebral hemodynamic image contrast that can characterise the heterogeneity of neurodegenerative diseases.
Infrared Model-based Eye-tracking for Smartphones
Keywords: convolutional neural network
eye tracking
gaze estimation
machine learning
smartphone

Estimating a subject’s point of gaze is known as gaze estimation or eye-tracking and is used in many domains including as an indicator of cognitive, psychiatric and neurological states of individuals. The most accurate remote Point of Gaze (PoG) estimation methods that allow the highest amount of free head movements use infrared (IR) light sources and IR cameras. This type of IR hardware has already arrived on flag-ship smartphones to enable facial identification algorithms but is not yet accessible to developers. If manufactures granted access to this hardware on future commercial smartphones, it has the potential to enable low-cost, robust, and accurate infrared mobile eye-tracking. However, desktop eye-tracking methods assume, both implicitly and explicitly, that the system is stationary. This assumption is not valid for hand-held mobile-device-based eye-trackers, and this thesis aims to address the new sources of error associated with the free movement of the device for mobile eye-tracking. First, current gaze estimation models assume that the relative roll between the system and the subjects’ eyes (the ’R-Roll’) is roughly constant. We developed a new method to determine the PoG which compensates for the effects of R-Roll on the accuracy of the PoG. Then to accurately determine input parameters of the model (pupil center and corneal reflections) in eye images that exhibit large variability due to free device motion, we use an efficient hierarchy of Convolutional Neural Networks (CNNs) with a novel center-of-mass output layer. Finally, we combined these innovations in a complete end-to-end hand-held eye-tracking system using an industrial prototype smartphone with integrated infrared illumination and infrared camera. Experimental results using this system show that across 8 unsupervised subjects looking at 20mm square targets (with the device free to move) 96% of all gaze estimates were within the intended targets with an average bias of 0.72 degrees . Our hybrid approach of a 3D gaze estimation model with a CNN feature extractor achieved a gaze bias that is significantly (400%) better than mobile systems in prior approaches during a higher degree of device motion than was reported in any prior work.
The Use of Digital Video Games in an Elementary Teacher Education Program: Exploring Teacher Candidates’ Attitudes and Interest towards Physics
Keywords: efficacy
gender
identity
physics education
social cognition theory
video games

For decades, digital video games (DVGs) have been used in various educational contexts. However, there has been limited exploration into how they could be used in teacher education programs to investigate how DVGs, in their play, could affect teacher candidates’ (TCs) attitudes towards and interests in physics and physics education. Using a mixed method approach, and a multiple case study design and methodology, data were collected from a single Ontario university for two cases - primary/junior (PJ) and junior/intermediate (JI) TCs enrolled in science education – to explore how TCs engaged with, and responded to physics-focused DVGs. Portraits for each case were constructed from data collected on influencers, (in)formal physics education, physics experiences, physics teacher self-efficacy, as well as personal and professional gaming habits and exposure, to understand their experiences with two DVGs: Huje Tower and Vita: Saving Sutom. Data included: surveys, audio recordings of gameplay think-alouds (GPTA), post-gameplay small group discussions (SGD), field notes and photographs. Case portraits revealed that prior to gameplay PJ TCs had taken fewer formal physics courses, engaged with fewer hands-on practical experiences, and had less gaming experience than JI TCs. Using a gender lens, female participants were also found to have significantly lower physics-teacher self-efficacy than male participants. A multiple case analysis showed DVGs affected participants’ physics learning and physics identity, and a modest increase in physics teacher self-efficacy was found, which some participants directly attributed to gameplay. This study’s findings have implications for researchers, teacher educators and video game designers. For researchers, DVGs continue to occupy a space for yet unexplored growth, in terms of how DVGs could be used to shape a player’s feelings towards subject matter, affect TCs’ efficacy, and support independent learning. For teacher educators, meaningfully selected DVGs have untapped potential to provide virtual experiences for players, and highlight areas of need for further support. For designers, DVGs are still met with skepticism beyond being used as either a motivator or time filler within the classroom. As such, there is a need for better designed serious games (e.g. storyline, purpose, learning outcome) to make them part of a larger learning strategy.
Copyright and Human Development: Towards a Capabilities Approach to Copyright Law
Keywords: Capabilities Approach
Copyright
Development
Human Development
India
Intellectual Property

This project has two core objectives. The first is to build a critique of the current Anglo-American approach to copyright law from a human development perspective. I argue that copyright law has the potential to promote human development and human capabilities. Notwithstanding this, I identify and discuss several key aspects of the current copyright regime that undermine rather than support human development goals and capabilities. The second objective of this thesis is to develop an argument for a more human development-centered approach to copyright law and explore what such an approach ought to look like. I posit that the goal of copyright law ought to be promoting human development and identify two fundamental ways in which the current approach to copyright law needs to be reformed in order to realize copyright’s human development potential. First, the focus of copyright law must shift from promoting the creation and dissemination of works of authorship to promoting dialogue and cultural participation. Second, copyright law and policy should account for socio-economic inequalities and forms of marginalization at both the local and global levels. Based on these two principles, I explore a set of copyright reform proposals, such as permitting uncompensated transformative use of copyrighted works; the abolition of the derivative work right and the translation right; limiting the moral right to integrity; building safeguards into anti-circumvention regimes to protect copyright exceptions and limitations; instituting a more licensee-friendly compulsory licensing regime; and adopting a hybrid approach to fair use/fair dealing that combines the certainty of rules with the flexibility of standards.
Extended Techniques in Jorge Peixinho's (1940-1995) Three Late Pieces for Saxophone: Sax-blue (1982-84), Passage Intérieur (1989), and Fantasia-Impromptu (1990)
Keywords: extended technique
Kientzy
multiphonic
Peixinho
saxophone

Jorge Peixinho’s Sax-Blue (1982-84), Passage Intérieur (1989), and Fantasia-Impromptu (1990) demonstrate an expressive exploration of saxophone sound through extended techniques. Timbral exploration is an essential element of the composer’s “new and personal sound world.” These techniques create sound transformations that interact with the ensemble in creative and varied ways. In Sax-Blue, Peixinho worked closely with French saxophonist Daniel Kientzy. The various extended techniques, especially multiphonics derived from Kientzy’s Les Sons Multiples Aux Saxophones (1982) interact with jazz-inspired musical language and electronics to create layers of saxophone sound. Passage Intérieur was written for Kientzy and his Barocko ensemble. The composer also worked closely with Kientzy and Barocko in preparing this piece. Peixinho uses a wider variety of extended saxophone techniques in Passage Intérieur, this time derived from Kientzy’s Saxologie (1990). These techniques interact with electric guitar, electric bass, synthesizer and electric drums in various textures. Fantasia-Impromptu was written for Portuguese saxophonist José Massarrão and pianist Ana Mafalda. Peixinho and Massarrão worked closely, once again in consultation with Kientzy’s Saxologie, to curate the extended techniques for the piece. These techniques interact in a colourful and virtuosic conversation with the piano. The performance considerations of the extended saxophone techniques in Sax-Blue, Passage Intérieur and Fantasia-Impromptu are discussed. Interviews with key performance collaborators clarify the role the performer had in the creation and ongoing performance history of these idiomatic saxophone pieces. My interviews with Robert Aitken, António de Sousa Dias, Mario Falcão, Daniel Kientzy, José Machado, José Massarrão and Reina Portuondo inform my performance discussion. In addition, I created an edition of Sax-Blue that reconciles the differences between the various versions and the revision of the piece. This allows for the use of a single score in the study and performance of the piece. An introduction and theoretical analysis of all three pieces is presented and also informs the performance discussion.
A Figure of Rhetoric: Holiness, Hyperbole, and Embodied Subjectivity in the Later Writings of Emmanuel Levinas
Keywords: Literature
Philosophy
Religion

Later in his life the philosopher Emmanuel Levinas characterized his work in terms of holiness, famously commenting to Jacques Derrida, “You know, one often speaks of ethics to describe what I do, but what really interests me in the end is not ethics, not ethics alone, but the holy, the holiness of the holy.” Throughout the four chapters of A Figure of Rhetoric holiness is discussed as giving priority to the needs of others over my own, as the response of “here I am,” and as the “non-indifference” towards the other, all of which reveal the possibility of a saintly existence. Saints do not consider their vulnerability to others to be a hindrance, but rather, they allow this vulnerability and exposure to others to become a central aspect of their lives. From this viewpoint, holiness consists of a hyperbolic condition wherein the self is answerable both to and for the other. In A Figure of Rhetoric I maintain that this depiction of the hyperbolic structure of our subjectivity in the thought of Emmanuel Levinas indicates a lived possibility. Driven to give an account for why we witness and carry out acts of generosity and responsibility, and heavily influenced by Edith Wyschogrod, my dissertation follows and explicates the ethical framework of Levinas’s later work. I argue that responsibility and compassion emerge from a pre-reflective susceptibility to others and from an understanding of ourselves as primordially and inescapably responsible. In short, this project highlights the significance of affectivity and corporeality for the ways in which one incurs and expresses responsibility. It is in my proximity to the other that I experience a claim of responsibility and I signify to the other my own selfhood of devotion. In A Figure of Rhetoric I insist that the themes of holiness and hyperbole provide a hermeneutical key for better understanding Levinas’s later writings, but more directly and perhaps more boldly, I argue that holiness and hyperbole denote or delineate the original mode of the religious and the ethical. Lastly, my project addresses the various objections from the psychoanalytic tradition concerning the possibility of other-centered living.
Troubled Knowledge: Land, Race, and Logics of Extraction in Alberta’s Tar Sands
Keywords: extraction
human geography
labour
pluriverse
race
settler colonialism

This dissertation examines how tar-sands extraction comes to be seen as normal and an inevitable consequence of present-day lifestyles. The research is built from interviews with 30 white oil-industry workers involved in oil-extraction projects in the Athabasca tar-sands deposit. The ways in which oil has shaped economic and social relations not only in Fort McMurray, AB, but in the Canadian state generally are significant to unravel and examine. This study attempts to capture the ways that tar sands are made possible through state policy, investment, and economic structuring, as well as how these things are experienced at the level of the individual. I analyze the logics, and rationales used to justify continued extraction in this region, and I work to debunk them and also to understand how and why they are so powerful. Furthermore, I contrast the ways in which oil extraction comes to make sense to itself, besides the ways in which Indigenous people have demonstrated this logic to be limited and, in many cases, untrue. I work through these different ways of relating to—and understanding—oil, in order to contrast the different worlds that are competing in this place.
Relative Entitlements: Reckoning Recipients’ Access to Publicly-funded Assisted Reproductive Technologies (ARTs) Cultural Understandings of Kinship and Gender in Quebec (Canada)
Keywords: anthropology
assisted reproductive technologies (ARTs)
gender
in vitro fertilization (IVF)
kinship
public funding

Between August 2010 to November 2015, Quebec was the only jurisdiction in North America to fund assisted reproductive technologies (ARTs). This government financing was comprehensive. It provided three rounds of in vitro fertilization along with a host of other fertility treatments and medications. Though public funding removed economic constraints to ART usage, not everyone gained equal access. This followed from regulatory gaps, which set the stage for uneven access among recipients. Recipients experienced processes of inclusion or exclusion, which unfolded in keeping with cultural ideas concerning kinship and gender. Kinship and gender were meaningful in the way recipients were recognized as being more or less “worthy” of reproducing than others. This corresponded with new forms of stratified reproduction that redefined reproductive autonomy. This dissertation will focus on those who were most recognizably in need of public ARTs, such as heterosexual and same-sex couples (in particular lesbians). It will also follow those who were pushed aside: women with advanced maternal age, single women, and women deemed to have a high body mass. Among all these recipients, ART access entailed paradoxes tied to kinship and gender. Inevitably, this caused some recipients to be considered more “worthy” than others of public ARTs. Public ARTs might have been used in novel ways, but my work will show reproductive possibilities often replicated comprehensible kinship and gender relations. Financial means remained an index of who was seen as a worthy recipient and deserved to have a family. Gay and lesbian ART access was conditional and tied to family law and financial means. Women's age, social status, and body mass were troubling conditions of exclusion. Moreover, contrary to the program’s aims, public ARTs encouraged an already robust ART market. Based on participant observation at three clinical sites in Montreal (Quebec) between 2011 and 2013, and over 100 interviews with patients and a small group of providers, I will illustrate how ART access and availability is a contested arena that (re)produces kinship and gender relations in certain ways. This shows that access is much more complex than whether the state decides to fund ARTs.