VictorJuiz/thesis huggingface dataset:
Roles of microRNAs in AML Cell Survival and Drug Response
Keywords: Acute Myeloid Leukemia
CRISPR/Cas-9
Drug Resistance
Essentiality
microRNA
Screening

There are numerous cellular processes that contribute to progression and treatment resistance of Acute Myeloid Leukemia (AML). In this thesis, I examine the role of microRNAs (miRNAs), which are small RNAs that function as key modulators of gene expression and participate in oncogenic and chemoresistance related pathways. For this, I generated a microRNA-only Knock-Out (miRKO) CRISPR/Cas-9 library to screen for essential miRNAs in the AML cell lines OCI-AML2, OCI-AML3 and U937. These screens revealed 10 candidate essential miRNAs: miR-19b-1, miR-19b-2, miR-29b-2, miR-302a, miR-3678, miR-3713, miR-3910-1, miR-4447, miR-4718, and miR-6795. miR-19b-1 and miR-29b-2 were validated as pro-survival genes. miR-19b-1 originates from the well-known oncogenic miRNA cluster known as miR-17~92. Targeted knockout of miR-19b-1 demonstrated that its loss is sufficient to slow the growth and limit the colony forming potential of AML cells. Phenotypic profiling of miR-19b-1 deficient and miR-19b-1 overexpressing cells demonstrated that it plays a role in regulating cellular metabolism. Similarly, targeted knockout of miR-29b-2 was demonstrated to slow growth, reduce colony formation and negatively affect cell metabolism in AML cells. However, overexpression of miR-29b-2 also reduced growth and metabolic output, indicating that miR-29b-2 may have a complex role regulating AML cell homeostasis. Notably, miR-eCLIP analysis of miR-19b-1 and miR-29b-2 targets in OCI-AML2 confirmed that the vast majority of mRNA binding partners play a role in metabolism. In a second miRKO screen, I identified miRNAs involved in mediating resistance to Daunorubicin (DNR) or Cytarabine (Ara-C). In a parallel aim, DNR or Ara-C resistant AML cell lines were generated and profiled by small-RNA sequencing to identify miRNAs with altered expression. This identified: miR-146a-5p, let-7b-3p, let-7b-5p, miR-181b-5p, miR-29b-2-5p, miR-210-3p as candidate miRNAs that promote chemoresistance and miR-99a-5p, miR-363-3p, let-7i-5p, miR-106b-3p and miR-143-3p as candidate miRNAs that promote chemosensitization in AML cells. Altogether, this work identifies miRNAs that can support AML survival, are implicated in drug response, and may predict patient survival. This work also identifies metabolic processes as underlying mechanisms that could be regulated by miRNAs in AML cell survival.
Application of Visualization-based Analytic Methods in Population Health and Health Services Research to Rehabilitation Sciences
Keywords: data visualization
health services research
population health
rehabilitation
visual analytics

Visualization-based analytic methods have evolved rapidly over the last two decades, allowing knowledge generation from large healthcare datasets. However, their application in the rehabilitation sciences, particularly related to population health and health services research is limited. This research is divided into two main parts. The first presents two systematic literature syntheses of two information visualization methods, visual analytics and interactive visualization, both applied in these areas of healthcare. The second part presents two use cases illustrating the application of these methods. The first use case is an interactive visualization dashboard prototype for the Canadian Institute for Health Information's Population Grouping Methodology, where the candidate was placed as an embedded fellow. The second use case presents a proof-of-principle dashboard exploring data on rehospitalizations from a multicenter practice-based evidence study on outcomes of persons with spinal cord injury. Rehabilitation health services' research can benefit from the use of visualization-based methods alone or combined with exploratory visual and confirmatory statistical analysis to advance the field. In addition, this thesis highlights the opportunity for organizations to leverage embedded research for advancing and improving healthcare through integrated knowledge translation initiatives and building Learning Health Systems inclusive of rehabilitation services.
Off the Bench, Sing and Play: Lived Experiences in Dalcroze-inspired Piano Lessons for Amateur Adults
Keywords: Adult Piano
Career-Aged
Dalcroze Eurhythmics
Interpretative Phenomenological Analysis (IPA)
Piano Education
Piano Pedagogy

The lived experiences of career-aged adults (30-55 years of age) greatly impact how they learn a new skill. As adult piano lessons become more popular, a lack of training in adult piano education means many piano instructors are forced to adapt their methods used for children with little guidance. An increasing number of piano method books for adults are being published, but these materials often neglect the notion of musical expression and the process of feeling music through their entire body. This disconnection between the body and the music can lead to a lack of fulfillment in lessons for this age group. In this research, I explored a piano teaching approach that incorporates Dalcroze Eurhythmics, a multi-sensory music learning approach, to gain a better understanding of these experiences and expand the possibilities in adult piano education. Interpretative Phenomenological Analysis was the methodology I applied to answer the following research questions:1) What are the perceptions of career-aged amateur adults learning piano through Dalcroze-inspired activities? 2) How do the perceptions of the lived experiences of adult students participating in Dalcroze-inspired piano lessons further inform and broaden adult piano education? Three career-aged adults who had taken Dalcroze-inspired piano lessons for a minimum of two years participated in this study. Thematic findings were organized into two domains. First, examination of the experiences of amateur adult students returning to piano lessons later in life revealed themes of fulfilling dreams, learning with autonomy, acknowledging challenges, and feeling joy from music. The second domain explored the experiences specifically in Dalcroze-inspired piano lessons, and revealed that adult learners who stepped out of their comfort zone and used this whole-body approach became more engaged in their learning and enhanced their musical abilities from both physical and mental perspectives. The findings suggest that career-aged amateur adults have specific purposes and approaches to learning piano due to various social, physiological, and psychological factors. Dalcroze-inspired lessons provided them a holistic learning environment to incorporate a whole- body multi-sensory approach to learning, creating, and connecting music with their daily lives. This study offers insight to a unique student age group and aims to broaden the possibilities in piano adult education.
Beyond the Youth Athlete: Exploring Concussion Education and the Provision of Social Support
Keywords: Concussion
Education
Mild Traumatic Brain Injury
Social Support
Youth

Youth can experience a concussion through many mechanisms including motor vehicle collisions, sports, falls, recreational play, assault and other causes. Despite the many mechanisms of sustaining a concussion, to date, most concussion education has been provided to athletes or within sport settings and focused on concussion reporting behaviours. Following a concussion, youth can experience a range of concussion symptoms that are cognitive, physical, sleep and emotional/behavioural, with these symptoms impacting youths’ ability to meaningfully participate in activities. Specifically, the influence of emotional symptoms on participation has been highlighted within the literature and the provision of social support has been suggested as one way to decrease these symptoms. Therefore, the motivation for this thesis is to inform concussion education interventions for all youth (athletes and non-athletes) in order to promote positive concussion-related behaviours and health outcomes. To do so, this thesis will explore: (1) existing concussion education and (2) youths’ intentions to provide social support to a peer with a concussion. This thesis is comprised of four studies. Study 1 identifies online concussion resources that are up-to-date, accurate and designed for Canadian youth by assessing the resource content as well as the readability, usability and suitability. Study 2 involves the completion of a scoping review that explores peer-reviewed concussion education delivered in the school setting. This scoping review included 27 studies and focused on the education context, delivery method, development and evaluation. Study 3 and 4 highlight relationships between demographic variables, concussion knowledge and social support-related constructs, and identify youth who may be more likely to provide social support. Study 3 involves the delivery of a novel concussion survey based on the Theory of Planned Behaviour to 200 youth (athletes and non-athletes). Study 4 builds on preliminary work conducted in Study 3 by delivering a shortened and more feasible version of the survey to 1330 Canadian high school students. The findings from this thesis highlight the opportunity to develop concussion education that fills existing gaps by delivering education to all youth and including content specific to the provision of social support to youth with a concussion.
User Recognition System based on PPG Signal
Keywords: Biometrics
Deep Learning
Fusion
Generative Models
PPG

People are connected to various online and off-line systems that facilitate their interactions performed on a daily basis. In all these activities, individuals use their credentials to create, share and pay which could be related to the individual’s information. This sensitive data should be highly secured and thus, user recognition systems are highly empowered and invested recently.Biometric system is a technology which takes an individual’s traits as input and identifies the individual as a genuine or malicious user. In this work, our goal is to develop the verification system based on a physiological signal which has unique properties for each individual and simultaneously ensures the liveness of user since it is one of its inherent characteristics. Among diverse physiological signals, we focus on the photoplethysmography (PPG) since it can be acquired from low cost, more accessible and portable devices. The advantages correlated to the PPG signal bring it more practical and appealing to be utilized in real applications. However, the PPG signal has theoretical challenging aspects to be considered which include time variability and inherent randomness. To this end, we focus on investigating the feasibility of employing the PPG signal for person verification by developing time-stable and distinguishable features. To achieve our goal, there are five main objectives to be considered. First, a large and reliable PPG database with multi-sessions should be recorded to investigate the time stability of verification system. Second, the appropriate pipeline of PPG verification system needs to be suggested. Third, the conventional machine learning and deep learning models are investigated to understand the suitable model for PPG verification. Fourth, we develop the Generative Adversarial Network which generates the synthetic PPG with holding the unique and time-stable features. Last, we proposed the score-level fusion method of single modality (PPG) with different representations to achieve the better results with less complexity. In the collected database, we achieved up to 11.5% Equal Error Rate (EER) whereas recent works in the literature showed 23.2%, 19.1% EER in their databases. The obtained results guarantee that our PPG verification system has a high possibility to be considered in real world.
Methane Fluxes from Living and Dead Trees in a Temperate Forest
Keywords: Forestry
Methane budgets
Methane sink
Methane source
Methanogens
Methanotrophs

Trees have been identified as an important source of methane in forest ecosystems, but little research exists on fluxes beyond their stems, such as those from foliage, branches, wounds, and coarse woody debris. Recent instrumentation advances allow rapid and accurate measurements of relatively low methane flux rates in-situ; this thesis takes advantage of such technology to explore methane fluxes from these tree components in northern hardwood forests of central Ontario, Canada. Foliage was found to represent a substantial component of forest methane budgets, acting as a sink in upland forests and a source in lowland forests (averages = -0.54, 6.06 nmol m-2 s-1; n = 27, 12, respectively). Uptake is hypothesized to occur through methanotrophs within foliage, and emissions from channelling of methane that originates in soil. In an upland site tree branches, wounds, and stems emitted methane (averages = 0.61, 10.58, 0.59 nmol m-2 s-1; n = 18, 83, 79, respectively), and at the stand scale represented 83%, 8%, and 9% of emissions from trees respectively. Emissions are hypothesized to occur through anoxic decomposition within the tree, which often occurs due to wounding. Coarse woody debris was found to act as a methane source in early decay classes and a sink in later decay classes (average flux rates ranged from 0.78 to -1.58 nmol m-2 s-1; n = 94). Immediately after harvest there was a large pulse of emissions from the cut surfaces of trees (>4000 nmol m-2 s-1 for Acer saccharum boles), but on average coarse woody debris was a methane sink in both managed and unmanaged stands. These results represent some of the first and most comprehensive in-situ methane flux measurements from tree branches, wounds, foliage, and coarse woody debris, and help to improve estimates of forest methane budgets. Inclusion of wounds and branches into calculations of tree methane fluxes will increase net emissions, but inclusion of upland foliage and dead wood as methane sinks can offset them. Strengthening forest methane sinks and reducing sources is an attractive policy option for “climate-smart” forestry, and this research can be built upon to support future efforts in this field.
A ‘Truly European Language:’ Europeanization and Supranational Language Regimes in the Case of Romani Language, 1998-2018
Keywords: Council of Europe
Europeanization
language policy
Roma
Romani

What impact has integration with Europe had on state language regimes in Central and Eastern European countries? This dissertation investigates supranational and state treatment of Romani – the language spoken by many Roma communities in Europe – through an illustrative study of the Council of Europe and case studies of Slovakia and Croatia. Changes in state treatment of Romani in both countries have been significant on paper. In reality, however, implementation is limited or nonexistent. What explains this superficial and attenuated change? The Council of Europe’s language regime, centred on its valuation of diversity, led the organization to support Romani and push member states to do the same. In the context of Central and European countries’ integration into the EU, and into ‘Europe’ more generally, the mechanisms of Europeanization have resulted in the diffusion of elements of this supranational language regime to the domestic level. First, normative pressure and membership conditionality from European institutions have led to increased 'paper promises' – legal and policy commitments to support Romani – that follow the norms and standards of the supranational language regime at the Council of Europe. Secondly, Europeanization has resulted in new tools, opportunities, and political space for Romani language advocates within each country. But the penetration of such of supranational language regimes is also limited by two factors. State resistance emerges from the continued durability of state traditions that delegitimize Romani and exclude it from minority language rights frameworks. Secondly, the remedies for linguistic minorities proposed by both state and supranational language regimes are often a poor fit for Roma communities. Studying state treatment of Romani language helps illustrate the impact of integration with Europe on what I term marginal policy areas: those domestic policy areas which are subject to European pressure but not directly subject to EU rules. I also contribute to recent literature on continuity and change within state language regimes. The study of the politics of Romani language illuminates not only the situation of a specific minority language, or even linguistic minorities more generally, but also the complex interactions between institutions and actors at the state and supranational levels in Europe.
The Acute Effects of Alcohol on Response Inhibition: An Evaluation of Meta-analytic and Laboratory-based Outcomes
Keywords: Alcohol
Meta-Analysis
Response Inhibition

Individuals with and without an alcohol use disorder frequently report loss of control over alcohol use, described as escalations of drinking both within a drinking episode and across time. Dual-process and triadic neurocognitive models provide explanatory frameworks of loss of control. Within these frameworks, response inhibition – the ability to withhold a prepotent response – figures prominently. Alcohol is postulated to acutely impair response inhibition, thereby contributing to loss of control over alcohol use. The effect of alcohol on response inhibition has been extensively studied in the literature. Discrepant findings have been reported, particularly around the magnitude of this effect. Recent extensions of dual-process models postulate a role of interoception – the perception of internal bodily states – in regulating alcohol use behaviour. In the triadic model, the product of the interoceptive system, alcohol craving, is thought to reduce cognitive resources available for cognitive control, resulting in attenuated response inhibition ability and higher levels of alcohol consumption. Partial support for the triadic neurocognitive model is evident in the literature, but central hypotheses from this model have yet to be tested empirically in the laboratory. Therefore, the present work has two aims: (1) to meta-analytically aggregate the literature on the acute effects of alcohol on response inhibition, and; (2) test the hypothesis that interoceptive sensitivity moderates craving elicited by alcohol, and that heightened craving results in diminished response inhibition, and increased alcohol consumption in a laboratory setting. The meta-analysis revealed a detrimental effect of acute alcohol administration on response inhibition, and this effect was moderated by intoxication level, indicators of task difficulty, and comparison type (Stop Signal Task only). The laboratory-based study failed to identify any significant effects, perhaps due to the use of a low priming dose and/or limited statistical power. The current work reinforces extant research showing a detrimental acute effect of alcohol on response inhibition and establishes the size and moderators of this effect. Ultimately, this work furthers the understanding of the potential mechanisms underlying loss of control over alcohol use in a drinking episode and to this end, the findings herein may be used in future studies to examine this construct.
Some Topics in the Arithmetic of Hodge Structures and an Ax-Scanuel Theorem for $GL_n$
Keywords: Ax-Schanuel
Height bounds
Unlikely Intersections
Variations of Hodge structures
Zilber-Pink

In the first part of this thesis, we consider smooth projective morphisms $f:X\rightarrow S$ of $K$-varieties with $S$ an open curve and $K$ a number field. We bound the Weil height $h(s)$ polynomially from above by $[K(s):K]$ at points $s\in S(\bar{K})$ that are ``exceptional'' with respect to the variation of Hodge structures $R^n(f^{an}_{\mathbb{C}})_{*}(\mathbb{Q}_{X^{an}_{\mathbb{C}}})$, where $n=\dim X-1$. For this variation, we assume that its generic special Mumford-Tate group is $Sp(\mu,\mathbb{Q})$, that it degenerates strongly over some point $s_0$ of a curve containing $S$, the Hodge conjecture holds, and that what we define as a ``good arithmetic model'' exists for the morphism $f$ over $\mathcal{O}_K$.\\ In the second part of this thesis, we prove an Ax-Schanuel type result for the exponential functions of general linear groups over $\mathbb{C}$. We prove the result first for the group of upper triangular matrices and then for the group $GL_n$ of all $n\times n$ invertible matrices over $\mathbb{C}$. As a corollary we obtain Ax-Lindemann type results for these maps, characterizing the bi-algebraic subsets of these maps.
Investigating Regulation of Cyclin-Dependent Kinases by SCF Ubiquitin Ligases and Pharmacological Kinase Inhibitors
Keywords: Cell cycle
Kinase
Kinase inhibitor
Structural biology
Ubiquitin
X-ray crystallography

Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that control both transcription and progression through the cell cycle. CDKs are catalytically inactive as monomers and only become fully active upon heterodimerization with cyclin proteins and phosphorylation of their activation segment. Conversely, CDKs can be inhibited by binding to CDK inhibitor proteins and phosphorylation of the glycine-rich loop of the kinase domain. Whether or not a particular CDK is active depends on the abundance of their intermolecular regulators, which is controlled by the ubiquitin-proteasome system. Because CDKs play important roles in directing cell cycle events, dysregulation of their kinase activity is commonly associated with many cancers. For this reason, it is important to understand the biology underlying CDK regulation during the cell cycle and how CDKs can be targeted by small molecule kinase inhibitors. The work conducted in this thesis focuses on two different CDKs, namely CDK2 and CDK11. In Chapter 2, I investigated the binding between the CDK2-cyclin A complex and the F-box protein Skp2. Skp2 is the substrate recognition subunit of the multi-subunit E3 ubiquitin ligase, SCFSkp2. SCFSkp2 regulates CDK2 by ubiquitinating CDK inhibitor proteins. Aside from the domains required for E3 ubiquitin ligase function, Skp2 contains a disordered N-terminus that is known to bind CDK2-cyclin A via cyclin A. The functional significance of this interaction is unknown. I determined a crystal structure of the N-terminus of Skp2 bound to cyclin A and investigated how Skp2 binding cyclin A affects CDK2-cyclin A kinase activity. In Chapter 3, I focused on determining how the small molecule inhibitor OTS964 binds CDK11. OTS964 is the first reported CDK11 specific inhibitor; however, how OTS964 achieves its CDK11 specificity is unclear. To answer this question, I solved a crystal structure of OTS964 bound to CDK11 and investigated the basis of the selectivity of OTS964 by mutagenesis both in vitro and in cells.