VictorJuiz/thesis huggingface dataset:
Elucidating the Role of Alternative RNA Export Promoting Signal Sequence Coding Regions in Potentiating Translation

Elucidating the Role of Alternative RNA Export Promoting Signal Sequence Coding Regions in Potentiating Translation Kohila Kulendra Doctor of Philosophy Graduate Department of Biochemistry University of Toronto 2015 Abstract In vertebrates, a sub-population of mRNAs encoding secreted, membrane-bound and mitochondrial proteins contain nucleotide elements that promote the alternative mRNA nuclear export (ALREX) of microinjected mRNAs. This RNA element is present within the signal sequence coding region (SSCR) or mitochondria targeting sequence coding region (MSCR) and located at the 5'end of the mRNA just after the start codon. It is typically depleted of adenines and present in genes that lack introns in their 5'UTRs. I demonstrated that ALREX-promoting elements can potentiate translation in the presence of nuclear factors such as Nup358/RanBP2. To determine which domains of RanBP2 are required to enhance translation, I expressed mutant and/or truncated versions of RanBP2 in cells depleted of the endogenous protein and tested the translation of various reporters. I found that the entire C-terminal portion of RanBP2, including its E3 sumo ligase domain, is not required to enhance translation. In contrast, an N-terminal region, which includes eight zinc fingers and a tetratricopeptide repeat region that can bind to ALREX-promoting SSCRs, is required. Incorporating point mutations in the N-terminal domain of RanBP2, which disrupt its ability to bind SSCR RNAs in vitro, also impaired RanBP2's ability to enhance the translation of a reporter mRNA in vivo. Furthermore, N-terminal domain mutations in RanBP2 are known to be associated with the autosomal dominant genetic disorder Acute Necrotizing Encephalopathy 1 (ANE1). In these individuals, influenza viral infection triggers a cytokine storm which leads to coma and death. I found that RanBP2 depletion promotes the translation of the interleukin 6 mRNA, which encodes a cytokine that is overproduced in ANE1 children during infection. Overall, the data suggests a novel mechanism by which RanBP2 may regulate the translation of mRNAs and thus impact human health.

Keywords: nuclearpore
RanBP2
Advisor: Palazzo, Alexander F
Nonlinear Multivariate Time-space Threshold Vector Error Correction Model for Short Term Traffic State Prediction

The time-space threshold vector error correction (TS-TVEC) model is proposed and developed in this research for short term (hourly) traffic state prediction. The theory and method of cointegration with error correction mechanism is employed in the general design of the new statistical model TS-TVEC. An inherent connection is revealed between the error correction model and the transformed fundamental diagrams in macroscopic traffic flow theory. Error correction model is a linear model established on difference space, whereas, the fundamental relations between traffic variables exhibit piecewise linearity when they are transformed to difference space. Meanwhile, dynamics of traffic variables can be reflected in difference space. A threshold regime switching framework is implemented to deal with unknown structural breaks in non-stationary traffic time series to capture multiple traffic states. Spatial cross-correlated information is incorporated with a piecewise linear vector error correction model. As the TS-TVEC model is designed for nonlinear multivariate forecasting, it is compared to Neural Network, and Support Vector Regression model that are commonly used in this regard to test the effectiveness and robustness of the new statistical model. The TS-TVEC model was experimented on a small scale case in our empirical study and applied on a larger scale case thereafter. Both cases show that the TS-TVEC model is an effective tool that is capable of modelling the complexity of stochastic traffic processes and potentially applicable to real time traffic state prediction.

Keywords: cointegration
neural network
short term traffic state prediction
threshold regime switching
traffic time series
vector error correction
Advisor: Abdulhai, Baher
Zhou, Zhou
In Search of Quality: Evaluating the Impact of Learning Outcomes Policies in Higher Education Regulation

This study presents evidence on the impact of learning outcomes policies in quality enhancement and accountability in higher education regulation. The purpose of this research was to determine how learning outcomes polices are being used in regulatory schemes, and what (if any) impact the policies have had. In order to answer these two questions the research employed and then triangulated findings from a survey, case study analyses, and meta-evaluation research methods. Seventy-four regulatory agencies participated in a global survey, providing insight on the policy trends in articulating, incorporating and measuring learning outcomes. A primary aim of the survey was to identify policy evaluations that had taken place. While few policy evaluations were reported, the survey findings show a substantial difference in the impressions of impact and the research findings on impact. Nine policy evaluations uncovered through the global survey were analysed and coded as cases studies. The case studies determine positive, neutral or negative implications of the policies, and also provide qualitative insight into operational challenges leading to policy success or failures. The coded case studies were then pooled into a meta-evaluation to uncover the relative impact of policies. When analysed in a meta-evaluation, the results of existing research show learning outcomes policies are having limited impact. When triangulated, findings from the three research methods confirm the limited impact of learning outcomes policies and also reveal possible reasons for failures. One explanation is that the policies are poorly designed (being misaligned, misapplied, or misdirected), and that rectifying the policy issues will produce positive change. Another reason is that the way the regulatory agencies operate is a hindrance to policy success: that their roles, goals, and spheres of power are incongruent with the desired impact of learning outcomes. The most significant finding from this study is the critical role of policy evaluation in higher education regulation in order to provide summative information on impact. In both the microcosm of learning outcomes cycles of ‘articulate, incorporate, measure’, and the macrocosm of the ‘formulate, implement, evaluate’ policy cycle, the value of closing the loop through evaluation is critical for success.

Keywords: accreditation
international
learning outcomes
policy evaluation
quality assurance
regulation
Advisor: Jones, Glen A
An Examination of Neuromuscular Fatigue and Adaptations to Exercise and the Effect of Seal Oil Omega-3 Fatty Acid Supplementation in Trained and Untrained Males

Exercise performance is controlled and limited by the neuromuscular system. In response to exercise training, the neuromuscular system is able to rapidly adapt to novel exercise. However, few studies have investigated the effect of nutritional interventions on neuromuscular adaptations to exercise in trained or untrained males. Omega-3 polyunsaturated fatty acids (N-3 PUFA) are integrally involved in the development and maintenance of nerve tissue. Therefore, I hypothesize that N-3 PUFA supplementation will enhance neuromuscular adaptations to training in trained and untrained males. First, a comparison of neuromuscular fatigue from a 10 km cycling time trial between trained cyclists and untrained cyclists demonstrated that both groups showed neuromuscular fatigue proportional to their training experience. Then, two studies examined the effect of seal oil N-3 PUFA supplementation on neuromuscular adaptations to training. Untrained males performed two-weeks of sprint interval training (SIT), while trained individuals complete three-weeks of sport specific training. Seal oil N-3 PUFA supplementation did not enhance neuromuscular adaptations to SIT, as the training caused significant neuromuscular fatigue. Seal oil N-3 PUFA supplementation increased muscle activation (+22% SD 20 (ΔN-3 PUFA vs. ΔPlacebo)) and attenuated sprint cycling fatigue in well-trained males (+4.8% SD 3.4 (ΔN-3 PUFA vs. ΔPlacebo)). In conclusion, seal oil N-3 PUFA supplementation appears to enhance neuromuscular adaptations to training in trained but not untrained males.

Keywords: Exercise
Neuromuscular
Omega-3
Advisor: Wolever, Thomas MS
Wells, Greg D
Negotiating Multiple Literacies: Student Teachers' Conceptions, Experiences, and Practices

This longitudinal and qualitative study makes an important contribution to literacy teacher education because it highlights the need for more systematic research to examine how the concept of multiple literacies is engaged in teacher education to prepare beginning teachers for the demands of contemporary literacy teaching. This study examined how a group of middle school student teachers constructed conceptions of literacy, enacted literacy pedagogy, and negotiated their role as teachers of literacy, over two years of teacher education studies. Data collection methods included questionnaires (n=22), four stages of semi-structured interviews with a purposive sample of eight student teachers (32 interviews), and document analysis. Findings suggest the student teachers entered teacher education with restricted notions of literacy due in large part to their school literacy histories. While the student teachers participated in a rich array of literacy practices in their out-of-school interactions (e.g., home, community, peer), their initial conceptions of literacy were largely grounded in the autonomous model of literacy they encountered in their prior schooling (Street, 1984). However, as the student teachers entered into conversation with the broader field of literacy (e.g., multiliteracies, critical literacy, out-of-school literacies) in their literacy methods courses, their conceptions of literacy steadily broadened and they developed a more nuanced understanding of literacy pedagogy. They came to recognize the need for contemporary literacy pedagogy to foster students' critical navigation of diverse texts and digitally mediated technologies. Moreover, the student teachers who had the opportunity to teach literacy during practice teaching sought to translate their expanded conceptions of literacy to the middle school classroom. This research identified several factors that facilitated student teachers' expanded conceptions of literacy including: specific course content (e.g., understanding literacy as a situated social practice), particular pedagogies (e.g., integration of digital technologies), and having ample opportunity to observe and enact a multifaceted approach to literacy teaching during practice teaching. This research contributes to our understanding of the role literacy teacher education plays in the lives of beginning teachers.

Advisor: Kosnik, Clare
Study of the Higgs Boson Produced in Association with a Weak Boson and Decaying to WW* with a Same Sign Dilepton and Jets Final State in √ s =8 TeV pp Collisions with the ATLAS Detector at the LHC

The research described in this thesis is aimed at studying production of a Higgs boson in association with a W boson, in the H → W W ∗ decay mode, using 20 fb −1 of 8 TeV data collected in 2012. The specific final state studied in this thesis has the associated W boson and one of the W bosons from the Higgs decaying leptonically, while the last W boson decays hadronically, giving two leptons, jets, and missing transverse energy as the final state signature in the ATLAS detector. The two leptons are required to have the same sign charge in order to suppress the many Standard Model background processes with oppositely charged di-lepton final states. The most important backgrounds are the W Z process where a lepton is not correctly identified, the W +jets process where a jet is misidentified as a lepton, and the W γ process where a photon converts and is incorrectly identified as a lepton. The ultimate goal of the analysis is to measure the rate of W H production.

Keywords: Associated production
ATLAS experiment
Global sequential corrections
Higgs boson
Advisor: Savard, Pierre
Knowledge Mobilization in Ontario: A Multi-case Study of Education Organizations

In recent decades, there has been growing interest among governments and research funders to mobilize knowledge and strengthen evidence-informed decision-making. Knowledge mobilization (KMb), the process of connecting research to policy and practice, is about individual and organization-level efforts to increase the use of research findings by education stakeholders such as policymakers, practitioners and the public. Using a multi-case design (Stake, 2006; Yin, 2014;), this study draws from the KMb literature, examines the contextual factors affecting organizational KMb (social and political context, mission, culture, and capacity) and analyzes the KMb approaches and activities in organizations (purpose, evidence production, target audience, strategies, mediation, impact, and challenges). The sample consists of four different education organizations within the province of Ontario, Canada: a university (York University), an urban school board (Toronto District School Board), a professional teacher organization (Ontario College of Teachers), and a non-profit (People for Education). Data sources include publicly available documents on organizational websites (e.g., products, events, networks, and capacity-building). Key informant interviews (N =18) were conducted with senior leadership and researchers in order to gain insight into the KMb approaches and activities. Overall, the organizations differed greatly not only in their mission, culture and capacity for KMb, but, also, in their understanding of KMb. This study identified ten common challenges to KMb, which included limitations to the organizational culture and capacity for KMb, a misalignment between the strategic direction and organizational mandate, and a limited understanding of dissemination mechanisms. Altogether, measures of impact were found to be weak across the cases. The study makes recommendations for strengthening KMb efforts in organizations and across the education sector. The results may help educators, researchers and policymakers understand how to develop and enhance efforts to mobilize research knowledge.

Keywords: case study
educational leadership
evidence-based policy
knowledge mobilization
organizations
research use
Advisor: Campbell, Carol
Cellular and Molecular Mechanisms of Vascular Regenerative Poly(methacrylic acid-co-methyl methacrylate)-based Biomaterials

Biomaterials containing methacrylic acid (MAA) were termed “vascular regenerative” as they were previously shown to improve vascularization, diabetic wound healing and graft survival. It has been unclear how these biomaterials elicit such biological responses. The goal of this thesis was to follow up on earlier observations of an increase in the expression of sonic hedgehog (Shh) and inflammation associated genes in diabetic wounds using both targeted and unbiased approaches. The cellular and molecular mechanisms were studied in non-diabetic models of wound healing and subcutaneous injection in Shh-Cre-eGFP/Ptch1-LacZ and CD1 mice in vivo and macrophages in vitro. Additionally, sex-based differences in response to MAA-based biomaterials were investigated by including females in experiments and performing sex specific analyses. The vascular potency of MAA-based biomaterials was confirmed as the application of MAA beads to wounds or subcutaneous injection of these beads promoted vessel formation in non-diabetic mice in the absence of the compounding effects of diabetes; a stronger effect on vascularization was seen in males than females. The use of Shh-Cre-eGFP/Ptch1-LacZ mice demonstrated MAA-mediated increase in density of cells expressing GFP (Shh) and β-Gal (Ptch1), suggesting Shh pathway activation since Ptch1 is a target of this pathway. Treatment with MAA beads also increased the expression of a Gli3 transcription factor involved in modulating the vascular effect of Shh signaling. Additionally, MAA-based biomaterials increased Shh expression in macrophages, enhanced macrophage density and altered macrophage phenotype, as observed through phosphorylation changes and an increase of M2 surface markers. MAA-based biomaterials activate a complex network of biological mechanisms that results in the vascular regenerative effect, and Shh signaling and an altered inflammatory response are two of the mechanisms involved in it. It is believed that understanding this network will expand the knowledge of biomaterial-host interactions and facilitate the development of MAA-based and other therapeutic biomaterials.

Keywords: biomaterials
macrophages
methacrylic acid
sex differences
sonic hedgehog
vascularization
Advisor: Sefton, Michael V.
Leading for Equity: Principals' Strategies

LEADING FOR EQUITY: PRINCIPALS’ STRATEGIES Doctor of Education, 2016 Jane Macpherson Department of Educational Leadership and Policy University of Toronto ABSTRACT The purpose of this research was to learn about the strategies principals use in leading for equity in their schools. This study is intended to illuminate the status of principals’ equity efforts following the four year implementation of Ontario’s Equity and Inclusivity Strategy and to better understand the supports necessary for doing school site equity work. A qualitative research approach was used which included personal interviews with twelve principals who self identify as leaders for equity in an Ontario school district. The participants shared a rich breadth of understanding of equity issues that included the notion of equity as fairness, and recognized the barriers that exist for marginalized groups as a result of the interplay of power and privilege. The obstacles to equity work identified by participants included system constraints that result from workload issues, standardized testing, funding policies, and frequent transfers of principals. Other barriers identified by participants were the perceived lack of value placed on equity work, resistance encountered from staff, parents and senior administration, ignorance of equity issues, the preponderance of a deficit mindset amongst educators, inequitable hiring practices, collective agreement constraints, the political context surrounding administrators, and the personal toll equity efforts often takes on principals. The participants described strategies they employ in moving understanding and conditions for equity forward in their schools. They articulated a strong ability to gather data and formulate goals, strategies and monitoring measures in school improvement plans. The principals described the importance of building relationships with staff, parents and students to create an environment where open and honest discourse might take place. They expressed a belief in the importance of shifting their knowledge of equity to action through their ability to challenge existing inequities, advocate for marginalized groups, and empower others to act. The principals spoke to the need to develop and utilize political savvy to navigate the difficult waters that often exist in schools and throughout the district. The thesis concluded that there are current and desired supports that can enable the work of equity leaders in schools. These supports include professional development for principals, human resource support, increased accountability for equity initiatives (at the Ministry and District levels), and validation by system leaders of the efforts of leaders for equity.

Keywords: equity
principal leadership
strategic leadership
Advisor: Ryan, James
Mid-level Cues for Bottom-up Grouping

Bottom-up perceptual grouping is an essential but often elusive component of computer vision that occurs in support of object recognition. We base our analysis on Gestalt grouping principles that range from low-level cues, which lack contextual scope but are computationally attractive, to mid-level cues, which cover larger scope but are difficult to incorporate in a computationally efficient manner. Our thesis begins with object categorization as motivating context for perceptual grouping, highlighting the issues of complexity and learning, and the importance of feature representation in handling variability. We then make inroads into bottom-up grouping in three steps. First, we focus on the mid-level cue of symmetry, which we extend to handle curvature and taper. We make effective use of symmetry to handle a wide range of input variability, and demonstrate significant improvements from formulating symmetry-based grouping as an optimization problem. Second, we develop an energy-based superpixel grouping framework that has expressive power to accommodate multiple grouping cues that range from low-level to mid-level, and from contour-based to region-based. We demonstrate the benefit of combining multiple mid-level cues to eliminate false positives. Finally, we reformulate bottom-up perceptual grouping as a prediction task to enable us to use the framework of structured prediction to tackle grouping as a single, unified problem. We bring performance to a level competitive with recent state-of-the-art baselines to close the gap between bottom-up grouping and recognition.

Advisor: Dickinson, Sven
Fidler, Sanja
Manufacturing Optimal Nanocrystalline Microtruss Materials

Fabrication of optimal ultra-lightweight hybrid cellular materials via a two-step synthesis method of rapid prototyping followed by electrodeposition was accomplished in three distinct stages: modelling, fabrication, and validation. For the first stage, a baseline microtruss architecture with multiple geometric and material degrees of freedom was optimized with relation to the expected failure mechanisms. An intrinsic link between material selection and architectural variables was discovered and quantified. For a given electrodeposited polycrystalline Ni/polymer microtruss that has already been optimized for maximum load carrying capacity with minimal mass, substituting a nanocrystalline coating shifts the location of optimal design. It is possible through the redistribution of metal and polymer in this nanocrystalline microtruss to further decrease the total beam mass by a factor of three, showcasing this material-geometry dependency. The second stage hinged on developing a novel processing technique to deposit metal coatings on the as-printed polymer parts. The critical step of adhesion was solved using an 18~M sulphuric acid wash to preferentially smoothen the inherent 0.6~mm roughness on the samples. Finally, the models were validated through the testing of as-printed and coated rods and microtrusses. Nanocrystalline microtrusses showed a 60x increase in peak flexural strength with only a 6x increase in density. Further optimization can more than halve the final density while maintaining the same load carrying capacity by removing the sacrificial polymer core using the same sulphuric acid wash. The experimental values fit very well to those predicted in stage one for varying slenderness ratios, scales, and material systems.

Keywords: 3D Printing
Cellular Materials
Electrodeposition
Failure Mechanisms
Optimization
Sandwich Panels
Advisor: Hibbard, Glenn D
Steeves, Craig A