VictorJuiz/thesis huggingface dataset:
Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and lineage Relationship
Keywords: Adult
Adult Stem Cells
Myelin
Neural Stem Cells
Regenerative Medicine
Spinal Cord Injury

Adult neural stem cells (NSC) reside in the periventricular region along the entire neuaxis. It is thought that a subset of mature astrocytes, expressing glial fibrillary acidic protein (GFAP), known as definitive NSCs (dNSC) are responsible for neurogenesis within the adult forebrain. We have identified a novel population of a rare, primitive NSC (pNSC) expressing low level of the pluripotency marker, Oct4. Both dNSC and pNSC can be isolated in vitro using neurosphere assays and differentiate into glial and neuronal cell types. Transplantation studies of pure pNSCs into the anterior rostral migratory stream of mice produced migrating neuroblasts and neurons in the olfactory bulb suggesting a potential lineage relationship between pNSCs and downstream progenitor cells. Using transgenic mouse models whereby dNSCs are labeled using a Cre-Lox system then subsequently ablated using the thymidine kinase system under the GFAP promoter, we have shown that pNSCs are non-GFAP expressing and can give rise to dNSCs in the forebrain. By taking advantage of the unique marker expression of Oct4 in pNSCs, we used Oct4CreERT2;ROSAyfpfl/fl;GFAPtk mice to selectively label pNSCs followed by complete depletion of dNSCs. As predicted, some dNSCs that returned over time expressed YFP, revealing a direct contribution from pre-labeled Oct4 expressing pNSCs. Together, these findings confirm the NSC lineage relationship in vivo, whereby the dNSC lies downstream of the pNSC in the adult forebrain. In the non-neurogenic spinal cord niche, we have isolated pNSC and dNSC populations throughout development. We suggest a similar lineage relationship based on in vitro passaging experiments. Interestingly, the most abundant protein within mature myelin, myelin basic protein (MBP), inhibits proliferation which terminates NSC derived sphere formation in vitro. In a transgenic mouse model with conditional knock-out of MBP, the shiverer-/- mouse, there is a significant enhancement of the number of NSCs isolated both naively and following injury compared to littermate or non-injured controls respectively. In conclusion, we have identified two distinct NSC populations within the adult central nervous system that can be activated following injury but suppressed by MBP. Understanding the factors and conditions that impact these distinct populations of cells will shed light into developing novel stem cell-based regenerative medicine strategies.
Investigating the Practices of Literacy Teacher Educators
Keywords: Literacy
Literacy Teacher Educators
Student Teachers
Teacher Education

Investigating the Practices of Literacy Teacher Educators Doctor of Philosophy 2017 Belinda Longe Graduate Department of Curriculum, Teaching and Learning University of Toronto Abstract This research investigated the practices of six literacy teacher educators and explored the influences on their teaching practices in their literacy courses. This qualitative case study involved two interviews for each participant and classroom observations for some of the participants over a three-year period. Four main findings emerged from this research. First, participants’ vision for teaching, and their vision for teaching literacy was not static. The participants’ visions evolved over time and was influenced by their teaching and research experiences. Second, the participants emphasized continuous learning as an integral part of their vision, both for themselves and for their student teachers. They recognized that in their role as literacy teacher educators, a commitment to on-going learning was essential and fostering that commitment to life-long learning in their student teachers was equally important. Third, the participants had a range of pedagogical approaches that they implemented, although there were some approaches that were common across participants. Fourth, the participants focused on infusing components of balanced literacy into their literacy course and many drew on children’s and young adult literature as a springboard for teaching literacy concepts. The analysis of the data includes a discussion of the conceptual framework for the study and gives a brief overview of the interconnectedness of the concepts of social constructivism, vision for teaching literacy, and the elements of a pedagogy of teacher education. Implications for literacy teacher educators include developing literacy courses that aim to broaden student teachers’ notion of what counts as literacy. Other implications include encouraging literacy teacher educators to remain responsive and adaptive in their literacy teaching, and creating opportunities for literacy teacher educators to regularly review, participate, and conduct scholarly research in the field of literacy teacher education, which could inform and improve their practice.
Generating Evidence to Streamline the Clinical Pathway in Autism Spectrum Disorder Using Simulation Models: Cost-effectiveness Comparisons of Screening and Genetic Testing Strategies
Keywords: Autism spectrum disorder
Health economics
Health services

The clinical pathway to diagnosis in autism spectrum disorder (ASD) is complex. The objective of this thesis was to estimate the health and monetary impact of changes in the provision of select ASD screening and diagnostic health services. First, a meta-analysis estimated that the Modified Checklist for Autism in Toddlers, a commonly used ASD screening tool, performed at a low-to-moderate accuracy among children with developmental delay (pooled sensitivity: 0.83, 95% credible interval [CrI] 0.75, 0.90; specificity: 0.51, 95% CrI: 0.41, 0.61; positive predictive values [PPV] in high-risk children: 0.55, 95% CrI: 0.45, 0.66; PPV in low-risk children: 0.07, 95% CrI: <0.01, 0.16) and its performance changed with patient characteristics. The second study evaluated the cost-effectiveness of universal or high-risk screening compared to standard care, surveillance monitoring, in ASD using discrete event simulation. Results demonstrated that universal screening would greatly burden the healthcare system by heightening demand for diagnostic services and increasing healthcare expenditure. High-risk screening, on the other hand, could be a cost-effective strategy, yielding incremental cost-effectiveness ratios (ICERs) of $1100-1900/child initiated treatment or diagnosed earlier. The last study compared the cost-effectiveness of genome (GS) or exome sequencing (ES) to chromosomal microarray (CMA) using a microsimulation model. The use of ES in children with syndromic features after a negative CMA could be cost-effective compared to CMA alone (ICERs $5800-6000/child with pathogenic variant). If CMA was to be replaced by sequencing, GS would be the more cost-effective option. Findings from this thesis indicate that strategic resource allocation is crucial in ASD. Given the network of health, psychosocial and educational services required by individuals with ASD, changes in one component can have a large impact on the wait time, resource use and expenditure on downstream services that can affect children without ASD and extend beyond the healthcare system.
Alcohol Withdrawal Syndrome Assessment based on Tremor Time-Frequency Analysis
Keywords: Alcohol Withdrawal
Empirical Mode Decomposition
Regression Model
Signal Processing

In this thesis we established signal processing techniques to objectively evaluate the severity of Alcohol Withdrawal (AW) tremors. Many medical protocols were used pre- viously to help the physicians in assessing the severity of alcohol withdrawal, but those techniques were subjective and relied on the experience level of the physicians. The key objective throughout this thesis is investigating the logarithmic nature of the energy emitted from tremor signals. We are able to use the energy from tremor recordings in the frequency range of [5, 15] Hz to train a logarithmic model to estimate the severity of tremors. The next step in validating the effectiveness of the logarithmic model is the validation of the methodology in a clinical setting. The model is being validated in the emergency department for a 10-month period. During this period, each of the AW patients have been evaluated by one nurse and have been videotaped while acquiring the signal. The model provides the severity score in realtime after recording the signal. Our model is validated by comparing the score given by the model and the consensus severity rating from a panel of three expert physicians after viewing the videos. We concluded that there is a reliable agreement (kappa 0.92, 95% CI: 0.86, 0.99) between the score given by the model and the rating from our panel. Further contributions of this thesis include an investigation of the features of AW tremors in classifying factitious vs. real tremors, based on the mean peak frequency and band-limited energy. Additionally we evaluate the differences between AW tremors in both hands and observe that by averaging the tremor ratings of each hand, a more ac- curate result can be obtained compared to taking either of the individual hand ratings. Lastly, to remove the noise from the tremor signal, an Empirical Mode Decomposition (EMD) algorithm was utilized. EMD decomposes the signal into different Intrinsic Mode Functions (IMFs) and IMFs with the peak frequency in the frequency range of the tremor will be a part of the reconstructed signal. Using this technique, we successfully enhanced the accuracy of our logarithmic model.
Effect of Pore Structure and Chemistry on the Performance of Activated Oil Sands Petroleum Coke Electrodes for use in Electrochemical Double-Layer Capacitors
Keywords: Electrical Doube Layer
Energy Storage
Oil Sands Petroleum Coke
Pore Structure
Porous Carbon
Supercapacitors

Electrical energy storage is a limiting barrier to widespread usage and commercialization of sustainable and renewable energy sources, such as wind and solar energy, as well as integration of electric vehicles. Electrochemical double-layer capacitors (EDLCs) are a promising energy storage technology that offers the benefits of high power density, long cycle life, rapid charging rates, and moderate energy density. The energy storage mechanism of EDLCs is physical ion adsorption on the surface of porous carbon electrodes. This thesis is an investigation of three different sections relating to EDLCs: 1) techniques to properly characterize novel porous carbon electrode materials, 2) investigation of activated oil sands petroleum coke (APC) as the electrode material for EDLCs, and 3) a systematic study of the effects of porous carbon structure and chemistry on EDLC performance. In the first section, it was shown that variations in operating conditions and testing techniques can lead to discrepancies in measured and reported capacitance. Therefore, it was concluded that a standardized approach is necessary in order to properly compare different porous carbon electrodes. In the second section, APC was investigated as a novel electrode material for EDLCs. PetCoke is a carbon dense material that can be activated with potassium hydroxide to generate high surface area porous carbon materials. These materials show promising electrochemical performance in EDLCs, with capacitance values up to 400 Fg-1 in 4M potassium hydroxide aqueous electrolytes, depending on the operating conditions. Additionally, the power density of these materials is comparable to that of other carbon nanomaterials, which are more costly and challenging to produce. Finally, the third section investigates the relationship between measured capacitance, and carbon macrostructure, meso-structure, microstructure, and oxygen content. In each of these studies, the desired parameter was varied, while all others (surface area, pore size, chemistry) were maintained constant. Through this systematic approach, this thesis investigates and quantifies the relationship between EDLC performance and important characteristic parameters through isolation of each individual parameter. By understanding the key structural and chemical features that improve EDLC performance, focus can be placed on engineering a sustainable and economic porous carbon material that has these desired features.
A FRAMEWORK FOR MULTI-PLATFORM ANALYTICAL AND EXPERIMENTAL SIMULATIONS OF REINFORCED CONCRETE STRUCTURES
Keywords: Beam-Column Joints
Hybrid Simulation
Multi-Platform Nonlinear Analysis
Reinforced Concrete
Repaired Structures
Shear Behavior

This study presents a framework for multi-platform analysis and hybrid (experimental-analytical) simulation of reinforced concrete structures. In this approach, each potentially critical member, based on its mechanical characteristics, is modelled using the most suitable finite element analysis tool or is represented with a test specimen, while the rest of the structure is modelled with computationally fast global analysis software. The interaction between substructure modules is fully considered by satisfying compatibility and equilibrium requirements. The framework is based on object-oriented methodology and uses a standardized data exchange format, facilitating addition of new analysis tools or test equipment. The effectiveness of the framework is evaluated by several verification examples including analysis of structures repaired with fibre-reinforced polymer sheets. The multi-platform analysis computes the behaviour of structures with a level of accuracy that was previously difficult to achieve with most single-platform analysis software. In addition, a new interface element, named F2M, is introduced to connect layered beam elements to membrane elements. Compared to existing methods, the F2M element provides more realistic stress distributions and allows for transverse expansion at the connection section between substructures. The accuracy of the proposed element is verified through mixed-dimensional modelling of a series of beam specimens presented in the literature. A small-scale experimental program was conducted using a six degree-of-freedom hydraulic testing equipment to verify the hybrid simulation framework and provide additional data for small-scale testing of shear-critical reinforced concrete frames. The physical models were 1/3.23-scale representations of a beam and two columns. A multi-platform modelling technique was employed to analyze the remainder of the frames. The hybrid simulation results were compared against those obtained from a similar large-scale test and finite element analyses. The study found that, with proper precautions, small-scale hybrid testing can sufficiently well simulate the behaviour of shear-critical frames. However, to draw general conclusions, additional test data are required.
Snap, Twang, and Blue Note: A Cross-Cultural Examination of Features that Accompany Temporal Deviations in African-American Musics
Keywords: BeyoncĂŠ Knowles
John Coltrane
Judaic Studies
Kendrick Lamar
Linguistics
Western Music

The present study establishes meaning and linkage among a cluster of specific structural features —the snap, twang, and blue note— and between this cluster and the temporal deviations they can be found accompanying. These features are explored through their perceived sonic, textual, and motional properties, as they have emerged across cultures and historical periods, with distinct ethos. Consideration is taken for the ethnic, social, and spiritual meanings invoked by each feature, their interrelationships as a cluster, and with temporal deviation. Interrelationships include: snap and temporal deviations both emerging from polytempic interactions, yet contrasting in their respective grounded and floating qualities; snap and twang each articulating (i.e.: ‘worrying’) flexible blue note pitch regions; and twang and blue note’s respective articulations of vocal harmonics. I propose an isomorphic continuum may explain the ratios of temporal deviations identified in a number of African-American musics, suggesting deep interrelationships among snap, twang, blue note, and temporal deviations. If the blue note and certain temporal deviations are isomorphic, we can also learn about temporal deviation by studying the ethos of the blue note: I compare the ‘blue third’ with the diatonic minor third. The relationships between these features and temporal deviations suggest they function as co-expressions of, or redundant cues for, the performer’s awareness and commitment. I interpret the consistency of heightened arousal invoked by these features, as embodied understanding across cultural contexts. When embodied, the cue is perceived directly: for example, commitment and intensity is experienced, not merely represented, in the snap. Such cross-cultural consistency of meaning does not preclude the possibility that the features function as code-switching cues to mark transformative moments in music, since consistency of meaning doesn’t indicate consistency of ideology. Connecting the features to their subdivided variations opens the door to understanding the relevance and applicability of this study’s findings across an even wider breadth of musical practices. The spontaneous participant —artist, witness, researcher— kinesthetically channelling the creative spirit, stands to gain appreciation for the compatibility and complexity of different gestures, their consonances and dissonances, across disciplines and traditions.
TARGETING THE MITOCHONDRIAL DNA POLYMERASE GAMMA IN ACUTE MYELOID LEUKEMIA
Keywords: AML
mitochondria
mtDNA
nucleoside kinase
nucleotide salvage
POLG

Part I Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human AML samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared to normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared to normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we employed a nucleoside analog 2’3’-dideoxycytidine (ddC), which is phosphorylated to the activated anti-metabolite, 2’3’-dideoxycytidine triphosphate (ddCTP) by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase, POLG. ddC was preferentially activated in AML cells compared to normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitors cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML. Part II Human mitochondrial DNA is replicated by the mitochondrial DNA polymerase gamma. Using proximity dependent biotin labelling (BioID), we characterized the POLG interactome and identified new interaction partners involved in mtDNA maintenance, transcription, translation and protein quality control. We also identified interaction with the nuclear AAA+ ATPase Ruvbl2, suggesting mitochondrial localization for this protein. Ruvbl2 was detected in mitochondria-enriched fractions in leukemic cells. Additionally, transgenic overexpression of Ruvbl2 from an alternative translation initiation site resulted in mitochondrial co-localization. Overall, POLG interactome mapping identifies novel proteins which support mitochondrial biogenesis and a potential novel mitochondrial isoform of Ruvbl2.
Medium-Strength Modality in Science
Keywords: Contingency
Explanation
Generality
Modality
Models
Science

Alethic modality is typically understood in terms of necessity, truth in all possible cases, and possibility, truth in at least one possible case. But a great deal of our scientific knowledge falls in between necessity and contingency. We build models which apply to many, but by no means all, possible cases under consideration. Further, alethic modal (henceforth just â modalâ ) claims have typically been understood as applying to very broad domains, like conceptual, logical, or physical necessity. But many more local domains could likewise be considered modal. This thesis is a contribution towards characterizing this middle ground of medium-strength modality, which is graded and local. To show that such domain-relative and graded modality can be given a precise formulation, I develop a measure theoretic model of generality. This is meant mainly as a possibility proof, that we can at least sometimes make graded and domain-relative modal talk formally precise. Using this formal model as a backdrop, I argue that generality and contingency should be understood as modal concepts. Something is general to the extent that it applies to a large measure of a domain of possibilities, and contingent to the extent that it applies to a small measure. Chapter 3 ties this notion of generality to explanatory depth. This way of understanding modality also helps to clarify the relationship between laws and models (chapter 4). Laws, I claim, define domains of possibilities by drawing their limits. Since generality and contingency are best understood as domain-relative concepts, laws set the standard for what counts as general or contingent in a given context. Models operate to fill in the structure and content of domains of possibilities. Finally, medium-strength modal concepts help to clarify the difference between mechanistic and self-organized systems, which corresponds to the traditional distinction drawn between merely resultant and emergent properties. I argue that a system is mechanistic if its system-level regularities are the result of parts-level regularities (general features of its parts). Conversely, a system is self-organized if it displays system-level regularities, despite the contingent behavior of its parts. This analysis shows how we can be non-reductive physicalists.