VictorJuiz/thesis huggingface dataset:
Coricobasal Syndrome: Clinical, Neuropsychological, Imaging, Genetic and Pathological Features
Keywords: corticobasal syndrome
mutation
Progranulin
brain SPECT
heterogeneity
apraxia
dementia
movement disorder

Corticobasal Syndrome (CBS) is a rare movement and cognitive disorder. There is significant heterogeneity observed in it clinical presentation, neuroimaging, pathology and genetics. Understanding this heterogeneity is a priority and may help to shed light on underlying pathogenic mechanisms. We first demonstrated that truncating mutations in the progranulin gene (PGRN) can cause familial CBS associated with frontotemporal lobar degeneration (FTLD)-ubiquitin pathology. This study identified a mutation in PGRN (Intervening Sequence 7+1 guanine > adenine [IVS7+1G>A]) that segregated with CBS in a family. The mutation was predicted to result in a shortened messenger RNA (mRNA) sequence and the absence of the mutant PGRN allele was confirmed in the reverse transcriptase-polymerase chain reaction (RT-PCR) product, which supported the model of haploinsufficiency for PGRN-linked disease. In a second familial study, clinical, radiological, genetic, and pathological studies were performed to contrast clinical features of the affected members. Sequencing PGRN revealed a novel, heterozygous cytosine-adenine dinucleotide deletion in exon 11 (g.2988_2989delCA, P439_R440fsX6). The proband`s clinical diagnosis was frontotemporal dementia and parkinsonism (FTDP). The proband’s brother with the same mutation presented initially as a progressive non-fluent aphasia (PNFA), and later evolved into a CBS. Pathological analysis revealed Frontotemporal Lobar Degeneration-Ubiquitin (FTLD-U)/ TAR DNA-binding protein 43 (TDP43) positive pathology. The next studies shift away from pathogenic mechanisms to focus on brain-behavioural correlations and phenotypic heterogeneity in a prospective sample of 31 CBS cases. We provide the first direct correlative analysis between the severity of ideomotor apraxia, a common sign in CBS, and cerebral SPECT perfusion imaging. Reductions in perfusion within the left inferior parietal lobule (t=5.7, p=0.03, Family-Wise Error [FWE] corrected), including the left angular gyrus (t=5.7, p=0.02, FWE corrected), were associated with more severe ideomotor apraxia. We stratified the sample into CBS presenting with early motor features (CBS-M; n=9) or early dementia (CBS-D; n=22), which identified that CBS-M were more likely to have cortical sensory loss than CBS-D (p=0.005). In contrast, the presence of aphasia was found to be more common and severe in CBS-D compared to CBS-M (p=0.02). CBS-M patients had significantly reduced perfusion in the right supplementary and premotor areas compared to CBS-D (p<0.05).
The Transtheoretical Model of Behaviour Change and Possible Selves in Criminal Offenders
Keywords: transtheoretical model of change
possible selves
criminal offenders
stages of change

In order to assist people in making positive changes of problematic behaviour it is necessary to examine how people change and what factors influence the process. Criminal offenders represent a group of individuals who often have difficulty desisting from problematic behaviour and continue to engage in illegal activity. Offenders in provincial correctional institutions were administered questionnaires to determine stage of change and processes utilized as outlined in the Transtheoretical Model (TTM) of change (Prochaska & DiClemente, 1984). Additionally, offenders were asked about their visions of the future using the Possible Selves (PSs) Model (Markus & Nurius, 1986). Taken together, this study looked at the contribution of the PSs Model to our understanding of the TTM, which has been criticized in recent years as lacking therapeutic significance for treatment providers as they guide individuals through the change process. More specifically, this study compares chronic criminals with first time offenders on psychological variables such as readiness for change, vision of possible selves, and hope for the future, as well as on legal variables such as risk for recidivism and institutional behaviour. The results indicate that most offenders acknowledged their behaviour as problematic and some even reported they were actively taking steps to change; however, chronic offenders admitted having less hope than first time offenders. Interestingly, both groups rated similarly on the dimensions of PSs. The outcomes would suggest that research efforts to incorporate other complimentary theories of change into the TTM, like the PSs model, may be helpful for understanding the process of change. While it seems these models may not be useful for predicting institutional behaviour, the data perhaps demonstrates the complexity of criminal behaviour and speaks to the necessity of further research in this population.
Interspecific and Size-dependent Variation in Carbon Concentration and Wood Chemical Traits of Tropical Trees
Keywords: forest
tree
carbon
wood chemistry
carbon accounting
volatile carbon
tropical forest
tropical tree

Tropical forests play a major role in global carbon (C) dynamics and maintain some of the highest biological complexity on Earth; however, little is known about how variation in wood chemical traits contributes to tropical forest structure and function. This research examines inter- and intraspecific patterns in wood chemical traits in order to understand 1) the role wood chemical traits play in tropical forest C dynamics, and 2) the adaptive significance of wood chemical traits in tropical trees. I found wood C concentration varies widely among co-occurring tropical tree species, with average C concentration (47.4 ± 0.33% w/w (S.E.)) being significantly lower than values assumed in prominent forest C accounting protocols. Failing to account for this variation leads to overestimates of ~3.3 – 5.3% in tropical forest C accounting, an error that compounds significantly at larger spatial scales. I also show that oven drying samples prior to elemental analysis underestimates wood C concentration by 2.5 ± 0.17%, due to the loss of the “volatile C fraction”. Counter to expectations, I found wood C concentration is not ii phylogenetically conserved nor correlated to species demography or life history traits. Wood chemical traits showed consistent size-dependent patterns: wood C (in 16 of 24 species) and lignin (in 15 of 16 species) was higher in saplings vs. conspecific canopy trees. These patterns, complimented by phylogenetic analyses, suggest saplings require wood chemical traits that confer greater pathogen defense. When analyzed across a continuous size spectrum, I found wood C concentration (and leaf structural traits) increases linearly, while wood starch concentration (and leaf traits associated with C gain) shows “hump-shaped” patterns with peak values closely preceding reproductive onset; the latter result suggests C may limit growth in larger trees. Overall, my dissertation provides one of the first comprehensive examinations of wood chemical trait variation in tropical trees. In doing so it provides novel, timely, and critical insights into how wood chemical traits contribute to tropical forest structure and function.
Investigation of Activated Tyrosine Kinases in Myeloproliferative Neoplasms
Keywords: Cancer
Molecular Biology

Myeloproliferative neoplasms (MPNs) are a group of disorders characterized by an excess production of a specific, fully functional blood cell type. Many cases involve deregulation of a protein tyrosine kinase. JAK2 is one such kinase, involved in a subset of MPNs. JAK2-selective inhibitors are currently being evaluated in clinical trials. In order to identify inhibitor-resistant JAK2 mutations before they appear in the clinic, we utilized TEL-JAK2 to conduct an in vitro random mutagenesis screen for JAK2 alleles resistant to JAK Inhibitor-I. Isolated mutations were evaluated for their ability to sustain cellular growth, stimulate downstream signalling pathways, and phosphorylate a novel JAK2 substrate in the presence of inhibitor. When testing the panel of mutations in the context of the Jak2 V617F allele, we observed that a subset of mutations conferred resistance to inhibitor. These results demonstrate that small-molecule inhibitors select for JAK2 inhibitor-resistant alleles. Chronic myeloid leukemia is an MPN characterized by the presence of the BCR-ABL fusion gene. We determined that a specific cohort bearing deletions near the ABL gene, which is associated with poor prognosis, do not suffer from genomic instability. We also examined the role of a putative tumour suppressor gene EXOSC2 as an explanation for the reduced survival time, and suggest it may have a role in disease progression.
Towards a Meta-theory of Career Integration: The Vocational Well-being of New Immigrant Professionals in Canada
Keywords: Career Counselling
Immigrant/Immigration
Vocational Psychology
Career Development
Cross-cultural Psychology
Work

The purpose of this study was to empirically support and elaborate upon an integrative theory of career development by examining the worklife adjustment and career development experiences of new Canadian immigrant professionals. In focusing on the participants’ subjective views, the study provided an understanding of the lived experiences of this unique life-career transition, and in so doing, aimed to elaborate upon existing theories of career development towards the development and empirical substantiation of a comprehensive, diversity- and culturally- sensitive integrated meta-theory of the career development of immigrants in Canada. A qualitative methodology was employed and transcripts of in-depth interviews were analyzed using a grounded theory approach to data analysis. The central themes within the narratives that emerged were contrasted against an integrative career development theory and career development theoretical constructs, with the goal of elucidating the role and function of such constructs in immigrants’ Canadian career development. The study’s findings and contribution of a diversity- and culturally- informed, integrated, and enriched meta-theory of career development have implications for career counselling, cross-cultural, immigrant, and vocational psychology literature and practice.
Effects of Distributed Leadership on Teachers' Academic Optimism and Student Achievement
Keywords: Distributed leadership
Academic Optimism
Student Achievement

Distributed Leadership is often considered an optimal form of leadership to improve student achievement. The challenge though is that previous research on distributed leadership has often described what distributed leadership is as opposed to what distributed leadership's impact on student achievement might be. Since leadership has an indirect effect on student achievement, exploring organizational factors that may have a more direct impact on student achievement is important. Academic optimism describes teachers' perceptions of the staff's collective efficacy, the trust experienced between teachers, and between teachers and administrators, and the extent to which academic press (high expectations) is evident in the school. Academic optimism is an organizational factor that improves student achievement according to previous research. This thesis examined patterns of distributed leadership and their correlation to academic optimism. Further I examined the impact that academic optimism has on student achievement. By surveying 2122 teachers in 113 schools in a large school board in south-central Ontario, I determined that planfully aligned distributed leadership had a significant correlation to academic optimism but academic optimism did not have a significant correlation to student achievement. Rather, academic press, one of the variables within academic optimism, did have a significant correlation to student achievement in language and math. This study concluded that planfully aligned distributed leadership mediated by academic press had a significant impact on student achievement.
A Comparative Study of Elite-English-medium Schools, Public Schools, and Islamic Madaris in Contemporary Pakistan: The Use of Pierre Bourdieu’s Theory to Understand "Inequalities in Educational and Occupational Opportunities"
Keywords: Education
Sociology of

A Comparative Study of Elite-English-Medium Schools, Public Schools, and Islamic Madaris in Contemporary Pakistan: The Use of Pierre Bourdieu’s Theory to Understand "Inequalities in Educational and Occupational Opportunities" Doctor of Education, 2012 Akhtar Hassan Malik Department of Sociology and Equity Studies in Education University of Toronto ABSTRACT This thesis has attempted to understand the role of mainstream schools: elite English-medium schools, public schools and Islamic madaris in reproducing various social classes in Pakistan. Bourdieu’s theory of social reproduction serves as a major conceptual framework in this study, and it has been complemented by Anyon’s thesis about social class and school knowledge. My study suggests that an unequal availability of capital resources, agents’ class-habitus, and the type of their “cultural currency” act as selection mechanisms that clearly favour some social groups over others. This consolidates existing social-class hierarchy. The ruling classes ensure the transfer of their power and privilege to their children by providing them quality education in elite schools. The disadvantaged classes have no other option than to educate their children either in public schools or Islamic madaris. The new non-elite private schools have blatantly made education a commodity. This has contributed towards educational apartheid in the country. My study underscores that the working-class parents possess cultural capital which they transmit through building efficient learning environments in family settings. Yet, their class-habitus plays a causal role in keeping aspirations low. The three types of schools constitute distinct fields of education and provide a fairly different schooling experience to their students. For instance, these schools have different standards of material/human resources that are likely to instil a hierarchical view of the world among students. Likewise, differing curricular, pedagogical, and student evaluation practices emphasize different cognitive and behavioural skills. These differences can become central features for the reproduction of the division of labour at work and in society between those who plan and manage and those in the work force whose jobs primarily entail carrying out policies made by others. Public school knowledge has some exchange value in the marketplace, but it legitimates the ideology of production for consumption. I recommend that an integrated and equitable system of “national education” is vital for nation building. For future research, I suggest both considering different components of cultural capital other than exposure to high culture and exploring a wide range of dispositions to better understand how they influence one’s actions.
Functional Characterization of the Membrane Glycoprotein CD133
Keywords: CD133
N-glycosylation
AF4
HDAC6
β-catenin

The AC133 epitope of the pentaspan transmembrane glycoprotein CD133 has been used as a cell-surface marker for normal and cancer stem cells from a broad range of tissue types. Despite the utility of CD133 as a marker, little is known regarding its regulation and biological function. To study these poorly understood aspects of CD133, I took two main experimental approaches: RNA interference (RNAi) screening and affinity purification coupled with mass spectrometry (AP-MS) to identify CD133 regulatory genes and CD133 protein-protein interactions (PPIs), respectively. Both of these experimental approaches relied on a human embryonic kidney (HEK) 293 cell line that exogenously expresses affinity tagged CD133 (HEK293/AC133). This cell line allowed me to perform a large-scale RNAi screen to interrogate 11,248 genes for their involvement in cell-surface AC133 recognition. This resulted in the identification of the N-glycosylation pathway as a direct contributor to CD133 plasma membrane localization and cell-surface AC133 detection. I used the same RNAi screening approach on the colon adenocarcinoma cell line Caco-2, which express CD133 from its native promoter, to identify factors that regulate endogenous CD133 transcription. I was able to demonstrate that AF4 promotes CD133 transcription in a number of cancer cell lines. Furthermore, I showed that CD133 expression in an acute lymphoblastic leukemia (ALL) cell line SEM, which is dependent on the mixed-lineage leukemia (MLL)-AF4 gene fusion, is critical for the viability of these cells. To gain further insight into the function of CD133, I performed AP-MS using HEK293/AC133 cells to identify CD133 PPIs. I identified histone deacetylase 6 (HDAC6) as a CD133 protein interaction partner. I found that HDAC6 negatively regulates CD133 trafficking into the endosomal-lysosomal degradation pathway. CD133 binds HDAC6 to prevent inhibition of HDAC6 deacetylase activity by phosphorylation. Protection of HDAC6 from phosphorylation promotes HDAC6 deacetylation of β-catenin, which results in β-catenin dependent signalling and the suppression of cancer cell differentiation. My thesis provide functional roles for CD133 as a pro-proliferative protein and as a key signalling protein in certain cancer cell lines.
Three Essays in Corporate Finance
Keywords: Corporate Finance
Executive Compensation

In the first chapter, I study a recent and important innovation, the shift towards independent compensation consultants that provide advice only to boards. I construct a theoretical model to conceptualize the potential impact of independent consultants and then develop an empirical strategy to quantify the impact. One contribution of the paper is to provide strong identification of the impact of independent advice, something that has been challenged by the lack of appropriate data. I use a unique sample of Canadian firms which allows me to directly measure the impact of non-compensation related consulting fees on compensation advice. I conduct a number of empirical experiments but the main tests exploit a "quasi-natural experiment" provided by the creation of an independent consultant, Hugessen Consulting, as a spin-off from Mercer. I show that switching from an a ffiliated consultant to an independent consultant is associated with an increase in managerial incentives. Despite the benefits of independent advice, independent consultants may not be hired due to higher fees, the influence of powerful CEOs, or because boards already possess adequate expertise. In the second chapter, using a simple model of incentive contracting as a guide, I examine empirically whether some aspects of executive stock option backdating may be an optimal response of firms to distortions in the institutional environment, in particular tax law and accounting rules. Some of the findings suggest that firms may attempt to effi ciently lower the exercise price of the executive options in order to enhance managerial incentives for risk averse and poorly diversified executives. In the presence of restrictive accounting and tax rules, backdating may be a mechanism by which to achieve this objective of better incentives. Consistent with this explanation I find that backdating is associated with lower CEO pay levels but higher CEO incentives. In the final chapter, I use a dynamic structural model to show that on average firms excessively smooth their payout while maintaining larger than optimal levels of cash (excess cash) on their balance sheets. I provide an agency explanation for the positive correlation between dividend smoothing and cash savings. I show that the dynamic effect of managerial perceived cost to cutting payout results in accumulation of excess cash and distortion of shareholder value.
Integrating Science, Technology, Society and Environment (STSE) into physics teacher education: Pre-service Teachers' Perceptions and Challenges
Keywords: STSE
Science education
Physics education
Pre-service teaching
Scientific Literacy
Grounded Theory
Case study
Socio-scientific issues

Although STSE has recently received attention in educational research, policy, and science curricula development, fewer strides have been made in moving theory into practice. There are many examples of STSE-based and issues-based teaching in science at the elementary and secondary levels, which can be found in the literature (Alsop, Bencze, & Pedretti, 2005; Hodson, 1993, 2000; Pedretti & Hodson, 1995), yet little has focused specifically on physics education. This doctoral thesis will examine pre-service physics teachers’ beliefs and perceptions, challenges and tensions which influence their adoption of STSE education in the context of a pre-service physics education course (Curriculum and Instruction in Physics Education at the B.Ed level). An interpretive case study design as described by Merriam (1988) has been employed for this research (Merriam, 1988; Novodvorsky, 2006). The specific phenomena this case study examined and explored were the pre-service physics teachers’ beliefs and perceptions, challenges and tensions influencing their adoption of physics curricula that explicitly emphasizes an STSE orientation to physics education. The pre-service physics teachers’ evolution of perceptions and attitudes show growth in the areas of curricula understanding and implementation issues, potential student concerns, and general fit of the subject within the context of a student’s learning journey. This study contributes to our understanding of the challenges pre-service physics teachers face when considering teaching physics through an STSE lens, and provides some implications for both pre-service and in-service teacher education.