VictorJuiz/thesis huggingface dataset:
The Role of the Retinoblastoma Protein Family in Skeletal Myogenesis

The retinoblastoma tumor suppressor (pRb) is thought to orchestrate terminal differentiation by inhibiting cell proliferation and apoptosis and stimulating lineage-specific transcription factors. In this thesis I have shown that in the absence of pRb, differentiating primary myoblasts fused to form short myotubes that never twitched and degenerated via a non-apoptotic mechanism. The shortened myotubes exhibited an impaired mitochondrial network, mitochondrial perinuclear aggregation, autophagic degradation and reduced ATP production. Bcl-2 and autophagy inhibitors restored mitochondrial function and rescued muscle degeneration, leading to twitching myotubes that expressed normal levels of muscle-specific proteins and eventually exited the cell-cycle. A hypoxia-induced glycolytic switch also rescued the myogenic defect after chronic or acute inactivation of Rb in a HIF-1-dependent manner. These results demonstrate that pRb is required to inhibit apoptosis in myoblasts and autophagy in myotubes but not to activate the differentiation program. I next tested the effect of retinoblastoma protein family members – p107 and p130 – on skeletal myogenesis in the absence of Rb. Chronic or acute inactivation of Rb plus p130 or Rb plus p107 increased myoblast cell death and reduced myotube formation, yet expression of Bcl-2, treatment with autophagy antagonist or exposure to hypoxia extended myotube survival, leading to long, contracting myotubes that appeared indistinguishable from control myotubes. Triple mutations in Rb family genes further accelerated cell death and led to elongated myocytes or myotubes containing two nuclei, some of which survived and twitched under hypoxia. Whereas nuclei in Rb-/- myotubes were unable to stably exit the cell-cycle, myotubes lacking both p107/p130 became permanently post-mitotic, suggesting that pRb, but not p107 or p130 may be lost in cancer because of the unique requirement for cell-cycle exit during terminal differentiation. This thesis demonstrates that pRb is required to inhibit apoptosis in myoblasts and autophagy in myotubes but not to activate the differentiation program, and reveal a novel link between pRb and cell metabolism.

Keywords: skeletal myogenesis
muscle
differentiation
retinoblastoma
pRb
autophagy
p107
p130
Rb
cell cycle
Advisor: Zacksenhaus, Eldad
Potential Use of Umbilical Cord Blood Cells in Spinal Cord Injury

Spinal cord injury (SCI) pathophysiology occurs as a primary traumatic event followed by secondary injury, resulting in the loss of neurons, oligodendrocytes and demyelination of residual axons. Unfortunately, endogenous spontaneous regeneration of oligodendrocytes is minimal. Previously, a method to generate multi-potential stem cells (MPSC) from umbilical cord blood (UCB) has been reported using lineage negative cells (Linneg) grown in fibroblast growth factor 4 (FGF4), stem cell factor (SCF) and fms-like tyrosine kinase receptor-3 ligand (Flt-3l) supplemented serum free medium. These MPSC have the ability to differentiate into bone, muscle and endothelial cells. In this thesis, the ability of MPSC to differentiate into oligodendrocytes was investigated as a potential treatment for SCI. Culturing MPSC under conditions that mimic normal timing of oligodendrocyte differentiation resulted in cells that expressed oligodendrocyte markers in vitro and were morphologically similar to them. I next investigated the ability of MPSC to improve functional recovery in a SCI compression injury model. Although the cells did not differentiate into oligodendrocytes in vivo as we initially hypothesised, a modest but significant improvement in hindlimb function was observed. A cytokine assay revealed that MPSC secrete elevated levels of anti-inflammatory, angiogenic and neurotrophic factors, possibly contributing to indirect mechanisms of repair by reducing secondary injury. Shiverer mouse neonates were next used as an alternative non-injury model to investigate the differentiation potential of MPSC. We hypothesised that transplanting MPSC into a host with an immature immune system and an actively myelinating environment would lead to engraftment and differentiation into oligodendrocytes. However no MPSC that differentiated into oligodendrocytes could be detected. Altogether, our in vitro data adds support for the reprogramming of cells, with further studies needed to test the functionality of resulting oligodendrocyte-like cells. Although MPSC failed to differentiate in both in vivo models, several potential therapeutic targets to treat SCI were found.

Keywords: Umbilical Cord Blood
Oligodendrocytes
Spinal Cord Injury
Advisor: Casper, Robert
Essays on the Impact of Investors Speculation and Disagreements on Security Prices and Trading Volume

The essays empirically show the impact of investors speculation and disagreements on the returns and trading volume of securities. The results also shed light on the central issues of price formation and investors’ trading motives in security markets. The first essay investigates whether the trading activities of retail investors affect option prices through volatility speculation. This essay empirically shows that higher retail trading proportions are related to lower delta-hedged option returns. The phenomenon is more pronounced before earnings announcements and among stocks with more time-varying and positively skewed volatility. The results suggest that retail investors speculate and pay a lottery premium on the expected future volatility, resulting in more expensive options in terms of higher implied volatilities. This systematic deviation of option-implied volatility from realized volatility suggests retail investor clientele as a behavioral-based driving force of volatility risk premium. The second essay investigates the motive of option trading. It is shown that option trading is mostly driven by differences of opinion, a finding different from the current literature that attempts to attribute option trading to information asymmetry. First, option trading around earnings announcements is speculative in nature and mostly dominated by small, retail investors. Second, around earnings announcements, option turnovers do not predict stock returns, once prior stock returns are controlled for. Third, regression results reveal that option trading is also significantly explained by differences of opinion at ordinary times. While informed trading is present in stocks, it is not detected in options. The third essay provides strong evidence of reduction in informational efficiency when there are short-sale constraints and disagreements. Post earnings announcement returns are found to be significantly lower for stocks with more dispersed opinions and stocks that are exogenously short-sale prohibited by the Hong Kong Stock Exchange, supporting Miller’s (1977) overvaluation hypothesis. The results also suggest short-sale constraint as an explanation to negative post earnings announcement drift.

Keywords: Speculation
Disagreements
Trading volume
Advisor: Wei, Jason
The Loss of the 'World-Soul'? Education, Culture and the Making of the Singapore Developmental State, 1955 - 2004

This dissertation examines the role of education in the formation of the Singapore developmental state, through a historical study of education for citizenship in Singapore (1955-2004), in which I explore the interconnections between changes in history, civics and social studies curricula, and the politics of nation-building. Building on existing scholarship on education and state formation, the dissertation goes beyond the conventional notion of seeing education as providing the skilled workforce for the economy, to mapping out cultural and ideological dimensions of the role of education in the developmental state. The story of state formation through citizenship education in Singapore is essentially the history of how Singapore’s developmental state managed crises (imagined, real or engineered), and how changes in history, civics and social studies curricula, served to legitimize the state, through educating and moulding the desired “good citizen” in the interest of nation building. Underpinning these changes has been the state’s use of cultural constructs such as Confucianism and Asian values to shore up its legitimacy. State formation in Singapore has been very successful, as evidenced by its economic prosperity and education has played a key role in this success. However, the “economic growth at all costs” ethos comes, arguably, at a price – the potential loss of zeitgeist, or the loss of the “World-Soul”. Nation building in the sense of fostering a sense of rootedness and belonging to the country in its citizenry – the “World-Soul” – had to be relegated to the backburner in the relentless pursuit of economic development, in order to sustain and legitimize the developmental state. By harnessing the educational sphere for its economic growth objectives through the discourse of crisis, the developmental state gained political legitimacy in the eyes of a citizenry increasingly accustomed to educational mobility and material wealth, even if at the expense of political freedoms.

Keywords: citizenship education
developmental state
state formation
Advisor: Sandwell, Ruth W.
Resource Allocation Algorithms for Event-Based Enterprise Systems

Distributed event processing systems suffer from poor scalability and inefficient resource usage caused by load distributions typical in real-world applications. The results of these shortcomings are availability issues, poor system performance, and high operating costs. This thesis proposes three remedies to solve these limitations in content-based publish/subscribe, which is a practical realization of an event processing system. First, we present a load balancing algorithm that relocates subscribers to distribute load and avoid overloads. Second, we propose publisher relocation algorithms that reduces both the load imposed onto brokers and delivery delay experienced by subscribers. Third, we present ``green" resource allocation algorithms that allocate as few brokers as possible while maximizing their resource usage efficiency by reconfiguring the publishers, subscribers, and the broker topology. We implemented and evaluated all of our approaches on an open source content-based publish/subscribe system called PADRES and evaluated them on SciNet, PlanetLab, a cluster testbed, and in simulations to prove the effectiveness of our solutions. Our evaluation findings are summarized as follows. One, the proposed load balancing algorithm is effective in distributing and balancing load originating from a single server to all available servers in the network. Two, our publisher relocation algorithm reduces the average input load of the system by up to 68%, average broker message rate by up to 85%, and average delivery delay by up to 68%. Three, our resource allocation algorithm reduces the average broker message rate even further by up to 92% and the number of allocated brokers by up to 91%.

Keywords: computer engineering
publish/subscribe
content-based routing
load estimation
resource allocation
overlay construction
publisher relocation
subscriber relocation
load minimization
green IT
load balancing
event processing
load minimization
delivery delay minimization
event processing
ESB
Advisor: Jacobsen, Hans-Arno
Between Attrition and Acquisition: the Dynamics between Two Languages in Adult Migrants

In the context of language use of Romanian migrants living in Canada, this thesis examines the linguistic changes and the contributing social, personal, and affective factors involved in the maintenance of a migrant’s first language (L1) as she or he simultaneously acquires a second language (L2) in an L2-dominant environment. Specifically, it investigates the incidence of L1 attrition in the bilingual group, the existence of a possible systematic relationship between the levels of L1 and L2 proficiency, and the influence of sociolinguistic and cognitive factors on L1 attrition and L2 acquisition in bilingual contexts. L1 attrition is defined here as both the reduction of L1 language skills and the restructuring of the L1 according to L2 patterns to the point where communication in the L1 is impaired. The present study involves extensive elicitation of written and oral data in both Romanian and English. First, an assessment of the participants’ history of language acquisition, their attitudes, their patterns of language use, and the nature of their social networks was conducted via sociolinguistic questionnaires and individual interviews. The language aptitude tests used in this project examined phonetic memory, vocabulary learning, and grammatical inferencing abilities. As an indicator of overall language proficiency, formal tests (a C-test and a verbal fluency task) and samples of spontaneous speech in the form of film commenting tasks were analyzed for fluency and grammatical complexity. The results showed that L1 attrition is a possible, but not obligatory, outcome in the first generation of migrants. With the exception of two participants, the majority of the bilinguals in this study, while not perfect matches for the L1 monolinguals, remained within the L1 native range even after a long residence in the L2 country. While proficiency trade-off patterns are not observable at the group level, they were evidenced in the cases of the two attriters identified in this study. With respect to cognitive predictor variables, L1 maintenance does not appear to be a direct function of linguistic aptitude. At the same time, levels of L1 attrition and L2 achievement are dependent on a combination of attitudinal and personal background variables.

Keywords: language attrition
bilingualism
Advisor: Bhatt, Parth
Responses to Difference in Initial Teacher Education: A Case of Racial and Linguistic Minority Immigrant Teacher Candidates

Despite recent rhetoric advocating the diversification of the teacher workforce, teachers in Canada continue to be disproportionately white and of northern European heritage. By investigating responses to difference experienced by racial and linguistic minority immigrant teacher candidates in an initial teacher education program, this thesis sheds light on dynamics that challenge or support the induction of minoritized individuals as members of the teaching profession in Canada. Data collected through interviews with eight immigrant teacher candidates, four instructors, and five student support staff of an initial teacher education program at an urban Canadian university (UCU) indicated that teacher candidates at UCU experienced varied responses to difference. Influences of both hegemony and collaboration were found in the university and practice teaching contexts where individuals representing regimes of competence enacted challenging assimilationist or supportive multiculturalist ideologies. In practice teaching contexts, although all of the teacher candidates engaged with at least one collaborative mentor teacher and they all persisted to complete the program, six of the eight teacher candidates (i.e., all of the linguistic minority teacher candidates in this study) encountered a challenging and significantly discouraging relationship with a mentor teacher. In these hegemonic contexts the legitimacy of the teacher candidates appeared to be measured against a conception of “real teachers” as “real Canadians” who are native English-speakers and who are familiar with the culture of schooling in Canada. Within the university context, student support staff were consistent in their critical awareness of the challenges and supports experienced by teacher candidates while instructors demonstrated a range of familiarity with these issues and with concepts of equity as they relate to the experiences of teacher candidates. Implications of this study support the following: continuation of programs offered through student support services; educative collaborative implementation of UCU’s equity policy to promote greater consistency in its influence; application of inclusive pedagogy; greater curricular emphasis on social power and constructions of difference; recognition of immigrant teachers’ linguistic capital; development of a collaborative method to evaluate teacher candidates in practice teaching contexts; and continued effort to advance a more profound and consistent influence of multiculturalist ideology in Canadian schools.

Keywords: diversity
teacher induction
immigrant settlement
inclusive policy
integrative theory
initial teacher education
teacher professional development
diversification of teacher workforce
Advisor: Bascia, Nina
Policy Windows and Changing Arrangements: An Analysis of the Policy Process Leading to the Colleges of Applied Arts and Technology Act, 2002

This case study focuses on Ontario higher education policy and the Colleges of Applied Arts and Technology (CAATs). A sequence of policy shifts occurred during the last decade of the twentieth century and the early years of the new millennium. By 2002, the Government of Ontario had reviewed its position with regard to baccalaureate degree credentials being the exclusive domain of publicly supported universities. Governance arrangements for the CAATs had also changed. The new policy framework was set with two pieces of legislation, the Postsecondary Education Choice and Excellence Act, 2000, and the Ontario Colleges of Applied Arts and Technology Act, 2002. The purpose of this case study is to explain why these policy changes occurred. To facilitate inquiry, John W. Kingdon’s Multiple Streams Model was used as a platform and lens to guide data collection and organize the findings. For Kingdon, policy is the outcome of a complex pre-decision process that requires the ‘coupling’ of the problem, policy, and political streams at the time of an open policy window. A qualitative approach was adopted, and primary and secondary documents covering the period 1990 to 2002 were collected. In addition, in-depth semi-structured interviews were conducted with key policy actors and policy entrepreneurs.  The study found evidence to support the Multiple Streams Model's contention of streams of processes. However, with respect to this study, two types of policy problems were found flowing in the problem stream: macro-structural policy problems shaped conditions and the scope of options available with respect to policy goals and policy solutions; and micro-specific policy problems were localized, actor identified, constructed, and linked to specific interests. The study also found that historical institutional structures, and intermediate institutions, had a significant impact on policy development. The policy changes occurred as the result of two open policy windows, and in both instances, policy entrepreneurs were able to couple the policy streams to effect change. In view of the findings, a Structured Dynamics Model of Policy Development is offered as an explanation of the policy changes and for consideration in future inquiry.

Keywords: Ontario higher education policy
Colleges of Applied Arts and Technology
Ontario Colleges of Applied Arts and Technology Act, 2002
Multiple Streams Model
macro-structural policy problems
micro-specific policy problems
Structured Dynamics Model
Postsecondary Education Choice and Excellence Act, 2000
policy change
policy windows
policy development
governance
Advisor: Jones, Glen A.
Arctic Aerosol Sources and Continental Organic Aerosol Hygroscopicity

Atmospheric particles can affect climate directly, by scattering solar radiation, or indirectly, by acting as the seed upon which cloud droplets form. These clouds can then cool the earth's surface by reflecting incoming sunlight. In order to constrain the large uncertainties in predicting the ultimate effect of aerosol on climate, the sources of atmospheric particles and their subsequent ability to turn into cloud droplets needs to be better understood. This thesis addresses two parts of this issue: the sources of Arctic aerosol and the hygroscopicity of continental organic aerosol. Small particles were observed in Baffin Bay during September 2008 that coincided with high atmospheric and ocean surface dimethyl sulphide (DMS) concentrations suggesting that the aerosol formed from oceanic sources. An aerosol microphysics box model confirmed that local DMS could have produced the observed particles. In addition, the particle chemical composition was measured using aerosol mass spectrometry in the central Arctic Ocean in August 2008 and particles were found to be 43% organic and 46% sulphate. Factor analysis further apportioned the aerosol mass to marine biogenic and continental sources 33% and 36% of the time, respectively, with the source of the remaining mass unidentified. The second part of the study parameterises the hygroscopicity of the ambient organic aerosol fraction (κorg) at Egbert, Ontario and Whistler, British Columbia. This was done using two methods: 1) by assuming that the oxygenated organic component was hygroscopic and that the unoxygenated organic component was non-hygroscopic, κ of the oxygenated component was found to be 0.22 ± 0.04, and 2) by assuming that κorg varied linearly with the atomic oxygen to atomic carbon ratio, it could be parameterised as κorg = (0.29 ± 0.05) × (O/C). Calculations predict that knowing κorg is important in urban, semi-urban, and remote locations whenever the inorganic mass fraction is low.

Keywords: Arctic aerosol
cloud condensation nuclei
aerosol-cloud interactions
aerosol nucleation
Advisor: Abbatt, Jonathan P. D.
Synthesis of Heterocycles and Carbocycles Through Tandem and Domino Palladium-catalyzed Reactions

We have described two important classes of palladium-catalyzed reactions for the synthesis of heterocycles and carbocycles: tandem Pd-catalyzed reactions of gem-dibromoolefins and domino Pd-catalyzed reactions via an ortho C−H functionalization. Chapter 1 describes the tandem Pd-catalyzed reaction of gem-dibromoolefins via an intramolecular direct arylation and an intermolecular Suzuki-Miyaura cross-coupling. A number of aromatic carbocycles were synthesized by this method. Chapter 2 describes the tandem Pd-catalyzed reactions of β,β-dibromoenamides via an intramolecular C−O bond formation and an intermolecular Suzuki-Miyaura cross-coupling. Depending on the substituent on the nitrogen of β,β-dibromoenamides, either aromatic heterocycles or acyclic compounds can be synthesized. Chapter 3 and 4 describe the domino Pd-catalyzed reactions via an ortho C−H functionalization of aryl iodides. 2-Pyrrole substituted phenyl iodides were coupled with alkyl bromides in the presence of norbornene to provide aromatic tetracyclic compounds through three C−C bond formations (Chapter 3). However, the reaction between 2-methyl substituted phenyl iodides and the alkyl bromides in the presence of norbornene provided tetrasubstituted helical alkenes with the norbornene incorporated in the final product through four C−C bond formations (chapter 4). In Chapter 5, detailed mechanistic studies including kinetic and NMR studies were described for the regioselective C−H functionalization of 2-pyrrole substituted phenyl iodides. The studies provided advanced and important understanding of the mechanism, and a rationale for the high regioselectivity.

Keywords: tandem and domino reactions
palladium catalyzed reactions
Advisor: Lautens, Mark