VictorJuiz/thesis huggingface dataset:
Truth Commissions and Public Inquiries: Addressing Historical Injustices in Established Democracies
Keywords: transitional justice
truth and reconciliation commission
Mackenzie Valley Pipeline Inquiry
Berger Inquiry
Thomas Berger
Indian residential schools
public inquiries
commissions of inquiry
truth commissions
TRC

In recent decades, the truth commission has become a mechanism used by states to address historical injustices. However, truth commissions are rarely used in established democracies, where the commission of inquiry model is favoured. I argue that established democracies may be more amenable to addressing historical injustices that continue to divide their populations if they see the truth commission mechanism not as a unique mechanism particular to the transitional justice setting, but as a specialized form of a familiar mechanism, the commission of inquiry. In this framework, truth commissions are distinguished from other commissions of inquiry by their symbolic acknowledgement of historical injustices, and their explicit “social function” to educate the public about those injustices in order to prevent their recurrence. Given that Canada has established a Truth and Reconciliation Commission (TRC) on the Indian Residential Schools legacy, I consider the TRC’s mandate, structure and ability to fulfill its social function, particularly the daunting challenge of engaging the non-indigenous public in its work. I also provide a legal history of a landmark Canadian public inquiry, the Mackenzie Valley Pipeline Inquiry, run by Tom Berger. As his Inquiry demonstrated, with visionary leadership and an effective process, a public inquiry can be a pedagogical tool that promotes social accountability for historical injustices. Conceiving of the truth commission as a form of public inquiry provides a way to consider the transitional justice literature on truth commissions internationally along with the experiences of domestic commissions of inquiry to assemble strategies that may assist the current TRC in its journey.
A Model-based Approach to Limb Apraxia: Evidence from Stroke and Corticobasal Syndrome
Keywords: Apraxia
Stroke
Corticobasal Syndrome
Motor Control

This thesis provides new insights about how the brain controls skilled movements, through the study of limb apraxia in two major neurological disorders: Stroke and Corticobasal Syndrome (CBS). Limb apraxia is a cognitive-motor deficit characterized by impairment in the performance of skilled movement. The Conceptual-Production systems model, used as framework in this thesis, proposes that skilled movement is under the control of three systems: a sensory/perceptual system, a conceptual system and a production system. Deficits in any of these systems produce limb apraxia, and depending on which system is affected, a distinct pattern of apraxia emerges. This information processing approach was used to evaluate performance levels, study brain asymmetries and discern patterns of deficits in each population. In addition, longitudinal assessments in sample subsets revealed patterns of recovery after stroke and of progression in CBS. The first study examined acute-subacute and chronic stroke patients with left (LHD) and right hemisphere damage (RHD) for their ability to pantomime and imitate transitive and intransitive gestures. The results indicated that LHD and acute-subacute were more severely impaired. Concurrent deficits in pantomime and imitation were most common, especially after LHD. Since acute-subacute patients were more severely impaired, in the absence of any therapies, it is likely that some degree of recovery occurs over time. The second study study examined longitudinal recovery in a series of transitive gestures tasks among stroke patients and indicated that patients significantly recovered in all tasks, except in Action Identification, a conceptual apraxia task which probes knowledge of actions. Finally, two comparative studies were conducted in CBS, a neurodegenerative disorder in which apraxia is common, making this one of the first studies that evaluated patient performance on a complete limb apraxia battery. The first study found that patients were often impaired on all gesture production tasks, while conceptual knowledge of gestures and tools was usually preserved. A case series constituted the second study, which documented the progression of apraxia in CBS demonstrating that, while deficits in gesture production usually are present at first examination, deficits in conceptual knowledge are infrequent and in many cases do not develop at all. Study limitations were discussed and it was suggested that future research should expand on our findings for recovery in stroke and progression in CBS.
Using System Structure and Semantics for Validating and Optimizing Performance of Multi-tier Storage Systems
Keywords: Storage Systems
Database
Optimization
Performance
Analysis
Computer

Modern persistent storage systems must balance two competing imperatives: they must meet strict application-level performance goals and they must reduce the operating costs. The current techniques of either manual tuning by administrators or by over-provisioning resources are either time-consuming or expensive. Therefore, to reduce the costs of management, automated performance-tuning solutions are needed. To address this need, we develop and evaluate algorithms centered around the key thesis that a holistic semantic-aware view of the application and system is needed for automatically tuning and validating the performance of multi-tier storage systems. We obtain this global system view by leveraging structural and semantic information available at each tier and by making this information available to all tiers. Specifically, we develop two key build- ing blocks: (i) context-awareness, where information about the application structure and semantics is exchanged between the tiers, and (ii) dynamic performance models that use the structure of the system to build lightweight resource-to-performance mappings quickly. We implement a prototype storage system, called Akash, based on commodity components. This prototype enables us to study all above scenarios in a realistic rendering of a modern multi-tier storage system. We also develop a runtime tool, Dena, to analyze the performance and behaviour of multi-tier server systems. We apply these tools and techniques in three real-world scenarios. First, we leverage application context-awareness at the storage server in order to improve the performance of I/O prefetching. Tracking application access patterns per context enables us to improve the prediction accuracy for future access patterns, over existing algorithms, where the high interleaving of I/O accesses from different contexts make access patterns hard to recognize. Second, we build and leverage dynamic performance models for resource allocation, providing consistent and predictable performance, corresponding to pre-determined application goals. We show that our dynamic resource allocation algorithms minimize the interference effects between e-commerce applications sharing a common infrastructure. Third, we introduce a high-level paradigm for interactively validating system performance by the system administrator. The administrator leverages existing performance models and other semantic knowledge about the system in order to discover bottlenecks and other opportunities for performance improvements. Our evaluation shows that our techniques enable significant improvements in performance over current approaches.
A Case Study on Multi-level Language Ability Groupings in an ESL Secondary School Classroom: Are We Making the Right Choices?
Keywords: English language learner
multi-level language ability
motivation
participation
self-regulation
imagination
alignment
secondary school

This research examines a multi-level language ability ESL secondary school classroom in relation to Lave and Wenger’s (1991) community of practice and Dörnyei and Ottó’s (1998) L2 motivation conceptual frameworks. Both qualitative and quantitative methodologies were employed. Case study data were collected through monthly interviews, semi-monthly observations, and monthly written journals over 3 months in Toronto from 6 participants (5 students and 1 teacher). Also, students who had been in Canada 5 years or less, and ESL teachers were invited to complete an on-line questionnaire. Results indicate that the multi-level classroom positively and negatively impacts participation and motivation. Participants define the most striking factor to impact participation and motivation as themselves; this links the two conceptual frameworks because “self-regulation” in the Actional Phase (Dörnyei & Ottó, 1998) can be better understood by legitimate peripheral participation or the ability to “imagine” and “align” oneself (Lave & Wenger, 1991). In this multi-level classroom, self-regulation is when students actively imagine possible selves who are aligned with their family or peer goals, or when faced with disengagement, students envision new roles for themselves in the classroom to overcome barriers and realign themselves with shared family or peer goals. In these cases, alignment drives imagination; however, students also use imagination to create alignment. When lower level learners see advanced students as possible selves, they feel hope for their future. Similarly, advanced learners recall their past selves when seeing their lower level peers and feel empathy for them. This interaction cements student alignment and sets a context conducive to cooperative learning which enhances students’ abilities to remain aligned with their families. Overall, this research highlights the interplay of imagination and alignment which impacts student identity. Moreover, it reveals that one aspect of the Post-actional Phase in Dörnyei and Ottó’s (1998) model, “self-concept beliefs,” can be enhanced by the notion of identity in Lave and Wenger’s (1991) framework. Finally, these findings could serve to change policy and improve programming and serve as an archive for future research.
The Role of TIMP3 in Models of Inflammation and Immunity
Keywords: TIMP3
MMP
TNF
LPS

The inter-relation between inflammation, the immune system and leukocytes is multifaceted, with communication between stroma and immune cells mediated by cytokines, growth factors, chemokines, integrins and other molecules. Proteolysis plays an important role in regulating these molecules. Proteolytic cleavage can not only destroy some molecules but can activate or shed others, converting local juxtacrine signalling proteins into effectors that act at a distance. Shedding can also convert membrane-bound receptors into soluble ligand-binding inhibitors. Finally, cleavage can convert agonist molecules into antagonists. As a wide-ranging inhibitor of metalloproteinases, tissue inhibitor of metalloproteinase 3 (TIMP3) has the potential to down-regulate many of these activities. We explore the role of TIMP3 in the regulation of inflammation, revealing that loss of TIMP3 leads to a more rapid increase of soluble TNF, higher levels of soluble TNF receptors and ultimately to increased TNF signalling in systemic inflammation. We also demonstrate TIMP3 loss impacts local inflammation. In addition we investigate the importance of TIMP3 in the expansion of hematopoietic cells.
Query-based Annotation and the Sumerian Verbal Prefixes
Keywords: Sumerian
applicatives
internal aspect
corpus linguistics

The study of Sumerian has traditionally been carried out in isolation from mainstream linguis- tics, thus limiting our ability to understand the language and to situate it in a cross-linguistic context. This dissertation shows how the tools of corpus linguistics and modern syntactic the- ory can be gainfully applied to Sumerian. Existing corpora of Sumerian texts are largely lacking in morphological annotation, with query facilities consisting only of basic string searches. Two existing corpora (one completely unannotated and one tagged for part-of-speech) are given morphological annotation using a process of query-based annotation. A query language (based on CQL and XPath) is used to query this corpus, and as queries are made, the results are tagged so that the resultant query objects can be used as the basis for subsequent queries. In this fashion a morphologically- annotated corpus is built up without having to rely on the services of a skilled annotator. This annotated corpus is then used to provide evidence for two important problems in Sumerian morphosyntax: the dimensional prefixes and the conjugation prefixes. The dimen- sional prefixes, which have previously been considered to represent concord between the verb and the associated nominal phrases, are shown instead to be a system of applicative heads which serve to introduce the verb’s arguments. The conjugation prefixes, whose purpose has been the subject of a century of debate, are shown to be the manifestation of inner aspect features which express the speaker’s perspective on the structure of the event. By using a corpus to provide the underlying data and by considering Sumerian morphosyntax in light of cross-linguistic evidence and modern syntactic theory, previously misanalysed aspects of Sumerian are shown to have analogues in other languages. The dimensional prefixes and conjugation prefixes are not oddities specific to Sumerian, but represent variations on morphological systems found elsewhere.
An Investigation of Nicotine Metabolism in Mice: The Impact of Pharmacological Inhibition and Genetic Influences on Nicotine Pharmacology
Keywords: Nicotine
Mice
CYP2A5
CYP2A6
Selegiline
Methoxsalen
Nicotine Self-administration
Genetic
Tail-flick
Hot-plate
Mechanism-based Inhibition
Smoking
Metabolism

INTRODUCTION: Smoking is one of the single greatest causes of numerous preventable diseases. We were interested in developing an animal model of nicotine metabolism that can be used to examine the effects of potential CYP2A6 inhibitors on nicotine metabolism and nicotine-mediated behaviours. Pharmacogenetic studies have demonstrated that in humans, smoking behaviour is associated with rates of nicotine metabolism by the CYP2A6 enzyme. Mouse CYP2A5 shares structural and functional similarities to human CYP2A6 and has been implicated in nicotine self-administration behaviours in mice, therefore the mouse represents a potential animal model for studying nicotine metabolism. METHODS: We characterized nicotine and cotinine metabolism in two commonly used mouse strains (DBA/2 and C57Bl/6). We also examined the association between nicotine self-administration behaviours and nicotine metabolism, and the impact of direct manipulation (i.e. inhibition) of nicotine metabolism on nicotine pharmacodynamics (hot-plate and tail-flick tests) in mice. Finally, we studied the effect of selegiline (a known cytochrome P450 mechanism-based inhibitor) on nicotine metabolism in mice and in human CYP2A6. RESULTS: Nicotine metabolism in mice in vitro was mediated by CYP2A5, and this enzyme was responsible for over 70% and 90% of the metabolism of nicotine to cotinine and cotinine to 3-hydroxycotinine as shown by immuno-inhibition studies, respectively. A polymorphism in CYP2A5 between mouse strains, known to alter the probe substrate coumarin’s metabolism, did not affect nicotine metabolism but dramatically altered cotinine metabolism. Nicotine self-administration behaviour in mice was associated with level of hepatic CYP2A5 proteins and rates of nicotine metabolism in male mice. In inhibition studies, the CYP2A5/6 inhibitor methoxsalen inhibited both in vitro and in vivo nicotine metabolism in mice and substantially increased the anti-nociceptive effect of nicotine. Finally, selegiline was found to be an inhibitor of CYP2A5 decreasing nicotine metabolism in vitro and in vivo in mice. Moreover, we showed that selegiline is a mechanism-based inhibitor of CYP2A6 inhibiting nicotine metabolism irreversibly. CONCLUSION: The above data suggested that the mouse model may be suitable for examining the impact of inhibition (and genetic variation) on nicotine metabolism and nicotine-mediated behaviours and may potentially be used to screen for novel inhibitors of nicotine metabolism.
Structural and Inhibition Studies of Human Intestinal Glucosidases
Keywords: glycoside hydrolases
X-ray crystallography
maltase glucoamylase
sucrase isomaltase
starch digestion
alpha-glucosidase inhibitors
Type 2 diabetes

Human maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) are the small-intestinal glucosidases responsible for catalyzing the last glucose-releasing step in starch digestion. MGAM and SI are each composed of duplicated catalytic domains, N- and C-terminal, which display complementary substrate specificities for the mixture of short linear and branch oligosaccharide substrates that typically make up terminal starch digestion products. As MGAM and SI are involved in post-prandial glucose production, regulating their activities with α-glucosidase inhibitors is an attractive approach to controlling blood glucose levels for the prevention and treatment of Type 2 diabetes. To better understand the complementary activities and mechanism of inhibition of these intestinal glucosidases, this thesis aims to characterize the individual N- and C-terminal MGAM and SI domains using a combination of X-ray crystallographic structural studies, enzyme kinetics, and inhibitor studies. First, the structure of the N-terminal domain of MGAM (ntMGAM) was determined in its apo form and in complex with the inhibitor acarbose. In addition to sequence alignments and kinetics studies, the structures provide insight into the preference of the N-terminal MGAM domain for short linear substrates and the C-terminal domain for longer substrates. Second, the structure of ntMGAM was determined in complex with various α-glucosidase inhibitors, including those currently on the market (acarbose and miglitol), a new class of inhibitors from natural extracts of Salacia reticulata (salacinol, kotalanol and de-O-sulfonated kotalanol) and chemically synthesized derivatives of salacinol. These studies reveal the features of the Salacia reticulata inhibitors that are essential for inhibitory activity and highlight their potential as future drug candidates. Third, the crystal structure of the N-terminal domain of SI (ntSI) was determined in apo-form and in complex with kotalanol. Structural comparison of ntSI and ntMGAM reveal key differences in active site architectures, which are proposed to confer differential substrate specificity.
Breast Cancer Survival in Ontario's First Nations Women: Understanding the Determinants
Keywords: Breast cancer
survival
First Nations
diagnosis
Indigenous
Ontario

This study builds on previous research showing that breast cancer survival is poorer for First Nations (FN) women compared to other Ontario women. Few studies have examined breast cancer survival in Indigenous populations compared to general populations; all of these report poorer survival among Indigenous people. Fewer still have examined potential factors related to the poorer survival, but these often suggest poorer prognosis even after adjustment for them. Study objectives were: to compare the distribution of demographic, prognostic and treatment factors between FN and non-FN women; to investigate factors associated with later diagnosis in FN women; to compare stage specific survival for FN and non-FN women controlling for important factors potentially associated with breast cancer survival; and to examine potential determinants of survival for FN women by stage at diagnosis. A case-case design was employed to compare FN women (n=287) diagnosed with invasive breast cancer to a frequency-matched random sample of women (n=671) from the general population diagnosed with breast cancer within the Ontario Cancer Registry. Women were matched (2:1) on period of diagnosis (1995-1999 and 2000-2004), age at diagnosis (<50 vs. 50≥), and Regional Cancer Centre (RCC). Stage at diagnosis and data relevant to the determinants of breast cancer survival were collected from medical charts at the RCCs. FN women were diagnosed with breast cancer at later stages compared to non-FN women. Having a non-screened method of detection and increasing BMI were associated with a later breast cancer diagnosis. FN women with comorbidity however were less likely to be diagnosed at a later stage. An unforeseen novel finding was that the survival disadvantage occurred after an early breast cancer diagnosis, whereas the survival experiences for those diagnosed at stages II+ were similar. In a multivariate analysis, elevated risk was observed for FN women in stage I, and significant risk was seen in women with comorbidity. These findings are actionable and can be used to improve the prognosis of FN women with breast cancer. It is likely that the same or similar factors are largely responsible for the survival disadvantage observed among Ontario FN people for most other major cancers.
Utopie et idéologie dans la science-fiction canadienne-française et québécoise
Keywords: science-fiction
utopie
idéologie
littérature canadienne-française et québécoise
Daniel Sernine
dystopie
uchronie
allégorie

Cette thèse porte sur la reconstitution imaginaire de l’histoire et de la société dans la science-fiction (SF) uchronienne et utopienne du Canada français et du Québec. À partir d’un survol de la poétique des genres dont il est question et d’un panorama historique de leur production globale et locale, ainsi que de l’approfondissement de l’exploitation particulière des notions d’idéologie et d’altérité dont ces œuvres font preuve, nous proposons une lecture allégorique du phénomène culturel d’après une étude de cas de la SF canadienne-française et québécoise (SFCFQ) contemporaine : La Suite du temps (1983/2004-2008), une trilogie romanesque de Daniel Sernine. Bien que les littératures de SF nationales aient progressivement fait place à une littérature mondiale régie par des codes qui déterminent leur appartenance à une poétique spécifique, l’allégorie nationale se réalise de façon récurrente : est mise en œuvre une configuration dominante dans laquelle sont présentés des modèles mondiaux comme systèmes alternatifs, qui, tout en étant éloignés ou distanciés, évoquent inéluctablement le paysage, la langue, les mœurs et les valeurs des milieux culturels dans le cadre desquels les œuvres paraissent. Au delà d’une possibilité théorique de lecture, il y a des preuves empiriques de ce phénomène, surtout dans le cadre des sous-genres de l’utopie, de l’uchronie et de l’anticipation, où abondent des visions de soi et de la « nation » altérées qui sont inextricablement déterminées par le lieu de leur production. Nous cherchons à mettre en valeur cet aspect de la SF à partir d’un survol des récits précurseurs de la SFCFQ contemporaine et d’une analyse approfondie d’une de ses œuvres charnières. Cette analyse comprendra deux lectures allégoriques, l’une au niveau régional, l’autre à l’échelle globale. Ainsi, nous espérons démontrer en quoi la SFCFQ s’inscrit dans la poétique de la SF dans son ensemble tout en constituant sa propre innovation critique ou « Novum », ce qui lui permet de se distinguer en tant que courant particulier.