VictorJuiz/thesis huggingface dataset:
Kallikrein-related Peptidase Signalling via Proteinase-Activated Receptors
Keywords: kallikrein-related peptidases
proteinase-activated receptors
cancer
inflammation

The family of human kallikrein-related peptidases (KLKs) numbers 15 serine proteinases implicated in tumour progression. Despite the wide tissue distribution of KLKs and the numerous reports of their differential expression in pathological settings, the signalling mechanism(s) whereby these enzymes regulate tissue function are not yet known. Further, knowledge of the levels of their activity, as well as of their potential endogenous targets, has only been extracted from in vitro studies and cell culture systems. We hypothesized that KLKs can trigger tumour signalling via proteinase-activated receptors (PARs), a family of G-protein-coupled receptors. To test our hypothesis, we evaluated the ability of KLKs 5, 6, and 14: to activate or prevent signalling via PARs 1, 2, and 4 in cells and tissues expressing these receptors. Further, we used a novel activity-based probe approach, coupled with conventional immunoassay (ELISA), to determine the abundance of active KLK6 relative to total immunoreactive KLK6 in cancer-related biological fluids. We concluded that KLKs can regulate multiple signalling pathways triggered by PARs 1, 2, and 4, resulting in calcium release, platelet aggregation and vascular relaxation, and they can cause murine inflammation. Further, our activity-based ELISA demonstrated the presence of active KLK6 in ovarian cancer ascites fluids and cancer cell supernatants. We, therefore, suggest that tumours can produce active KLKs, which can potentially control tumour behaviour by regulating PAR activity.
Public Reason and Canadian Constitutional Law
Keywords: Public Reason
Canadian Charter of Rights and Freedoms
Liberalism
Separation of Church and State
Constitutional Law
Rawls

Liberals claim that the exercise of state power must be justified on terms that all citizens can reasonably accept. They also support democracy. The challenge is to bring these two desideratum in line-- to ensure that democratic deliberations are somehow predicated on claims that all citizens can reasonably accept. Put differently, the challenge is to set the terms of public reason. Liberal philosophers advance grand theories of political justice towards this end. They claim that a reasonable argument in the political sphere is one that conforms to theory x. The difficulty is that there will be those who reasonably reject theory x, preferring theory y or z, or eschewing theory altogether. Pessimism at the prospect of agreement on higher-order theories of justice leads some to advocate simple majority rule. The thesis argues that convergence on higher order theory is not essential to public reason. The Supreme Court of Canada’s method of adjudication under the Canadian Charter of Rights and Freedoms is used as a model. Where basic rights are engaged, or are alleged to be engaged, the Court examines the reasonableness of law and policy using a series of open-ended tests. These tests discipline their deliberations by focusing attention on generally accepted facts and values (notably, the values expressed by the Charter). The thesis contends that the Court’s open-ended, contextual approach can serve as a model for broader public reasoning. The thesis then explores the role of religious arguments within this model. In a polity committed above all to Charter values, what is the place of religion in the justification of law? It is argued that religion is understood to be private and inscrutable under the Charter. This is what justifies the Court’s generous reading of the right to religious freedom. It also justifies our forbidding state coercion in the name of religion. With the preceding ideas in mind, the thesis examines Canadian law and public discourse on the issues of therapeutic cloning (ch.4) and same sex marriage (ch.5).
International Patent Law: Cooperation, Harmonization and An Institutional Analysis of WIPO and the WTO
Keywords: patent
internatioinal
WIPO
WTO
cooperation
harmonization
law
institutional analysis

This work considers international cooperation or harmonization in patent law and analyzes the two main international patent law governance institutions: the World Intellectual Property Organization (WIPO) and the World Trade Organization (WTO). A welfarist approach is adopted, proposing that international patent law should improve global welfare, subject to assumptions that the preferences of the world population are heterogeneous, that governments try to maximize the welfare of their citizens, and that international legal organization faces collective action problems. Normatively desirable patent law harmonization reconciles strong reasons for preserving diversity (including the static and dynamic satisfaction of local preferences and adapting to unpredictable change) with strong reasons for cooperation (reducing duplication in patent prosecution, and reconciling imbalanced national externalities, incentives to innovation and costs). The last reason leads to a system of national treatment and minimum standards. The risks presented by the skewed nature of invention are addressed in the international patent system through a form of regional insurance. These reasons for cooperation present two linked but separable collective action problems, supporting the existence of two international institutions to govern patent cooperation. WIPO is best positioned to address duplication in patent prosecution. The WTO is best positioned to address imbalanced national externalities, incentives and costs. However, both the WIPO and the WTO are needed to provide a comprehensive international governance system. Questions about the WTO dispute resolution system, the TRIPs Council, and the WTO’s legitimacy are addressed by advocating a trade stakeholders’ model. Whether international patent law should be seen as a multilateral obligation or a nexus of bilateral obligations is explored. Given diverse national preferences and high uncertainty surrounding the welfare effects of specific patent policies, the process of harmonization is inevitably a political process. This political aspect directly connects the topic of patent law harmonization with the institutional analysis of WIPO and the WTO. The implementation of welfare-enhancing patent law cooperation is best guarded by a process with a wide range of political inputs and transparency. Ultimately, only good international governance can deliver on the potential of the international patent system to promote international innovation, economic growth and world-wide prosperity.
Functions of Lunatic and Manic Fringe in Regulating the Strength and Specificity of Notch Receptor-ligand Interactions during Hematopoiesis
Keywords: Immunology
hematopoiesis
T cell development
Notch signaling
lymphocyte development

Notch signals are required to promote T lineage commitment and development and suppress alternative cell fates in the thymus. Although the Notch activating ligand(s) in the thymus is(are) not known, studies have shown that hematopoietic progenitors are sensitive to Delta-like (DL), but not Jagged (Jag)-type ligands. In Chapter 3, I show that DL-expressing bone marrow stromal cell lines exhibit Notch ligand-independent functional heterogeneity in their capacity to support T cell development in vitro. These findings thus suggest the existence of stromal cell-derived signals that work with Notch to support T cell development. In Chapters 4 and 5, I investigated the ability of Fringe proteins to modulate Notch ligand-receptor interactions and the developmental consequences of these interactions for hematopoetic progenitors. Fringe proteins are glycosyl-transferases that enhance Notch activation by DL ligands and inhibit Notch activation by Jag ligands. In Chapter 4 I show that Lunatic Fringe (Lfng) enhances the strength of DL-mediated Notch activation to drive proliferation and expansion of early thymocytes and that DL4 and DL1 display different potencies to induce Notch-dependent outcomes. In Chapter 5, I demonstrate for the first time in a mammalian system that Lfng and Manic Fringe (Mfng) co-operate to enhance DL-Notch interactions and inhibit Jag-Notch interactions in hematopoietic stem cells. Thus, Lfng and Mfng function together to induce T cell development and inhibit B cell, myeloid and NK cell development. Collectively, these data highlight the importance of Fringe proteins in modulating the strength and specificity of Notch signaling levels during hematopoieisis.
Successful Priority Setting: A Conceptual Framework and an Evaluation Tool
Keywords: priority setting
evaluation
health services reserach
conceptual framework

A growing demand for services and expensive innovative technologies is threatening the sustainability of healthcare systems worldwide. Decision makers in this environment struggle to set priorities appropriately, particularly because they lack consensus about which values should guide their decisions; this is because there is no agreement on best practices in priority setting. Decision makers (or ‘leaders’) who want to evaluate priority setting have little guidance to let them know if their efforts were successful t. While approaches exist that are grounded in different disciplines, there is no way to know whether these approaches lead to successful priority setting. The purpose of this thesis is to present a conceptual framework and an evaluation tool for successful priority setting. The conceptual framework is the result of the synthesis of three empirical studies into a framework of ten separate but interconnected elements germane to successful priority setting: stakeholder understanding, shifted priorities/reallocation of resources, decision making quality, stakeholder acceptance and satisfaction, positive externalities, stakeholder engagement, use of explicit process, information management, consideration of values and context, and revision or appeals mechanism. The elements specify both quantitative and qualitative dimensions of priority setting and relate to both process and outcome aspects. The evaluation tool is made up of three parts: a survey, interviews, and document analysis, and specifies both quantitative and qualitative dimensions and relates to both procedural and substantive dimensions of priority setting. The framework and the tool were piloted in a meso-level urban hospital. The pilot test confirmed the usability of the tool as well as face and content validity (i.e., the tool measured relevant features of success identified in the conceptual framework). The tool can be used by leaders to evaluate and improve priority setting.
The Spatiality of Social Identities: Taiwanese Migrant Women Practice Everyday Spaces in Toronto
Keywords: Spatiality
Social Identity
Migration

What part does migration play in the construction and reconstruction of social identity? What kind of social relations are produced and reproduced through the migration process? What are the manifestations of power involved in the process of constructing and negotiating social identities through space? These are the central questions in this research. This research not only draws upon current literature on migrant women, but also expands it to address the complexity of construction of social identities and places through migration processes by incorporating critical social theories and feminist geography into the research. I examine embodied geographical experiences and the geography of emotions, by looking at current Taiwanese migrant women’s everyday practices in Toronto. This research provides concrete examples – from a substantial sample of individuals – to support feminist geographers’ arguments on women’s experiences in space. I employ Bourdieu’s concept of habitus to illustrate how personal and private space is constructed and reconstructed by a complex interplay between different discourses and practices, and how new spaces and practices are created for new identity claims. I also examine how the dynamics of habitus shifts through displacement. By looking at the generative aspect of habitus, this research extends the existing scope of the notion of habitus. Collecting more than 125 hours of in-depth interviews with Taiwanese migrant women in Toronto, I examine multidimensional re-configurations of the everyday practices of Taiwanese migrant women in Toronto. Research findings regarding the hidden geography of everyday language practice, the reconstruction of food culture and the exploration of culinary practice, the negotiation of home practice, and the creation of new spaces for new identity claims provide a complicated picture that grasps the contingency and fluidity of identity construction. In addition to concepts of ‘third space’ and ‘paradoxical space,’ my research shows that metaphoric expressions, what I call ‘glass wall’, ‘comfort zone’, ‘unlocked spaces’, ‘dialogical space’ and ‘provocative space’ are important to unveil dynamic pictures of geographical experiences along migration. Indeed, space plays an integral role in the making of social identity.
Marginal Regions in Discursive Space: An Examination of Socio-economic Conditions, Development Paths and Spatial Differentiation in the Economic Systems of the Canadian and Russian North
Keywords: Canadian and Russian North
economic development
economic geography
regional policy

Marginal regions in discursive space: an examination of socio-economic conditions, development paths and spatial differentiation in the economic systems of the Canadian and Russian North Andrey N Petrov Degree: Doctor of Philosophy Department of Geography University of Toronto 2008 This dissertation is an effort to provide a new insight into the problem of regional development in remote areas under changing global and national political and economic conditions. It undertakes an assessment of shared economic histories, recent changes and future possibilities of socioeconomic prosperity and sustainability in marginal regions of Canada and Russia. The first chapter re-examines the structure of Canada’s and Russia’s space-economies by evoking the concept of regional multichotomies and economic marginality. I consider whether outcomes, geographic patterns and spatial logics of regional differentiation in the two countries are similar and explore the evidence of similarity between the North(s). Finding development outcomes in the Russian and Canadian North strikingly similar, the second chapter uses a combination of discursive analysis and regulation theory to re-interpret the origins of present-day problems and examine the genealogy of northern development. It argues that the Canadian and Russian northern development regimes shared profound commonalities. From these positions, the chapter compares and critiques past and present policies of regional development in the two Norths, and discusses their viability. The third chapter dwells upon a concept of ‘development regimes’ to analyze and compare contemporary regional development policies. It further investigates how recent economic development policies in the two Norths are adapting to changing economic and political realities, and if they were able to deliver desirable results to northern communities. The chapter compares and critiques contemporary policies and discusses possible alternative perspectives that reconcile an emerging postcolonial paradigm of development and realities of post-Fordism. It introduces the notion of the neo-staple development regime and describes its manifestations (Impact and Benefit Agreements). The fourth chapter presents a case for fostering knowledge based development and creative capital in the North. It builds on the innovation systems and institutional geography literatures to argue that the creative capital in the periphery is a pivotal factor of regional development. The chapter provides a conceptualization and empirical analysis of the creative class in remote regions. Contrary to the metropolitan bias, I argue that creative ‘hot spots’ beyond metropolis exist, and could become the centres of regional reinvention, if appropriate policies are introduced in support.
Dynamic Two-place Indirect Verbs in French: A Synchronic and Diachronic Study in Variation and Change of Valence
Keywords: French
linguistics
diachronic syntax
verbs
argument structure

This dissertation provides an account of an often-noted change in the history of French: the shift in the expression of the internal argument of a small class of dynamic two-place verbs best represented by aider ‘to help’ from “dative”, i.e., as an indirect object with the preposition à, to “accusative”, i.e., as a direct object with no preposition. The change does not appear to be correlated with a change in the meaning of the verbs. Traditional commentators have viewed it as random, affecting only a few lexical items, rather than systematic. One of the central results of this thesis is that the valency change affects a class of some twenty verbs at approximately the same period and it follows the same time course. Moreover, three properties distinguish this class of verbs from all others taking indirect objects in French: following current ideas about the syntactic manifestation of verbs and their arguments, they have a non relational argument structure, they do not possess lexical directionality, and they select for first or third order entities. These facts suggest that a structural change underlies the change in the realization of the internal argument. Adopting Lightfoot’s (1999, 2006) “cue-based” approach to language change, it is proposed that the valency change is a result of the loss of a functional item encoding directionality. Directionality is a derived property in Medieval French, available in particular to prepositions. It is demonstrated that when à was able to encode direction, it was also able to license first and third order complements in a broader range of contexts, namely, with aider-type verbs. The loss of this functional item is also correlated with several other structural changes that occurred in the 16th and 17th century.
Economic Analyses of Ontario's Stumpage Pricing System
Keywords: Stumpage Pricing System
Softwood Lumber
Trade Dispute

The softwood lumber trade dispute between Canada and the United States has centered on the debate over the existence of a stumpage subsidy in Canada and recently on dumping by the Canadian softwood lumber producers in the U.S. markets. This thesis contains three essays that investigate the subsidy and dumping issues in this dispute. The results of these analyses indicate the economic performance of Ontario’s stumpage system. The first essay investigates the market performance of Ontario’s stumpage system by examining the long-run equilibrium and Granger-causality relationships between the stumpage prices and the market prices of various end products (lumber, pulp and wood composites) from June 1995 to February 2005 using Johansen’s multivariate co-integration approach and the Granger-causality test. Test results indicate that in terms of SPF (spruce, pine, fir) for lumber and pulp, Ontario’s stumpage system can establish stumpage prices that have the potential to reflect the market values of timber. However, there is a need to modify the system for the other products. In the second essay, an Enhanced Parity Bounds Model (EPBM) is developed and used to examine the discrepancy between the stumpage price of SPF timber for producing lumber and its market value from June 1995 to January 2007. The results show that in the short run, the stumpage prices were below or above the market values. However, in the long run, the underpayment and overpayment will even each other out. The results, therefore, imply that Ontario’s stumpage system has the ability to capture the full economic rents in the long run and thus does not confer a subsidy to Ontario’s softwood lumber producers. The third paper examines the issue of whether Ontario’s softwood lumber industry had dumped softwood lumber into a major US market from April 1996 to September 2006 using the EPBM. This is a critical issue for Ontario’s stumpage system because dumping could lead to lower stumpage prices under the current stumpage system. This analysis indicates that the industry gained considerably more profit from the U.S market than from the home market and did not dump lumber in the US market during this period.
Clearcut Solutions? An Evaluation of Partial Harvesting in the Black Spruce Boreal Forest
Keywords: alternative silviculture
black spruce
boreal forest
dendrochronology
growth response
natural disturbance emulation
neighbourhood analysis
partial harvesting
simulation modelling
tree mortality

Bringing together field-based empirical studies, a simulation modelling experiment, and a critical analysis of the natural disturbance emulation paradigm, this thesis evaluates partial harvesting in the black spruce boreal forest. Forest management in Ontario is required to emulate natural disturbances, but in regions of the boreal forest where fire cycles are long, regulated even-aged management by clearcutting has truncated forest age-class distributions. Partial harvesting has been proposed as a means to maintain the structural complexity and biodiversity associated with old forests while allowing continued timber production. Despite the potentially important role of partial harvesting in a strategy for sustainable boreal forest management, little research has examined post-harvest stand development, a critical determinant both of habitat and timber supplies.I used a chronosequence approach in combination with dendroecological techniques, a neighbourhood modelling framework, and maximum likelihood statistical methods to quantify stand dynamics over the first decade after partial harvest in the black spruce (Picea mariana) boreal forest of northeastern Ontario, Canada. Residual trees displayed large but time-lagged growth responses to partial harvest. The largest responses were found in young trees, while old trees were largely unable to react to improved post-harvest resource availability. Growth responses were offset by elevated rates of residual-tree mortality, which peaked in the first year after harvest at nearly 13 times the pre-harvest level. Proximity to harvest machinery trails severely escalated the risk of mortality for residual trees. Considering growth and mortality responses together in a forest simulator model, I found that stand development proceeded most rapidly where skidding intensity was reduced and retention areas were aggregated. Given appropriate prescriptions, my results indicate that partial harvesting can be a viable silvicultural option for black spruce boreal forests. However, the ability of partially harvested stands to emulate natural disturbance is questionable, particularly given the strong influence of harvest machinery impacts on post-harvest stand development. I argue that the natural disturbance emulation framework has important flaws and falls short of a justifiable approach for forest management in Ontario.