VictorJuiz/thesis huggingface dataset:
The Effect of Molecular Targeted Agents used in Combination with Chemotherapy to Inhibit the Repopulation of Tumour Cells and Xenografts

Chemotherapy is often administered once every three weeks to allow repopulation of essential normal tissues such as the bone marrow. Repopulation of surviving tumour cells can also occur between courses of chemotherapy and can decrease the efficacy of anticancer treatment. This thesis aims to characterize repopulation, to study the effect of targeted cytostatic agents to inhibit repopulation, and to determine the optimal scheduling of chemotherapy and molecular targeted treatment. The distribution of proliferating and apoptotic cells in human squamous cell carcinoma (A431) xenografts was studied following chemotherapy using fluorescence immunohistochemistry. There was an initial decrease in cell proliferation and in the total functional blood vessels, and an increase in apoptosis observed following treatment with paclitaxel chemotherapy. A rebound in cell proliferation occurred approximately 12 days following treatment, which corresponded with a rebound in vascular perfusion. The effect of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, to inhibit repopulation between courses of chemotherapy was determined using EGFR-overexpressing A431 cells and xenografts. Furthermore, concurrent and sequential schedules of combined chemotherapy and molecular targeted treatment were compared. Gefitinib inhibited the repopulation of A431 cells in culture when administered sequentially between chemotherapy; sequential treatment was more efficacious than concurrent treatment probably because concomitant scheduling rendered quiescent cells less responsive to chemotherapy. However, in vivo studies using chemotherapy in combination with gefitinib or temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor, showed that concurrent scheduling of combined treatment was more effective at delaying regrowth of xenografts than sequential treatment; this was likely due to dominant effects on the tumour microenvironment. The work completed in this thesis has shown that repopulation occurs in A431 xenografts following paclitaxel treatment, and these changes are associated with changes in the tumour vasculature. Repopulation of A431 cells was inhibited by gefitinib administered sequentially with paclitaxel. However, studies in mice showed better inhibitory effects when chemotherapy was given concomitantly with cytostatic agents such as gefitinib or temsirolimus. Our in vivo data highlight the importance of characterizing changes in the tumour microenvironment when determining optimal scheduling of chemotherapy and molecular targeted treatment.

Keywords: Solid tumours
Repopulation
Advisor: Tannock, Ian
Essays in Political Economy and the Economics of Organisations

This thesis groups three papers in applied microeconomic theory that focus on political economy and the economics of organisations. The first chapter studies the equilibrium outcomes of a dynamic game of electoral competition between two policy-motivated parties. I model incumbent policy persistence: parties commit to implement a policy for their full tenure in office, and hence in any election only the opposition party is free to choose a new platform. The model gives rise to novel equilibrium policy dynamics: governments alternate in power; parties compromise, that is, starting from differentiated ideological positions, they gradually move towards proposing platforms which resemble one another; however, they never capitulate, that is, party labels matter and parties maintain distinct policy goals. The second chapter studies a directed search model of competition between sellers that control the quality of buyers' private information about goods. As better informed buyers extract more informational rents from trade, sellers may try to attract buyers by offering better information. First, I establish how the characteristics of exogenously fixed sale mechanisms determine equilibrium information provision. Information provision is higher under competition than under monopoly, yet partial information is provided for many sale mechanisms. Second, when sellers commit to both information provision and mechanisms, I identify simple conditions under which every equilibrium has full information. In these equilibria, sellers capture the efficiency gains of information provision and compete only over non-distortionary rents offered to buyers. Retaining the option to develop a currently inactive project often requires maintaining specialised stocks of knowledge. However, standard models of experimentation treat the choice of one project over another as entailing only an implicit opportunity cost. In the third chapter, I characterise the optimal experimentation policy in a model in which undeveloped projects have explicit maintenance costs and can be irreversibly discarded. Projects which in the absence of maintenance costs would be developed only after more promising projects fail are sometimes developed first and then discarded early. Maintenance costs alter optimal project development by providing incentives to bring the option value of less promising projects forward.

Keywords: Microeconomic Theory
Political Economy
Advisor: Osborne, Martin
Investigating the Interaction of Semiconductor Quantum Dots with in vivo and Cellular Environments to Determine Disposition and Risk

Nanomaterial toxicity is a major concern and could potentially hamper the progress of biomedical nanotechnology development. Dispelling these concerns requires that the consequences of nanomaterial exposure are evaluated, and the findings will determine whether developmental hurdles can be overcome. This thesis evaluates the both in vivo and in vitro impact of quantum dots (QD , zinc sulphide capped cadmium selenide semiconductor nanocrystals) a fluorescent nanoparticle label with potential as an optical in vivo imaging agent. This work reviews nanoparticle characterization techniques and their importance to biological responses, and surveys QD interactions both in vivo and in vitro. We collected pharmacokinetic and toxicity data by a) quantitatively surveying the in vivo absorption, distribution , metabolism and excretion of QDs, and b) measuring the impacts of QDs on relevant organs (in vivo) and cells (in vitro). Neither of these areas had been explored when this thesis was started. In vivo, intravenous QD dosing in Sprague-Dawley rats showed uptake into reticuloendothelial cells with surface coating dependent kinetics, slow degradation, no excretion detected in feces or urine, and no indications of toxicity. The liver took up the majority of dose after 90 minutes and small amounts of QDs appeared in the spleen, kidney, and bone marrow. After 30 days, the cadmium concentration in the kidneys increased to 3µg/g without a proportional amount of zinc, indicating QD breakdown. In vitro we noted phagocytic capacity comparable to in vivo results, QD breakdown, and a retention of normal macrophage function thereby demonstrating that primary rat liver macrophages (Kupffer cells) are an appropriate in vitro system with which to investigate the cellular responses to quantum dots. Such an in vitro model will facilitate faster evaluation of individual nanotechnologies intended for in vivo use. This dissertation addresses a lack of in vivo background information needed to understand the consequences of QD exposure; though QD fail to demonstrate pharmacokinetics desirable for in vivo imaging agents, they are not toxic. Importantly, we provide in vitro data that will lead to the development of accurate and efficient in vitro primary screening methods that will be central to the further development of biomedical nanotechnologies.

Keywords: quantum dots
pharmacokinetics
nanoparticle
toxicity
Advisor: Chan, Warren C. W.
From BAH to ba: Valence Theory and the Future of Organization

This thesis traces the history of organization from the society of Ancient Athens, through the medieval Church, the Industrial Age, and the 20th century – the latter characterized by the Bureaucratic, Administratively controlled, and Hierarchical (BAH) organization – until today’s contemporary reality of Ubiquitous Connectivity and Pervasive Proximity (UCaPP). Organizations are rarely, if ever, entirely BAH or entirely UCaPP, but do tend to have tendencies and behaviours that are more consistent with either end of a spectrum delineated by this duality. Valence Theory defines organization as being an emergent entity whose members (individuals or organizations) are connected via two or more of five valence (meaning uniting, bonding, interacting, reacting, combining) relationships. Each of these relationships – Economic, Socio-psychological, Identity, Knowledge, and Ecological – has a fungible (mercantile or tradable) aspect, and a ba-aspect that creates a space-and-place of common, tacit understanding of self-identification-in-relation, mutual sense of purpose, and volition to action. Organizations with more-BAH tendencies will emphasize the fungible valence forms, and primarily tend towards Economic valence dominance; more-UCaPP organizations tend to emphasize ba-valence forms, and are more balanced among the relative valence strengths. The empirical research investigates five organizations spanning the spectrum from über-BAH to archetypal UCaPP and discovers how BAH-organizations replace the complexity of human dynamics in social systems with the complication of machine-analogous procedures that enable structural interdependence, individual responsibility, and leader accountability. In contrast, UCaPP-organizations encourage and enable processes of continual emergence by valuing and promoting complex interactions in an environment of individual autonomy and agency, collective responsibility, and mutual accountability. The consequential differences in how each type of organization operates manifest as the methods through which organizations accommodate change, coordination, evaluation, impetus, power dynamics, sense-making, and view of people. Particular attention is paid to the respective natures of leadership, and effecting organizational transformation from one type to the other. Set in counterpoint against Zen-like, artistically constructed conversations with a thought-provoking interior sensei, the thesis offers a new foundational model of organization for the current cultural epoch that enables people to assume their responsibility in creating relationships and perceiving effects in the context of a UCaPP world.

Keywords: organization
leadership
organization development
organization behaviour
organization change
business history
management
human relations
organization theory
organizational complexity
bureaucracy
hierarchy
administration
collaboration
Advisor: Laiken, Marilyn
Transfer of Learning from the Classroom to the Cooperative Education Workplace in a Baccalaureate Program in an Ontario College of Applied Arts and Technology

This research used case study methodology with both qualitative and quantitative research tools to examine the transfer of learning from the classroom to the cooperative education workplace and the relationship of students’ learning styles to this transfer of learning in a Bachelor of Applied Business program at a large comprehensive College of Applied Arts and Technology in Ontario. Kolb’s experiential learning theory was used as the conceptual framework. A purposive convenience sample of six students (28.6%) who had completed the second of three cooperative education work terms in the program participated and completed all components of the study. The research findings led to six conclusions: 1. Foundation skills learned in the classroom, such as communication and technical skills, and in this case general business concepts, are used in all of the cooperative education workplace experiences in this study. 2. The co-op work term experience itself, including the workplace environment and culture, is more important than the student’s learning style in explaining the learning from the classroom that a student is able to transfer to the co-op workplace. 3. Co-op experiences may not challenge students to the level they may be capable of with respect to what they have learned in class. 4. A co-op work term learning plan, opportunity to use previous learning, and a supportive co-op environment are important for students to be able to transfer their learning from the classroom to the cooperative education workplace experience. 5. Perceived barriers to transfer of learning can also provide the opportunity for learning experiences. 6. The program curriculum design plays a role in enabling transfer of learning. Several recommendations related to implications for practice were also identified. These included the need to reinforce the importance of communication and technical skills with students, providing a variety of learning experiences, designing curriculum to link classroom learning with the co-op experience, selecting co-op experiences so as to ensure alignment between the students’ knowledge and abilities and the opportunities available, providing formal orientation and training to cooperative education employer supervisors, and aligning the work term learning plan with the program curriculum.

Keywords: cooperative education
transfer of learning
baccalaureate degree
Kolb's experiential learning theory
Kolb's learning styles
Ontario College of Applied Arts and Technology
Advisor: Skolnik, Michael
“Fitting a Square Peg into a Round Hole” — Understanding Kinship Care Outside of the Foster Care Paradigm

This exploratory grounded theory study is a comparative analysis of kinship and foster care in the province of Ontario. This study sought the perspective of three constituent groups—caregivers (N=22), workers (N=14) and youth (N=9)—from both kinship and foster care constituent populations. The total number of participants was 45. This is one of the first comprehensive qualitative studies in the province of Ontario since the inception of the kinship model of practice implemented by the child welfare system in 2006. The study resonates with important practice, policy and research implications for Ontario and beyond. Recruitment for the study was generated through various child welfare organizations and a kin grandparents support network. Findings from each of the three groups include the following: (1) specialized kin workers recognize the complexities and unique needs of kinship placements; (2) foster parents and kin caregivers have very different needs related to training, financial remuneration and support; and (3) youth experience feelings of loneliness and frustration when moving to different placements, but also acknowledge the importance of relationships, particularly to their assigned worker. The analysis of these three group converges to a very simple but poignant conclusion: kinship programs are unique and require a level of intervention that is separate and discrete from the current foster care paradigm.

Keywords: Kinship Care
Foster Care
Child Welfare Placements
Advisor: MacFadden, Robert
The Role of ALK3 in Urogenital Development

The mammalian kidney and reproductive systems both derive from a common embryological origin, the intermediate mesoderm. Abnormal intermediate mesoderm development can result in congenital abnormalities of the urogenital system, yet the molecular mechanisms that govern intermediate mesoderm development are incompletely defined. The spatial and temporal expression of the proteins BMP2 and 4 and their receptor ALK3, in urogenital tissue, suggests a function for BMP-ALK3 signaling in the intermediate mesoderm. It was found that Alk3IM null kidneys display renal hypoplasia, associated with a decrease in kidney size and nephron number. The phenotype of renal hypoplasia in Alk3IM nulls was associated with early decreased number of developing nephron structures and secondary defects in branching morphogenesis. While neither apoptosis nor cell proliferation differed in metanephric mesenchyme cells in Alk3IM nulls, markers of renal progenitor cells were decreased in mutant animals. It was observed that Alk3 expression in the intermediate mesoderm also controls mesonephric tubule number. Alk3IM nulls had fewer mesonephric tubules and fewer derivative Leydig cells. The reduction in Leydig cells resulted in decreased levels in serum testosterone and defects in seminal vesicle formation and fertility. Alk3 expression was also required for normal development of the corpus epididymis. The morphological defects in nephrogenesis were associated with decreased phospho-p38 MAPK expression and in the testis with decreased Phospho-SMAD1/5/8. These results elucidated a requirement for Alk3 signaling in controlling progenitor cells derived from the intermediate mesoderm.

Keywords: Kidney Development
Bone Morphogenetic Protein
Mesonephros
Testis Development
Nephron
Testosterone
Advisor: Rosenblum, Norman D.
Bringing Books to the Public: British Intellectual Weekly Periodicals, 1918-1939

My dissertation investigates the role of intellectual weekly periodicals such as the Nation and Athenaeum and the New Statesman as mediators between the book trade and the audience for so-called serious books. The weeklies offer a productive lens through which to examine the labels commonly applied to early twentieth-century intellectual culture. The rise of a mass reading public and the proliferation of print in this period necessitated cultural labels with a sorting function: books, periodicals, and people were designated as "highbrow," "middlebrow," "modernist," "Georgian," "Bloomsbury." Through an analysis of the intellectual weeklies, a periodical genre explicitly devoted to the appraisal of intellectual culture, I argue for a critical revaluation of cultural labels as they were used in the early twentieth century and as they have been adopted in later scholarship. Using quantitative methodologies influenced by book history, Chapter One argues that the weeklies' literary content was characterized by the periodicals' reciprocal relationship with the book trade: publishers were the weeklies' most significant advertisers, and the weeklies, in turn, communicated information about new books to their book-interested readers. Through an analysis of two series of articles published in the Nation and Athenaeum in the mid-1920s, Chapter Two considers the weeklies' negotiation of their dual roles as forums for public debate about intellectual culture and advertising partners with the book trade. Chapter Three analyzes the book review itself, which found its evaluative function called into question as the number of books and periodicals multiplied rapidly in the late nineteenth and early twentieth centuries. Chapter Four examines the vituperative discourse directed at the intellectual weeklies by the Cambridge quarterly Scrutiny. These attacks reveal not only Scrutiny's disappointment with the specific weeklies of its day but also the paramount cultural responsibility it ascribed to the intellectual weeklies as a genre. By considering the intellectual weeklies' relationships with the book trade, the book-buying public, reviewing, and other intellectual periodicals, my dissertation emphasizes the importance of the intellectual weeklies within the cultural field of interwar Britain and argues for a reconsideration of their role in the production and labeling of intellectual culture during this period.

Keywords: book history
periodical studies
Advisor: Cuddy-Keane, Melba
The Properties and Effects of Metro Network Designs

Since 2008, more than half of the world population lives in cities. To cope with this rapid urbanization in a sustainable manner, transit systems all around the world are likely to grow. By studying 33 networks in the world, this thesis identifies the properties and effects of metro network designs by using a graph theory approach. After the literature review, a new methodology was introduced to translate networks into graphs; it notably accounts for various transit specificities (e.g., presence of lines). Metro networks were then characterised according to their State, Form, and Structure; where State relates to the development phase of metros; Form investigates the link between metros and the built environment; Structure examines the intrinsic properties of metros, by notably looking at their connectivity. Subsequently, the complexity and robustness of metros were studied; metros were found to possess scale-free and small-world features although showing atypical topologies; robustness emphasizes on the presence of alternative paths. Three network design indicators (coverage, directness and connectivity) were then related to ridership (annual boardings per capita), and positive relations were observed, which suggests that network design plays an important role in their success. Finally, these concepts were applied to the Toronto metro plans announced by the Toronto regional transportation authority, Metrolinx; it was found that the grid-pattern nature of the plans could hinder the success of the metro; seven possible improvements were suggested. Overall, the topology of metro networks can play a key role in their success. The concepts presented here can particularly be useful to transit planners; they should also be used along with conventional planning techniques. New transit projects could benefit greatly from an analysis of their network designs, which in turn may play a relevant role in the global endeavour for sustainability.

Keywords: public transportation
network
transit
properties
effects
graph theory
network science
metro
Advisor: Kennedy, Christopher A.