VictorJuiz/thesis huggingface dataset:
Building Learning Community in Post-Secondary Large Lecture Courses: A Blended Approach to Fostering Communities of Learners
Keywords: active learning
collaborative learning
inquiry learning
learning community
social constructivism

This design-based research study examined the ways in which a learning community approach can be enacted in large undergraduate lecture courses through a scaffolded, complex curricular design that utilizes active and inquiry-based learning. By combining a traditional lecture with breakout tutorials, the study involved two iterations, firstly by adopting the Fostering Communities of Learners (FCL) pedagogical model (Brown Campione, 1996) then by augmenting the model by blending its methodology with elements from the Knowledge Community and Inquiry (KCI) model (Slotta Peters, 2008; Slotta Najafi, 2010). The first iteration ( N = 236) consisted of a twelve week course, combining lectures with 12 breakout tutorial sections (N = 20). The course addressed a variety of foundational business concepts for undergraduate media students. The second iteration (N = 231), conducted the following year, included a digital Collaborative Knowledge Base (CKB) which was populated by student inquiry exercises and served to coordinate or index their subsequent inquiry activities. Both iterations were evaluated for adherence to, and enactment of, the FCL principles. The second iteration was further evaluated for adherence to the newly introduced KCI-inspired CKB, which measures included the enactment of the curricular design, achievement of course learning outcomes, the group inquiry project, tutorial activities, pre- and post-term surveys and focus groups for TAs and students. Findings provided evidence of the viability and effectiveness of a learning community approach in large lecture courses at the undergraduate level when combining FCL learning principles with a student-populated dynamic knowledge base. Students achieved both individual and group success in meeting learning outcomes through individual inquiry and collaborative, active learning, with the CKB providing a forum for students to share their research and access ideas for their inquiry. It also served as a nexus, connecting lectures and tutorials with community content, thereby encouraging a class-wide learning community. This dissertation outlines a promising source of evidence and guidelines for instructors who seek to adopt a learning community approach for large lecture courses. It adds to the existing body of research on learning communities and makes connections to emerging areas of active learning for higher education.
Dielectrophoresis microdevice design for selective lysis of circulating tumor cells in blood
Keywords: Circulating Tumor Cell
Dielectrophoresis
Electroporation
Genetic Optimization
Microfluidics
Thrombogenesis

Cancer is a leading cause of death in industrialized nations. A major contributor to the lethality of cancer lies in its ability to undergo metastasis, a process in which cancer spreads from its originating site to other locations in a patientâ s body. One of the pathways that cancer spreads is through a patientâ s bloodstream. Circulating tumor cells (CTCs) detach from tumors and enter blood vessels. Studies have shown that patients with high numbers of CTCs have lower survival probabilities than cancer patients with low CTC counts. We hypothesize that it may be possible to reduce the risk of metastatic disease in cancer patients by removing CTCs from the bloodstream. To this end, this thesis investigates the design of a microfluidic device capable of isolating and destroying cancer cells mixed with blood cells. This work acts as a first step and proof-of-concept towards the development of a therapeutic platform to filter CTCs from patient blood. Dielectrophoresis (DEP), a contact-free, electrode-based cell manipulation technique is used to spatially separate CTC analogue cells (MCF7 breast cancer cells) from blood cells. Larger cancer cells experience a greater DEP force and, therefore, levitate higher than smaller blood cells. Cancer cells are lysed using irreversible electroporation, an electrode-based technique that uses high magnitude electric fields to permanently open cell membranes. Cancer cells are levitated via DEP into proximity of electroporation electrodes to localize the lysis effect in the prototype device. Localized lysis of cancer cells is demonstrated through experiments with a fabricated prototype device. A novel electrode optimization protocol was developed to aid in the design of dielectrophoresis electrodes used in cell separation. To generate new electrode geometries, electrodes are designed in a pixel-based manner using a genetic solver. Optimal electrodes obtained through this protocol are fabricated in University of Toronto cleanrooms and used in experiments. Additionally, due to the stated design goal of separating CTCs from blood cells, thrombogenesis (blood clot formation) due to DEP-based cell separation is investigated. Experiments reveal that dielectrophoresis has a suppressive effect on blood clot formation, a finding that may be extended to applications requiring clot suppression beyond the device proposed in this thesis.
The Effects of Transmediation on Students' Creativity Through Collaborative Composing
Keywords: 21st century skills
collaborative composing
creativity
multiliteracies
music education
transmediation

The purpose of this action research was to investigate the process and the effect of the transmediation (translation of content from one media to another) on students’ creativity. The goal was achieved by focusing on: (a) students’ collaborative strategies of translating non-musical sources to musical compositions; (b) the effects of the level of abstraction of the sources on students’ creative processes and products; and (c) the effects of transmediation on students’ general and domain-specific creativity compared to the general music classes. This study was conducted in a Grade 8 beginner strings’ class of thirteen students. The study was divided into two phases: the teacher taught six classes, then the students were divided into groups of four or five to compose musical pieces through transmediating the given source. Six classes were spent translating verbal, visual, and video sources, with each mode containing one direct and one abstract source. Students were tested three times throughout the study (before and after phase 1, and after phase 2) with two tests on musical and general creativity. The results revealed that students were able to use multiple modes of communication effectively to face the challenge of transmediation: verbal expression to describe and give precise directions; musical sound to demonstrate musical ideas; and gestures to point, demonstrate, and express rejection or acceptance of ideas. Second, when students were working with more abstract sources, the number of interactions significantly increased, and the products demonstrated more complex levels of transmediation. Third, the increase of the test scores was significantly greater after the transmediation unit, suggesting that it had greater positive effects on students’ creativity than the general music classes. Overall, the findings suggest that the right level of transmediation task is effective in fostering students’ domain-specific and general creativity.
Structural and Functional Characterization of RAF Allosteric Regulation
Keywords: cancer
kinase
oncology
RAF

The RAS-ERK/MAPK pathway is a critical signalling pathway regulating cell growth, proliferation, and survival. As such, aberrant signalling through this pathway is often associated with tumourigenesis. At the apex of the ERK/MARK pathway are the RAF kinases, a family of Ser/Thr kinases that initiate the phosphorylation cascade following pathway activation. Consequently, RAF kinases are often mutated or dysregulated in cancers, especially malignant melanomas where RAF is mutated in ~70% of cases (Dhomen and Marais 2007). While all five members of the RAF kinase family have been implicated in cancer, over 90% of all RAF-related tumours are due to mutation of BRAF alone (Forbes et al. 2011). In addition to activation by interaction with upstream signalling components, most notably RAS, RAF kinase activity is regulated through dimerization of its kinase domain (Rajakulendran et al. 2009). Although structures of RAF dimers reveal the kinase-active conformation, how dimerization allosterically activates RAF remains unknown due to an absence of kinase-inactive RAF structures as a basis for comparison, precluding a full picture for how cancer-related RAF mutants lead to aberrant kinase activity. Importantly, a poor understanding of the nuances that govern RAF activation has clinical consequences, as RAF inhibitors used in the clinic can unexpectedly promote RAF activity and lead to exacerbation of tumourigenesis through unclear mechanisms (Hatzivassiliou et al. 2010; Poulikakos et al. 2010; Heidorn et al. 2010). The work described in this thesis was conducted with the aim of: (1) determining the structural basis for how kinase dimerization promotes RAF activity; (2) understanding how cancer-related RAF mutations promote kinase activity; and, (3) identifying inhibitors that avoid unexpected activation of RAF in cells. In Chapter 1, I provide relevant background on RAF signalling. In Chapter 2, I present the crystal structure of a dimer-promoting ATP-competitive inhibitor in complex with RAF and, in collaboration with others, I present a model for how inhibitors promote RAF dimerization through stabilization of a rigid, closed, conformation of the kinase domain. In Chapter 3, I present the crystal structure of BRAF in complex with a monomer-inducing ATP-competitive inhibitor and validate the structure as being reflective of the native RAF kinase-inactive conformation. Importantly, the structure and accompanying biochemistry provide formal proof for an allosteric link between the RAF dimer interface, the kinase activation segment, and the catalytic infrastructure housing the ATP binding site. Together this work establishes the structural basis for how RAF is regulated through dimerization and reveals the chemical features of inhibitors that limit paradoxical RAF activation. Lastly, in chapter 4, I discuss future avenues in RAF research.
Procedural Fairness and Citizen Control: Addressing the Legitimacy Deficit in the Canadian Administrative State
Keywords: Administrative Law
Canadian Law
Civic Republicanism
Comparative Law
Law and Democracy

The Canadian administrative state has changed significantly since the first half of the twentieth century, but legal scholarship has paid scant attention to how such changes might affect the administrative stateâ s legitimacy. This thesis argues that the traditional mechanisms for legitimating the increasingly complex and diffuse administrative state are no longer sufficient, particularly in the context of delegated law-making. It uses a republican model of legitimacy to argue for the necessity of citizen control over administrative decision-making. It is incumbent on Canadian administrative law to help provide this citizen control. A concern with legitimacy is consistent with the first principles of administrative law and judicial review, and the doctrine of procedural fairness is well placed to further the participatory vision of legitimacy the thesis employs. Further, the history of procedural fairness shows that legitimacy of decision-making has always been a core concern of the doctrine. However, more recent developments, including a fixation on adjudicative decision-making and the refusal to apply procedural fairness to delegated law-making, mean that Canadian administrative law does not sufficiently facilitate citizen control. This is inconsistent with both the internal values of Canadian administrative law and the civic republican vision of legitimacy. There is, however, a separate line of bylaws jurisprudence which more generously extends procedural fairness to delegated law-making. The thesis argues this bylaws jurisprudence is a good starting point to build from. The experience of comparative administrative law makes it even clearer that Canadian administrative law is able to do this legitimating work. The United Kingdom, New Zealand, and Australia all provide broader participation rights in the law-making sphere with weaker tools than are available in Canada. Further, the domestic aboriginal law duty to consult and accommodate make it clear that the Canadian courts are already comfortable imposing broadly applicable procedural rights. Building from this comparative and cognate jurisprudence and the bylaws cases mentioned above, the thesis argues that it is possible with only limited substantive changes to the law to develop the doctrine of procedural fairness to provide broad participatory rights in the delegated law-making sphere, thereby securing the legitimacy of the administrative state.
Memory as Politics: Narratives of Communism and the Shape of a Community
Keywords: collective memory
electoral politics
mnemonic capital
nationalism and ethnicity
Poland

This work traces how the past is politicized in post-transition spaces, how it enters the political language, and what effects it produces. Expanding the framework of collective memory literature and anchoring the story in Poland, I argue that the narratives of past communism structure political competition and affect the present-day imaginary of common belonging - that is, they determine political positions of players and they reveal who is included in and excluded from the conception of the ‘we.’ First, I develop the concept of mnemonic capital - a politically productive symbolic resource that accrues to political players based on their turn to, and judgment of, the past - and demonstrate how the distribution of that capital results in sharply differentiated political identities. (I identify four positions generalizable to other post-transition settings.) Second, I trace how narratives of the past constitute the boundary of the ‘we’. I find that in their approaches and judgments of communism, the current political elites conflate communism and Jewishness. In doing so, they elevate the nation and narrow its meaning to ascriptive, religion-inflected, ethnicity. Third, I argue that the field of politics and the field of belonging interact and do not simply exist on parallel planes. I develop a concept of a mnemonic procedure - a patterned and relational way of narrating the past - to show how the narrative techniques performed for present-day political payoffs, constrain the vision of a polity. The concepts of mnemonic capital and mnemonic procedure intervene in the literature on transitions to democracy in that they help to apprehend how a politics contines to be organized by the repudiated ancien régime, now inserted into the political space as a productive symbolic trope. In other words, the concepts explain how the past continues to haunt and affect the quality of post-transition democracy and post-transition belonging.
The role of human bone marrow mesenchymal stromal cells in pancreatic cancer growth
Keywords: interleukin-6
mesenchymal stromal cells
pancreatic cancer
STAT3
stroma
tumor stromal interactions

Pancreatic cancer is one of the most lethal cancers characterized by local invasiveness, early metastasis, recurrence and high resistance to current therapies. Extensive stroma or desmoplasia is a key histological feature of the disease. Interactions between pancreatic cancer cells and tumor stroma are critical for pancreatic cancer development and progression. Mesenchymal stromal cells (MSC) are multipotent stromal progenitors that exhibit preferential tropism to primary and metastatic tumor sites. While MSCs represent a potential source of pancreatic cancer stroma, their contribution to pancreatic tumor growth remains poorly known. Here, we show that bone marrow MSC (BM-MSC) significantly contribute to pancreatic cancer growth in vitro and in vivo. Furthermore, MSC create a pro-carcinogenic microenvironment through the release of key factors mediating growth and angiogenesis including IL-6 and VEGF, and activation of STAT3 signaling in tumor cells. IL-6 released by MSC was mainly responsible for the pro-tumorigenic effects of MSC. In fact, knockdown of IL-6 expression in MSCs by small interference RNA (siRNA) abolished MSC-growth promoting effect in vitro reducing tumor cell proliferation and clonogenic potential. In addition, blocking of IL-6 classic- and trans-signaling by anti-IL-6 receptor antibody Tocilizumab or IL-6 trans-signaling by transfusion protein sgp130Fc in a heterotopic nude mouse model of human BxPc3 xenografts abrogated MSC mediated tumor-promoting effects delaying tumor formation significantly. In addition, Tocilizumab inhibited cancer growth remarkably resulting in smaller tumors compared to MSC control groups and tumor alone group. Moreover, anti-IL-6 therapy inhibited the profibrogenic effects of MSC leading to a significant reduction in tumor fibrosis in comparison to MSC control groups. Our data demonstrate that IL-6 produced by stromal cells plays a pivotal role in pancreatic cancer growth and is a new potential therapeutic target for patients with pancreatic cancer.
Understanding the Role of Oncogenic Human Papillomavirus (HPV) Status on Adherence Behaviors Among Women with Abnormal Cervical Cytology
Keywords: Cervical Cancer Prevention
Cervical Screening
Colposcopy
HPV testing
Human Papillomavirus

The discovery of oncogenic Human Papillomavirus (HPV) as the precursor to cervical cancer is a significant advancement in public health. However, the use of HPV testing has increased the complexity of cervical screening, as it is associated with elevated psychosocial burden and perceived risk of cancer in some women. What remains to be seen is if knowledge of oneâ s oncogenic HPV status impacts on adherence to follow-up recommendations for cervical screening abnormalities, a modifiable health behavior that is strongly associated with the primary prevention of cervical cancer. Insomuch as adherence rates remain low in women with cervical screening abnormalities, it is crucial that we understand which factors impact on adherence to follow-up recommendations across a range of clinical manifestations. Therefore, the purpose of this study was to: 1) to identify if clinical, demographic or psychosocial factors predict non-adherence with recommended follow-up after initial consultation; 2) to identify clinical, demographic and psychosocial variables associated with HPV related burden and; 3) to describe the clinical and demographic characteristics of participants according to pre-post smoking and HPV vaccine immunization patterns. This study examined 186 women referred to a large Toronto colposcopy clinic. The HPV Status Adherence Conceptual Framework was used to guide survey development and to contextualize results. The findings suggest that non-adherence to colposcopy follow-up exists and is problematic. Specifically, younger women (OR=0.73, p
CCL5-CCR5 Interactions in Breast Cancer Regulate Cell Metabolism
Keywords: Anabolism
Breast Cancer
CCL5
CCR5
Chemokine
Metabolism

Chemokines are chemotactic cytokines that recruit and activate leukocytes. It is now apparent that they also participate actively in the neoplastic process in cancer. This thesis describes the importance of the activation of CCR5 by the inflammatory chemokine CCL5/RANTES in the context of cancer metabolism. Specifically, CCL5-CCR5 interactions promote anabolic metabolism in breast cancer cells and enhance cell proliferation. CCL5 activation of CCR5 invokes the mTOR/AKT signaling pathway and, within minutes, induces phosphorylation of downstream substrates, including GSK-3Î˛ and 4E-BP1. Using a panel of CCR5-expressing breast cancer cells, we show that CCL5 also increases surface GLUT-1 expression, glucose uptake, ATP production and the glycolytic capacity of these tumor cells. Using metabolomics, we demonstrate that the metabolic signature of primary mouse mammary tumor cells that express CCR5 is altered by CCL5 treatment and reflects enhanced anabolic metabolism, resulting in the accumulation of biosynthetic precursors. Concomitant with enhanced anabolic metabolism, we show that CCL5 increases the proliferation and invasive capacity of breast cancer cells. Moreover, in an immune-deficient tumor transplant mouse model, we identify a direct correlation between reduced tumor proliferation and decreased metabolic activity, specifically associated with the absence of CCR5 expression by tumor cells. Using Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry imaging, we provide evidence that the rapid early growth of CCR5+/+ triple negative breast cancer cells in vivo is attributable to increased levels of glycolytic intermediates required for anabolic processes, in contrast to the slower growth rate of their corresponding CCR5-/- cells, that exhibit reduced glycolytic metabolism. Collectively, these studies suggest that CCL5-CCR5 interactions in the tumor microenvironment modulate metabolic events during tumor onset to promote tumorigenesis.