VictorJuiz/thesis huggingface dataset:
Application of carbamoylimidazolium salts in small molecule and combinatorial synthesis

This thesis is a summary of research conducted since February 2000 in the laboratories of Professor Robert A. Batey at the University of Toronto and is continuation of work performed here on carbamoylimidazolium salts. Chapter A covers the synthesis of the imidazolium salts, as well as their application in small molecule preparation. The salts are prepared in two steps with minimal purification, and have been successfully applied to the generation of amides from carboxylic acids. The amides are generated under mild conditions in excellent yields and are pure after aqueous work-up. Previous work in our laboratory has shown that derivatized anilines are unreactive towards the salts. Here the conditions were optimized for the reaction of salts with derivatized anilines to generate substituted ureas. Since imidazolium salts are capable of reacting with various nucleophiles a comparative study was carried out to determine the order of reactivity of the nucleophiles towards the salts. It was shown that sulfur based nucleophiles react significantly faster than any other nucleophile, while aliphatic alcohols and anilines do not react to any significant amount under weakly basic conditions. Synthetically useful selectivity levels between alkyl amines, phenols and carboxylic acids were not obtained. Chapter C covers the application of carbamoylimidazolium salts in the generation of heterocyclic alkaloids. Very poor reactivity of anilines under mild basic conditions allowed for a 4-component Povarov reaction of unprotected p-aminophenol with carbamoylimidazolium salt, aldehyde and 2,3-dihydrofuran. Lastly, the imidazolium salts were used in a short synthesis of fused bicyclic lactams. Chapter B focuses on combinatorial synthesis. Firstly, a semicarbazide library was generated. Hydrazides were reacted with N, N '-carbonyldiimidazole to generate 1,3,4-oxadiazol-2-ones, which were ring opened with amines to generate semicarbazides. Secondly, N, N'-diacylated imidazolidines exhibit herbicidal activity. Thus, we attempted to create a combinatorially friendly method for their synthesis. A common imidazolium salt intermediate was generated from monoacylated imidazolidine, which was then reacted with various amines. Lastly, a small library of ureas, carbamates, thiocarbamates and amides was synthesized to demonstrate the utility of the salts as a common precursor to various functionalities, which can be synthesized in parallel and under same conditions with minimal purification.
Alternate user interfaces for the manipulation of curves in 3D environments

In the design industry, profile drawings are typically sketched from various perspectives and combined in some sort of CAD system to build a digital representation of a 3D model. Limited virtual systems are available for this sketching process, as the current interfaces for manipulating curves typically use a standard point cursor to indirectly adjust curve parameters. Furthermore, limited functionality is available for allowing artists to integrate their profile sketches into a 3D environment, allowing them to survey the model as they design it from multiple viewpoints. In this thesis we will describe the design and implementation of interaction techniques for the creation, manipulation, and integration of curves in 3D environments. The systems which we present have been demonstrated to various users, from colleagues to professional artists, and user feedback is reported.
Pre-TCR and TCRab signaling during T cell development

During thymic development, the TCR$\beta$-containing pre-TCR complex mediates signaling at the DN to DP transition, whereas TCR$\alpha\beta$-mediated MHC recognition triggers maturation at the DP to SP transition. Various studies have examined the role of the Src PTKs Fyn and Lck in pre-TCR/TCR$\alpha\beta$ signaling. Although thymic development is normal in $fyn\sp{-/-}$ mice, the generation of DP cells as well as the development of TCR$\alpha\beta$ and TCR$\gamma\delta$ cells is partially compromised in $lck\sp{-/-}$ mice. Since Fyn and Lck expression levels are comparable during T cell development, Fyn may play a role in pre-TCR or TCR signaling in $lck\sp{-/-}$ mice. This study assessed thymic development in $lck\sp{-/-}fyn\sp{-/-}$ mice and demonstrated that it is completely impaired with virtually all thymocytes arrested at the immature CD25$\sp+$ DN stage, and no detectable peripheral TCR$\alpha\beta\sp+$ and TCR$\gamma\delta\sp+$ cells. Additionally, expression of the activated fyn (TFF) transgene completely restores the production of DP thymocytes and peripheral TCR$\gamma\delta$ cells in $lck\sp{-/-}$ mice. The TFF transgene also partially improves development of transitional/SP thymocytes but fails to increase the number of peripheral TCR$\alpha\beta$ cells in $lck\sp{-/-}$ mice. Collectively, these results suggest that Fyn mediates development of DP thymocytes in $lck\sp{-/-}$ mice, and transgenic expression of constitutively activated fyn can almost completely replace Lck during the DP to SP transition. Another aspect of this thesis examined the TCR$\alpha\beta$ signaling requirements in the maturation of DP thymocytes. Using an in vitro model to assess the response of purified TCR$\rm\sp{lo}$ DP cells to immobilized TCR specific antibodies, the results demonstrated that DP cells undergo multiple changes associated with positive selection in vivo. Following TCR stimulation, DP thymocytes undergo increased expression of CD5 and Bcl-2, a reduction in RAG1 and pre-T$\alpha$ gene expression, and a switch in lck promoter usage. Signals provided by CD4 and CD28 synergize with TCR signals to mediate various aspects of positive selection. However, TCR-mediated signals fail to trigger all hallmarks of DP cell maturation because clonal deletion, CD4/CD8 lineage commitment, and other aspects associated with positive selection are not observed.
Characterization of the in vivo roles of the adapter proteins ADAP and CBL-3

Communication between cells is critical for the development and survival of multicellular organisms. Intercellular communication is mediated by stimulation of cell surface receptors by extracellular signals, which activate multiple intracellular signaling pathways. By virtue of their multiple intermolecular interaction domains, adapter proteins allow the activation or inhibition of signaling cascades that govern cellular responses. Initial investigations of adapter protein function often utilize overexpression techniques in cell lines, however these studies can yield contradictory results that obscure the adapter's physiological role. The work herein characterizes the in vivo requirements for the adapter proteins adhesion- and degranulation-promoting adapter protein (ADAP) and Cbl-3 via the generation and phenotypic analysis of gene targeted mice. ADAP is expressed in T lymphocytes of the immune system, and was previously demonstrated to regulate T cell receptor signaling, however ADAP's role remained controversial since ADAP overexpression either positively or negatively regulated signaling depending on the experimental system used. To determine ADAP's physiological functions, gene targeted mice lacking ADAP expression in T and B lymphocytes were generated. ADAP was found to be required for T cell activation, proliferation, and in vivo immune responses. Although receptor proximal signaling appeared unaffected by the loss of ADAP, signaling between the T cell receptor and integrins was disrupted, resulting in reduced integrin clustering and impaired integrin-mediated T cell adhesion. These findings demonstrate a novel role for this adapter protein in coupling T cell receptor stimulation to integrin activation. In contrast to ADAP, Cbl-3 has been previously shown to be expressed in the gastrointestinal tract and to regulate epidermal growth factor receptor signaling and ubiquitination. Our detailed analysis of Cbl-3's expression pattern showed that this gene is expressed exclusively in epithelial tissues of organs including skin, trachea, intestine, kidney and bladder. However, gene targeted deletion of cbl-3 in mice showed that this gene is not essential for development, and that basal levels of proliferation in the gastrointestinal tract and epidermis were not affected by Cbl-3 deficiency. This work clarifies the physiological functions of ADAP and Cbl-3, and illustrates the diverse roles that adapter proteins play in regulation of intracellular signaling networks in vivo.
The experience and practice of adult educators in addressing the spiritual dimensions of their workplace

This thesis reports on the life history research with 5 adult educators who work in a variety of workplace contexts. Its purpose was to examine the experience and practice of these adult educators, as they were involved in the growing phenomenon of addressing spirituality within their workplace settings. More specifically this research explores (a) how their spirituality impacts them in their roles as adult educators within their work and (b) how their workplaces' commitment and ability to address the spiritual dimensions of the organization impact their roles. As the participants in this study explored their personal spirituality, religion was subsumed under the broader context of spirituality and they connected their spirituality with a higher being, listening to their inner voice and the importance of maintaining a close community. As they reflected on incorporating their spirituality into their practice as adult educators within their workplaces, a central theme that emerged was their role as a social advocate for the individual, for the group and for ethical and just business practices within their organization. Within the broader context of social advocacy, the participants also reflected upon specific “soulful spaces” within their workplace; ascribing the characteristics of connectedness, transformation and authenticity to these experiences. As they looked back on these moments, there were certain types of sessions that seemed to cultivate these moments such as change management, leadership development and the identification of organizational values because these events often require deep reflection and the full engagement of individuals and groups. As the participants guided these events, they cited the importance of establishing a trusting atmosphere, asking open-ended questions and using the processes of storytelling and open and honest dialogue.

Keywords: Work environment, Psychological aspects
Organizational behavior, Psychological aspects
Spirituality
Adult education educators, Attitudes
The effect of reference pricing of nitrates on targeted and non-targeted beneficiaries' expenditures on angina medications

Background. Drug plans commonly use reference pricing (RP) to control programme costs. The literature explores RP on seniors, however, less is known about how RP affects other beneficiaries, including those not targeted. The RP of nitrates in British Columbia (BC) targeted senior and welfare beneficiaries, while long-term care recipients were exempted. Research design. Using OLS regression, the pre-RP trend was extrapolated in to the post-RP period to estimate the impact of RP on the average Pharmacare daily expenditure on angina therapy. Data. Claims submitted to Pharmacare, the BC government drug plan, from January 1990-December 2001. Conclusion. RP reduced Pharmacare daily expenditures on angina medications without shifting the costs to beneficiaries. The spill-over effect, the habit of prescribing low cost medications to beneficiaries not targeted, led to substantial decreases in Pharmacare daily expenditures on angina medications of 50%. The effects of RP on beneficiaries' health status require further study.
The use of blocking antibodies targeting E-cadherin as sensitizing agents for anti-cancer therapy

Together, the results suggest that antibodies targeting cell-cell adhesion molecules such as E-cadherin may be useful as sensitizing agents for anti-cancer therapies, including those designed to involve a host anti-cancer immune response. Multicellular resistance, a subtype of therapeutic resistance manifested in cancer cells grown as three-dimensional multicellular masses, such as spheroids in vitro and solid tumors in vivo, occurs with respect to a wide variety of anti-cancer treatment strategies. Building upon previous work from our laboratory, this thesis describes proof-of-principle studies examining the ability of a monoclonal antibody targeting the potent cell adhesion molecule E-cadherin to disrupt three-dimensional aggregates of human cancer cells as a means of overcoming multicellular resistance. Chapter 3 outlines a separate but related set of experiments in which disruption of E-cadherin-mediated adhesion via SHE78-7 was shown to sensitize multicellular spheroids of HT29 in vitro to treatment with 5-fluorouracil, paclitaxel, vinblastine and etoposide, but not cisplatin. Anti-adhesion via SHE78-7 caused the release of cells from contact-mediated growth arrest, increased intracellular accumulation of administered chemotherapeutics, and decreased expression of particular PKC isoforms shown previously to influences the therapeutic resistance of HT29 cells; however, the expression and activity levels of one of these isoforms, PKC beta1, were shown to be unrelated to the manifestation of multicellular resistance. Chapter 2 describes the novel ability of one such anti-E-cadherin antibody, called SHE78-7, to play a dual role as participant in, and sensitizing agent for, host immune-mediated anti-tumor activity. SHE78-7 disrupted preformed multicellular aggregates of HT29 human colorectal carcinoma cells both in vitro and in vivo, but had no direct cytotoxic effect in vitro. In vivo, however, i.p. injection of SHE78-7 significantly prolonged the survival of nude mice carrying established i.p. HT29 ascites tumor xenografts. This anti-tumor effect was subsequently shown to be dependent upon both the anti-adhesive effect of SHE78-7 and its ability to recruit an Fc-mediated host immune response, namely antibody-dependent cellular cytotoxicity.
Educator acquisition and application of recent neurological and cognitive research

The purpose of this exploratory study was to analyze the source and manner by which educators obtain information related to neurology and cognitive psychology (commonly referred to as "brain research") and how educators apply this research to their classroom practice. In addition, a comparison was made between educators' practice and what neurological research suggests educators should be including in their practice. Recently, a great deal of attention has been paid to the research of neurologists and cognitive psychologists and the relationship of their findings to learning. However the consideration of work by neurologists, cognitive psychologists and other "brain scientists" is a new concept in the field of education. As most educators' educational background does not include neurology and cognitive psychology, they are reliant upon someone else to help them understand the primary sources of the findings from these fields. To explore how and where educators obtain their knowledge of this area, a survey of educators actively involved in improving their practice was undertaken. This was followed by classroom observations to observe how these educators, who had identified themselves as using "brain-based" strategies, were applying these strategies to their classrooms. Neurologists were also asked to complete a questionnaire to determine their understanding of the application of neurology to education. Data from a previous research project that had been abandoned by other researchers provided another source of information and was included in this study as a comparison. The results of this study indicate that educators believe findings from neurology and cognitive psychology are important to their practice and that these findings will change their practice. However, their knowledge base and use of this knowledge was limited. The results of this study also indicated that a need exists for the establishment of reliable sources of information as well as more opportunities for educators to learn about the findings from neurology and cognitive psychology and how these findings affect their practice. This would include the offering of courses in brain research for teachers as well as the development of interdisciplinary programs of study to research the science of teaching.
Emotional intelligence as a field of research: a comparative study between scientific theory and practice

This paper presents a comparative study between scientific theory and practice in the field of emotional intelligence (EI). The body of scientific theory can be divided into two main schools of thought. The purist position, supported by Salovey, Mayer and colleagues, states that emotional intelligence is an "ability" similar to spatial or verbal skills which have long been recognized as markers of human intelligence. The more popular "mixed" models, supported by Goleman, Bar-On and others, combine emotional processing with other aspects of personality such as optimism, persistence and zeal. It is the more popular "mixed" models that are predominantly being applied in practice. A thematic analysis of the scientific and popular literature reveals that there exists a split between scientific theory and practice in the field of EI. Suggestions for closing these gaps will result in a more integrated 'theory into practice' relationship in the field of EI.
Freud's theory of the drives as critical impulse in Adorno's aesthetic thought

The aim of this study is to analyse the aesthetic thought of Theodor W. Adorno with reference to two distinct systems of thought, first, the idealist aesthetics of Kant, and second, Freud's theory of the drives. Adorno is shown to posit a dualism that divides aesthetic experience into two opposing modes, which could be termed the aesthetic of identity and the aesthetic of negativity, and this dual aesthetic has significant parallels in both the Kantian and the Freudian systems. The study concludes that, while Adorno devotes a great deal of overt attention to Kant's (idealist) conception of the artwork in his construction of a dual aesthetic, and while many of Adorno's arguments display a deep affinity with German idealism, Adorno's aesthetic thought is nevertheless informed by Freud's theory of the drives, resulting in an understanding of the artwork that emphasises its material and sensuous aspects. Chapter 1 argues that there is an epistemological parallel between Adorno's distinction between the aesthetic of identity and the aesthetic of negativity and Kant's distinction between the determinant judgement and the reflective aesthetic judgement of taste. This analogy, however, is a limited one, and in Chapter 2, it is argued that a more satisfactory paradigm for Adorno's dual aesthetic can be found in Freud's theory of the drives. Whereas the aesthetic of identity can be explained in terms of drive that is distorted or diverted by repression, repetition compulsion, fetishism, narcissism, masochism, aggression, cathexis on past objects (archaic attachments), and a consequent generalised ego weakness, the aesthetic of negativity relies on a specific variety of sublimation that Adorno terms “spiritualisation,” whereby the energy of the libidinal drive that gives rise to the artistic impulse is preserved. Chapter 3 examines the ways in which Adorno's dual aesthetic manifests itself in artistic and cultural phenomena. After demonstrating the parallels between Marcuse's affirmative culture, with its principal category of repressive desublimation, and Adorno's identitarian culture industry, with its principal category of false pleasure, the study concludes with an analysis of how Adorno's aesthetic of negativity is instantiated in the authentic artworks of European Modernism, particularly those of Kafka.
Data spatial aggregation issues in public health analysis case study for the Toronto's inner city

This study examines the impacts of spatial aggregations of data on the outcomes of univariate and bivariate statistical analyses in an epidemiological context. Health and socioeconomic variables are used to examine a changing interdependency between these two elements at various levels of spatial aggregation. In order to complete these tasks a series of spatial data aggregations (scaling) and regroupings (zoning) are conducted and selected standard statistics are calculated at each of these levels. This study evaluates also the appropriateness of the use of standard statistical units in the settings of public health studies. An overview of selected contemporary issues in spatial statistics and epidemiology precedes the case analysis. The findings of this study reveal that spatial aggregation and rezoning of health and SES data have a substantial influence on the results of statistical analyses. Standard spatial units show less desirable characteristics for the study of the impacts of an income variable on the rates of avoidable hospitalizations than the custom units constructed in this study. These alternative spatial units are proposed as more informative than the standard ones based on comparative statistical outcomes for the area of Toronto's inner city at the neighbourhood level.
Twenty-four hour activity budget and scent-marking behaviours of captive margays (Leopardus wiedii) in naturalistic enclosures, Belize

I present the first study of the twenty-four hour activity budget and scent-marking repertoire of margay. My results indicate that the sexes had remarkably similar activity budgets with the following exceptions: males (i) spent considerably more time roaming and (ii) sprayed more frequently than females, which fits the observation that males have larger territories than females. Females tended to spray on broad-leafed plants while males preferred thin vertical branches, indicating that margays may be able to selectively search for information depending upon the substrate. Two semi-novel behaviours are described: caching (previously not observed in tropical felids) and sliding (function unknown). I also show that a scent-based lure that has been used to attract the sister group to margay, ocelots, to census stations does not work well with margay. I conclude with recommendations for ways to improve non-invasive censusing techniques for margay based on the results of my research.