Doctoral Theses (2009 - )

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The Role of Innate Immunity in the Pathogenesis and Treatment of Experimental Pulmonary Hypertension
(2006-06) Ormiston, Mark Leonard ; Courtman, David ; Stewart, Duncan John ; Biomedical Engineering
In this thesis, the monocrotaline (MCT)-induced rat model of pulmonary arterial hypertension (PAH) was used to investigate the role of innate immunity in the pathogenesis of PAH and the mode of action of experimental therapies. The first section of this thesis is an investigation of the therapeutic mechanism of human, early and late-outgrowth endothelial progenitor cells (EPCs) in the MCT-induced, nude rat model of PAH. While late-outgrowth EPCs provided no therapeutic benefit in this model, early EPCs (E-EPCs) prevented the elevation of right ventricular systolic pressure (RVSP, P<0.001) and right ventricular (RV) hypertrophy (P<0.01). Ablation of natural killer (NK) and natural killer T cells with anti-asialo GM-1 antiserum (ASGM-1) enhanced human cell retention in the lung but abrogated the therapeutic capacity of E-EPCs. In vitro studies demonstrated that E-EPCs are similar to monocyte-derived regulatory dendritic cells (DCs) and possess the capacity to stimulate both autologous and rat NK cells in co-culture. Imatinib mesylate has been reported to reverse established PAH both clinically and in the MCT model. Imatinib can also induce NK activation through inhibition of c-kit signaling in DCs, suggesting that imatinib and the DC-like E-EPCs may prevent PAH through a similar, NK-mediated mechanism. In the second section of this thesis, imatinib prevented MCT-induced increases in RVSP (P<0.001) and RV hypertrophy (P<0.01) in immunocompetent Fisher 344 rats, but not in nude rats or Fisher rats following ablation of NK cells and T lymphocytes with ASGM-1. These data suggest that the stimulation of NK activity by imatinib is insufficient to prevent disease in the absence of T lymphocytes. Hyaluronan (HA) fragments are a potent inflammatory stimulus, capable of inducing macrophage activation and DC maturation. In the third section of this thesis, HA synthesis and degradation were investigated in the MCT model of PAH. While the early stages of disease were characterized by enhanced hyaluronidase-1 activity and a loss of high molecular weight (HMW) HA, severe disease was associated with HMW HA synthesis and HA accumulation in the lungs. The early degradation of HMW HA may drive inflammation and stimulate pathological vascular remodeling in PAH.
Structure/Function Studies of the High Affinity Na+/Glucose Cotransporter (SGLT1)
(2006-06) Liu, Tiemin ; Silverman, Mel ; Medical Science
The high affinity sodium/glucose cotransporter (SGLT1) couples transport of Na+ and glucose. Investigation of the structure/function relationships of the sodium/glucose transporter (SGLT1) is crucial to understanding co-transporter mechanism. In the first project, we used cysteine-scanning mutagenesis and chemical modification by methanethiosulphonate (MTS) derivatives to test whether predicted TM IV participates in sugar binding. Charged and polar residues and glucose/galactose malabsorption (GGM) missense mutations in TM IV were replaced with cysteine. Mutants exhibited sufficient expression to be studied in detail using the two-electrode voltage-clamp method in Xenopus laevis oocytes and COS-7 cells. The results from mutants T156C and K157C suggest that TM IV participates in sugar interaction with SGLT1. This work has been published in Am J Physiol Cell Physiol 295 (1), C64-72, 2008. The crystal structure of Vibrio parahaemolyticus SGLT (vSGLT) was recently published (1) and showed discrepancy with the predicted topology of mammalian SGLT1 in the region surrounding transmembrane segments IV-V. Therefore, in the second project, we investigated the topology in this region, thirty-eight residues from I143 to A180 in the N-terminal half of rabbit SGLT1 were individually replaced with cysteine and then expressed in COS-7 cells or Xenopus laevis oocytes. Based on the results from biotinylation of mutants in intact COS-7 cells, MTSES accessibility of cysteine mutants expressed in COS-7 cells, effect of substrate on the accessibility of mutant T156C in TM IV expressed in COS-7 cells, and characterization of cysteine mutants in TM V expressed in Xenopus laevis oocytes, we suggest that the region including residues 143-180 forms part of the Na+- and sugar substrate-binding cavity. Our results also suggest that TM IV of mammalian SGLT1 extends from residue 143-171 and support the crystal structure of vSGLT. This work has been published in Biochem Biophys Res Commun 378 (1), 133-138, 2009 Previous studies established that mutant Q457C human SGLT1 retains full activity, and sugar translocation is abolished in mutant Q457R or in mutant Q457C following reaction with methanethiosulfonate derivatives, but Na+ and sugar binding remain intact. Therefore, in the third project, we explored the mechanism by which modulation of Q457 abolishes transport, Q457C and Q457R of rabbit SGLT1 expressed in Xenopus laevis oocytes were studied using chemical modification, the two-electrode voltage-clamp technique and computer model simulations. Our results suggest that glutamine 457, in addition to being involved in sugar binding, is a residue that is sensitive to conformational changes of the carrier. This work has been published in Biophysical Journal 96 (2), 748-760, 2009. Taken together our study along with previous biochemical characterization of SGLT1 and crystal structure of vSGLT, we propose a limited structural model that attempts to bring together the functions of substrate binding (Na+ and sugar), coupling, and translocation. We propose that both Na+ and sugar enter a hydrophilic cavity formed by multiple transmembrane helices from both N-terminal half of SGLT1 and C-terminal half of SGLT1, analogous to all of the known crystal structures of ion-coupled transporters (the Na+/leucine transporter, Na+/aspartate transporter and lactose permease). The functionally important residues in SGLT1 (T156 and K157 in TM 4, D454 and Q457 in TM 11) are close to sugar binding sites.
The Impossible Tempest: Giorgio Strehler or the Director as Interpreter
(2006-06) Colli, Gian Giacomo ; Astington, John H. ; Drama
During his fifty-year career, the Italian director Giorgio Strehler (1921-1997) staged more plays by Shakespeare than by any other playwright, but only a few of his most recent and successful Shakespearean productions have received international critical attention, and The Tempest he directed in 1978 is among them. Thirty years before however, in 1948, he directed a first, completely different production of the same text. Starting from the theoretical assumption that a theatre performance, as object, exists only in the moment in which it is actually produced, that is, in its reception by the audience, this dissertation has a twofold purpose: to explore the different contexts in which the two productions directed by Strehler were staged, and to underline how, from the beginning of his career he developed a crucial attention for interpretative techniques culminating in the 1978 Tempest. Aside from being based on the same text and from being produced by the same ensemble, the Piccolo Teatro of Milan, though with two radically different acting and technical troupes, the two productions of The Tempest directed by Strehler enlighten the variety of dynamics – from historical, political, and cultural, to more specifically theatrical, technical, and dramaturgical – which interacted within him while he was working at the staging of the play, and emphasizes the centrality of the director in contemporary theatre. Finally, this dissertation examines how the pragmatic process of rehearsal might modify the director's theoretical approach to a text, and shows how the study of a performance consists not just in the quest for its meaning, but in the investigation of how the text is brought to the stage, to that coalescent point that, in order to materialize, demands active participation and involvement from both interpreters and spectators.
The Identification and Characterization of New Small Molecule Probes of Cell Expansion and Cytokinesis
(2006-06) Alfred, Simon ; Cutler, Sean ; Cell and Systems Biology
Plant form and structure is remarkably diverse encompassing a myriad of shapes and sizes, and is a result of coordinated instances of cell growth and division. This varied form and structure represents adaptive strategies enabling plants to exploit and endure their environment maximizing fitness. Common to both cell growth and division processes, is the requirement of growth material and effectors via the secretory system. The secretory system is a dynamic pathway of organelles connected via vesicular traffic, responsible for protein modification and delivery. Challenges in studying secretion are related to its' dynamic flow between organelles, and the prevalence of redundancy and lethality, which cause difficulties in interpretation and genetic modulation. To further our understanding of the secretory process, we employed a chemical genetic approach to identify small molecule probes of secretion by first screening for inhibitors of cell expansion, followed by a microscopy based screen of GFP marker lines for perturbagens of subcellular structures. Small molecules offer the advantages of temporal and spatial application, have been shown to overcome redundancy and can be varied in concentration to control the severity of effects. We identified twenty-five small molecule probes of secretion and pursued two chemicals with striking properties, polarazine and eroonazole. Polarazine was identified as a cell division inhibitor, affecting phragmoplast structure and function, while eroonazole remodels the endoplasmic reticulum into small vesicles and is implicated in auxin signaling. This approach shows the utility of small molecule probes in furthering our understanding of secretory processes.
Boredom Escapes Us: A Cultural Collage in Eleven Storeys
(2006-06) Kenny, Lesley ; Bodemann, Y. Michal ; Sociology
Few sociologists have addressed the concept of boredom despite interest in the subject and experience of boredom from psychology, philosophy, the arts and popular culture. Classical sociological concepts of alienation, anomie and disenchantment are related to boredom, but do not address it directly. The history of the word boredom itself is not clear, though it appears it was first used in the late 19th century. Most authors agree that an increase in individualism and the concomitant rise in secularization, combined with industrial changes in labour and increased bureaucracy, help to explain a perceived increase in the experience of boredom. This dissertation is a phenomenological exploration of boredom, informed by the writings of Martin Heidegger and Walter Benjamin on the subject. Inspired by Benjamin’s method of literary montage, from his monumental Passagenwerk, I construct a cultural collage of the subject of boredom. I use the metaphor of storeys (the levels of a building) as an organizing device to construct the empirical work of this project. These storeys include a consideration and analysis of: billboards, internet advertising, the reflections of an overseas development worker, art installations, a poem, a greeting card, a play, song lyrics and Kafka’s short story character, the hunger artist. Each storey serves to inspire a sociological meditation on the subject of boredom, all of which are grounded in the historical, social and philosophical reviews in the first four chapters. These extensive reviews, as well as the eleven storeys, contribute a preliminary sociological analysis of the ambiguous yet ubiquitous experience of boredom in modernity.
"The kind of people Canada wants": Canada and the Displaced Persons, 1943-1953
(2006-06) Gilmour, Julie Frances ; Bothwell, Robert ; History
In 1947 the federal government of Canada began a program to move European Displaced Persons (DP) out of the International Refugee Organization (IRO) camps in Germany and Austria. This program, designed to fill chronic labour shortages in Canada’s resource industries and contribute to a solution for Europe’s refugee crisis, occurred in a transitional moment in Canadian society. Canadians emerged from World War Two with a new sense of Canada’s role in the world, but despite a changed international climate, a new discourse of human rights and a potentially robust economy, old perceptions of race, immigration and economic management lingered in the postwar years complicating the work of a new generation of civil servants, politicians and industry operators. This is a history of the transition. It demonstrates the ways that old and new ideas of the nation, citizenship, race and immigration co-existed. It highlights the significance of the beginnings of a debate on the elimination of discrimination based on race in Canada’s immigration policy; shows the link between economic prosperity and popular support for immigration; and demonstrates the importance of individuals within industry, the civil service and in government in national decision-making. This is an international history, spanning the Atlantic and bringing a global perspective to local experience in Canadian industries. Chapters on the federal decision making process are supplemented by evidence from the United Nations Relief and Rehabilitation Administration (UNRRA), the IRO, the Ontario Ministry of Education and forestry, mining and hydro industries. It uses a variety of methodologies including policy history, oral history, public opinion polling, gender, ethnicity and labour studies to investigate the implications of these decisions for Canadian society. It demonstrates that the 1947-1951 movement of DPs was initiated primarily under dual pressure from Canadians who had served abroad and industry leaders who had previously used POW labour to solve on going shortages in the bush. These decisions were strongly informed by both the crisis in Europe and Canadian assumptions about race, labour and citizenship. By examining the expectations Canadians had for the behaviour of its newest arrivals and future citizens this study highlights the foundations of Canadian citizenship in 1947: community participation, contribution to the development of the economy, and political loyalty to the nation.
Weak Gravitational Lensing Uncertainties
(2006-06) Lu, Tingting ; Pen, Ue-Li ; Astronomy and Astrophysics
Dark matter dominates the mass distribution of the universe, and dark energy determines its expansion. The two are the most mysterious and attractive subjects in modern cosmology, because they provide an opportunity to discover new fundamental physics. Cosmological weak gravitational lensing, which describes the deflection of photons by the gravitational force from large-scale structure in the universe, has been an active area of research in the past decade with many completed, ongoing, and upcoming surveys. Because weak lensing is sensitive to the growth of structure and expansion history of the universe, it is a great tool for improving our understanding of both dark matter and dark energy problems. Cosmic structures have become non-linear by gravitational clustering. The non-linear structures are important to weak lensing, and cause non-Gaussianity in the lensing maps. In this thesis, I study the influence of non-linearity and non-Gaussianity on the uncertainty of lensing measurements. I develop a new method to robustly measure the co-variance matrix of the lensing convergence power spectrum, from simulations. Because 21-cm intensity map may soon cover half sky at redshift 1-4, I build optimal estimators for reconstructing lensing from the 21-cm sources. I develop Gaussian optimal estimators which can be derived analytically, and non-Gaussian optimal estimators which can be constructed numerically from simulation data. I then run a large number of N-body simulations. For both lenses and 21-cm sources, I explore the statistical uncertainties in the simulation data. We show that the non-Gaussianity nature of lensing decreases the dark energy figure of merit by a factor of 1.3 to 1.6 for a few future surveys. We also find that the non-Gaussianity nature of the 21-cm sources reduces the signal to noise ratio by several orders of magnitude. The reconstruction noise saturates at mildly non-linear scales, where the linear power spectrum of the source is Δ2 ∼ 0.2 – 0.5. For 21-cm sources at z ∼ 2 – 4, the lensing reconstruction is limited by cosmic variance at ℓ [special characters omitted] 100, which is in the linear regime of gravitational growth, and robustly predicted by theory. This allows promising constraints to various modified gravity and dark energy models.
"The Amusement World": Theatre as Social Practice in Eighteen-Nineties Toronto
(2006-06) Gardiner, Jessica ; Plant, Richard ; Drama
This thesis places a selection of performances that took place in Toronto’s commercial theatres during the eighteen nineties in their historical context in order to consider determinants of meaning that influenced the social practice in one Canadian city - Toronto. These performances are selected to explore a range of performance activity across the decade and include: the debut performance by Canadian violinist Nora Clench at the Academy of Music in 1889; a fund-raising amateur “entertainment” The Marriage Dramas, performed for local adolescents at the Grand Opera House in 1892; The Second Mrs. Tanqueray, an example of the touring legitimate drama, performed by veteran acting couple the Kendals in 1894; another touring performance , in this instance a popular- theatre favorite, True Irish Hearts, by Dan McCarthy at the Toronto Opera House in 1893 and a rare example of Canadian playwriting from the decade, a performance of Catherine Nina Merritt’s United Empire Loyalist history play When George the Third was King in 1897. The analysis of all performances in this dissertation considers a range of determinants of meaning that Toronto audiences may have drawn upon when viewing a given performance and argues that the following constraints not only influenced the construction of a situated identity in Toronto but also suppressed domestic professional theatre production: a) a system of patronage that stigmatized the professional commercial theatre as frivolous or decadent; b) a utilitarian bias that was at odds with the post-materialist sensibilities of newer and more innovative forms of the late nineteenth-century drama; c) an economic and business practice that centralized production outside of the country to assure profit; and perhaps most significantly: d) a cultural hegemony that deemed Canadian drama to be immature and thus deterred works of aesthetic expression. This thesis is further informed by an understanding that history is written under the influence of the author’s own situated set of determinants and its goal in conducting an associative reading of Toronto’s nineties theatre practice is to locate theatre and performance history as part of a struggle among social, economic, cultural and political hierarchies.
Investigation into the Role of CBL-B in Leukemogenesis and Migration
(2006-06) Badger-Brown, Karla Michelle ; Barber, Dwayne ; Medical Biophysics
CBL proteins are E3 ubiquitin ligases and adaptor proteins. The mammalian homologs – CBL, CBL-B and CBL-3 show broad tissue expression; accordingly, the CBL proteins play roles in multiple cell types. We have investigated the function of the CBL-B protein in hematopoietic cells and fibroblasts. The causative agent of chronic myeloid leukemia (CML) is BCR-ABL. This oncogenic fusion down-modulates CBL-B protein levels, suggesting that CBL-B regulates either the development or progression of CML. To assess the involvement of CBL-B in CML, bone marrow transduction and transplantation (BMT) studies were performed. Recipients of BCR-ABL-infected CBL-B(-/-) cells succumbed to a CML-like myeloproliferative disease with a longer latency than the wild-type recipients. Peripheral blood white blood cell numbers were reduced, as were splenic weights. Yet despite the reduced leukemic burden, granulocyte numbers were amplified throughout the animals. As well, CBLB(-/-) bone marrow (BM) cells possessed defective BM homing capabilities. From these results we concluded that CBL-B negatively regulates granulopoiesis and that prolonged latency in our CBL-B(-/-) BMT animals was a function of perturbed homing.To develop an in vitro model to study CBL-B function we established mouse embryonic fibroblasts (MEFs) deficient in CBL-B expression. Transduction of the wild-type and CBL-B-deficient MEFs with BCR-ABL did not confer transformation; nevertheless, the role of CBL-B in fibroblasts was evaluated. The CBL-B(-/-) MEFs showed enhanced chemotactic migration toward serum in both Transwell migration and time-lapse video microscopy studies. The biochemical response to serum was extensively evaluated leading to the development of a model. We predict that CBL-B deficiency either: (a) augments GRB2-associated binding protein 2 (GAB2) phosphorylation leading to enhanced extracellular signal-regulated kinase (ERK) and protein kinase B (PKB / Akt) signaling, or (b) alleviates negative control of Vav3 resulting in stimulation of Rho effectors. In either case, our results reveal a negative regulatory role for CBL-B in fibroblast migration. The two studies detailed herein expand our knowledge of CBL-B function. They strongly suggest that CBL-B can modulate granulocyte proliferation and point toward a role for CBL-B in the motility of numerous cell types.
Derivation and Characterization of Bone Cells from Human Umbilical Cord Blood and Harakiri Deficient Mice
(2006-06) Sukhu, Balram ; Casper, Robert ; Dentistry
There is a growing need for bone cells to be used in the generation and repair of bone tissues that have become destroyed as a result of disease (e.g. osteoporosis), injuries and genetic deficiencies. Human umbilical cord blood has been a source of cells that is being investigated for its ability to generate cells for repair of various tissues including bone, which is the focus of this investigation. Similarly cord blood can also be used as a source of progenitors for osteoclasts that might be used for management of other diseases of bone characterized by defects in these cells (e.g. osteopetrosis). Moreover, there are few reliable in vitro models for human osteoclasts and so the ability to develop a cell model for human osteoclasts will also permit more meaningful studies on regulation of these cells than possible in the past. One of the setbacks suffered by researchers in designing therapeutic uses for stem cells is that in laboratory animals tumours can arise from these transplanted and pleuripotential cells. This suggests that stem cells might also have a dysregulated apoptosis pathway, which is critically important to understand before the safe use of stem cells can be assured. In order to increase our understanding of apoptosis in bone cells in particular, studies were done to try to understand the role of harakiri, a pro-apoptotic gene, in the development of osteoblasts and osteoclasts. Therefore, this series of study had two main foci; the development of human bone cells, particularly osteoclasts and osteoblasts, from human umbilical cord blood, and to understand further the mechanisms regulating apoptosis in bone cells. This study showed that osteoblasts could not be derived easily from human cord blood cells while it was possible to generate fully functional osteoclasts, which demonstrated unique properties. Studies done on harakiri deficient mice showed that absence of this gene caused an increase in osteoblast formation and a decrease in osteoclast formation. These findings can be exploited when considering the development of pharmacological agents that might be used in the future to modulate osteoclast cell development, function, and apoptosis.
DIispersion of Cellulose Nanofibers in Biopolymer Based Nanocomposites
(2007-11) Wang, Bei ; Sain, Mohini ; Forestry
The focus of this work was to understand the fundamental dispersion mechanism of cellulose based nanofibers in bionanocomposites. The cellulose nanofibers were extracted from soybean pod and hemp fibers by chemo-mechanical treatments. These are bundles of cellulose nanofibers with a diameter ranging between 50 to 100 nm and lengths of thousands of nanometers which results in very high aspect ratio. In combination with a suitable matrix polymer, cellulose nanofiber networks show considerable potential as an effective reinforcement for high quality specialty applications of bio-based nanocomposites. Cellulose fibrils have a high density of –OH groups on the surface, which have a tendency to form hydrogen bonds with adjacent fibrils, reducing interaction with the surrounding matrix. The use of nanofibers has been mostly restricted to water soluble polymers. This thesis is focused on synthesizing the nanocomposite using a solid phase matrix polypropylene (PP) or polyethylene (PE) by hot compression and poly (vinyl alcohol) (PVA) in an aqueous phase by film casting. The mechanical properties of nanofiber reinforced PVA film demonstrated a 4-5 fold increase in tensile strength, as compared to the untreated fiber-blend-PVA film. It is necessary to reduce the entanglement of the fibrils and improve their dispersion in the matrix by surface modification of fibers without deteriorating their reinforcing capability. Inverse gas chromatography (IGC) was used to explore how various surface treatments would change the dispersion component of surface energy and acid-base character of cellulose nanofibers and the effect of the incorporation of these modified nanofibers into a biopolymer matrix on the properties of their nano-composites. Poly (lactic acid) (PLA) and polyhydroxybutyrate (PHB) based nanocomposites using cellulose nanofibers were prepared by extrusion, injection molding and hot compression. The IGC results indicated that styrene maleic anhydride coated and ethylene-acrylic acid coated fibers improved their potential to interact with both acidic and basic resins. From transmission electron micrograph, it was shown that the nanofibers were partially dispersed in the polymer matrix. The mechanical properties of the nanocomposites were lower than those predicted by theoretical calculations for both nanofiber reinforced biopolymers.
Sadomasochism Once Removed: S/m in the Socio-legal Imaginary
(2007-11) Khan, Ummni ; Cossman, Brenda ; Law
This dissertation considers sadomasochism (s/m) as an object of knowledge that incites multiple and interpenetrative discourses. I deconstruct psychiatric, feminist, and cinematic articulations of s/m, and consider the ways in which these narratives interact with each other and influence the legal regulation of s/m. My analysis is framed by Foucault’s account in the History of Sexuality, which helps to bring s/m into focus as a discursive product that emerges out of a “knowledge-power-pleasure” regime. Viewed in this light, I argue that when the scientific, feminist, cinematic and legal actors flex their power in producing truth-claims about s/m, this does not shut down pleasure, but proliferates it. To further interrogate the discursive underpinnings that uphold these truth-claims, I draw upon theories of abjection, disgust and expulsion. Part I traces the construction of s/m within the scientific realm, from the early pioneers in sexology, to the recent academic literature that challenges the pathologization of s/m in the Diagnostic and Statistical Manual of Mental Disorders. Part II surveys the “sex wars” in the eighties and nineties, where the issue of s/m (along with other sex-related issues) violently ruptured feminist communities. In Part III, I analyze the cinematic representation of s/m in popular culture, arguing that while the prevailing tone is pejorative, the narratives nonetheless betray a desire for s/m sexuality and its imagined forbidden pleasures. Part IV reviews the legal treatment of s/m pornography in Canada, which until recently has invariably found s/m imagery to be violent, degrading and/or dehumanizing, conspicuously reflecting the anti-s/m feminist perspective. Part V examines the legal treatment of s/m practice in Canada, in which the pathologizing gaze of psychiatry gets replicated. I argue that the law, rather than being a haven of rationality and coherence in its consideration of s/m, has reflected certain essentialist notions of sexuality produced in the non-legal cultural arena. In conclusion, I posit that the reification of s/m in the socio-legal imaginary allows for multiple entries of epistemic resistance. Attempts to foreclose s/m from the realm of acceptable sexuality have ironically offered sadomasochists frameworks for asserting their own subjectivity and membership in the community.
The Cuckold, His Wife, and Her Lover: A Study of Infidelity in the Cent nouvelles nouvelles, the Decameron, and the Libro de buen amor
(2007-11) Bialystok, Sandra ; Ross, Jill ; Comparative Literature
This dissertation compares representations of women in erotic triangles. I contend that despite the stability implied by the triangular shape, the erotic triangle can be made unstable through women’s language. The first chapter examines medieval and contemporary writing on an essential relationship in the triangle: the friendship between the husband and the lover. Amicitia, chaste friendships between men, had its roots in Greek and Latin philosophy, and recently these relationships have been investigated according to mimetic desire (Girard) or homosocial desire (Sedgwick). In both medieval and modern configurations, these relationships are usually predicated upon the exchange of women. Claude Lévi-Strauss, Gayle Rubin and Luce Irigaray provide anthropological and literary explorations of the economic model where men exchange women to strengthen their homosocial bond. In the three texts, women use linguistic techniques to destabilize the erotic triangle. One is irony: frequently, one character does not understand an ironic statement and is excluded from the relationship between the other two participants. A second is pragmatic implicature, which is also used for exclusionary purposes. Other women adopt economic terminology to negotiate with their husbands or lovers for control of their bodies. Through these linguistic devices women speak exclusively to another member of the triangle, thereby undermining male friendships and denying their bodies be used as objects of exchange. Although their strategies are not always successful and some women remain exchangeable objects, we nevertheless see that erotic triangles can be destabilized. Furthermore, counter to the prevailing anthropological theory, certain women are aware of their position as commodities. From this insight, a new perspective on sexuality is exposed. The formerly strong male relationship, built on classical ideals and predicated on equality, breaks down when one man’s virility is pitted against his rival’s. Sometimes even, the supposedly chaste male relationship reveals erotic undertones. Women’s sexuality is also transformed when certain women prove to be desiring subjects, able to manipulate the system of exchange. In the end, institutionalized notions of chaste male friendships and women as objects of exchange are disrupted, sometimes even undermined, by capable women who determine who should have access to their bodies.
Visual Discrimination of Speed-accuracy Tradeoffs
(2007-11) Young, Scott Jason ; Chau, Tom ; Pratt, Jay ; Biomedical Engineering
Although research has highlighted the importance of decisions when learning and performing motor actions, few studies have focused on individuals’ ability to choose between potential motor actions. To help bridge this gap, this thesis presents a series of studies that investigate the behaviour of able-bodied individuals when attempting to choose movements based on a speed-accuracy tradeoff. In the first study, a two-alternative forced-choice task was used to determine whether people are consistent with Fitts’s law when choosing the movement they perceive to require the least movement duration. Participants performed almost perfectly when clear visual cues were available—when one of the targets was closer, wider, or both. Contrary to Fitts’s law, however, participants showed a preference for closer targets when visual cues were not informative—when one of the targets was closer and narrower. This study demonstrates that motor decisions are not always optimal, especially when participants are naïve at the task. To determine the basis of individuals’ preference for closer targets, a pair of studies explored the relation between motor decisions, imagined movements, and visual perception. Participants showed a similar deviation from Fitts’s law when imagining movements—believing that movement duration increased with distance within the same index of difficulty. Participants did not behave similarly, however, in a perceptual version of the decision task. These results suggest that imagined movements and motor decisions are linked, but they are not always based on veridical representations of actual movement. To further probe the origin of individuals’ erroneous belief about movement duration, the final study of this thesis measured movement duration for movements made at speeds other than ‘as fast as possible’. Movements made at more natural movement speeds shared important similarities with decisions and imagined movements. This study suggests that the biases seen in naïve motor decisions might originate from participants considering movements for which they have more experience, such as target-directed movements made at a naturally-selected pace. Together, the findings presented in this thesis may help to identify the ways that motor decisions can deviate from optimal, suggesting how those decisions must change with practice to better accomplish a task.
Measuring and Navigating the Gap Between FPGAs and ASICs
(2007-11) Kuon, Ian ; Rose, Jonathan S. ; Electrical and Computer Engineering
Field-programmable gate arrays (FPGAs) have enjoyed increasing use due to their low non-recurring engineering (NRE) costs and their straightforward implementation process. However, it is recognized that they have higher per unit costs, poorer performance and increased power consumption compared to custom alternatives, such as application specific integrated circuits (ASICs). This thesis investigates the extent of this gap and it examines the trade-offs that can be made to narrow it. The gap between 90 nm FPGAs and ASICs was measured for many benchmark circuits. For circuits that only make use of general-purpose combinational logic and flipflops, the FPGA-based implementation requires 35 times more area on average than an equivalent ASIC. Modern FPGAs also contain "hard" specific-purpose circuits such as multipliers and memories and these blocks are found to narrow the average gap to 18 for our benchmarks or, potentially, as low as 4.7 when the hard blocks are heavily used. The FPGA was found to be on average between 3.4 and 4.6 times slower than an ASIC and this gap was not influenced significantly by hard memories and multipliers. The dynamic power consumption is approximately 14 times greater on average on the FPGA than on the ASIC but hard blocks showed promise for reducing this gap. This is one of the most comprehensive analyses of the gap performed to date. The thesis then focuses on exploring the area and delay trade-offs possible through architecture, circuit structure and transistor sizing. These trade-offs can be used to selectively narrow the FPGA to ASIC gap but past explorations have been limited in their scope as transistor sizing was typically performed manually. To address this issue, an automated transistor sizing tool for FPGAs was developed. For a range of FPGA architectures, this tool can produce designs optimized for various design objectives and the quality of these designs is comparable to past manual designs. With this tool, the trade-off possibilities of varying both architecture and transistor-sizing were explored and it was found that there is a wide range of useful trade-offs between area and delay. This range of 2.1 X in delay and 2.0 X in area is larger than was observed in past pure architecture studies. It was found that lookup table (LUT) size was the most useful architectural parameter for enabling these trade-offs.
The Material Culture of Women's Accessories: Middle-class Performance, Race Formation and Feminine Display, 1830-1920
(2007-11) Beaujot, Ariel ; Loeb, Lori ; History
This dissertation investigates the cultural meaning ascribed to feminine fashionable objects such as gloves, fans, parasols and vanity sets. I pay particular attention to issues of middle-class formation, the performance of gender, and the materiality of race, empire and colonialism. While these issues lie at the heart of British historiography, this project is written from a unique perspective which privileges cultural artifacts through material culture analysis. While the emergence of the middle class is typically studied as a masculine/public phenomenon, this project corrects the overemphasis on male activity by showing that middle-class women created a distinctive ‘look’ for their class via the consumption of specific goods and through participation in daily beauty rituals. Adding to these ideas, I argue that Victorian women performed a distinct type of femininity represented as passivity, asexuality, innocence, and leisure. By studying the repetitive gestures, poses and consumption practices of middle-class women, I show that certain corporeal acts helped to create Victorian femininity. This work also suggests that women participated in the British colonial project by consuming objects that were represented in the Victorian imagination as imperial spoils. As such, I argue that imperialism penetrated the everyday lives of Britons through several everyday objects. Empire building also created anxieties surrounding questions of race. Women’s accessories, such as gloves and parasols, helped British women to maintain their whiteness, an important way of distinguishing the ‘civilized’ Britons from the ‘uncivilized’ tanned colonial peoples. Overall this project showed that within the everyday objects consumed by women we can identify the anxieties, hopes and dreams of Victorians.
Distorted Historical Fictions of the Holocaust, the Chilean Dictatorship, and the Algerian War of Independence
(2007-11) Berdichevsky, Leon Ernesto ; Hutcheon, Linda ; Comparative Literature
The desire and need for historical representation in postmodernism are coupled with the self-reflexive acknowledgement of our inability to faithfully represent the past. This dissertation examines the ways in which certain historical events are represented in postmodern fiction. More specifically, it introduces the term ‘distortion’ to designate various ways that postmodern authors have attempted to convey traumatic and violent histories through intentional permutations of historical facts. In this study, I analyse six texts, representative works that present the multi-faceted nature of what I call ‘distorted’ historical fiction. Each text is devoted to one of three historical events: the Holocaust in Martin Amis’s Time’s Arrow and Art Spiegelman’s Maus; the Chilean dictatorship in Diamela Eltit’s Lumpérica and Isabel Allende’s La Casa de los espíritus; and finally, the Algerian War of Independence in Kateb Yacine’s Nedjma and Mohammed Dib’s Qui se souvient de la mer. The analyses of each text are guided by three main questions: How is the depicted history distorted in the narrative? Why is the historical reality distorted? And lastly, what are the hermeneutical effects for the reader of engaging with the distorted historical text? I contend that these historical fictions apply various modes of distortion to create a specific and often peculiar effect on the reader. These include distortions of narrative form and voice, as well as distortions of temporality and space. I argue that the reader’s encounter with distorted historical fiction creates a peculiar hermeneutical effect of ‘defamiliarisation,’ which has affinities with Viktor Shklovsky’s use of the term and Bertolt Brecht’s ‘V-effekt.’ The sense of defamiliarisation creates a conflict in readers, in which their foreknowledge of a past event clashes with the event's distorted depiction. This conflict demands that the reader be responsible, implying that the reader should not be ‘swept away’ by the distorted narrative. Instead the responsible reader is encouraged to interact with the text, apply previous historical knowledge to correct said distortions, and through this interaction gain a greater intimacy with the past.
The Influence of Release Modality on Synaptic Transmission at a Developing Central Synapse
(2008-06) Fedchyshyn, Michael John ; Wang, Lu-Yang ; Physiology
The auditory brainstem is comprised of a number of synapses specialized for the transmission of high-fidelity synaptic signals. Within the first three postnatal weeks, these pathways acquire the ability to process high-frequency signals without compromising timing information. However, little is known regarding developmental adaptations which confer this ability. Situated in the sound localization pathway, the calyx of Held-medial nucleus of the trapezoid body synapse provides an ideal model for investigating such adaptations as both the pre- and postsynaptic neurons are accessible to electrophysiological experimentation. Using this synapse, we have shown herein that the spatial coupling between voltage-gated calcium channels (VGCCs) and synaptic vesicles (SVs) tightens during development. Immature synapses use a loosely-coupled arrangement of many N- and P/Q-type VGCCs (“microdomain” modality) while mature synapses use a tightly-coupled arrangement of fewer P/Q-type VGCCs, to release SVs (“nanodomain” modality). As a consequence of this tightening, synaptic delay (SD) shortens. By fluorescence- and electron microscopy of SVs near active zones, we further identified the filamentous protein septin 5 as a molecular substrate, differentiating the two release modalities, which may act as a spatial barrier separating VGCCs and SVs in immature synapses. Finally, we have demonstrated that changes in release modality affect the nature of short-term plasticity observed at this synapse. Using trains of action potentials as presynaptic voltage-commands, we showed that, downstream of calcium influx, the microdomain modality promotes short-term facilitation in excitatory postsynaptic currents (IEPSC), and calcium-dependent decreases in SD, with these being absent in synapses employing the nanodomain modality. In contrast, we found that as a result of depletion of SVs, short-term depression of IEPSC dominates in synapses using the nanodomain modality, and correlates with calcium-dependent increases in SD. These findings imply that the type of release modality has a significant impact on the strength and timing of synaptic responses. The microdomain modality imparts greater dynamic range in timing and strength, but does so at the cost of efficiency and fidelity, while the nanodomain modality is a key accomplishment consolidating the high-fidelity abilities of this synapse.
Mechanisms of Presynaptic CaV2.2 (N-type) Modulation
(2008-06) Chan, Allen ; Stanley, Elise F. ; Physiology
Neurotransmitter release at presynaptic terminals is a complex process involving calcium ion influx through voltage-gated calcium channels (CaV). In addition to their role as entry points through which calcium influx may occur, CaV are now understood to be fundamental components of a common release-site complex that is highly adapted for modulation. Consistent with this model, I investigated mechanisms of modulating a presynaptic calcium channel, CaV2.2, via a heterotrimeric G-protein pathway. Using the patch-clamp technique, I demonstrated in chick dorsal root ganglion (DRG) neurons that the slow kinetics of G-protein inhibition of CaV2.2 via GTPgammaS were limited by the rate of GDP dissociation from the G-protein nucleotide binding site. In addition, I investigated the role of G-protein regulation of CaV2.2 currents evoked by action potential-like stimuli. Here, I characterized an inhibited current that was advanced in time with respect to uninhibited controls. These currents exhibited a shorter latency to current activation and faster deactivation. These findings may have important physiological ramifications on signal transduction and timing. In addition to G-protein regulation, presynaptic CaV2.2 have been demonstrated to exhibit a resistance to voltage-dependent inactivation (VDI), a property thought to be important in determining channel availability and synaptic excitability. I demonstrated a role for dynamic palmitoylation in conferring resistance to VDI in presynaptic terminals of the chick ciliary ganglion. Using tunicamycin, an inhibitor of palmitoylation, I induced a hyperpolarizing shift in the steady-state-inactivation (SSI) profile of presynaptic CaV2.2. Finally, I examined the role of a CaV interacting protein, Munc18, as a potential regulator of CaV. I probed for alterations in CaV2.2 function in DRG neurons that had been transfected with Munc18 or Munc18 siRNA. Despite the intimate interaction between Munc18 and CaV2.2, no major effects on the fundamental characteristics of CaV2.2 function were observed. However, a hyperpolarizing shift in the inactivation profile of CaV2.2 was determined in DRG neurons in which Munc18 was knocked down. It is not clear if this was a direct consequence of Munc18 perturbation.
Development of a High-throughput Electrokinetically-controlled Heterogeneous Immunoassay Microfluidic Chip
(2008-06) Gao, Yali ; Li, Dongqing ; Sun, Yu ; Mechanical and Industrial Engineering
This thesis was on the development of a high-throughput electrokinetically-controlled heterogeneous immunoassay (EK-IA) microfluidic chip for clinical application. Through a series of experimental studies, a high-throughput EK-IA was developed. This EK-IA was capable of automatically screening multiple analytes from up to 10 samples in parallel, in only 26 min. Flow control in an integrated microfluidic network was realized by numerical simulation of the transport processes. This EK-IA was successfully applied to detect E. coli O157:H7 antibody and H. pylori antibody from human sera with satisfactory accuracy. Simultaneous screening of both antibodies from human sera was also achieved, demonstrating the potential of this EK-IA for efficiently detecting multiple pathogenic infections in clinical settings. Preliminary work on the application of EK-IA to detect biomarkers of embryo development in embryo culture media also yielded good results. In addition to the experimental studies, the reaction kinetics of this microfluidic EK-IA has also been investigated, using both numerical simulation and a modified Damköhler number. Targeted towards a more sensitive assay, the influences of several important parameters on the reaction kinetics were studied. This EK-IA holds great promise for automated and high-throughput immunoassay in clinical environments.

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