title: IN VITRO ANALYSIS OF HUMAN FEMORAL CANCELLOUS BONE AS A VIABLE SOURCE OF OSTEOPROGENITOR CELLS AND THE EFFECTS OF BONE MORPHOGENETIC PROTEIN 2 AND DOXYCYCLINE ON THEIR DIFFERENTIATION INTO BONE FORMING COLONIES

contributor: Medical Sciences, Division of Physiology/Pharmacology

subject:
Medicine and Health Sciences
Pharmacy and Pharmaceutical Sciences
Medicine and Health Sciences

abstract: The purpose of this investigation was 1) to establish an optimal technique for isolating osteoprogenitor cells in vitro using human femoral cancellous bone as a donor site, and 2) to evaluate the effects of various factors on differentiation of osteoprogenitor cultures. Two isolation techniques evaluated were enzyme digestion and primary explant technique. Furthermore, bone morphogenetic protein 2 (BMP-2) and doxycycline were supplemented in a dose dependent manner into various osteoprogenitor cell containing culture dishes. To compare isolation techniques and the effect of supplemented factors, we isolated cell populations from cancellous bone of the femoral neck from 7 and 6 patients, respectively, with osteoarthritis undergoing total hip replacement surgery. Bone derived osteoblasts and their bone nodules were identified using Von Kossa stain. The cell yield of the two isolation techniques was quantified by hemocytometer counts. The ability of the cells to differentiate into bone forming osteoblasts was evaluated by comparing numbers of Von Kossa positive nodule counts. Using alkaline phosphatase (ALP) staining, ALP quantitative assay and osteocalcin polymerase chain reaction, our study is the first attempt to determine the effects of doxycycline, along with the more commonly used BMP-2, on the differentiation of osteoblasts into bone forming colonies.

abstract: Master of Science (MS)


title: Anorexia and inflammation: Food intake studies in a rat model of intestinal inflammation.

contributor:
Collins, S.M.
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract:
This research examines the hypothesis that in rats inflammation of the gastrointestinal tract results in a specific decrease of food intake. A model for examining gastrointestinal inflammation, the trinitrobenzene sulphonic acid model, and its effects on feeding is developed and investigated in the rat. The TNB model results in a predictable and reproducible colonic inflammation that is accompanied by a rapid but transient decrease in food intake. Experiments are presented which: i)investigate if the anorexia is due to nonspecific malaise. ii)investigate, by meal pattern analysis, the profile of food intake displayed by TNB treated animals iii)investigate specifically, which mediators released from the sight of inflammation could be an anorexigenic signal to the central nervous system.

To demonstrate that the anorexia is not due to malaise we have shown that the anorexia: is not specific to the TNB model, is accompanied by no decrease in water intake and develops even when animals are maintained on highly palatable or low residue liquid diets. More importantly animals specifically decrease meal size not meal frequency. Decreased meal size with maintenance of meal frequency is consistent with the generation of abnormal satiety signals and not a "general malaise." These findings show that rats are capable of performing the behaviours necessary for food intake, and do not show specific conditioned taste aversions.

The hypothesis that the generation of abnormal gastric and/or post-gastric satiety signal is responsible for TNB induced anorexia was also investigated. I demonstrated removal of both gastric and post-gastric satiety signals in a sham feeding preparation resulted in normal intake even in otherwise anorexic animals. I also show that animals with TNB induced colonic inflammation, present with a decreased rate of gastric emptying. These data raise the possibility that abnormal satiety signals, generated as a result of decreased gastric emptying result in decreased meal size and an overall anorexia.

Finally, by specifically inhibiting synthesis of leukotrienes and prostaglandins respectively, or by using an interleukin-1 receptor antagonist (rhIL-1ra), I examined the role of these inflammatory mediators in the anorexia seen in the TNB model of colitis in the rat. I demonstrate that inhibition of prostaglandin synthesis and blockage of interleukin-1 receptors particularly in the brain, result in a significant attenuation of the anorexia. I conclude that the full expression of the anorexia observed in TNB treated animals is dependant on the production of prostaglandins and occupation of centrally located interleukin-1 receptors. Thus, here I specifically describe a model suitable for the investigation of the mechanisms of gastrointestinal inflammation induced anorexia and generally a model that may be used to examine how peripherally generated signals can alter behaviour by communication with the central nervous system.

abstract: Doctor of Philosophy (Medical Science)


title: A multi-media bioassay-directed investigation of the hamilton harbour area of western lake ontario

contributor:
McCarry, B.E.
Chemistry

subject: Chemistry Chemistry

abstract:
A methodology for the extraction, clean-up and compound class fractionation of complex environmental mixtures was developed and tested using standard reference materials and sediment from Hamilton Harbour. Samples were extracted using a Soxhlet apparatus or an ultrasonication apparatus and the resulting organic solvent extracts were fractionated into compound classes using an alumina/Sepahadex LH20 clean-up procedure and high performance liquid chromatographic techniques.

In the next phase of the study, sediment samples, sediment trap samples, and air particulate material from the Hamilton Harbour area of western Lake Ontario were fractionated using the developed methodology. These samples were chosen with the aim of evaluating the contributions of a variety of sources to chemical and genotoxic contamination in the harbour. The resulting fractions were analyzed by chromatographic techniques and tested for genotoxicity using Ames Salmonella/microsome assay with TA98-like and TA100-like bacterial strains modified by the inclusion of genes for the activating enzymes nitroreductase and O-acetyltransferase. These data were used to construct chemical and biological profiles of the samples and to identify specific compounds and compound classes responsible for mutagenic activity observed in the sample extracts.

The majority of the mutagenic activity displayed by a Randle Reef sediment sample extract was found to be present in the fraction containing the polycyclic aromatic hydrocarbons (PAH). Extracts of the PAH-containing fraction displayed dramatically higher responses with the TA100-type strains with metabolic activation. The PAH fraction was further fractionated and analysed to identify the compound(s) responsible for the mutagenic activity. The biological activity of this PAH-containing fraction was found to co-elute with compounds of molecular mass 252, 276, 278, and 302 amu.

In contrast to the results obtained from the investigation of the Randle Reef sediment sample, extracts of sediment trap samples displayed significantly higher responses with the TA98-type strains. The compound(s) responsible for this biological activity were contained in the more polar polycyclic aromatic compound (PAC) fractions and did not require oxidative metabolism to manifest their activity. Further separation of the most biologically active fraction from the sediment trap samples revealed that the biological activity was contained in a very narrow elution time range in the reversed-phase high performance liquid chromatography (RP-HPLC) chromatogram. This narrow band of activity was collected and analysed usign gas chromatography-mass spectrometry (GC-MS). While alkyl-benzocarbazole derivatives were identified in these fractions, they were not considered to be the agents responsible for the observed biological activity.

The use of ultrasonic extraction and the alumina/Sephadex LH2- clean-up and normal phase HPLC compound class fractionation procedures were found to be effective for the preparation of a number of complex environmental samples. The chemical and biological profiles of the harbour sediment and suspended sediments indicate that PAH from resuspended coal tar contaminated sediment is a principal contributor to the chemical profile of suspended sediments in the harbour and a significant contributor to the genotoxicity of extracts of these samples. However, the biological profiles of the suspended sediments indicate the presence of additional mutagens other than PAH that are not present in the Randle Reef sediment sample. A comparison of the biological profiles of extracts of suspended sediments and air particulate material indicate that there may be a common mutagenic contaminant in both of these sample matrices.

abstract: Doctor of Philosophy (PhD)


title: Advances in space mapping optimization of microwave circuits

contributor:
Bandler, John W.
Electrical Engineering

subject:
Electrical and Computer Engineering
Electrical and Computer Engineering

abstract: This thesis concerns itself with advances in Space Mapping optimization of microwave circuits and with the developments in Parameter Extraction. Space Mapping (SM) optimization aims at efficiently optimizing microwave circuits using the accurate and time-intensive electromagnetic simulators. Such simulators represent "fine" models of the circuit under consideration. SM exploits the existence of a less accurate but fast "coarse" model, e.g., an empirical model. A mapping is established between the parameter spaces of the coarse and fine models. The fine model design is the inverse mapping of the optimal coarse model design. A crucial step for any SM-based optimization algorithm is Parameter Extraction (PE). In this step a coarse model point that corresponds to a given fine model response is obtained through an optimization process. The nonuniqueness of PE can lead to divergence or oscillation of the optimization iterates. We introduced the Trust Region Aggressive Space Mapping (TRASM) algorithm. This algorithm integrates a trust region methodology with SM optimization. The iterate is confined to a trust region in which the utilized linearization can be trusted. TRASM also exploits a recursive multi-point parameter extraction step to enhance the uniqueness of PE. The Aggressive Parameter Extraction (APE) algorithm addresses the optimal selection of parameter perturbations used to increase trust in PE uniqueness. We establish an appropriate criterion for the generation of these perturbations. The APE algorithm classifies possible solutions for the PE problem. Two different approaches for obtaining subsequent perturbations are utilized based on a classification of the extracted parameters. The algorithm is demonstrated through parameter extraction of microwave filters and transformers. The Hybrid Aggressive Space Mapping (HASM) algorithm addresses the case of a poor coarse model. HASM utilizes SM optimization as long as it is converging. Otherwise, it switches to a direct optimization phase. We developed a relationship that relates the established mapping and the first order derivatives of the coarse and fine models. This relationship is utilized in switching between the SM phase and the direct optimization phase. We also present a Surrogate Model-based Space Mapping (SMSM) optimization algorithm. SMSM integrates two approaches for efficient optimization: SM optimization and surrogate model optimization. It exploits a surrogate model in predicting new iterates. This model is a convex combination between a mapped coarse model and a linearized fine model. The mapped coarse model exploits a frequency-sensitive mapping. During the optimization iterates, the coarse and fine models are simulated at two different sets of frequencies. Utilizing a frequency sensitive mapping is shown to enhance the uniqueness of PE. It also overcomes severe frequency misalignments between the responses of both models.

abstract: Doctor of Philosophy (PhD)


title: Functional Crosslinked Polymer Microspheres

contributor:
Stöver, Harald D.
Chemistry

subject: Chemistry Chemistry

abstract:
Novel procedures for the preparation of highly crosslinked polymer microspheres by single step process have been developed. Poly(divinylbenzene) microspheres with narrow size dispersity have been prepared using dispersion polymerization techniques. Moreover, monodisperse Poly(divinylbenzene) microspheres have been produced by precipitation polymerization with acetonitrile as solvent. The process does not require stabilizers of any type, and produces monodisperse microspheres with diameters between 2 and 8.5 micron depending on the conditions. The stability of microspheres during polymerization is attributed to their rigid, crosslinked surfaces. The mechanisms of particle formation and growth are discussed. This new process has been used to prepare a series of mono-disperse functional and crosslinked microspheres.

In addition, polymer resins containing chiral crown-ether binding sites have been prepared by template (or imprinting) polymerization using chiral ammonium salts. The ability of these resins to separate enantiomers of the original template molecules have been evaluated.

abstract: Doctor of Philosophy (PhD)


title: The Life Writings of Mary Baker McQuesten (1849--1934): Victorian Matriarch of Whitehern

contributor:
Ballstadt, Carl
English Literature

subject:
English Language and Literature
English Language and Literature

abstract: My aim in this research is the recovery and presentation of Mary Baker McQuesten's life writings which will add to the growing body of women's literary, cultural and political history in Hamilton, in Ontario and in Canada. Mary Baker McQuesten (1849-1934) was an exceptional and enlightened women of the Victorian and Edwardian age in Canada, yet she is little known. Her writings reveal the political strength and matriarchal power that were possible for women in Ontario during the extended Victorian era. Although Mary never wrote for publication, she was a prolific and uninhibited letter writer; more than five hundred of her letters are extant, mostly those written to her children. She was also a forceful and impassioned speaker and wrote and delivered many Presbyterian missionary society addresses. Mary's letters record the development of her matriarchal power after she suddenly became a widowed single-parent of six young children, and was forced to raise and educate them in a state of genteel poverty. Her writings give details of the family's financial problems and health concerns, such as inherited mental disease and tuberculosis. I have included extensive annotations to the letters to provide background material for the family's social scene, education, literature, politics, religion and social reform. Mary was a dynamic and determined matriarch in both the domestic sphere and in her public leadership, and she was a keen observer and an outspoken critic of her times. The theoretical section of the thesis offers an approach to the literary aspects of the McQuesten life writings through a review of critical and cultural theory, and provides the precedents that establish personal letter writing and auto\biography within the genre of life writing. The theoretical section also shows how the McQuesten writings are important to cultural and interdisciplinary studies in the Humanities and Social Sciences. The writings are a rich repository of Canadian Victorian ideas and ideals, and they are important cultural artifacts that provide insights into the Victorian family and society during a period of great change in Canada.

abstract: Doctor of Philosophy (PhD)


title: Active site studies of two target enzymes: reverse transcriptase and aspartate transcarbamoylase

subject: Biochemistry Biochemistry

abstract: Two target enzymes for chemotherapy were investigate by probing their active sites with various methods. The reaction catalyzed by Aspartate Transcarbamoylase from Escherichia coli is thought to involve a tetrahedral transition state. Several bisubstrate analogs with a charged tetrahedral moiety were synthesized and tested for inhibition. The results suggest that the enzyme exhibits no preference for a tetrahedral over a trigonal moiety which casts some doubt as to the actual reaction mechanism. The carbamoyl region of the active site of the enzyme was further probed with various anionic inhibitors to investigate the structural basis for the strong inhibition observed with phosphonoformate and carbonyldiphosphonate. A second target enzyme, reverse transcriptase taht is also effectively inhibited by these two anionic compounds was studied. The active site of this enzyme was probed with a variety of anionic ligands to determine the structural features necessary for inhibition. Phosphonoformate prevailed as the most effective inhibitor of three different reverse transcriptases. Combined inhibitor studies with the enzyme from Human Immunodeficiency Virus Type-1 were performed to further investigate the mode of binding of PFA with the active site. Finally, the interaction of the metal chelator ortho-phenanthroline with the enzyme was investigated. A kinetic analysis and protection/inactivation studies were performed to probe the site of metal chelation and its proximity to the binding sites for various active site ligands.

abstract: Doctor of Philosophy (PhD)


title: Interior point least squares estimation

contributor:
Luo, Zhi-Quan (Tom)
Electrical and Computer Engineering

abstract: Adaptive filters are used in linear estimation problems when no a priori knowledge of signal statistics is available or when systems are time varying. They have become a popular signal processing tool and have found application in many diverse areas. The work in recent years has led many to regard the recursive least-squares algorithm (RLS) and its variants as the state of the art. The principal advantage of RLS over the rivalling least mean square algorithm (LMS) is its fast rate of convergence, which in many applications justifies the higher computational complexity of RLS. Mathematically speaking, both RLS and LMS result from the application of particular iterative optimization algorithms to the minimization of the least-squares criterion. The purpose of this thesis is to investigate the applicability of a new class of optimization methods, interior point optimization algorithms, to the adaptive filtering problem. We develop a new recursive algorithm, called Interior Point Least Squares or IPLS, that can be efficiently implemented with a computational cost comparable to (but higher than) RLS. IPLS matches RLS in asymptotic performance, but has a faster transient convergence rate. This is significant because until now "...[RLS'] convergence speed [has been] considered to be optimal in practice, and [thus] a measure for comparison for other algorithms.", (Moustakides, in a paper in the IEEE Transactions on Signal Processing , October 1997). Additional properties of IPLS are its insensitivity to variations in initialization, numerical stability in the presence of limited precision arithmetic, and versatility in that it readily allows the inclusion of additional constraints on the weight vector. Some of the above mentioned properties are further investigated and exploited in applications to adaptive equalization and adaptive beamforming. Numerical simulations are used throughout the thesis to illustrate, confirm, and extend our analytical results.

abstract: Doctor of Philosophy (PhD)


title: Modulating expectations regarding (in)equities in social exchanges: The impact of friendship and kinship ties

contributor:
Wilson, Margo
Daly, Martin
Schmidt, Louis
Psychology

subject: Psychology Psychology

abstract: In a series of five interrelated studies, college students' sensitivities to inequities in their own relationships and in other people's relationships were examined. In the first two studies, I analyzed reactions to feeling underbenefited in different types of personal relationships (i.e., sibling, cousin, close friend and acquaintance). People expressed more concern about being underbenefited by an acquaintance than in the other types of relationships, which did not differ from each other. The second study extended these findings by examining the role of a personality profile (shy but sociable) expected to be particularly sensitive to social threats, including those associated with inequities. As predicted, highly shy/highly sociable participants were particularly concerned about inequities, but in keeping with the first study, these differences were observed only in acquaintance relationships. In the third study, a longitudinal design focused on reactions to inequities in the course of friendship development. Participants were university students who had just moved into a university residence. Their concerns about reciprocation and perceptions of friendship quality were measured at 9 and at 75 days after first meeting their new roommates. It was found that changes in expectations and obligations of reciprocation, rather than a stable "trait" orientation to reciprocation, were particularly informative about the developmental trajectories of perceived friendship quality. In those relationships that progressed from acquaintanceship to close friendships, concern about receiving reciprocation decreased, showing a similar pattern to the data obtained in the first study, comparing acquaintances and friends. In the fourth and fifth studies, participants were cast in the role of observer, reacting to evidence of inequities in others' relationships. Here the experimental variations included genetic relatedness, terms of a monetary transfer from parent to child, and whether the child voluntarily disclosed the terms to siblings later. The results revealed that subjects engaged in 'distributive justice' (taking funds away from those who were overbenefited and redistributing these funds to those who were underbenefited) only when a half-sibling was underbenefited but not when a full sibling was underbenefited. The various studies' findings are discussed within an integrative evolutionary social psychological and personality framework.

abstract: Doctor of Philosophy (PhD)


title: Figures of mind in the poetry of W. B. Yeats and Wallace Stevens

contributor:
John, Brian
English

abstract: This study examines representations of thinking and consciousness in the poetry of W. B. Yeats and Wallace Stevens. This thesis is divided into two sections, "The Noetics of Form" and "The Noetics of Figure". Each section contains two chapters each on the poetry of Yeats and Stevens respectively. In the first section, I argue that the poetry of both Yeats and Stevens imitates a meditative mode of thinking. In Chapter One I explore Yeats's poetry as a dialectical mode of meditation. For Yeats, the process of containment is repeatedly undermined or postponed through an imitation of internal argument. His dialogues imitate an ongoing process of differentiation--a splitting of the objective and the subjective modes of thinking--in a struggle to enact containment through a transcendence or reconciliation of opposing lines of thought. In Chapter Two, I illustrate how Stevens's meditative poetry often imitates a process of thinking which is less determined and more observational than Yeats's. While there is still an implicit split between subjective and objective thought in Stevens' poetry, he more often imitates modes of thinking which recognize the co-dependency of human consciousness and objective reality, resulting in the imagined objective. Section II concerns the Noetics of Figure in the poetry of Yeats and Stevens, examining how their most dominant imagery represents a paradigm of human consciousness. In Chapter Three, I illustrate how Yeats's images suggest transcendence, a movement towards and beyond the margins of consciousness. I ground this discussion in Northrop Frye's view of images of ascent as being connected with an intensifying consciousness. Yeats's figures of mountains, trees, towers, and ladders represent consciousness, while his images of birds represent various forms of thinking within--and in an attempt to transcend--its limits. In Chapter Four, I look at Stevens's images of colour and shape as major noetic figures. These figures represent a movement towards the centre of human consciousness, and a model of consciousness as an ever-expanding container of reality. In my concluding chapter, I look at two late poems from each of the poets in order to illustrate the contrasts and comparisons between these paradigms of human consciousness. (Abstract shortened by UMI.)

abstract: Doctor of Philosophy (PhD)


title: Systems modelling of municipal solid waste collection operations

contributor:
Baetz, Brian W.
Civil Engineering

subject:
Civil Engineering
Civil Engineering

abstract: Curbside collection of municipal solid waste is an expensive and increasingly complex operation. Municipalities across North America have been expanding their waste collection fleets steadily over the past decade due to population growth, the introduction of new collection services such as curbside recycling, and a decline in the number of active landfill sites. Despite the increasing cost and complexity of municipal solid waste collection systems, many collection programs are designed and operated without a clear understanding of the parameters responsible for those costs or the relationships between those parameters. Existing models of municipal waste collection operations often deal only with average system performance, ignoring large variations in important parameters such as the quantity of waste set out for collection or the percentage of households participating in a collection program. This research develops two different analytic models of municipal solid waste collection that explicitly address the variability of municipal solid waste collection operations. The first model is based on probability theory and vehicle dynamics, while the second model is based on queuing theory. Despite different starting assumptions, both models provide similar results and both models agree well with Monte Carlo computer simulation results. Both models are easier to use than computer simulations of the waste collection process, can be applied to any municipal waste collection operation, and can be coded on spreadsheets. The potential utility of the developed models has been demonstrated by application to a number of practical municipal solid waste collection problems. The models are not used to optimize systems of collection vehicles in this research, although they are used to generate improved strategies for the specific problems presented. However, either of the two models could be further incorporated into large scale optimization models for complete waste management systems. The models are of interest primarily to solid waste management practitioners. It is anticipated that they would make use of the models both to design new collection systems and to improve existing collection operations. Application of the models to local design and operational problems should result in more efficient and less costly waste collection operations. Specifically, these models can be used to minimize the size of the collection fleet and the amount of time required to collect municipal solid wastes, resulting in lower capital and operating costs, lower fuel consumption, and reduced air emissions from collection vehicles.

abstract: Doctor of Philosophy (PhD)


title: Houses and Furnishings in Selected Novels by Dickens

contributor:
Petrie, Graham
English

abstract: This thesis is intended to improve our understanding and appreciation of Dickens' novel through an examination of his symbolic use of houses and furnishings. Five novels have been selected -- two from the early writings, one from the middle period, and two from the later fiction -- in order to trace Dickens' development as an artist. The first chapter explores the traditional symbolic associations of the house in general as well as the additional significance that house acquires in the Victorian era. Each succeeding chapter relates these general ideas to the specific novels themselves. The basic tenet of the thesis is that Dickens' symbolic use of houses is not only particularly suited to his imaginative vision of the world but it is also especially appropriate for the thematic concerns of the novels. His focus on houses and furnishings suggests that emphasis on externalities and material commodities that this society fosters. In fact special emphasis is placed on the relationships between social concerns in the fiction and the symbolic use of houses. Dickens frequently uses houses to suggest social forces such as alienation, dehumanization and moral disorder. Throughout the thesis, scholarly research on houses in general and on the intellectual, cultural and social background of Victorian society in addition to critical theories about Dickens' life and writings are used in order to view Dickens' work from a broad perspective.

abstract: Master of Arts (MA)


title: Ingesting Jesus: Eating and drinking in the Gospel of John

contributor:
Reinhartz, Adele
Religious Studies

subject: Religion Religion

abstract: The Gospel of John often uses ingesting language. First, it refers to concrete elements of food and drink (such as bread, water, fish and wine) and the actions of eating and drinking. Second, it uses metaphors of food and drink; for example, Jesus is the "bread of life" and the "source of living water." Third, it uses meals as the setting for much of the narrative. The prevalence of ingesting language in various contexts and genres establishes it as a primary literary motif in the Gospel of John. While the individual passages involving food, drink and ingesting have not gone unnoticed in the history of Johannine scholarship, no major monograph has addressed the motif as a whole nor drawn specific conclusions about its function in the Gospel. Drawing on the literary theory of William Freedman, this study first extends the limits of the ingesting motif to include phrases drawn from the semantic domain of ingestion as well as narrative contexts that have been excluded, for the most part, from previous studies. By extending these limits, this study affirms more emphatically the relationship between eating and drinking and the death of Jesus. In particular, ingesting language provides a way to describe both the role of Jesus as the one who is incarnate as "flesh" but who must die in order that others might eat and live, and the role of the believer who is "to eat and drink Jesus." This study will thus argue that the ingesting motif serves as a vehicle for Johannine soteriology. This conclusion has implications for the extended debate concerning Eucharist traditions in the Johannine literature, for although the Eucharist is not specifically mentioned in the Gospel, the prevalence of the ingesting motif suggests that eating and drinking play a significant role in the Johannine understanding of salvation.

abstract: Doctor of Philosophy (PhD)


title: Modulation of ozone-induced airway hyperresponsiveness by cyclooxygenase and nitric oxide synthase

contributor:
Daniel, Edwin E.
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract: A large number of studies have identified that bronchoconstricting agents have increased potency and effect following inhaled ozone, but the contribution of bronchodilatory mediators to attenuation of the airway hyperresponsiveness observed following inhaled ozone remains unclear. The purpose of this investigation was to identify the contribution of nitric oxide synthase (NOS) and cyclooxygenase (COX) to the regulation of ozone-induced airway hyperresponsiveness. These mediators are derived largely from the airway epithelium and ozone exposure is likely, through epithelial damage, to alter the effect of NOS and COX in the airway. Using an ozone exposed guinea pig model of airway hyperresponsiveness, the in vivo responses to inhaled histamine were compared to responses in sham treated animals. Administration of the NOS inhibitor L-NAME (5120 μg/mL) increased the histamine sensitivity after ozone treatment. The non-selective COX inhibitor indomethacin (10 mg/kg) also increased the histamine sensitivity after ozone treatment. The COX-2 selective inhibitor DFU (1 or 10 mg/kg) caused a 2-fold leftward shift after ozone exposure, similar to that observed with indomethacin. The thromboxane antagonist, SQ 29,548 (1 mg/kg i.p.) attenuated the histamine responsiveness in a time dependent manner. The combination of COX and NOS inhibition produced a histamine-induced airway hyperresponsiveness greater than that observed with either NOS or COX inhibition alone. Pre-administration of dexamethasone inhibited the ozone-induced histamine hyperresponsiveness at all time points. Biochemical measurements of NOS activity identified an increase in NOS enzyme activity following ozone. Bronchoalveolar lavage revealed an inflammatory cell profile that did not correlate to the in vivo airway hyperresponsiveness. In vitro tissue bath experiments identified the presence and biological activity of NOS in the guinea pig trachea. Liquid chromatographic detection of nitric oxide metabolites and Western blot detection of COX-2 and NOS isoforms did not provide reliable data. This thesis demonstrates that histamine airway responsiveness following ozone changes rapidly and that both NOS and COX are upregulated a few hours after ozone exposure and, through functional antagonism, modulate ozone-induced histamine airway hyperresponsiveness.

abstract: Doctor of Philosophy (PhD)


title: Indium gallium arsenic phosphide/gallium arsenide quantum well lasers: Material properties, laser design and fabrication, ultrashort-pulse external-cavity operation

contributor:
Haugen, H.K.
Mascher, P.
Engineering Physics

subject:
Engineering Physics
Engineering Physics

abstract: A detailed characterization of the In1- x Gax Asy P 1-y quaternary material system lattice matched to GaAs, grown by gas source Molecular Beam Epitixy (MBE) has been performed. Photoluminescence, X-ray diffraction and Transmission Electron Microscopy (TEM) were used to study the lateral composition modulation (LCM) which was observed in this material system. Optimization of the growth process and the substrate orientation resulted in a significant reduction of the LCM. Additionally, a comprehensive analysis of the optical constants was performed which resulted in the first publication of wavelength and composition dependent index of refraction data for this material system. The combination of growth optimization and index of refraction data lead to the demonstration of efficient, low threshold operation of InGaAsP/GaAs based multiple quantum well lasers. In order to efficiently couple the above laser diodes to an external cavity to facilitate the generation of ultrashort pulses, antireflection facet coatings were required. As such, optical interference filters have been fabricated using a plasma enhanced chemical vapor deposition system, based on the SiO x Ny material system. High quality antireflection facet coatings, suitable for application to the InGaAsP/GaAs diode lasers have been designed and fabricated, resulting in modal reflectivities of 1-2 × 10-4 . Finally, an ultrashort-pulse external-cavity diode laser system was designed and manufactured which allowed the laser diode to be wavelength tuned and emit mode-locked ultrashort optical pulses. Pulses with sub 2 ps duration and greater than 1 mW average output power have been achieved. A study of the novel application of an asymmetric quantum well structure to the generation of ultrashort optical pulses has been proposed and initiated.

abstract: Doctor of Philosophy (PhD)


title: Liminal Readings: Framing Strategies in Selected Romantics Texts

contributor:
Goellnicht, Donald C.
English

abstract: This thesis explores narrative framing strategies in five Romantic texts: Wordsworth's The Ruined Cottage. Coleridge's Kubla Khan and an episode from Chapter Six of Biographia Literaria, Shelley's Julian and Maddalo, and Keats's The Fall of Hyperion. Using Freud's analysis of "the uncanny" and Alice Jardine's conception of "gynesis" as key elements, the introductory chapter proposes a view of "framing" as a strategy of interpretive and narrative control aligned with culturally masculine ideals of mastery and authority while identifying that which is represented within the frame as manifesting a strange alterity, often coded as feminine, which exceeds the terms established in the framing argument. Within this type of framing structure, Romantic anxieties about the authority of the writing subject play themselves out. The texts by Wordsworth, Coleridge and Shelley studied here exemplify framing as a strategy to control interpretation of a polysemous interior discourse. Keats's text furnishes a counter-example, deploying the apparatus of the interpretive frame only to subvert its conventions. Barthes's distinction between texts of "pleasure" and of "bliss" contributes to an understanding of the contrast between representations of textual closure and textual openness.

abstract: Doctor of Philosophy (PhD)


title: The contribution of mitochondrial function to the energetics of cell cycle progression

contributor:
Singh, Gurmit
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract: Mitochondria play a critical role in the provision of energy to individual cells through the synthesis of ATP. The relationship between mitochondrial energy production and cell cycle progression has been explored in this work with the intention of defining the fuel requirements of the cell cycle engine. Because mitochondrial physiology and cell division proved to be intimately linked, we also examined the feasibility of disrupting mitochondrial properties in order to alter cell cycle dynamics. We show that the rate of utilization of mitochondrially-derived ATP fluctuates throughout the cell cycle and that stages where ATP levels are lowest correspond to stages most sensitive to pharmacologic inhibition of mitochondrial function. These particular transition points comprise theoretical "energetic checkpoints" of cell cycle progression. It is here that the biochemical events that are sensitive to changes in the cellular energy status will determine whether the cell continues through its cycle or pauses until a favourable energetic balance is restored. The increase in the number of cells in the G1 component of the cell cycle that results from antagonizing mitochondrial function is accompanied by an augmented proportion of persistently active Retinoblastoma protein (Rbp). Failure to inactivate this tumour suppressor protein, whose role it is to brake cell cycle progression in response to suboptimal conditions, does not result from an upregulation of the "classical" G1 inhibitory proteins but rather does so secondary to a decrease in the availability of a critical G1 cyclin. This sensitive regulatory protein, cyclin D, is essential for the activation of kinases responsible for the initial phosphorylation of Rbp, which renders it inactive and allows passage out of the G1 component of the cell cycle. This is the first work to report cell cycle-specific periods of increased ATP utilization which correlate with checkpoints through which a cell will not pass if its energetic balance is sufficiently disrupted. We also demonstrate that changes in mitochondrial function elicit changes in the core proteins of the cell cycle machinery suggesting some intracellular link between the energy balance within the cell and the proteins responsible for cell cycle progression. Finally this report confirms previous suggestions that mitochondria represent viable targets for altering the division characteristics of a cell population, particularly in the context of the altered mitochondrial phenotype of many tumour cells.

abstract: Doctor of Philosophy (PhD)


title: An investigation of iron losses due to rotating flux in three phase induction motor cores

contributor:
Findlay, Raymond D.
Electrical Engineering

abstract: In the past, the discrepancy between predicted and measured core loss values has led to the use of empirical scaling factors to improve correlation. Accurate prediction of core loss is important in the design of electrical machinery. Machine customers often demand guaranteed efficiency values at the quotation stage. If the guaranteed value is missed on delivery, they may impose penalties of as much as $5000 for every additional kW of loss. This thesis addresses one possible source of this discrepancy, that is, the failure to account for rotational iron losses. A significant portion of an induction motor stator is exposed to flux that rotates in the plane of the machine laminations. Iron losses in rotating magnetic fields differ from those obtained under alternating flux conditions and are not accurately estimated from alternating loss measurements. In recent years, a great deal of research has occurred for the explicit purpose of developing a standardized test for measuring rotational iron losses. Work in this field has been motivated by the opinion that rotational iron loss data will be used by machine designers to refine the accuracy of core loss predictions in rotating machines. The hypothesis of this dissertation is that if iron losses due to rotational flux in the stator are calculated rigorously, some portion of the discrepancy between tested and calculated values of no-load iron loss will be accounted for. To test this hypothesis, the iron losses due to the fundamental frequency variation of the flux density have been calculated in several ways. The stator losses were calculated using alternating loss data available from standard tests and by rigorously accounting for the losses caused by rotational flux. While some differences have been noted, they are too small to account for any major portion of the discrepancy between tested and calculated values of no-load core loss. The results of our investigation show the hypothesis to be false. If a standardized test apparatus for making rotational iron loss measurements were realized in the near future, it would benefit producers of electrical sheet and provide useful information to machine designers. However, as this investigation will show, the refinement to core loss calculation methodologies will not likely improve the correlation of tested to calculated values of core loss.

abstract: Doctor of Philosophy (PhD)


title: The Second Chinburg Conjecture for Quaternion Fields

contributor:
Snaith, V.P.
Mathematics

subject: Mathematics Mathematics

abstract: This thesis is a part of a program to study the Second Chinburg Conjecture. Let N be a quaternion extension of the rational; containing Q(√d₁,√d₂), where d₁ ≡ 3 (mod 8) and d₂ ≡ 10 (mod 16). A projective Z[Q₈]-module inside the ring of integers ON is constructed and is used, together with a cohomological classification of cohomologically trivial, 2-primary Q-modules, to compare Ω(N/Q,2), Chinburg's second invariant, with WN/Q, the root number class defined by Ph. Cassou-Nougès and A. Fröhlich. The Second Chinburg Conjecture for this extension N/Q is confirmed. Together with results of J. Hooper and S. Kim this calculation verifies the Second Chinburg Conjecture for all quaternion extensions of the rationals.

abstract: Doctor of Philosophy (PhD)


title: An Analytical and Experimental Investigation of Bubble Waiting Time in Nucleate Boiling

contributor:
Judd, Ross L.
Mechanical Engineering

subject:
Mechanical Engineering
Mechanical Engineering

abstract:
An analytical and experimental study of bubble waiting time for dichloromethane boiling on a glass surface is reported in this thesis. Bubble waiting time data for boiling at heat fluxes of approximately 8000, 10000, 12000, 14000, 16500 and 19000 BTU/hr ft² and subcooling values of 1.6, 14.7 and 30.0 ºF is presented.

In as much as bubble nucleation theory formulated on the basis of diffusion of heat to the thermal layer predicted results for bubble waiting time that were inconsistent with experimental data, a bubble nucleation theory incorporating both diffusion and convective transport of heat to the liquid in the vicinity of active sites was developed. The bubble waiting time results predicted by this theory agreed very well with experimental observation and therefore the evidence suggests that the convective contribution of heat transfer to the liquid layer adjacent to the heat transfer surface is a significant parameter in bubble nucleation.

abstract: Master of Engineering (ME)


title: Attentional and Non-attentional Effects of Prequestioning

contributor:
Begg, Ian M.
Psychology

subject: Psychology Psychology

abstract: Educators occasionally present students with prequestions before the students read textual material. Prequestions increase retention of the prequestioned portion of the text. The consensus in the educational psychology literature is that the increased retention is caused by selective displacement of attention from unprequestioned to prequestioned material. The experiments in this dissertation employ techniques and theories from generation effect research to show that the memorial benefits of prequestioning derive from more complex process changes than mere shifting of attention. Experiment 1 establishes that the materials used in the dissertation (general knowledge statements) support a prequestion effect in a traditional within-subject design. Experiments 2 and 3 employ a between-subjects manipulation of prequestioning. The presence of a prequestion effect within these experiments demonstrates that selective displacement of attention is insufficient to explain the full prequestion effect. In Experiments 4-6, alternative explanations for the effect of prequestions are explored. Question recognition and answer recognition are tested in Experiment 4, in order to assess the impact of prequestions on item-specific information. Item-specific effects of prequestioning were strong for the questions, but not the answers. In Experiment 5, the effect of time lag on prequestion effectiveness was examined. No appreciable lag effect was found. Experiment 6 examined the importance of the relationship between a prequestion and a provided answer. The absence of a prequestion effect for meaningless question-answer pairs in this experiment rules out explanations based solely on cue-specific information. Experiment 7 examines the effectiveness of prequestioning in comparison with dual presentation of the to-be-learned material. For the factual prequestions employed, dual presentation provided a much greater benefit in cued recall. Finally, a proposal is presented to explain the effects of prequestions. The proposal is a supplement to explanations based on selective displacement of attention.

abstract: Doctor of Philosophy (PhD)


title: Effects of extended kindling in hippocampal and olfactory cortical systems on measures of transfer, inhibition, cell loss and sprouting

contributor:
Racine, Ronald J.
Psychology

subject: Psychology Psychology

abstract:
Human epilepsies are a family of disorders of the nervous system, characterized by transient, recurring episodes of neuronal hypersynchronous seizure activity. These often begin locally, but they may generalize to produce convulsions. The basic mechanisms responsible for the seizures are unknown, but several animal models of epilepsy are available for the study of the neuronal abnormalities associated with these events. One of these is the kindling model in which repeated application of electrical stimulation to certain brain regions results in the progressive development of electroencephalographic and behavioural seizures.

In this thesis, we compared two excitatory monosynaptic systems for rates of transfer kindling effects, levels and alterations in inhibition, kindling-induced cell loss and mossy fiber sprouting. Animals were kindled for 30 or more stage 5 seizures. The two monosynaptic systems studied were: 1) entorhinal cortex-perforant path-dentate-gyrus system and 2) olfactory bulb-lateral olfactory tract-piriform cortex.

Our major findings may be summarized as follows: a) there was immediate transfer in the olfactory bulb-lateral olfactory tract-piriform cortex system but not in the entorhinal cortex-perforant path-dentate gyrus system. We hypothesized that the difference in transfer rates was due to differences in the spatio-temporal patterns of discharge at the network level. b) In both systems, the levels of inhibition were increased following kindling, remained increased throughout administration of kindling simulations and then returned towards baseline levels after discontinuation of the kindling stimulations. This suggests that a disturbance in the inhibitory system of the dentate gyrus or the piriform cortex can not explain the epileptogenesis. c) We found a decrease in the number of hilar cells of the dentate gyrus following kindling in the entorhinal cortex-perforant path-dentate gyrus system but not following kindling of the olfactory bulb-lateral olfactory tract-piriform cortex system. d) Sprouting of mossy fibers was found into the IML of the dentate gyrus following kindling of the lateral olfactory tract but only after at least 14 stage 5 seizures had been elicited. There was no evidence of sprouting of these fibers into the stratum oriens of area CA3.

These findings suggest that kindling results in a remarkable specificity in the seizure circuitry dependent on the site of stimulation and does not require cell loss in the hilus or mossy fiber sprouting into either the CA3 or the IML for it to occur. Since we found enhanced inhibition in both systems with kindling, a failure of inhibition, at least in these systems, can not explain epileptogenesis.

abstract: Doctor of Philosophy (PhD)


title: Early pregnancy disruption in mice (the Bruce effect): The role of sexual satiety, castration, and excreted steroids of novel males

contributor:
deCatanzaro, Denys
Psychology

subject: Psychology Psychology

abstract: Early pregnancy in mammals is vulnerable to various environmental factors, one of which is exposure to novel males (the Bruce effect). It is well established that androgen-dependent chemical excretions from novel male mice prevent ovoimplantation in proximate previously-inseminated females. The chemical nature of these pheromones has not been determined. This thesis explores the role of steroids in the Bruce effect after castration and sexual satiety and also analyzes excreted steroids released by novel males. Experiments 1 and 2 demonstrated that recent sexual experience can reduce novel males' capacity to disrupt pregnancy. Novel males were allowed to mate with stimulus females prior to exposure to inseminated females during the implantation period. Unmated males disrupted pregnancy more often than did mated males. Experiment 3 was designed to examine the time course of males' ability to disrupt pregnancy following castration. The probability of retention of pregnancy increased as a linear function of time since castration. Castrated males continued to disrupt pregnancy during the initial weeks after surgery, but by 6 weeks, the majority of females remained pregnant. Males' excretion of testosterone and 17β-estradiol in urine, measured via ELISA procedures, diminished gradually during the weeks after castration. In Experiments 4 and 5, the concentrations of urinary steroids from novel males were measured during exposure to inseminated females. These studies revealed that males' urinary excretions of testosterone and 17β-estradiol correlated with females' pregnancy loss. Also, males excreted higher concentrations of 17β-estradiol but not testosterone when exposed to females on day 3 of pregnancy compared to when males were isolated. In Experiment 6, steroids were applied to the nasal region of recently inseminated females. Nasal application of testosterone propionate did not disrupt pregnancy. However, topical application of either 17β-estradiol or 17β-estradiol benzoate completely prevented implantation at very low doses. Results from these studies suggest that steroids play an important role in novel-male-induced pregnancy disruption. As endogenous levels of androgens are diminished, either through castration or sexual satiation, novel males' ability to disrupt pregnancy decreases. Furthermore, novel males' urine contains 17β-estradiol, the quantity of which rises during exposure to inseminated females. Also, this steroid can disrupt pregnancy through nasal application on the female. Levels of 17β-estradiol are known to be elevated in females experiencing early pregnancy disruption. Thus, 17β-estradiol may be a potential pheromone involved in the Bruce effect.

abstract: Doctor of Philosophy (PhD)


title: "Those who are obliged to pretend that they are gentlefolk": The construction of a clerking identity in Victorian and Edwardian London

contributor:
Rempel, Richard A.
History

subject: History History

abstract: This dissertation examines the means in which an identity was constructed by male clerks of the lower middle class through shared work, social and cultural experiences during the Victorian and Edwardian eras. Because clerks displayed characteristics of the middle and working classes, historians have not fully explored the common culture that bound them together. While individual clerks varied significantly in incomes, socio-economic backgrounds and job descriptions, they had a set of attributes that helped them create a common cultural experience. This study explores the culture of clerks through work and office experiences; educational and commercial training; social activities in London; the discourses of self-improvement and respectability; and the culture of the suburban lifestyle. Although clerks failed to realize their ambition of becoming substantive members of London's middle class, they did construct a distinct identity. An identity built neither on reaction nor agitation, but on work, masculine and social experiences, dominated by an ideology of self-improvement. This ideology of self-improvement served as the central means clerks used to counter their material anxieties and an office culture based on deference and docility. In addition, this dissertation also explores the interaction between this identity and the Victorian and Edwardian "visions" and portrayals of the clerk in the press, social criticism and literature. This portrayal by the middle classes which clerks aspired to join, was overwhelmingly negative and condescending. Its veracity served to conceal the various positive aspects of the clerk's identity from contemporary opinion and, unfortunately, later scholarship.

abstract: Doctor of Philosophy (PhD)


title: A phenomenological study of the mysticism of St. John of the Cross

contributor:
Mitscherling, Jeffrey A.
Philosophy

subject: Philosophy Philosophy

abstract: The goal of this dissertation is to understand the nature of mystical knowledge. After rejecting the perceptual model and the "pure consciousness" model for mystical knowledge due to their inaccuracies, I try to develop a new model for mystical knowledge using the phenomenological method. This new model is based on the mystical experience of St. John of the Cross, the famous Spanish mystic of the sixteenth century. To ensure the accuracy of the model, the mystical theology of St. John is exposed in sufficient details, with special emphasis on St. John's characterization of different types of mystical knowledge. Then, drawing on the insights of Edmund Husserl, Martin Heidegger, Max Scheler and other phenomenologists, I develop a new model for mystical knowledge called knowledge through the resonance of love . According to this model, the mystical knowledge of St. John has the nature of an affective self-knowledge through love. Suggestions are also made on how the model can be applied to other mystics. The conclusion to be drawn from this model is that mystical knowledge is not an Absolute Knowledge of an extra-linguistic nature, but an event of understanding that takes place within the linguistic horizon of the mystic's religious tradition.

abstract: Doctor of Philosophy (PhD)


title: Clothed encounters: The power of dress in relations between Anishnaabe and British peoples in the Great Lakes region, 1760--2000

contributor:
Preston, Richard
Anthropology

subject: Anthropology Anthropology

abstract: The purpose of this study is to show the ways in which clothing reflected and influenced the shifting balance of power in the relations between and among Anishnaabe (Ojibway) and British peoples in the Great Lakes region. Clothing is embedded in cultural and economic systems, exerting a powerful force on the lives of individuals and nations. A specific objective is to reveal how clothing contributed to the economic and political subordination of Anishnaabek, as well as how it has facilitated gradual re-empowerment. This thesis makes a significant contribution to knowledge of the history of Great Lakes Native clothing by presenting and analyzing new data on clothing styles during the fur trade era, on the transformation from culturally distinct styles to the adoption of European styles, and on contemporary Native fashion and everyday styles. The resultant history of Anishnaabe clothing and original use of neglected sources, such as commercial records and language, contribute new insight to existing studies of ceremonial dress of the modern period. The interdisciplinary approach of this study reveals new perspectives on the history of colonial relations. The emphasis on clothing provides a window into cultural, social and economic aspects of inter-cultural relationships that are difficult to perceive through the study of words and events alone. As well, an innovative adoption of anthropological theories of narrative is used to elucidate historical processes in colonial relations. Original combinations and applications of theoretical concepts contribute new approaches to the interpretation of material culture and dress. These show how objects participate in cultural constructions of "the self" and "the environment" that vary across cultures and therefore influence relations between cultures. Application of the theories of narrative noted above demonstrates how dress functions to embody roles in "master narratives" which are shared among members of societies.

abstract: Doctor of Philosophy (PhD)


title: Turbo-BLAST: A novel technique for multi-transmit and multi-receive wireless communications

contributor:
Haykin, Simon
Electrical and Computer Engineering

abstract: Wireless communications technology is presently undergoing a tremendous expansion, which is brought on by the proliferation of many diverse and very compelling applications. These trends are continually pushing the demand for substantially increased information capacity, which can only be realized through the development of novel communication techniques. In this context, we may mention a ground-breaking wireless communication technique that offers a tremendous potential to increase the information capacity of the channel, namely, the multi-transmit and multi-receive (MTMR) antenna system, which is popularized as the Bell-Labs Layered Space-Time (BLAST) architecture. In particular, the Diagonal-BLAST (D-BLAST) and the Vertical-BLAST (V-BLAST), developed by Bell labs of Lucent Technologies, permit signal processing complexity to grow linearly, with the capacity increase being made possible through the use of a large number of transmit and receive antennas. However, from a practical perspective, D-BLAST is inefficient for short packet transmissions due to its boundary space-time wastage. Meanwhile, V-BLAST suffers from error propagation due to deep fades in the wireless channel. In this thesis, we propose Turbo-BLAST, a novel multi-transmit and multi-receive antenna system that can handle any configuration of transmit and receive antennas. It presents a framework of simple yet highly effective random space-time transmission and iterative joint-decoding receivers for BLAST architectures. Specifically, we show that the embodiment of turbo principles and the BLAST architecture provides a practical solution to the requirement of high data-rate transmission in a reliable manner for future wireless communication systems.

abstract: Doctor of Philosophy (PhD)


title: Multiband models of high temperature superconductors

contributor:
Carbotte, J.P.
Physics

subject: Physics Physics

abstract: In order to understand the complex electromagnetic properties of high temperature superconductors the details of the electronic band structure must be included. In this thesis we go beyond the simple free electron model in which the electromagnetic properties are determined by a single, spherical, Fermi surface (which is adequate for most conventional superconductors) to more realistic models containing multiple, anisotropic tight binding bands. Using these models we are able to calculate several electromagnetic properties, including the magnetic penetration depth, Josephson tunneling currents, the density of states and the optical conductivity, we find our results are in good agreement with experimental observations. One of the banes of the field of high temperature superconductivity is that many experiments are carried out on materials that are less than ideal. Often the presence of impurities or less than ideal stoichiometries can have a large impact upon the measured properties. We are able to calculate the effect of impurities upon the above mentioned electromagnetic properties in both the unitary and Born scattering limits and find significant differences between them. We find that the presence of impurities in the chain band has little effect upon the critical temperature which is consistent with the experimental observations that Ni impurities (which go into the chains) and overdoped materials (in which the excess oxygen also goes in the chains) have little effect upon the critical temperature, while Zn impurities (which go into both the chains and planes) and underdoped materials (in which both the chains and planes are oxygen deficient) have a significantly lower critical temperature. Another of the difficulties with the experimental results is caused by the presence of twin domains in the orthorhombic materials. The presence of twins in a material can mask some of the significant anisotropies that are observed in untwinned materials such as the magnetic penetration depth in the a and b directions and the c direction Josephson tunneling into a conventional superconductor. We calculate these properties in models that take into account the large anisotropies that are present in these materials. We find that the c direction Josephson tunneling can not only be non-zero, but can actually be quite large in a pure d wave superconductor if the band is anisotropic (i.e . orthorhombic). This result helps explain one of the few experiments that was considered inconsistent with d wave superconductivity.

abstract: Doctor of Philosophy (PhD)


title: Mechanistic Studies on the Reactions of Dialkoxycarbenes with Carbonyl Compounds

contributor:
Warkentin, John
Chemistry

subject: Chemistry Chemistry

abstract:
Syntheses of 2.2-dimethoxy-5,5-dimethyl-Δ³-1,3,4-oxadiazoline (51) were performed from either lead (IV) acetate or iodobenzene diacetate oxidation of the carbomethoxy hydrazone of acetone (200) in methanol. The synthesis of 2-acetoxy-2 methoxy-5,5-dimethyl-Δ³-1,3,4-oxadiazoline (207) was achieved by lead (IV) acetate oxidation in dichloromethane solvent. The synthesis of 51 from substitution by methanol on 2-acetoxy-2-methoxy-5,5-dimethyl-Δ³-1,3,4-oxadiazoline (207) was also performed. Synthesis of 2-methoxy-5.5-dimethyl-2-(2,2.2-trifluoroethoxy)-Δ³-1,3,4-oxadiazoline (210) was achieved by substitution by 2.2,2-trifluoroethanol on 2-acetoxy-2-methoxy-5,5-dimethyl-Δ³-1,3,4-oxadiazoline (207).

Thermolyses of 51 and 210 in the presence of a variety of cyclic anhydrides 215 yield the products 216. Dialkoxycarbene reactions with unsymmetrically substituted anhydrides have been shown to occur preferentially at the most electron deficient carbonyl group. Competition studies between substituted maleic anhydrides show a preference for carbene attack on the most electron deficient anhydride. On the basis of these studies, the mechanism for the formation of 216 is believed to occur by inital attack of the dialkoxycarbene onto the carbonyl group of the anhydride.

Thermolyses of 51 and 210 in the presence of benzoyl cyanide 122b and benzoyl fluoride 122c were found to yield the products 127b-e. The mechanism of formation of these compounds was also attributed to initial attack of dialkoxycarbene onto the carbonyl group. In keeping with literature results, dimethoxyoxadiazoline 51 was found to react with benzoyl chloride (122a) to yield methyl benzoylformate (125). Thermolysis of 51 in the presence of benzalphthalide (224) was found to yield the product 225. The results are discussed in terms of the mechanism of the 1.2-group migration common to all these reactions and those of dialkoxycarbene addition to anhydrides.

Reaction of 51 with 9-fluorenone (230) and coumarin (231) yield products from intramolecular methoxy migration. The mechanism was established by deuterium and ¹⁸O labelling experiments. This mechanism involves the intermediacy of an oxirane 235. Although 235 can be identified in the reaction mixture after shortened thermolysis times it does not survive attempts at isolation.

N-Phenylmaleimide (270) was found to intercept dimethoxycarbene (10) to give a cyclopropane product 271. The regiochemistry of addition to maleimide and maleic anhydride was examined by ab initio molecular orbital calculations. The computational results reflect the observed sense of regioselectivity only when higher level basis sets employing polarization functions are used to calculate the energies.

Thermolyses of 51 and 210 in the presence of the stable 1,2-bisketene 292 yielded products of overall [4 + 1] addition of the dialkoxycarbene to the π-system of the bisketene. This result is in keeping with dialkoxycarbene addition to the less hindered side of the bisketene.

Thermolyses of dimethoxyoxadiazoline 51 in the presence of β-dicarbonyl compounds 302a-d yield the products of formal insertion of the carbene into the C-H bond of the keto tautomer. The presence of the enol tautomers of these compounds is expected to be substantial on the basis of literature values for the equilibrium constants in benzene. The results indicate that the reaction is likely to proceed through O-H insertion of the dialkoxycarbene through an ion pair intermediate. This is fitting for the mechanism of O-H insertion for nucleophilic carbenes.

abstract: Doctor of Philosophy (PhD)


title: Liberal cultural coercion

contributor:
Simpson, Evan
Philosophy

subject: Philosophy Philosophy

abstract: Hereditary self-government, the lack of a personal property system, and coercive healing practices are contemporary aboriginal cultural practices that conflict with liberalism. Is it legitimate for a liberal state to coerce peoples with these and more illiberal practices to change them when most members of the culture are opposed, all-things-considered? This thesis argues that a liberal theory of justice like Rawls's cannot adequately justify such liberal cultural coercion. The best interpretation of political liberalism rejects war and strong economic sanctions against peoples with nonliberal cultural practices, and includes liberal cultural toleration through formal political autonomy rights of peoples of self-determination, secession and independence. These political autonomy rights lead to less civil unrest and despotism compared to the political assimilationism of all to a dominant people's political conception in multipeople states, and are fairer to all peoples. Liberal legitimacy requires that sufficient actual and not merely hypothetical or future persons endorse the reasoning and conclusions of parties in Rawls's original position. Rawls's hypothetical reasoning binds actual persons with obligations by engaging with their considered convictions. When the considered convictions that can be presumed in a liberal domestic public culture are not present in a people, the conditions that legitimate liberal state coercion are not present. Yet the partisan imposition of a liberal public culture would undermine political liberalism's freestanding nature and political objectivity. Similarly, the lack of agreement of peoples that human rights violations, except of peoples' self-determination, are a ground for war means imposing this standard is illegitimate. Peoples with nonliberal cultures can be credited with conceptions of reasonable disagreement that reasonably disagree with political liberalism's conception of reasonable disagreement, undercutting the latter's claim to political objectivity for a people. Without endorsing a coercive imposition that it takes to be illegitimate, political liberalism cannot justify coercively vindicating its standards among opposed nonliberal peoples.

abstract: Doctor of Philosophy (PhD)


title: Gas flows and mixing in models of the Inco flash smelting furnace

contributor:
Baird, Malcolm H.I.
Diaz, C.M.
Irons, G.A.
Chemical Engineering

subject:
Chemical Engineering
Chemical Engineering

abstract: The flow of gases in the Inco flash smelting furnace has been studied, with the primary objective of improving the mixing of gases in the uptake. Experimental trials were performed in physical models of the furnace gas space in which the flow patterns were examined by means of flow visualization, tracer mixing studies and velocity distribution measurements. Two different models of the flash furnace and uptake have been built and operated: a 1/20 linear scale water model and a 1/5 linear scale air model. Similarity of the flow patterns in the uptake was expected between the models and the plant, given the close agreement of the scaling criteria. These experiments indicated that the most significant factor affecting the mixing in the uptake is the afterburner configuration. In the range applicable to the plant operation, Reynolds number and jet momentum were found to have little effect on the mixing in the uptake. The afterburner configuration which provided the best mixing conditions, had staggered opposite pairs of jets flowing at 90° to the longitudinal axis of the furnace. The staggered jet arrangement allowed for maximum coverage of the uptake cross-section while keeping the opposing jets close enough that they still interact. This configuration was implemented in the plant at Copper Cliff in 1996. A mathematical model has been developed using the computational code FLUENT v 4.5 to simulate the flow of gases in the air model. The principal objective was to determine whether the mathematical model could successfully simulate the flow patterns observed in the air model without the addition of afterburner flow in the uptake. The mathematical model predictions suggest that the furnace flow is very prone to become asymmetric. The results of the numerical simulations indicated that very small inequalities in the jet angles or jet flows can lead to asymmetric flow. The predicted asymmetric flow conditions and measured dimensionless fields were qualitatively similar. The steady state numerical model cannot account for the temporal flow instability at the transition between the furnace and uptake, as was observed in the physical models. The flow instability at this transition produced a pulsating-type flow pattern, which was driven by cyclic imbalances of pressure in the system. In the furnace space, the turbulent jets from adjacent nozzles flowed directly toward the model floor where they combined to form a single jet stream. The strong jet flows make it inevitable that extensive separation from the side walls and roof occurs. This effect is amplified by the abrupt junction to the uptake. Projecting the air model findings to the plant, the amount of recirculation was estimated to be about three times the flow through the burner jets.

abstract: Doctor of Philosophy (PhD)


title: Growth Related Phenomena in MBE Films of InGaAsP on InP substrates

contributor:
Weatherly, G.C.
Materials Science and Engineering

subject:
Materials Science and Engineering
Materials Science and Engineering

abstract:
Heteroepitaxial growth of In₁_ᵪGaᵪAsᵧP₁_ᵧ alloy thin films on InP(001) substrates using molecular beam epitaxy (MBE) is technologically important for the fabrication of optoelectronic devices. Recent progress in MBE, for example the use of hydride gas sources such as AsH₃ and PH₃ has improved the control of the P to As ratio and added more versatility to this thin film growth technique. In this thesis, transmission electron microscopy (TEM) studies of some unique growth-related phenomena occurring in In₁_ᵪGaᵪAsᵧP₁_ᵧ films grown with gas-source MBE are described. The experiments were intended to understand the growth mechanism of the films and the characteristics of structural "defects", rather than to obtain practical knowledge which can directly be applied to the manufacturing of optoelectronic devices.

The initial stage of strain relaxation in compressively-strained InAsᵧP₁_ᵧ ternary alloy films was studied. The compressive misfit strain in 190Å thick films ranged from -0.96% to -2.43% (0.30≤y≤0.77). Both TEM and cathodoluminescence imaging revealed the existence of new types of misfit dislocations aligned close to [100] and [010] directions generated from heterogeneous dislocation sources at the InAsᵧP₁_ᵧ/ InP (001) interfaces. The new types of misfit dislocations were found to be pure edge in character, formed probably by slip on {011} planes. Contrast profiles were computed for misfit dislocations parallel and adjacent to one of the free surfaces of a plan-view TEM foil by taking into account the significantly modified elastic fields associated with such misfit dislocations. The calculated profiles were useful when Burgers vectors of misfit dislocations generated from dislocation source were analyzed.

A composition modulation occurring only along the [110] direction with a small wavelength (100Å) was repeatedly observed in 3000Å thick In₁_ᵪGaᵪAsᵧP₁_ᵧ alloy films having a wide range of nominal composition being lattice-matched to InP. This modulation is different from the "classical" spinodal decomposition along elastically soft [100] and [010] directions with long-wavelength (1000-1500Å), commonly observed in In₁_ᵪGaᵪAsᵧP₁_ᵧ films grown by liquid phase epitaxy. A simple free energy argument including the effect of constraint from the InP substrate suggests that the observed modulation is not directly caused by the minimization of free energy but is driven by kinetic processes occurring at the surface of growing films.

The morphological instability of a strained film surface was also studied. Cross-sectional TEM investigation revealed the coexistence of prominent composition modulation and surface undulation in tensile-strained In₁_ᵪGaᵪAsᵧP₁_ᵧ films. The surface morphology of the strained films showed a clear correlation with the degree of the composition modulation, occurring predominantly along the [110] direction. When the film was under tension, the surface undulation developed at relatively low strains (as low as 0.5%); on the other hand, films with the same magnitude of compressive strain did not exhibit any surface undulation. In addition, the surface undulation was composition dependent; it was enhanced as the degree of composition modulation increased. These features distinguish the present morphological instability induced by the inherent composition modulation from the "classical" three-dimensional island growth mode of compressively strained films having strains larger than 2%.

abstract: Doctor of Philosophy (PhD)


title: A Study of Kant's Method in the Critique of Pure Reason: Hypothetical and Transcendental Proofs

contributor:
Ajzenstat, S.
Philosophy

subject: Philosophy Philosophy

abstract:
This essay is intended as a general study of the transcendental method employed by Immanuel Kant in his Critique of Pure Reason. Norman Kemp Smith's views on its relation to the hypothetico-experimental method of the natural sciences will receive special attention in this study. In the "Second Preface" to the Critique, Kant himself maintains that philosophy must emulate the method of the sciences if it is to become successful. One of our main tasks must therefore be to ascertain Kant's estimation of the extent to which transcendental philosophy is indebted to the scientific method in general and to the method of the natural sciences in particular. While Kemp Smith contends that the methods employed in Kant's philosophy and in the natural sciences are fundamentally akin, we would like to show that, despite some important similarities, there are also radical discrepancies between the two. Kemp Smith's case will be briefly summarized in Chapter 1.

In Chapter 2, a close look at several passages in the "Second Preface" will do much to shed light on these issues. First, it should aid us in understanding what Kant believes can be gained by emulating the sciences. Secondly, such a study should make it possible to isolate the characteristics of the sciences which may be profitably emulated by philosophy. As we shall see, Kemp Smith suggests that only the natural sciences offer a useful example to be followed by philosophy. An examination of the "Second Preface", thirdly, should enable us to assess this view; it should enable us to determine whether or not the other disciplines which Kant regards as sciences have something additional to offer to philosophy.

Concerning the natural sciences, I would like to show that Kant regards Francis Bacon as the primary exponent of the hypothetico-experimental method and, thus, as a seminal influence on his own work. Clear indications of this, I shall argue, are given in his epigraph to the Critique, in a key reference in the "Second Preface" and in some crucial passages appended to the "Introduction". While this issue - as well as our interpretation of the 'Copernican analogy' - will be discussed in Chapter 2, our final comments on these matters will appear in Chapter 4.

The Transcendental method of proof will be the topic of Chapter 3. A large portion of that chapter is devoted to reconstructing the "Second Analogy of Experience" - Kant's attempt to prove the principle of causation. We believe this to be a paradigm of a transcendental proof, for three main reasons. First, because, once understood, it is relatively simple. Second, because the "Second Analogy" contains at least one transcendental disproof, which is convenient for our purposes. Third, because, at the end of the section on the "Analogies" as a whole, Kant himself shows that he is unmistakeably pleased with the success of his proof. Our reconstruction of Kant's proof is contrasted with a brief account of Hume's views on causation, in order to further highlight Kant's novel approach. In this chapter then, we have deemed it useful to present an exemplar of the transcendental method of proof. This will be done particularly in order to discuss Kant's notion of "possible experience", though also so that we may have a concrete basis from which to educe some general observations about transcendental proofs.

In Chapter 4 conclusions will be drawn concerning the extent and limitations of the debt of the transcendental method to the method of the natural sciences. This, as we stated above, involves finalizing our arguments concerning Kant's references to Bacon and Copernicus. Once that has been done, we shall turn our attention back to Norman Kemp Smith's views on the relationship between the two methods and contrast them with our own findings.

Throughout our study we shall have to offer brief accounts of what amount to some very controversial notions in Kantian scholarship. To mention but a few: terms like "critique", "transcendental logic", "synthetic" and "analytic", "a priori" and even "transcendental" itself, must weave in and out of our discussion without the benefit of a fully adequate definition - if such a thing is possible. However, as careful analyses of terms like these would not permit us to carry on with our study, we shall have to make do with summary definitions.

A brief "Afterword" has been added to this essay. Its purpose is to qualify our treatment of Norman Kemp Smith and to suggest areas for further study.

abstract: Master of Arts (MA)


title: Religion and Morality in Ovid: A Survey of the Poet's Worldview

contributor:
McKay, A.G.
Classics

subject: Classics Classics

abstract:
This study attempts an overview of Ovid's attitudes, beliefs, feelings, and thoughts with respect to the religious, moral, and social framework of his day. It proceeds by extensive quotation from the poet's works, and these quotations are arranged by topic and theme. The rationale for this approach is set forth in the "Introduction".

There are three major chapters: the first and third deal respectively with religion and morality (using those terms with their widest connotations); these chapters examine Ovid's interaction with both native Roman and Hellenistic Greek traditions; the second chapter deals with Ovid's beliefs about those important subjects poetry and love.

For each chapter and each new topic relevant background information is given, while a running commentary strings the quotations together. The conclusions proceed from what the poet has written, and each chapter has its own concluding section. There is also a formal "Conclusion" to the thesis which examines the relationship between the poet's subject matter and his on-going popularity.

This thesis attempts to add more definition to Ovid's worldview than has hitherto been possible. For each topic the relevant quotations are given, and the relations among topic areas are indicated. Thus this work can serve variously as a reference for specific topics, as a guide to the place of individual topics in the context of Ovid's thought, or as an overview of the poet's attitudes and beliefs.

Although the nature of this thesis precludes any claim to startling originality, it does happen that this approach sometimes shows the poet in a new light. Examples of this would include the evidence of estrangement between the poet the his third wife cited in Chapter Two; and, in Chapter Three, the intimations of parody of imperial marriage legislation (in the abortion elegies), and of a female audience for Ovid's works.

abstract: Doctor of Philosophy (PhD)


title: Characterization of the NADP(+)-dependent malic enzyme of Sinorhizobium (Rhizobium) meliloti and investigations into the requirements of malate uptake and malic enzyme activity in bacteroids

contributor:
Finan, T. M.
Biology

subject: Biology Biology

abstract: Malic enzymes are responsible for the conversion of malate to pyruvate with the concomitant reduction of a nicotinamide cofactor. Previous experiments revealed that Sinorhizobium ( Rhizobium ) meliloti has both a diphosphopyridine (NAD + ) dependent enzyme (DME), which is essential for nitrogen fixation, and a triphosphopyridine (NADP + ) dependent enzyme (TME), which is not required for symbiotic N 2 fixation. Sequence analysis of tme revealed that it encodes a protein of 761 amino acids, which is much larger than previously described prokaryotic malic enzymes. The elongated structure comprises an unusual chimeric organization with the N-terminal region of the protein showing similarity to other malic enzymes, including six conserved domains implicated in malic enzyme function. The C-terminal region shows similarity to phosphotransacetylase enzymes (PTA) and deletion of this PTA-like domain results in a decrease, but not an abolishment of malic enzyme activity, indicating that this region is not essential for the conversion of malate to pyruvate. To investigate the requirements of the malic enzyme in symbiotic nitrogen fixation several metabolic engineering experiments were carried out. The NAD + -dependent malic enzyme (SfcA) from E. coli , which lacks the PTA-like extension, was expressed in S. meliloti dme mutant strains. The S. meliloti dme - , sfcA derivatives formed nodules that fixed N 2 at rates indistinguishable from those formed by wild type S. meliloti . Hence, the SfcA protein can functionally replace DME. Other metabolic engineering attempts were made by overexpressing dme in S. meliloti bacteroids. The resulting increase in DME levels in bacteroids did not result in increased symbiotic N 2 fixation or improved plant growth. In order to determine if cofactor specificity is responsible for the requirement of DME during symbiosis attempts were made to alter the cofactor requirement of TME. Regions of dme corresponding to the putative co-factor binding site were exchanged for the corresponding regions of tme to produce chimeric proteins. To investigate the carbon source utilized during symbiosis a malate specific permease from S. bovis was expressed in S. meliloti strains lacking the dicarboxylic acid transporter DctA. When expressed as a single copy construct on the chromosome using either the dme or dctA promoter no nitrogen fixation was detected. When the constructs were expressed from a high copy number plasmid the resulting plants showed 40% nitrogen fixation and 25% plant dry weights relative to wild type inoculated plants. (Abstract shortened by UMI.)

abstract: Doctor of Philosophy (PhD)


title: MLE and RBF for AOA Estimation in A Multipath Environment

contributor:
Litva, John
Electrical and Computer Engineering

abstract:
The problem of estimation of angle-of-arrival (AOA) in multipath environments is addressed in this thesis. In particular, two new estimation techniques are developed. The first technique is based on the maximum likelihood estimation (MLE). This algorithm is unique in that a highly deterministic multipath signal model is used when formulating the likelihood function, which is then maximised with respect to the AOA. The deterministic multipath signal model that has been developed to describe the physics underlying the propagation of signals from a signal radio source to a receiver is much more complete than the general AOA model commonly used in other maximum likelihood formulations. This model makes use of the geometrical information and a priori knowledge of a number of physical parameters. By using the deterministic multipath signal model with the MLE estimator, one is essentially making more information available to the estimation process. The net result is that the estimator's performance can be greatly enhanced. The Cramer-Rao bounds that apply specifically to this model have been derived to provide a performance measure for the mean-squared errors (MSE) in the estimated AOAs.

Although the MLE method is optimum in a statistical sense, the computational load of the nonlinear optimisation procedure inherently required by the MLE method is too heavy for real-time processing. Accordingly, we propose a novel approach to the AOA estimation problem, which is based on the use of an associative memory. The functionality of an associative memory is identical to that of the inverse mapping network. This provides a more comprehensive explanation for the rationale of exploiting the inverse mapping concept in the AOA estimation problem. In particular, the AOA problem is considered as a mapping from the space of AOA to the space of the sensor output. A nonlinear associative memory is used to form the inverse mapping from the space of sensor output to the space of AOA and this memory is realised using the generalised radial basis function (RBF) neural network. In the actual implementation of the RBF network for AOA estimation, the second order statistics of the signals are used as the input vector of the network. The use of second order statistics eliminates the need to deal with the initial phase of the signal. Furthermore, it is suitable for the application to the minimum redundant array. The RHF network is much more efficient in terms of computation than the MLE algorithm. This makes the RBF network attractive for real-time implementation.

Simulations are carried out to understand the efficiency of the RBF neural network approach. The learning and estimation performance is inversely proportional to the number of learning samples and the number of hidden units. At relatively low SNR, the estimation performance of the RBF network becomes insensitive to both the number of learning samples and the number of hidden units. The estimation performance of both the MLE technique and the RBF network is also evaluated as functions of the number of snapshots and SNR. The performance of the MLE algorithm is consistent with the Cramer-Rao bound. The MLE method is more efficient in terms of estimation than a RBF network, provided that the search resolution used in the MLE method is sufficiently high. For equivalent computational complexity, the RBF network gives much better performance than the MLE method. In terms of estimation, with the same computational complexity, the MSE produced by the RBF network is much less than that produced by the MLE method. In summary, for the same performance, the computational complexity required by MLE method is much higher than that required by the RBF network. It follows that the advantage to be gained by using a RBF network for AOA estimation is a considerable reduction in computational complexity. Finally, both the MLE technique and the RBF network are validated using real data, which were collected using a 32-element sampled aperture antenna. The results obtained using the RBF network are very similar to those obtained using the MLE method.

abstract: Doctor of Philosophy (PhD)


title: Factors governing prolonged swimming performance of juvenile rainbow trout (Oncorhynchus mykiss)

contributor:
McDonald, Gordon
Biology

subject: Biology Biology

abstract: This study investigated the factors governing prolonged swimming performance in juvenile hatchery-reared rainbow trout. The primary exercise test used was a fixed velocity sprint test in which fish were rapidly accelerated to a speed of 6-7 body lengths s-1 . Time-to-fatigue was recorded as the measure of endurance. The ultimate goal of this research was to develop a model describing the limitations of sprint performance in juvenile trout under conditions of imposed velocity. This was accomplished through the completion of five studies. The specific objectives of the first study were to examine the effects of varying the rate of acceleration and the influence of experience (i.e. training) on sprint endurance. The second study examined the relationship between endurance and fuel depletion in white muscle [i.e. glycogen, phosphocreatine (PCr) and ATP], to determine whether a specific metabolic change within the muscle evoked fatigue. The dependence of endurance on muscle glycogen levels was also assessed by manipulating glycogen in two ways, through elevated ration and through sprint training. The third study examined the effect of creatine supplementation on muscle total creatine levels and endurance to determine the importance of creatine and PCr stores. The fourth study exploited individual variability in sprint performance to correlate other physiological performance measures [e.g. growth, critical velocity (Ucrit ) and response to induced stress] with endurance. The fifth and final study examined the effect of oxygen supply on swim performance. Together, these five studies have produced the following results: slowing the rate of acceleration and periodic sprint training both increase endurance; chronic stress reduces the ability to train; the reduction of ATP appears to evoke fatigue in both Ucrit and sprint tests; glycogen levels do not determine endurance; creatine loading enhances endurance via a mechanism independent of muscle free creatine and PCr levels; fish with high sprint performance have a higher Ucrit , but most other physiological performance measures do not correlate with swim performance; Ucrit performance is oxygen diffusion limited in high performers, but is more convectively limited in low performers; convection limitations are more important following a rapid acceleration in both groups; and neither sprint nor Ucrit performance is influenced by blood oxygen carrying capacity. This study has led to the conclusion that endurance is determined by cardiovascular response, specifically the ability to perfuse white muscle, rather than by the amount of fuel in the muscle to power swimming.

abstract: Doctor of Philosophy (PhD)


title: Roman settlement of northern Bruttium: 200 B.C.--A.D. 300

contributor:
Dunbabin, Katherine M.D.
Classics

subject: Classics Classics

abstract: Long-held views regarding the presumed depopulation and economic stagnation of northern Bruttium (modern Calabria) during the Roman period of occupation must now be abandoned. Instead, the examination of evidence has demonstrated that the Republican and imperial period settlement was significant. It took the form of cities, smaller nucleated settlements and dispersed rural sites, and its existence depended on the exploitation of land as well as on local and regional trade. The first two chapters deal with the preliminaries where an historical outline and a selection of relevant contemporary literary sources are presented. Chapters three and four offer an in-depth commentary and functional interpretation of the archaeological remains from the urban and rural contexts. This is the first such detailed account that this material has received in one place. Chapters five and six seek to put all this material into a wider historical context, as well as to address some issues raised by the bibliography, and, where possible, to carry this discussion further.

abstract: Doctor of Philosophy (PhD)


title: Theoretical synthesis of macromolecules from transferable functional groups

contributor:
Bader, Richard F. W.
Chemistry

subject: Chemistry Chemistry

abstract: The theory of Atoms In Molecules (AIM) generalizes quantum mechanics by deriving the physics of an atom in a molecule. This is accomplished by associating an atom with a quantum mechanical open system , a region of real space capable of exchanging electrons and properties with the rest of the molecule. AIM recovers the basic cornerstone of chemistry: that atoms and functional groups possess characteristic and additive properties. When the properties of an atom or functional group are found to be transferable, the theory makes possible the synthesis of macro-molecules from the corresponding pieces. Many molecules of biological importance are composed of repeating structural units that appear to be highly transferable. These repeating units, when defined by AIM, are found to account for and recover this transferable behavior. As a consequence, theory can be used to construct a biological macromolecule from repeating units previously defined in simpler systems. The properties of amino acid residues, the building blocks of proteins, are determined in this thesis by sandwiching each residue between two simpler amino acids to form a three-residue protein. The form and properties of the residues determined in this manner are found to be highly transferable. Thus, this thesis reports the tabulation of a library of amino acid residues that can then be linked together to form any desired protein or portion thereof. Such a synthesis makes possible the theoretical prediction of the properties of large molecules and does so using modest computing resources. The resulting availability of the electron density distribution, among other properties of the protein, enables one to apply in a quantitative manner the models and tools, such as the electrostatic field and the van der Waals shape, presently employed in the investigation of problems in molecular recognition and docking. Perhaps more importantly, it makes possible new approaches to the study of these problems.

abstract: Doctor of Philosophy (PhD)