title: Abstraction in Conceptual Model Design

contributor:
Archer, Norman P.
Management Science/Systems

subject:
Management Information Systems
Management Information Systems

abstract:
The provision of software support for conceptual model design processes has been an important issue in Model Management Systems research. This study examines the issue by empirically studying design behaviour and the techniques used during design, with a focus on the use of abstraction in the design process.

A framework that explains the relationships between the use of abstraction and the output of the design process is proposed. We classify abstraction into vertical, horizontal and general abstraction techniques. We then propose that three dimensions of a design: the completeness of the design, higher level concepts in design, and the organization of the design, are affected by effective use of these abstractions. We also propose aids to support these three types of abstraction, and develop measures to evaluate their effectiveness.

A software prototype was developed to illustrate the implementation of the proposed abstraction aids. A pilot study was also conducted to test the effectiveness of these aids using different versions of the prototype.

Three hypotheses that test the effectiveness of the proposed abstraction aids were tested in an experimental study with treatments that included three design environments and two training methods. The three design environments were two which were supported by pencil and paper design, and one which was supported by a software prototype. The two training methods used were based on our proposed abstraction aids. The results of the experiment indicate some significant differences in the performance of the participants in different treatment groups.

abstract: Doctor of Philosophy (PhD)


title: Solidification Of Peritectic Alloys

contributor:
Purdy, G.R.
Metallurgy

subject: Metallurgy Metallurgy

abstract:
This thesis presents the results of a study of two aspects of peritectic alloy solidification: 1. an experimental
and theoretical study of the phenomenon of banding (alternate
deposition of layers of primary (α) and peritectic (β) phases)
during plane front solidification and 2. a theoretical study
of microsegregation during the non-isothermal diffusion
controlled peritectic transformation in an alloy system where
the solute diffusivities differ greatly, ie. Fe-C-Mn.

Plane front solidification experiments using Sn-Cd
alloys produced specimens which solidified as metastable α
phase. The β phase was observed in only those specimens which
were purposely disturbed during solidification; the α phase
did not re-nucleate at the interface once β phase
solidification was established. Banding was observed in one of
these specimens, however, the α phase never entirely
disappeared from the interface. Mathematical model predictions
of the growth transient of the β phase and nucleation
considerations showed that the α phase would not be renucleated
at the β/liquid interface. It is thus expected that
when banding occurs in Sn-Cd peritectic alloys, α is never
completely removed from the growth front.

The treatment of microsegregation during the non-isothermal
diffusion controlled peritectic transformation used
in this work exposed several aspects of the problem which are
obscured by some of the more sophisticated mathematical
treatments of this problem; the transformation was modelled as
a series of non-isothermal steps. For the binary Fe-C system,
these calculations showed that, while cooling rate and solute
diffusivity are important, closure of the δ-ferrite/austenite
two phase field ultimately determines the temperature at which
the transformation ends and what phases exist at that point.
In the ternary case, Fe-C-Mn, the combined influence of
constitutional and diffusional solute interactions promotes
the following: 1. the concentration gradient of the fast
diffusing solute in austenite is minimized with a
corresponding greater segregation of the slow diffusing solute
in all phases, compared to predictions based on no diffusion
in the austenite or complete diffusion in all phases. 2.
diffusional solute interaction may increase or decrease the
effect of constitutional solute interaction on
microsegregation. 3. At the liquid/austenite interface, the
possibility of metastable austenite solidification or
nucleation of δ-ferrite exists throughout the transformation.

abstract: Doctor of Philosophy (PhD)


title: Mechanisms of reparative growth in adult peripheral cutaneous nerves

contributor:
Diamond, J.
Biomedical Sciences

abstract:
This thesis involved the use of mutant and transgenic mice to examine the role of
various factors in reparative growth of the adult peripheral nervous system. These animals
have genetic defects that could be anticipated to affect reparative growth of sensory nerves,
and included mice that are transgenic for the heavy chain neurofilament (NFH)lacZ fusion
construct, mice mutant either in the steel or the c-kit locus, and mice with a null mutation in
the gene coding for the low-affinity neurotrophin receptor (p75^NGFR).

Both collateral sprouting and regeneration occurred in the NFHlacZ mice at a rate
similar to that observed in control mice. Therefore, overexpression of the NFHlacZ construct
had no effect on reparative growth of sensory nerves.

Interestingly, regeneration of all three fibre types examined was impaired in mice
that have a mutation in the gene coding for Steel or c-Kit, and occured at a rate of 1/2 to 2/3
of that observed in control animals. However, the rate ofcollateral sprouting was normal.

Although the sensory nerves of p75^NGFR mice underwent normal regeneration,
collateral sprouting was completely absent. Interestingly, exogenous NGF induced this form
of growth in these animals.

In addition, there was a significant decrease in the number of axons comprising all three fibre types in the sensory nerves in both the SI/Sld, WIW and p75^NGFR mice,
suggesting that the molecules involved also play a role in the development of sensory
neurons.

NGF-induced hyperalgesia was not evident in the control or knockout animals upon
exogenous administration of either 1 or 2.5μg/g of NGF. However, administration of
2.5μg/g of NGF resulted in a significant mechanical hyperalgesia in both the control and
knockout mice. Thus, it appears that the low-affinity neurotrophin receptor does not play a
role in NGF-induced hyperalgesia.

abstract: Doctor of Philosophy (PhD)


title: Numerical Simulations of Astrophysical Jets from Keplerian Accretion Disks

contributor:
Pudritz, Ralph E.
Astrophysics

subject:
Astrophysics and Astronomy
Astrophysics and Astronomy

abstract:
This thesis presents a series of magnetohydrodynamic (MHD) simulations which
were designed to study the origin and evolution of astrophysical jets (galactic and
extra-galactic). \Ve developed and extended a version of the ZEUS-2D code which
served as the numerical basis of our simulations and attached to it a complete analysis
package that was developed in order to make contact with the theory and observations
of jets.

With our version of the code, we managed to establish an initial state which
consists of an accretion disk and its cold corona in stable eqailibrium around a central object.
No softening paranleter was used to model the Newtonian gravitational
potential of the central object. The corona and accretion disk are initially in pressure
balance with one another. These initial states were constructed so as to be
numerically stable. The corona is Inagnetized with the magmetic field lines extending
smoothly into the disk without kinks or discontinuities, avoiding, in this way, any
undesired currents in the initial set up. The disk is set in Kepler rotation and gas is
continuously injected into the corona above at the very snlalll speed of 10⁻³ times the
Kepler velocity.

In this thesis, we only considered magnetic configurations for which the Lorentz
force is initially zero (J x B = 0). In particular initial J = 0 configurations are
studied. \Ve carefully set the boundary conditions to be open conditions so as to avoid any collimation due to grid reflection effects.

To test the theory of winds centrifugally driven from the surface of Keplerian accretion
disks, we started with an open magnetic field line configuration. The magnetic
field lines have opening angles (with respect to the disk surface) less than the critical
angle (≃ 60°), as required for a centrifugally driven wind to start. We found that a
steady jet is quickly established allowing direct comparison with the theory. We find
the gas to be centrifugally accelerated through the Alfvén and the fast magnetosonic
surfaces and collimated into cylinders parallel to the disk's axis. The collimation is
due to the pinch force exerted by the dominant toroidal magnetic field generated by
the outflow itself. The velocities achieved in our simulations are of the order of 250
km/s for our standard young stellar object (a 0.5 M proto-star) and of the order
or 10⁵ km/s for our standard active galactic nuclei (a 10⁸M black hole). Our jet
solutions are very efficient in magnetically extract.ing angular momentum and energy
fronl the disk.

The second magnetic configuration we have studied consists of a uniform vertical
structure wherein the magnetic field lines are parallel to the disk's axis. Here, the
rotation of the disk twists the magnetic field lines and generates a toroidal field
component. Because of the Keplerian scaling of the rotational velocity with the disk
radius, the twisting of the field lines is higher in the inner parts of the disk. The
strong lnagnetic gradient thus generated opens up the initial magnetic configuration
in a narrow region located at 1rᵢ < r < 8rᵢ, with rᵢ being the innermost radius of the disk. Within this narrow region a wind is ejected from the field lines that have
opened to less than the critical angle (≃60°), as expected from the centrifugally
driven wind theory. Our simulations show that the strong toroidal magnetic field
generated recollimates the flow towards the disk's axis and, through MHD shocks,
produces knots. The knot generation mechanism occurs at a distance of about z ≃ 8rᵢ from the surface of the disk.

We have discovered that no special initial magnetic field structure is required in
order to launch episodic outflows in our simulations. Rather, conditions favorable for
the formation of an outflow set themselves up automatically through the production
of a toroidal magnetic field whose pressure readjusts the structure of the field above
the disk. The knot generator is episodic, and is inherent to the jet. Thus, jets
are apparently capable of producing the variability that leads to episodic events, independently of the underlying source.

abstract: Doctor of Philosophy (PhD)


title: Oncostatin M Regulation of the Tissue Inhibitor of Matrix Metalloproteinases-1 Promoter

contributor: Molecular Immunology, Virology and Inflammation

subject:
Immunology and Infectious Disease
Immunology and Infectious Disease

abstract:
The progression of an inflammatory response is largely dictated by soluble
factors termed cytokines reknown for their redundant and pleiotropic nature in
modulation of both immune and stromal cells. Individual members of the
interleukin-6 (IL-6)-type cytokine family possess both unique and shared biological
activities. These cytokines may participate in tissue remodelling by promoting
reconstruction ofextracellular matrix (ECM) following nonspecific tissue damage by
inflammatory cells. Consistent with this view, these cytokines upregulate expression
of an ECM protease inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1) and
thus may alter net enzymatic degradation of ECM. The overall goal of this thesis
is to examine mechanisms by which TIMP-1 is regulated by IL-6-type cytokines,
especially by the cytokine oncostatin M (OSM). The promoter of TIMP-1 has
therefore been studied in detail to address the mechanisms by which OSM (and IL-6
type cytokines) regulate the transcription of the TIMP-1 gene. The approaches
undertaken have included deletion analysis of the TIMP-1 gene nucleotide
sequences proximal to the start of transcription to define DNA sequences
necessary/sufficient for cytokine-induced TIMP-1 promoter activity. In addition, the
binding of nuclear factors to these DNA elements and cytokine-response elements, their expression and involvement in the regulation of TIMP-1 transcription have been explored.

We have identified sequences proximal to the start of TIMP-1 transcription
that are necessary for maximal responsiveness to OSM and IL-6. Deletion analysis
of the proximal TIMP-1 promoter (-95 to +47 TIMP-1 sequences) has identified a
nucleotide sequence within -59 to -53 ofthe murine TIMP-1 promoter that harbours
an AP-1 consensus DNA binding element. This element is necessary for maximal
OSM or IL-6 induced promoter activity of TIMP1-CAT reporter gene constructs
transfected into human hepatoma HepG2 cells. OSM is the most potent stimulus
(approx. 11-fold for OSM, and 4-fold for IL-6) of this response and additional
sequences 3-prime to +1 ofthe TIMP-1 gene are also necessary for maximal OSM
responsiveness.

Electrophoretic mobility shift assays demonstrated two gel-shifted complexes
which bind the TIMP-1 AP-1 site. An AP-1 gel-shifted complex is present in the
absence of cytokine stimulation ("complex 1"), while OSM and not other IL-6-type
cytokines, stimulated the formation of a second AP-1 gel shifted complex.
Nuclear factors binding to TIMP-1 AP-1 complex 1 include junB, junD and fosrelated
antigens. However, unlike complex1, c-fos is present and necessary for the
formation of the OSM-induced TIMP-1 AP-1 complex2. Consistent with this, OSM
is a potent inducerofc-fos protein expression among IL-6-type cytokines. Both the
formation of complex2 and c-fos expression require new protein synthesis. JunB
and junO are constitutively expressed, while the expression of fos-related antigens are induced in response to OSM. In addition, although PMA was also a potent
inducer of c-fos expression, induction of TIMP-1 promoter activity by the
combination of PMA and IL-6 was comparable to IL-6 alone and did not equal the
significantly higher induction by OSM. Within the same cells, OSM and IL-6 equally
induced STATDNA-binding activity. An Ets-consensus site (nucleotides -45 to -40)
flanking the 3-prime end of the AP-1 site is a weak binding site for Ets-related
nuclear factors, and an SP-1 site near +1 (-11 to -6) is a strong binding siteforSP1
nuclear factors and related SP-1 site binding proteins. No STAT nuclear factor
binding to the proximal TIMP-1 promoterwas detected. Taken together, the TIMP1
AP-1 site and c-fos represent a unique target of OSM signalling and activation of
AP-1 complexes (possibly containing c-fos) by OSM as well as sequences
downstream of TIMP-1 +1 contribute to maximal responsiveness of the promoter
to this cytokine among IL-6 family members.

The contribution of c-fos to OSM-induced TIMP-1 expression was further
explored in murine cells. OSM stimulates the expression of c-fos and activates
STATs 1, 3 and 5 DNA-binding activity in murine fibroblasts. As observed in
human cells, OSM but not other IL-6-type cytokines upregulated c-fos expression
which participated in complexes binding the TIMP-1 AP-1 site. OSM was also
unique among IL-6 family members in activating STAT5 DNA-binding activity in
murine fibroblasts. However, in contrast to observations in human HepG2 cells,
deletion analysis of the TIMP-1 promoter showed that the AP-1 site (-59/-53) was
v not necessary for OSM-mediated upregulation of the TIMP-1 proximal promoter
activity over basal levels in murine NIH3T3 fibroblasts and co-transfection of a
dominant-negative of AP-1 had no effect. However, transfection of dominant-negative
STATs1, 3 or5 (especially STAT3) could diminish cytokine-induced TIMP1
promoter activity. In addition, c-Fos was dispensable for OSM-mediated
upregulation ofTIMP-1 mRNA levels as TIMP-1 expression was detected in wildtype
and c-fos knockout murine lung fibroblasts. Consistent with deletion analysis
ofthe TIMP-1 promoter in human cells, dominant-negative AP-1 expression vectors
abrogated OSM-mediated TIMP-1 promoter activity, while Stat-dominant negative
expression vectors did not. Taken together, the examination of murine and human
systems suggests that AP-1 and STAT nuclear factors can contribute to the
regulation of the TIMP-1 promoter.

abstract: Doctor of Philosophy (PhD)


title: Synthesis and Modelling of High Tg Copolymers Through Suspension Copolymerization with Bifunctional Initiators

contributor:
Hamielec, Archie E.
Wood, Philip E.
Chemical Engineering

subject:
Chemical Engineering
Chemical Engineering

abstract:
In this thesis, the copolymerization theory has been extended to account for the unique phenomenon of multiple initiation/propagation/termination cycles, experienced by copolymer chains in free radical copolymerization with bifunctional initiators. A comprehensive model for the most general free radical copolymerization scheme, involving simultaneous and competitive statistical and donor-acceptor propagation mechanisms, has been developed. The effects of multiple chain recombination during bifunctionally initiated batch free radical copolymerization, on copolymer microstructure and compositional drift, have been evaluated. As a result, the concepts of effective instantaneous copolymer composition, and number of segments per copolymer chain have been introduced as an addition to the copolymerization theory.

The ability to control the segment composition of the multi-segment copolymers formed during bifunctionally initiated free radical copolymerization, has been the basis for the design and synthesis of four different high T₀ engineering copolymers. Styrene/α-methylstyrene (T₀-115°C), styrene/N-phenylmaleimide (T₀-215°C), and α-methylstyrene/N-phenylmaleimide copolymers (T₀-260°C), as well as styrene/α-methylstyrene/n-phenylmaleimide terpolymers (T₀-220ºC), have been synthesized in bulk and suspension, and fully characterized. The performance of these four copolymer systems in suspension polymerization with bifunctional initiators has been evaluated at pilot plant scale, to assess the technical feasibility for their commercial production.

In addition, a novel route for the synthesis of suspension expandable polystyrene with bifunctional initiators, in a highly productive simultaneous polymerization/impregnation stage, has been developed and fully tested in pilot plant scale.

From the comprehensive kinetic and micro-structure models proposed in this thesis, two computer simulation programs (BIPEN and BICOP), have been developed. Both programs, predicting the most important phenomena of the polymerization processes studied herein, have been used as a product design tool, throughout this thesis, with very good results.

abstract: Doctor of Philosophy (PhD)


title: Effects of Planar Anisotropy on Eliashberg Superconductors

contributor:
Carbotte, J.P.
Physics

abstract:
Within the context of Eliashberg theory, we have studied the effects
of planar anisotropy on many superconducting properties. Planar anisotropy
is of interest for superconductors with layered crystal structure, such as the
metallic transition metal dichalcogenide and high-Tc oxide superconductors.

To describe planar anisotropy we use a model dispersion relation
which gives free-particle-like electronic states in the direction parallel to the
layers and the tight-binding form in the direction perpendicular to the layers.
Using this dispersion relation and the Fermi-Surface-Harmonic (FSH)
expansion technique, we specify the general anisotropic Eliashberg equations
for the problem of planar anisotropy.

We begin with the study of the effects of planar anisotropy on the superconducting
transition temperature, the thermodynamic critical magnetic field, and the quasiparticle density of states in the superconducting state. For all these properties, especially the quasiparticle density of states, the effects
of planar anisotropy are usually qnite significant.

Next, we study some thermodynamic and transport properties, namely,
the specific heat, the thermal conductivity, and the ultrasound attenuation.
The effects of planar anisotropy on these properties are closely related to the
changes in the quasiparticle density of states due to anisotropy. The changes
in the quasiparticle lifetime due to the superconducting phase transition and
anisotropy are also important for the unusual behaviors of thermal conductivity
at low temperature.

Several electromagnetic properties are also studied. The introduction of anisotropy usually reduces the value of the London penetration depth below its isotropic value, and strongly depresses the Hebel-Slichter peak in the nuclear spin relaxation rate. The theorerical results for the nuclear spin relaxation rate with strong coupling, anisotropy and Fermi liquid corrections have been compared with the experimental data for the high-Tc oxides. The
major effect of planar anisotropy on the infrared conductivity is to reduce
the frequency at which the absorption starts.

Finally, we have examined the changes of the phonon self-energy when the superconducting phase transition occurs. It is found that there
is a qualitative difference between the results for isotropic superconductors
and for anisotropic ones. This may be displayed in experiment under certain
conditions. Anisotropy also complicates the analysis of the structures in the
phonon self-energy.

It is generally true, for all the properties which we have studied,
that the effects of anisotropy will be diminished if we increase the coupling
strengths, and/or introduce impurity scatterings.

Besides the problem of planar anisotropy, we briefly discuss the problem
of an energy dependent electronic density of states (EDOS) for Eliashberg
superconductors. This is of interest for a model of two-dimensional
tight-binding dispersion relation. For a Lorentzian form for EDOS around the
Fermi level, we have discussed the modifications of the Eliashberg equations
and, then, calculated the quasiparticle density of states in the superconducting
state. The effects of an energy dependent electronic density of states on
the temperature evolution of the quasiparticle density of states below Tc is
particularly interesting.

abstract: Doctor of Philosophy (PhD)


title: Factors Affecting Secretion From Electropermeabilized Human Platelets

contributor:
Haslam, Richard J.
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract:
Comparative studies on the regulation of secretion from
dense and α-granules of electropermeabilized human platelets
indicated the involvement of three distinct factors, Ca²⁺, protein
kinase C (PKC) and an unidentified GTP-binding protein (GE). Any
two of these factors must be present for marked secretion from
dense or α-granules to occur. Thus, Ca²⁺ was not essential to the
exocytotic mechanism and the combination of phorbol ester (a PKC
activator) and a metabolically-stable GTP analogue (GTP[S]) could
produce marked Ca²⁺-independent secretory response. Ca²⁺ appeared
to have a more modulatory role, enhancing both the rate and extent
of secretion. Secretion did not correlate with phospholipase C (PLC) activity or with the accumulation of 1,2-diacylglycerol (DAG), both of which required Ca²⁺ and were inhibited by phorbol ester. The Ca²⁺-independent activation of phospholipase A₂ was shown for the first time in platelets, but moderate to complete inhibition of this enzyme had no effect on secretion or other hospholipase activities. Only the activation of phospholipase D, assayed by the formation of [³H]phosphatidic acid (PA) and
[³H]phosphatidyl-ethanol (PEt), in the absence and presence of ethanol, respectively, correlated with secretion under all
conditions tested. BAPTA and analogues, known inhibitors of Ca²⁺--independent secretion in other permeabilized cells, caused parallel dose-dependent inhibitions of PLD activity and secretion. PKC activity detected by the phosphorylation of its major endogenous substrate, pleckstrin, was enhanced by GTP[S] apparently by stimulating the formation of PA, as well as of DAG in the presence of Ca²⁺. An optimal dose of the protein kinase inhibitor staurosporine could not block secretion produced by GTP[S] in the presence of Ca²⁺, suggesting an additional role for PLD activation, independent of protein phosphorylation. However, although correlations between PLD activity and secretion were also been in intact platelets, this enzyme is known to account for only 10 - 20% of the total PA formed in intact thrombin-stimulated platelets .. This PA may be different from that formed via the
PLC - DAG kinase pathway and therefore the nature and subcellular
localization of this PA will have to be investigated in order to
establish whether PLD has a major role in secretion. The possible
existence of an alternate GTP[S]-stimulated effector protein
cannot be excluded.

abstract: Doctor of Philosophy (PhD)


title: Spectral Properties of 1.3 μm InGaAsP Semiconductor Diode Lasers

contributor:
Cassidy, D.T.
Engineering Physics

subject:
Engineering Physics
Engineering Physics

abstract:
Physical mechanisms responsible for the above-threshold spectral output of 1.3 μm InGaAsP semiconductor diode lasers are presented and discussed. Measurements
of the facet emission of a large number of devices indicate modulations in the below-threshold
RmGm product which can be used to predict and explain the shape of the above-threshold mode profile for output power levels of less than approximately 5 mW. Above-threshold
measurements using devices incorporated into a shon-external-cavity
configuration show that a symmetric, nonlinear gain mechanism is required to explain the
spectral properties for output power levels in a single mode which are greater that 5 mW. Thus it is concluded that both the effects of scattering centres and nonlinear gain are required to model accurately the spectral output of 1.3 μm InGaAsP semiconductor diode lasers.

abstract: Doctor of Philosophy (PhD)


title: Defects in Silicon-Germanium Strained Epitaxial Layers

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

subject:
Materials Science and Engineering
Materials Science and Engineering

abstract:
The energies of one and two-dimensional dislocation arrays lying near
a free surface are evaluated directly from the stress fields of single dislocations
in a half-space. These results are used to obtain expressions giving the
equilibrium spacings of a number of different arrays relieving misfit in a
strained epitaxial system. Numerical calculations are performed for the case of
edge and 60º dislocations relieving strain in a silicon-germanium layer
deposited on a silicon substrate. This method is also used to calculate the
energies of various low angle grain boundaries in a half-space.

Single-ended dislocation sources are observed using transmission
electron microscopy in two short-period Si-Ge superlattices grown on Si(100).
Their formation is linked to the development of non-planar layers during the
growth of the superlattices. The relaxation of these superlattices takes place
at significantly lower temperatures than equivalently strained homogeneous
epilayers.

Si-Ge short period superlattices deposited on Si(100) are shown to
relax through twinning on {111} planes if the deposited layers become grossly
non-planar. Twinning is accompanied by the formation of a diamond
hexagonal phase. No 60· a/2(110) dislocations relieving misfit are present in the strained layer structure.

The nature and origin of a new type of defect in Si₁_ᵪGeᵪ/Si strained
layer structures, the "pagoda" defect, is studied using transmission electron
microscopy. The defects are found to propagate in a direction determined by
the position of the Si source in unrotated substrates, and to have their origin
in the role played by SiC particles (left after cleaning the substrate) during
the growth process. Pits that form at the SiC particles are preserved during
MBE growth and perturb the strained layers, leading to the formation of
pagodas.

abstract: Doctor of Philosophy (PhD)


title: Marginality and Detachment in the Poetry of A. M. Klein

contributor:
Hyman, Roger L.
English

subject:
English Language and Literature
English Language and Literature

abstract:
The following study deals with the published poetry of A. M. Klein. While on the surface, the poetry reflects a man who seems comfortable with his Jewish past and his present life as a Canadian living in Montreal, closer examination reveals that this poet is, in fact, marginal to much of his life. This study examines only this aspect of marginality as it is shown in Klein's poetry, and the Preface outline both the argument and its conclusion.

The first chapter of this study focuses on marginality, which is defined as the state of being aware of an environment, but feeling apart from it. I show that Klein is marginal to the religious traditions of his ancestors, to many aspects of his life in Montreal, to Palestine, and to many of the expressions of contemporary Judaism.

The second chapter concentrates on the poetic devices which Klein utilises to enable him to write about those areas of life to which his poetry shows that Klein felt marginal or that he found particularly painful. In the main, I note that Klein distances or detaches himself or his audience, using a variety of distancing techniques.

Chapter III, the conclusion, discusses Klein's perception of his role as a poet and how this is reflected in his poetry.

abstract: Master of Arts (MA)


title: Studies of Jet Flow in Enclosures

contributor:
Wood, P.E.
Mechanical Engineering

subject:
Mechanical Engineering
Mechanical Engineering

abstract:
The flow of jets in confining enclosures has significant application in many engineering processes. In particular, two jet flows have been studied; the impingement of axisymmetric jets in a confined space and a turbulent inlet wall jet in a confining enclosure.

The impingement ofaxisynunetric jets in a cavity has been examined using
flow visualization, laser Doppler anemometry, and numerical simulations. When the
flow fIeld was examined under various geometrical and fluid parameters several flow
regions were found, depending on the geometrical and fluid parameters. Initially, a
steady flow field existed for all arrangements for Red < -90 but subsequent increments in the fluid velocity caused an oscillating flow field to emerge. The onset of the
oscillations and the upper limit of fmite oscillations were found to be a function of the
nozzle diameter to chamber dimeasion ratio. Although steady numerical simulations
predicted the steady flow field well. steady simulations of the oscillating flow field
over-predicted the peak axial velocities. The oscillating flow field is considered to be
a class of self-sustaining oscillations where instabilities in the jet shear layer are
amplified because of feed back from pressure disturbances in the impingement region.

The turbulent wall jet in a cavity has been studied using flow visualization,
laser Doppler anemometry (LDA), particle streak velocimetry (PSV) and numerical
simulations. Instantaneous PSV measurements agreed well with time averaged LDA measurements. Two dimensional simulations using an algebraic stress turbulence
model (ASM) were in better agreement with the experimental data than two and three
dimensional simulations using a k - ɛ turbulence model in the wall jet region. A wall jet growth rate was found to be 54% higher than a wall jet in stagnant surroundings due to the enclosure boundaries.

abstract: Doctor of Philosophy (PhD)


title: The role of pertussis toxin in intestinal hypersensitivity

contributor:
Perdue, Mary H.
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract:
Immediate hypersensitivity (allergy) is a very common disorder, which may
develop after exposure of an individual to an antigen. Intestinal hypersensitivity
to luminal antigens has been postulated as a possible cause or triggering
mechanism in the pathogenesis of ulcerative colitis, Crohn's disease, eosinophilic
gastroenteritis, celiac disease and peptic ulcer. The mechanism by which
individuals became sensitized is not known but naturally occurring adjuvants
(bacteria and their products) may be crucial for the development of
hypersensitivity. In my studies, I investigated in the role of pertussis toxin, a
product of Bordetella pertussis, in intestinal hypersensitivity, since pertussis
vaccine containing attenuated bacteria was used previously for the induction of
anaphylaxis in experimental animals. Pertussis toxin has the enzymatic activity
of ADP-ribosyltransferase. which can block the function of some G proteins,
important elements in the transduction of signals into the cell. I sensitized rats
or mast cell-deficient mice with ovalbumin (OVA) plus recombinant wild type
pertussis toxin (wPT) as adjuvant. The reaction to secondary antigen challenge
was evaluated 14 days later by determining changes in short-circuit current (Isc, indication of net ion transport) in small intestinal segments mounted in Ussing chambers. Other parameters measured included evaluation of antibody levels in the circulation and histological enumeration of mast cells in the intestinal mucosa.

Sensitization of rats with OVA and wPT resulted in enhancement of the
jejunal ion secretory response to secondary antigen challenge as compared to
rats sensitized with OVA. Injection of doses of wPT as low as 10 ng with OVA
caused significantly elevated secondary responses to OVA, while 50 ng wPT
resulted in the maximal response. The responses to OVA challenge were
enhanced 18.7 fold when OVA was added to the luminal side of the tissues
while on serosal side this effect was enhanced 2.2 fold in sensitized rats. The
induction of hypersensitivity by wPT adjuvant was dependent on the enzymatic
activity of wPT. since the enzymatically inactive mutant (mPT) did not influence
responses to secondary antigen challenge. This suggests that ADP-ribosylation
of G proteins is involved in the elevation of hypersensitivity by wPT.

Two classes of antigen-specific antibodies, IgE and IgG₂s., were measured
in the circulation of sensitized rats. The levels of both antibody isotypes were
increased at day 14 in wPT but not mPT plus OVA injected rats, which indicates
that enzymatically active wPT influences antibody production. The role of
particular classes of antibodies was examined by passive sensitization of naive
animals with serum from actively sensitized rats. Ion transport responses to
secondary antigen challenge of intestine were present in those animals.
Blockage of IgE receptors (with myeloma IgEI prior to passive sensitization
showed that the response to OVA was totally abolished. This finding shows that
in this model of hypersensitivity. IgE antibodies are crucial for the response to antigen. Experiments on mast cell-deficient mutant mice revealed that mast cells
are a necessary element for the responses to antigen. Additionally, the number
of stainable mast cells in rat intestinal mucosa was significantiy increased by
40% on day 14 in wPT but not mPT plus OVA injected rats. This indicates that
wPT-induced increases in mast cell numbers are partially responsible for elevated
hypersensitivity responses to antigen. Experiments with the neural toxin,
tetrodotoxin (TTX), showed that responses to luminal (but not serosal) OVA
were neurally regulated in that these responses to OVA were diminished by 66%
after treatment of the tissues with TTX.

Evaluation of tne responses to OVA at different days after primary
sensitization with OVA plus wPT revealed that the responsiveness to antigen
appeared between day 3 and 7 after sensitization, and it was still present on day
228. In rats sensitized with OVA, the responsiveness to OVA was highest on
day 7 and than it decreased very rapidly, showing no responses on day 56.
Evaluation of IgE levels in rats demonstrated a similar pattern: the IgE levels were
detectable for a long time in wPT plus OVA treated rats but only on day 7 in
OVA treated rats. This suggest that elevated IgE levels caused by wPT may
account for the long lasting hypersensitivity responses.

My data showed that wPT is a very potent adjuvant for hypersensitivity
reactions and that the mechanism involves elevation of antigen-specific
antibodies, increases in the number of mucosal mast cells and enhanced neurally-mediated
antigen uptake.

abstract: Doctor of Philosophy (PhD)


title: The Properties of Lead Titanate Thin Films produced by Chemical Vapour Deposition

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

abstract:
This project focused on advancing the knowledge of chemical vapour
deposition (CVD) PbTiO₃ thin films for future work on lead zirconate titanate or PZT
(PbZrᵪT₁_ᵪO₃) through an understanding of the structural, chemical and electrical
properties of the material.

A study of the individual oxides, TiO₂ and PbOᵪ, prepared also by CVD, was
made using transmission electron microscopy (TEM), scanning electron microscopy
(SEM), Raman spectroscopy and x-ray diffraction (XRD), before a low pressure, low
temperature process for PbTiO₃ was developed. The major factors in controlling the
film composition and thickness uniformity were identified. The formation sequence
for CVO PbTiO₃ films involved individual oxides of Ti and Pb, rather than
pyrochlore-type phases. A Pb-rich composition ensured the formation of perovskite,
however it resulted in the formation of a thin PbOᵪ surface layer. Removal of this
layer by etching gave improved electrical properties. Capacitance measurements
typically varied less than 1% over the frequency range and gave ε' values from
60-155. At 1 kHz, tan δ was ~0.01 and the resistivity was ~10¹¹Ω.cm.

TEM examination of as-deposited films of PbTiO₃ revealed no macro-domains existed. After post-deposition annealing twinned structures acting as domains were
found in grains, ~0.1 μm in size. The origin of the theoretical minimum grain size
for twinning in PbTiO₃ thin films is discussed. A classification scheme for domain structures was developed based on thin films of PbTiO₃ and PZT. Similarities were
drawn between these domain structures and their bulk counterparts.

The multi-layered bottom electrode of Pt and Ti used in this study was found
to react at temperatures ≤515°C. At higher temperatures (698°C), the Ti layer was
completely consumed, however the top surface of the Pt layer remained unaffected.

abstract: Doctor of Philosophy (PhD)


title: Structural and Magnetic Properties of the Oxides AB₂O₆ (A²⁺ = Mn, Fe, Co, Ni, Cu; and B⁺⁵ = As or Sb)

contributor:
Greedan, J.
Chemistry

subject: Chemistry Chemistry

abstract:
The structural and magnetic properties of a number of transition metal oxides of the general formula AB₂O₆, where A is Mn, Fe, Co, Ni, and Cu, and B is Sb⁵⁺ or As⁵⁺, have been investigated.

CuSb₂O₆ crystallizes in a monoclinically distorted trirutile structure in the space
group P2₁/n. Magnetic suscepnbility is characterized by a broad maximum at 60 K
indicative of the presence of significant short range correlations in this system, and an
abrupt decrease in the susceptibility suggesting the presence of a magnetically ordered
state. Further analysis of the susceptibility provided that the magnetic correlations in this system are dominant along the chains; this is the first trirutile compound that gives the
clearest evidence for 1-d magnetic correlations. Long range magnetic order was further
studied by low temperature neutron diffraction. This reflection was indexed with a
propagation vector k =(½, 0, ½) in accordance with some of the trirutile phases such
as CoSb₂O₆ and FeTa₂O₆. The magnetic moment of Cu²⁺ was estimated at about 0.5 μʙ. The presence of long range order was further supported by the registration of the spin
flop transition on a single crystal of CuSb₂O₆.

CoAs₂O₆, NiAs₂O₆, and MnAs₂O₆ are isostructural and adopt the lead antimonate structure and crystallize in the space group P-3lm. Magnetic susceptibility data were
characterized by the absence of short range correlations. The long range order in these materials was studied in detail using low temperature neutron diffraction.

For NiAs₂O₆ and CaAs₂O₆, a number of superlattice reflections appears in their
respective low temperature neutron diffraction profiles which were indexed with the
propagation vector k =(0, 0, ½). The profiles of both materials were refined using the
Rietveld method in the space group P-3lm. The refinement was handled by the Rietan
program in which the refined magnetic moment of Ni²⁺ was found to be 2.11(1)μʙ, and
for Co²⁺ was 2.66(30).

The low temperature neutron diffraction profile of MnAs₂O₆ was much more
complicated than those of NiAs₂O₆ and CoAs₂O₆. An exhaustive list of propagation
vectors were used in order to fit the pattern without much success.

Lastly, in preparing the iron member of this series, Fe₂As₄O₁₂ was obtained instead of the isostruetural member of the lead antimonate structure which has a markedly different crystal structure. Although the crystal structure contains Fe₂O₉ dimers, the magnetic susceptibility did not fit the predictions of the S = 5/2 - 5/2 dimer model.
This peculiarity is attnbuted to the details ofthe crystal structure. As for the magnetically
ordered state, the superlattice reflections were indexed with the wavevector k =(0,0,0)
and the Rietveld refinement was carried out in the space group P3.

abstract: Doctor of Philosophy (PhD)


title: An Experimental and Numerical Investigation of Mixed Convection in Rectangular Enclosures

contributor:
Shoukri, M.
Wood, P.
Mechanical Engineering

abstract:
The cooling of a hot surface by fluid motion has many applications in engineering. For
these mixed convective problems, the forced component of fluid motion may be in the direction
of the buoyancy vector or it may oppose the buoyancy force. In the present study, the opposing
mode is used to study the interaction of inertia and buoyancy forces in a fluid. Both numerical
and experimental techniques are used to study the flow in a rectangular cavity of aspect ratio 2.

The inlet Reynolds number is varied between 800 and 1300 and the Grasbof number
based on the height of the enclosure is varied between 0 and 2.4 X 10¹⁰. The cases considered
correspond to Archimedes numbers of approximately 0, 1, 10 and 20.

The flow field is observed qualitatively using laser induced fluorescence and a detailed
flow field is generated using a laser doppler anemometer. Temperature profiles are found using
fine wire thermocouple probes. These detailed measurements may provide a data base for the
verification of computer programs used to predict mixed convection as there are no such detailed
chita bases in the present literature.

Numerical modelling is based on the SIMPLER algorithm with QUICK differencing. The
observed flow field indicated that some regions in the cavity were turbulent while other regions
were laminar. This observation suggests the necessity of a low Reynolds number turbulence
model. In this study, two forms of the low Reynolds number k-ε model are used. In addition,
the commercial computational fluid dynamics program, FLUENT, is used to predict the flow.

Comparison of the experimental and computational results suggest that for isothermal and buoyancy dominated flow cases the computational modelling is adequate. Difficulties arise in the prediction of the intermediate Archimedes number cases as the predicted flow is dominated by
buoyancy while the experiments show more of a balance. Sources for this discrepancy are
discussed.

abstract: Doctor of Philosophy (PhD)


title: Template-Directed Condensations between Acyl Units

contributor:
Harrison, Paul
Chemistry

subject: Chemistry Chemistry

abstract:
Glycoluril 1 acts as a bifunctional template, allowing efficient and repetitive
Claisen-type condensations between attached acyl units. Thus acetoacetyl
derivative 3 was prepared from 1 via 2. After conversion to the crotonate
derivative 4 (2 steps, β-carbonyl reduction and dehydration), a second cycle of
acylation and condensation gave crotonyl-transferred product 5. Repetition ofthe
sequence gave the 8-carbon derivative 6. Reduction of 4 with L-Selectride
afforded the butyryl derivative 7. allowing further acetylation and condensation
reactions leading towards long fatty acid chains. The product ratio from
condensation of the acetyl butyryl derivative of 1 is 4:1 in favour of deprotonation
of the acetyl group and transfer of the butyryl group. Reaction of 7 with lithium
benzyloxide gave recovered 1 and benzyl butyrate. Treatment of crotonyl acetyl

[diagram removed]

derivative 8 with L-Selectride produced only the acetyl transferred condensation
product 9. A similar regioselectivity was observed with L-Selectride reduction of
other α,β-unsaturated compounds (e.g., the acetyl acryloyl derivative). Results
of isotopic-labelling experiments support an intramolecular acyl transfer
mechanism for these condensations. This system mimics some of the features of polyketide and fatty acid synthases, allowing intramolecular acyl transfer and
repetitive additions of acetate units to make linear carbon chains while the
growing chain remains attached to the template. This is a potentially useful
method for the synthesis of some natural products and some useful organic
intermediates, such as putative oligoketide biosynthetic precursors.

abstract: Doctor of Philosophy (PhD)


title: Climate Change and Vegetation Dynamics at the Subarctic Alpine Treeline in Northwestern Canada

contributor:
MacDonald, G.M.
Geography

subject: Geography Geography

abstract:
It is expected that anthropogenic increases in atmospheric levels of CO and
other greenhouse gases will have a substantial impact on climate in the next 100
years. Knowledge of the response of high latitude vegetation to past climate
variation is useful for understanding the possible response of such vegetation to
potential future anthropogenic climate changes. The objectives of this thesis were
to investigate climate change, treeline dynamics and vegetation-climate relationships
at the subarctic alpine treeline in northwestern Canada on a variety of spatial and
temporal scales. In order to address these objectives, three hypotheses were tested:
1) Postglacial treeline change in the Mackenzie Mountains, N.W.T. was driven
by changes in the seasonal and latitudinal distribution of solar radiation; 2)
Establishment and mortality patterns of trees at treeline are episodic, controlled by
climate variations; and 3) The position of the treeline in the Mackenzie Mountains
is in equilibrium with current climatic conditions.

The first hypothesis was tested using the palynological analyses of cores
from three lakes in the tundra, forest-tundra and open forest of the central
Mackenzie Mountains. Although there was no evidence for higher treeline in this
region at any time during the Holocene, the data suggest that Picca populations in
the forest-tundra were greater than present between about 8000 and 5000 yr BP,
and have since declined steadily. These results are consistent with predicted
changes in summer insolation based on the Milankovitch theory.

The second two hypotheses were addressed using tree-ring analyses of white
spruce at a number of sites in the alpine treeline zone of northwestern Canada.
Dendroecological analyses of climate-growth relationships indicated that the
response of trees to climate at these sites varied with tree age, which violates a
basic assumption of standard dendroclimatic research. Age dependent modelling
was therefore used to produce a 350 year record of summer temperatures in
northwestern Canada from five sites in the N.W.T. and Yukon. Comparison of
this record with white spruce recruitment/survival and mortality patterns indicated
that the patterns are episodic, and controlled primarily by climatic variations. A
warming trend during the last 150 years has resulted in increases in forest-tundra
density, although there is evidence for only minor increases in treeline. The
establishment of white spruce seedlings at sites within the upper forest-tundra,
including several treeline sites, indicates that the treeline is in equilibrium with
current climatic conditions.

These results indicate that 1) climate-growth relationships are complex, and
the simplifying assumptions made in order to reconstruct climatic records from
radial growth records may in some cases be invalid; 2) in this region the response
of white spruce populations to climate change on a variety of timescales has been
manifested primarily as an increase in forest-tundra density, with little change in
treeline altitude; and 3) seedlings are currently being produced within forest-tundra
white spruce populations, and thus a rapid response to further climatic amelioration may be possible.

abstract: Doctor of Philosophy (PhD)


title: The Physiological Adaptations of Two Salmonids, the Rainbow trout (Oncorhynchus mykiss) and the High pH Tolerant Lahontan Cutthroat Trout (Oncorhynchus clarki henshawi), to Highly Alkaline Environments

contributor:
Wood, Chris M.
Biology

subject: Biology Biology

abstract:
Efforts to stock salmonids into alkaline waters have had little success. Accordingly,
this thesis examined the survival and physiology of two salmonids, the rainbow trout (RBT;
Oncorhynchus mykiss) and the high pH tolerant Lahontan cutthroat trout (LCT; Oncorhynchus
clarki henshawi) experimentally exposed to alkaline pH. ExPosure of RBT (acclimated at pH
8.0) to pH 9.5, for up to 4 weeks, led to minimal mortality and was characterized by
transiently inhibited ammonia excretion rates (JAmm), and chronically elevated plasma and
white muscle total ammonia stores (TAmm = NH₃ + NH₄⁺). Elevated plasma TAmm facilitated recovery of JAmm by maintaining positive NH₃, gradients across the gill epithelium. Temporarily elevated urea excretion rates prevented internal TAmm from reaching toxic levels
while JAmm was inhibited. A chronic respiratory alkalosis (decreased blood Pcon) rapidly developed at high pH, but a counterbalancing metabolic acidosis (decreased blood [HCO₃⁻]), which initially resulted from elevated white muscle lactic acid production, stabilized blood pH after 1 day. Transient and chronic decreases in gill Cl⁻ transporter (J^cl max) and Na⁺ transporter (J^Na max) number, respectively, resulted in decreased Cl⁻ and Na⁺ uptake and led to reduced plasma [Cl⁻] and [Na⁺]. A complete recovery of J^cl max (by 3 days) and counterbalancing reductions in gill Na⁺ losses, re-estahlished internal ion balance beyond 3
days. In contrast, the LCT (reared at pH 8.4) never before exposed to alkaline pH, rapidly
adapted to the alkaline (pH 9.4) waters of Pyramid Lake, Nevada, their natural adult habitat.
These adaptions included permanently reduced basal ammonia production which was reflected in chronically lowered JAmm and minimal, temporary increases in plasma TAmm. Chronic elevations in plasma NH₃, were not required for maintenance of JAmm in the LCT. The LCT also underwent a chronic respiratory alkalosis and a transient metabolic alkalosis but increases in gill chloride cell exposure quickly mitigated the continual base load by facilitating HCO₃⁻ excretion. No disturbances to internal ion balance were observed. The responses of LCT to challenge in more alkaline (pH 10) lake water resembled those of RBT at pH 9.5 (15ºC) and greatly increased plasma NH, and reduced plasma ion concentrations, resulted in 50 %
mortality by 72 h. In conclusion, alterations in N-waste metabolism and gill functional
morphology facilitate salmonid survival at high pH. However, the ability of LCT to rapidly
make these adjustments, with minimal disblrbance to its pre-exposure physiological status,
enables it to survive in an environment which is unsuitable for other salmonids.

abstract: Doctor of Philosophy (PhD)


title: Drag Coefficient for Tethered Spheres In a Vertical Pipeline With and Without Polymer Addition

contributor:
Latto, B.
Mechanical Engineering

abstract:
This thesis is concerned with experimental study of the drag coefficient of tethered spheres in a vertical pipeline of approximately 0.05 m diameter using water and dilute polymer solutions.

Experiments were conducted using four different sphere-to-tube diameter ratios ranging from 0.439 to 0.87. The liquid velocities as well as the associated drag forces and pressure drops were measured, which enabled both the drag coefficients and pressure functions to be computed.

Semi-empirical correlations were obtained for the drag coefficient and the pressure function in the range of tube Reynolds number of 3.9 x 10³ to 9.2 x 10⁴.

In the experiments using Reten 423 for the diluted polymer solutions, it was observed that a maximized drag reduction would occur at concentration of about 24 wppm for spheres of d/D > 0.74. Drag reductions of up to 60% were obtained which are of a higher order of magnitude than that for non-tethered spheres which has been previously observed.

abstract: Master of Engineering (ME)


title: Biogenesis of peroxisomes in the yeast Candida tropicalispK233: Genes, proteins and organellar targeting

contributor:
Rachubinski, R.A.
Biochemistry

subject: Biochemistry, Biophysics, and Structural Biology

abstract:
Studies concerned with peroximes biogenesis have established that peroxisomal proteins are encoded exclusively by nuclear genes, synthesized (with few exceptions) on free polyribosomes at their mature size and posttranslationally imported into preexisting oganelles. From this, it was realized that the information responsible for the specificity of protein targeting to peroxisomes must reside within the mature amino acid sequence of the imported protein. Knowledge of the targeting sequences of peroxisomal proteins is, however, limited. Consequently, using the yeast C. tropicalis pK233 as a model system, this work endeavoured to clone and sequence a cDNA or gene encoding a peroxisomal protein so that the subsequent creation of deletion mutants of this cDNA/gene, together with the development of and in vitro and/or in vivo expression and translocation system for the corresponding polypeptides, would allow the amino acid sequence(s) comprising the peroxisomal addressing signal of this protein to be identified.

Related efforts resulted in the cloning of two genes (and one composite full-length cDNA) encoding different enzymes associated with the C. tropicalis peroxisomes. Sequencing of the gene encoding acyl-coenzymes A oxidase (AOx), revealed a single open reading frame, without intervening sequences, of 2,127 nucleotides which encodes a polypeptide of 709 amino acids (Mr 79155). The deduced amino acid sequence of C. tropicalis AOx exhibits significant identity and homology with that of several other acyl-coenzyme A oxidases of C. tropicalis, as well as other yeasts (C. maltosa and S, cerevisiae) and rat. By comparison, sequencing of the C. tropicalis gene (or cDNA) encoding catalase (Cat) revealed a single open reading frame of 1,455 nucleotides, without intervening sequences, which encodes a polpeptide of 485 amino acid (Mr 54944). The deduced amino acid equence of C. tropicalis Cat shows sigificant identity and homology with that of catalases from the yeast S. cerevisiae mammals (rat, human and bovine), plants (maize, sweet potato and cottonseed) and Drosophila. COdon usage in the genes encoding C.tropicalis AOx and Cat is nonrandom, exhibiting a strong bias towards a group of preferred codons of S. cerevisiae and E. coli, as weel as other C. tropicalis genes encoding peroxisomal proteins.

Having achieved the charaterization of the genes encoding C. tropocalis AOx and Cat, attempts were made to establish an in vitro system for the translocation of Cat into peroxisomes purified from C. tropicalis which could be used to determine the peroxisomal targeting signal (PTS) of Cat. For this purpose, N-terminal, C-terminal, N-/C-terminal and internal deletion mutants of Cat were constructed, expressed in cell-free systems and assayed for translocation into purified C. tropicalis perxisomes. Unfortunately, all attempts at in vitro imports proved to be inadequate for the translocation of Cat into purified C. tropicalis peroxisomes. Since a functional in vitro system could not be established, studies concerned with the in vivo expression and targeting of Cat from C. tropicalis to the peroxisomes of C. albicans and S. cerevisiae were initiated. Although, the in vivo expression of Cat sequences could not be attained in C. albicans, the expression of full-length and truncated Cat polypeptides was achieved in S. cerevisiae. Subsequent determination of the subcellular location of the full-length Cat polypeptide suggested that Cat from C. tropicalis was targeted to the peroxisomes of S. cerevisiae, reaffirming that heterologous signals for import into peroxisomes are recognized in S. cerevisiae. Interestingly, the deletion of amino acids 182 to 344 of Cat negated the targeting of Cat to S. cerevisiae peroxisomes. These preliminary in vivo studies suggest that at least part of the PTS of Cat from C. tropicalis resides at an internal location within its mature amino acid sequence.

abstract: Doctor of Philosophy (PhD)


title: Kinetics, mechanisms and modelling of calcium treatment of steel

contributor:
Irons, G.A.
Lu, W-K.
Materials Science and Engineering

abstract: Steel-clad calcium wire was fed into 40 kg heats of AISI steel with various sulphur and aluminum contents under argon atmosphere. Samples were taken continuously during and after calcium injection for chemical and inclusion analysis from more than twelve heats of injection. Calcium dissolution was found to be enhanced by instantaneous reactions with oxygen and sulfur in the boundary layer. The unreacted calcium diffuses through the gas-liquid film into the melt for oxide and sulfide inclusion modification. The overall interaction between oxides and sulfides with the bulk drives towards the equilibrium of (CaO) + S = (CaS) + O. The system paths from the initial state to the final state were kinetically studied with the assistance of aCaS-aMnS diagrams, which were calculated by applying a regular solution model to the solid phase and an ideal model to the liquid phase of the CaS-MnS phase diagram at various steelmaking temperatures. A mathematical model for the multiphase kinetics was developed to interpret the calcium dissolution, deoxidation, desulphurization, oxide and sulfide inclusion modification during and after calcium injection. The implications for full-scale operation were discussed.

abstract: Doctor of Philosophy (PhD)


title: Boron Cosmochemistry

contributor:
Shaw, D.M.
Geology

subject: Geology Geology

abstract:
The efforts I made for the analysis of boron isotope composition in meteorites are first discussed. Alkali
fusion followed by boron-selective anion exchange resin
purification is not suitable for the analysis of silicate
rocks because of precipitation in the sample solution and
consequent loss of boron. An HF dissolution followed by
cation exchange resin and anion exchange resin purification
needs improvement to remove some interference elements.
Mass spectrometry of boron converted to potassium borate has
a standard deviation of 0.08% (2σ) which is acceptable for
boron isotope analyses.

Thirty six fragments of meteorite falls, never touched
by water or other possible sources of boron contamination
were analyzed for B by prompt gamma-ray neutron activation
analysis at McMaster University and at the U.S. National
Institute of Standards and Technology. Boron concentrations
are close to the sensitivity limit in both laboratories.
Results between the two laboratories agree well, but with
slight systematic differences attributable to blank and
background correction factors.

The mean B concentrations in different meteorites are similar, from 0.5 to 0.9 ppm, and the ranges in different
carbonaceous chondrite (CC), ordinary chondrite (OC) and
achondrite (ACH) classes overlap, mostly from 0.3 to 1.4
ppm. similar to previous measurements on falls. H, Land LL
ordinary chondrites overlap in B content with Antarctic
chondrites.

The solar system abundance, taken as the mean B content
of the matrix in all carbonaceous chondrites was calculated
from seven samples and is 0.69 ± 0.09 ppm. When normalized,
this abundance is 16.9 ± 2.2 (atoms/10^σSi). Normalized B
and S concentrations show a linear relationship in the CC;
the average OC lies on the sarne line, but individual OCs are
dispersed.

This solar system abundance supports a nucleosynthesis
model, in which boron was formed by continual bombardment of
interstellar medium (ISM) by the galactic cosmic rays
(GCRs), to which a very intense low energy is added.

The Si and CI meteorite normalized abundances of
moderately volatile and low-refractory elements in
carbonaceous chondrites show a linear correlation with their
condensation temperatures. Compared with other elements, the normalized boron abundances in CM, CO, and CV meteorites indicate that the boron condensation temperature is about 910 ºK, similar to gallium.

abstract: Doctor of Philosophy (PhD)


title: Thermal rearrangements of 3H-pyrazoles, 4H-pyrazoles, and cyclopentadienes

contributor:
Warkentin, John
Chemistry

subject: Chemistry Chemistry

abstract:
3H-Pyrazoles generally undergo thermal rearrangement by concerted [1,5]-sigmatropic migrations. It has been discovered that 3H-pyrazoles 111a-e undergo thermal rearrangement by an alterative mechanism. A stepwise, ion-pair, mechanism operates in these rearrangements, in benzene/toluene, chloroform, and methanol solvents. This mechanisms operates because the R sustituents can form relatively stable cations. Large rate enhancements for these rearrangements combined with ion-pair trapping by methanol support this mechanism

[Figure Removed]

Since, 3H-pyrazoles 111b and 111e rearrange to afford 4H-pyrazoles 120b and 120e, respectively, the thermal rearrangements of these more stable isomers were investigated. Ion-pair trapping experiments with methanol suggest that these 4H-pyrazoles also rearrange by a stepwise mechanism and that different ion-pair intermediates are formed from these 4H-pyrazoles compared to the isomeric 3H-pyrazoles.

The sensitivity of the stepwise mechanism to the stabilization of the pyrazoles nucleus was explored in the study of the thermal rearrangements of 128b-e. Based on cation trapping experiments with methanol it appears that 3H-pyrazoles 128b-e rearrange by a stepwise mechanism in methanol, but with "tighter" ion pair intermediates. A concerted mechanism, with some charge separation, seems to operated in the thermal rearrangements of 128f.

The generality of rearrangement by a stepwise mechanism was explored by studying the thermal rearrangements of cyclopentadienes 148 a-e. Cyclopentadienes 148 a-d undergo stepwise rearrangement in methanol solvent, based on ion-pair trapping experiments, while cyclopentadiene 148e rearranges by concerted [1,5]-sigmatropic migrations of carbomethoxy.

This work has shown that thermal rearrangements, where a concerted sigmatropic mechanism can in theory operate, do not necessarily proceed by this mechanism. Furthermore, transition states for such rearrangements seem to run from those with little or no charge seperation, through transition states with increasing charge separation, to the two-step, ion-pair extreme.

abstract: Doctor of Philosophy (PhD)


title: Characterization of A Ca²⁺ release channel in smooth muscle

contributor:
Kwan, Chiu-Yin
Daniel, Edwin E.
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract:
Ryanodine, a neutral alkaloid, is a widely used pharmacological tool in the studies
of muscle excitation-contraction coupling. The specific binding sites for ryanodine have
been identified to exist on sarcoplasmic reticulum (SR) in both skeletal muscle and
cardiac muscle. The ryanodine receptor has been purified from different tissue types. The purified ryanodine receptor from skeletal muscle was found to be identical with foot
structure, a protein spanning the gap between t-tubule and SR membrane. The ryanodine
receptor was also found to have Ca²⁺ channel activity, a Ca²⁺-induced Ca²⁺ release channel.
In functional studies with isolated SR vesicle or single channel, ryanodine was found to
have dual effects on Ca²⁺ channel. At lower concentrations, ryanodine locked Ca²⁺ channel
in the open state, but fully closed the channel at higher concentrations. In smooth muscle,
ryanodine was also found to affect intracellular Ca²⁺ movement in the functional studies
using intact tissue. However, direct evidence was not available for the presence of
ryanodine receptor in smooth muscle before this research was carried out.

In the present study, a high affinity binding site was found located on SR
membranes of rat vas deferens (RVD) smooth muscle (Kd=5.6 nM, Bmax=435 fmol/mg).
The ryanodine receptor in smooth muscle shared many similarities with that of skeletal
muscle, but was not identical. The time required for [³H]ryanodine binding to microsomal
fraction was about two hours to reach a steady state, and [³HJryanodine could be dissociated from its binding site by 20 fold dilution. However, the dissociation was very
slow and incomplete when initiated by excess ryanodine. The [³H]ryanodine binding in
smooth muscle was Ca²⁺ dependant. The affinity was increased with increased Ca²⁺
concentrations, but the Bmax was unchanged. The [³H]ryanodine binding also increased
with higher ionic strength and higher osmolarity, but later has less effect. Many factors
that affect Ca²⁺-induced Ca²⁺ release (CICR) channel activity were also found to affect [³H]ryanodine binding in my study; e.g., both Mg²⁺ and ruthenium red inhibited binding
and caffeine potentiated it, especially in the presence of a low Ca²⁺ concentration. In the
present study, I also showed that varied levels of [³H]ryanodine binding site existed among different smooth muscles. This variation was not correlated with the density of innervation or the SR content of different smooth muscles.

In dog mesentery artery smooth muscle, a low affinity binding site (Kd=269 nM) was also identified, in addition to the high affinity binding site.

In the present study, I also tried to show functional effect of ryanodine on the
CICR channel using subcellular membrane vesicles from vas deferens. Ryanodine, at
higher concentrations, inhibited oxalate-stimulated Ca²⁺ uptake, an effect which was observed as early as 5 minutes after uptake was initiated. This inhibitory effect was partially additive to that of cyclopiazonic acid (CPA), a potent SR Ca²⁺ pump inhibitor,
when this agents were used at submaximal concentrations. However, when CPA was used at a maximal concentration, ryanodine had no additional effect. Ryanodine at concentrations of 10⁻⁹ to 5x10⁻⁴ M, did not significantly change the Ca²⁺ release rate. In Ca²⁺ release experiments, no functional Ca²⁺ channel was observed, but the data are consistent with an inhibition of the SR Ca²⁺ pump at high ryanodine concentrations.

My study provided the first direct evidence ofthe existence ofryanodine receptors located on smooth muscle SR which may represent a CICR channels. Since another type of Ca²⁺ channel, IP₃-induced Ca²⁺ release channel (IICR), has also been identified in different smooth muscles, the varied levels of ryanodine binding site observed in the present study may be correlated to the ratio of occurrences of the two types of Ca²⁺ channel. This suggests that different excitation-contraction coupling mechanisms may exist in different tjpes of smooth muscle depending on different expression of these two channels. The present study also suggests that ryanodine, at higher concentrations, may inhibit the Ca²⁺ pumps located on SR. Suitable conditions for membrane isolation and Ca²⁺ transport experiment must be defmed to restore a functional Ca²⁺ release channel in smooth muscle, in order to study the functional effect of ryanodine on this channel.

abstract: Doctor of Philosophy (PhD)


title: Pseudo-Differential operators

contributor:
Sawyer, Eric
Mathematics

subject: Mathematics Mathematics

abstract:
The theory of pseudo-differential operators is one of the most important tools
in modern mathematics. It has found important applications in many mathematical
developments. It was used in a crucial way in the proof of the Atiyah-Singer
Index theorem in [AtSi] and in the regularity of elliptic differential equations.
In the theory of several complex variables, pseudo-differential operators
are indispensable in studying the [symbol removed]-Neumann problem. The theory of subelliptic
and hypoelliptic differential operators achieved its current satisfactory
state largely because of pseudo-differential operators. In the solution to the
local solvability problem for differential equations by Beals-Fefferman [BeFe], pseudo-differential operators played the key role. Many boundary value problems for differential equations can be reduced to pseudo-differential equations, see for example, Hörmander [Hor2]. Roughly speaking, almost everything involving pseudodifferential operators can be reduced to two parts: the mapping
properties and the compositions of the associated special pseudo-differential
operators.

In this thesis, we consider the mapping properties and symbolic calculus
of an important class of pseudo-differential operators, the symbolic class of
Hörmander type with rough coefficients. We will prove some new results for
these operators. These operators arise naturally from problems in nonlinear partial differential equations. After the introduction of the classical symbol
class [symbol removed] in [KohNi], Hormander considered symbolic class [symbol removed] in [Horl]. Eventually, such classes of pseudodifferential operators played a key role in the local solvability problem for differential operators (see Beals-Fefferman
[BeFe]). It is observed by Guan-Sawyer in [GuSa1] that the oblique derivative
problem can be reduced to the problem of pseudodifferential equations on the
boundary with a parametrix in the class [symbol removed]. That discovery led them to establish complete optimal regularity for the oblique derivative problem with
smooth data. Later, they used the class [symbol removed] to study some nonlinear oblique
derivative problems in [GuSa2]. While observing that the symbols arising here
lie in the symbol class [symbol removed], P. Guan and E. Sawyer [GuSal] discovered that such symbols actually behave much better than where [symbol removed].

Indeed,

[equation removed]

where [symbol removed], and [symbol removed]. Thus τ decomposes into two pieces, one term having order worse by ½ but no loss in smoothness, another term having
1 degree less smoothness but no loss of order. Moreover this property persists
for each of the symbols τ₁ and τ₂, etc., resulting in such symbols enjoying the
mapping properties of the better behaved class [symbol removed].

There have been many developments regarding the mapping properties
and compositions of symbols in the class [symbol removed]. Specifically, the works of C.
Fefferman, C. Fefferman and E. Stein, A. Calderon and R. Vaillancourt, R.
Coifman-Y. Meyer, A. Miyachi, we refer to [St2] for the complete references.
Our results in this paper can be viewed as a further step in this direction.

In this thesis mapping properties of pseudo-differential operator are studied in various symbol classes.

In the first result (Theorem 2.3.1) we consider the symbol class [symbol removed] and obtain L2 results extending those of [CoMe].

For the symbols in the class [symbol removed], mapping properties are obtained for
Hʳp sobolev spaces (Theorem 2.3.2) and finally we consider pseudo-differential
operators of symbol class [symbol removed], and prove that they have better mapping
properties (Theorem 2.3.3).

abstract: Doctor of Philosophy (PhD)


title: EFFECTS OF [symbol removed]3-POLYUNSATURATED FATTY ACIDS ON TIlE FORMATION OF sn-1,2-DIRADYLGLYCEROL, CYTOKINE SECRETION AND THE REGULATION OF PROTEIN KINASE C ACTIVITY

contributor:
Sebaldt, Rolf J.
Medical Sciences

abstract:
The focus of my thesis was to investigate changes in the formation of
second messenger sn-1,2-diradylglycerol (DG) and phospholipids (PL) in murine
peritoneal macrophages in vitro and in vivo in response to varying concentrations
of the 3-olyunsaturated fatty acids ([symbol removed]3PUFA), eicosapentaenoic (EPA, 20:5[symbol removed]3) and docosahexaenoic (DHA, 22:6[symbol removed]3) acids. My findings establish for the first time that the incorporation of EPA and DHA into DG and membrane PL occurs
independently and dose-dependently, with EPA being incorporated to a greater
extent than DHA.

It was of interest to investigate the functional correlations of the substitution
of [symbol removed]3PUFA into DG and PL molecular species. DG is classically known as the physiological activator of protein kinase C (PKC). I investigated the effects on
PKC activation by pure species of diacylglycerol (DAG) with oleoyl, arachidonoyl,
eicosapentaenoyl or docosahexaenoyl at the sn-2 position. These results showed
that DG species with DHA or EPA incorporated at the sn-2 position activate PKC.
However, while DG with DHA at the sn-2 position activated PKC to a similar
extent as did DG with AA at the sn-2 position (representative of physiological DG),
DG with EPA at the sn-2 position activated PKC to a significantly lesser degree.
To the best of my knowledge, this is the first demonstration in the literature that the activation of PKC in vitro differs significantly among these molecular species
of DAG.

The immunoregulatory cytokine, interleukin-6 (IL-6), is produced in
response to tissue injury and inflammation and in vitro by LPS-stimulated
macrophages. I investigated the correlation of [symbol removed]3PUFA substitution into DC and
secretion of IL-6 by LPS-stimulated murine peritoneal macrophages. These results
show for the first time that IL-6 secretion is attenuated by [symbol removed]3PUFA, and to a
greater extent by DHA than by EPA.

I have obtained several novel findings that contribute to improved
understanding of the underlying mechanisms by which [symbol removed]3PUFA function at the
level of signal transduction. The ability to modify the fatty acid composition of the
signalling molecule, DG, with [symbol removed]3PUFA can now be used for future research to
further elucidate the functional ramifications of [symbol removed]3PUFA in cell signal
transduction.

abstract: Doctor of Philosophy (PhD)


title: Characterization of the human pulmonary fibroblast derived from the normal lung and from the lung of patients with idiopathic pulmonary fibrosis

contributor:
Gauldie, Jack
Medical Sciences

subject:
Medicine and Health Sciences
Medicine and Health Sciences

abstract:
The proliferative behaviour of human lung fibroblasts in vitro was examined. Fibroblasts derived from the lung of patients with idiopathic pulmonary fibrosis proliferated faster compared to fibroblasts from control lung tissue. An examination of clonally-derived fibroblast lines showed a substantial degree of fibroblast heterogeneity which followed a normal distribution, and also the existence of a significantly greater number of fast-growing clones in the panels of clones derived from primary fibroblast lines established from fibrotic tissue. Heterogeneity with respect to the expression of collagen genes was also documented.

The effect of an acute challenge of peripheral blood monocyte and/or alveolar macrophage supernatants on fibroblast proliferation was examined. Supernatants from peripheral blood monocytes and alveolar macrophages stimulated with lipopolysacharide elicited a dose-dependent inhibition of fibroblast proliferation, likely induced by interleukin 1. This effect could be prevented by pre-treating the fibroblasts with indomethacin and reconstituted by adding exogenous prostaglandin E$\sb2$, thus indicating the involvement of the prostaglandin E$\sb2$ pathway of the fibroblast. Exogenous prostaglandin E$\sb2$ directly caused an inhibition of fibroblast proliferation, and fibroblasts derived from fibrotic tissues were shown to be hyporesponsive to this mediator. Supernatants from unstimulated alveolar macrophages obtained from rats which had been given intratracheal bleomycin caused a similar effect on the proliferation of rat lung fibroblasts.

Primary lines of fibroblasts chronically exposed to peripheral blood monocyte supernatants became hyporesponsive to both these supernatants and prostaglandin E$\sb2$, and released greater amounts of prostaglandin E$\sb2$, upon rechallenge compared to unexposed fibroblasts. An examination of clonally-derived lines showed marked heterogeneity in the responsiveness of individual clones to peripheral blood monocyte supernatants and prostaglandin E$\sb2$ as well as a change in the clonal distribution after chronic exposure to peripheral blood monocyte supernatants. Chronic exposure of sensitive clones to peripheral blood monocyte supernatants did not alter their level of responsiveness.

abstract: Doctor of Philosophy (PhD)


title: Mechanism of action of vasoactive intestinal peptide on ion channels in endothelial cells

contributor:
Daniel, E.E.
Biomedical Sciences

abstract:
Endothelial cells contain a high density of vasoactive intestinal peptide (VIP) receptors. Since VIP is a potent vasodilator, activation of these receptors may lead to the release of endothelium-dependent relaxing factor (EDRF). Using patch-clamp techniques it was demonstrated that VIP modulates plasma membrane K$\sp+$ channels in bovine pulmonary artery endothelial cells. VIP inhibited activity of inwardly rectifying K$\sp+$ channels (I$\sb{\rm Kin}$) and activated opening of the Ca$\sp{2+}$-dependent K$\sp+$ channels (K$\sb{\rm Ca}$). Activation of K$\sb{\rm Ca}$ channels tends to hyperpolarize the cell membrane. This transient hyperpolarization increases the driving force for influx of extracellular Ca$\sp{2+}$ through nonselective cation channels. This way VIP may contribute to Ca$\sp{2+}$ influx necessary for the potential EDRF production.

Although VIP activates adenylate cyclase and production of cyclic AMP (cAMP) in many cell types, this study provides evidence allowing us to exclude cAMP as a second messenger for VIP action in endothelial cells. Direct evidence comes from the measurements of cAMP level in bovine pulmonary artery endothelial cells stimulated with VIP and isoproterenol. Isoproterenol increased cAMP level, whereas VIP did not, or even decreased cAMP production in some cases. Indirect evidence comes from the results of patch-clamp experiments. VIP strongly suppressed I$\sb{\rm Kin}$ channel activity, whereas the inhibitory effect of isoproterenol on this channel was very weak (about 20% of the VIP effect). cAMP elevation may reduce the activity of I$\sb{\rm Kin}$ channel, but is not a mediator for the inhibitory effect of VIP on these channels. In addition, VIP was still able to inhibit I$\sb{\rm Kin}$ channel activity in outside-out patches, where the second messenger system is not operating. This effect was mediated by a G protein that most likely couples directly to the channel. This unidentified G protein revealed GTP-$\gamma$-S and cholera toxin sensitivity and resistance to pertussis toxin.

Since elevated intracellular Ca$\sp{2+}$ is a trigger for EDRF production, it has been demonstrated that modulation of the calcium fluxes at the level of internal stores did influence an influx of extracellular Ca$\sp{2+}$. Cyclopiazonic acid (CPA), an inhibitor of SR/ER Ca$\sp{2+}$ pump, (i) induced K$\sb{\rm Ca}$ currents, presumably as a consequence of the spontaneous leakage of Ca$\sp{2+}$ from internal stores, (ii) reduced the I$\sb{\rm Kin}$ currents, and (iii) enhanced influx of extracellular Ca$\sp{2+}$ through nonselective cation channels. Moreover, CPA activated K$\sb{\rm Ca}$ currents in endothelial cells by a mechanism independent of 1,4,5-triphosphate (IP$\sb3$). An expected consequence of this action of CPA may be an influx of extracellular Ca$\sp{2+}$. In parallel studies, it has been demonstrated that CPA relaxed rat aorta in endothelium-dependent manner, suggesting CPA-induced release of EDRF. Ca$\sp{2+}$ enters the endothelial cell through nonselective cation channels, which can be activated by an agonist or a mechanical stimulus (e.g. stretch). It is still unclear whether these nonselective cation channels in bovine pulmonary artery endothelial cells are controlled by free intracellular Ca$\sp{2+}$, empty Ca$\sp{2+}$ ER stores or an agonist.

abstract: Doctor of Philosophy (PhD)


title: The Effect of Highway Traffic on the Noise Levels Produced by Aircraft Overflight

contributor:
Dokainish, M. A.
T., J. H.
Mechanical Engineering

abstract:
The problem of highway traffic noise in conjunction with the noise levels produced by aircraft overflight in the vicinity of a general aviation airport is studied. The Toronto-Buttonville airport has been examined and specific examples to illustrate the influence of surface traffic moving along two arterial roadways, the Queen's Highway No. 7 and the regional road Woodbine Avenue, on the noise levels in the vicinity of the airport.

Based on actual measurements for both air and surface traffic and utilizing predicted increases for the year 1980, the results from both sound sources have been analysed, combined and presented in the form of contour lines using computer programs developed in this study.

abstract: Master of Engineering (ME)


title: STUDIES ON THE GROWTH, DISSOLUTION AND EQUILIBRIUM SOLUBILITY OF Sa, Pb AND Ra SULFATES IN AQUEOUS SULFATE MEDIA: WITH APPLICATIONS TO THE SULFURIC ACID LEACHING PROCESS FOR URANIUM MILLING

contributor:
Hileman, O. E.
Chemistry

abstract:
The formation of hetero-epitaxial deposits of Sa, Pb and
mixed Ba/Pb and Ba/Ra sulfates on quartz and mica surfaces
has been demonstrated. The kinetics of their growth and
dissolution has been established. The importance of the
formation and dissolution of these deposits is found in the
observation that they are all host solids for the formation of
solid solutions of 228-radium (and by extension 226-radium).

Desorption studies caried out on Ba²⁺, Ca²⁺ and SO₄²⁻ from quartz and mica surfaces into water indicate that these
ions are strongly retained by mica surfaces, with retention
times which are of sufficient duration to permit the formation
of the potential host solids required by the National Uranium
Mine Tailings model.

The equilibrium solubility of PbSO₄ in Na₂SO₄ solutions
and in H₂SO₄ solutions from 0 to 6m has been measured
experimentally at 60ºC with subsequent modelling by means of
the Pitzer formulation for ion activities at high ionic strength.
The equilibrium solubility of BaSO₄ in H₂SO₄ solutions from 0
to 6m has been measured experimentally at both 25ºC and
60ºC with subsequent modelling. Such data are a necessary requirement for the modelling of the evolution of uranium mill wastes by the National Uranium Mine Tailings model and for
understanding the fate of radium during the milling and
leaching processes.

abstract: Doctor of Philosophy (PhD)


title: Interrelationships of deformity, impairment, disability and handicap in adolescent idiopathic thoracic scoliosis

contributor:
Killian, K.J.
Campbell, E.J.M.
Physiology and Pharmacology

subject: Pharmacology Physiology Pharmacology

abstract:
The purpose of this thesis was to quantify spinal deformity (nature and extent), pulmonary impairment (mechanical and gas exchanging properties), disability (working capacity) and handicap (exertional symptoms) in a large group of subjects with idiopathic scoliosis, so that the relationships between these elements could be determined. It was anticipated that these relationships would be more variable (weaker) than is commonly implied. A further aim therefore, was to identify additional factors which contribute to pulmonary impairment, disability and exertional symptoms in these subjects. The influences of respiratory muscle, peripheral muscle and cardiac factors on these relationships were considered to be potentially important.

Seventy-nine subjects (M:F 13:66; age 21 (SD 10.1)) with mild-moderate idiopathic thoracic scoliosis (Cobb angle 45° (SD 18.4)) were studied.

Pulmonary impairment in the group as a whole was moderate, with the vital capacity being reduced to 79% of predicted (SD 13.6). Angle of scoliosis was one of four features of the spinal deformity which contributed to pulmonary impairment; longer curves (number of vertebrae), higher curve position and loss of the normal thoracic kyphosis also had an additive influence.

Disability was significant, with exercise capacity being reduced to 86% (SD 17.4) of predicted; nature and extent of spinal deformity was unrelated to disability. Similarly, there was no direct relationship between pulmonary impairment and the extent of disability.

Application of psychophysical symptom rating scale showed that both the intensity of breathlessness and leg effort were increased during exercise, but most subjects stopped exercising due to leg effort rather than breathlessness. This finding focused attention on the relationship of disability to peripheral muscle factors.

Leg muscle volume and lean body mass were closely related to maximum working capacity. The relationship of leg muscle volume to maximum oxygen consumption was similar to that previously reported in normal subjects; this suggests that reduced muscle bulk, rather than qualitative muscular differences, is a particularly important contributor to disability. Once between subject differences in muscularity were taken into account, an additional influence of pulmonary impairment on disability was evident.

A higher heart rate response during exercise was also found in more disabled subjects, suggesting that cardiac performance may also influence work capacity in this group. (Abstract shortened by UMI.)

abstract: Doctor of Philosophy (PhD)


title: Biogenesis of peroxisomes in the yeast Candida tropicalis pK233: Genes, proteins and organellar targeting

subject: Biochemistry Biochemistry

abstract: Related efforts resulted in the cloning of two genes (and one composite full-length cDNA) encoding different enzymes associated with the $\beta$-oxidation pathway of C. tropicalis peroxisomes. Sequencing of the gene encoding acyl-coenzyme A oxidase (AOx), revealed a single open reading frame, without intervening sequences, of 2,127 nucleotides which encodes a polypeptide of 709 amino acids (Mᵣ 79155). The deduced amino acid sequence of C. tropicalis AOx exhibits significant identity and homology with that of several other acyl-coenzyme A oxidases of C. tropicalis, as well as those of other yeasts (C. maltosa and S. cerevisiae) and rat. By comparison, sequencing of the C. tropicalis gene (or cDNA) encoding catalase (Cat) revealed a single open reading frame of 1,455 nucleotides, without intervening sequences, which encodes a polypeptide of 485 amino acids (Mᵣ 54944). The deduced amino acid sequence of C. tropicalis Cat shows significant identity and homology with that of catalases from the yeast S. cerevisiae, mammals (rat, human and bovine), plants (maize, sweet potato and cottonseed) and Drosophila. Studies concerned with the in vivo expression and targeting of Cat from C. tropicalis to the peroxisomes of C. albicans and S. cerevisiae were initiated. Subsequent determination of the subcellular location of the full-length Cat polypeptide suggested that Cat from C. tropicalis was targeted to the peroxisomes of S. cerevisiae, reaffirming that heterologous signals for import into peroxisomes are recognized in S. cerevisiae. Interestingly, the deletion of amino acids 182 to 344 of Cat negated the targeting of Cat to S. cerevisiae peroxisomes. These preliminary in vivo studies suggest that at least part of the PTS of Cat from C. tropicalis resides at an internal location within its mature amino acid sequence. (Abstract shortened by UMI.)

abstract: Doctor of Philosophy (PhD)


title: Consequences of quinolinic acid-induced lesions of the neostriatum and frontal neocortex in rats: Behaviour, neuroanatomy and neurochemistry

contributor:
Mazurek, Michael F.
Neurosciences

subject: Neurosciences Neurosciences

abstract: Animals with kainate- and ibotenate-induced lesions demonstrated significant nocturnal hyperactivity; however, no such effect was found in the quinolinate lesioned animals. Further, the hyperactivity in the kainate- and ibotenate-lesioned animals attenuated over prolonged testing. This study indicates that spontaneous nocturnal activity may not always be an adequate measure of striatal dysfunction. Secondly, the behavioural profile of rats with quinolinic acid-induced lesions of the medial striatum was characterized. The lesioned rats were found to be impaired in two tests of cognitive behaviour, the Morris Water Maze and the spontaneous alternation task, but were apparently unimpaired on a host of motor tests, thus strengthening the interpretation that the impairment demonstrated on the two cognitive tasks was indeed indicative of impaired visuospatial processing. The behavioural data also suggested that the lesioned animals showed impaired cognitive flexibility, and an inability to change learning strategies. Histological analysis revealed significant striatal degeneration seemingly in the absence of cortical degeneration, thus suggesting that lesions largely restricted to the medial striatum are sufficient to produce a behavioural impairment. Animals were found to be impaired in the Morris Water Maze, but were unimpaired on a number of motor tests. Histological analysis demonstrated the presence of marked cortical degeneration; interestingly, striking ventricular dilation was also present in most of these animals. The results were discussed in relation to the pathology of HD. Lastly, a morphometric study was performed on rats with chronic excitotoxin-induced striatal lesions. Degenerative changes were noted in the striatum, substantia nigra and thalamic nuclei, but no changes were found in the thalamus as a whole or the cortex. The negative cortical finding was supported by a neurochemical study of various neuropeptides in rats with chronic quinolinic acid-induced lesions of the medial striatum. (Abstract shortened by UMI.)

abstract: Doctor of Philosophy (PhD)


title: Seismic performance of reinforced concrete frames with nominal ductility

contributor: Civil Engineering and Engineering Mechanics

abstract: An analytical and experimental study is undertaken in this thesis to evaluate the seismic performance of Nominally Ductile Moment Resisting Frames (NDMRFs) designed to conform to the current Canadian provisions. Buildings of different heights and typical configurations are considered. The frames of such buildings are designed as nominally ductile frames for the combined gravity and seismic loading in accordance with the National Building Code of Canada, NBCC 1990. The designed frames are then analyzed statically under monotonically increasing static lateral loading to study their force-deformation characteristics and order of hinge formation among members. Following the static analysis, the frames are analyzed dynamically under earthquake excitation. Several deficiencies are observed in the seismic performance of NDMRFs designed strictly following the minimum Code requirements. First, the interstorey drifts are substantial which implies excessive non-structural damage. Second, the beam ductility demands are much larger than what is implied in the Code. Third, the beam shear demands can exceed the capacity of the provided stirrups. An experimental investigation is carried out to evaluate the reliability of the concrete shear resistance when the beams are subjected to ductility demands similar to those obtained in the dynamic analysis. To ensure no beam shear failure in this type of frame, a procedure is proposed to modify the factored design shears in the beams of NDMRFs to be more reflective of the demand shears. The modified design shears calculated based on the proposed procedure are shown to be in good agreement with the response values. Therefore, shear failure in the beams of NDMRFs can be avoided if the capacity of the provided stirrups is based on the modified design shears with the concrete contribution to the beam shear resistance neglected. Finally, an alternative design procedure, based partially on the capacity design philosophy, is proposed for the design of gravity-dominated frames in seismic regions. Reinforced concrete frame design using the proposed procedure can avoid many of the deficiencies observed in the seismic performance of NDMRFs designed strictly following the minimum Code requirements, and is therefore a preferred design procedure to enhance seismic performance. (Abstract shortened by UMI.)

abstract: Doctor of Philosophy (PhD)


title: Crystal chemistry of Ca-doped and Ca-free Pb₂Sr₂RCu₃O₈₊δ (R = rare earth): Synthesis, structure and physical properties

contributor:
Greedan, J.E.
Chemistry

subject: Chemistry Chemistry

abstract: A novel PbO/NaCl flux growth method has been developed to grow single crystals of Ca-doped Pb2Sr2(R/Ca)Cu3O8+δ with R = Nd, Sm, Gd, Dy, Er, Tm, Yb, Lu and Y. The absence of CuO flux enables the crystals to be extracted nondestructively from the melt using an ultrasonic bath and methanol. The as grown Pb2Sr2(Y/Ca)Cu2O8+δ crystals are of high quality, reasonable size and superconducting with Tc up to 80K. The role of NaCl in the crystal growth process has also been investigated. The same method was applied to grow a series of Ca-free Pb2Sr2RCu3O8 (R = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, and Y) crystals. X-ray diffraction was used to determine the crystal structures of these compounds. A monoclinic symmetry was found for those crystals with R = Pr, Nd and Tb, orthorhombic for R = La and tetragonal for R = Eu and Dy. Different crystal symmetries can be understood in terms of order/disorder among oxygens in the PbO layers which is driven by an orientational ordering of the Pb2+ lone pairs. Bond valence sum calculations were also performed to evaluate the residual strains existing in the crystal structures. A transition from insulating to metallic and superconducting character occurs as a function of decreasing rare-earth size in this Ca-free crystal series. Structural and chemical analyses revealed that the electronic properties of these crystals are closely related to the rare-earth deficiency. Therefore, a cation vacancy carrier-doping mechanism has been proposed for the first time as the most plausible origin of the metallic and superconducting behaviour observed in the Pb2Sr2RCu3O8 crystal series.

abstract: Doctor of Philosophy (PhD)


title: The role of reactive oxygen species in Walker 256 tumour cell and platelet interactions with the vessel wall

contributor:
Orr, F.W.
Biology

subject:
Molecular Biology
Molecular Biology

abstract: Walker 256 cells (W256 cells) were shown to generate oxygen-derived free radicals when activated with the chemotactic peptide N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLP). fMLP-stimulated W256 cells, suspended to a concentration of 5x106 cells/ml, produced luminol chemiluminescence equivalent to that generated by 6.5x10-3 units/ml xanthine oxidase. We also examined human platelets for their ability to generate reactive oxygen species since these are often found at sites of tumour cell arrest in vivo. While others had inferred that human platelets generate reactive oxygen species, we have obtained direct morphological evidence confirming that this can occur. Preliminary studies showed that in the presence of the reactive oxygen species-generating system xanthine-xanthine oxidase, the release of 3H-2-deoxyglucose from prelabeled endothelial cell monolayers was a sensitive index of endothelial cell perturbation. Since the previous experiments suggested that tumour cell contact with the endothelium was required in order to observe isotope release, we asked if the release of 3H-2-deoxyglucose was dependent upon the adhesion of W256 cells to the endothelium. We suggest that W256 cell adhesion to endothelial cell monolayers is partially regulated by vitronectin receptor expression and that endothelial cell perturbation by reactive oxygen species is dependent on tumour cell adhesion. We have also obtained evidence suggesting that W256 cells degrade subendothelial cell matrices by a process involving both the generation of hydrogen peroxide and the secretion of a metalloproteinase. We suggest that the W256 cells can secrete a latent metalloproteinase of molecular weight 94 kD which may be activated, with a loss in molecular weight, by hydrogen peroxide or APMA. In summary, we provide evidence which supports the novel concept that some tumour cells may mediate vessel wall injury by generating reactive oxygen species and suggest that this may promote the metastasis of these cells in vivo. Such a hypothesis has not been postulated previously. (Abstract shortened by UMI.)

abstract: Doctor of Philosophy (PhD)


title: Investigation of diffuse multipath at low grazing angles

contributor: Radiation Sciences (Medical Physics/Radiation Biology)

subject: Radiation

abstract:
In the present thesis, an experimental database is used to investigate multipath, focusing mostly on the diffuse component. The experimental conditions cover the case of CW, coherently received microwave radiation, with a sampled aperture linear array, scattered at low-grazing angles, over the sea surface. A variety of frequencies covering the entire X-band and grazing angles were employed to explore the diffuse multipath structure.

A new technique, Thomson's multiple-window-method (MWM), proves to be the proper tool for this experimental investigation. The following characteristics of diffuse multipath, for this particular class of experimental conditions, are extracted for the first time ever:

Amplitude statistics (1st order statistics).

Complete wavenumber and frequency domain power spectra (2nd order statistics).

Bispectra (3rd order statistics).

Coherencies and transfer functions between channels at different frequencies and grazing angles.

An improved method for estimating angles of arrival.

Theory plays supportive role only, since the general problem of electromagnetic scattering from rough surfaces still remains to be solved. The main contributions from this research regarding diffuse multipath at low grazing angles are:

The shape of wavenumber/frequency domain power spectra.

Confirmation that amplitude statistics for the Lpol channel are K distributed.

The wavenumber/frequency domain bispectra indicate a non-Gaussian structure for the diffuse multipath component.

Any theory that deals with microwave scattering, over the sea surface, at low grazing angles, how to take these findings into account.

abstract: Doctor of Philosophy (PhD)