title: Twin-Screw Extrusion for the Production of Lipid Complexed Pea Starch as a Functional Food Ingredient

title: Twin-Screw Extrusion for a Functional Food Ingredient

contributor:
Thompson, Michael R.
Liu, Qiang
Chemical Engineering

subject: Extrusion-cooking, food processing, lipid complex, starch-lipid complexes, pea starch, functional food, twin-screw extrusion

abstract:
Canada is a major global producer of pulse products including pulse starch, which notably contributes to a healthy diet.  Strategically, Canada is taking steps to research methods of adding greater value to these crop products, and functional foods like resistant starch are particularly interesting. The primary objectives of this study were to develop an effective reactive extrusion process to produce gelatinized lipid complexed pea starches with enhanced enzyme resistance and examine the effects of bulk lipid complexing conditions on physicochemical and functional properties of extruded pea starches. One type of commercially available pea starch, Nutri-Pea, was chosen as the research subject in this study. A number of methods including; Englyst digestion method, differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), contact angle, titrations, residence time distribution (RTD) and rapid visco analysis (RVA) were used to characterize the properties of extruded pea starches.
The effects of feed formulation and extrusion conditions on lipid complexing and Englyst digestion profiles were systematically examined on two mixing devices. An extensive kinetics study was conducted on a lab scale twin-screw compounder, DSM-Xplore. The process was then scaled up to produce bulk lipid complexed pea starch on a Leistritz twin-screw extruder.  The results showed that lipid complexing and digestion profiles were highly dependent on feed moisture and induced screw shear. Reactive extrusion of pea starches under optimized conditions achieved a significant but moderate increase in either resistant starch (RS) content (from 13.3% to 20.2%) or slowly digestible starch (SDS) content (from 7.85% to 23.3%) compared to their native counterparts. However, RS and SDS content could not be improved simultaneously based on the pea starch and extrusion process in this study. Increased degree of substitution (DS) was found for myristic acid complexed pea starches (nominal DS= ~0.8) when compared to palmitic acid complexed pea starch (nominal DS= ~0.5). Contact angle measurements, FTIR and DSC thermograms confirmed the presence of lipids. Lipid complexed starch films showed increasing hydrophobicity with increasing lipid content.
As an alternative product compared to functional foods, the modified starch was considered as a biodegradable film for industrial applications. The material was produced at the highest moisture content for extruded native starch and two concentrations of lipid complexed starch using an intensive screw design. Preliminary results show that increasing lipid content and adding 1% glycerol to samples decreases the force per film thickness required to puncture films. However further investigation is required to determine effect of heat and moisture deformation.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Incorporation of pulses into food products has been a major area of Canadian research for its potential to create new avenues of enzyme resistant food starches. Extrusion cooking is commonly used in industry for producing various food products such as snacks and cereals but little research has been reported on using an extruder to rapidly produce resistant pulse starches as a functional ingredient on a large scale; resistant starch is a functional food beneficial to humans in the same manner as insoluble fiber but exhibits improved textural properties. This study aimed to develop an effective reactive extrusion process to produce lipid complexed pea starches with enhanced enzyme resistance (i.e. increased slowly digestible starch (SDS) and resistant starch (RS) content) by an examination of the effects of reaction conditions on the properties of extrusion products. The lipid complexed pea starches under optimized conditions achieved a significant but moderate increase in either RS content or SDS content depending on the sample formulation compared to their native counterparts. However, RS and SDS content could not simultaneously be improved in this study.


title: A Fluorescence Based Method for Studying the Membrane Topology of the Anti-Apoptotic Protein BCL-XL

contributor:
Andrews, David W.
Biochemistry

subject: membrane-associated protein, topology,mammalian cells, spectroscopy,E.coli

abstract:
Bcl-XL is a membrane-associated protein that inhibits programmed cell death
(apoptosis) in mammalian cells. Very little is known about the membrane topology of
Bel-XL or how its association with membranes contributes to its function. It was the aim
of this thesis to use fluorescence spectroscopy to investigate the location of a specific
amino acid ofBcl-XL relative to the membrane.
Bel-XL purified from E. coli could bind both to large unilamellar vesicles and
endoplasmic reticulum (ER) microsomes isolated from canine pancreas. A cysteine
residue at position 151 in Bcl-XL could be covalently labelled with the environmentally
sensitive fluorescent molecule NBD. Emission intensity measurements in the presence
and absence of membranes, combined with aqueous and lipophilic quenching
experiments, indicate that Cys 151 is inserted into the interior of the membrane bilayer
when Bcl-XL is bound to membranes. The methods outlined in this thesis form the basis
for an experimental system that can be used to determine the membrane topology ofBclXL
under a variety of conditions.

abstract: Thesis

abstract: Master of Science (MSc)


title: Structure and Function of Soluble Glycoprotein G of Vesicular Stomatitis Virus

contributor:
Ghosh, H.P.
Biochemistry

subject:
soluble
glycoprotein G
vesicular stomatitis

abstract: Membrane fusion plays a crucial role in many biological processes from virus infection to release of neurotransmitters (Hughson 1999). Membrane -bound surface glycoproteins are involved in the fusion process. The enveloped animal virus infection is initiated by interactions between the virus and the cell membrane through the surface glycoproteins called fusion glycoproteins (Eckert and Kim 2001). The fusion glycoproteins are responsible for both receptor binding and membrane fusion activity. The fusion proteins are characterized by a large ectodomain containing fusion peptides, a transmembrane (TM) domain, and a cytoplasimic domain. The viruses can enter cells either at neutral pH or at acidic pH. When exposed to appropriate conditions, the fusion protein undergoes conformational changes, which in turn drives the fusion process. The fusion glycoproteins can be classified as Class I and Class II fusion proteins (Lescar eta/. 2001 ). The Class I fusion proteins are synthesized as a precursor molecule, which then undergoes proteolytic cleavage to generate a mature molecule containing the hydrophobic fusion peptide at the N -terminal. The class II fusion glycoproteins are not synthesized as precursor molecules, and they have internal fusion peptides. The vesicular stomatitis virus (VSV) glycoprotein G is a class Ill fusion protein. It has a neutral internal fusion peptide and upon exposure to low pH, the protein undergoes reversible conformational change (Gaudin 2000, Yao eta/. 2003). A 62kDa soluble ectodomain of VSV G (Gs) has been generated by limited trypsin digestion. The SDS PAGE gel electrophoresis indicates that the trypsin has possibly cleaved near the transmembrane (TM) domain. Liposome binding experiment suggests that Gs can bind to liposomes in a pH dependent manner. Liposome fusion studied by RET assay suggests that the Gs can induce significant amount of hemifusion. However, it failed to induce any content mixing mainly due to considerable amount of membrane leakage activity. This indicates that the binding to the membrane through the TM domain is required for complete membrane fusion. Unlike TBE E soluble ectodomain, Gs can form dimers and trimers at neutral and fusion active pH. Light scattering experiment shows that the aggregation of Gs increases with a decrease in pH. The conformational change with changes in pH was evident from the trypsin sensitivity assay and CD spectroscopy. It was observed that Gs became resistant to trypsin digestion at low pH and a-helicity content of the molecule increased upon lowering the pH. However, the maximum amount of a-helicity was observed at pH 6. The removal of the TM domain also shifts the optimum fusion pH towards more acidic pH in comparison to VSV G. These results indicate that the TM domain is not required for the oligomerization of G protein, but some role has been reserved for the TM domain during membrane fusion. The CD spectroscopic data also indicated that the G protein undergoes structural rearrangement between pH 7.4-6, which could be responsible for the exposure of fusion peptide and subsequent target membrane binding.

abstract: Thesis

abstract: Master of Science (MSc)


title: Assembly of SRP Receptor

contributor:
Andrews, David
Biochemistry

subject:
assembly
SRP Receptor

abstract:
Co-translational targeting of secretory and integral membrane proteins to the endoplasmic reticulum (ER) requires two key mediators, the signal recognition particle (SRP) and its receptor. The SRP receptor is composed of two tightly associated subunits termed SRα and SRβ. Very little is known about the mechanism of membrane assembly of these two subunits of the SRP receptor. Therefore, it is the aim of this thesis to study the interactions between SRα and SRβ on the ER membrane as well as the role of SRα and SRβ in membrane assembly of functional SRP receptor.
Unlike typical endoplasmic reticulum (ER) integral membrane proteins, both subunits of the SRP receptor were extracted from the ER membrane with 0.08% deoxycholate; 0.2M Tris pH 9.0. Nevertheless, SRβ could be targeted to the ER only when the SRP dependent pathway of translocation was functional, similar to other integral membrane proteins of the ER. Urea resistant anchoring of SRa on the ER membrane was sensitive to limited digestion of the membranes with trypsin (Andrews eta/., 1989). However, anchoring of SRα was restored by incorporating exogenous  SRβ into trypsin treated membranes, confirming that one function of SRβ is anchoring of SRα. Consistent with this is the observation that, SRβ could be immunoprecipitated in a complex with SRα but not with SRα mutants containing deletions in the anchoring domain. Finally, an antiserum to the GTP binding domain of SRβ inhibited translocation of the secretory protein preprolactin suggesting that SRβ also has a direct role in translocation.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Larval Requirement for Matrix Metalloproteinase-Mediated Remodelling of the Cardiac Extracellular Matrix in Drosophila melanogaster

title: Matrix Metalloproteinase Remodelling of the Extracellular Matrix

contributor:
Jacobs, J. Roger
Biology

subject: ECM Drosophila MMP heart TIMP remodelling Collagen Pericardin

abstract: The Drosophila heart is a tubular vessel surrounded by a dynamic scaffold of extracellular matrix (ECM) proteins. Heart development and function rely upon protease-mediated remodelling and turnover of the ECM, and changes in ECM composition correlate with age and cardiac disease. Previous research has shown that a family of proteases called matrix metalloproteinases (MMPs), and their inhibitors (TIMPs), are necessary for normal cardiac cell migration and lumenogenesis. The Drosophila heart expands considerably throughout growth, but the role of MMP activity has not been elucidated at this time. I examine the role of the two Drosophila MMPs, MMP1 and MMP2, as well as TIMP, in defining larval heart structure and ECM protein distribution. I observe heart phenotypes via immunofluorescence labelling and confocal microscopy using loss-of-function mutants, gene over-expression, and gene knock-down techniques. Reduced MMP1 function during embryogenesis correlates with myofibrillar disorganisation, whereas reduced MMP2 function or TIMP over-expression both result in cardia bifida as well as increased density and ectopic localisation of Collagen-IV and Pericardin. Post-embryonic MMP reduction compromises cardiac structural integrity but does not affect Pericardin localisation. Live imaging of the larval heart with optical coherence tomography (OCT) and light microscopy reveals that reduced MMP2 function correlates with decreased heart rate but not impaired dilation or contraction. These data suggest that MMP2 activity during embryogenesis is critical for larval heart development. In contrast, post-embryonic protease function appears to have a less pronounced effect on ECM protein distribution throughout larval development.

abstract: Thesis

abstract: Master of Science (MS)

abstract: The fruit fly (Drosophila) heart undergoes significant changes in organisation and size throughout development and growth. The heart is surrounded and supported by a network of extracellular matrix (ECM) proteins, which is regulated by proteases, including matrix metalloproteinases (MMPs). Previous research has shown that MMPs are required for normal heart formation. I demonstrate that a reduction in MMP activity during embryonic development results in larval heart defects and an increase in the disorganisation of ECM proteins around the heart, whereas reduction during larval development results in less pronounced protein mislocalisation. These findings are corroborated via over-expression of an MMP inhibitor.


title: Modelling, characterization, and therapeutic targeting of human brain metastasis

contributor:
Singh, Sheila Kumari
Biochemistry and Biomedical Sciences

subject:
Brain Metastasis
Patient-Derived Xenograft

abstract:
Brain metastases (BM) are the most frequently diagnosed neoplasm to affect the adult central nervous system (CNS), occurring in 20-40% of all cancer patients throughout the course of the disease. The significant advancements to the treatment and control of primary cancers have unfortunately resulted in an increased incidence of BM, however, this complication of cancer progression continues to be met with a dismal outcome and limited therapeutic options. There remains a poor understanding of the several cellular hallmarks of BM, encompassing various molecular, genetic and epigenetic changes that underlay the stages of metastasis, which requires the development of clinically relevant models of metastasis. Our group has previously established the existence of a cancer stem cell/tumor initiating population with patient samples of BM, which established the foundation of this thesis. Thus, I postulate that there exists a subpopulation of cancer stem-like cells, termed brain metastasis initiating cells (BMICs), that is responsible for the initiation of BM and is identifiable by an exclusive subset of genes that regulate self-renewal and metastasis.

To support this hypothesis, I established novel experimental models of BM by inoculation of BMICs derived from patient samples of lung-to-brain metastases into intracranial (ICr), intracardiac (ICa), and intrathoracic (IT) routes into NOD/SCID mice. ICr injections validated the presence of a tumor initiating cell (TIC) capacity of BMICs in the secondary environment (brain). From ICa injections I was able to recapitulate macro-metastatic growth, whereas with IT injections I was able to capture the complete metastatic process, from primary lung tumor formation to micro-metastasis growth. Utilizing these models, I determined that the STAT3 pathway and genes SPOCK1 and TWIST2 all contribute to the regulation of BM development, where SPOCK1 may pose as a potential BMIC marker. Further interrogation of the metastatic process utilizing the IT model of BM led to the characterization of “pre-metastasis”, a stage where BMIC cells have crossed the blood-brain barrier and employ mechanisms to invade and seed the neural environment, while simultaneously repressing mechanisms of proliferation and cell growth that would indicate tissue colonization.

In summation, I propose a shift in the cancer research paradigm to target the metastatic process itself, to prevent the dissemination of primary tumor cells to the brain. I present models of clinically relevant models of human BM that have proved to be reliable as platforms to interrogate the process of BM, providing insight into the stage of pre-metastasis as a novel therapeutic window into BM prevention and possible extension of patient survival.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Dysmenorrhea, Menstrual Cycle Phase, and Previous Childbirth Pain Experience Responsiveness to Laboratory Pain

contributor:
deCatanzaro, D.
Psychology

subject: dysmenorrhea labour childbirth menstruation responsiveness

abstract:
The present studies were designed to investigate responsiveness of women to laboratory pain. The purpose of this investigation was manifold in that the effects of several different variables on pain perception were examined. First, the studies sought to determine whether the experience of menstrual pain, otherwise known as dysmenorrhea, had any relationship to the perception of laboratory induced pain, namely, cold pressor pain. Second, it was asked whether menstrual phase had any relationship either on its own, or in interacting with dysmenorrhea, to pain perception. Third, based on observations from the two previous studies, it was asked whether age and/or previous experience of childbirth pain had any influence on pain perception. The first study employed a within-subjects design of young university women in order to investigate the relationship of dysmenorrhea and menstrual cycle phase to pain threshold, tolerance, and subjective pain intensity ratings. The second study employed a between-subjects design of young university women as well, in order to replicate the menstrual phase effect obtained in the first study. The third study employed a between-subjects design of older women as it dealt with the relationships of age and/or the experience of childbirth pain to the same measures of pain perception. It also dealt with defining further characteristics of dysmenorrhea as occurring in an older group of women (over 30 yrs of age). Results from the first two studies indicated a significant increase in pain sensitivity, measured as pain threshold, from the follicular to the luteal phase of the cycle but no overall significant effects of dysmenorrhea on laboratory-induced pain. In the second study, there was a significant interaction between menstrual phase and dysmenorrhea with respect to subjective pain ratings. These results
partially replicated previous findings in the literature while employing a clinically relevant method of pain induction. Results from the third study indicated that previous experience of childbirth pain, independent of age, is a significant factor in the perception of laboratory-induced pain. These latter results have never before been reported in the pain literature and thus deserve further investigation. Possible implications for an adaptation-levels model are discussed.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The "Problem of Health Care" in Canada's Federal Prisons

contributor:
Kouyoumdjian, Fiona
Global Health

subject:
Prison Health
Essential Health Care
Carol Bacchi
Inequity

abstract:
ABSTRACT:
Background: The United Nations states that "prisoners should enjoy the same standards of health care that are available in the community." However, persons in custody continue to face barriers to care worldwide. The health of persons in federal custody in Canada is governed by the Corrections and Conditional Release Act (CCRA), which states that Correctional Services Canada is responsible for the provision of "essential health care" to all inmates. In the absence of concrete definition, these "essential" services provided in Canadian federal prisons often fall below standard. More research is needed into how "health care" is represented as a problem in Canada's federal prisons, and the impact on the incarcerated population.

Methodology: Carol Bacchi's "What's the Problem Represented to Be?" (WPR) (Bacchi, 2009) framework was applied to the CCRA with a specific focus on health care. Questions one, three, and five of the WPR approach were applied, respectively, in order to analyze how the "problem" of "health care" is represented, how this particular representation came about, and the effects of this representation on the health of persons in custody.

Findings: In applying the WPR approach to the CCRA, three main themes emerged. First, the notion of what services are constituted as "essential" in the context of federal prisons is more limited compared to the broader community. Second, the creation of the CCRA involved a great deal of discussion around the rights of persons in custody versus the protection of society, a dichotomy that has significant bearings on the treatment of those in prison. Third, this representation has negative effects on the health of those in custody.

Conclusion: The representation of health care in the CCRA has negative effects on the health of persons in custody. Greater attention must be paid to these inequities in health care provision in order to meet UN standards.

Keywords: Prison Health, Essential Health Care, Carol Bacchi, Inequity

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
LAY ABSTRACT

The United Nations states that "prisoners should enjoy the same standards of health care that are available in the community." Despite this, persons in custody around the world continue to experience barriers to care and face unique health challenges. In Canada, the health of persons in federal custody is governed by the Corrections and Conditional Release Act. This legislation states that Correctional Services must provide "essential health care" and "reasonable access to non-essential mental health care" to inmates. Without clear definition, the interpretation of which services are "essential" is left to the discretion of correctional authorities, and as a result access and quality of care are significantly reduced in Canada's prisons when compared to the broader community. This thesis applied Carol Bacchi's "What's the Problem Represented to Be" analytical framework to examine how "health care" is uniquely represented as a "problem" for Canada's federal prison population, and the concerning inequities that are produced by this representation.


title: Developing a better understanding of resource withdrawal from medical services through examination of its characteristics, government policies and an initiative

title: Resource withdrawal from medical services

contributor:
Randall, Glen E
Health Policy

subject:
Health Policy
Resource Withdrawal
Qualitative Research
Decision Making
Government
Priority Setting
Problem Frames
Grounded Theory

abstract: Resource withdrawal from unnecessary medical services is an important issue as the cost of health care continues to rise. In many countries, resource withdrawal is primarily determined by government policies that remove, restrict, reduce, or limit the availability of publically insured medical services. Ideally, resource withdrawal is the result of a careful assessment of clinical and economic evidence regarding a service’s safety and effectiveness in order to ensure that it is the most efficient use of resources. Despite advocacy for a routinized and systematic approach to the withdrawal of resources from medical services, research has indicated that political and social factors often influence government, resulting in decisions that are neither consistent nor transparent.  In this dissertation  I seek to understand factors that may influence resource withdrawal decisions in an attempt to promote a more routinized and systematic approach. In order to understand the resource withdrawal landscape and provide greater conceptual clarity, the first study in this dissertation identifies and explores its characteristics (antecedents, attributes, and outcomes). Definitions of two prominent terms, disinvestment, and rationing are proposed. In the second study, a qualitative analysis of two examples of resource withdrawal reveals how the characteristics of problem frames affect the shape and timing of government resource withdrawal policies. Findings support the proposition that the complexity of the story told within the problem frame affects the shape of the policy; while visibility affects the timing. In the third study, I analyzed the perspectives of key informants about the Choosing Wisely Canada (CWC) campaign, which has the aim of reducing unnecessary services by encouraging a discussion between physician and patient. Findings reveal that CWC was designed to address pressures from government, patients, and the public. However, CWC was not designed in a way that is expected to address the underlying reasons unnecessary services are provided, including limited time in the clinical encounter, patient demands, uncertainty in the care pathway, and physician fear of litigation. Results from all three studies help establish a common language, identify influences on government led resource withdrawal and reasons why CWC is unlikely to reduce unnecessary services. Together this thesis provides insights into some of the factors affecting resource withdrawal from medical services, and findings may be used to help assess ways to improve the formulation of resource withdrawal policies.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Currently several governments pay for unnecessary medical services, leading to suboptimal patient health outcomes and a waste of public resources. Several researchers and organizations have proposed methods to identify and assess medical services to determine if they are unnecessary; however, governments have been slow to adopt such methods on a routine basis. It is clear that evidence is rarely sufficient to motivate governments to withdraw resources from unnecessary medical services. Instead, governments are often influenced by social and political factors when they make such decisions. Through a better understanding of these factors, we may be able to find ways to incorporate evidence into governments’ decisions to withdraw resources from medical services. Qualitative methods were used to investigate how resource withdrawal is defined, factors influencing government resource withdrawal decisions in Ontario, and the effectiveness of Choosing Wisely Canada, an initiative led by the medical community to reduce unnecessary services.


title: The health of Indigenous peoples living in Canada: Understanding distal, intermediate and proximal determinants of health

contributor:
Mulvale, Gillian
Health Policy

subject:
Indigenous health
Determinants of health

abstract: Understanding how proximal, intermediate, and distal determinants of Indigenous peoples’ health in Canada, relate to the physical and mental health of First Nations, Métis, and Inuit, can shed light on how to allocate health-related resources to address well documented health disparities in these groups. This dissertation contributes to the literature by addressing two population-level quantitative research questions pertaining to Indigenous peoples’ physical and mental health, and a qualitative case study examining what factors maintain and improve Indigenous community health workers’ mental wellness and access to mental health supports. First, this thesis establishes a link between being Indigenous and health-related quality of life using multivariate regressions, as well as decomposition techniques. Second, the relationship between having an ancestor who survived the Residential School System, and five physical and mental health outcomes, controlling for determinants of health are estimated using multivariate ordered logistic and logistic regressions. Third, given that Indigenous self-government is an important determinant of health and wellbeing, an explanatory single-case study design is used to explore what factors maintain and improve, or create barriers to mental wellness and access to mental health supports for Indigenous community health workers in an Indigenous-governed health system. These chapters build on each other, and use a variety of methodological approaches, to identify if and to what degree observable determinants of health account for the physical and mental health of Indigenous peoples living in Canada. Substantively, this thesis evaluates empirically, the relationship between determinants of health and health outcomes for Indigenous peoples. Findings could be used to advocate for adequate and sustained investment in programs and services responsive to the contexts and needs of Indigenous men and women living in Canada. Methodologically, novel applications of statistical/econometric methodologies, furthers understanding of quantitative relationships examined with respect to Indigenous peoples’ physical and mental health at the population-level. In terms of a theoretical contribution, this dissertation contributes by lending further insight into the empirical relationships between determinants of Indigenous peoples’ health and health outcomes, and by introducing a framework for conceptualizing factors that strengthen mental wellness of Indigenous community health workers in remote Northern contexts in Canada.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: First Nations, Métis, and Inuit make up 4.3% of the Canadian population and together represent the three distinct identities of Indigenous peoples living in Canada. Indigenous peoples’ experiences of colonization have had impacts on their physical and mental health. Additionally, experiences of colonization have also affected many determinants of Indigenous peoples’ health ranging from access to food and clean drinking water, to the availability of appropriate education, social, and healthcare services. The following chapters explore how certain experiences of being Indigenous in Canada are associated with physical and mental health outcomes, taking into consideration determinants of health. Even after controlling for all of the things known to be related to Indigenous peoples’ physical and mental health, and that are typically used to explain any differences in health between groups, there is still a difference in health outcomes between Indigenous and non-Indigenous peoples in Canada. There is also still a difference in physical and mental health outcomes between Indigenous adults with and without an ancestor who attended the Residential School System. The effects of colonization also influence Indigenous community health workers’ mental wellness, and access to mental health supports while living and working in a remote, Northern community.


title: What are the outcomes of importance for patient education in breast cancer?

title: Outcomes of patient education in breast cancer

contributor:
Reiter, Harold
Levine, Mark
Sinding, Christina
Health Science Education

subject: Patient education

subject: Breast Cancer

subject: Outcomes of patient education

subject: Patient education assessment instruments

abstract: Patient education is an important component of quality cancer care. However, there remains much debate about its effects, merits and limitations. The primary objective of this thesis was to identify outcomes of importance for patient education interventions in breast cancer. Through the process of this inquiry, a systematic review of all patient education assessment instruments, a literature review of patient education studies in chronic diseases and cancer, and ultimately a qualitative study using interpretive description was conducted. The systematic review of assessment instruments revealed a lack of psychometrically sound instruments developed to assess quality and efficacy of patient education materials. There was also a lack of consensus as to what aspects of materials should be appraised to constitute good quality. The review of patient education intervention studies in both chronic diseases and cancer identified a general lack of consensus on the intended effects of educational interventions. Multiple outcomes were used without consistency and in differing combinations in the literature making it difficult to compare relative efficacy of interventions. To discover what key stakeholders in the process of patient education in breast cancer (patients, physicians and nurses) would identify as outcomes of importance, a generic qualitative study using interpretive description was conducted. Five common themes to all groups with respect to outcomes of importance were discovered: improving knowledge, improving coping ability, providing an orientation to the cancer system, enabling shared decision making and impacting behaviour during cancer treatment. Despite the surprising variability and inconsistency of outcomes discovered in the patient education literature, this qualitative study demonstrated that patients, physicians and nurses generally agree on what constitute important outcomes and serves as a first step in the process of developing validated outcomes for patient education interventions in cancer.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: This thesis explores what are considered important outcomes of patient education in breast cancer. Firstly, a systematic review of all instruments created to judge patient education materials was completed and showed a lack of valid instruments for use in judging quality or outcomes in patient education. Secondly, a review of patient education studies in chronic conditions and cancer revealed a paucity of consistent or recommended outcomes for patient education. Lastly, the major focus of this thesis was a qualitative study that used focus groups to discover what breast cancer patients, physicians and nurses identify as important outcomes of patient education interventions at the Juravinski Cancer Centre. It identified that patients, physicians and nurse have five common beliefs about important outcomes of education interventions: improving knowledge, improving coping ability, providing an orientation to the cancer system, enabling shared decision making and helping to direct behaviour during cancer treatment.


title: Fragile magnetism in rare earth XY pyrochlores

contributor:
Gaulin, Bruce D.
Physics

abstract:
The topic of investigation in this thesis is the pyrochlore titanates A2Ti2O7 where A3+ is a
magnetic rare earth ion and Ti4+ is non-magnetic. The pyrochlore is a cubic structure composed
of two inter-penetrating networks of corner-sharing tetrahedra and is the archetypal platform
for the study of magnetic frustration in three dimensions. Magnetic frustration in rare earth
pyrochlores favors the stabilization of various exotic magnetic phenomena such as the classical
and quantum spin liquid states. The degree of magnetic frustration in these systems depends
strongly on the local spin anisotropy of the rare earth ion. In this thesis, we studied the magnetic properties of XY pyrochlore magnets where the spins have a preference to point perpendicular to the centers of the two tetrahedra they connect. XY local anisotropy is obtained in the rare earth pyrochlores Yb2Ti2O7 and Er2Ti2O7, which are the primary subjects of this thesis. Using elastic and inelastic neutron scattering techniques, we study the magnetic ground state of Yb2Ti2O7 and Er2Ti2O7 as a function of various perturbations such as disorder, dilution, hydrostatic pressure and chemical pressure. Our results on Yb2Ti2O7 reveal a spin liquid ground state at ambient pressure. The spin liquid state of Yb2Ti2O7 is found to be unstable upon the application of hydrostatic pressure, from which a ferromagnetic ground state is obtained. Er2Ti2O7 is known to magnetically order into an antiferromagnetic  2 state at 1.2 K. Diluting the Er3+ site with non-magnetic Y3+ ions causes a transition from the  2 antiferromagnetic state found in Er2Ti2O7 to a frozen mosaic of psi2 and psi3 at a critical dilution of about 20%-Y. Furthermore, it will be demonstrated that Er2Ti2O7 has a rich phase diagram in both an applied magnetic field as well as with the application of chemical pressure. The fragile magnetism in both Yb2Ti2O7 and Er2Ti2O7 is discussed in terms of multiphase competition that promotes spin liquid behaviour and order-by-disorder phenomena.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Ataxin-1 Nuclear Bodies are Subnuclear Sites of Ataxin-1 Function

title: Ataxin-1 Nuclear Bodies

contributor:
Truant, Ray
Biochemistry

subject: Ataxin-1

subject: nuclear

abstract: Ataxin-1 is the protein affected in Spinocerebellar Ataxia Type 1 (SCA1) polyglutamine neurodegenerative disease. The biological function of ataxin-1 is unknown. By using live cell fluorescence microscopy and cultured human HeLa cells, we have shown that ataxin-1 nuclear inclusions (ataxin-1 NIs) are unique subnuclear sites of ataxin-1 function that do not resemble typical ataxin-1 polyglutamine nuclear aggregates or neuronal intranuclear inclusions (NIIs). Ataxin-1 NIs form independent of polyglutamine expansion in ataxin-1, and we found that ataxin-1 NIs are capable of recruiting the mRNA export factor TAP /NXF1. We propose that ataxin-1 NIs may be more accurately termed ataxin-1 nuclear bodies (ataxin-1 NBs) and suggest that ataxin-1 NBs play a role in mRNA processing and transport. We discovered that the serine to alanine mutation at position 776 of ataxin-1 (S776), known to inhibit spinocerebellar ataxia type 1 (SCA1) pathogenesis, plays a critical role in the frequency and size of ataxin-1 NBs. We found that polyglutamine expansion was not essential for ataxin-1 NB formation, and that serine 776 may be important in turnover regulation of polyglutamine expanded ataxin-1. In addition, we found that serine 776 does not significantly affect nuclear localization of ataxin-1, and that the ataxin-1 associated protein, 14-3-3 zeta, does not have a role in the nucleo-cytoplasmic transport of ataxin-1. These findings reveal that the serine 776-mediated 14-3-3 zeta co-localization with ataxin-1 is likely not important to SCA1 pathogenesis, but that the role of serine phosphorylation of ataxin-1 does have an effect on the formation of ataxin-1 NBs, thereby implicating ataxin-1 NB formation as important for understanding SCA1 disease.

abstract: Thesis

abstract: Master of Science (MSc)


title: PHOSPHORUS BINDING TO MODIFIED WOOD PULP FIBERS DESIGNED FOR SOILLESS AGRICULTURE

contributor:
Pelton, Robert
Chemical Engineering

abstract:
The long-term goal of this work was to develop a new organic plant substrate from wood pulp that can be used in soilless (hydroponics) agriculture. This work explored the usage of wood pulp as disposable plant substrate that is chemically active and has the capacity to bind and release important plant nutrients such as phosphorus.
The cationic cellulosic pulp fibers had been prepared from softwood bleached kraft pulp according to a water-based modification method involving first the oxidation of pulp with 2,2,6,6-tetramethyl-1-piperidinyoxy radical (TEMPO) followed with the adsorption polyvinylamine (PVAm) on pulp surface. The total carboxyl group contents of the TEMPO oxidized pulp fibers were determined via conductometric titration. After treating the oxidized fibers with PVAm, polyelectrolyte titration was used to determine the nitrogen (cationic charges) content on fibers. The fibers’ nitrogen content varied with the fibers’ carboxyl charge content; 45.5 μmol/g-pulp of carboxyl group content had 18.6 μmol/g- pulp nitrogen content (least observed nitrogen content adsorbed onto pulp), and 207.1 μmol/g-pulp of carboxyl group content had 69.75 μmol/g-pulp nitrogen content (highest observed nitrogen content adsorbed onto pulp).
The adsorption and the release of negatively charged phosphate ions onto/from the treated and untreated pulp were evaluated. A maximum adsorption of ~ 10 μmol/g-pulp of phosphate ions was achieved on oxidized fibers treated with PVAm. Although a layer of adsorbed PVAm greatly increases the anion exchange capacity of cellulose fibers, the modified pulp showed a very low phosphate binding capacity of 0.16 mol phosphates per mol of nitrogen. Phosphates adsorbed on the PVAm coated fibers release depended on the pH and ionic strength of the surrounding media. Neutral pH conditions (6.0-7.5) released the least amount of phosphates, which was 30%-40% of the phosphates initially retained on pulp fibers. However, high molarity salt solutions (5 mM) and sulfonic groups (in buffer solutions) released 90%-100% of the adsorbed phosphates at all pH ranges.
Cationic pulp fibers matrices with varying phosphate treatment were used to grow Arabidopsis (phosphate sensitive seeds). Arabidopsis grown on cationic pulp fibers displayed the highest total fresh weight, highest leaves weight, and healthiest look. The total fresh weight of the Arabidopsis increased upon growing on cationic pulp fibers by 57% - 67% at the low phosphate treatments. The free phosphates destination in the plant growing media is unpredictable. Free phosphates could end up adsorbing to mineral surfaces or forming secondary compounds with plant nutrients, which make them unavailable for the plants. Even though the PVAm coated fibers had very low phosphate binding capacity, the fibers’ cationic surface can bind enough phosphates, at low phosphate treatment, needed for Arabidopsis cultivation. By binding the phosphates on the fibers’ surface, less phosphates are available in the plant growing media to react or precipitate with other plant nutrients. However, at intermediate or high phosphate treatment PVAm coated fibers didn’t have a great impact on the Arabidopsis plant growth; this is because phosphates available in the plant growing media were relatively greater than the bound phosphates on the PVAm coated fibers.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Building, Bridging, Being: The Transition to Clinical Practice for New Registrant Midwives in Ontario

contributor:
Murray Davis, Beth
Health Science Education

subject:
midwifery
transition to practice
midwifery education
new registrant

abstract:
Background:  The transition to clinical practice is a phenomenon that all health care professionals experience and one that has been studied in many fields of health care, yet remains largely unexamined for Canadian midwives.  This study asked the question: How do new registrant midwives in Ontario navigate the transition from student to clinician during their first year of clinical practice?
Methodology:  In this grounded theory study, a total of 13 semi-structured interviews were conducted with Ontario midwives from three participant groups: A) New registrants in their first year of clinical practice; B) Registered midwives with 1-5 years of clinical experience; C) Registered midwives who work with new registrants as supervisors or mentors.
Findings:  The Building, Bridging, and Being theory describes how new registrants transitioned to clinical practice.  During the Building phase, individuals developed the knowledge and skills for clinical practice; midwifery students experienced elements of this phase during their final clinical placement.  The Bridging phase occurred when new registrants embarked on independent clinical practice; this phase was characterized by providing clinical care without the safety net of a preceptor.  Finally, the Being phase occurred when new registrants developed confidence in their skills and professional identity as midwives.  A final theme, Bettering, encompassed participants’ suggestions of ways to help improve the transition process.
Conclusion:  The Building, Bridging, Being theory contributes to the present understanding of the transition to clinical practice for midwives in Ontario.  This study highlighted the importance of strengthening the Preparation, Orientation, Mentorship, and Ongoing Education of new registrants through their transition to clinical practice.  The findings of this study are relevant to individuals and organizations invested in educating and integrating midwives into the Ontario health care system and provides a starting point for further research centered on the transition to clinical practice for midwives in Ontario and throughout Canada.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The transition to clinical practice is a phenomenon that all health care professionals experience and one that has been studied in many fields of health care, yet remains largely unexamined for Canadian midwives.  This study asked the question: How do new registrant midwives in Ontario navigate the transition from student to clinician during their first year of clinical practice?  Thirteen interviews were conducted with Ontario midwives from three participant groups: A) New registrants in their first year of clinical practice; B) Registered midwives with 1-5 years of clinical experience; C) Registered midwives who work with new registrants as supervisors or mentors.  The findings of this study led to the development of the Building, Bridging, and Being theory, which helps explain how midwives in Ontario transition to clinical practice and provides a starting point for further research centered around the transition to clinical practice midwives in Ontario and throughout Canada.


title: Unraveling the selective importance of RNA-binding proteins in malignant hematopoietic stem cells

contributor:
Hope, Kristin
Biochemistry and Biomedical Sciences

abstract: RNA-binding protein (RBP) directed post-transcriptional control of stem cell fate represents an underexplored mechanism through which stemness and transformation may be regulated in the blood system. Interestingly, a unique set of RBPs was found to be specifically enriched in the leukemic stem cell fractions of human primary acute myeloid leukemia (AML) but repressed in normal primitive hematopoietic cells. By using a CRISPR-Cas9-mediated dropout screening approach, key RBPs essential for in vivo propagation of MLL-AF9/NrasG12D driven AML were identified. With additional loss-of-function strategies in normal and malignant hematopoietic stem and progenitor cells (HSPCs), the therapeutic relevance of the RBP ELAVL1 was furthermore shown. In healthy murine bone marrow, Elavl1 knockdown allowed for the selective sparing of the HSPC fraction in vivo, whereas both the colony-forming capacities and in vivo engraftment of MLL-AF9 cells in both primary and secondary transplant settings was significantly impaired upon Elavl1 disruption. Moreover, decreased proliferation and survival as well as increased differentiation in human AML cells upon Elavl1 downregulation was observed. These results shed light on the potential role of specific RBPs as unique and critical regulators of LSCs, paving the way for identification of important novel therapeutic targets in AML.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Mechanism of Action of Caloxin

contributor:
Grover, A.K
Biology

subject: plasma membrane, second putative extracellular domain, leaky ghosts

abstract:
The plasma membrane Ca2+-pump (PMCA) is a Ca2+-Mg2+- ATPase that expels
Ca2+ from cells to help them maintain low concentrations of cytosolic Ca2+. Four genes
(PMCAl to PMCA4) encode various isoforms ofthis pump. Caloxin is a novel peptide
that was selected for binding to the second putative extracellular domain of PMCAl.
Caloxin inhibits the Ca2+- Mg2+-ATPase in human erythrocyte leaky ghosts which
primarily contain PMCA4. The objectives of this thesis are to delineate the mechanism
of this inhibition and to determine its PMCA isoform selectivity.
Caloxin inhibition of the PMCA pump in erythrocyte ghosts is non-competitive
with respect to the substrates Ca2+ and ATP and the activator calmodulin. This was
expected because the high affinity binding site for Ca2+ and sites for ATP and calmodulin
are intracellular whereas caloxin is a peptide selected for binding to the second
extracellular domain of the pump. In the reaction cycle, PMCA forms a 140 kDa
acylphosphate enzyme intermediate from ATP (forward reaction) or orthophosphate
(reverse reaction). Caloxin inhibits the acylphosphate formation in the forward but not in
the reverse reaction. These results suggest that caloxin inhibits conformational changes
required during the reaction cycle of the pump.
In COS-M6 cells overexpressing PMCA4, caloxin inhibited the Ca2+ -Mg2+ATPase
but with a marginally lower affinity than in the erythrocyte ghosts. Caloxin
inhibition was also observed in insect cells overexpressing PMCA2. Several
unsuccessful attempts were made to overexpress functional PMCAl. The work on isoform selectivity would require high level of expression of various PMCA isoforms and
problems related to this requirement are discussed.
Caloxin appears to inhibit the PMCA pumps by binding to the second putative
extracellular domain and thus affecting the conformation of the protein. This is the first
identified role of an extracellular domain of a PMCA pump.

abstract: Thesis

abstract: Master of Science (MSc)


title: Activation-Dependent Enhancements of Synaptic Strength in Pyriform Cortex Efferents to the Entorhinal Cortex

title: Synaptic Plasticity in the Entorhinal Cortex

contributor:
Racine, Ronald
Psychology

subject:
synaptic strength
pyriform
entorhinal cortex

abstract:
The entorhinal cortex is reciprocally connected with both neocortical sensory areas and the hippocampal formation, and is thought to play a pivotal role in learning and memory. Changes in synaptic strength are thought to provide the major neurophysiological basis for memory formation, but little is known about synaptic plasticity in the entorhinal cortex. The objectives of this research were to provide a basis for the interpretation of evoked potentials recorded from the entorhinal cortex following pyriform (primary olfactory) cortex stimulation 𝘪𝘯 𝘷𝘪𝘷𝘰, and to determine the conditions under which synaptic enhancements in this pathway may occur and contribute to lasting changes in the processing of olfactory information. The synaptic currents which generate field potentials in the entorhinal cortex following pyriform cortex and medial
septal stimulation were first localized to the superficial layers of the entorhinal cortex using current source density analysis techniques in the anesthetized rat. This allowed changes in the strength of these synaptic inputs to be monitored in the awake rat by measuring evoked field potential amplitudes at a single cortical depth. Long-term synaptic potentiation (LTP) in this pathway was reliably induced following stimulation of the pyriform cortex with either epileptogenic stimuli, or with prolonged subconvulsive high-frequency trains. Further, stimulation which results in short-term frequency potentiation effects, was found to increase the amount of LTP induced. Concurrent stimulation of the medial septum at a frequency similar to that of the endogenous theta rhythm also resulted in a cooperative enhancement of the LTP produced. Computational modelling techniques were then used to formalize the heterosynaptic contribution of frequency potentiating medial septal inputs to Hebbian synaptic modification in entorhinal cortex. These results indicate that the frequency of rhythmic activity in sensory afferents and the activity of the medial septum may play critical roles in the regulation of synaptic plasticity in the entorhinal cortex.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Molecular Modeling of L-Type Calcium Channel with Calcium Ions and Ligands

title: Molecular Modeling of L-Type Ca^2+ Channel with Ligands

contributor:
Ananthanarayanan, V. S.
Biochemistry

subject: L-Type Calcium ligands

abstract:
In the absence of X-ray structure of L-type Ca²⁺ channel (LCC), we have built a homology model of LCC based on the crystal structure of KcsA channel and have performed a series 0° docking simulations. The search for lowest-energy conformations was performed by the Monte Carlo energy-minimization method. To obtain the conformation with the lowest energy where dihydropyridine (DHP) ligand forms optimal
contacts with the DHP-sensing residues of the channel, we have tested different sequence alignments between KcsA and LCC, and have docked the ligand inside the pore of the channel as well as into the interface between repeats IIIS5-IIIS6-IVS6. The LCC ligand tetrandrine was used during the studies of the selectivity filter of the channel. Conformational studies of the drug and its interaction with Ca²⁺ ions in a non-polar solution were performed by NMR spectroscopy. These experiments have demonstrated
the binding of Ca²⁺ ions to the ligand. In the model based on the alignment proposed by Lipkind and Fozzard (2000), the DHP ligand nifedipine fits inside the pore and forms favorable contacts with several hydrophobic DHP-sensing residues, and forms hydrogen bonds with conserved tyrosines in repeats HI and IV. These interactions stabilize the portside-down docking mode of nifedipine, in which this blocker exposes its hydrophobic methoxy group to the bracelet of hydrophobic residues forming the gate of the channel near the crossing of the bundle of helices. The stabilizes the closed state of the channel. In contrast, the agonist has the hydrophilic group at its portside. The favorable interaction of this group with
hydrated Ca²⁺ ion facilitates its permeation through hydrophobic gate. We have simulated the passage of the hydrated ion along the pore with the agonist bound inside and determined several residues crucial for this passage. The role of these residues can be tested experimentally.

abstract: Thesis

abstract: Master of Science (MSc)


contributor:
Frager, Ruth
History

subject:
German Canadians
Kitchener, Ontario
Berlin, Ontario
ethnicity
citizenship

abstract: “From Wilhelm to Hans: Ethnicity, Citizenship, and the German Community of Berlin/Kitchener, Ontario, 1871-1970s,” examines how the ethnic elite, a group of politicians, businessmen, professionals, and leaders of cultural organizations defined German ethnicity. It argues that claiming a place for Germans as loyal Canadian citizens was central to how the ethnic elite defined German ethnicity. The ethnic elite, however, did not define German ethnicity in isolation. Rather, German ethnic identity was arrived at through the interaction between the ethnic group and the host society. In forums such as public celebrations, newspaper debates, politics, and business, immigrants and established Canadians negotiated their respective identities and their relationship to one another. This relationship was shaped by factors such as the two World Wars, Canada’s relationship with Britain, and Canadians’ changing attitudes towards race and racism. German ethnicity, therefore, was not a static inheritance from the Old World. It was dynamic, continually being contested, negotiated, and redefined. Recently historians have looked to ethnic group identities to locate the origins of Canada’s multicultural identity. By studying German ethnicity through the lens of citizenship, however, this dissertation demonstrates that multicultural citizenship was not the inevitable result of immigration and ethnic diversity. To seek a place for Germans as Canadian citizens, the ethnic elite’s definition of German ethnicity was premised on the exclusion of others who did not fit the class, gender, or religious distinctions of Canadian citizenship. Furthermore, throughout the period under study, Anglo-Canadian critics challenged the place of Germans as Canadian citizens. At times, these critics were only a small minority, but there were others, such as the First World War, when the rights of Germans as Canadian citizens were challenged more broadly. Thus, the acceptance of Germans as Canadian citizens was always contingent and never fully settled.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: CHARACTERIZATION OF THE END BRIDGING COMPLEX OF NON-HOMOLOGOUS END JOINING REPAIR OF DNA DOUBLE STRAND BREAKS

contributor:
Junop, Murray
Biochemistry and Biomedical Sciences

subject:
Structural biology
DNA repair

abstract:
DNA double strand breaks represent the single most dangerous type of damage that can afflict the genome. Given the severity of such a lesion, higher eukaryotes possess two distinct pathways to repair such damages. The work presented here focuses on the role of different protein complexes formed during within Non-Homologous End Joining (NHEJ). Specifically, how the C-terminal tails of XRCC4 and XLF regulate higher-order complex formation of end bridging filaments prior to terminal ligation and release of the intact DNA following repair.  The crystal structure of full length XRCC4 was solved to 3.43Å and confirmed that the C-terminal tails or XRCC4 mediate tetramerization but are not required for end bridging of DNA ends.  A cluster of residues that stabilized the XRCC4 multi helix bundle were mutated and determined to result in an XRCC4Mutational analysis and SEC-MALS further revealed that this 4-helix bundle stabilizes tetramers, interestingly tetramerization was found to not be required for bridging of DNA ends.
Additional work aimed at determining the mechanism by which XLF binds DNA and how complex filaments are formed was carried out using a combination of structural and biochemical techniques. Mutational analysis of the yeast XLF homologue, Nej1, revealed that the tails of these proteins bind their DNA substrates through an extended interface that may involve wrapping DNA to further stabilize interaction. Also, it was determined that phosphorylation of key residues within this extended DNA binding domain results in a decreased affinity for DNA and may play a role in DNA repair pathway choice in Saccharomyces cerevisiae.
Transmission electron microscopy showed that when bound to DNA, XLF is capable of forming DNA dependent filaments that are capable of bridging DNA ends in a linear manner. Addition of XRCC4 resulted in extensive remodelling of these filaments. Crystals of the XRCC4/XLF/DNA were optimized to diffract to a resolution of greater than 5Å, however further work will be required to determine the structure of this key NHEJ complex.
Finally, attempts to determine the optimal combination of DNA substrates and NHEJ factors to crystallize the terminal repairosome were carried out and initial hit conditions have been identified.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Comprehensive Metabolomic Analyses of Diabetic Atherosclerosis

contributor:
Werstuck, Geoff
Chemical Biology

subject: Diabetes Atherosclerosis Metabolomics

abstract:
The prevalence of diabetes mellitus is increasing dramatically worldwide. Approximately three out of four diabetic patients will die of cerebro- and cardiovascular disease (CVD). Atherosclerosis, a chronic inflammatory disease of the medium-large arteries, is the major underlying cause of most CVDs. Despite the established progressive relationship between diabetes and CVD, the molecular mechanisms by which diabetes promotes atherosclerosis are not well understood. This has impeded the development of strategies to block or slow atherogenesis in diabetic patients. The objective of my thesis is to investigate the molecular alterations by which diabetes accelerates the development of atherosclerosis using comprehensive metabolomics techniques.
We first investigated the development and progression of atherosclerosis at the molecular level in apolipoprotein E-deficient mice. We identified specific changes in plasma-borne metabolites that are associated with the pathogenesis and progression of atherosclerosis. In addition, glycerophospholipid and sphingolipid metabolism were found to be the most significantly altered pathways. Using comprehensive metabolomics techniques, we were able to differentiate atherosclerotic plasma metabolome from healthy control and delineate different stages of atherosclerotic progression.
Next, we characterized multiple mouse models of hyperglycemia-induced accelerated atherosclerosis. We showed that the vascular effects of glucosamine supplementation are comparable to streptozotocin-induced and genetically-induced (Ins2Akita) hyperglycemia in terms of lesional glucosamine, endoplasmic reticulum (ER) stress levels and atherosclerotic burden. In addition, we showed that a chemical chaperone (4-phenylbutyric acid) reduces ER stress levels and attenuates accelerated atherogenesis in each of these models. Together these findings support the mechanism involving glucosamine-induced ER stress in hyperglycemia-induced accelerated atherosclerosis.
Lastly, metabolomics techniques were used to investigate the molecular alterations by which hyperglycemia promotes the accelerated development of atherosclerosis in several disease models. The three mouse models induced both unique and common changes in the plasma metabolome. Identification of the commonly altered metabolite features revealed alterations in glycerophospholipid and sphingolipid metabolisms, and key atherosclerosis-associated processes including inflammation and oxidative stress.
Together, we showed that comprehensive metabolomics techniques can be used to identify specific alterations in the metabolome that are associated with a particular disease genotype and phenotype. These data highlight the important roles of the glycerophospholipid and sphingolipid metabolisms in the pathogenesis of atherosclerosis and diabetic atherosclerosis.  The clear difference in the level of several metabolites supports the use of plasma lipid profiling as a diagnostic tool of atherogenesis.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: USING AUTHENTIC SUBSTRATES TO PROBE WALL TEICHOIC ACID ASSEMBLY

contributor:
Brown, Eric
Biochemistry and Biomedical Sciences

subject: Wall teichoic acid

abstract:
Some of the most successful antibiotics in the clinic inhibit bacterial cell wall assembly. However, the continued emergence of multidrug-resistant bacteria is rapidly eroding the efficacy of these drugs - like all other antibiotics - and is a significant threat to human health. New treatment options are urgently needed that hinder bacterial viability, growth, and/or pathogenesis. Wall teichoic acids (WTAs) are integral components of Gram-positive bacterial cell walls and are critical to physiology and pathogenesis. WTA assembly is a bona fide drug target in several pathogens like Staphylococcus aureus. Many whole-cell screens have
been performed to find small molecule inhibitors of this process. These efforts require a deep understanding of WTA assembly to help identify, characterize, and exploit high potential targets and therapeutic strategies. Challenges involved in the isolation of authentic substrates have hampered detailed biochemical study of WTA biosynthesis. Many features of the process remain uncharacterized. In this thesis, I detail a novel chemoenzymatic method to prepare authentic WTA substrates. I show that these materials can be used to study WTA biosynthetic enzymes in vitro and to probe enigmatic features of WTA assembly. With authentic WTA substrates, I reconstituted the final step of B. subtilis WTA synthesis in vitro, which involves ligation of WTAs to peptidoglycan. This process eluded biochemical characterization for decades. I investigated the catalytic requirements and substrate preferences for the LytR-CpsA-Psr family of enzymes that mediate this glycopolymer transfer reaction. Further, I discuss the attractiveness of these enzymes as antibiotic drug targets. Authentic WTA substrates will likely continue to be useful tools in understanding molecular features of WTA assembly and serve to assist drug discovery and development efforts targeting this process.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Studies on the Mechanism of Prokaryotic Translational Termination

title: Prokaryotic Translational Termination

contributor:
Ganoza, M. C.
Neilson, T.
Biochemistry

subject: prokaryots translation termination

abstract: Using an in vitro prokaryotic termination assay, it was demonstrated that sequences neighbouring UA are recognized by RF-1 and stimulate cleavage of ribosome-bound f-met-tRNA_fmet. The ability of UA to signal release depends upon the nature of nucleotides adjacent both 3' and 5' to this sequence. RF-1 exhibits different specificity when potential termination sequences are covalently linked to AUG within the same polynucleotide, as in mRNA. Under these circumstances, within certain base context, (1) UA functions as a termination signal, (2) UA-containing terminator signals can be read out of the AUG-aligned reading frame and (3) RF-1 competes with aminoacyl-tRNA for sequence UUA. Another factor has been discovered, which partially corrects the specificity of RF-1. This factor (designated Specificity Factor) appears to be a protein, or a protein-containing component, and enhances RF-1-mediated termination caused by UAA but inhibits termination caused by UA. The factors known to participate in protein synthesis are not responsible for conferring specificity to the RF-1-mediated termination reaction. For this reason, it is believed that the Specificity Factor may be a new protein.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Effects of Dopamine Antagonists on Sham and Real Feeding of Sucrose Solutions: Are Peripheral Dopamine Receptors Implicated?

contributor:
Weingarten, H. P.
Psychology

subject: dopamine sucrose sham real psychology

abstract: The present thesis examined the relative contribution of dopamine (DA) receptors in the brain and periphery in the control of sucrose intake. Intraperitoneal (ip) administration of pimozide, an antagonist at peripheral and brain DA receptors, suppressed both sham and real sucrose intake in a dose-related manner. In contrast, ip injections of the peripheral DA antagonist domperidone affected neither sham nor real sucrose intake. The inability of domperidone to influence sucrose intake did not result from a lack of biological activity because doses of domperidone that did not alter sucrose intake significantly inhibited gastric acid secretion. The results indicate that central, but not peripheral DA receptors are involved in the control of feeding of sucrose solutions and that sham sucrose intake appears to be more sensitive to disruption of DA activity than real sucrose intake.

abstract: Thesis

abstract: Master of Science (MSc)


title: Interaction of Winter Flounder Antifreeze Protein With Ice

contributor:
Yang, Daniel S.C
Biochemistry

subject: antifreeze proteins, molecular modeling,H-bonds

abstract:
Interpretation of crystallographic and mutational studies of antifreeze proteins
(AFPs) requires molecular modeling of AFPs with ice. Most models proposed so far
suggested H-bonds as the major driving force of AFP-ice association. However, the bulk
water offers optimal network of H-bonds and van der Waals contacts to the isolated AFP
and ice suggesting that corresponding components of free energy would not decrease
upon AFP-ice association. In an attempt to resolve this controversy, we Monte Carlominimized
complexes of several AFPs with taking into account, in addition to nonbonded
interactions and H-bonds, the hydration potential for proteins (Augspurger and Scheraga,
1996). Parameters of the hydration potential for ice were developed basing on an
assumption that at the melting temperature the free energy of water-ice association is
small. Simulations demonstrate that desolvation of hydrophobic groups in the AFPs upon
their fitting to the grooves at the ice surface presents the major stabilizing contributions to
the free energy of AFP-ice binding. Our results explain available data on structure of
AFPs and their mutational analyses, in particular, a paradoxical fact that substitution of
Thr residues to Val does not affect potency of Winter Flounder AFP.

abstract: Thesis

abstract: Master of Science (MS)


title: Characterization and inhibition of interstrand crosslink repair nuclease SNM1A

subject:
SNM1A
beta-CASP nuclease
small molecule inhibitors
translesion nuclease
chemoresistance
structure-specific endonuclease
interstrand crosslinking repair
high throughput screening

abstract: Interstrand cross-links (ICLs) are a type of DNA damage that prevents strand separation required for basic cellular processes. ICL-based anti-cancer therapies exploit the cytotoxic consequences of replication and transcription inhibition, however, they are limited by the ability of the cell to repair DNA crosslinks. The challenge of ICL repair involves coordinating multiple DNA repair pathways to remove damage occurring on both strands of DNA. Participation of factors that are both exclusive and essential to crosslink repair suggests a pathway requirement to process unique structures and/or intermediates arising only in ICL repair. SNM1A is a nuclease required for survival of human cells in response to ICL exposure, but the specific function and role of SNM1A remain unclear. Here we show that, in addition to known 5’-3’exonuclease activity, SNM1A possesses single-strand specific endonuclease activity. Furthermore, SNM1A exhibits translesion nuclease activity on crosslinks which deform the helical backbone, but not non-distorting stable ICLs. We report the identification and characterization of nine small molecules inhibitors of SNM1A, isolated from an in vitro high-throughput screen of nearly 4,000 bioactive compounds. Finally, we demonstrate that inhibitors of SNM1A potentiate the cytotoxicity of ICL-inducing agent cisplatin in HeLa cells. The work in this thesis expands the possible roles of SNM1A in ICL repair and lays the groundwork for SNM1A inhibition in ICL sensitization efforts.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Analysis of Kaiso as A Transcription Factor

contributor:
Daniel, Juliet
Biology

subject: transcriptional repressor, physiological target, Kaiso, mechanism

abstract:
Recently, through reporter gene studies, the novel BTB/POZ protein, Kaiso,
has been identified as a transcriptional repressor. The purpose of this study was
to determine if Kaiso recruited the Histone Deacetylase Complex to mediate
repression and if the previously identified Kaiso Binding Site (KBS; TCCTGCNA)
is a physiological target regulated by Kaiso. The two objectives are
complementary because an HDAC interaction identifies the mechanism of
transcriptional regulation used by Kaiso and regulation of the KBS element
identifies a novel, non-methylation dependent, physiological target under
transcriptional regulation by Kaiso. Through coimmunoprecipitation and Western
blot analyses, Kaiso does not interact with HDAC1, HDAC2 or mSIN3A. These
results were surprising since all three of these proteins are common to a variety
of repression complexes. mSIN3A is a common component of SIN3 mediated
repression and HDAC1/HDAC2 are part of various repression complexes
including SIN3, NuRD and CtBP. Although the remaining HDAC proteins were
not assayed for an interaction, Kaiso transcriptional activity was demonstrated to
be insensitive to the HDAC inhibiting drug, Trichostatin A (TSA). These results
indicate either a non-HDAC mechanism of action or alternatively, transcriptional
activation. Complementary to the observations of no Kaiso-HDAC interaction
and TSA insensitivity was the findings that Kaiso activates transcription of the
KBS cis-element in HCT116, HCA-7 and 293 cells, but not MOCK cells in
reporter gene assays. Taken together, these results indicate that Kaiso is a dual
functioning protein capable of both transcriptional activation and repression and
that the mechanism of repression is not through the direct recruitment of HDAC
proteins.

abstract: Thesis

abstract: Master of Science (MSc)


title: Synthesis and Biological Activity of Novel Antimitotic Nucleoside Derivatives of Podophyllotoxin and 4'-Demethylepipodophyllotoxin

contributor:
Gupta, R.S.
Biochemistry

subject: synthesis, biological activity, novel antimitotic nucleoside derivatives, Podophyllotoxin, hydrophobic properties, mutants

abstract:
 The objective of this study was to synthesize and biologically evaluate a series of novel nucleoside derivatives of the naturally occurring lignans, podophyllotoxin and 4'-demethylepipodophyllotoxin. Epipodophyllotoxin derivatives display two types of  biological activity: while the naturally occurring compounds are potent inhibitors of microtubule polymerization, two semi-synthetic glycoside derivatives, viz VP16-213 (etoposide) and VM26 (teniposide), are specific inhibitors of mammalian DNA topoisomerase II. The latter two compounds have proven to be very useful in the treatment of many different types of cancer. In this study, the glycoside moiety of VP16-213/VM26 was replaced with either a thymidine or a 2'-deoxyadenosine group. The synthetic approach involved protective group chemistry, where functional groups on the nucleosides and DMEP were selectively blocked prior to their condensation in the presence of boron trifluoride etherate catalyst. These compounds are of interest because they involve substitution of the glucoside moiety with a nucleoside residue, whose effect on the biological activity of epipodophyllotoxin derivatives has not been examined. The biological activity of these compounds was assessed by examining their cross-resistance patterns towards a set of Chinese hamster ovary mutants resistant to podophyllotoxin VP16-213/VM26, mitotic index, and by a competition assay. From the cross resistance assay, all of the thymidine derivatives were found to be considerably less active than the parent podophyllotoxin and 4'-demethylepipodophyllotoxin molecules, while the 2'-deoxyadenosine derivatives were found to be completely inactive. The cross-resistance
patterns of the thymidine derivatives suggests that these compounds display podophyllotoxin-like activity in vivo and show no VP16-213/VM26-like activity. Treatment of wild type cells with the active thymidine derivatives (compounds 1.2, 2.2, 2.3, and 2.4) increased the mitotic indices approximately ten-fold in a dose-dependent manner, which parallels the results of the dose-response curves in the initial cross-resistance assay. Furthermore, there was a marked increase in the levels of drug required to elevate the mitotic index in second-step mutants resistant to podophyllotoxin, again lending support to the initial results indicating that the cellular target of these compounds is tubulin. Only one compound (1.2), was found to out compete the binding of radiolabelled podophyllotoxin to purified calf brain tubulin. However, due to their low activity relative to podophyllotoxin, most of these compounds were insoluble at concentrations required to out compete the binding of radiolabelled podophyllotoxin. Molecular modelling studies have provided useful insights regarding the structure/activity
relationships among the active and inactive nucleoside derivatives showing podophyllotoxin-like antimitotic activity. There appears to be steric limits for substituents attached at the C4 moiety that maintain the antimitotic activities of the parent molecules. The electrostatic potential and hydrophobic properties of these groups also seem to play a role in the degree of activity these compounds show, but remain unclear at this point. By simple comparison of the three-dimensional structures of these compounds there appears to be a very limited spacial and electrostatic requirement for the bulky glycosidic moiety attached to C4 which is essential for targeting VP16-213 and VM26 to DNA topoisomerase II. Thus, several important structural features which may distinguish the selectivity POD derivatives show for either tubulin or DNA topoisomerase II are described.

abstract: Thesis

abstract: Master of Science (MSc)


title: Stochastic Heuristic Program for Target Motif Identification

contributor:
Jiang, Tao
Computer Science

subject: stochastic heuristic program, target motif, identification, computational biology, solution algorithms

abstract: Identifying motifs that are "close" to one or more substrings in each sequence in a given set of sequences and hence characterize that set is an important problem in computational biology. The target motif identification problem requires motifs that characterize one given set of sequences but are far from every substring in another given set of sequences. This problem is N P-hard and hence is unlikely to have efficient optimal solution algorithms. In this thesis, we propose a set of modifications to one of the most popular stochastic heuristics for finding motifs, Gibbs Sampling [LAB+93], which allow this heuristic to detect target motifs. We also present the results of four simulation studies and tests on real protein datasets which suggest that these modified heuristics are very good at (and are even, in some cases, necessary for) detecting target motifs.

abstract: Thesis

abstract: Master of Science (MSc)


title: Context-Free Codon Alignment

subject: context-free, codon alignment, DNA sequences, protein, quadratic time complexity function, heuristic

abstract:
 We study an alignment model for coding DNA sequences recently proposed by J. Hein in [4] that takes into account both DNA and protein information, and attempts to minimize the total amount of evolution at both DNA and protein levels[4,5,6]. Although there are two quadratic algorithms (i.e. Hua-Jiang algorithm[8] and PLH algorithm[9]) for Hein's model if the gap penalty function is affine, both of them are impractical because of the large constant factor embedded in the quadratic time complexity function. We therefore consider a mild simplification named Context-free Codon Alignment and present a much more efficient algorithm for the simplified model. The algorithms have been implemented and tested on both real and simulated sequences, and it is found that they produce almost identical alignments in
most cases. Furthermore, we extend our model and design a heuristic algorithm to handle frame-shift errors and overlapping frames.

abstract: Thesis

abstract: Master of Science (MSc)


title: On-chip Tracing for Bit-Flip Detection during Post-silicon Validation

contributor:
Nicolici, Nicola
Electrical and Computer Engineering

subject:
Post Silicon Validation
Trace Signal Selection
Silicon Debug
Hardware Assertion Checker
Co-selection of trace and assertion

abstract:
Post-silicon validation is an important step during the implementation flow of digital integrated circuits and systems. Most of the validation strategies are based on ad-hoc solutions, such as guidelines from best practices, decided on a case-by-case basis for a specific design and/or application domain. Developing systematic approaches for post-silicon validation can mitigate the productivity bottlenecks that have emerged due to both design diversification and shrinking implementation cycles.

Ever since integrating on-chip memory blocks became affordable, embedded logic analysis has been used extensively for post-silicon validation. Deciding at design time which signals to be traceable at the post-silicon phase, has been posed as an algorithmic problem a decade ago. Most of the proposed solutions focus on how to restore as much data as possible within a software simulator in order to facilitate the analysis of functional bugs, assuming that there are no electrically-induced design errors, e.g., bit- flips. In this thesis, first it is shown that analyzing the logic inconsistencies from the post-silicon traces can aid with the detection of bit-flips and their root-cause analysis. Furthermore, when a bit-flip is detected, a list of suspect nets can be automatically generated.

Since the rate of bit-flip detection as well the size of the list of suspects depends on the debug data that was acquired, it is necessary to select the trace signals consciously. Subsequently, new methods are presented to improve the bit-flip detectability through an algorithmic approach to selecting the on-chip trace signals. Hardware assertion checkers can also be integrated on-chip in order to detect events of interest, as defined by the user. For example, they can detect a violation of a design property that captures a relationship between internal signals that is supposed to hold indefinitely, so long as no bit-flips occur in the physical prototype. Consequently, information collected from hardware assertion checkers can also provide useful debug information during post-silicon validation. Based on this observation, the last contribution from this thesis presents a novel method to concurrently select a set of trace signals and a set of assertions to be integrated on-chip.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Toward Identification of Disco Regulatory Proteins via Genetic Interaction Screens

contributor:
Campos, Ana
Biology

subject:
disco proteins
genetics

abstract:
The Disco protein has been identified as a transcription factor involved in the development of the 𝘋𝘳𝘰𝘴𝘰𝘱𝘩𝘪𝘭𝘢 𝘮𝘦𝘭𝘢𝘯𝘰𝘨𝘢𝘴𝘵𝘦𝘳 nervous system (Steller et al., 1987; Heilig et al., 1991; Lee et al., 1991). Although, its loss of function phenotype is well characterized, the specific function of Disco in development remains unknown. One method of elucidating the role of 𝘥𝘪𝘴𝘤𝘰𝘯𝘯𝘦𝘤𝘵𝘦𝘥 is to identify additional signaling components with which it interacts. The GAL4-UAS system (Brand and Perrimon, 1993) was used to create gain of function mutant phenotypes of the embryonic central nervous system, larval visual system and adult compound eye. These dominant phenotypes had in
common perturbations in cell differentiation and axonogenesis. Thus, these dominant phenotypes have provided an opportunity for further genetic interaction screens that would lead to the identification of proteins that interact with Disco. A putative binding site for Disco itself, called s120, has been identified in the 5' flanking region of the 𝘥𝘪𝘴𝘤𝘰 locus (Lee et al., 1999). To discern whether tissue-specific Disco expression is regulated by this sequence, we utilized a promoter-𝘭𝘢𝘤𝘡 fusion that included this regulatory sequence. The germ-line transformant lines carrying this construct showed β-galactosidase expression patterns that resembled wildtype 𝘥𝘪𝘴𝘤𝘰 expression, both in embryos and in the larval central nervous system (previously described by Lee et al., 1991). The expression of β-galactosidase remained like wildtype in the presence of excess Disco protein. Thus, this s120 regulatory sequence and the 5' flanking region studied were not sufficient to regulate Disco expression in the optic lobe primordium. Upon sequencing and analysis of this region, several transcription factor binding site consensus sequences were identified. These sequences, as well as others, may be required for interaction with Disco to confer tissue-specific autoregulation. Further sequencing and expression from deletion constructs is necessary to identify additional 𝘤𝘪𝘴-acting
regulatory regions of Disco.

abstract: Thesis

abstract: Master of Science (MSc)


title: Optics of Disposability: Documentary Photography and the Struggle to Appear

contributor:
Giroux, Henry
Searls Giroux, Susan
Clark, David
English and Cultural Studies

subject: Photography Neoliberalism Disposability Visuality

abstract:
Amplifications in photographic production and the increased access to images in the 21st century uniquely position photography to articulate and intervene in social structures of power and provide new opportunities for civic engagement. In particular, photography has the potential to articulate and resist what can be understood as a politics of disposability, or the ways in which particular populations are rendered superfluous to the economic and social logic of neoliberalism and channeled out of society. I assert that neoliberal violence must be understood, in part, as a visual problem: the particularities of representation and visibility must be examined in light of the need to consider neoliberal social and economic policies as something other than an inevitability. This dissertation explores the ways that photography can serve to make visible not only the people and discourses that have been marginalized and suppressed, but the structures of disposability itself.
Developments in artistic practices and departures from traditional documentary genres converge with precarious labor conditions for cultural workers to widen the parameters for photographic production. The resulting work engages both with the ontological questions of what documentary photography has become as well as with its ability to operate as a potential site of activism—rather than mere representation—through new modes of mediation. This dissertation examines new photographic work that addresses the multiple facets of a neoliberal politics of disposability, the effects of which are compounded by race, class, and gender: police violence and domestic militarization, the skyrocketing rate of women’s incarceration, and the institutional threats to youth and activism in the public sphere. These emergent photographic practices employ new strategies of visualization in order to complicate the viewer’s relationship to representations of violence, contributing to a discourse that broadens the possibility for a critical and productive use of photographs, and imagining alternatives to the material and ideological conditions of neoliberal disposability.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This dissertation examines the ability of emergent modes of documentary photography to articulate and resist social and political violence that is characteristic of neoliberalism, for example the domestic militarization and increased incarceration rates, the shrinking of access to the public sphere, and the particular ways in which certain populations become especially vulnerable to such violence. Shifts in photographic production thanks to new media platforms and the reconfigurations of traditional photography genres have produced photographic strategies that are crucially poised to address such issues.  The photographers and projects explored in this dissertation employ new ways of visualizing violence, speaking back to the ways that photography can be used to stultify discourse and misrepresent populations, and harnessing innovative modes of proliferating their work to produce new photographic and political communities.


title: Comparison of Normalization Methods in Microarray Analysis

contributor:
Canty, Angelo
Statistics

subject: normalization methods, microarray analysis, comparison, gene expression, high-density oligonucleotide, Robust Multi-chip Average

abstract:
 DNA microarrays can measure the gene expression of thousands of genes at a time to identify differentially expressed genes. The Affymetrix GeneChip system is a platform for the high-density oligonucleotide microarray to measure gene expression using hundreds of thousands of 25-mer oligonucleotide probes.

 To deal with Affymetrix microarray data, there are three stages of preprocessing to produce gene expression measurements/values. These are background correction, normalization and summarization. At each stage, numerous methods have been developed.

 Our study is based on Affymetrix MG_U74Av2 chip with 12488 probe sets. Two strains of mice called NOR and NOR.NOD_Idd4/11 mouse are hybridized for the experiment. We apply a number of commonly used and state-of-art normalization methods to the data set, thus compute the expression measurements for different methods. The major methods we discuss include Robust Multi-chip Average (RMA), MAS 5.0, GCRMA, PLIER and dChip.

 Comparisons in terms of correlation coefficient, pairwise expression measures plot, fold change and Significance Analysis of Microarray (SAM) are conducted.

abstract: Thesis

abstract: Master of Science (MSc)


title: SELECTIVE OXIDATION AND REACTIVE WETTING OF FE-0.1C-6MN-2SI-xSN ADVANCED HIGH STRENGTH STEELS DURING CONTINUOUS HOT-DIP GALVANIZING

contributor:
McDermid, Joseph R
Materials Science and Engineering

subject: Third generation advanced high strength steels

subject: Continuous hot-dip galvanizing

subject: Selective oxidation

abstract:
Third generation advanced high-strength steels (3G-AHSS) have received significant interest from leading auto steel industries and OEMs as candidate materials for reduced mass Body In White (BIW) components due to their unique combination of high specific strength and ductility. However, the continuous hot-dip galvanizing of these steels is challenging due to selective oxidation of the main alloying elements such as Mn, Si, Al and Cr at the steel surface during the annealing step prior to immersion in the galvanizing Zn(Al, Fe) bath, as extensive coverage of the substrate surface by these oxides is detrimental to reactive wetting, good coating adhesion and integrity.
Simulated galvanizing treatments were conducted on two prototype Fe-0.1C-6Mn-2Si (wt pct) 3G steels; one as the reference steel and the other with 0.05 wt pct Sn added to the composition. The combined effects of annealing temperature, time, process atmosphere oxygen partial pressure and 0.05 wt pct Sn addition on the selective oxidation of the steel substrates were determined. Subsequently, the reactive wetting of the steels with respect to the pre-immersion surface structures of the samples annealed for 120 s was examined. Annealing heat treatments were carried out at 800˚C and 690˚C in a N2-5 vol pct H2 process atmosphere under three dew points of –50˚C, –30˚C and +5˚C, covering process atmosphere oxygen partial pressures within the range of 1.20  10-27 atm to 1.29  10-20 atm. MnO was present at the outmost layer of the external oxides on all samples after annealing. However, the morphology, distribution, thickness and surface coverage were significantly affected by the experimental variables. Annealing the reference steel under the low dew point process atmospheres, i.e. –50˚C and –30˚C, resulted in the highest Mn surface concentration as well as maximum surface oxide coverage and thickness. The oxides formed under these process atmospheres generally comprised coarse, compact and continuous film forming nodules, whereas the surface morphologies and distributions obtained under the +5˚C dew point process atmosphere, which was consistent with the internal oxidation mode, exhibited wider spacing between finer and thinner MnO nodules. The grain boundary internal oxide networks had a multi layer structure with SiO2 and MnSiO3 at the oxide cores and shells, respectively. Significant morphological changes were obtained as a result of Sn addition. The continuous film-like external MnO nodules were modified to a fine and discrete globular morphology, with less surface coverage by the oxides and reduced external oxide thickness. Both the external and internal oxidations followed parabolic growth kinetics, where the depth of the internal oxidation zone decreased with Sn addition and decreasing oxygen partial pressure.
Poor reactive wetting was observed for the reference steel substrates that were annealed for 120 s under the –50˚C and –30˚C dew point process atmospheres at 800˚C and under the –50˚C dew point atmosphere at 690˚C, such that no integral metallic coating was formed after the 4 s immersion in the Zn(Al, Fe) bath. By contrast, excellent coating quality was obtained for the Sn-added steels when the –30˚C and +5˚C dew point process atmospheres were employed when annealing at 690˚C. The remainder of the experimental conditions demonstrated good reactive wetting with intermediate coating quality. For the two reference steels annealed at 800˚C under the –50˚C and –30˚C dew point process atmospheres, poor reactive wetting was due to full coverage of the surface by 116 nm and 121 nm thick and continuous MnO films. In the case of the 690˚C  –50˚C reference steel with the external layer thickness of only 35 nm, however, poor wetting was attributed to substantial coverage of the surface by continuous, film-like oxides. In both cases, exposure of the underlying substrate to the bath alloy and an intimate contact between the substrate Fe and the bath dissolved Al could not take place and the formation of the Fe2Al5Znx interfacial layer was hidered.
For the processing conditions that satisfactory reactive wetting was obtained despite the pre-immersion selective oxidation of the surfaces, several reactive wetting mechanisms were determined. For the samples with a sufficiently thin external MnO layer, good reactive wetting was attributed to partial reduction of MnO by the bath dissolved Al, as well as bridging of the Mn sub-oxides by the Zn coating or Fe2Al5Znx interfacial intermetallics. Partial or full formation of the Fe2Al5Znx interfacial layer was observed in the successfully galvanized substrates with Fe-Al crystals formed between, underneath and also on top of the reduced oxides. Furthermore, for cases with widely-spaced, fine oxide nodules, it was found that the liquid bath alloy was able to infiltrate the external oxide/substrate interface, resulting in surface oxide lift-off and enhanced coating adhesion. It was globally concluded that the thin, discrete and fine globular morphology of external MnO, resultant of annealing the steel substrates with 0.05 wt pct Sn addition under the process atmosphere oxygen partial pressures consistent with internal oxidation, allowed for an enhanced reactive wetting by the Zn(Al, Fe) galvanizing bath which was manifested by increased amount of Al uptake and population of the Fe2Al5Znx intermetallics at the coating/steel interface.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: Enhanced Optical/Electrical Conversion in Indium-doped Silicon Thin Films for Applications in Photovoltaic Cells and UV-A Detectors

contributor:
Knights, Andrew
Engineering Physics

subject:
UV-A
Detectors
Solar cells
Photovoltaic
Thin-film photovoltaic
Crystalline silicon

abstract:
Efficient optical-to-electrical conversion is a fundamental requirement of a range of silicon devices such as those which employ photodetection, solid-state-imaging and photovoltaic power generation. This thesis investigates the effects of using indium, a deep-level acceptor in silicon, as a dopant for thin film single crystalline silicon solar cells and UV-A detectors. Indium acts as a p-type dopant in silicon and has been proposed previously as a substitutional lattice defect that would enable sub-band gap transitions as described by the so-called impurity photovoltaic (IPV) effect. The physical mechanisms responsible for operation of the devices presented in this work are described. Models for electrical performance, optical absorbance and device fabrication are used as methods to interpret data and optimize device parameters. Specifically, a two-diode model is used to account for the electrical loss mechanisms within a device, while modeling optical absorption by a multilayer structure consisting of Silicon-On-Insulator (SOI) is approached using a novel multi-wavelength numerical model that describes the reflections and transmissions at each of the device’s layers. Additionally, Technology Computer Aided Design (TCAD) simulations were used to optimize the critical fabrication parameters associated with the ion implantation and thermal annealing techniques used during the device fabrication process.
Selected from multiple devices fabricated during the course of this work, the most efficient solar cells in SOI (2.5 μm thick active layer) exhibited a maximum conversion efficiency of 4.74 % for indium-doped and 4.16 % for boron-doped layers. The most efficient UV-A detector fabricated in SOI (100 nm thick) exhibited a maximum responsivity to 365 nm light of 20 mA/W for indium-doped and 16 mA/W for boron-doped devices. In both types of devices, indium doping consistently resulted in a relative increase in efficiency when compared to equivalently fabricated, boron doped devices, despite experimental carrier decay measurements confirming the action of the indium as a recombination centre. External and internal quantum efficiency measurements confirm a relative enhancement in absorption, for solar cells and detectors doped with indium, which is correlated with the p-type dopant concentration and the ratio of n-type to p-type concentrations. The origin of the enhancement is postulated to be caused by a relaxation of the momentum-space restrictions associated with undoped silicon, a postulate supported by previously reported absorption data. This thesis presents the first comprehensive data from indium doped silicon devices designed for optical-to-electrical conversion. The implications for a range of widely deployed devices may be significant.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)