title: SOLID STATE NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY OF CHEMICALLY MODIFIED GRAPHITIC MATERIALS FOR THE PERFORMANCE ENHANCEMENT OF HYDROGEN FUEL CELLS

contributor:
Goward, Gillian
Chemistry and Chemical Biology

subject:
graphene
graphene oxide
solid state NMR
hydrogen fuel cells
nanotubes

abstract:
Solid-state nuclear magnetic resonance (ssNMR) spectroscopy was used to anal-
yse numerous graphene-sheet based materials in an attempt to study their effects
on the performance of polymer electrolyte membrane fuel cell (PEM-FC) mate-
rials. It has been noted in the literature that fuel cells which incorporated these
materials (e.g. functionalized graphene, doped carbon nanotubes (CNTs), etc.)
displayed increased performance over a wider range of environmental conditions,
chiefly temperature and relative humidity. The inter-material interactions behind
this phenomenon are poorly described at best. Due to its extreme site speci ficity
and sensitivity to minute differences in nuclear electromagnetic environments, ss-
NMR is an ideal tool for investigating the complicated interactions at work in these
systems. While the electronically conductive, amorphous, non-stoichiometric, and
low spin-density nature of these materials presented challenges to the collection
of NMR spectra, the results presented here display the remarkable utility of this
method in the study of analogues and derivatives of graphene.
Graphene Oxide (GO), a derivative of graphene, has intrinsic proton conduc-
tivity which is similar to Na fon, the most popular proton exchange membrane
material currently used in fuel cells. Research into acid-functionalized graphene
oxides and determining the role of acidic groups in increasing proton conductivity
will help to improve polymer electrolyte membrane performance in fuel cell sys-
tems. Multinuclear solid-state NMR (ssNMR) spectroscopy was used to analyse
the structure and dynamics of GO and a number of sulfonic acid derivatives of
GO, both novel and previously reported. 13C spectra showed the disappearance
of surface-based oxygen groups upon GO functionalization, and can be used to
identify linker group carbon sites in previously synthesized and novel functional-
ized GO samples with high speci city. Dehydration of these samples allows the
collection of 1H spectra with resolved acidic proton and water peaks. The effect of dehydration on the proton spectrum is partially reversible through rehydration.
Deuteration of the acidic groups in high temperature and acidic conditions was
virtually unsuccessful, indicating that only the surface and not the intercalated
functional groups play a role in the enhanced proton conductivity of ionomer /
functionalized GO composites. Increased surface area and increased delamination
of functionalized GO is suggested to be important to improved PEM-FC perfor-
mance. This synthesis and method of analysis proves the utility of ssNMR in the
study of structure and dynamics in industrially relevant amorphous carbon ma-
terials, despite the obvious di culties caused by naturally broad signals and low
sensitivity. Graphene and carbon nanotubes (CNTs) have been investigated closely in re-
cent years due to their apparent positive effect on the electrochemical performance
of new fuel cell and battery systems as catalyst stabilizers, supports, or as metal-
free catalysts. This is particularly true for doped graphene and CNTs, where
only a small amount of doping with nitrogen and/or phosphorus can have a re-
markable effect on materials performance. A direct link between structure and
function in these materials is, as of yet, unclear. Doped graphene and CNTs
were synthesized using varied chemical vapour deposition (CVD)-based methods,
and ssNMR was used to unambiguously identify dopant atom sites, revealing that
these particular synthesis methods result in highly homogeneous populations of
installed phosphorus and nitrogen atoms. We present the  first experimental 15N
spectrum for graphitic nitrogen in N-doped graphene. 15N-labeled nitrogen doped
graphene synthesized as reported here produces mainly graphitic nitrogen sites
located on the edges of sheets and around defect sites. 1H-1H and 1H-15N corre-
lations were also used to probe dopant nitrogen sites in labelled and unlabelled
N-doped graphene. A nearly homogeneous population of phosphorus in P-doped
graphene is found, with an overwhelming majority of graphitic phosphorus and
a small amount of phosphate oligomer. Similar  findings are noted for the phos-
phorus sites in phosphorus and nitrogen co-doped CNTs with a minor change in
chemical shift, as would be expected from two chemically similar phosphorus sites in carbon allotropes (CNTs versus graphene sheets) with signifi cantly different electronic structures.
Ionomeric sulfonated polyether ether ketone (SPEEK) membranes were doped
with functionalized graphenes, and the proton conductivities of these composite
membranes was measured at fuel cell operational temperatures and percent relative
humidities (%RH). The differences in proton conductivity between pure SPEEK
membranes and composites with different dopants and doping levels at varied
conditions were investigated through high-fi eld 1H ssNMR. It was found that high-
speed MAS was able to dehydrate membranes under water-saturated conditions,
and so lower %RH conditions were better able to produce reliable ssNMR results.
The addition of graphitic dopants appeared to have an overall detrimental effect
on the bulk proton conductivity of membranes, while concurrently these doped
membranes had a broadened operational temperature window.
In an attempt to explore the positive influence of nitrogen doping on the effec-
tive lifetime of carbon-supported platinum catalysts used in automotive hydrogen
fuel cell systems, solid-state NMR was employed to probe the difference (if any)
between doped catalyst supports made from different carbon and nitrogen sources.
1H spectroscopy showed a variety of sites present in the doped samples; some likely
from residual starting material but others from novel sites within the doped cat-
alyst supports. Double-quantum and 2D 1H experiments were used to examine
the structure of these catalysts, while 13C CPMG experiments (see Chapter 2)
revealed subtle differences in the nuclear relaxation rates of these materials, poten-
tially related to their electronic conductivity. The results of the ssNMR analysis
were insuffcient to provide an unambiguous picture of the dopant sites within
these carbon black samples; this was due in equal parts to the lack of isotopically
labelled dopants, the effects of electronic induction and ring current shifts on data
acquisition and analysis, and the broad array of different 13C chemical shift en-
vironments present in the carbon black itself. While the data is still interesting
spectroscopically, suggestions are made at the end of this chapter to expand upon
the lessons learned through this study to produce more useful results from similar
samples in the future.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Solid-state nuclear magnetic resonance (ssNMR) spectroscopy was used to anal-
yse numerous graphene-sheet based materials in an attempt to study their effects
on the performance of polymer electrolyte membrane fuel cell (PEM-FC) materials.
It has been noted in the literature that fuel cells which incorporated these materials
(e.g. functionalized graphene / graphite, doped carbon nanotubes (CNTs), etc.)
displayed increased performance over a wider range of environmental conditions,
chiefly temperature and relative humidity. The inter-material interactions behind
this phenomenon are poorly described at best. Due to its extreme site specifi city
and sensitivity to minute differences in nuclear electromagnetic environments, ss-
NMR is an ideal tool for investigating the complicated interactions at work in these
systems. While the electronically conductive, amorphous, non-stoichiometric, and
low spin-density nature of these materials presented challenges to the collection
of NMR spectra, the results presented here display the remarkable utility of this
method in the study of analogues and derivatives of graphene.
Covalently functionalized graphene / graphite was synthesized, and the struc-
tures of several derivatives were recorded with remarkable resolution, such that
functional group carbons were resolvable. The proton dynamics of this material
were remarkably slow, and so improvements in composite PEM ion conductiv-
ity were proposed to be caused by surface interactions between dopant and poly-
mer. The proton dynamics of ionomer graphene composites were also investigated
through ssNMR. A number of graphene and CNT samples doped with phosphorus
and 15N-labelled nitrogen were also analysed, and the synthesis methods employed
were found to produce chemically homogeneous dopant sites with few by-products.
Absent isotopic labelling, nitrogen dopant sites in carbon black samples were found
to affect the relaxation properties of protons within nitrogen doped carbon black.


title: Expression Analysis of ABC Transporters in Sinorhizobium meliloti

contributor:
Finan, T. M.
Biology

subject:
sinorhizobium meliloti
sinorhizobium
transport
expression

abstract: Soils contain a complex mixture of compounds many of which can be transported and metabolized by microorganisms. 𝘚𝘪𝘯𝘰𝘳𝘩𝘪𝘻𝘰𝘣𝘪𝘶𝘮 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 is a soil bacterium whose gene sequence was recently determined. The diversity of the carbon and nitrogen sources than can be utilized by this organism is reflected in the large number of annotated ATP-binding cassette transporters in its genome. Although many of these genes are not necessary for survival, it is hypothesized that they arid in the competitive fitness of 𝘚. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 in the field. Many of these transporters remain uncharacterized. In this study a high throughput screen was developed to measure β-glucuronidase activity in a 96 well microtitre plate format to quantify expression of many reporter gene fusions under a variety of conditions. This system was used to analyze the expression of putative small molecule ABC transporters in 𝘚. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪. 45 𝘨𝘶𝘴𝘈 reporter gene transcriptional fusions to these transport genes were generated and recombined into the genome. These strains were grown in 96 well plates in minimal media containing a large number of carbon sources and carious legume root and seed exudates to be tested as inducers of transporter gene expression. Two transport systems were found to be induced by glucosamine and galactosamine and others were found to be induced by various sugars including mannose, arabinose, xylose and palatinose as well as protocatechuate and hydroxybenzoate. The bacteria-plant symbiosis of 𝘚. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 and alfalfa plays an important role in agriculture. To further understand the role of ABC transporters in the competition of 𝘚. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 the 𝘨𝘶𝘴𝘈 reporter fusions strains will also e inoculated onto alfalfa roots and nodules will be assayed for GusA activity to give a more complete picture of the role of ABC transporters in the competition and symbiosis of 𝘚. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪. Two substrates, galactitol and hydroxyproline found to induce transport systems were studied in depth in order to more fully understand the transport, metabolism and regulation of these compounds.

abstract: Thesis

abstract: Master of Science (MS)


title: Ultra-Violet Transcription Unit Mapping of Adenovirus Type 2

contributor:
Rainbow, A. J.
Biology

subject: ultra-violet adenovirus map

abstract: At late times during the infection of human KB cells with Adenovirus type 2 (Ad 2), the ultraviolet (uv) sensitivity of transcription was assayed by DNA-RNA hybridization across the length of the genome. Assuming that the majority of the nuclear transcripts at this time of infection are read from the rightward transcribing DNA strand, the resulting plot of the surviving fraction of viral transcription vs. genome position indicates two transcription units are responsible for the transcription from selected DNA restriction fragments of the genome were also obtained. The uv inactivation cross sections generated from such curves identified a long, uv sensitive transcript originating from the major late promoter at approximately 17 map units, and a shorter, less uv sensitive from approximately 63 map units on the genome. The shorter transcription unit accounts for about one third to a half of the viral nuclear RNA synthesized from the right hand 30 to 40% of the genome. The majority of the late viral nuclear transcripts, however, originated at approximately 17 map units and terminated at around 60-70 map units. Similar experiments examining the uv sensitivity of cytoplasmic poly A RNA production at various sites across the length of the genome are consistent with two rightward transcribing transcription units expressed during late Ad 2 infection. The transcriptional organization of late Ad 2 gene expression was also approached through uv transcription unit mapping experiments by examining the uv sensitivities of the synthesis of late Ad 2 proteins for which the approximate gene locations are known. The effect of uv on Ad 2 nuclear transcription was also reflected at the polypeptide level indicating two transcription units are responsible for the synthesis of mRNA coding for late viral proteins. The differential radiosensitivities of late protein synthesis confirmed the relative gene positions on the Ad 2 genome.

abstract: Thesis

abstract: Master of Science (MS)


title: Effect of Vanadium Addition on Deformation and Fracture Behavior of DP1300 Dual Phase Steels

contributor:
Wilkinson, David
Engineering

subject:
Microscopic DIC
DP1300
SEM
Nano-indentation

abstract:
Advanced high strength steel (AHSS) provides a lightweight material solution in response to the stringent regulation on fuel economy and greenhouse gas emissions in the automotive industry. Dual phase (DP) steels that consist of a hard martensite phase embedded in a soft ferrite matrix are the most widely used AHSS due to their simple microstructure, robust thermo-mechanical processing and attractive mechanical properties. However, DP steels are prone to deform heterogeneously with strong strain partitioning between phases. The addition of Vanadium in DP steels can form nano-precipitates of vanadium carbonitrides (V (C,N)) that strengthen the ferrite and thus reduce the strain partitioning. This study considered the influence of V (C,N) on the deformation and damage behavior of ferrite-martensite DP1300 steels at the microscopic level. The hardness of the embedded ferrite and martensite regions are determined through nano-hardness testing. In-situ uniaxial tension tests were conducted on DP steels with similar martensite volume fractions within a scanning electron microscope (SEM) chamber. Microscopic-digital image correlation (µDIC) was then employed to analyze the local strain partitioning between ferrite and martensite. Local damage events such as void formation at ferrite martensite island interfaces and in the martensite islands were observed and rationalized with the µDIC results. X-ray computed tomography (XCT) were conducted to quantitatively analyze the microstructure damage.
It was found that vanadium addition helps refine the microstructure and improve mechanical compatibility between the two phases. The overall ductility of the steel is enhanced especially in terms of post-uniform elongation and true strain to fracture.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Roles of the Malic Enzymes of Rhizobium (Sinorhizobium) Meliloti in Symbiotic Nitrogen Fixation

title: Roles of Malic Enzymes of R. Meliloti in Symbiosis

subject:
rhizobium meliloti
sinorhizobium
malic
enzyme
fixation
nitrogen
symbiotic

abstract: The genome of 𝘙. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 contains two genes for malic enzymes. One uses NAD⁺ as a cofactor (𝘥𝘮𝘦) and one utilizes NADP⁺ (𝘵𝘮𝘦). The two enzymes have been purified and the genes cloned and sequenced. Loss of TME enzyme function gives no detectable phenotype in either 𝘙. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 grown in culture or in bacteroids. Loss of DME function gives no detectable phenotype in 𝘙. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 grown in culture but does result in bacteroids that are unable to fix nitrogen (Fix⁻). Expression of 𝘵𝘮𝘦 is reduced in bacteroids whereas 𝘥𝘮𝘦 expression remains unchanged. In order to overexpress 𝘵𝘮𝘦 in bacteroids a fusion gene was constructed with the 𝘥𝘮𝘦 promoter driving expression of the 𝘵𝘮𝘦 structural gene (𝘥𝘵𝘮𝘦). The 𝘥𝘵𝘮𝘦 gene was expressed and functional in 𝘙. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 cells grown in culture, but alfalfa plants inoculated with strains expressing only the 𝘥𝘵𝘮𝘦 gene were Fix⁻. In addition the NAD⁺-dependent malic enzyme gene from 𝘚𝘵𝘳𝘦𝘱𝘵𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘣𝘰𝘷𝘪𝘴 (𝘮𝘢𝘦𝘌) was similarly cloned downstream of the 𝘥𝘮𝘦 promoter. The fusion gene 𝘥𝘮𝘢𝘦𝘌 was expressed in 𝘙. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 cells grown in culture, surprisingly plants inoculated with strains expressing only the 𝘥𝘮𝘢𝘦𝘌 gene showed a Fix⁻ phenotype. A truncated 𝘥𝘮𝘦 gene was constructed which contained only the N-terminal, malic enzyme domain of the protein (𝘥𝘮𝘦Δ𝘗𝘴𝘵). The truncated enzyme was expressed and active in 𝘙. 𝘮𝘦𝘭𝘪𝘭𝘰𝘵𝘪 cells grown in culture and gave a Fix⁺ phenotype when inoculated onto alfalfa plants.

abstract: Thesis

abstract: Master of Science (MS)


title: Characterization of the chlamydial type III secretion translocator proteins CopB and  CopD

title: Characterization of the chlamydial T3S translocator proteins

contributor:
Mahony, James
Medical Sciences

abstract:
Chlamydiae spp. are a significant cause of disease worldwide. Chlamydia
pneumoniae is a respiratory pathogen which is believed to cause approximately
10% of community-acquired pneumoniae. Furthermore, C. pneumoniae infections
have been associated with the development of atherosclerosis, exacerbation of
asthma, multiple sclerosis and Alzheimer’s. Chlamydia trachomatis, the causative
agent of trachoma, is responsible for over 6 million cases of preventable
blindness each year. Furthermore, C. trachomatis is the leading bacterial sexually
transmitted infection in North America. Yet, given how prevalent chlamydial
infections are, there is still limited information regarding the pathogenic
mechanisms by which Chlamydia infects its host.
Type III secretion is a conserved pathogenic virulence factor used by
gram-negative bacteria. Type III secretion has been extensively studied in other
bacterial genera, but given the difficulty of working with Chlamydia, there have
been few advances in our understanding of the role of type III secretion in
chlamydial pathogenesis. A set of proteins, called translocators, are believed to
be indispensable for infection; however, a comprehensive biochemical
characterization of them has not been undertaken. Using GST-pulldown assays,
interactions between Chlamydia outer protein (Cop) B and D from C. pneumoniae
and other components of the type III secretion system are characterized.
Furthermore, site-directed mutagenesis was used to elucidate the critical amino
acids involved in interaction between the putative chaperone, LcrH_1, and both CopB and CopD. We also demonstrate that CopD is capable of forming higher
ordered structures, and that CopD and LcrH_1 interact in a 1:1 ratio. Using
polyclonal antibodies directed towards the translocator proteins, we demonstrate
that CopB and CopD may be surface exposed prior to host cell contact and
critical to infection. A synthetic peptide consisting of the chaperone binding
domain was capable of blocking the interaction between LcrH_1 and the
translocator proteins, as well as inhibiting infection in vitro. Lastly, an animal
model of Chlamydia infection was developed to explore whether the use of type
III secretion system proteins could be used to protect against Chlamydia infection
and Chlamydia induced pathology.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Chlamydia species are gram-negative bacteria that cause a wide range of
human disease, including pneumonia, blinding trachoma, and sexually
transmitted infections. However, our current understanding of the mechanisms by
which Chlamydiae infects its host is relatively unknown. Using various
biochemical techniques, the function of two proteins that are believed to be
important for chlamydial pathogenesis are explored. Using an animal model for
chlamydial genital infections, a novel vaccine was developed to evaluate its
ability to protect against a live Chlamydia challenge and reduce the prevalence of
sequelae.


title: Analysis of C4-Dicarboxylic Acid Transport Genes in Rhizobium Meliloti

title: C4-Dicarboxylic Acid Transport Genes in R. Meliloti

subject:
c4
dicarboxylic acid
transport gene
gene
rhizobium meliloti

abstract:
Rhizobium meliloti mutants defective in  C₄-dicarboxylic acid transport (Dct⁻) were previously isolated by  Tn5 mutagenesis, and divided into two groups based  on complementation of Dct- with cosmid clones. In this work  further characterization was carried out on the two loci.  Group I mutants were found to be defective in dicarboxylate  transport (Dct⁻), nitrate utilization, and symbiotic nitrogen fixation. Subcloning and complementation work  confined the Group I mutations to a 3.5 kbp BamHI-EcoRI fragment containing the ntrA  gene. Group V mutants were defective in dicarboxylate transport and demonstrated  varying levels of nitrogen fixation. Complementation  and site-directed Tn5 mutagenesis revealed three transcriptional units, corresponding to dctA,
dctB, and dctD, localized within a 6 kbp HindIII fragment. The use of dctA::TnphoA fusions determined  the expression of dctA to be ntrA, dctB, and dctD dependent. Dct+ revertants of dctB and dctD mutants were selected which carried second-site mutations responsible for restoring the Dct⁺ phenotype.

abstract: Thesis

abstract: Master of Science (MS)


title: An Examination of UV-Induced Bystander Effects and the Repair of a UV-Damaged Reporter Gene in Human Cells

title: Bystander Effects and DNA Repair Following UV Exposure

subject: UV bystander repair human cell

abstract:
We have used a non-replicating recombinant adenovirus, AdCA17𝘭𝘢𝘤𝘡, which expresses the β-galactosidase (β-gal) reporter gene under the control of the human cytomegalovirus immediate early
(HCMV-IE) promoter, to examine host cell reactivation (HCR) of a UVC-damaged reporter gene in human fibroblasts. Since β-gal expression in mammalian cells is expected to occur following
transcription of a lesion-free 𝘭𝘢𝘤𝘡 reporter gene, the removal of UV-induced DNA lesions and subsequent β-gal expression is a measure of the DNA repair capacity of the infected cell. In the
present work, we have examined HCR and UV-enhanced HCR of the UV-damaged reporter construct, AdCA17𝘭𝘢𝘤𝘡, in normal and nucleotide excision repair (NER) deficient fibroblasts. Xeroderma
pigmentosum (XP) group C and E fibroblasts are deficient in the global genome pathway (GGR) of NER, while Cockayne syndrome (CS) fibroblasts are deficient in the transcription-coupled repair
pathway (TCR) of NER and XP group A fibroblasts are deficient in both TCR and GGR. HCR of the UV-damaged reporter gene activity was significantly reduced in XP-A, XP-C, XP-E and CS-B cell
strains relative to that in normal human fibroblasts, indicating that both TCR and GGR contribute to expression of the UV-damaged reporter gene in human cells. Pre-treatment of human
fibroblasts with UVC (12 J/m²) immediately prior to infection results in enhanced HCR of the UV-damaged reporter gene. UV-enhanced HCR of the UV-damaged reporter gene was detected in normal
fibroblasts at 12 hr post-infection and in CS-B, XP-C and XP-E fibroblasts, but not XP-A fibroblasts at 24 and 40 hr post-infection. These results indicate that both TCR and GGR are
UV-inducible in human cells. We have examined the colony survival of various human cells following exposure to UVC and UVA radiation. HaCAT, an immortalized human keratinocyte cell line,
demonstrated increased resistance to UVC exposme compared to glioma (U373, T98G) and colon carcinoma (HT29) cell lines, while exhibiting increased sensitivity to UVA radiation and H₂O₂
treatment. This increased sensitivity towards both UVA and H₂O₂ treatment suggests that HaCAT cells have a reduced capacity to repair oxidative DNA damage. In addition, we show that p53-null
keratinocytes (HPV-G) have reduced clonogenic survival compared to p53-mutant keratinocytes (HaCAT) following H₂O₂ treatment, consistent with an involvement of p53 in the survival of
keratinocytes following H₂O₂ treatment. We also examined whether the interaction of H₂O₂ with growth media resulted in chemical by-products that were toxic to cells. Even though the H₂O₂
levels in the media were reduced following 24 hr incubation, similar clonogenic survival curves of HaCAT cells were observed following treatment of cells with immediately-prepared or
24hr-incubated H₂O₂-containing media solutions. Thus, extended incubation (24 hr) of H₂O₂ with media did not alter its cytotoxicity towards HaCAT cells, indicating that no detectable levels
of toxic chemical by-products were produced. Ultraviolet irradiation of cells can have both cytotoxic and/or mutagenic consequences, resulting in increased levels of cell death or the
induction of a state of genomic instability that persists for several cell generations after irradiation. However, the extent of the effects induced in non-irradiated cells by UV -irradiated
cells has not been fully investigated. Using the medium transfer technique, we have tried to address whether UV irradiation of cells can induce biological effects in non-irradiated cells.
Medium obtained from UVA, but not UVC, irradiation of various human cell lines in phosphate-buffered saline (PBS) solution was capable of reducing the relative clonogenic survival and colony
size of non-irradiated HaCAT cells. In the absence of cells, UVA-irradiation of PBS reduced the clonogenic survival, but not the colony size, of various non-irradiated human cells. These
results indicate a cytotoxicity of UVA-irradiated PBS towards non-irradiated cells. Hydrogen peroxide, a reactive oxygen species (ROS) generated following UV A irradiation, was measured
following UV A treatment (or mock-treatment) of PBS (in the presence or absence of cells) either immediately or 24 hr post-irradiation. Hydrogen peroxide levels increased immediately
following UV A irradiation, suggesting that it may contribute to the reduced survival of non-irradiated human cells. However, human glioma T98G and U373 cells produced elevated H₂O₂ levels
in mock-irradiated conditions at 24 hr post-incubation, while demonstrating different sensitivities towards treatment with medium containing UVA-irradiated PBS. These results suggest that
UVA-induced H₂O₂ is not responsible for the reduction in clonogenic survival of non-irradiated human cells. We also examined colony number and size at different times following the addition
of media containing UVA-irradiated PBS and media from UVA-irradiated cell cultures. Increasing the time before scoring for colonies resulted in an increased clonogenic survival and a
decrease in relative colony size for HaCAT cells. These preliminary results suggest that the relative survival and relative colony size of non-irradiated cells are inter-related, and
indicate that treating non-irradiated HaCAT cells with medium from UVA-irradiated cells or medium containing UVA-irradiated PBS reduced the growth rate of HaCAT colonies. Therefore, in order
to properly evaluate clonogenic survival, a time-dependent examination of relative survival and relative colony size should be conducted in order to address whether the treatment results in
an inhibition of cell growth and/or true cell killing.

abstract: Thesis

abstract: Master of Science (MS)


title: The Response of Radiation Resistant Bacteria Deinococcus Sp. to Oxidative Stress

title: The Response of Deinococcus So. to Oxidative Stress

contributor:
Schellhorn, H. E.
Biology

subject: deinococcus oxidative stress radiation bacteria

abstract: Bacteria of the radiation resistant genus 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 have a high resistance to the lethal and mutagenic effects of many DNA damaging agents, however, the mechanisms involved in the response of these bacteria to oxidative stress are poorly understood. To investigate antioxidant enzyme responses in 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp., the types of catalase and superoxide dismutase (SOD) produced by these bacteria were identified by visualization of the enzyme activities on non-denaturing polyacrylamide gels (PAGE) and the growth inhibition of selected strains by various concentrations of hydrogen peroxide and paraquat (a superoxide generating agent) was tested. 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp. were found to be more resistant to hydrogen peroxide and more sensitive to paraquat than 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 K12. They possess relatively high levels of catalase and exhibit similar electrophoretic patterns on catalase zymograms compared to 𝘌. 𝘤𝘰𝘭𝘪, but all the tested strains produce only one SOD except 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘳𝘢𝘥𝘪𝘰𝘱𝘩𝘪𝘭𝘶𝘴 which produces two. The two catalases of 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴 were found to be regulated independently. Cultures of 𝘋. 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴, when pretreated with sublethal levels of hydrogen peroxide, became relatively resistant to the lethal effects of H₂O₂ and exhibited higher levels of catalase than untreated control cultures. The pretreated cells were also relatively resistant to UV-and γ-ray-mediated lethality. These results suggest that 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp. possess inducible defense mechanisms against the deleterious effects of oxidants and ionizing and UV radiation. The resistance to the lethal effects of hydrogen peroxide and UV radiation can not be induced by pretreatment with sublethal levels of hydrogen peroxide in 𝘋. 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴 rec30 mutant. Effects of manganese and magnesium on the growth and catalase activity of 𝘋. 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴 were determined. Homology between 𝘌. 𝘤𝘰𝘭𝘪 catalase and SOD genes and those of 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp. was tested by Southern blot analysis using previously cloned genes from 𝘌. 𝘤𝘰𝘭𝘪.

abstract: Thesis

abstract: Master of Science (MS)


title: ONE-DIMENSIONAL HIGH-FIDELITY AND REDUCED-ORDER MODELS FOR THREE-WAY CATALYTIC CONVERTER

contributor:
Yan, Fengjun
Mechanical Engineering

subject:
Three-way catalytic converter
Converter model
High-fidelity model
Reduced-order model

abstract:
To improve the performance of the three-way catalytic (TWC) converter, advanced control strategies and onboard diagnostics (OBD) systems are needed. Both rely on a relatively accurate but computationally efficient TWC converter model. This thesis aims to develop a control-oriented model that can be employed to develop the control strategies and OBD systems of the TWC converter.
The thesis consists of two parts, i.e., the high-fidelity model development and the model reduction. Firstly, a high-fidelity model is built using the energy and mass conservation principles. In this model, a constant inlet simulation is used to validate the warming-up characteristics, and a driving cycle simulation is used to calibrate the reaction rate parameters. The results of the simulation show that the high-fidelity model has adequate accuracy. Secondly, a reduced-order model is developed based on phase and reaction simplifications of the high-fidelity model. The aim of the development of the reduced-order model is to propose a computationally efficient model for further development of control strategies and state estimators for OBD systems. The accuracy of the reduced-order model is then validated by means of simulations.

abstract: Thesis

abstract: Master of Science (MSc)


title: Various Aspects of Profiling the Metabolome in Human Pathogenic Yeasts Using Gas Chromatography-Mass Spectrometry

title: Profiling the Metabolome in Pathogenic Yeasts

contributor:
Xu, Jianping
Biology

subject: metabolome human pathogen yeasts gas chromatography spectrometry

abstract: Human pathogenic yeasts of the genus Candida and 𝘊𝘳𝘺𝘱𝘵𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘯𝘦𝘰𝘧𝘰𝘳𝘮𝘢𝘯𝘴 are responsible for about 10% of hospital-acquired infections. In addition, drug-resistant yeasts are rapidly emerging with the use of anti-fungal drugs. Common drugs such as Fluconazole and Amphotericin B target the ergosterol pathway in yeast. Learning about other metabolic differences in yeasts may also give a new understanding to their role as pathogens. Metabolomics is a field of study about the large spectrum of metabolites necessary for the growth and survival of an organism. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the metabolome of different yeasts in three different studies. The first study was a targeted analysis of the ergosterol pathway in 𝘊𝘢𝘯𝘥𝘪𝘥𝘢 𝘢𝘭𝘣𝘪𝘤𝘢𝘯𝘴 and a double drug-resistant mutant was found to have several changes in its sterol composition while Fluconazole-resistant strains were similar to the wild-type. In the second study, a comprehensive analysis of the polar and lipid metabolite profiles of six pathogenic yeasts revealed that lipid profiles were more conserved than polar profiles, thereby better reflecting their taxonomical relationship according to 265 rRNA sequences. However, there were several potential species-specific metabolites and short regions in the metabolite profiles with enough peak differentiation that could be used to rapidly distinguish between these yeasts by visual inspection. In the third study, the metabolic phenotypes of three strains of 𝘊𝘳𝘺𝘱𝘵𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘯𝘦𝘰𝘧𝘰𝘳𝘮𝘢𝘯𝘴 were analysed to determine the extent of contribution of the metabolite phenotypes from two parents to their hybrid offspring. While the lipid metabolite phenotypes of all strains resembled each other, the polar metabolite phenotype of the hybrid offspring strongly resembled one parent but not the other.

abstract: Thesis

abstract: Master of Science (MS)


title: Meta-Analysis: The Effect of the Drug Fosamax on Bone Mineral Density in Multi-Dose and Multi-Year Osteoporosis Clinical Studies

title: Meta-Analysis: Effect of the Drug Fosamax on Osteoporosis

contributor:
Willan, Andrew
Statistics

subject: meta-analysis fosamax drug bone mineral osteoporosis

abstract:
Thesis
Master of Science (MS)


IMPACT OF GUT MICROBIOTA ON INTESTINAL BARRIER FUNCTION AND INTEGRITY


title: Regulation of PSTSCAB-PHOUB Genes in Sinorhizobium Meliloti

contributor:
Finan, Turlough
Biology

subject:
regulate
sinorhizobium
sinorhizobium meliloti
genes

abstract: Previous studies in this laboratory have identified two phosphate transport systems in Sinorhizobium meliloti encoded by the phoCDET and orfA-pit genes respectively. The PhoB regulatory protein is required for transcriptional activation of the phoCDET genes but repress the transcription of orfA-pit. Determination of the DNA sequence upstream of phoU-phoB revealed the presence of genes homologous to the pstA-pstB genes, which encode components of an ABC-type high affinity Pi specific transport system in E. coli. Further analysis of sequence from the S. meliloti genome project (unpublished) revealed the phoR-pstS-pstC genes upstream of pstA-pstB. Using an R-prime approach, we cloned a 7.5 kb Hindlll gene fragment which included the above phoR-pstS-pstC-pstA-pstB and partial phoU genes. Using Tn5-B20 and lacz-aacc1 cassette gene disruption/fusions, we mutated pstA, pstB and phoR gene respectively. We found that: a) pstA-pstB-phoU-phoB are in one operon, b) pstB expression is not regulated by the media phosphate concentration and is independent of phoB, c) in free-living cells, pstB mutants, like phoU or phoB mutants, exhibit alkaline phosphatase negative phenotypes, d) in plant tests, a pstB mutant had normal nitrogen fixation ability and like phoB mutations, the pstB mutation suppressed the Fix- phenotype of phoCDET mutants, e) phoB expression is neither regulated by phosphate concentration nor does its expression appear to be auto-regulated, and f) a phoR mutant exhibited an alkaline phosphatase negative phenotype. Sequence analysis showed that there is no pho box in the upstream of pstA-pstB-phoU-phoB operon and the phoR, but pstS gene has one putative pho box in its promoter region. Also discussion and some ideas for future study were presented.

abstract: Thesis

abstract: Master of Science (MS)


title: Method to estimate cancer overdiagnosis with prostate screening

contributor:
Walter, Stephen
Mathematics and Statistics

subject:
cancer overdiagnosis
prostate cancer

abstract:
Aim: Several studies have tried to quantify overdiagnosis of prostate cancer with Prostate-specific antigen(PSA) screening, but estimates vary widely. This study aims to evaluate the degree of overdiagnosis of prostate cancer with 10 or 14 follow-up years after the stop of screening in Finland.
Methods: We selected 80379 men aged 55-69 years who were randomized to a screening or a control arm, distinguishing four birth cohorts: 1941-44,1937-40, 1933-36 and 1929-32. The first PSA screening test occurred during1996-1999. Men without detected as prostate cancer in the previous screening would be invited to the next screening 4 years later. The estimate of overdiagnosis is the ratio of the cumulative excess incidence to the cumulative incidence of prostate cancer in the screened group after the year-specific incidence became stable.
Results: The patterns of all incidences in these four cohorts have not become stable yet, and the difference of cumulative incidence in the current longest follow- up years is the best estimate of overdiagnosis so far.
Conclusion: Overdiagnosis rates of prostate cancer in people who received screening in Finland was estimated as 2.27%,15.4%, 11.4%, and 10.2% for 1929-32, 1933-36,1937-40, and 1941-44 cohorts, respectively.

abstract: Thesis

abstract: Master of Science (MSc)


title: On the Study of Health in Prehistory

contributor:
Herring, Ann
Anthropology

subject: prehistory health cahokia disease mississippi

abstract: This thesis examines the approaches used in the study of health in prehistory, focusing in particular on the potential of archaeology to contribute to this field. Archaeological data have been under-used in studies of prehistoric health; obstacles to their utilization include the popular conception of archaeological information as less direct than osteological data, the idea that scientific research must produce testable hypotheses to be valid, and the challenge of integrating large quantities of information of different temporal scales into synthetic interpretations. Alternative conceptions of scientific research, and the use of the Braudelian model of historical time as an organizing structure,circumvent these obstacles and permit a fuller use of archaeological data in reconstructing patterns of past health. In particular, archaeological information about social behaviour as well as subsistence and factors pertinent to disease ecology, can form a basis of inferences about health in prehistoric communities. A demonstration of this approach, using recent archaeological data and interpretations for the Mississippian site of Cahokia, suggests that prevailing negative opinions of the health of Mississippian groups and early agriculturalists may not be supportable with regard to the people of Cahokia.

abstract: Thesis

abstract: Master of Arts (MA)


title: The Metabolism of 1,8-Dinitropyrene by Salmonella typhimurium

contributor:
McCalla, D. R.
Biochemistry

subject: salmonella metabolism

abstract: S. typhimurium strain TA98/1,8-DNP₆ is resistant to mutagenesis by 1,8-dinitropyrene and is deficient in an acetyl-CoA dependent acetyltransferase activity. Strains TA98 and TA98NR which are acetyltransferase competent are sensitive to 1,8-dinitropyrene mutagenesis. The coincidence of acetyltransferase deficiency and 1,8-dinitropyrene resistance in strain TA98/1,8-DNP₆ implicates acetylation as an important process in the metabolic activation of 1,8-dinitropyrene to a mutagenic intermediate. The acetyltransferase activity can be assayed by observing the formation of 1-N-acetylamino-8-aminopyrene and 1,8-N,N'-diacetyldiaminopyrene from 1,8-diaminopyrene. Reduction of the nitro-function is also an important enzymatic step involved in the activation of 1,8-dinitropyrene. Evidence is presented which suggests that a nitroreductase-acetyltransferase enzyme complex may exist. Further investigations of nitroreductase activity have yielded results which indicate that three distinct nitroreductases exist, one specific for 1,8-dinitropyrene, one specific for 1-nitropyrene and one specific for nitrofurazone. The implications of these findings are discussed and an explanatory model is proposed.

abstract: Thesis

abstract: Master of Science (MS)


title: Purification and Characterization of Acyl-CoA Synthetase in Escherichia Coli: Relation to Fatty Acid Uptake and Metabolic States of the Cells

title: Acyl-CoA Synthetase in Escherichia Coli

contributor:
Gerber, G. E.
Biochemistry

subject:
e. coli
acyl
CoA
metabolism
cells
fatty acid

abstract: The Gram-negative bacterium 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 can live on long chain fatty acids as its sole carbon source. However, the rate of fatty acid uptake was reduced after starvation (Mangroo, 1992). In this study, it was found that this starvation effect of reducing oleate uptake rate could only be observed in the initial minute post starvation. The starvation effect was not due to the depletion of its substrates ATP or reduced coenzyme A. Neither was the effect caused by a lowered acyl-CoA synthetase level. This reduction in oleate uptake rate can be reversed by incubation in oleate. It has been reported that lactate activated oleate uptake in 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 (Mangroo and Gerber, 1993). In the present study, it was discovered that when [9, 10-³H]oleate was used as the radioactive tracer in uptake assay, the majority of the radioactivity effluxed from the cells. It was found that lactate did not have an effect on the overall oleate uptake. Its apparent activation on oleate uptake was due to the reduction in the efflux rate of radioactive probes, instead of increasing the uptake rate of oleate. Acyl-CoA synthetase in 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 has always been described as a protein of around 45 kDa (Kameda and Nunn, 1981; Kameda 𝘦𝘵 𝘢𝘭., 1986). However, the 𝘧𝘢𝘥𝘋 gene that encodes the 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 acyl-GoA synthetase predicts a 62 kDa protein (Black 𝘦𝘵 𝘢𝘭., 1992; Fulda 𝘦𝘵 𝘢𝘭., 1994). This new form of acyl-CoA synthetase has been partially purified. This form, which has a size of around 62 kDa, can be converted to its 45 kDa counterpart in a Triton X-1 00 and temperature dependent manner. This induced processing of the 62 kDa enzyme was found to be inhibited by oleate, a natural substrate of acyl-CoA synthetase. The two forms of acyl-CoA synthetase have also been shown to be immunologically related. A much simpler purification scheme was developed for the 45 kDa acyl-CoA synthetase using the membrane bound form of acyl-CoA synthetase. The selective extraction of the 62 kDa acyl-CoA synthetase from the membrane, together with the induced processing into the 45 kDa form has provided the basis for this comparatively simple process. The availability of the expression system made the low yield associated with this simple process acceptable. Using oleate as substrate, the Kₘ and Vₘₐₓ for the 45 kDa acyl-CoA synthetase were determined to be 85 ± 18μM and 1550 ± 165 nmole/min/mg protein respectively, whereas the Kₘ and Vₘₐₓ for the 62 kDa enzyme were determined to be 38 ± 12μM and 633 ± 79 nmole/min/mg protein respectively. This suggested that the 62 kDa enzyme has higher affinity towards oleate than its 45 kDa counterpart under standard assay conditions while the ratio of Vₘₐₓ /Kₘ remained relatively constant. Evidence suggesting Triton X-1 00 activates acyl-CoA synthetase by providing a surface for catalysis was presented. This interaction between acyl-CoA synthetase and the Triton X-1 00 I oleate mixed micelle could be affected by the surface charge of the mixed micelle.

abstract: Thesis

abstract: Master of Science (MS)


title: Meta-Analysis: A Comparison of Fixed Effects and Random Effects Models with Illustrative Examples

contributor:
Willan, A.
Statistics

subject: fixed random effect model meta-analysis

abstract:
Meta-analysis has been widely used in clinical research because it provides a useful tool for combining results from a series of trials addressing the same question. Two major approaches for study-to-study variation can be used in a meta-analysis: the fixed effects model which assumes that each study has the same true effect size, and the random effects model which assumes that the true effect size is a random variable that varies between studies. When there are covariates arising from the study, regression models can be used to explain the effects of these covariates on the between study variation in effect size. The purpose of this project is to draw some general conclusions about the
statistical methods used in meta-analyses by re-examining several clinical examples which presented some problems. Four illustrative examples of recent meta-analyses were selected and re-examined. Both fixed effects and random effects models were used. In addition, regression models were used in two examples. Some general conclusions were made about the statistical aspects of meta-analysis
from this project. The overall estimate of the fixed effects model tends to be overly influenced by large trials and may results in contradictory conclusions when extreme trials (small vs. large samples) are combined. Therefore, it is advocated that the weights allocated to each trial in any meta-analysis should be explicitly calculated and displayed. The random effects model takes a more balanced account of all studies and considers other unknown factors which may affect the effect size. Therefore, the random effects model and random effects regression model are more appropriate for these clinical data meta-analyses.

abstract: Thesis

abstract: Master of Science (MS)


title: A Sense of Self: Reconceptualizing Autoimmunity

contributor:
Brophy, Sarah
English

subject: autoimmunity conception self patient language immunology

abstract: In its essence, this thesis is concerned with how the language of immunology affects eventual patient conceptions of self,. Specifically, I examine how biomedical discourse affects both the mental and physical experience of autoimmune disease. Typically described in militaristic terms as an 'attack on self,' autoimmunity, (when an individual's immune system response to 'self' tissues), encourages the following questions: what is self, in a biological sense? What is the effect of medical intervention on a patient's sense of selfhood, when the offending other to be removed is actually an integral part of one's own body? Is there a mental readjustment of what constitutes selfhood in the wake of such a diagnosis? In my attempt to answer these questions I have divided the thesis into three chapters. Chapter one is an exploration of the semantics and methodology of basic biomedical research, eventually culminating in a discussion of two different paradigms of immunity currently in operation. One of the main points of this thesis is that scientific representations of the body are indeed constructions, rather than reflections of the truth of our selves, and that these constructions are in constant flux. By comparing and contrasting two different immunological paradigms used to frame research and articulate the body, I aim to show how different the mental body could be according to which paradigm is followed. In particular, I want to show that autoimmunity is not necessarily an attack on self, or a rejection of self. This thesis is therefore also a search for a 'better' metaphor for autoimmunity that does not involve the rejection of the diseased self. Chapter two examines the language of immunology from a cultural perspective. Paradigms of the immune system have their roots in cultural ideology as much as in the laboratory. This chapter aims to show how research and sociopolitical and economic systems serve to mutually reinforce a common view of 'reality.' Chapter three then looks at personal narratives of individuals living with autoimmune disease in light of how basic research methodology and culture construct and treat disease and the diseased individual. By showing the link between supposedly objective science and the personal experience of illness, I am hoping that work such as mine affects not only patients that might be grappling with confusing diagnoses and searching for alternate ways of conceptualizing their diseased bodies, but also how scientists and medical practitioners explain the body to others.

abstract: Thesis

abstract: Master of Arts (MA)


title: Checking Compliance with ISO 26262 using Conceptual Modeling as a Tool

contributor:
Maibaum, Thomas S.E.
Computing and Software

abstract: With the advancement in technology in the automotive sector, there is an increase in the need of safety assurance of road vehicles. ISO 26262 is a safety critical standard intended to be applied to safety-related E/E systems in passenger cars. The standard also addresses the possible hazards caused by the failure of these systems and uses a risk-based approach to ensure functional safety of the systems. It is important, during the design and development phases of a product, to ensure that the product is in compliance with the standard. Therefore, we present an idea of using conceptual modeling to help verify the E/E systems with ISO 26262. The standard categorizes the requirements and recommendations into what is known in the standard as a Work Product. Building conceptual models of these work products not only gives us a visual representation of the contents of a standard but also helps standardize the process of compliance checking of a product against the standard. The process of using conceptual modeling for checking compliance of a product with the standard is explained in this thesis. The technique of using conceptual modeling not only proved to be efficient for product verification against the standard but was also helpful in exposing important structural aspects of the standard.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Bayesian Meta-Analysis of Trials of Chemotherapy with Radiotherapy in the Management of Patients with Newly Diagnosed Locally Advanced Squamous Cell or Undifferentiated Nasopharyngeal Cancer

title: A Bayesian Meta-Analysis

contributor:
Thabane, Lehana
Statistics

subject: bayesian meta-analysis chemotherapy radiotherapy patients cell nasopharyngeal cancer

abstract: Meta-analysis is a set of statistical procedures used to aggregate results from independent studies. These techniques are widely used in clinical research to get the overall picture from a series of trials addressing the same question. We used Bayesian hierarchical models to evaluate effect of the addition of chemotherapy to radiotherapy treatment in patients with newly diagnosed locally advanced squamous cell or undifferentiated nasopharyngeal cancer. We also performed subgroup analysis to determine the best timing and regimen of chemotherapy. It is demonstrated that the Bayesian model does not only efficiently incorporate all sources of variability, but is also robust under different likelihood functions. The results based on Bayesian hierarchical models assuming a non-informative prior are similar to those from classical random effects models. A significant effect was observed in favour of patients who received radiochemotherapy versus those who received radiotherapy alone. The analysis revealed that neoadjustant chemotherapy is the best timing for treatment.

abstract: Thesis

abstract: Master of Science (MS)


title: A Dissection of the Functional Interactions of the Morphogenetic Protein BLDB of Streptomyces coelicolor

title: Functional Interactions of BLDB of Streptomyces coelicolor

contributor:
Nodwell, Justin
Biochemistry

subject:
dissection
streptomyces
streptomyces coelicolor
protein
BldB

abstract: 𝘚𝘵𝘳𝘦𝘱𝘵𝘰𝘮𝘺𝘤𝘦𝘴 initiate a complex developmental program during their 5-day life cycle, consisting of aerial mycelium formation and antibiotic production. Several developmental genes are involved in regulating these events, one of which is 𝘣𝘭𝘥𝘉. I have complemented a 𝘣𝘭𝘥𝘉 null mutant, which demonstrated the loss of aerial mycelium formation and antibiotic production, restoring both characteristics. This demonstrated that 𝘣𝘭𝘥𝘉 is essential for 𝘚. 𝘤𝘰𝘦𝘭𝘪𝘤𝘰𝘭𝘰𝘳 morphogenesis but not viability. Using a bacterial two hybrid system devised, I screened the 𝘚. 𝘤𝘰𝘦𝘭𝘪𝘤𝘰𝘭𝘰𝘳 genome using BldB as "bait" for binding partners of BldB. The two most compelling candidates were bbpl, a homologue of UspA in 𝘌. 𝘤𝘰𝘭𝘪, and bbp2, a homologue of SrmR in 𝘚. 𝘢𝘮𝘣𝘰𝘧𝘢𝘤𝘪𝘦𝘯𝘴. Furthermore, I have investigated these interactions biochemically by affinity chromatography to further elucidate the details involved in these interactions. Preliminary results showed three protein bands obtained at approximately 68kDa, 55kDa and 35kDa, respectively.

abstract: Thesis

abstract: Master of Science (MS)


title: RAMC Production by Developmentally Impaired Mutants of Streptomyces coelicolor

title: RAMC Production by Mutants of S. coelicolor

subject:
development
impair
mutant
streptomyces
streptomyces coelicolor
RamC

abstract: The RamC protein is required for the production of spore-forming cells called aerial hyphae in colonies of 𝘚𝘵𝘳𝘦𝘱𝘵𝘰𝘮𝘺𝘤𝘦𝘴 𝘤𝘰𝘦𝘭𝘪𝘤𝘰𝘭𝘰𝘳. RamC can be detected during the period between 24 and 48 hours following spore germination however there is a dramatic drop in RamC levels thereafter. This could be explained either by the existence of an active means of RamC removal or by the fact that at later time points in the 𝘚. 𝘤𝘰𝘦𝘭𝘪𝘤𝘰𝘭𝘰𝘳 lifecycle non-RamC producing cells vastly outnumber RamC-producing cells. characterized a large number of 𝘣𝘭𝘥 mutants and found that most of them do not produce RamC. In the majority of the 𝘣𝘭𝘥 mutants that do produce RamC, we observed the same pattern of accumulation and loss during colony growth as in wildtype colonies. Furthermore, we identified a small number of mutants that produced RamC such that it persisted at detectable levels for a longer duration or only appeared after a substantial delay relative to the wildtype. None of these RamC-producing 𝘣𝘭𝘥 mutants was complemented by plasmids containing a cloned 𝘣𝘭𝘥𝘔, 𝘣𝘭𝘥𝘕 or 𝘳𝘢𝘮𝘙 gene, mutations in which also cause persistent or delayed RamC production. These results suggest either that there is more than one differentiated cell type within the substrate mycelium or that 𝘚. 𝘤𝘰𝘦𝘭𝘪𝘤𝘰𝘭𝘰𝘳 colonies actively rid themselves of RamC once the protein's biological function has passed.

abstract: Thesis

abstract: Master of Science (MS)


title: Exploitative Competition in the Chemostat for Two Perfectly Substitutable Resources

title: Competition for Two Perfectly Substitutable Resources

contributor:
Wolkowicz, G. S. K.
Mathematics

subject: competition substitute resource chemostat

abstract: A model of the chemostat involving two populations of microorganisms competing for two perfectly substitutable, growth limiting nutrients is developed. To describe nutrient uptake, a general class of functions is used which allows for the effects that the consumption of one resource may have on the consumption of the other. It includes as a special case the model studied by Waltman, Hubbell and HSu [21] in which they generalize Michaelis-Menten functional response for a single resource to two perfectly substitutable resources. It also generalizes the model studied by Leon and Tumpson [12] where the consumption of each resource is unaffected by the consumption of the other. Analytical methods are used to obtain information about the qualitative behaviour of the model. Interesting similarities are found between both the local and global behaviour in this model and in the model for perfectly complementary resources.

abstract: Thesis

abstract: Master of Science (MS)


title: Methods for 3D Structured Light Sensor Calibration and GPU Accelerated Colormap

contributor:
Spence, Allan
Anand, Christopher
Computational Engineering and Science

subject:
GPU acceleration
3D Structured Light Sensor
CMM 3D sensor calibration
GPGPU
Coordinate Measuring Machines
Accelerated colormap
Weighted total least squares
CUDA
Blue LED sensor
Point cloud to CAD
Snapshot sensor
Angled calibration artefact
Synergistic hybrid sensor
Graphics Processing Unit

abstract:
In manufacturing, metrological inspection is a time-consuming process.
The higher the required precision in inspection, the longer the
inspection time. This is due to both slow devices that collect
measurement data and slow computational methods that process the data.
The goal of this work is to propose methods to speed up some of these
processes. Conventional measurement devices like Coordinate Measuring
Machines (CMMs) have high precision but low measurement speed while
new digitizer technologies have high speed but low precision. Using
these devices in synergy gives a significant improvement in the
measurement speed without loss of precision. The method of synergistic
integration of an advanced digitizer with a CMM is discussed.
Computational aspects of the inspection process are addressed next. Once
a part is measured, measurement data is compared against its
model to check for tolerances. This comparison is a time-consuming
process on conventional CPUs. We developed and benchmarked some GPU accelerations. Finally, naive data fitting methods can produce misleading results in cases with non-uniform data. Weighted total least-squares methods can compensate for non-uniformity.  We show how they can be accelerated with GPUs, using plane fitting as an example.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: An Analysis of Nucleotide Polymorphism in the Human MT-IIa Gene Promoter Region

subject: polymorphism nucleotide human gene promoter

abstract: Previous research has shown varying degrees of renal damage on exposure to equal amounts of cadmium in occupationally exposed mining and factory workers. Further work has shown that in vitro exposure of human peripheral lymphocytes to the same cadmium levels resulted in significant variation in Metallothionein (MT) mRNA transcriptional induction over basal MT mRNA expression in a series of individuals. This variation could account for the differences in renal Cd toxicities identified previously. In this study, the human MT-IIₐ gene was cloned from 12 individuals, and the 5'promoter region was sequenced for each to determine the extent of promoter nucleotide variation. This is of interest since such an analysis has not been done in the past. No study has been done to look at the degree of polymorphism in a particular promoter region. Thus, there are no data on the degree of nucleotide drift or change which can occur in promoter regulatory elements. Such a study could provide insight into whether promoter changes could result in the type of variation described above. It could also give some insight into the degree of variation in sequences in the literature. The results obtained indicated that the human MT-IIₐ promoter region is highly conserved, with only one polymorphic site identified at position 557, between the glucocorticoid responsive element and the fourth metal regulatory element sequences. This suggests that promoter variation is not likely a significant yfactor in MT mRNA induction variability, although further analysis would be needed to show this since only 12 people were analyzed. The results were compared against a study of nucleotide polymorphism in Drosophila melanogaster, which is the only other data on nucleotide variation specifically (Kreitman, 1983; Kreitman and Hudson, 1991). As well, a number of discrepancies were noted from the original published sequences in the literature, suggesting that errors are likely published in genomic sequence which are never identified, except through trial and error. This has potential repercussions when considering the use of such sequence in cloning and sequencing projects, like the sequencing of the human genome, since this would depend on the accuracy of previously published data.

abstract: Thesis

abstract: Master of Science (MS)


title: Characterization of Cathode Materials for Alkali Ion Batteries by Solid-State Nuclear Magnetic Resonance Methods

contributor:
Goward, Gillian
Chemistry

subject:
Physical Chemistry
Lithium Ion Batteries
Nuclear Magnetic Resonance
DFT Calculations
Sodium Ion Batteries

abstract: This thesis concerns the use of advanced solid-state NMR methods to investigate local structural features and ion dynamics in a series of paramagnetic cathode materials for lithium and sodium ion batteries.  A variety of polyanionic phosphate and fluorophosphate derivatives were explored to identify characteristics that ultimately improve battery performance.  Solid-state NMR is an excellent method to probe such materials, as it offers the unique ability to track the charge-carrying alkali ion (Li or Na) over the course of the electrochemical process, adding insight not obtainable by bulk characterization techniques.  Selective inversion exchange experiments were used to elucidate ion diffusion pathways in low-mobility Li ion conductors Li2MnP2O7 and Li2SnO3. Contrasting experimental results highlight significant differences observed when the method is applied to paramagnetic versus diamagnetic systems, with the former being much more complicated to study with traditional exchange spectroscopy methods.   Selective inversion was similarly applied to a new lithium iron vanadate framework, LiFeV2O7, where the changing ion dynamics as a function of electrochemical state of charge were quantified, allowing for the development of a model to explain the corresponding phase changes in the material. This represents the first example of an ex situ Li-Li exchange study for a cathode material, particularly where the conductivity changes are linked directly to a change of ion exchange rates.  Additionally, 23Na NMR spectroscopy was additionally used to investigate Na2FePO4F as a potential Na ion battery cathode, where ex situ NMR measurements successfully determined the local Na ion distribution in the electrode as a function of electrochemical cycling.  In combination with density functional theory (DFT) calculations, the NMR results lead to the construction of a biphasic desodiation model for Na2FePO4F cathodes. Finally, possible defect formation in sodium iron fluorophosphate was investigated with a variety of methods including 23Na NMR, DFT calculations, powder X-ray diffraction and Mössbauer spectroscopy.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Lithium ion batteries are considered to be at the forefront of current energy storage development, offering high energy density in a small and lightweight package.  This thesis delineates the investigation of materials for both lithium and sodium ion batteries via nuclear magnetic resonance methods.  Slow Li ion dynamics were investigated and quantified in three lithium-conducting materials: Li2MnP2O7, Li2SnO3, and LiFeV2O7 via the use of selective inversion NMR experiments. In the case of the latter, the ion dynamics were probed ex situ during the course of battery cycling, where a maximum in Li mobility is observed approximately half way through the charge-discharge cycle.  Additionally, a potential Na ion cathode material, Na2FePO4F, was found by ex situ methods to reveal a biphasic mechanism for the desodiation of the electrode during charging.  This mechanism and the NMR data used to discover it were further supported by ab initio calculations.


title: The Effects of Starvation, Exercise, and Exercise with Pre-Training on Aerobic Fuel Use in Juvenile Rainbow Trout (Oncorhynchus Mykiss Walbaum)

title: Aerobic Fuel Use in Rainbow Trout, Oncorynchus Mykiss

contributor:
Wood, C. M.
Biology

subject:
starvation
exercise
aerobic
rainbow trout

abstract: Metabolic fuel use in rainbow trout (𝘖𝘯𝘤𝘰𝘳𝘩𝘺𝘯𝘤𝘩𝘶𝘴 𝘮𝘺𝘬𝘪𝘴𝘴 W.) was investigated using closed system respirometry and proximate body analysis. During short term starvation (15 days, routine activity) the utilization of protein as a substrate, as determined by respirometry, increased from 14 to 24% of total fuel supply. However, even by the end of the experiment, the contribution of protein (24%) did not approach the classically reported values for fish of between 40 and 90%. Indeed, from respirometry data, during the first quarter of the experiment lipid contributed the majority of the fuel ( >60%) while carbohydrate contributed about 20%. Thereafter, lipid and carbohydrate became essentially equivalent in importance (about 37% each). However, from proximate body analysis, a more traditional fuel mixture was found (protein, 58%; lipid, 40%; carbohydrate, 2%) suggesting the possibility that the two procedures were measuring fundamentally different parameters. Instantaneous fuel use during sustainable swimming at different speeds was investigated by respirometry using three day test periods. While protein catabolism remained constant over time, and uniform between groups, its relative contribution tended to increase with time as total M₀₂ declined with sustained swimming. Protein catabolism was highest in nonswimming fish (30-45%) and lowest in the high speed swimmers (20%); lipid was the most abundant (41-55%) fuel used in all groups at all times. In the nonswimmers and lowspeed swimmers, lipid use tended to increase slightly over time whereas in the high speed swimmers, lipid use dropped from 54 to 44%. Carbohydrate use (up to 38%) was higher than predicted by earlier literature, but decreased greatly in both the nonswimmers and low speed swimmers over the three days, whereas in the high speed swimmers the contribution increased with time. The low speed swimmers from the last set of experiments were used as controls for the final set of experiments in which another group of fish were trained for two weeks at 1.0 L·s⁻¹ prior to testing using an otherwise similar regime. Even though there was no difference in gas exchange, the make-up of the fuel mixture was different for the two groups. Protein use was significantly lower, while lipid use was higher in the trained fish. In addition, relative protein use in the trained fish was constant over the three day period, a feature found only in the the high speed swimmers of the previous experiment. A critical evaluation of the respiratory quotient is given since its use by fish physiologists has been without complete conversion from that used by the mammal physiologists. In addition, the often quoted term "fuel use" is differentiated into 𝘪𝘯𝘴𝘵𝘢𝘯𝘵𝘢𝘯𝘦𝘰𝘶𝘴 𝘧𝘶𝘦𝘭 𝘶𝘴𝘦 and 𝘤𝘰𝘮𝘱𝘰𝘴𝘪𝘵𝘪𝘰𝘯𝘢𝘭 𝘧𝘶𝘦𝘭 𝘶𝘴𝘦 since the two describe fundamentally different principles, though this has not always been recognized in the literature.

abstract: Thesis

abstract: Master of Science (MS)


title: Sustainable Aquaponics

title: Trophic controls for optimization of sustainable food production methods

contributor:
Kolasa, Jurek
Biology

subject:
Sustainable Agriculture
Aquaponics
Trophic controls
Ecology
Biology

abstract: Aquaponics has the potential to be a superior food production method compared to traditional agriculture through its potential for sustainability. This is particularly important in advanced aquaponic systems that integrate waste disposal (e.g., kitchen waste) and involve several steps linking waste decomposition to protein production. In such systems a success of one type of organism propagates down the food chain and may have negative impact on contribution of other organisms, which reduces system efficiency.  I hypothesised that a combination of top-down and bottom-up regulations, concepts borrowed from resilient natural ecosystems, would allow to optimize environment for aquaponics systems to avoid such negative impacts.  First, I conducted an experiment using simplified systems with two trophic levels only to determine productivity, resistance and resilience of the various combinations of top-down and bottom-up forces.  The simple systems contained algae and Daphnia magna and were placed under a light removal disturbance to observe the abilities of these different combinations to resist and recover from a generic negative environmental impact.  Next, a similar light disturbance was implemented on a large complex aquaponics system to discover if it would react differently from the smaller ones. The resistance and resilience of algae in the small systems was not found to have any relationship to predation.  The resilience of algae was better at low nutrient levels compared to high ones.  There was evidence that low nutrient treatments had better resistance and resilience of abiotic factors.  The larger systems appeared to have inferior resistance and resilience as compared to the simple, small systems.  However, a time series analysis indicates that these large systems, in contrast to the simpler systems, actually improved in the amount of algae after the disturbance.  New methods for accounting for this in resilience calculations are needed to eliminate potential statistical artifacts that might lead to some of my observations.

abstract: Thesis

abstract: Master of Science (MSc)


title: Ara h 1 Peptide Immunotherapy in a Mouse Model of Peanut-Induced Anaphylaxis

contributor:
Larché, Mark
Medical Sciences

subject:
Anaphylaxis
Peanut allergy
Peptide immunotherapy
Mouse model

abstract:
Background: Despite the clinical severity and rising prevalence of peanut allergy, there is a marked absence of widespread, practical treatments available for peanut-allergic patients. Peptide immunotherapy, a disease-modifying treatment that uses short peptides recognized by T cells, has been shown to reduce allergic symptoms of allergic rhinoconjunctivitis. This project investigated the ability of peptides from the major peanut allergen Ara h 1 to protect against peanut-induced anaphylaxis and induce immunomodulatory changes in a mouse model. Methods: Mice transgenic for the human leukocyte antigen DRB1*0401 were sensitized to peanut epicutaneously and treated with two intraperitoneal injections of peptides from Ara h 1. Mice were then challenged with intraperitoneal whole peanut and observed for signs of anaphylaxis. Flow cytometry was used to isolate peanut-specific CD4+ T cells labelled with Ara h 1 peptide-loaded tetramers and additional Th1, Th2, and regulatory markers.
Results: Peptide-treated mice were protected from severe peanut-induced anaphylaxis. Control mice treated with a sham peptide experienced a mean maximum temperature drop of 3.2°C, while mice treated with Ara h 1 peptides experienced a drop of 1.6°C (p=0.067 vs control). Maximum clinical score was 2.5 in control mice, and 1.4 in treated mice (p=0.0097). Mean hematocrit for control mice was 52.5%, and 47% for treated mice (p=0.013). PD-1+CD4+ T cells were significantly increased in the mesenteric lymph nodes (p = 2.28e-0.05) and spleens (p = 0.014) of peptide-treated mice. MIP1-a+CD4+ T cells were significantly decreased in the peritoneal lavage (p = 0.008).
Conclusion: Ara h 1 peptide immunotherapy protected against severe peanut-induced anaphylaxis in a mouse model. Peptide-treated mice experienced significantly reduced drops in core body temperature, clinical signs of allergic reaction, and hemoconcentration. Clinical
protection was associated with decreased expression of the pro-inflammatory chemokine macrophage 1-a and increased expression of the surface marker programmed cell death protein 1.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Peanut allergy is a growing public health concern. Its prevalence has doubled in the past 10 years and currently stands at 2%. Reactions to peanut account for the majority of food-induced fatal allergic reactions, termed anaphylaxis. Currently, there are no treatments available for patients with peanut allergy. Healthcare workers can only offer peanut-allergic patients advice on peanut avoidance and rescue medications in case of accidental ingestion. This research project investigated the ability of a new treatment called peptide immunotherapy to prevent severe allergic reactions to peanut in a mouse model of peanut allergy. Peptide treatment uses small portions of the peanut allergen to shift the immune response from pro-inflammatory to anti-inflammatory. After peptide treatment, peanut-allergic mice were protected from severe allergic reactions in response to peanut and their immune cells produced lower levels of pro- inflammatory molecules.


title: The social construction of telemedicine in Ontario: A historical narrative analysis

contributor:
Giacomini, Mita
Egan, Michael
Kapiriri, Lydia
Kohler, Jillian
Health Policy

subject:
health policy
qualitative research
grounded theory
historical narrative analysis
telemedicine
health technologies
social construction

abstract:
The term telemedicine is broadly defined as the use of information and
communication technology to deliver health care at a distance. However, the concept of
‘telemedicine’ still lacks consensus both in the literature and in practice. Generation of
telemedicine knowledge and evidence for clinical practice is still controversial within the
telemedicine scholarship and among decision-makers as telemedicine objectives remain
ill-defined and outcomes vary in time. In Ontario, despite the fast pace of information and
communication technology change and the increased interest in its health applications,
telemedicine is not a mainstream model of care delivery within the medical system.
This study empirically investigates the social construction of telemedicine
technologies to understand how telemedicine expectations shaped telemedicine in Ontario
(Canada) from 1993 to 2017. Drawing from the Social Construction of Technologies
framework (SCOT) and historical narrative analytical techniques, it identifies the shared
understandings of what telemedicine is (and is not) and what role telemedicine plays in
the health care system. I used grounded theory methodology to develop a narrative theory
of how the future of telemedicine in Ontario has been constructed over the last 24 years
from national newspaper articles, stakeholder documents, service provider websites, and
semi-structured interviews with relevant telemedicine stakeholders. Findings show that
the development of telemedicine narratives in Ontario is a multi-storied process of
conflicting and overlapping visions and expectations among stakeholders and interests.
Telemedicine expectations focus mostly on the process of innovation, the provideroriented
approach to telemedicine, and the advantages and risks of adopting consumercontrolled
telemedicine in a publicly insured health care system. The telemedicine visions
result fragmented among different stakeholders and practices, overall inhibiting
telemedicine’s future agenda. These findings intend to help researchers, policy makers,
private vendors, and health care providers to create a vision of telemedicine that
accommodates competing expectations among the clinical, technical, political, and
commercial worlds.

abstract: Thesis

abstract: Doctor of Science  (PhD)

abstract:
Telemedicine delivers health care at a distance by letting doctors talk to patients
or other doctors via video, email, or text messages. However, as simple as this idea is,
researchers, physicians, policy-makers, and entrepreneurs have speculative, overlapping,
and conflicting views about what it should be. These differing views create ambiguity and
often confuse the aims of health policy decision-makers and end-users limiting
telemedicine’s development.
I intend to clarify telemedicine’s shared and diverging understandings of what
telemedicine should be by analyzing how stakeholders in Ontario have told and tell
stories about telemedicine’s future over the last three decades. I view stories of the
technology’s future as persuasive policy arguments that stakeholders adopt to shape and
use telemedicine according to their visions and goals. These findings will help
researchers, policy-makers, doctors, and businesspeople understand what telemedicine is
(and is not) to help them define policies and guidelines for its adoption and
implementation.


title: An Electrophysiological Measure of NMDA Activation in Perforant Path Kindling

title: Electrophysiological Measure of NMDA Activation in Kindling

contributor:
Racine, R. J.
Psychology

subject: NMDA activation perforant path

abstract:
High frequency stimulation of the perforant pathway triggers a prolonged field potential in the dentate gyrus that
far outlasts that obtained with single pulses. The late rising component of this field potential has recently been
shown to be mediated by N-methyl-D-aspartate (NMDA). In the present thesis, rats were implanted with stimulating
electrodes in the perforant pathway and recording electrodes in the dentate gyrus of the hippocampus. Baseline
input/output functions of field potentials (or population EPSPs) were established for each rat. Ketamine, an NMDA
receptor antagonist, was then administered to confirm its effects on the late component of the EPSP. The late component was measured by subtracting the pulse-evoked from the train-evoked response. Ketamine was shown to significantly attenuate the late component. Diazepam, a GABA agonist, had no significant effect on the late component. Having established an NMDA component in the field potential allows for the monitoring of the levels of NMDA activation over prolonged periods. Hence, the effect of kindling, an animal model of temporal lobe epilepsy, was also determined. Fully kindled rats--defined as those who had experienced four stage 5 seizures--also had significantly attenuated late components. In contrast to decreased late components, kindled rats displayed increased population spike amplitudes and EPSP slopes. Such a decrease in the late component suggests that the NMDA receptor plays a role in kindling. Subjects were also given ketamine and diazepam following kindling, whereby the effects were proportionately the same as those observed prior to kindling.

abstract: Thesis

abstract: Master of Science (MS)


title: Inter-Species Comparison of Promoter Sequences of the Ets Transcription Factor PEA3

title: Inter-species Comparison of the PEA3 Promoter

contributor:
Hassell, J. A.
Biochemistry

subject: species promotor sequence transcription PEA3 Ets

abstract: Chicken and pufferfish genomic libraries were screened with the intent of isolating PEA3 orthologues from evolutionarily removed vertebrate species. The chicken PEA3 gene was found to reside within 15 kb of genomic sequence, and approximately 2 kb of promoter sequence has been identified. Although the pufferfish PEA3 genomic sequence has yet to be completed, exons 2, 3, 4, 5, 12 and 13 have been found, and approximately 1 kb of sequence upstream of the putative start codon has been determined. In addition to the genomic sequence that was isolated, 5' RACE using pufferfish heart RNA produced a 334 bp cDNA sequence encompassing exons 2 to 5 of pufferfish PEA3. A pufferfish homologue of the human RNA helicase 1 (HRH1) gene was also found 3' of the PEA3 gene. Given that HRH1 is also found 3' of human PEA3 (E1AF) on chromosome 17q21, this finding would seem to indicate that chromosomal synteny is maintained between the human and pufferfish PEA3 loci. A four-way alignment of the mouse, human, chicken and pufferfish PEA3 promoters revealed that a region spanning from +1 to -260, relative to the transcriptional start site of mouse PEA3, is well conserved across the four promoters. Conserved transcription factor binding sites for SRY, HNF3β, NFY, AP-1, TCF, AP-2, v-myb, δEF1, and c-Ets-1 were found in three, and in some cases four of the promoters. An additional outcome of the pufferfish genomic library screen was the isolation of a pufferfish orthologue of the Ets transcription factor ERM. The relevance of these findings to the issue of transcriptional regulation of PEA3 expression is discussed.

abstract: Thesis

abstract: Master of Science (MS)


title: Mitochondrial DNA Sequence Variation and Human Population Structure in the Indian Subcontinent

title: MTDNA Variation and Human Population Structure in India

contributor:
Singh, R. S.
Biology

subject: mitochondria DNA human population india sequence

abstract: An analysis of mitochondrial DNA (mtDNA) sequence variation among individuals of Indian origin was performed to compare mtDNA diversity within the Indian population to that of other human populations, and to examine Indian population substructure related to geographical location, spoken language and the caste system. A 195 bp non-coding segment of mitochondrial DNA was amplified and sequenced from 84 individuals representing a broad geographical distribution and three of the major castes. Sixty-one different haplotypes, and 54 polymorphic sites, corresponding to 28% of the sites analyzed, were found. The results obtained from the analysis of distributions of pairwise sequence differences, as well as phylogenetic analysis, are in agreement with rapid population expansion or steady growth as opposed to the maintenance of a constant population size. At 4 out of the 54 variable sites detected there was a significant difference between northern and southern populations. However, phylogenetic analysis revealed no significant population substructure with respect to either geographical distribution, language or the caste system. Some minor effects were observed in a significant under-representation of Dravidian language speakers, corresponding to individuals of south Indian origin, within one cluster, and a similar under-representation of members of the Vaisya caste in another cluster. The phylogenetic tree obtained from integration of the Indian sequences with sequences from other human populations produced a starlike cluster encompassing both Indian and non-Indian individuals. Clustering of Indians within the tree was not completely random as there were significantly fewer Indians than expected within one cluster. The results suggest that the time elapsed since the origin of the caste system has not been sufficiently long to produce significant differentiation between the major castes. Alternatively, the mtDNA fragment chosen for analysis may contain too few major polymorphisms to balance out background noise, and is therefore not adequately sensitive to detect local population structure.

abstract: Thesis

abstract: Master of Science (MS)


title: The Effects of Bilayer Sidedness and Flip-Flop of Lysophosphatidylcholine on Viral Fusion with Model and Biological Systems

title: Bilayer Stabilization and Viral Fusion

contributor:
Epand, Richard
Biochemistry

subject: bilayer flip-flop lysophosphatidylcholine virus fusion model

abstract: Intermediate lipid structures such as inverted micelles and interlamellar attachment are thought to play a crucial role in different biological processes like viral infection. Lysophosphatidylcholine has been shown to inhibit membrane fusion at stabilizing concentrations (between 1 and 10% with respect to membrane lipids). Studies in this thesis looked at the effects of Lysophosphatidylcholine (LPC) properties on the inhibition of Sendai viral fusion. The effects of bilayer sidedness preference as well as flip-flop of Lysophosphatidylcholine (lyso PC) were examined. Octadecylrhodamine (R₁₈) lipid mixing assays were used to measure the fusion of Sendai virus with different biological, erythrocyte ghosts, and artificial systems consisting of different lipids and different viral receptor compositions. The data showed that external addition of LPC exhibits a dependency between the incubation time of the lysolipids and the inhibition of viral fusion. The results also demonstrate a relationship between the location of LPC in the bilayer and its ability to inhibit lipid mixing. LPC present only on the outer monolayer plays a role in the inhibition of viral fusion. Reorientation of LPC was also measured for the same incubation periods. A method using Bovine Serum Albumin (BSA) and radioactivity labelled LPC, was applied to measure the flip-flop. Significant transbilayer reorientation of Lyso PC in the bilayer was shown to take place. The rate of flip-flop was measured at 0.32 ± 0.08% LPC /min. Such reorientation can explain the time dependency observed earlier. The conclusions of this thesis lend support to stalk intermediate mechanism of viral membrane fusion. The ability of LPC to inhibit only when present on one side of the bilayer supports the idea of a negatively curved stalk intermediate. Moreover, it showed that the shape and curvature tendencies of the bilayer stabilizer determine its effects on viral fusion.

abstract: Thesis

abstract: Master of Science (MS)


title: Conducting polymer-based electrodes for electrochemical supercapacitors

contributor:
Zhitomirsky, Igor
Materials Science and Engineering

abstract: The growing interest in the application of polypyrrole (PPy) for electrodes of electrochemical supercapacitors (ES) is attributed to the relatively high specific capacitance (SC), low cost, high electrical conductivity, advanced chemical and mechanical properties of PPy. However, it is found that swelling and shrinkage occurred during charge-discharge, resulting in higher impedance, gradual adhesion loss and poor cycling behavior of PPy electrode. Moreover, mass normalized capacitance decreased significantly with increasing electrode mass, especially at high charge-discharge rates. Therefore, it is challenging to achieve good electrochemical performance, cyclic stability and good capacitance retention at high charge-discharge rates for electrodes with mass loadings above 20 mg/cm2, which is required for many practical applications.To address this problem, PPy-MWCNT (multiwalled carbon nanotube) composites were prepared using polycharged aromatic anionic redox active molecules as dopants for PPy and dispersants for MWCNT. New dopants offer the advantages of their reduced movement during charge-discharge process and reduced PPy swelling because of large molecular size. In addition, polycharged dopants, containing several charged groups, can be linked to different polymer macromolecules, thus increasing interchain mobility of charge carriers and increasing PPy conductivity. Moreover, new dopants exhibit redox active properties and thus contribute to the total electrode capacitance. The reasons for adding MWCNTs are following: first, they can enhance charge storage properties of PPy by increasing the conductivity of composites, which is more obvious when the scan rate is high. Second, the network formed by MWCNTs can restrict the swelling of PPy and improve the cyclic stability.In this research, new promising PPy-MWCNT electrodes were fabricated. 7 different molecules were used as new dopants for chemical synthesis of PPy. The molecular size and functional groups of the anionic dopants and dispersants have great influence on the morphology and capacitive properties of PPy and PPy/MWCNT composites. Moreover, PPy-MWCNT-FeOOH composite was also prepared in order to shift the working voltage window of PPy/CNT composite to more negative direction, which can facilitate the utilization of PPy as negative electrode. The results showed that dopants with large size, multiple charges and high charge to mass ratio can decrease PPy particle size, reduce agglomeration and thus improve PPy capacitive properties. The highest SC of 118.26 F/g was achieved at 2 mV/s by using PMSS-SR31 doped PPy-MWCNT electrodes. The highest SC of 65.09 F/g at 100 mV/s was achieved by using Potassium Benzene-1,2-disofulnate doped PPy-MWCNT electrodes. Adding FeOOH to PPy-MWCNT composite with mass ration between PPy and FeOOH of 7/2 allowed for enhanced performance in a working voltage window of -0.8 - +0.1 V, which facilitated the utilization of PPy as a negative electrode in asymmetrical device.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Translating Editor COI Values to Action: The Missing Link

contributor:
Brouwers, Melissa
Health Research Methodology

subject:
Editor
Conflict of Interest
Policy

abstract:
Introduction: Conflict of interest (COI) exists when an individual in the publication process has a competing interest that could compromise their publication process responsibility. COI is commonly associated with authors and less so with editors. Many organizations (e.g. World Association of Medical Editors (WAME)) provide resources and recommendations for addressing COIs at medical journals. However, there are no data describing journals’ utilization of these resources for editor COI policy development or adoption, and little data on the value of editor COI policies. This study aimed to understand current editor COI practices and editors’ perceptions of COI policies, along with barriers to their implementation.
Methods: An online survey developed in LimeSurveyTM was distributed to editorial board members of oncology and health care sciences and services journals to measure respondents’ attitudes about COI definitions and features and COI policy experience; barriers to implementing editor COI policies; and editors’ perceptions of COI policies. Frequency analysis of survey data was conducted. Free-text responses were summarized.
Results: Response rate was 20.2% (66/327), and comprised complete and partial survey respondents. The majority of respondents were editors-in-chief. Overall, respondents agreed that defined WAME COI domains were important components of an editor COI policy. Nearly 50% of respondents belonged to journals with existing editor COI policies, which they continued to use. Nearly 25% were unaware of the current editor COI policy status at their journal. Few implementation barriers were identified, the most common being challenges with verification of disclosures. Overall, respondents did not report strong attitudes in favour of or against editor COI policies, but respondents agreed that journals with an editor COI policy were more credible and trustworthy.
Conclusion: This study shows that editor COI policy development and utilization is not a universal standard of practice and suggests that recognition of the value of an editor COI policy may not be widespread among editorial board members.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Conflict of interest (COI) can play an important role in the stages of getting research published. However, COI of journal editors has not been studied. The aim of this study was to find whether COI policies for editors exist and to probe editors’ perceptions about the policies. The study found that editors believe COI policies are important but for the most part, whether a journal has an editor policy or not, does not affect their perception of the journal’s validity, quality, and transparency. This study also suggests there are few barriers to implementing an editor COI policy. Additional research is needed to demonstrate the role COI plays in the research enterprise with regard to research integrity, and journal credibility and trustworthiness.


title: Perceptions of teamwork from Nursing Resource Team nurses

contributor:
Baumann, Andrea
Nursing

subject:
Teamwork
Perceptions
Q-methodology
Nursing resource team
Teams

abstract:
Introduction/Background: Nursing Resource Teams (NRT) are a staffing strategy utilized by acute care hospitals to fulfill daily staffing vacancies caused by sick calls, vacation, and patient acuity. Effective teamwork is a critical component to providing safe patient care and the literature suggests that transient team membership, such as NRT nurses, are a barrier to teamwork. NRTs are being used more frequently than ever and yet their perspective on teamwork has not been addressed in the literature. The purpose of this study was to identify NRT nurses' perceptions of teamwork.
Methods: Q-methodology was used for this study. Statements about teamwork were derived from the literature and a focus group with NRT nurses. A convenience sample of 34 NRT Registered Nurses and Registered Practical Nurses at a local hospital organization sorted a representative list of 41 statements about teamwork along a scale of -5 (strongly disagree) to +5 (strongly agree) on a Q-sort table. Iterated principal factor analysis and varimax rotation were performed using the qfactor program in Stata.
Results: Three factors emerged with the following themes: (1) feeling underappreciated, (2) being flexible and confident, and (3) being unintegrated. A total of 30 participants loaded across the three factors, with no statistically significant demographic correlations. Distinguishing statements helped to define the characteristics of each factor. Four participants did not load on to any factor and therefore were excluded from further analysis.
Conclusion: These findings represent perceptions from only one group of NRT nurses and no opportunity was given for participants to explain their sorting decisions. More research should be conducted to expand upon these perceptions of teamwork using an in-depth qualitative approach. NRT nurses perceive themselves to be knowledgeable, skilled, and able to provide effective care across a variety of patient units; however, some of the nurses feel underappreciated and unintegrated into the unit teams.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: This study explores nursing resource team (NRT) nurses’ perceptions of teamwork as well as their barriers and facilitators to effective teamwork. Q-methodology was used for this study. A literature review on NRTs and a scoping review on teams and teamwork were conducted. The literature and a focus group with NRT nurses were used to identify a representative list of statements about teamwork (n=41). Thirty-four NRT nurses sorted these statements into a table, and using a by-person exploratory factor analysis, three groups of NRT nurses emerged with the following themes: (1) feeling underappreciated; (2) being flexible and confident; and (3) feeling unintegrated. Future research should focus on exploring in-depth the perceptions of teamwork from NRT nurses and comparing unit-based and NRT nurses perceptions of teamwork.


title: A SCOPING STUDY TO DESCRIBE ‘FOR WHAT’ AND ‘HOW’ PATIENT CONTRACTS ARE BEING USED IN THE SCIENTIFIC LITERATURE FOR THE MANAGEMENT OF CHRONIC MEDICAL CONDITIONS

contributor: Clinical Epidemiology/Clinical Epidemiology & Biostatistics

subject:
patient contract
chronic condition management

abstract:
Introduction: Prevalence of chronic conditions continues to rise in North America. Despite the lack of evidence supporting their use, patient contracts are commonly used by medical professionals to manage such conditions. To date, literature reviews on patient contracts has been limited to randomized controlled trials, with specific purposes and limited populations.  The purpose of this study is to describe ‘for what’ and ‘how’ medical contracts are being used for the management of chronic medical conditions.
Methods: In order to capture and describe the breadth of knowledge around medical contracts in the literature, a scoping review was conducted. This inclusive approach allowed for analytic reinterpretation of research activity, gaps in the literature to be identified and further avenues of inquiry to be opened. Database searches included Medline, EMBASE, AMED, PsycINFO, Cochrane, CINAHL and Nursing & Allied Health.
Results: A total of 7,528 articles resulted from the original search. Seventy-six articles were included in the final review. Multiple types of studies were represented with limited follow-up durations. Extensive variety was seen for contract target population, clinical setting and co-interventions. Purposes for initiating contracts included: 1) behavior change and skill development, including goal development and problem solving; 2) altering beliefs and knowledge, including motivation and perceived self-efficacy; 3) improving interpersonal relationships and role clarification; 4) improving the quality and process of chronic care; and 5) altering objective and subjective health indices. In relationship to how contracts are used, their development, application of behavioral theory, inclusion of patient input, training for their use and implementation processes were inconsistently described.
Conclusion: More research is required to determine if contracts are capable of accomplishing their intended purposes. Questions remain regarding their rationale, development and implementation.

abstract: Thesis

abstract: Master of Public Health (MPH)

abstract: Rates of chronic medical conditions continue to rise in North America. To manage such conditions, medical professionals commonly use patient contracts, defined as any type of agreement by which one or both parties agree to a set of behaviors related to the care of the patient. The purpose of this study is to describe ‘for what’ and ‘how’ medical contracts are being used for the management of chronic medical conditions. A scoping literature review was undertaken. Extensive variety was seen in the literature for contract target population, clinical setting and co-interventions. Purposes for initiating contracts included: 1) behavior change and skill development; 2) altering beliefs and knowledge; 3) improving interpersonal relationships; 4) improving the quality and process of care; and 5) altering objective and subjective health indices. Contract development and implementation processes were inconsistently described. More research is required to determine if contracts are capable of accomplishing their intended purposes. Questions remain regarding their rationale, development and implementation processes.