title: Formation and positioning of the magnetosome chain in Magnetospirillum Magneticum AMB-1

contributor:
Fradin, Cécile
Hitchcock, Adam
Physics and Astronomy

subject: Biomagnetism Magnetotaxis Magnetosomes Microscopy

abstract:
Magnetotactic bacteria are a group of prokaryotes that share the ability to align
with external magnetic ﬁelds, due to the presence within their cytoplasm of one or
several chains of nanometer-sized magnetic crystals called the magnetosomes. The
orientation of the chain within the cell is critical for magnetotaxis, which allows these
bacteria to swim along the geomagnetic ﬁeld lines. To do so, the magnetic moment
and thus the chain need to lie parallel to the swimming direction which, for elongated
bacteria such as AMB-1, is roughly parallel to the long axis of the cell. In most
studies, the alignment between the magnetic moment and the cell axis is taken for
granted, however no precise measurement has been performed to conﬁrm this. In this
thesis, experiments performed to test this assumption are presented, and the results
show that for most studied bacteria the alignment is not perfect. The eﬀect on the
orientation distributions is discussed and accounted for in the analysis performed to
measure the magnetic moment of individual bacteria.

A second project presented in this thesis is focused on the biomineralization process in
AMB-1. Magnetotactic bacteria synthesize crystals characterized by a well-controlled
morphology and a high chemical purity, which makes them interesting for biomedical
applications. To study how these crystals are produced, we used scanning trans-
mission X-ray microscopy, and preliminary results show that this tool is suitable for
studying this complex process. The methods developed and improved during this MSc
to perform these experiments are presented, and the ﬁrst results show an evolution
in the spectroscopy of the magnetosomes as they grow.

abstract: Thesis

abstract: Master of Science (MSc)


title: Nurses' Experiences with Responsive Behaviours of Dementia in Acute Care and Perceptions of P.I.E.C.E.S. Education: An Interpretive Description

contributor:
Ploeg, Jenny
Nursing

subject:
Dementia
Responsive Behaviours
Nurses
Healthcare Professionals
Acute Care
Education

abstract:
Background: Approximately 56,000 persons with dementia are admitted to hospitals annually and 75% of them experience responsive behaviours. Responsive behaviours are words/actions used to make one's needs known (e.g. wandering, yelling, hitting, and restlessness) and are perceived by healthcare professionals to be a challenging aspect of dementia care.
Aims: This study explores the perceptions of nurses about: (a) caring for older adults with dementia experiencing responsive behaviours in acute medical settings and (b) an educational intervention in dementia care called P.I.E.C.E.S. (Physical, Intellectual, Emotional, Capabilities, Environmental, and Social assessment).
Methods: Thorne's interpretive description approach was used. In-person, semi-structured interviews were conducted with 15 nurses and allied health professionals from acute medical settings in a hospital in Ontario. Data were analyzed using experiential thematic analysis.
Findings: Themes related to caring for individuals with responsive behaviours included the following: (a) providing nursing care for older adults with responsive behaviours of dementia is a complex experience, (b) there are many barriers to dementia care within acute medical settings, (c) nurses use a combination of pharmacological and non-pharmacological strategies to care for older adults with dementia, (d) there is limited continued use of P.I.E.C.E.S. education although the program and its approaches were seen as relevant for dementia care, and (e) participants viewed organizations as responsible for improving dementia care in acute medical settings.
Conclusions: Findings provide guidance for improved support for nurses who provide care to persons experiencing responsive behaviours in acute medical settings such as increasing staffing. Strategies should be implemented to provide continuous educational reinforcements to help staff apply P.I.E.C.E.S such as interdisciplinary rounds focusing on responsive behaviours.

abstract: Thesis

abstract: Master of Science (MSc)


title: Bio-Ownership: Property Theory and Our Separated Biospecimen

contributor:
Sciaraffa, Stefan
Emerson, Claudia
Philosophy

abstract: As medical and information technologies advance the uses of our human tissues follow. These advancements lead to legal cases that show the gaps in our understanding of how to control the biospecimen we have separated from our bodies. Such cases offer us glimpses into the normative difficulties that the control of separated biospecimen bring up in modern liberal democratic societies. I argue for the utility of property theory and law for control of these tissues as a means to combat the normative issues that arise out of tissue use. Property theory does not come without its downsides though. In order to deal with the issues that come about through regulating our biospecimen use through property law, I argue for the importance of liability rules. Tort law and fiduciary obligations in particular offer valuable legal protections that can both limit and strengthen property law’s applicability in context of biospecimen use. In the end I conclude that the limited-property framework is the best legal regime we currently have to regulate our separated human tissues.

abstract: Thesis

abstract: Master of Philosophy (MA)


title: The Concept of Martyrdom in Twelver Shi'ism: Ideas and Development

contributor:
Takim, Liyakat
Religious Studies

subject: Martyrdom Shi'ism

abstract: Iran’s Islamic Revolution in 1979 and, later, the Iran-Iraq war (1980-1988) created unprecedented zeal and enthusiasm for martyrdom among the Shī‘a. As Imām Ḥusayn’s martyrdom in Karbalā (680 CE) more and more was read into the revolutionary taste, the concept of martyrdom then transformed into an empowering tool for the Shī‘a. The Islamic Republic’s leaders understood the importance of cultivating the culture of martyrdom among the youth; as it was that culture that helped to topple the Shah’s regime and pushed Iraq’s forces out of Iran’s borders. Thus, martyrs of the revolution and the war were praised as national heroes who sacrificed everything for the sake of the revolution and the Islamic state under the leadership of the charismatic Ayatollah Khomeini. The Shī‘a understanding of martyrdom developed more with the recent Syrian crisis and the war on ISIS and other Salafī groups in the region. The new martyrs, known as martyred shrine defenders, go beyond national heroes and act as the protectors of the legacy of the Prophet’s family. Unlike the martyrs of the revolution and the Iran-Iraq war who were known as wronged martyrs (as they were in a fight against superior military powers), the shrine defenders have the upper hand; they somehow act as the awaited al-Mahdī and what he is supposed to do at the end of the time, that is, avenging the blood of Ḥusayn and other wronged martyrs of the Shī‘a. In this dissertation, I will examine the development in the perception of the concept of martyrdom in Twelver Shī‘īsm by focusing on modern Iran. For a better understanding of the concept of martyrdom, I will start with speculations on the formation of the concept of martyrdom in early Judaism and Christianity before turning my attention to martyrdom in Islam.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Mapping Allosteric Sites and Pathways in Systems Unamenable to Traditional Structure Determination

title: Mapping Allostery in Unconventional Systems

contributor:
Melacini, Giuseppe
Health Sciences

subject:
Allostery
Protein Regulation
Protein-Ligand Interactions
Cell Signaling
Cyclic Nucleotides
NMR Spectroscopy
Protein Dynamics
Drug Development
Disease Mutations
Biochemistry
Ion Channels
Enzyme Inhibition

abstract: Allostery is a regulatory process whereby a perturbation by an effector at one discrete locus creates a conformational change that stimulates a functional change at another. The two sites communicate through networks of interacting residues that respond in a concerted manner to the allosteric perturbation. These allosteric networks are traditionally mapped with high resolution structure determination techniques to understand the conformational changes that regulate protein function as well as its modulation by allosteric ligands and its dysfunction caused by disease-related mutations (DRMs). However, high resolution structural determination techniques, such as X-ray crystallography, cryo-electron microscopy and nuclear Overhauser effect NMR spectroscopy are not always amenable for systems plagued by poor solubility and line broadening caused by μs-ms dynamics or systems where allostery relies primarily on dynamical rather than structural changes. This dissertation discusses methodologies to map the allosteric sites and pathways for such challenging systems. The foundation of this approach is to model allosteric pathways in the context of their respective thermodynamic cycles. In chapter 2, the thermodynamic cycle of a DRM in the hyperpolarization-activated cyclic nucleotide-gated ion channel 4 (HCN4) is analyzed with respect to structure, dynamics and kinetics, revealing how the DRM remodels the free energy landscape of HCN4 and results in a loss-of-function disease phenotype. In chapter 3, the mechanism of action of an uncompetitive inhibitor for the exchange protein activated by cAMP is elucidated by characterizing its selectivity for distinct conformations within the thermodynamic cycle that are trapped using a combination of mutations and ligand analogs. In chapter 4, we discuss two new protocols for the chemical shift covariance analysis (CHESCA). The CHESCA is an approach that identifies allosteric signaling pathways by measuring concerted residue responses to a library of chemical perturbations that stabilize conformational equilibria at different positions. Overall, the approaches discussed in this dissertation are widely applicable for mapping the mechanisms of allosteric perturbations that arise from ligand binding, post-translational modifications and mutations, even in systems where traditional structure determination techniques remain challenging to implement.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Allostery is a regulatory mechanism for proteins, which controls functional properties of one distinct site through the perturbation of another distinct, and often distant, site. The two sites are connected via a series of residues that undergo conformational changes once perturbed by the allosteric effector. Mapping these communication pathways reveals mechanisms of protein regulation, which are invaluable for developing pharmacological modulators to target these pathways or for understanding the mechanisms of disease mutations that disrupt these pathways. Allosteric pathways have been traditionally determined using structure determination approaches that provide a static snapshot of the protein’s structure. However, these approaches are typically not effective when allostery relies extensive changes in dynamics. The goal of this thesis was to develop methods to characterize systems that are dynamic or otherwise unsuitable for traditional structure determination. Herein, we utilize NMR spectroscopy to analyze the allosteric mechanisms of three cAMP-binding proteins involved in cardiovascular health.


title: Development of Dewatering Textile Materials Incorporating Slit-Pore Geometries

contributor:
Latulippe, David
Chemical Engineering

subject: Geotextile Dewatering Sludge Wastewater

abstract: The treatment of municipal, industrial and agricultural wastewater produces a semi-liquid mixture known as sludge. The costs associated with pumping, transporting, treating, storing, and disposing of sludge are significant. Therefore, sludge dewatering techniques are employed to increase the solids content of the material by separating the solid and liquid components, thus reducing the overall volume requiring further handling. Non-mechanical dewatering methods require large areas of land and favorable climatic conditions, while mechanical dewatering technologies require significant capital investment and ongoing operation and maintenance by highly trained personnel. Due to these shortcomings, the conventional methods of sludge dewatering are not applicable to scenarios where: the quantity of sludge is small, there is limited budget, there are land restrictions, or dewatering is performed seasonally. An alternative approach that has recently attracted considerable attention is the use of dewatering fabrics; specially engineered textiles supplied in the form of very large bags into which the sludge is pumped. The concept itself is simple, pressure inside the bag pushes the free water through the fabric while the solid material is retained within. Unfortunately, these products have exhibited poor dewatering performance for certain feed materials. In this work, a series of ‘next-generation’ engineered dewatering fabrics featuring elongated ‘slit’ pores were produced using laser cutting techniques. A comprehensive analysis of the effect of the filter properties on dewatering performance was performed using sludge sourced from two different operations: municipal wastewater treatment and precious metal mining.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: In recent years, the use of engineered dewatering fabrics has emerged as a viable alternative to conventional methods of sludge dewatering in numerous application areas including municipal wastewater, mining, and pulp and paper. Previous studies have focused on the development of empirical ratios between dewatering performance and the porous properties of the textile material. The limitation of this approach is that the latter is difficult to characterize using currently available techniques due to the complex, nonuniform pore structure of conventional woven and nonwoven dewatering fabrics. In this study, a series of dewatering fabrics were produced using advanced microfabrication techniques featuring well-defined slit-pore geometries. Full-factorial design-of-experiment frameworks were employed to evaluate the effects of slit-pore dimensions and slit-pore spacing on cake layer development and key dewatering performance metrics. Laboratory scale dewatering performance tests were performed using both anaerobic digested sludge from the Woodward Avenue Wastewater Treatment Plant in Hamilton, Ontario and metal precipitate sludge from a nickel-copper mine in Ontario, Canada. The results from this study provide new insights into the importance of the cake layer in geotextile dewatering and the impact of pore geometry, porosity, and polymer performance on cake layer development.


title: THROMBOPROPHYLAXIS IN PATIENTS WITH ACUTE SPINAL CORD INJURY

contributor:
Schulman, Sam
Health Research Methodology

subject: Thromboprophylaxis, Spinal Cord Injury, Pilot Study

abstract:
Patients with acute spinal cord injury (SCI) have a high risk of venous thromboembolism (VTE) despite receiving thromboprophylaxis. The current standard of care recommended by guidelines is to use low-molecular-weight heparin (LMWH) for thromboprophylaxis for 90 days. This entails once- or twice-daily subcutaneous injections of LMWH for this duration, which is inconvenient for the patients and only partially effective. There are uncertainties about risk factors and the true incidence of SCI-associated VTE, the optimal time to commence thromboprophylaxis, and the optimal duration of thromboprophylaxis. Furthermore, there are currently no studies on the use of direct oral anticoagulants (DOACs) for thromboprophylaxis in patients with SCI. The use of DOACs for prophylaxis in this group can eliminate the inconvenience associated with daily subcutaneous injections for 3 months.
To examine the incidence and risk factors of SCI-associated VTE, we performed a retrospective chart review of consecutive adult patients with acute SCI admitted to Hamilton General hospital from 2009 to 2015. The incidence of symptomatic VTE despite the use of thromboprophylaxis was 11% within 90 days of acute SCI; age and presence of other sites of injuries (such as lower limb fractures or pelvic fractures) along with SCI were independent risk factors for symptomatic VTE.
To determine the opinion of Canadian spine surgeons about the optimal timing of starting LMWH after acute SCI, a short 5-question electronic survey was sent to the Canadian Spine Society. Data from our survey showed that the understanding about thromboprophylaxis after acute SCI was variable and that most spine surgeons were comfortable with starting LMWH after consultation with the surgeon. Future studies should focus on educational strategies to improve the knowledge base in this area.
We will perform a pilot study at the Hamilton General Hospital comparing apixaban versus LMWH for thromboprophylaxis in patients with acute SCI. The use of apixaban for this indication can contribute to cost savings for the healthcare system and increased convenience for the patient. The protocol for the pilot study as well as steps towards a multi-center randomized controlled trial will be detailed in this thesis.

abstract: Thesis

abstract: Master of Science (MSc)


title: Direct Effects of Pesticides on Brown Adipose Tissue

title: In vitro Effects Of Pesticides On Brown Adipose Tissue Function

contributor:
Holloway, Alison
Health Sciences

abstract:
Obesity and its associated comorbidities can occur when energy consumption exceeds energy expenditure. Brown adipose tissue (BAT) is an important contributor to energy expenditure as its mitochondria are rich in uncoupling protein 1 (UCP-1). UCP-1 uncouples oxidative phosphorylation from the generation of ATP to induce a futile cycle and consequently the generation of heat.   Recent studies demonstrate that reduced BAT activity is correlated with many chronic metabolic diseases including obesity and type 2 diabetes, but the mechanisms mediating these effects are currently unclear. There are an increasing number of reports describing how pesticides, currently used to increase crop production, contribute to the development of metabolic syndrome including effects on adipogenesis, food intake, glucose and lipid homeostasis being reported. However, the effects of these compounds on BAT remain largely unknown. The objective of this study was to examine the direct effects of pesticides used to increase crop production on BAT function.

Nine pesticides and their primary metabolites were chosen to enter a 3-tiered screening process. Compounds were selected based on widespread usage and/or reports of metabolic perturbations in epidemiological studies, or animal experiments. Immortalized BAT cells derived from UCP-1 luciferase reporter mice, or wild-type FVB/N mice were treated with compounds at 1pM, 1nM, and 1M doses. To elucidate the effects of selected pesticides on UCP-1 expression, UCP-1 promoter activity, mRNA and protein levels were quantified using a luciferase assay system, RT-qPCR, and western blotting respectively. The most consistent compound was further tested to determine its effects on BAT function by whole cell respiration assay and mitochondrial enzyme activity assays (i.e., citrate synthase, and cytochrome c oxidase assay).

Of the 18 compounds that entered the primary screen, 8 compounds reduced UCP-1 promoter activity by >25%. RT-qPCR revealed that 5 compounds reduced UCP-1 mRNA levels at the same doses by 25% or more. Of these 5 remaining compounds, 3 also exhibited a reduction in UCP-1 protein content by >25%. Of these 3 compounds, chlorpyrifos was most consistent and further analyzed for its effects on BAT function. Chlorpyrifos reduced the expression of genes important for mitochondrial function, while also reducing maximal respiratory capacity and the activity of cytochrome c oxidase of treated brown adipocytes.

These data demonstrate that the commonly used pesticide, chlorpyrifos, directly suppresses UCP-1 expression and BAT function of cultured brown adipocytes from mice at concentrations as low as 1pM. Furthermore, these data also show that its action might be in part, by perturbations in complex IV (cytochrome c oxidase) of the electron transport chain of BAT mitochondria, in addition to the suppression of UCP-1.

abstract: Thesis

abstract: Master of Science (MSc)


title: Physical health in individuals with cerebral palsy: from understanding cardiovascular disease to prevention of multimorbidity

contributor:
Gorter, Jan Willem
Rehabilitation Science

subject:
cerebral palsy
adolescent
adult
physical activity
cardiovascular disease
multimorbidity
sleep
nutrition

abstract: Cerebral palsy (CP) is no longer just a childhood disability. Children with CP grow up and become adolescents and eventually adults. However their risk of cardiovascular disease (CVD) and multimorbidity, defined as the presence of at least two chronic conditions, is poorly understood. This thesis sought to investigate CVD risk in individuals with CP and identify important health variables to understand and prevent multimorbidity development in this population. First, we discovered that adults with CP have an increased prevalence of CVD and an increased risk of death due to CVD compared to the general population, which raises concerns about CVD in people with CP and warrants further study. We investigated differences in cardiovascular health and moderate-to-vigorous physical activity (MVPA) in ambulatory adolescents and adults with CP between Gross Motor Function Classification System (GMFCS) levels I and II. Our findings suggest individuals who are GMFCS level II may be at increased risk for CVD in comparison to individuals who are GMFCS level I. We then evaluated longitudinal changes in risk factors of CVD in a cohort of individuals with CP. After a time interval of 4.0 ± 1.2 years, we found decreased absolute and relative brachial artery flow mediated dilation as measures of endothelial function, while carotid artery intima media thickness increased. We also discovered that 75% of participants with CP reported poor sleep quality, 80% engaged in less than the recommended 150 minutes of MVPA per week and 14% had poor eating behaviours. Taken together, this research suggests that individuals with CP experience accelerated aging for disease progression, specifically CVD, and that physical activity, sleep, and nutrition, together, could provide a framework for a lifestyle intervention to reduce and prevent multimorbidity risk in individuals with CP.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Cerebral palsy is the most common child-onset physical disability. The disability can result in low levels of physical activity, obesity, and risk for morbid conditions that get worse over the lifecourse. The studies in this thesis furthered our understanding of cardiovascular disease and cardiovascular disease risk, investigated the relationship between physical activity and cardiovascular health, and evaluated changes in cardiovascular disease risk over time in individuals with cerebral palsy. We investigated three modifiable behaviours in individuals with cerebral palsy, which told us that they have poor sleep quality, do not engage in the recommended amount of physical activity, and could be at risk for poor nutrition. This work suggests that individuals with CP may be at an accelerated risk for cardiovascular disease, and that physical activity, sleep, and nutrition are important and modifiable factors that should be assessed and managed in this population.


title: Equivalent Hypertrophy and Strength Gains in HMB or Leucine Supplemented Men

contributor:
Stuart, Phillips
Kinesiology

subject: HMB Leucine

abstract: Ingestion of proteins with high leucine content during resistance training (RT) can augment hypertrophy. There are data suggesting that a leucine metabolite, β-hydroxy, β-methylbutyrate (HMB), may, however, be substantially more anabolic than leucine. Purpose: We aimed to test whether supplementation with HMB versus leucine, added to whey protein, would result in different muscle hypertrophy and strength gains in young men performing resistance training (RT). Methods: Twenty-six resistance-trained men (23 ± 2 y) performed 12 wk of RT with 3 phases. Phase 1: 8 wk of periodized RT (3 training sessions/wk). Phase 2: 2 wk overreaching period (5 sessions/wk). Phase 3: 2 wk taper (3 sessions/wk). Participants were randomly assigned to twice daily ingestion of: whey protein (25 g) plus HMB (1.5 g) (Whey+HMB; n=13) or whey protein (25 g) plus leucine (1.5 g) (Whey+Leu; n=13). Skeletal muscle biopsies were performed before and after RT. Measures of fat and bone-free mass (FBFM), vastus lateralis (VL) muscle thickness and muscle cross-sectional area (CSA – both by ultrasound), muscle fiber CSA, and 1-repetition maximum (1-RM) strength tests were determined. Results: We observed increases in FBFM, VL muscle thickness, muscle CSA and fiber type CSA and 1-RM strength, with no differences between HMB and leucine at any phase. Furthermore, no differences were observed in hormone concentrations between groups, or in time-by-group interactions in hormone concentrations at any phase of the RT program. Conclusion: HMB did not result in greater increases in any measure of muscle mass, strength, or hormonal concentration compared to leucine during 12 weeks of RT.

abstract: Thesis

abstract: Master of Science in Kinesiology

abstract: Whey protein supplementation following resistance training (RT) is an effective strategy to enhance RT-induced gains in skeletal muscle mass and strength. The anabolic properties of whey protein are attributed, in part, to the branched-chain amino acid leucine. Leucine is a substrate for protein synthesis and a potent signal that turns on the protein synthetic machinery. A metabolite of leucine, β-hydroxy, β-methylbutyrate (HMB) has been claimed to share similar or greater anabolic properties of leucine. Recently, supplementation with HMB during RT has been shown to result in large gains in muscle mass and strength. The purpose of this study was to examine whether HMB, versus leucine, added to whey protein, would result in different muscle hypertrophy and strength gains in young men during RT. Body composition and maximum strength tests were performed before, during and after 12 weeks of RT. Following 12 weeks of RT, both groups experienced similar gains in muscle mass and strength. We observed that HMB is no more effective in stimulating RT-induced hypertrophy and strength gains than its parent amino acid, leucine.


title: EVALUATING THE RESPONSIVENESS OF THE PATIENT REPORTED OUTCOMES, BURDENS AND EXPERIENCES (PROBE) QUESTIONNAIRE

title: PROBE RESPONSIVENESS

contributor:
Iorio, Alfonso
Health Research Methodology

subject: Responsiveness

subject: Patient reported outcomes

subject: Hemophilia

subject: PROBE

subject: Patient Reported Outcomes Burdens and Experiences Questionnaire

abstract:
BACKGROUND. The study of patient reported outcomes (PROs) has seen an exponential increase in recent years. In order to be useful in practice, PRO questionnaires should be evaluated for validity, reliability, and responsiveness. Responsiveness, which assesses a questionnaire’s ability to capture changes in quality of life (QOL) when they occur, has not formally been evaluated in hemophilia-specific questionnaires.
PRIMARY OBJECTIVE. To evaluate the responsiveness of the Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire in individuals living with hemophilia A or B following events of interest.
SECONDARY OBJECTIVES. To evaluate the responsiveness of PROBE over periods in which no events occur. To explore the use of regression analysis in aiding interpretability. To assess the presence of response shift in the study population.
METHODS. Participants will be asked to complete PROBE, as well as questions indicating changes in QOL, following a bleed or surgical intervention, and every 6 months. Responses will be evaluated using anchor-based and distribution-based approaches.
OUTCOMES. Minimally important differences (MIDs) and minimally detectable changes (MDCs) will be calculated, graphically represented, and compared to determine a single or small range of MID values.
STUDY IMPLICATIONS. Understanding responsiveness will provide increased interpretability of PROBE scores. Using an MID value, one can be confident that a change in PROBE score greater than the MID is beyond measurement error and indicates a change in QOL. This will allow for the use of PROBE in future research trials of drug effectiveness and can offer patients’ perspectives on their changes in QOL when switching to novel therapies. In addition, physicians may be able to use PROBE as a method of tracking and better understanding changes in their patients’ health statuses in the clinical setting.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: This project hopes to identify the responsiveness of the Patient Reported Outcomes, Burdens, and Experiences (PROBE) Questionnaire. The responsiveness of a questionnaire is its ability to detect a change in health status when one has occurred. In order to measure whether PROBE can detect these changes, participants living with hemophilia A or B will be asked to fill out the questionnaire, as well as a few questions aimed at determining if their quality of life has changed, after they have a bleed or a surgery, as well as after 6 months. Collecting this information will help us understand how much the PROBE score needs to change in order for patients to consider a small but important change in health to have occurred. This will help with interpreting the PROBE score, which could then be used in research or in hemophilia clinics across Canada.


title: The Detection of Ischemic Stroke on the PSD Manifold of EEG Signals

contributor:
Wong, Max
Electrical and Computer Engineering

subject: PSD manifold

abstract: The study of ischemic brain stroke detection by Electroencephalography (EEG) signal is the area of binary signal classification. In general, this involves extracting features from EEG signal on which the classification is performed. In this thesis, we investi- gate the employment of Power Spectral Density (PSD) matrix, which contains not only power spectrum contents of each signal which complies with what clinical experts use in their visual judgement of EEG signals, but also cross-correlation between multi-channel (electrodes) signals to be studied, as a feature in signal classification. Since the PSD matrices are structurally constrained, they form a manifold in the signal space. Thus, the commonly used Euclidean distance to measure the similarity/dissimilarity between two PSD matrices are not informative or accurate. Riemannian Distance (RD), which measures distance along the surface of the manifold, should be employed to give more meaningful measurements. Furthermore, two classification methods, binary hypothesis testing and K-Nearest Neighbors (KNN), are applied. In order to enhance the detec- tion performance, algorithms to find optimum weighting matrix for each classifier are also applied. Experimental results show that the performance by the kNN method us- ing PSD matrix as features with RD as similarity/dissimilarity measurements are very encouraging.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Testing, Characterization, and Thermal Analysis of Lithium-Ion Batteries Toward Battery Pack Design for Ultra-Fast Charging

contributor:
Emadi, Ali
Mechanical Engineering

subject:
Thermal Analysis
Lithium-Ion Batteries
Ultra-Fast Charging
Battery Testing
Battery Characterization

abstract: Ultra-fast charging of electric vehicles will soon be available to charge the batteries in less than 15 minutes to 80% state of charge. However, very few studies of batteries under these conditions exist. To design a battery pack with ultra-fast charging in mind, more information about batteries is needed, both electrically and thermally. In this thesis, the performance of three specific commercial lithium-ion batteries during ultra-fast charging is investigated and their thermal behaviour is simulated for use in the battery pack design process. The cells are charged at 1C to 6C current rates, or as high as 10C, and the surface temperature of each cell is measured. The loss calculated from the charging tests are used in a thermal analysis of the three batteries using finite element analysis. The batteries are modeled in a simple cooling apparatus to determine their thermal management requirements in a pack, i.e., how effectively must the heat be removed from the cells to obtain a specific temperature in a pack. Test results show that ultra-fast charging is possible with very little loss; but, it is dependent on the battery. The analysis illustrates important trade-offs between the battery type, charge rate, and the thermal management system. This thesis presents a holistic view to the study of the batteries for eventual use in the design of a battery pack. The thermal performance of the batteries is equally important as their electrical (charge) performance. It also attempts to justify the observed behaviour of the batteries by their underlying chemical behaviour. The work here can be used as a jumping-off point for further work on the ultra-fast charging of batteries or the design of a battery pack.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Ultra-fast charging of electric vehicles, i.e., fully charging the vehicle in less than 15 minutes, will soon be more available. However, literature on the ultra-fast charging of the batteries used in these vehicles is limited. It is not widely known whether the batteries can effectively achieve ultra-fast charging or how the batteries behave under these conditions. Charging batteries this fast means that the battery cells will heat up. The temperature of the cell greatly impacts its longevity and safety. The thesis attempts to address these questions by studying three commercial lithium-ion batteries, selected for specific characteristics, that show potential for ultra-fast charging. The batteries are charged at different rates to ultra-fast charging levels and the charge performance at each rate is determined. The temperature of the batteries is simulated with different cooling systems to determine how effectively must heat be removed from the batteries to maintain the cells at a specific temperature.


title: Video Super-Resolution

contributor:
Chen, Jun
Electrical and Computer Engineering

abstract: Video super-resolution becomes significant desire recently to provide high-resolution contents for ultra high definition displays. Recent advances in video super-resolution have shown that convolutional neural networks combining with motion compensation, which can merge information from multiple low-resolution frames, to generate high-quality frames. But it has been demonstrated that most deep learning based video super-resolution methods heavily dependent on the accuracy of motion estimation and compensation. Other than before, here proposed a different end-to-end deep neural network that inexplicit compensates motion through the generates dynamic filters. The dynamic filters are computed depending on the local spatio-temporal neighborhood of each pixel. With this approach, a high-resolution frame has reconstructed directly from the low-resolution input frames by using a series networks combining with a dynamic local filter network. The proposed network can generate much sharper high-resolution videos with temporal consistency, compared to the previous methods.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Effects of Hyperglycemia on Early Endothelial Activation and Atherosclerotic Plaque Development

title: Hyperglycemia and the Endothelium in Early Atherosclerosis

contributor:
Werstuck, Geoff
Health Sciences

subject:
Atherosclerosis
Hyperglycemia
Diabetes
VCAM
Endothelial Dysfunction
Inflammation
Endothelial Activation
ICAM
Dyslipidemia
ApoE-/-
Akita
Insulin 2
Early Atherosclerosis
Plaque
Development
Mice
Subendothelial space
Macrophage
Initiation
Accelerated Atherosclerosis
Cardiovascular disease
Aortic Sinus
ApoE+/-
Young

abstract: A study of hyperglycemia and its effects on endothelial activation, macrophage recruitment, and atherosclerotic plaque development in mice. Hyperglycemic mice demonstrated greater VCAM but not ICAM expression along the endothelium, increased macrophage presence within the subendothelial space of these regions, and a greater volume of plaque in adulthood.

abstract: Cardiovascular disease is the leading cause of death in the world today. Atherosclerosis is the formation of plaque in the arteries and a major underlying cause of these fatalities. Type I and II diabetes are each strong independent risk factors for atherosclerosis. This study examines the effects of hyperglycemia on early atherosclerosis. Hyperglycemia did not promote atherosclerosis in the absence of hypercholesterolemia. Hyperglycemic mice demonstrated greater VCAM, but not ICAM, expression in regions of the endothelium susceptible to atherogenesis, prior to initiation of plaque development. Regions correlating to upregulation of VCAM exhibited a greater quantity of macrophages infiltrating the intima. This study suggests a unique and important role for VCAM in early atherosclerotic development and may explain the accelerated atherosclerotic plaque progression seen in hyperglycemic mice. This study also identifies VCAM as a potential target for the development of therapies to block or slow atherosclerotic plaque development in people with diabetes.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Cardiovascular disease is the leading cause of death in the world today. A major underlying cause of cardiovascular disease is atherosclerosis – a condition involving the thickening of the artery wall. Type I and II diabetes are each strong independent risk factors for atherosclerosis. The purpose of this study is to examine the effects of high blood glucose (hyperglycemia) on early events leading to atherosclerosis. This study found that hyperglycemia was not sufficient to promote atherosclerosis unless plasma cholesterol levels were also elevated. Hyperglycemia appeared to induce atherosclerosis by increasing the expression of factors responsible for recruiting white blood cells to the artery wall. This is consistent with the observation that hyperglycemic mice also had significantly more macrophages in the sites of plaque development. This study implicates one macrophage-recruitment factor in particular, vascular cell adhesion molecule (VCAM), as playing an important and unique role in the initiation of atherosclerosis by hyperglycemia. Therefore, VCAM is a possible target for the development of therapies to block or slow the development of atherosclerosis in individuals with diabetes.


title: ENHANCING PLASTICITY WITH FLUOXETINE AND ENRICHMENT IN THE ADULT RAT CORTEX

contributor:
Murphy, Kathryn
Neuroscience

abstract:
Developing brains have a great capacity for plasticity, whereas plasticity in adulthood is much more limited. However, the mature brain still retains a considerable amount of plasticity that can be augmented by a variety of plasticity-enhancing therapeutics. Two approaches include the antidepressant fluoxetine and environmental enrichment. Both induce functional improvements in multiple brain regions and produce alterations in both inhibitory as well as excitatory synaptic mechanisms. Multiple gene expression changes induced by fluoxetine and enrichment have been demonstrated including the alteration of mRNAs and proteins implicated in synaptic plasticity, dendritic spine morphology, cell signalling, survival, metabolism, molecular transport, transcription, histone deacetylation, and protein degradation. However, how these treatments work at the molecular level to bring about enhanced plasticity in adulthood is still not completely understood. We investigated the effects of fluoxetine, alone or in combination with monocular deprivation (MD), in the adult rat visual cortex and examined the impact of short- and long-term enrichment in the adult rat somatomotor cortex. We studied a collection of synaptic and non-neuronal proteins implicated in experience-dependent plasticity, including excitatory markers (PSD-95, GluN1); spine markers (Drebrin A - mature isoform, Drebrin E - immature isoform, Ube3A); and a myelin marker (Classic MBP). Protein expression was quantified using Western blot analysis. Enrichment produced modest changes in PSD-95 and GluN1 levels, with short-
 iv
term enrichment favouring a decrease in both excitatory markers. Interestingly, fluoxetine and enrichment elicited distinct effects on dendritic spine markers. Fluoxetine resulted in an overall reduction of dendritic spine markers, whereas enrichment shifted Drebrin levels to favour more Drebrin A relative to Drebrin E. Additionally, fluoxetine appeared to substantially rescue Ube3A losses that resulted from MD while enrichment exerted modest effects on Ube3A levels. We also found that MD increased MBP in the ipsilateral hemisphere but decreased MBP in the contralateral hemisphere, changes that were independent of fluoxetine. MBP was also elevated with enrichment. These findings suggest that changes in MBP are predominantly driven by changes in experience. This research identifies several plasticity mechanisms, including alterations in dendritic spine dynamics, effects on Ube3A-related plasticity, and experience-dependent MBP fluctuations, that fluoxetine and enrichment use to enhance adult brain plasticity and reactivate heightened plasticity in adulthood.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The brain’s ability to change in response to new experiences, called neuroplasticity, is high during development and declines into adulthood. Remarkably, the adult brain still retains a considerable amount of plasticity, but generally requires some assistance in order to activate it. My thesis investigates two treatments that aim to boost adult brain plasticity and reinstate the increased flexibility of young brains in adulthood. The first treatment is the drug fluoxetine. The second treatment is environmental enrichment. In my thesis, I measure the expression levels of several proteins to study how these treatments enhance plasticity in adulthood. I found that fluoxetine and enrichment exert distinct effects on dendritic spines, which are small protrusions on neurons that play a key role in processing and transmitting information. My findings also indicate that myelin, a physical structure that has generally been thought to prevent plastic changes, may actually help support plasticity.


title: Thermal Modeling and System Identification of In-Situ, Through-Ventilated Industrial DC Machines

contributor:
Cotton, James
Mechanical Engineering

subject:
DC Motor
Thermal Model

abstract:
Concerns of the impact of greenhouse gasses (GHG) are leading heavy industry users to explore energy reduction strategies such as the conservation of electricity use in ventilated machines by the use of variable-cooling systems. For these strategies to be implemented, a thermal model of the system is required. This study focuses on the thermal modelling of through-ventilated, industrial, electric machines that employ a variable-cooling strategy, using only on-line data collected during regular machine operation. Two empirical thermal models were developed: a first-order model, and a second-order model which was extended from the first-order based on its performance.

By means of an energy-balance, the first-order model was able to define an estimation of the motor temperature based on only a single variable, and thus was able to be fit directly to complete process-cycle data to determine the parameter. Over the 18 process-cycle samples, this parameter was found to vary by as much as $\pm$10\%, therefore, when a generalized model was proposed using the median value of the parameter, the maximum error seen over the process cycles was 9.0 $^{\circ}C$, with a maximum average error over a process-cycle of 4.2 $^{\circ}C$. An effort was made to determine the effects of reduced cooling on the model by performing reduced-cooling experiments during machine cool-downs, however the thermal-time constant, which directly relates the heat-transfer rate to the system capacitance, was found to vary by as much as 47\%, suggesting that the system's capacitance was changing, and that the first-order model was not accurate enough to distil these effects. A key obervation of the performance of the first-order model was that in heating it would under-predict the machine temperature, and in cooling would over-predict, suggesting that an additional heat-transfer path existed to the cooling air through some additional thermal capacitance.

In an effort to include higher-order effects so that reduced-cooling effects could be established, a second-order model was developed by adding an additional lumped-node to the system, introducing the supposed additional conduction/capacitive path, where the heat-generating node was considered analogous to the motor's armature, and the additional node was considered as a thermal-sink. This model was then numerically fit to the cool-down data for both maximum and reduced flow-rate cases in order to identify the system's main heat transfer parameters, however, once again, a large variance in the parameters was found. Through model simulation, this was determined to be the result of the system not starting at a steady-state temperature distribution, which resulted in the parameter estimation under-predicting the true values. As such, the upper-limits of the parameter spreads were used to identify the model. Assuming the system's heat generation was due to Joule-losses only, the second-order model was found to perform marginally better than the first-order model, with a maximum error of 8.6 $^{\circ}C$, and a maximum average error of 3.3 $^{\circ}C$ over the process-cycles. Though the second-order model typically performed better than the first-order model in cooling, it was found that the model would vary between over-predicting and under-predicting the machine temperature, indicating that additional and higher-order core losses may play a role in the heating of the machine.

Although the first-order model was found to be slightly less-accurate than that of the second-order, the first-order model has a much simpler and far less intrusive identification scheme than that of the second-order model with a relatively low loss in accuracy. As a result, it would be possible to to use the first-order model for on-line temperature monitoring of the machine by performing tests during operation where the cooling rate is reduced to identify the change in the model parameter. However a sufficient factor of safety ($\approx$10 $^{\circ}C$) would be required to account for the under-estimation that occurs in heating. For the second-order model to be implemented, more controlled testing is required in order to properly discern the effects of reduced cooling from the effects of the initial temperature distribution. Additionally, the inclusion of core-losses in the machine heat generation term should be investigated to improve model performance.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Self-Inscribed Waveguide Arrays In Soft Photopolymers: From Dynamic Lenses To Materials That Compute With Light Filaments

contributor:
Saravanamuttu, Kalaichelvi
Chemistry and Chemical Biology

subject:
Nonlinear optics
Photopolymers

abstract:
Nonlinear optical processes have been used for many years to cause light to behave in unique ways. These can influence various aspects of the light beams, including the spatial intensity profile. More specifically, a naturally divergent beam can maintain its initial beam profile when propagating through a nonlinear medium due to the increased refractive index causing focusing. This process is called self-trapping and can be elicited for both coherent and incoherent light in a number of nonlinear media. Analogous to this, modulation instability (MI) is a nonlinear process that causes a broad beam of light of break up into a large population of self-trapped filaments. When these processes occur in photopolymers, light guiding structures are inscribed within the material and persist even after the light is removed. Our group has previously studied the behaviour and interactions of light undergoing self-trapping and MI in photopolymer systems.
The studies presented in this thesis show novel interactions between multiple incoherent beams undergoing MI, utilization of these interactions, as well as the development of new polymeric systems capable of inducing MI. The filaments produced when orthogonal beams underwent simultaneous MI would align with themselves, forming highly ordered structures within the material. These interactions were used as the basis of an encoding and computing system based on the specific ordering of the resulting filaments. The mechanical properties of the resulting polymers were improved and tuned by developing a long-chain organosiloxane based system. The embedded waveguide structures are capable of guiding light when significantly deformed and restore to their initial parameters. A hydrogel system was also developed that was capable of producing self-trapping and MI with incoherent light. The samples were tested with biological systems and were also used to produce dynamic lens samples with enhanced angle of view.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The role of activated thrombin activable fibrinolysis inhibitor (TAFIa) in atherosclerosis progression

contributor: Medical Sciences (Thrombosis & Haemostasis & Atherosclerosis)

subject: atherosclerosis TAFI

abstract: Atherosclerosis is a chronic inflammatory condition of larger arteries characterized by build-up of plaques in the vessel wall. Disruption of plaques results in superimposed thrombus formation, or atherothrombosis, leading to the occlusion of the blood vessels. Atherosclerosis is the primary cause of heart attacks and strokes. Recent studies show that various fibrinolytic factors influence atherosclerosis progression. A healthy fibrinolytic system is fundamental to mitigating the worsening of the lesion and atherosclerosis progression by rapidly removing unwanted microthrombi that is otherwise incorporated into the plaque. In this regard, the activated thrombin-activable fibrinolysis inhibitor (TAFIa), a potent antifibrinolytic metallocarboxypeptidase that attenuates clot dissolution, could influence atherosclerosis progression. Aside from its antifibrinolytic property, TAFIa also affects inflammation by inactivating anaphylatoxins and kinins. Therefore, TAFIa possesses the potential to influence atherosclerosis via antifibrinolytic and anti-inflammatory facets. We utilized mice deficient in apolipoprotein E (ApoE-/-) as a model of atherosclerosis. Characterization of murine TAFIa determined that the functional half-lives at 37 and 25 ˚C were about 4.0 and 12.7 minutes, respectively. TAFIa was stable indefinitely at 0 ˚C. In vitro clot lysis assays were performed on the plasmas of C57BL/6J (wild-type) and ApoE-/- mice, aged 5, 10, 15 and 30+ weeks. No differences in clot lysis times were observed between the two genotypic classifications. TAFIa was directly quantified using our in-house assay, which showed decreased TAFIa levels in the ApoE-/- mice. Closer examination revealed that the plasma from the ApoE-/- mice was negatively influencing the TAFIa assay. Total TAFI zymogen levels in these samples appeared to increase with age. Other biomarkers of inflammation were quantified using ELISAs; however, only IL-10 levels were measurable with slight elevation in the ApoE-/- mice across age, while IL-1beta, TNF-alpha, and IL-6 was unquantifiable. Overall, TAFIa does not appear to influence atherosclerosis progression in ApoE-/- mice.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Atherosclerosis is an inflammatory disease of large blood vessels that leads to unwanted clot formation on these weakened/compromised vessel walls. Eventually, the blood flow is hindered by these clots and the supply of oxygen and nutrients to vital organs are disrupted, leading to irreparable damage and death of these organs. As such, it, is the primary cause of heart attacks and strokes depending on the location of vessel occlusion. Thrombin activable fibrinolysis inhibitor (TAFI), when activated to TAFIa, contains both anti-inflammatory and antifibrinolytic properties. Therefore, it is likely that TAFI(a) would be involved in atherosclerosis development and/or progression, especially since other fibrinolytic factors have shown to be involved. Despite promising preliminary data, we found that TAFI(a) alone may minimally be involved in the overall atherosclerosis progression and development using a mouse model of atherosclerosis. We further investigate whether TAFI(a) can be used as a biomarker for early diagnosis of atherosclerosis.


title: Nano-scale 4D mapping by Scanning Transmission X-ray Microscopy

contributor:
Hitchcock, Adam
Materials Science and Engineering

abstract:
Proton exchange membrane fuel cells (PEMFC) are a promising green energy resource for automotive applications. The cathode is a key rate limiting component of PEMFC. Typical cathodes are composed of Pt catalyst decorated carbon support particles, mixed with a perfluorosulfonic acid (PFSA) polymer. As the proton conduction medium in the cathode, the distribution of the PFSA ionomer will affect PEMFC efficiency, Pt utilization, and degradation kinetics. Optimization of ionomer loadings and distributions is a major goal of PEMFC research.
In this thesis, Scanning transmission X-ray microscopy (STXM) has been used to measure the porosity and component distributions in 3D.  Initial studies of PEMFC materials by STXM tomography have been presented. The high energy resolution of STXM collects an extra dimension of component information to be added to the 3 dimension of volume imaging. Multi chemical 3D imaging is defined as 4D imaging. To reduce the radiation damage to PFSA, the compressed sensing (CS) algorithm has been used. The results show that the total radiation damage can be reduced below the critical dose, and better reconstruction results with less measured angles are achieved using CS algorithm.
PFSA materials were also measured using ptychography STXM tomography to improve the spatial resolution. The spatial resolution was improved from 30 nm to < 15 nm at ~700 eV. 4D imaging using ptychography STXM tomography is presented.
Highly porous materials with functional coatings were also characterized by soft X-ray STXM-spectro-tomography and spectro-ptycho-tomography. The sample were Al2O3 aerogels coated with ZnO or TiO2 by atomic layer deposition (ALD). Quantitative analysis shows the ZnO ALD coatings are non uniform. Comparisons are made to electron microscopy imaging and X-ray fluorescence analysis of the same ZnO/ Al2O3 aerogel material. Together the results provide useful feedback for optimization of ALD coated alumina aerogels.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Optimizing meaningful engagement of older adults with multimorbidity and their caregivers as partners in health care research

contributor:
Markle-Reid, Maureen
Valaitis, Ruta
Carter, Nancy
McAiney, Carrie
Nursing

subject: patient and caregiver engagement in research

subject: older adults with multimorbidity

subject: informal caregivers

subject: optimizing meaningful engagement

subject: persona-scenario method

subject: co-design

subject: nursing research

subject: patient and public engagement in research

subject: patient involvement

subject: citizen engagement

abstract:
Background: The importance of engaging older adults (> 65 years) with multimorbidity and their caregivers as partners in health care research has been widely recognized. Inclusion of patients as research partners has resulted in largely positive effects. However, little is known about how best to engage and support them in this role. The objective of this study was to examine how to optimize meaningful engagement of older adults with multimorbidity and their caregivers as research partners.
Methods: The research objective was addressed using the persona-scenario method. Study participants were older adults with previous experience as a research partner or a research participant. Participants worked in pairs to create a persona and a scenario about how their persona(s) was involved on the research team. Analysis was conducted in two phases: (a) identification of themes, subthemes, and codes using a qualitative descriptive approach, and (b) interpretation of themes and subthemes into design specifications (actions and products).
Results: Four persona-scenario sessions were held with 8 patient participants. Three major themes emerged from the data: (a) recruitment of patient or caregiver research partners (PCRPs); (b) planning for meaningful engagement; and (c) establishing collaborative relationships. These major themes contained 15 corresponding subthemes, and design specifications (52 actions and 37 products). Findings highlight key factors influencing the engagement of older adults with multimorbidity and their caregivers as research partners, such as the need for: early engagement of PCRPs; clarification of PCRPs’ roles and responsibilities; a flexible patient-centred approach to PCRP involvement; identifying and addressing barriers to their engagement (e.g., caregiving support, transportation); training about research; and continued dialogue and feedback to clarify roles and manage expectations. The results are important for identifying ways to promote greater patient engagement in research and ensure that the research reflects the needs of the patients it strives to serve.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The importance of engaging patients with multimorbidity and their caregivers as partners in health care research has been widely recognized. However, little is known about how to best engage and support them in this role. The objective of this study was to examine how researchers can best engage and support older adults with multimorbidity and their caregivers as research partners in health care research teams. The persona-scenario method was used for participants to create fictional stories. These stories were analyzed to shed light on specific strategies that can support older adults and their caregivers as partners on health care research teams, such as a patient-centred approach, identifying and addressing barriers to engagement, and clarifying roles and responsibilities on the research team. The results from this study can be used to inform research, policy, and education on supporting older adults with multimorbidity and their caregivers as research partners.


title: A Machine Learning Approach to EEG-Based Emotion Recognition

contributor:
Sonnadara, Ranil
Becker, Suzanna
Computational Engineering and Science

subject:
Electroencephalography (EEG)
Emotion Recognition
Machine Learning
Affective Computing

abstract: In recent years, emotion classification using electroencephalography (EEG) has attracted much attention with the rapid development of machine learning techniques and various applications of brain-computer interfacing. In this study, a general model for emotion recognition was created using a large dataset of 116 participants' EEG responses to happy and fearful videos. We compared discrete and dimensional emotion models, assessed various popular feature extraction methods, evaluated the efficacy of feature selection algorithms, and examined the performance of 2 classification algorithms. An average test accuracy of 76% was obtained using higher-order spectral features with a support vector machine for discrete emotion classification. An accuracy of up 79% was achieved on the subset of classifiable participants. Finally, the stability of EEG patterns in emotion recognition was examined over time by evaluating consistency across sessions.

abstract: Thesis

abstract: Master of Science (MSc)


title: Robust Inventory Management under Supply and Demand Uncertainties

contributor:
Huang, Kai
Business

subject:
Inventory management
Robust optimization
Stochastic programming
Supply and demand uncertainties

abstract:
In this thesis, we study three periodic-review, finite-horizon inventory systems in the
presence of supply and demand uncertainties. In the first part of the thesis, we study
a multi-period single-station problem in which supply uncertainty is modeled by partial
supply. Formulating the problem under a robust optimization (RO) framework, we
show that solving the robust counterpart is equivalent to solving a nominal problem
with a modified deterministic demand sequence. In particular, in the stationary case
the optimal robust policy follows the quasi-(s, S) form and the corresponding s and S
levels are theoretically computable. In the second part of the thesis, we extend the RO
framework to a multi-period multi-echelon problem. We show that for a tree structure
network, decomposition applies so that the optimal single-station robust policy remains
valid for each echelon in the tree. Furthermore, if there are no setup costs in the network,
then the problem can be decomposed into several uncapacitated single-station
problems with new cost parameters subject to the deterministic demands. In the last
part of the thesis, we consider a periodic-review Assemble-To-Order (ATO) system with
multiple components and multiple products, where the inventory replenishment for each
component follows an independent base-stock policy and product demands are satisfied
according to a First-Come-First-Served (FCFS) rule. We jointly consider the inventory
replenishment and component allocation problems in the ATO system under stochastic
component replenishment lead times and stochastic product demands. The problems
are formulated under the stochastic programming (SP) framework, which are difficult
to solve exactly due to a large number of scenarios. We use the sample average approximation (SAA) algorithms to find near-optimal solutions, which accuracy is verified by
the numerical experiment results.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Towards an automated measure of levels of cognitive function in unresponsive patients

contributor:
Connolly, John F
Cognitive Science of Language

abstract:
This thesis aims to evaluate the clinical utility of several auditory paradigms designed to elicit various event-related scalp potentials (ERPs). Through four papers, this thesis (i) determines which paradigms best elicit the desired components in healthy controls, (ii) evaluates methods of confirming the presence of the MMN in clinical ERP data, and (iii) examines the use of spectral entropy, and specifically the use of wavelet signal decomposition to determine the periodicity of spectral entropy in order to target the use of these paradigms for diagnostic use.
Chapter 2 first sets out a framework for extended monitoring of patients in coma by selecting paradigms that performed well in healthy control populations. From an initial group of six paradigms designed to elicit the MMN, P300, and N400, two are selected that were able to elicit the desired ERPs from the healthy controls. This study is the first to examine these various paradigms within the same participants, as well as across two different age groups (younger and older adults).
Chapters 3 and 4 provide evidence that the MMN–a component previously thought to be stable over time–appears to fluctuate in detectability in patients in coma. In addition to the traditional visual inspection method of MMN detection, four other methods of verifying the presence of the MMN were evaluated: the topographic consistency test, a serial t-test, a spatiotemporal cluster analysis, and Bayesian t-tests. In all four patients presented, the MMN appears to change in detectability over a period of approximately 24 hours. The spatiotemporal cluster analysis and Bayesian t-tests both proved to be suitable for use in confirming visual inspection judgements of the presence of the MMN in this set of patient data, and were able to overcome problems from external noise in the signal. These results suggest that patients should be tested multiple times to increase the likelihood of capturing a period where the MMN is detectable and reducing the chance of a false negative.
Finally, Chapter 5 examines the application of a spectral entropy signal analysis to the same patient data. Period of higher spectral entropy are indicative of a more complex EEG signal, which in turn has been thought to index conscious experience. This analysis was used to determine both if the patients had periods of higher spectral entropy, and if they did, what the periodicity of that fluctuation of spectral entropy would be. Previous work has shown that patients in a minimally conscious state (MCS) can show periods of around 70 minutes, which is similar to healthy, conscious individuals. Of the three patients whose data was appropriate to use in this analysis, one showed a periodicity of around 70 minutes, one did not show a signal with a strong main periodicity, and one had two main periodicities which was indicative of being contaminated by external noise. Even though the analysis method is extremely sensitive to external noise, it does show promise as a means of targeting the cognitive assessments, as these should be given when the patient is likely to be more conscious. This is especially important considering the evidence presented that the MMN fluctuates in comatose patients, so targeting the delivery of these tests can further reduce the false negative rate.
Overall, we have established which ERP paradigms have the best chance of eliciting the components of interest, which in turn can be used for coma prognostication. We have presented evidence suggesting that the MMN fluctuates in its detectability, which provides a caution to clinicians using this methodology to perform repeat testing to better capture the MMN. As well, we have suggested methods to further confirm the presence of the MMN in noisy patient data. Finally, we provide a method of using spectral entropy for determining periods during which these tests should be performed to maximize the likelihood of capturing the components of interest. Taken together, this work brings us closer to an automated measure of the levels of cognitive function in unresponsive patients.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The role of extracellular polymers in Streptomyces growth and development

contributor:
Elliot, Marie
Biology

subject:
Microbiology
Molecular Biology
Peptidoglycan
Biofilm

abstract:
Bacteria in the environment face constant stress, due to lack of nutrients or presence of growth inhibiting compounds. As a result, they have developed several strategies to evade unfavourable growth conditions. These range from entering into dormant or quiescent states, through to motility, and biofilm formation. Using the model organism Streptomyces, we investigated how the bacterial cell surface regulates dormancy, biofilm formation, and motility.

Dormancy via spore formation allows cells to shut down metabolism in response to poor nutrient conditions. Spores can then be dispersed throughout the environment to encounter favourable conditions. This is an incredibly resilient survival strategy, so long as the spores resuscitate from dormancy and resume growth once favourable conditions are sensed. We established that peptidoglycan remodeling by resuscitation promoting factors is critical for rapid germination of dormant Streptomyces spores, which likely provides a competitive advantage over slower growing microbes in the same environment. Previously it was thought that these proteins produce a signal to stimulate germination in neighbouring cells. We determined that the resuscitation promoting factors are lytic transglycosylases, and were not capable of producing a germination signal on their own. Instead, they function by cleaving the peptidoglycan to make room for new cell growth. This work highlights the importance of peptidoglycan remodeling to the germination process. Biofilms are multicellular communities of microorganisms which are adhered to each other using a protective matrix. Formation of biofilms is thought to be inversely correlated with motility. We established that Streptomyces forms biofilms during the exploratory growth identifying potential extracellular matrix components. These biofilms use sliding motility to expand rapidly across their environment. Components of the biofilm matrix effect colony expansion, suggesting that biofilm formation and motility are intricately linked in Streptomyces. These works demonstrate the importance of surface polymers to the growth and development of Streptomyces.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Bacteria are all around us. In these different environments, whether in the soil, or inside our guts, or in a body of water, they will encounter stress. This can take the shape of nutrient stress, or the presence of growth inhibiting compounds. In response, bacteria can evade these poor conditions by entering into dormancy, analogous to hibernation, by building a biofilm, analogous to building a bunker, or by moving away. The surface of bacterial cells becomes decorated with different polymers as it transitions into one of these three modes of stress evasion. The cell wall holds the cell together and supports its shape, making it the most important surface polymer. I examined how rapid remodeling of the cell wall provides a competitive advantage to cells waking up from dormancy. I also examined the importance of additional polymers to the formation of biofilms that slide across surfaces, away from stressors. These works establish how important the surface of the bacterium is for surviving stressful conditions.


title: NOVEL DESIGN FOR PRODUCTION OF LIQUID FUELS WITH NEGATIVE EMISSIONS

title: NOVEL DESIGN FOR PRODUCTION OF TRANSPORTATION FUELS WITH NEGATIVE EMISSIONS

contributor:
Adams II, Thomas A
Chemical Engineering

subject: Modeling, design, simulation and techno-economic analysis

abstract:
Global pressure to reduce greenhouse gas (GHG) emissions, energy security concerns and increasing demand for liquid fuels incentivize the search for more sustainable and secure alternative methods for producing liquid fuels with improved efficiency and reduced environmental impacts. One of the economically attractive examples of these alternate methods is the gas-to-liquid process, however, its environmental impacts are worse than traditional petroleum refining. Carbon capture and sequestration is an option to reduce greenhouse gas emissions of processes, but it decreases the efficiency of the process and often results in economic infeasibility. Instead, integrating different processes and feedstocks was demonstrated to improve the efficiency, economic and environmental performance of the processes.
The focus of this thesis is to design and simulate a novel integrated biomass, gas, nuclear to liquids (BGNTL) process with negative greenhouse gas emissions. In this process, nuclear heat from a high temperature gas-cooled reactor (HTGR) is used as the heat source for a steam methane reforming (SMR) process. The integrated HTGR and SMR process requires detailed analysis and modeling to address key challenges on safety, operability, economic and environmental impacts of the integrated process. To this end, a rigorous first principle based mathematical model was developed in gPROMS modeling environment for the integrated HTGR/SMR process. The results for a large scale design of this system indicate that hydrogen rich syngas with H2/CO ratio in the range of 6.3 can be achieved.
To meet the desired H2/CO ratio (around 2) required for the downstream fuel synthesis processes, the HTGR/SMR derived syngas can be blended with a hydrogen lean syngas from biomass gasification. In this thesis, the large scale design of the BGNTL process to synthesize gasoline, diesel and dimethyl ether (DME) is investigated. The results from the gPROMS model of the integrated HTGR/SMR system are used for simulating the BGNTL process in Aspen Plus. The performance of the BGNTL process was compared with a biomass, gas to liquids (BGTL) process. The efficiency, economics, and environmental impact analyses show that the BGNTL process to produce DME is the most efficient, economic and environmentally friendly process among all the considered designs. The results demonstrate that process integration exploits certain synergies that leads to significantly higher carbon and energy efficiencies and lower greenhouse gas emissions. In addition, it was found that all the studied designs yield a net negative greenhouse gas emissions when carbon capture and storage technology is implemented.
As another sustainable alternative to meet the required H2/CO ratio of the syngas when biomass resources are not available, it is proposed to apply the nuclear heat to the mixed reforming of methane. This represents using steam and waste CO2 to reform methane into valuable syngas. The developed model for the integrated HTGR/SMR system is extended to the mixed reforming of methane (MRM) process and it was demonstrated that integrated HTGR/MRM process can be a promising option to achieve certain desired H2/CO ratios for the downstream energy conversion processes.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: RESILIENCE-BASED BLAST DESIGN OF REINFORCED CONCRETE MASONRY SYSTEMS

contributor:
El-Dakhakhni, Wael
Tait, Michael
Civil Engineering

subject:
resilience surface
reinforced masonry
recovery time
functionality loss
out-of-plane
resistance function
fragility surface
blast risk
Nonlinear analysis
Axial load

abstract: The use of fully grouted reinforced masonry shear walls (RMSWs) has been growing in several areas around the world owing to their relative ease of construction and their in-plane ductile behavior. However, RMSWs possess low out-of-plane ductility which amplifies the vulnerability of such components under blast loading. Furthermore, the long time and high costs of recovery following devastating (deliberate or accidental) explosions have created a need for resilience-based design for risk mitigation, especially considering the different sources of associated uncertainty. As such, this study aims to lay out the foundations of a probabilistic resilience–based blast analysis and design framework. The framework should have the capability of quantifying the overall building post-blast functionality in order to estimate its recovery cost and time, and thus the building resilience following such a demand. The proposed framework will be specifically applied for RMSW buildings incurring blast loads through a profound investigation for the behavior of rectangular RMSWs as being a primary structural element in reinforced masonry buildings. The investigation will subsume an experimental and analytical evaluation for the performance of load-bearing RMSWs with different in-plane ductility levels subjected to out-of-plane quasi-static loading. This will be followed by a numerical investigation of RMSWs to conclude the blast probabilistic performance of RMSWs that can be applied within the proposed probabilistic resilience-based blast framework. The work in this dissertation presents a key step towards adopting resilience based analysis and design in future editions of blast-resistant construction standards and provides the decisionmakers with a complete insight into post-blast building functionality and its recovery.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: “It’s hard enough for the people doing the work to access these services”: Sexual Healthcare Barriers that LGBTQ2S+ Populations Experience in a Rural Canadian Community

contributor:
Greene, Saara
Social Work

subject:
LGBTQ2S+
community-based research
collaboratives
barriers to services
resistance to barriers
social work

abstract:
Despite Canada’s universal healthcare system, there exist numerous barriers that prevent
LGBTQ2S+ populations from accessing healthcare services such as sexual health.
Through pulling from community-based research principles and utilizing a critical social
science framework, this research explores the availability and accessibility of sexual
health services for LGBTQ2S+ individuals living in a rural Ontario community. After
extensive consultations with multiple key informants, two focus groups were conducted
with individuals from a community-based collaborative where members had the dual role
of being service providers and community members. It is important to note that gaining
access to the collaborative was made possible due to the resources and networks provided
by the AIDS Network, a community charitable organization. Using a thematic analysis of
the data, three major themes surfaced: the negative effects of heteronormativity,
queerphobia, and transphobia within healthcare settings; barriers to accessing sexual
healthcare; and community responses and strategies. These findings are reflected in the
literature concerning issues of healthcare access for LGBTQ2S+ populations, but these
research findings are unique given they are specific to both sexual health and rural
communities. Implications for social work education, practice, and research include
tapping into the potential of collaboratives; creating LGBTQ2S+-specific policies;
making space for community voices, especially within academia; and recommendations
for healthcare providers.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Probes of new physics at the intensity and energy frontiers

contributor:
Burgess, Cliff
Yavin, Itay
Physics and Astronomy

subject:
Phenomenology
Milli-charged particles
Charged scalars
Heavy neutral dipoles
Large Hadron Collider
Neutrino experiments
Search for new physics

abstract: In this thesis, we review the basics of phenomenology in particle physics at neutrino beam dump experiments and hadron colliders. We then consider the phenomenology of various new particles, with masses between 1 MeV and 1 TeV, at the intensity and energy frontiers. We perform sensitivity analyses for physics beyond the standard model at particle colliders (LEP and LHC) and a number of past and future neutrino beam dump experiments (SHiP, DUNE, LSND, MicroBooNE, MiniBooNE and SBND). In particular, we motivate searches for new heavy neutral leptons in single photon events at neutrino and collider experiments (and also via supernova cooling), millicharged particles in single electron events at neutrino experiments, lepton flavor violating scalars via standard model induced mixed flavor neutrino trident production at neutrino experiments, and colored scalar doublets at colliders in events with many jets, soft leptons and low missing energy. In the process, we set novel new bounds on the parameters of these theories and propose powerful new searches that can be performed. We also motivate the construction of a new detector at the LHC called milliQan, and perform a full Geant4 simulation to calculate its projected sensitivity for millicharged particles. The milliQan experiment has since been approved and is currently undergoing construction.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: In this thesis, we review the basics of particle physics at neutrino experiments and particle colliders. We then motivate and develop key searches that can be performed to look for new particles at a series of existing and future experiments. We focus on new particles with masses between the electron mass and 1000 times the proton mass. The many searches we consider involve looking for processes that produce a single ray of light, a single electron, a pair of oppositely charged "electron-like" events, new collider signatures, and/or modifications of star explosions. In the process, we set novel new bounds on many theories. We also motivate the construction of a new detector at the Large Hadron Collider called milliQan, and perform a full simulation to assess its future performance. The milliQan experiment has since been approved and is currently undergoing construction.


title: Use of wrinkles for fabrication of stretchable electrodes and omniphobic surfaces

contributor:
Soleymani, Leyla
Engineering Physics

subject:
omniphobic
wrinkles
stretchable electrodes

abstract: The buckling of stiff film on a substrate had been of great interest as this response happen spontaneously and is self-organizing. This provides an unconventional, scalable and easy way to fabrication surfaces with tunable structures from the range of nanometers to micrometers. We optimized a process to fabricate stretchable electrodes by transferring wrinkled gold onto elastomer. We tested their electrochemical sensing functionality through detection of glucose concentration with or without strain. Results showed that the stretchable electrodes provide high sensitivity for the detection of glucose (860 ± 60 µA/mM.cm2), comparable to electrodes before transfer. The current detected was also consistent under strain. Investigation of the resistance indicates that the electrode configuration under strain is important as current running parallel to direction of strain is much more affected under tension. We also developed a fast and facile process to fabricate surfaces that consisted of wrinkles and nanoparticles. Using such surfaces, we tested the omniphobicity effect of hierarchical structures consisting of wrinkles and nanoparticles. Results show that all the fluorinated structured surfaces were hydrophobic, ranging from water contact angle of 125° for wrinkled surfaces to 155° for hierarchical surfaces. The surfaces that were either wrinkled or decorated with nanoparticles were oleophilic with low hexadecane contact angles (~26° and ~55° respectively). The combination of both structures achieved oleophobicity of more than 110°. The effectiveness of nanoparticles for low surface tension liquid were due to its re-entrant like structure. The omniphobic surfaces were also shown to be repellent to blood (>135°), making it a potential material for use medical devices.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Wrinkling is a phenomenon often seen in real life, such as on the skin of a dried plum or human. It is possible to fabricate such wrinkles through having a stiff thin film adhered to an elastic foundation and compressing the foundation. The wrinkles are useful for fabrication of stretchable electrodes as their structure allows the film to stretch without breaking through unfolding. Here, we fabricated stretchable electrodes by transferring such wrinkled structures onto elastic foundation. These stretchable electrodes are shown to be able to detect the concentration of glucose in solution even when stretched. These electrodes are important for creating wearable devices that can monitor glucose levels or other substance continuously. Wrinkles also work as part of hierarchical structure which are helpful for trapping air beneath droplets of fluids. Here we incorporate wrinkles with nanoparticles which helps to make surfaces repellent to both water and oil. Such a function is important for self-cleaning surfaces and can also be used for patterning of surfaces for selective deposition of fluid.


title: The Experience of Bereaved South Asian Family Caregivers of Adult Family Members

contributor:
Kaasalainen, Sharon
Ploeg, Jenny
Wahoush, Olive
Nursing

subject:
palliative apporach
South Asian
end-of-life care
caregivers

abstract: This study focuses on understanding the experiences of bereaved South Asian family caregivers living in Canada. Findings suggest that South Asian caregivers face several challenges and that there is a need for a more culturally sensitive palliative approach to care.

abstract:
The South Asian population faces several challenges when receiving palliative care, including language barriers, unawareness of resources, and poor cultural awareness among health care providers (HCP). However, little is known about the needs of South Asian family caregivers in Canada. The purpose of this study is to understand the experience of bereaved South Asian informal caregivers, who cared for a family member in their last year of life. An interpretive descriptive design was used.
Eleven participants were recruited by referral through a community hospice and a community health centre. Participants were South Asian informal caregivers and at least two months bereaved. Audio-recorded one-on-one interviews were conducted followed by a thematic analysis of the transcripts. Five themes were identified to describe the experience of bereaved South Asian informal caregivers: transforming perceptions of life and death, the influence of culture on the experience; the challenges of being a caregiver; coping with the challenges of care-giving; and getting support. Caregivers expressed feeling a sense of duty to their family members and were reluctant to utilize long-term care homes or hospices. The perceived hierarchy of HCP roles also affected their experience. In reflecting on their experiences, caregivers had a deeper appreciation for life and were more willing to talk about death and dying.
The experience of South Asian family caregivers is complex with several underlying cultural influences. This study has important implications in improving the delivery of culturally sensitive palliative care and developing supports that address the challenges experienced by caregivers in the South Asian community.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The South Asian community faces many challenges when receiving palliative care, including language barriers and health care providers (HCP) who do not understand the South Asian culture. However, little is known about the needs and experiences of South Asian family caregivers. In this study, South Asian caregivers of family members who recently died described their experience of being a family caregiver. Caregivers had a strong sense of duty to their family members and were against moving their family members into long-term care homes or hospices. Their understanding and views of HCPs’ roles affected their experiences. Caregivers also had more appreciation for life and wanted to talk about their wishes for their own death with their family members. The findings of this study can help improve the delivery of palliative care for the South Asian community and can help HCPs better support their South Asian patients and families.


title: ONLINE SOCIAL COMMERCE USERS BEHAVIORS: THREE STUDIES

contributor:
Yuan, Yufei
Business

abstract: Social commerce has emerged as a new platform that enables users to conduct shopping assisted by inputs from other members and to publicly comment on transactions or products. It therefore adds a social aspect to traditional online commerce environments. Nevertheless, the role of the social facet embedded in such transactions in influencing user behaviors is not fully understood. In this dissertation, I develop three empirical studies to better understand social commerce user behaviors and to specifically consider the biasing factors that exist in these social platforms and can skew user rational decision-making. The results of these studies highlight the importance of social context in influencing users’ behaviors. The first study’s results show the role of interactions among social commerce users in affecting users’ decisions. The second study shows that like most of social networking sites; the use of social commerce platforms are prone to become habitual. Furthermore, this study shows how the developed habit among users can influence their rational purchasing decision. Finally, the third study explores the role of group identification and it shows that social identity that will be developed among members can cause some bias and skew the rational behaviors of users.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: VOICE PITCH AFFECTS WOMEN’S PERCEPTIONS OF DOMINANCE, BUT NOT IN A WAY THAT RELATES TO COMPETITIVENESS

contributor:
Feinberg, David
Psychology

subject:
Voice pitch
Competitiveness

abstract:
A theory of the evolution of low voice pitch in men suggests that (a) voice pitch is used as an indicator of success in mate competition; (b) pitch is used as an indicator of dominance more for men’s voices than women’s; (c) pitch affects dominance ratings more than attractiveness ratings. While early studies supported these ideas, several subsequent studies have failed to replicate these results with mainly male raters, because of the idea that men’s perceptions affect selection more than women’s do.
We tested the extent to which these findings apply to women’s perceptions of the aforementioned characteristics, as well as to other characteristics related to voice pitch and dominance: perceived body size, competitiveness, cooperativeness, socio-economic status, and attractiveness. We manipulated pitch in men’s and women’s voices and tested women’s perceptions thereof. Women chose low voices as belonging to a speaker that is more physically/socially dominant, less cooperative, larger, higher in socio-economic status, and (for men’s voices) more attractive.  In contrast to hypotheses of theories on the evolution of low voice pitch in men, pitch had no effect on perceptions of competitiveness, nor did it affect either physical or social dominance ratings more than it affected attractiveness ratings.  Surprisingly, pitch affected dominance perceptions of women’s voices more than men’s. Thus, despite previous evidence that some men modify their voices in competitive scenarios, our data are unable to support the idea that this information is used by women to infer dominance related to competitiveness. We contribute to the growing literature that finds no difference in the amount that voice pitch affects dominance and attractiveness ratings or fails to find stronger effects for male than female voices. Our data are consistent with theories that dominance ratings are the result of a general response bias to stimuli varying in pitch.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Low voice pitch is associated with perceptions of dominance, size, attractiveness, higher socio-economic status, and low cooperativeness. Since men lower their voice pitch in competitive scenarios, we predicted low pitch would be tied to perceptions of competitiveness of the speaker. We manipulated pitch in men’s and women’s voices, and female participants chose which voice they thought belonged to the person who was more physically/socially dominant, competitive, cooperative, larger, higher in socio-economic status, and more attractive.  Women chose low voices as being more physically/socially dominant, less cooperative, larger, higher in socio-economic status, and (for male voices only) more attractive than higher voices. Pitch had no effect on perceptions of competitiveness, it did not affect perceptions of dominance for male speakers more than female speakers, neither did it affect perceptions of dominance more than attractiveness. This challenges the idea that low pitch in men evolved to primarily signal success in intrasexual competition.


title: THE PSEUDOMONAS AERUGINOSA BIOFILM INDUCTION RESPONSE TO SUBINHIBITORY ANTIBIOTICS REQUIRES oprF AND sigX

contributor:
Burrows, Lori
Biochemistry and Biomedical Sciences

subject: Pseudomonas aeruginosa biofilm antibiotics

abstract:
Pseudomonas aeruginosa is a Gram-negative pathogen that forms
biofilms, which increase tolerance to antibiotics. Biofilms are dense, surfaceassociated
communities of bacteria that grow in a self-produced matrix of
polysaccharides, proteins, and extracellular DNA (eDNA). Sub-minimal inhibitory
concentration (sub-MIC) levels of antibiotics induce the formation of biofilms,
indicating a potential role in response to antibiotic stress. However, the
mechanisms behind sub-MIC antibiotic-induced biofilm formation are unknown.
We show that treatment with sub-MIC levels of cefixime (cephalosporin),
carbenicillin (β-lactam), tobramycin (aminoglycoside), chloramphenicol
(chloramphenicol), thiostrepton (thiopeptide), novobiocin (aminocoumarin),
ciprofloxacin (fluoroquinolone), or trimethoprim (antifolate) induces biofilm
formation, with maximal induction at ~ ¼ to ½ MIC. We demonstrate that
addition of exogenous eDNA or cell lysate does not stimulate biofilm formation
to the same extent as antibiotics, suggesting that the release of common goods
by antibiotic action does not solely drive the biofilm response. We show that
increased biofilm formation upon antibiotic exposure requires the outer
membrane porin OprF and the extracytoplasmic function sigma factor SigX.
Through transposon mutant screening and deletion studies, we found that OprF
is important for biofilm induction, as mutants lacking this protein did not form
increased biofilm when exposed to sub-MIC antibiotics. OprF expression is
v
controlled by SigX, and its loss increases SigX activity. Loss of SigX also prevents
biofilm induction by sub-MIC antibiotics. Together, these results show that
antibiotic-induced biofilm formation may constitute a type of stress response.
This response may be useful to screen for new antibiotics due to its ability to
reveal antibiotic activity at concentrations below the MIC. Further study of this
response may also provide targets for adjuvant therapies that reduce biofilm
formation in P. aeruginosa infections and increase the efficacy of current
antibiotics.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Pseudomonas aeruginosa is a bacterium that causes illness in patients
with compromised immune systems, like patients with cystic fibrosis. This
bacterium forms biofilms, which are dense groups that stick to surfaces within a
protective slime that contains proteins, sugars, and DNA. Biofilms make the
bacteria harder to treat with antibiotics. If the bacteria are treated with low
levels of antibiotics, they respond by forming more biofilm but how this happens
is unknown. We showed that adding DNA does not increase biofilm formation,
while adding dead cell debris only causes a small increase. By testing a library of
mutant bacteria, we found that they need two genes, oprF and sigX, to form
more biofilm when they are treated with low levels of antibiotic. By studying
how bacteria respond to low levels of antibiotics, we can find ways to identify
new antibiotics and to make our current antibiotics work better.


title: Epistemic Certainty & Uncertainty in Sophocles' "Ajax"

contributor:
Mattison, Kathryn
Classics

subject: Sophocles Ajax Agency Personality Epistemology Philology Character Literary Criticism

abstract: The topic of the thesis is epistemic certainty and uncertainty in Sophocles’ Ajax. Epistemic certainty refers to the quality of a character’s knowledge. I coined the term to describe the aspects of the play which seemed to explain this gap between Ajax’s actual and perceived character. Ajax is typically assessed by scholars as a character who makes decisions purely on the basis of self-assertion in the pursuit of glory. My thesis challenges this view, which has become a point of near-consensus among scholars. This effort differs from other studies of the Ajax in that it acknowledges the existence of both paradigms of action and personality: based either on the reason or the will. I conclude that Ajax acts on the basis of reason, but misleads other characters (and the audience) because of the dynamics of epistemic certainty and uncertainty. I view the Ajax as deliberately thematizing these dynamics of knowledge for the sake of provoking reflective thinking and discussion about this phenomenon in the play’s audience. At the same time, it pursues this investigation while preserving the expanded scope of recent works on the Ajax to include its implications for the play’s marginal characters, particularly Tecmessa and the Chorus. To that end, the investigation encompasses the entirety of the play while still addressing a major aspect of criticism concerning Ajax himself. Meanwhile, I describe how these two planes of engagement, that is, being epistemically certain or uncertain, mimic the condition of theatre-goers (or readers) as they move from being an audience member, an objective observer, to someone implicated in the action of their own lives once the play has ended.

abstract: Thesis

abstract: Master of Arts (MA)

abstract: The topic of the thesis is epistemic certainty and uncertainty in Sophocles’ Ajax. Epistemic certainty refers to the quality of a character’s knowledge. I chose the topic because I was curious about the assessment of Ajax among scholars as a character who makes decisions purely on the basis of self-assertion in the pursuit of glory. The topic thus challenges what has become a point of near-consensus among scholars. This effort differs from other studies of the Ajax in that it acknowledges the existence of both paradigms of action and personality: based either on the reason or the will. It pursues this investigation while preserving the expanded scope of recent works on the Ajax to include its implications for the play’s marginal characters, particularly Tecmessa and the Chorus. To that end, the investigation encompasses the entirety of the play while still addressing a major aspect of criticism concerning Ajax himself.