title: Non-Coupled and Mutually Coupled Switched Reluctance Machines for an E-Bike Traction Application: Pole Configurations, Design, and Comparison

contributor:
Emadi, Ali
Mechanical Engineering

subject: Switched Reluctance Motor

subject: Mutually Coupled Switched Reluctance Motor

subject: Traction Motor

subject: Reluctance Machine

subject: Motor Modelling

subject: Magnetic Saturation

subject: Electric Bicycle

subject: SRM

subject: MCSRM

subject: E-Bike

subject: Concentrated Winding

subject: Mutual Coupling

abstract: This dissertation contains a comprehensive analysis of both non-coupled and mutually coupled switched reluctance motors with concentrated windings for an electric bicycle traction application. Multiple pole configurations are analyzed and compared for each motor type. Includes magnetic design, thermal analysis, and structural analysis. A prototype is designed, manufactured, and validated.

abstract:
This thesis discusses the design of both a conventional non-coupled
switched reluctance motor (CSRM) and a mutually-coupled SRM (MCSRM) for
an exterior rotor e-bike application. Several novel pole configurations were
analyzed for each machine type, and the performance of the final CSRM and
MCSRM designs were compared for this application.
A commercially available e-bike permanent magnet synchronous motor
(PMSM) was purchased, reverse engineered, and validated to define the geometry
constraints and performance targets for the designs. Since switched reluctance
motors do not use rare-earth permanent magnets, they are often seen as a potential
low-cost alternative to permanent magnet machines. The goal of this research is to
explain the relative advantages of CSRMs and MCSRMs when compared to PMSM
machines for a direct-drive e-bike application. The final CSRM and MCSRM
designs are analyzed in detail; electromagnetic, controls, thermal, and structural
considerations are all studied. A prototype of the final CSRM design was
manufactured and validated experimentally, using a dynamometer setup.
The finalized CSRM design is shown to be competitive with the PMSM
machine when considering torque output, and is superior in terms of peak
efficiency, and high speed torque performance. However, the CSRM noise output
and torque ripple were not compared to the PMSM, and a less-common
asymmetric-bridge converter is required for the CSRM, which may hinder the
ability for the machine to be implemented into existing e-bike packages.
The high speed torque performance of the MCSRM is shown to be inferior
to both the CSRM and PMSM, as is the torque quality and efficiency. The MCSRM
is shown to be highly resistant to saturation which gives it the potential for high
torque output at low speed (if thermal limits are not breached), though low
saturation levels also contribute to low machine power factor. The MCSRM may
be better suited to lower speed, high torque applications, for this reason.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
This thesis studies the design process and analysis of two different motor
types, for an electric bicycle application. They are designed to replace a
commercially available permanent magnet synchronous motor (PMSM). This type
of motor is typically expensive due to the rare-earth magnet material it requires.
The two motors discussed in this thesis are switched reluctance motors (SRMs),
which do not require magnet material, and thus have the potential to save cost (in
addition to other benefits). One of the SRMs has magnetic fields that are
independently controlled (CSRM), and one has fields that are controlled together
to produce torque (MCSRM). The magnetics, control, thermal, and structural
aspects of the CSRM and MCSRM are studied in detail. Novel geometry
considerations (i.e. novel pole configurations) which impact the magnetics of each
machine are compared to find the best-performing configuration for each machine
type.


title: Individual breastfeeding and weaning histories in a 19th century Spanish sample using stable isotope analysis of incremental dentine sections

contributor:
Prowse, Tracy
Anthropology

subject:
Weaning
Breastfeeding
Paleopathology
Stable Isotopes

abstract: Through stable isotope analysis of human tooth dentine, this thesis investigates breastfeeding and weaning patterns in relation to rickets in a sample of sub-adults (n=12) interred in the nineteenth century sub-adult cemetery located at the Church of the Trinitarias in Madrid, Spain. The main objectives of this research are to create early life feeding histories for each individual using dentine serial sectioning techniques and apply these histories to investigate the relationship between breastfeeding, weaning, and vitamin D deficiency. The early life feeding histories allows for the determination of the onset and complete age of weaning at an individual level. These stable isotope data are then used to estimate general trends in breastfeeding and weaning practices in nineteenth century Spain. The results of this study indicate that the onset age of weaning for most of the individuals in this sample was between 10 and 14 months of age. The age at which breastmilk consumption stopped entirely was more difficult to estimate, however, in individuals that did show evidence of completed weaning, it was estimated to occur around the age of three. These ages are slightly higher than those discussed in historical sources for nineteenth century Spain. When these results are compared to contemporaneous, more industrialized, European countries the comparison shows that the initialization of weaning occurred slightly later and was a more gradual process in this Spanish sample. The results also demonstrate that there is no direct relationship between weaning patterns and the occurrence of skeletal vitamin D deficiency. It may be that the high prevalence of vitamin D deficiency is linked with the nuances of breastfeeding and other biocultural variables, such as a lack of sun exposure, an inadequate weaning diet, or childcare practices.

abstract: Thesis

abstract: Master of Arts (MA)


title: Legitimate Authority and Raz

contributor:
Waluchow, WJ
Sciaraffa, Stefan
Philosophy

subject: Philosophy Law

abstract: The major emphasis of this thesis follows the broader survey in Chapter 1 about consent. Really, the attempt is to pull apart Raz’s theory from two particular points: (1) The three-thesis service conception and (2) the noninstrumental grounds argument. In both points, we have to contend with Raz’s claim that there is no general obligation to obey the law. We have to manage that claim against Raz’s insistence that legal authorities claim that there is not only a general obligation, but a wholly comprehensive obligation to obey. My first major contribution is to show that this represents a real descriptive problem for Raz’s account of authority. I acknowledge his attempt to argue in normative terms, and to forgo certain descriptive accuracy in the effort to vouch for what ought to be. My most pointed claim is that he strays too far from a reasonable description of authority in pursuing his justifiable version. My second major point is to argue that abstract judicial review can reconcile Raz’s theory with the central case, while also providing a more ethically justified alternative to the ‘case or controversy’ requirement that plagues so much of Western legal practice.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: SYNTHESIS OF IRON NANOPARTICLES MEDIATED BY CELLULOSE NANOCRYSTALS

contributor:
de Lannoy, Charles
Chemical Engineering

subject:
nZVI
Cellulose nanocrystals
Nanoparticles
Iron
Surface nanoroughness
Nucleation and growth
Capping agent

abstract: Colloidally-stable zero valent iron nanoparticles (nZVI) were synthesized through a classical redox reaction of iron sulfate with minor modifications using cellulose nanocrystals (CNCs) as stabilizers. We obtained spherical nZVI particles with high surface roughness and a mean size of 130nm. Particles remain colloidally stable after more than two months. Cellulose nanocrystals play a dual role in nZVI stability: a foreign surface to encourage stable nucleation over fast aggregation and a stabilizer to prevent iron nanoparticles aggregating into fractal colloids. Our results highlight the impact of the presence of CNCs on the rates and mechanisms of nucleation, growth, aggregation, and aging of nZVI particles, indicating promise in controlling size and morphology of similarly redox-generated nanoparticles. Cellulose nanocrystal-stabilized nZVI nanoparticles demonstrate properties well-suited for enhanced soil and groundwater remediation.  //Nanocomposites composed of carboxylated cellulose nanocrystals and iron (Fe-oxCNC) were prepared through a classical redox reaction of iron sulfate using TEMPO-oxidized cellulose nanocrystals (oxCNCs) as a template and stabilizer. Morphological control over Fe-oxCNC nanoparticles was realized by varying the amount of oxCNC added to the redox process. As the molar ratio between oxCNC and Fe was increased from 1 to 8, the morphology of Fe-oxCNC nanoparticles evolved from rounded iron aggregates supported by cellulose nanocrystals to thin film iron-coatings on cellulose nanocrystals. Transmission electron microscopy (TEM), Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), and chemical analyses (EDX, EELS) revealed that oxCNCs were coated by iron. Small changes to the density and type of functional groups on the CNC surface have large impacts on the morphology and the oxidation state of adsorbed iron nanoparticles.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Decision-making in youth with hoarding symptoms

contributor:
Soreni, Noam
Neuroscience

subject: Hoarding Youth Decision-making Endowment

abstract:
Hoarding symptoms are characterized by (1) a persistent difficulty discarding personal items (2) clutter that interferes with living areas and (3) clinically significant distress or impairment in functioning. Hoarding symptoms are common, affecting 2-6% of the general population and 20% to 56.7% of individuals with obsessive-compulsive disorder  (OCD). Research suggests that individuals who hoard have impaired decision-making, particularly when it involve making decisions about personal possessions. This is thought to be a key deficit in hoarding resulting in an inability to discard unneeded possessions. Although the onset of hoarding symptoms is usually during childhood or adolescence (youth), little research has investigated hoarding symptoms in youth.
   The present study compared different aspects of decision-making processes between youth with OCD and youth with OCD and hoarding symptoms. Specifically, we assessed decision-making and the influence of ownership using the Balloon Analogue Risk Task (BART) and an endowment trading task, respectively. Additionally, we assessed cognitive flexibility, inhibitory control and delay discounting using the Wisconsin Card Sorting Task (WCST),  the Stop Signal Task (SST) and Monetary Choice Questionnaire (MCQ), respectively. Participants included 52 youth (8-18 years old), all with a primary DSM-5 diagnosis of OCD. Parents completed the Child Saving Inventory to measure the presence of hoarding symptoms and to create hoarding severity groups.
     Youth with hoarding symptoms exhibited differences in ownership-based decision making; specifically, we found a larger endowment effect compared to the non-hoarding group. Compared to participants with OCD only, participants with hoarding exhibited significantly increased cognitive flexibility and lowered perseveration on the WCST. Performance of the hoarding and non-hoarding groups did not differ on other aspects of decision-making, including non-ownership decision-making, inhibitory control and delay discounting. Further regression analysis suggested that increased hoarding severity was associated with higher inattentive symptoms and improved performance on the WCST. These findings support the notion that hoarding is associated with specific differences in making decisions about personal items.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Efficient Simulation of Complex Radiation Sources

contributor:
Wadsley, James
Couchman, Hugh
Mathematics and Statistics

subject:
Physics
Astrophysics
Radiation
Radiative Transfer

abstract: We describe the implementation and testing of the TREVR (Tree-based REVerse Ray-tracing) radiative transfer algorithm in the ChaNGa (Charm N-body Gravity solver) code.  We calculated the optimal values for the source walk opening angle and  ray  trace  walk  refinement  parameter  of θ =  0.5 and τ =  0.01  respectively. We  then  studied  the  effects  of  the  merging  of  sources  on  the  accuracy  of  the calculated  flux  in  absorbing  regions,  noting  a  systematic  negative  error  and  an angular  dependence  across  all  optical  depths.   We  dubbed  this  the  “Complex Sources Problem” and provide suggestions to mitigate its effects

abstract: Thesis

abstract: Master of Science (MSc)


title: Influence of Free Ferrite Content on the Machinability of GCI using CBN Tool

contributor:
Veldhuis, Stephen
Mechanical Engineering

subject:
Gray cast iron
Free Ferrite
CBN

abstract:
Over the years, industrial partners experienced issues related to inconsistent free ferrite in gray cast iron. In the course of a hot summer and a cold winter, machinability balance varies up to 350%. During warm months it is better and cold months worse. The inconsistent machinability increases the scrap rates by up to 400% and reduces tool life by up to 70%. The ultimate objective of this research is to collaborate with an automotive industrial partner to investigate the periodic machinability variability of gray cast iron engine sleeves, with a goal to reduce the cost and scrap rate of tool inserts. In this study, a significant amount of work was conducted concerning sample preparation for a metallography check. Samples from different months with varying amount of “free ferrite” were collected to study the seasonal effect on their machinability and high-speed machining under similar industrial conditions. Furthermore, a room temperature age strengthening of gray cast iron was conducted to demonstrate how the hardness increase from aging could improve the machinability of gray cast iron.
A CBN insert is the second hardest cutting tool after the diamond insert, and is widely used in industry for machining cast iron.  It has a high cutting speed is commonly used due to its high hardness and impressive wear resistance. It is known that gray cast iron can naturally age at room temperature or artificially age under a controlled temperature. Under different aging temperatures and times, gray cast iron exhibits a greater hardness after age strengthening, which affects the CBN tool life. The latter is usually limited by flank wear length, however the content of free ferrite in gray cast iron can generate ferrous built-up on the CBN cutting edge and significantly shorten the tool life of the CBN cutting tool.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Designing, building and testing a UV photouncaging system to study the development of the auditory brainstem

contributor:
Gillespie, Deda
Neuroscience

subject:
Photouncaging
Microscopy
neuroscience
synapses
electrophysiology
refinement
engineering
laser optics

abstract:
New abstract (saved as much of your structure/wording as possible):
In mammals, sound localization along the azimuth is computed in part in the lateral superior olive (LSO), a binaural nucleus in the brainstem. Information about the location of the sound source is derived from differences in sound intensity at the two ears, the Interaural Level Difference (ILD). Within each LSO, principal cells compute ILDs by integrating an excitatory input carrying intensity information from the ipsilateral ear with an inhibitory input carrying intensity information from the contralateral ear. This computation requires that the phenotypically distinct inputs onto individual LSO cells be matched for sound frequency. The process of ‘aligning’ and refining the inputs for frequency information occurs during the first few postnatal weeks in rats, through modifications of synapse strength and cell morphology. Our lab studies the distribution, and re-distribution, of these converging inputs during the early period of circuit refinement.

A common strategy for examining spatial distribution of synapses is through anatomical techniques, including for example immunohistological methods for localizing specific synaptic proteins. Ultimately, however, we need to understand how synapse position affects the functional response. Asking this kind of question requires the ability to stimulate individual synapses while recording from dendrite or cell body, an approach for which we use laser scanning photostimulation (LSPS). I designed two LSPS systems in order to stimulate the post-synaptic sites of excitatory or inhibitory inputs on LSO principal neurons while recording at the cell body using whole-cell patch clamp. I researched many optical designs and technologies when fine-tuning my design. My designs and initial groundwork will help a future lab member finish one or both of the LSPS designs.

abstract: Thesis

abstract: Master of Science (MSc)


title: An Investigation of the Behavioural and Neural Correlates of Repetitive Behaviour in Autism Spectrum Disorder

contributor:
Hall, Geoffrey
Psychology

abstract: The existing research on repetitive behaviour in Autism Spectrum Disorder (ASD) is sparse. The identification of biomarkers through the use of brain imaging is an important area of research that can provide information about the etiology and function of repetitive behaviour, which is poorly understood. To date, results from brain imaging studies have implied that there may be a common neurobiological substrate involved in social deficits and repetitive behaviour in ASD. At the same time, it is becoming increasingly apparent that ASD may be described as a spectrum of multiple ‘autisms,’ that vary in their behavioural presentation and genetic loci. As such, the identification of biomarkers of distinct repetitive behaviour subtypes across the autism spectrum is a priority. To date, several gaps in the literature remain, and the current body of research was completed to address these gaps. In this body of work, Chapter 1 offers an introduction to the subject matter. Chapter 2 presents a review of neuroimaging studies on repetitive behaviour in ASD and creates an organized framework for future research. In Chapter 3, the results of an eye-tracking study, which investigated the common neurobiological substrate in social deficits and repetitive behaviour, are presented. Chapter 4 outlines the results of a brain imaging study that investigated the association between repetitive behaviour and patterns of resting-state functional connectivity in ASD. In Chapter 5, the results of a pilot study that examined the association between inhibitory control and cortical gamma-amino-butyric acid (GABA) in ASD are presented. Last, chapter 6 offers a summary of these original research studies, and a discussion of implications and future directions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Moral Requirements and Partiality

contributor:
Igneski, Violetta
Philosophy

subject: partiality, impartiality, morality, ethics, normativity, reasons, requirements, obligations, duties, special

subject: sui generis, relationships, wellbeing

abstract: What do we owe to our loved ones? What is the status of these requirements? How do we reconcile them with other requirements? Are we allowed to buy our child an expensive car when that money could save countless strangers overseas? What exactly does morality demand of us?

abstract: My thesis defends an account of partiality justified in terms of relationships. I develop the view that relationships are inextricably linked to wellbeing, and I defend the idea that morality must be concerned with our wellbeing. I try to make sense of this account of partiality with the idea that morality carries a requirement of impartiality. If wellbeing is an important part of morally right actions, and if acting in accordance with reasons of partiality (qua relationships) sometimes promotes wellbeing better than impartiality, then some reasons of partiality lead to morally right actions. Minimally, I argue that for why a strictly impartial (or, on the other extreme, a strictly partial) theory does not work. Both reasons (of partiality and impartiality) must be taken into account and carefully calibrated. More ambitiously, I argue for why partiality deserves its own place at the table in normative ethical theorizing. This is not to say that partiality always leads to right action, rather the suggestion is that there are some forms of partiality (found within relationships) which morality requires.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: Some forms of partiality seem clearly wrong, like racial bias or nepotism; in such cases, it is better to consider our reasons to be impartial, which seem to lead to more fairness or equality. Still, there seem to be other forms of partiality which are clearly right, like the love and care a parent has for their child; in these cases, considering our reasons to be impartial seem like (to quote Bernard Williams), “one thought too many.” This thesis tries fit reasons of partiality and reasons of impartiality together, and argues for a view of (moral) partiality grounded in relationships.


title: Determining Optimal Designs and Analyses for Discrete Choice Experiments

contributor: Clinical Epidemiology/Clinical Epidemiology & Biostatistics

subject:
discrete choice experiment
preferences
latent class
knowledge translation
relative importance
ranking

abstract:
Background and Objectives:
Understanding patient and public values and preferences is essential to healthcare and
policy decision making. Discrete choice experiments (DCEs) are a common tool used to capture and quantify these preferences. Recent technological advances allow for a variety of approaches to create and analyze DCEs. However, there is no optimal DCE design, nor analysis method.
Our objectives were to (i) survey DCE simulation studies to determine what design features
affect statistical efficiency, and assess their reporting, (ii) further investigate these findings with a de novo simulation study, and (iii) explore the sensitivity of individuals’ preference of attributes to several methods of analysis.
Methods:
We conducted a systematic survey of simulation studies within the health literature, created
a DCE simulation study of 3204 designs, and performed two empirical comparison studies. In one empirical comparison study, we determined addiction agency employees’ preferences on
knowledge translation attributes using four models, and in the second, we determined elementary school children’s choice of bullying prevention programs using nine models.
Results and Conclusions:
In our evaluation of DCE designs, we identified six design features that impact the
statistical efficiency of a DCE, several of which were further investigated in our simulation study. The reporting quality of these studies requires improvement to ensure that appropriate inferences can be made, and that they are reproducible. In our empirical comparison of statistical models to explore the sensitivity of individuals preferences of attributes, we found similar rankings in the relative importance measures of attributes’ mean part-worth utility estimates, which differed when using latent class models.
Understanding the impact of design features on statistical efficiency are useful for
designing optimal DCEs. Incorporating heterogeneity in the analysis of DCEs may be important to make appropriate inferences about individuals’ preferences of attributes within a population.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
This thesis focuses on the design and analysis of preference surveys, which are referred to
as discrete choice experiments. These surveys are used to capture and quantify individuals’
preferences on various characteristics describing a product or service. They are applied in various health settings to better understand a population. For example, clinicians may want to further understand a patient population’s preferences in regards to multiple treatment alternatives. Currently, there is no optimal approach for designing or analyzing preference surveys. We investigated what factors help improve the design of a preference survey by exploring the literature and conducting our own simulation study. We also investigated how sensitive the results of a preference survey were based on the statistical model used. Overall, we found that (i) increasing the amount of information presented and reducing the number of variables to explore will maximize the statistical optimality of the survey; and (ii) analyzing the data with different statistical models will yield similar results in the ranking of individuals’ preferences of the variables explored.


title: 3D Inkjet Printing Method with Free Space Droplet Merging for Low Viscosity and Highly Reactive Materials

contributor:
Selvaganapathy, Ponnambalam (Ravi)
Mechanical Engineering

subject:
3D printing
inkjet printing
highly reactive materials
droplet mixing
free space printing
silicone

abstract:
Silicones are industrially important polymers characterized by a wide spectrum of chemical and physical properties with a number of important applications including automotive components, construction materials, isolating parts in electronic devices, flexible electronics, and medical products. Development of additive manufacturing methods for silicones enable production of complex and custom designed shapes and structures at both the micro- and macro-scale, economically feasible. In general, such materials can be fabricated using stereolithographic, extrusion-based, or inkjet printing techniques, in which silicones are polymerized using either photo- or heat-initiators. Silicones can also be crosslinked based on chemical reactions. Although this approach is supposedly the simplest, it has not been widely applied in additive manufacturing, as suitable technology for mixing and curing reactive inks without clogging nozzles has not be developed yet. To address this issue, a new 3D printer, that enables the fabrication of highly reactive and low viscous materials, has been developed and tested experimentally.
The proposed fabrication method involves the ejection of two reactive droplets simultaneously from individual dispensers, merging and mixing them in free space outside the nozzle followed by deposition of the merged drop in a patterned format on a substrate. It was shown that the printing process is robust and stable more than 4 hours and it can be used on demand. By incorporating an XYZ positioner, it was possible to deposit droplets in an overlapping fashion to print any programmable shape featuring homogeneous structure, with a small number of pores. Moreover, due to the almost instantaneous reaction between two components (< 10s), the fabrication of very high aspect ratio (AR > 50) objects is possible. Lastly, the presented method can be easily adapted to print in free space without the use of support materials.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Characteristics of the Stress-Generated Electrical Potentials in Bone Induced by Mechanical Loading

contributor:
Wohl, Gregory
de Bruin, Hubert
Biomedical Engineering

subject:
stress-generated potentials
bone
piezoelectricity
streaming potentials

abstract:
Since the discovery of stress-generated potentials (SGPs) in bone by Fukada and Yasuda in 1957, researchers have tried to understand their origin and function in the maintenance of bone. There have been a variety of methods attempting to quantify these SGPs in both wet and dry bone. In this study, I prepared both dry and wet beams of cortical bovine bone and subjected them to mechanical deformation in cantilever bending. Mechanical testing was performed to explore how the magnitude of the SGPs was affected by hydration levels, strain, and pressure gradients associated with various load magnitudes and deformation rates. Signals that were collected from the dry bone samples were attributed to motion artifact resulting from the movement of the materials testing machine and load cell. The SGPs from wet bone, on the other hand, consistently produced exponentially decaying signals following deformation that were maintained throughout held deformation and produced an SGP of opposite magnitude upon release of deformation.
The exponentially decaying SGP signal produced after application of a step load to wet bone samples was determined to fit a two-term exponential equation (V(t) = Aet/τ1 + Cet/τ2). The first term, made up of the A-coefficient and τ1, was found to be dependent on deformation rate whereas the second term, containing the C-coefficient and τ2, was dependent on load magnitude. The sum of the two coefficients determine the maximum voltage the SGP can reach.
Additionally, samples were left to air dry for one hour and tested intermittently throughout that time period. SGP signals diminished significantly over the hour, therefore, it has been concluded that the majority of the SGP signal is due to streaming potentials caused by ionic fluid movement within the bone upon deformation.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
Mechanical deformation of bone produces electrical signals known as stress-generated potentials (SGPs). In this study, I mechanically tested wet beams of bone to assess how the SGPs were affected by hydration levels, load magnitudes, and deformation rates. Dry bone samples did not produce any acceptable SGP signals. The SGPs from wet bone, however, produced repeatable signals that decayed following deformation.
With a step load input, the decaying SGP signal fit a two-term exponential equation (V(t) = Aet/τ1 + Cet/τ2).  The first term, made up of the A-coefficient and τ1, was found to be dependent on deformation rate whereas the second term, containing the C-coefficient and τ2, was dependent on load magnitude. The two coefficients, the A and C-coefficient, together determine the maximum voltage the SGP can reach. The result of this work showed that SGPs in bone are dependent on tissue hydration and vary with load magnitude and deformation rate.


title: Molecular Basis of Diverse PagP::Lipid Interactions in Gram-Negative Bacteria

contributor:
Bishop, Russell
Biochemistry and Biomedical Sciences

subject:
PagP
Outer membrane protein
lipid A palmitoylation
protein conformation change
palmitoyltransferase diversity

abstract: PagP is an integral outer membrane enzyme that transfers a palmitoyl group from a phospholipid to lipid A and the polar headgroup of phosphatidylglycerol (PG). Palmitoyl-lipid A and palmitoyl-PG (PPG) have been implicated in resistance to host immune defenses. PagP proteins are diverse, the E. coli PagP belongs to the major clade of PagP homologs and palmitoylates lipid A regiospecifically at the 2-position, whereas P. aeruginosa PagP belongs to the minor clade of PagP homologs and instead palmitoylates lipid A regiospecifically at the 3’-position. Our objective was to understand how PagP has been adapted in nature to interact with multiple lipid substrates and products. We investigated the structure-function relationships of key major clade homologs, to show that Bordetella PagP palmitoylates lipid A at the 3’-position and employs surface residue T29 in its palmitoyltransferase reaction. Legionella PagP palmitoylates lipid A at the 2-position and was confirmed to select a palmitate chain from a pool including iso-methyl branched phospholipids characteristic of this species. PagP is usually encoded as a single copy on the chromosome in most bacteria, but two copies of pagP are found in endophytic bacteria. These duplicated PagP homologs from the major clade branch into two subclades, namely chromosomal and plasmid-based PagP homologs. The chromosomal PagP homologs exhibit interacting periplasmic D61 and H67 residues, which are naturally mutated in plasmid-based PagP homologs, and are associated with a conformational change in the -barrel that determines its ability to palmitoylate PG. Chromosomal PagPs can convert PPG to bis(monoacylglycero)phosphate (BMP) and lysophosphatidylglycerol (LPG) through a periplasmic active site controlled by the invariant Y87 residue of E. coli PagP. Plasmid-based PagP homologs appear to have been adapted instead as monofunctional lipid A palmitoyltransferases. These results points to a common ancestor for PagP proteins. Knowledge gained from these studies can be applied to protein engineering.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Numerical investigations of the early stages of planet formation

contributor:
Wadsley, James
Physics and Astronomy

subject: planets, formation, numerical simulations, instability

abstract: Dust grains are a crucial component of disks around young stellar systems where current observations and theory show that planets form. Dust grains must grow 10 orders of magnitude in size to become planets. However, one of the early steps in this growth phase faces stringent theoretical constraints. The metre barrier relates to two well-studied physical mechanisms which inhibit grain growth beyond centimetre sizes. We report on numerical studies which probe these early stages of planet formation including instabilities that promote dust concentration such as the streaming instability (SI). We explore several different SPH models for dusty gas evolution. We find the linear SI is difficult for SPH to capture because it begins with perturbations below the 1% level. We also employ the Athena 3rd order Eulerian code which has been used to study the SI in the linear phase and the non-linear or saturated phase. We present numerical confirmations of recent analytical predictions of enhancements to the SI growth rates caused by the dust settling to the disk midplane in the earliest stages of the protoplanetary disk evolution. Symmetric analytical predictions for SI growth are not directly relevant to the non-axisymetric, planar geometry of the saturated, non-linear phase. We lay the ground work to explore this in future work.

abstract: Thesis

abstract: Master of Science (MSc)


title: Early Health Economic Evaluation of Medical Devices

title: Early Health Economic Evaluation of a Novel Medical Device and the Development of a Conceptual Guiding Framework

contributor:
O'Reilly, Daria
Thabane, Lehana
Levine, Mitchell
Blackhouse, Gord
Health Research Methodology

abstract:
ABSTRACT

Background and objectives

To avoid unsuccessful implementation of new health technologies in clinical practice, it is important to investigate their potential cost-effectiveness before adoption, using the health technology assessment (HTA) process. Cost-effectiveness analysis (CEA) techniques tailored for the early stages of a health technology when there is limited evidence available, may guide more efficient resource investment in the development process, such as conducting additional studies that would inform key parameters to strengthen the economic model. However, knowledge and application of early CEA has been limited. A key challenge is trying to conceptualize an economic model with limited information regarding a product’s exact use in clinical practice, and how to use the existing limited data as input parameters for the model.

In this thesis, early CEA refers to the premarket stage of a product’s lifecycle. The objective of this thesis was to develop a guiding framework for conducting early-CEA for medical devices with limited evidence, by contextualizing all of the available methods in the literature, in order to help support conducting early-CEA and to increase its usefulness.

Methods
Project 1: A systematic review was conducted with the purpose of identifying and critically appraising all of the available methods for conducting early-CEA for medical devices with limited evidence, and to propose a conceptual guiding framework to conduct robust early-CEA.
Project 2: Appropriate methods identified in the systematic literature review from project 1 were applied to conduct an early-CEA of StraticyteTM, a novel prognostic tool, when used in combination with the current standard of care (SOC), histopathology, for diagnosing oral potential malignant or pre-malignant lesions (OPLs) in adults aged 35 years or older from a private and patients’ perspective.

Project 3: The lifetime costs, patients’ outcomes, and cost effectiveness of StraticyteTM in combination of histopathology compared to histopathology alone among oral cancer patients were assessed in an economic evaluation from the public payer perspective, by using the output from project 2 as a starting point.
Results

Project 1: Thirteen methods from 26 studies were identified and grouped based on their purpose in conducting CEAs with limited evidence. Based on these methods, a step-wise conceptual guiding framework of how to conduct CEA for medical devices with limited evidence was created, where the methods were introduced at each step based on their general aim for conducting CEA.

Project 2: The early-CEA demonstrated a high probability that StraticyteTM and histopathology will be cost-effective for the detection of OPLs, which in turn encourages continued investment by manufacturers into the product, and suggests that future investment by the healthcare system and individual patients may be worthwhile.

Project 3: The long-term economic evaluation demonstrated potential beneficial downstream effects to the healthcare system from introducing StraticyteTM to current clinical practice; due to fewer cancer cases requiring treatment over the long-term. This highlighted the considerable cost savings to the public healthcare system, if payers invest in a preventative technology in dentistry that could have downstream effects on publically funded cancer care.
Conclusions
The conceptual guiding framework of early-CEA of medical devices with limited evidence that was developed in this thesis classified and harmonized the available methods to support the utilization of early-CEA for key stakeholders in medical device development, and implementation. The premarket assessment of StraticyteTM demonstrated the high probability of it being cost-effective, which may encourage investment for manufacturers, and for public payers, in this health technology. The long-term CEA demonstrated the potential positive downstream impact of StraticyteTM on the healthcare system as a result of its adoption in the market. Further, given that StraticyteTM is developed for use in dentistry, a privately funded healthcare service, this thesis highlights the advantage of public payers’ investment in preventive health technologies in dentistry that have downstream effects in the publically funded medical healthcare system.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: The effects of metformin on colorectal cancer growth and the involvement of the gut microbiome

contributor:
Steinberg, Gregory R
Medical Sciences

subject: Metabolism, Type 2 Diabetes, Cancer, Colorectal Cancer

abstract: Metformin is the most common type 2 diabetes therapy, and may also reduce colorectal cancer growth. Currently, two mechanisms driving reduced cancer growth are considered: 1) Regulation of glucose and insulin levels, which may support cancer growth, and 2) Direct entry into cancer cells to activate the AMP-activated kinase (AMPK) protein, and inhibit cell growth pathways. The gut microbiome is the community of commensal microorganisms in the gastrointestinal tract. It is also affected by metformin, and may elevate production of short-chain fatty acids (SCFAs). Therefore, this thesis aimed to clarify how metformin may inhibit colorectal cancer growth and if the microbiome is involved. The hyperglycemic-responsive, murine-derived MC38 colon cancer cell line was used to test these effects. This model was confirmed to experience growth stimulation caused by high-fat diet (HFD) feeding in mice. Daily i.p. injections of metformin (100mg/kg) had no measurable effect on glucose and insulin sensitivity, or MC38 tumor growth. Oral metformin (250mg/kg) improved glucose tolerance and inhibited MC38 tumor growth in HFD-fed mice. To see if the gut microbiome is required for this effect, the antibiotic ampicillin was used to limit the gut microbiome. The addition of ampicillin blunted metformin’s glucose sensitization and tumor inhibition effects. A fecal microbiome transfer model was then used to isolate the role of the microbiome. Conventional mice fed HFD and gavaged with feces from metformin-treated donors experienced no glucose or insulin tolerance improvements. However, tumor growth was decreased by 30%, and serum SCFAs concentrations were elevated. The SCFA butyrate inhibited in vitro MC38 colony growth, but did not activate AMPK. These data suggest that metformin alters the gut microbiome, and fecal transfer from metformin-treated animals can uncouple MC38 tumor growth inhibition from the glucose homeostasis effects of metformin. These novel findings support a new mechanism for metformin to prevent cancer growth and development.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Metformin is the most commonly used type 2 diabetes therapy, and may also reduce colorectal cancer growth. Anti-cancer effects may be caused by: 1) decreased glucose and insulin levels, which support cancer growth; or 2) entry into cancer cells to directly decrease cell growth. The gut microbiome, microorganisms that live symbiotically in the gastrointestinal tract, is also affected by metformin. This thesis aimed to clarify how metformin can inhibit cancer, and if the microbiome is involved. Mice treated with metformin had improved glucose metabolism and decreased colorectal tumor growth; when an antibiotic was introduced, this effect was lost. A fecal microbiome transfer model was used to determine if the microbiome is driving this effect. Mice receiving feces from metformin treated mice also experienced tumor growth inhibition. This suggests that the gut microbiome is involved in the anti-cancer effects of metformin, and is a new potential mechanism of action.


title: Indirect Consequences of Exposure to Radiation in Doses Relevant to Nuclear Incidents and Accidents

title: INDIRECT CONSEQUENCES OF NUCLEAR INCIDENTS/ACCIDENTS

contributor: Radiation Sciences (Medical Physics/Radiation Biology)

subject: low dose radiation; alpha particles; surviving fractions; linear energy transfer; LET; genomic instability; bystander effects; low dose hyper-radiosensitivity; increased radioresistance; HRS; IRS; radium; ra-226; human keratinocyte; cell line; HaCaT; Chinook salmon; CHSE-214; CHSE/F; relative biological effect; RBE; progeny; lethal mutations; monte carlo; dose-response relationship; radiation exposure; radiation weighting factors; non-targeted effects; NTE; non-human biota; protection

abstract: At low doses, relevant to nuclear incidents and accidental releases of radioactivity, the detriment of radiation extends beyond direct effects. This thesis investigates genomic instability, a subclass of non-targeted effects where damage and lethality is transmitted vertically and expressed in the progeny of cells many generations after initial radiation exposure. Through a series of experiments using clonogenic assay of human and fish cell culture, studies described in this thesis describe lethal mutations, hyper radiosensitivity and increased radioresistance – processes involving repair mechanisms that dictate survival in cells exposed to low doses. Further study investigates the difference in the relative biological effect of alpha particle radiation compared to what is expected at high doses. Results demonstrate increased radioresistance in a human cell line while also revealing increased lethality in a fish cell line confirming the need for consideration of dose-dependence as well as variance in behaviors of different cell lines and species. It is hoped the conclusions of this thesis will inspire the creation of protocols with greater attention to the indirect consequences of exposure to radiation at doses relevant to nuclear incidents and accidents.

abstract: Thesis

abstract: Master of Science (MSc)


title: PHOSPHOLIPID FATTY ACIDS AS BIOMASS PROXIES AND THEIR USE IN CHARACTERIZING DEEP TERRESTRIAL SUBSURFACE MICROBIAL COMMUNITIES

contributor:
Slater, Gregory
Geography and Earth Sciences

subject:
Geochemistry
Astrobiology
Organic Chemistry
Biogeochemistry

abstract:
Understanding the distribution, abundances and metabolic activities of microbial life in the subsurface is fundamental to our understanding of the role microbes play in many areas of inquiry such as terrestrial biogeochemical cycling and the search for extraterrestrial life. The deep terrestrial subsurface is known to harbor microbial life at depths of up to several kilometers where, in some cases, organisms live independently from the photosphere and atmosphere. Ancient fracture fluids trapped within the crystalline basement of the Canadian Precambrian Shield have been shown to be preserved on geologic timescales (millions to billions of years). Significant challenges exist when probing the deep terrestrial subsurface including the low biomass abundance, heterogeneous distribution of biomass, and the potential for matrix effects during sampling and analysis.
This Master’s thesis project has two main parts. The first study utilizes phospholipid fatty acid (PLFA) analysis to determine the extent of mineral matrices on the effectiveness of PLFA extraction and analysis from deep terrestrial subsurface samples. This was done by creating a bacterial dilution series of known concentration to inoculate one of two mineral matrices, granite or bentonite. This study revealed the presence of significant influence of mineral matrices on PLFA extraction and demonstrated the unreliability of PLFA-based biomass conversion factors with respect to complex microbial communities. The second study in this thesis combine PLFA analysis with stable carbon isotope analysis to characterize microbial communities associated with fracture fluids with mean residence times of ~1.4 Ga from boreholes located ~2.4km below the surface in Kidd Creek Mine, in Timmins, Ontario. Characterizing communities in subsurface systems has large implications for the search for life on other planets and moons, acting as an analogue environment. Large volumes of water from two boreholes, 12261 and 12299, were passively filtered for 6-12 months to collect microbial biomass. Borehole adjacent biofilms were also collected along with mine service water, which served as a control. All samples had significant biomass associated with them but were distinct in PLFA fingerprint and δ13C – PLFA signatures indicating the presence of three distinct microbial communities living in association with the fracture fluids and gases. These results have implications for the potential existence of ancient deep subsurface communities that have survived geologic time in isolation, in particular with relation to the subsurface of Mars, as well as give us insight into life on the early Earth.

abstract: Thesis

abstract: Master of Science (MSc)


title: An Exploration of Death Cafés in Canada

contributor:
Badone, Ellen
Anthropology

subject: Anthropology, death

abstract:
Do people talk about death? Many scholars argue that people in our society do not talk about death; that it is taboo, it is denied or sequestered into hospitals and funeral homes and exists outside of everyday life. And yet, others argue that death is “a very badly kept secret” with hundreds of books published on the topic in the last few decades, most of them claiming that we cannot talk about death. This disconnect leads some to argue that there is a revival of death happening instead.
My research sits at the nexus of this tension; I attended death cafés around Southern Ontario to explore the dialogues that emerge in spaces set out to break the presumed taboo around death. At a death café people are meant to “drink tea, eat cake, and talk about death.” The objective of these events is “to increase awareness of death with a view to helping people make the most of their finite lives.” This statement, from the official death café website, assumes that facing death will help to make sense of, and give perspective to, life. I explore how and if death cafés accomplish their intended purpose of encouraging existential discussion, and if such a discussion was in fact beneficial to the attendees. I argue that the discussions at the death cafés I attended did not seem to fulfill the purpose stated on the website of encouraging existential discussion about one’s own death. I then situate this observation in the context of broader understandings of the denial of death thesis generally and in terms of residual Victorian romanticism and attachment to others.

abstract: Thesis

abstract: Master of Arts (MA)

abstract: Is death denied or revived in contemporary western society? Many people believe that death is a taboo subject, and to break this taboo people have hosted death cafés, which are pop up events where people are meant to talk about death. My research involved attending death cafés around southern Ontario to find out what happens at death cafés: who attends and what is talked about. Much of the literature in the social sciences on death and dying focuses on institutional settings where death is present, or focuses on how death is coped with in “other” cultures. This thesis explores how people think about death in casual settings where death is not immediately present.


title: Star Formation in the Galactic Context: A Quantitative Study

contributor:
Wadsley, James
Couchman, Hugh
Physics and Astronomy

abstract:
The processes that impact star formation operate not only on molecular cloud scales, but on the scales of full galaxies. This implies that the full galactic environment is crucial to the study of star formation. As observations and empirical relations on this scale become increasingly more detailed, simulations lag behind, still unable to explain the origins behind the Kennicutt-Schmidt relation, for example. We investigate star formation in the full galactic context through a series of isolated galaxy simulations. We favour purposefully controlled setups so that we can perform a systematic study of the drivers of star formation and the theoretical underpinning behind the formation of bound structures that lead to star formation.

We demonstrate the key role of pressure in regulating the star formation rate. We extend this to galaxies that include far-ultraviolet (FUV) heating implemented using radiative transfer. These simulations, the first of their kind, show that FUV heating is not sufficient to regulate star formation. Generally, we find that the scale height is a key driver in maintaining vertical hydrostatic balance. Simulated galaxies that do not resolve the scale height will be unable to explain fundamental relationships, becoming increasingly similar to semi-analytic models where all important relationships are imposed.

We develop a new method to study the formation of bound structure: we seed turbulent perturbations of known wavelength and velocity in quiet galaxy disks. The linear theory is a good approximation for the early phases of structure growth, which has a finite window to occur; the shear timescale. We find that clumps can form not just through central condensation but through rotation-driven fission and the fragmentation of tidal tails, a novel result. We find that these bound clouds, the direct progenitors of star clusters, do not exceed $\sim10^9$ M$_{\odot}$ in galaxies of gas mass up to $\sim5\times10^{10}$ M$_{\odot}$.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: UNDERSTANDING THE EFFECT OF POSTNATAL EXPOSURE TO ANTIBIOTICS ON THE MICROBIOTA-GUT-BRAIN AXIS

contributor:
Forsythe, Paul
Medical Sciences

abstract:
Introduction. A 100 trillion bacteria reside in the human gastro-intestinal tract. These microbes are involved in the gut-brain axis. Disruption to their pattern of growth can alter gut-brain communication, and thus health and disease outcomes. Probiotics are being explored for their therapeutic use relative to early-life insults that alter the microbiota, such as antibiotics and stress. In our study, we use a clinically relevant dose of PenicillinV, a beta-lactam antibiotic, and Lactobacillus rhamnosus JB-1, a probiotic, to examine their postnatal effects on long-term immune, nervous, and enteroendocrine status.
Methods. BALB/c male and female mice were orally feed, from postnatal day (PND) 14 to 21, twice a day for seven days with either PBS and antibiotics, antibiotics and probiotic,  or PBS for both feeding times. For the first experiment, all mice were subjected to behavior tests that measured their anxiety-like and social behavior at PND 70. Fecal samples were collected for microbial diversity analysis 24 hours and 3 weeks after treatment cessation. For the second experiment, mice were sacrificed at PND 22. After decapitation, tissue and serum was collected for analysis of immune, neurochemical, and enteroendocrine markers for both experiments.
Results. Antibiotic altered microbial diversity in the short and long term. Male mice exposed to antibiotics showed a decrease in social behavior associated with immune changes. JB-1 attenuated the effects on behavior and immunology. Sex-dependent antibiotic-induced differences in tight junction expression in the brain and ileum were prevented by concurrent JB-1 treatment.
Conclusion. Our findings support the principle that early-life perturbations to the gut microbiota can affect other physiological systems in a transient and lasting way. The results also confirm the psychoactive and immune-modulatory function of JB-1 in attenuating immune and behavioral defects induced by antibiotic treatment. The clinical relevance of the antibiotic treatment further shows that the postnatal period is a critical window for microbial, immune, and brain development and is vulnerable to environmental challenges.

abstract: Thesis

abstract: Master of Science in Medical Sciences (MSMS)


title: PagP-Mediated Signal Transduction:Link to the dmsABC  Operon in Escherichia coli.

contributor:
Bishop, Russell
Chemistry and Chemical Biology

subject: PagP, lipid A, phospholipids

abstract: In Escherichia coli, the integral outer membrane (OM) enzyme PagP covalently modifies lipid A by incorporating a phospholipid-derived palmitate chain to fortify the OM permeability barrier. We perturbed the bacterial OM in order to activate PagP and examined if it exerts transcriptional regulation through either of its extracellular or periplasmic active sites. Data from RNA-seq revealed the differential expression of 50 genes upon comparing the E. coli imp4213 (lptD4213) strain NR760∆pagPλInChpagP (shortened to NR760λp in this work), in which PagP is constitutively activated, and the mutant NR760λpY87F carrying the periplasmic residue mutation Y87F. 40 genes were upregulated, and encoded proteins related to anaerobic processes, whereas 10 genes were downregulated, and encoded proteins related to aerobic processes.  RNA-seq was followed by a study of differential gene expression using the NanoString nCounter system. Results confirmed a 2.7-fold upregulation of dmsA when we compared the strains NR760λp to NR760λpY87F.  We also found a 2.5-fold repression of dmsA transcription when we compared the lptD+ parental strain NR754λp to NR754λpS77A carrying the mutation S77A in the extracellular active site of PagP.  We then investigated dmsA transcription using a lacZ reporter gene in plasmid pRS551-lacZ.  High basal β-galactosidase activity became attenuated in pagP null mutants. OM perturbation using pentamidine showed that dmsA transcription was repressed. Complementation of the chromosomal ∆pagP deletion with a single copy pBADGr plasmid, expressing PagP under the control of an arabinose-inducible promoter, restored dmsA β-galactosidase activity. We observed partial complementation with the downstream cspE gene, which identified a polar effect of the ∆pagP allele. Through deletion of rpoS, rcsB, cpxA, cpxR, pmrA, pmrB, and fadD in E. coli MC4100, we showed that β-galactosidase activity of pdmsA-lacZ was affected by all of these regulators. Our results indicate that these regulators are involved in PagP-mediated regulation of dmsA transcription under aerobic conditions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Incorporating Historical Data via Bayesian Analysis Based on The Logit Model

contributor:
Narayanaswamy, Balakrishnan Jr
Mathematics and Statistics

subject:
Bayesian analysis
historical data

abstract: This thesis presents a Bayesian approach to incorporate historical data. Usually, in statistical inference, a large data size is required to establish a strong evidence. However, in most bioassay experiments, dataset is of limited size. Here, we proposed a method  that is able to incorporate control groups data from historical studies. The approach is framed in the context of testing whether an increased dosage of the chemical is associated with increased probability of the adverse event. To test whether such a relationship exists, the proposed approach compares two logit models via Bayes factor. In particular, we  eliminate the effect of survival time by using poly-k test. We test the performance of the proposed approach by applying it to six simulated scenarios.

abstract: Thesis

abstract: Master of Science (MSc)


title: ENGINEERING HYDROGEL CHEMISTRIES AND STRUCTURES FOR BIOMEDICAL APPLICATIONS

contributor:
Hoare, Todd
Sheardown, Heather
Chemical Engineering

abstract: Hydrogels have been widely applied for drug delivery and tissue engineering given their highly relevant physiochemical and biological properties such as hydrophilicity, biomimetic mechanics, low protein absorption, and non-toxicity. However, the practical and effective use of hydrogels in such applications demands the development of methods to (1) rapidly identify hydrogel compositions that can exhibit a desired set of properties and (2) fabricate hydrogels with the internal morphology, degradability, and mechanics required to match the needs of the application. In this thesis, new strategies for high-throughput hydrogel synthesis and characterization techniques and reactive electrospinning of reactive pre-polymers directly into hydrogel nanofibers have been developed and applied for drug delivery and tissue engineering applications, using hydrazide and aldehyde-functionalized precursor polymers as the basis for investigations. To optimize injectable hydrogels for protein delivery, high throughput robotics were used to mix 14 different types of precursor polymers functionalized with hydrazide or aldehyde groups to create 126 hydrogels within 30 mins. Coupled with the development of corresponding high-throughput screening strategies for measuring key hydrogel physicochemical and pharmacokinetic properties (e.g. swelling, degradation, mechanics, transparency, and protein release), correlations were identified between hydrogel composition and protein release. To better mimic the nanofibrous nature of native extracellular matrix, a reactive electrospinning method was developed to co-extrude hydrazide and aldehyde-functionalized polymers based on poly(oligoethylene glycol methacrylate) (POEGMA) into well-defined nanofibrous hydrogels with fast swelling responses. Reactive electrospinning of thermoresponsive POEGMA precursors resulted in fast reversible temperature-responsive macroporous nanofibrous hydrogels that could be reversibly thermally cycled and act as highly effective substrates for cell growth and triggered delamination. The inclusion of cells within the precursor polymers enables the direct development of cell-loaded scaffolds that maintain very high cell viability even when dried, facilitate effective cell proliferation, and can be stored in liquid nitrogen for a long period without any added cryoprotectants while preserving high cell viability, representing a “ready-to-use” tissue patch for the clinic. Finally, the morphologies of electrospun scaffolds can also be tuned from microbeads to nanofibers by controlling concentration of POEGMA in the system, enabling precise nanostructural control over the resulting scaffolds.  Overall, this work provides new insight into the design of hydrogels with more biologically-relevant properties for clinical applications.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Evaluating the Mechanical Response of Novel Synthetic Femurs Representing Osteoporotic Bone

contributor:
Quenneville, Cheryl
Mechanical Engineering

subject:
Sawbones
Finite Element Analysis
Mechanical Response
Osteoporotic
Femur

abstract:
Osteoporosis is a disease prevalent in older adults, characterized by increased bone porosity resulting in significant fracture risk. Orthopaedic implants are designed and validated against cadavers from the general ‘healthy’ population, but little is known about their response in osteoporotic bone. Orthopaedic implants can also be developed using synthetic bones, if they have been demonstrated to be representative of healthy bone, and offer a number of advantages. To date, no synthetic femur has been validated for the osteoporotic population. The purpose of this study was to assess novel synthetic femurs for representing this population.
	Custom jigs were manufactured to test two sets of ten synthetic femurs and five isolated cadaveric femurs in four-point bending, torsion, axial compression, axial failure, and screw pullout, using an Instron mechanical testing machine to record load-displacement data. Statistical significance was found in bending, torsion, and screw pullout between both synthetic sets and cadavers using one-way ANOVA with post-hoc Tukey analysis. In all instances, the synthetic femurs had lower coefficients of variation than natural specimens.
Both synthetic and cadaveric femurs were CT scanned prior to testing. The data were used to measure key anatomical details and to develop a series of numerical models of the synthetic bones, using Materialize Mimics® and ABAQUS® software, evaluated using axial and bending data. The model was modified by reducing cortical thickness and modulus in an attempt to make the synthetic model better represent osteoporotic bone.
Establishing synthetic femurs as suitable replacements for osteoporotic bone allows for improved orthopaedic implant development. The digital model constructed allows the synthetic to be further analyzed, improving expected response of the synthetic bones. These synthetic bones could provide a foundation for development of effective orthopaedics for this population.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
The considerations and parameters in the design of orthopaedic implants for osteoporotic bone are relatively unknown. Orthopaedic implants can be evaluated with synthetic bones, which offer a number of advantages to natural specimens, assuming they are sufficiently representative of natural bone. No physical synthetic model yet exists that represents an osteoporotic femur.
	In the present work, synthetic femurs were subjected to bending, torsion, axial compression, and screw pullout and compared to natural osteoporotic specimens. The synthetics were significantly different to natural specimens in bending, torsion, and screw pullout. A numerical model was created, evaluated, and tested in finite element software alongside modified models with reduced modulus and cortical thickness to assess stiffness. Recommendations were made to improve the accuracy of a future synthetic model.
	The synthetic femurs tested were not representative of osteoporotic femurs, but may be feasible alternatives with minor modifications and could be useful in future orthopaedics design.


title: THE EXPERIENCE OF HOMELESS YOUTH WITH LEARNING/DEVELOPMENTAL/ INTELLECTUAL DISABILITIES IN AN ONTARIO SCHOOL SYSTEM FROM AN INTERPRETIVE & CRITICAL APPROACH

contributor:
Baker Collins, Stephanie
Social Work

subject: Homelessness; Youth; Homeless youth; Disabilities; Learning disabilities; Developmental disabilities; Intellectual disabilities; School system; Interpretive approach: Critical approach; Ontario; Hamilton

abstract:
According to the literature, youth experiencing with either homelessness or disabilities face severe barriers throughout their life-time which would negatively impact their physical development, psychological development, and mental health, but also contribute to a vicious circle of homeless and poverty. However, the intersection between homeless youth with learning, developmental and/or intellectual disabilities (LD/DD/ID) in the school system has rarely been explored. This population is invisible to the school system which indicates an urgency in identifying and understanding their experience at school.
This research, as a part of the Partnering for Change initiative, aimed to provide some insight into the socially constructed problems which cause barriers for this invisible population. In this study, an interpretive lens and a critical approach were adopted as a guide to data analysis and as a means to identify constructed barriers based on the interviews with homeless youth with LD/DD/ID in Hamilton, Ontario, Canada.
The data on homeless youth with LD/DD/ID was analysed for impacts on relationships, academic performance, and the effects of invisibility on multiple levels of their school life. The data also revealed the way schools respond to disabilities and homelessness. In the discussion I investigate the way policy, funding structure and implementation of support are significantly affected by the neoliberal context with its emphasis on market-driven pedagogy and individuals conceptualized as agents of self- capitalization. This thesis argues for a better alternative, as referenced from Finland. The Finnish approach emphasizes human rights, equality, and inclusion, and aims to demonstrate how changes in fundamental beliefs and values can construct a barrier-free and supportive education system for everyone.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Body Relationship and the Fat Female Experience

contributor:
Fudge Schormans, Ann
Social Work

subject: fat studies, critical disability theory, feminist theory, embodiment, fat oppression, size oppression, dehumanization, acceptance, resistance, empowerment, disembodiment

abstract:
Background: Fat people are subjected to oppression including medical “obesity” rhetoric and fat discrimination which may affect their ability to experience an embodied relationship with their bodies.
Aims: The aim of this study was to discover how self-identified fat female-bodied people understand their relationship with their bodies.
Methods: Six participants were recruited for semi-structured interviews which were then analyzed in a constant comparative method.
Findings: Five themes emerged from the data: dehumanization, acceptance of (the fat) body, empowerment, resistance, and dis<-->embodiment. Relationship with (the fat) body was identified by the participants as fraught with tension in a context that involves considering the positionality of “non-normative’ bodies, the value and importance of community, and a high degree of effort.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: CROSSLINKING AND CHARACTERIZATION OF PRESSURIZED GAS EXPANDED LIQUID POLYMER MORPHOLOGIES TO CREATE MACROPOROUS HYDROGEL SCAFFOLDS FOR DRUG DELIVERY AND WOUND HEALING

contributor:
Hoare, Todd
Chemical Engineering

subject: supercritical fluids, hydrogels, wound healing, macroporous hydrogels, structured hydrogels, starch, pectin, alginate, chitosan, ibuprofen, in situ gelation, gas expanded liquids

abstract:
The development of structured macroporous hydrogels are of great interest in many industries due to their high permeabilities, large surface areas and large pore volumes.  In drug delivery and wound healing applications, these macropores may theoretically be utilized as large drug reservoirs to deliver anti-inflammatory drugs to a wound site, while simultaneously absorbing exudate and maintaining a hydrated environment in which the wound may heal.  However, current methods of generating macroporous structured hydrogels are low-throughput, expensive, and require the use of organic solvents, salts, and other additives that are difficult to remove from the crosslinked hydrogel scaffold.  In contrast, the Pressurized Gas eXpanded liquid (PGX) processing technology, patented by the University of Alberta and licensed for all industrial applications by Ceapro Inc., has been shown to generate purified and exfoliated biopolymer scaffolds in a less expensive and more efficient way.
Herein, the tunability of the PGX processing method was investigated in depth, varying solvent/anti-solvent ratios, nozzle mixing volume, polymer molecular weight, and polymer concentration to examine the resulting effects on produced polymer morphologies.  PGX-processed chitosan and alginate scaffolds were stabilized as bulk hydrogels through post-processing crosslinking methods using anti-solvents, solid-state chemistries, and/or rapid gelation kinetics.  The mechanical strength, swelling/degradation kinetics, affinity for protein uptake, and cytotoxicity of these stabilized scaffolds were subsequently examined and compared to hydrogels produced without the use of PGX processing.  Furthermore, in situ crosslinking methods were explored, in which alginate and poly(oligoethylene glycol methacrylate) polymers were shown to form stable aerogels during the standard PGX processing method.  Finally, the PGX apparatus was reconfigured to enable the impregnation of a model hydrophobic drug into pre-processed polymer scaffolds via circulation of supercritical CO2.  The total loading was calculated and the release kinetics from loaded-scaffolds examined.
In conclusion, this work outlines a novel method of creating structured macroporous hydrogels from PGX processed biopolymers with the potential to provide improved drug loadings and sustained release profiles.  It is expected that this work will provide a basis for a great deal of research into the further stabilization of scaffolds for use in other applications, the investigation of a larger range of bioactive molecules for impregnation and release, and the exploration of PGX hydrogel scaffolds for in vivo wound healing.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Pseudomonas aeruginosa Prairie Epidemic Strain Population Dynamics and Evolution of Disease in Cystic Fibrosis Airways of Adult Patients

contributor:
Surette, Michael
Biochemistry and Biomedical Sciences

subject:
Cystic Fibrosis
Comparative genomics
Population dynamics

abstract:
The lower airways of patients with chronic airway diseases including cystic fibrosis
(CF) are colonized by diverse communities of microorganisms. Over-time the
airways of some 60% of CF patients become permanently colonized and dominated
by Pseudomonas aeruginosa. Chronic infection of P. aeruginosa has been
associated with a decline in pulmonary function, worse prognosis, and eventual
patient mortality. Although P. aeruginosa evolves within the CF airways resulting
in complex populations, the mechanism by which these complex populations
contribute to disease progression is not well understood. Here we show diversity
among isolates by observed changes in genome sequences of a strain of
P. aeruginosa, known as Prairie Epidemic Strain (PES). Using whole genome
sequencing and comparative genomics we identified a large core genome across
195 PES isolates from 57 CF patients of the Calgary Adult Cystic Fibrosis Clinic
(CACFC) where 88% of the pangenome was categorized as core genes. Single
nucleotide polymorphism (SNPs) mutations were shown to be the largest
contributor of diversity at the nucleotide level compared to other polymorphism
types consisting of 87% of the total polymorphisms present across the 195 PES
isolates. CRISPR arrays and mobile elements such as prophage and plasmids
demonstrate this strain of P. aeruginosa was stable over 30 years. In a second
aim, I show variation in the populations of P. aeruginosa across an exacerbation
event further highlighting the complexity of the lung bacterial community. Distinct
populations of P. aeruginosa at the onset and resolution of an exacerbation within
a single CF patient were identified by SNPs. These results a model where adaptive
radiation as well as natural mutations contribute to the heterogeneity and
diversification within populations of P. aeruginosa in CF patients. Understanding
the evolution and population structure of PES through the identification of
important genes and mutations through the clinical course of an exacerbation can
aid in identifying new targets for patient treatment of P. aeruginosa in CF.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Cystic fibrosis is a life-threatening disease characterized by cycles of stability and
respiratory illness. Bacterial species within the lungs of these patients are the main
contributor to disease progression. I investigated a specific transmissible epidemic
strain, Pseudomonas aeruginosa Prairie Epidemic Strain, using a unique collection
of samples provided by collaborators at the adult cystic fibrosis clinic in Calgary.
Using these samples, I first explored the differences between patients over a period
of 34 years. I hypothesized that similar changes in genome sequences will be
observed in multiple patients with a possible commonality in disease progression.
Second, I explored the role this bacterial pathogen may play in cycles of respiratory
illness. I hypothesize that a specific bacterial subpopulation could initiate these
cycles and be identified by changes at the genome level. This research provides
further knowledge of an epidemic strain of cystic fibrosis.


title: Acute Psychosocial Stress Reactivity and Risky Decision-making in Gambling Disorder

contributor:
Balodis, Iris M.
Neuroscience

abstract: Gambling activates the hypothalamic-pituitary-adrenal and sympathoadrenal medullary (SAM) axes as evidenced by increased levels of cortisol in recreational gamblers, and in norepinephrine in problem gamblers. Further, Gambling Disorder (GD), the first non-substance related disorder in the DSM-V, is linked with stress-related conditions and psychiatric disorders. Few studies investigate interactions between stress reactivity and decision-making in GD; therefore, this study explored the effects of acute psychosocial stress induction on risky decision-making. Twenty-eight healthy control participants (HC) and 38 individuals with GD completed the Balloon Analogue Risk-taking Task (BART) and Iowa Gambling Task (IGT) following a stressor. Saliva samples, used to assess biomarkers cortisol and α-amylase, and gambling urge measures were collected at baseline, post-stressor and post-task. Results show stressor-induced increase in self-reported mood disturbance in the HC group from baseline, but not in the GD group. Stressor-induced cortisol reactivity, however, did not differ between or within groups. Unexpectedly, the stressed GD group showed reduced α-amylase reactivity following the stressor, and this decrease was significantly greater relative to the stressed HC group. The stressed GD group also made significantly less risky choices on the BART, relative to the non-stressed GD group. Further, increased α-amylase reactivity correlated with increased risky decision-making (blocks 4 and 5) on the IGT in this group. The GD group did not report stressor-induced changes in gambling urges. Overall, the differential effects of acute stress in GD is indicative of altered SAM function, possibly a result of norepinephrinergic dysfunction, that may be suggestive of changes in risk/reward appraisal and dysregulated motivational processes.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Gambling Disorder (GD), the first non-substance-based (“behavioural”) addiction, may also encompass dysregulated stress responses, including different levels of biomarkers cortisol and alpha-amylase (a proxy measure of the hormone norepinephrine), and impaired risky decision-making. To date, few studies investigate the effects of acute stress on these biomarkers and risky decision-making in those with GD. This thesis explores psychosocial stressor-induced release in biomarkers and its effects on risky-decision-making. In addition, those with GD also experience gambling urges, which can influence subsequent gambling behaviour. Other potent motivators for gambling include wanting to escape negative emotions and boredom; therefore, understanding the effects of stress reactivity in GD are of great importance. The findings have broader implications for informing the neurobiology of stress processing, decision-making and motivation, as well as in guiding potential treatment options and strategies.


title: I am sorry, we are sorry: A critical analysis of discursive strategies in contemporary public apologies

title: Discursive strategies in contemporary public apologies

contributor:
Stroinska, Magda
Cognitive Science of Language

subject:
pragmatics
public apology
discourse analysis
communication strategy
speech act theory
linguistics

abstract:
In the current ‘Age of Apology’, public apologies have become everyday occurrences; from corporate CEOs to Hollywood celebrities to political figures, the adage of ‘never apologize, never explain’ has been eschewed in favour of ‘always apologize, always explain’. In a society where news travels at the speed of the internet, and content can go ‘viral’ in hours, there are new pressures for all public figures to apologize when things go wrong. These public apologies are available for public consumption almost immediately after an offense, released through mainstream media (e.g. broadcast news, physical/online newspapers) or, as is becoming more frequent, over social media (i.e. Twitter, Facebook, and Instagram). Some researchers (e.g. Kampf, 2009; Thaler, 2012) have suggested that public apologies are not true apologies as defined by Speech Act theory – that they may serve another social function, but not to apologize. Such ‘fauxpologies’ are made without meeting the traditional felicity conditions for the speech act of apology (Ogiermann, 2009). If this is the case, what makes a public apology (in)felicitous?
The aim of this thesis is to describe what makes a public apology felicitous. I present a critical analysis of the discourse strategies used in three types of public apologies – corporate, celebrity, and historical political – examining how these discursive strategies are used according to varying contextual factors using Critical Discourse Analysis and Speech Act theory as a framework. To counter the claim that the discourse strategies used in public apology do not meet the felicity conditions for the speech act of apology, I present evidence that, despite using some non-apology strategies, many public apologies are felicitous. However, I argue for the adoption of a revised set of felicity conditions as laid out by Murphy (2014, 2015), which can properly encompass public apology as a performative speech act. This study also extends the framework of semantic formulae previously used in apology analysis (Blum-Kulka & Olshtain, 1984; Olshtain & Cohen, 1983) to include ‘fauxpology’ strategies particularly useful in examining public apologies, which provides a more robust description of how public apologies are performed.

abstract: Thesis

abstract: Master of Science (MSc)


title: Beyond Spa Days and Self-Care: An Examination of Workplace Culture and Wellness in Child Protection Work

contributor:
LaRose, Tara
Social Work

subject:
Compassion Fatigue
Vicarious Trauma
Child Welfare
Workplace Culture
Worker Wellness
Neoliberalism
Burnout
New Public Management
Social Work
Performance Management
Managerialism
Organizational Change
Austerity
Chronic Stress

abstract:
Social work practice in child welfare is widely acknowledged as a challenging field. Most social workers who choose to enter this field of practice do so with the knowledge that they will be exposed to difficult, at times traumatic, situations.  They expect that the job will be stressful; that they will need to manage complex and challenging cases; and they will do so with few resources and often little public support.  They also expect to be supported by their workplace in carrying out their mandated roles, however increasingly, a disconnect exists between those administer child welfare services and their understanding of front-line work (Herbert, 2007).  Social workers’ wellbeing in child protection practice is directly affected by workplace culture; a subject that is often unexamined when addressing the high turnover of staff in the field.  Instead, workers who leave child welfare practice – as well as though who stay while experiencing compassion fatigue or vicarious trauma - are viewed by administrators as being unsuitable for the work, a way of individualizing systemic issues (La Rose, 2009).
This study sought to understand the ways that the culture of the workplace contributes to worker experiences of vicarious trauma, compassion fatigue and burnout.  Survey research was conducted anonymously with child protection workers in Southern Ontario to understand the aspects of workplace culture that child welfare workers find helpful and supportive in managing the day-to-day of their work, as well as in addressing mental health in the workplace. From the seventy responses that were received, a number of themes emerged including Workplace Culture; Worker Well-being; Agency Support; Safety; Systemic Issues and Training.
In this study, participants identified informal peer support and reflexive, supportive supervision as key areas that either sustained their practice or worsened their experiences.  Workplace culture emerged as a significant factor in determining worker well-being and resiliency. Survey participants provided examples that illustrated clearly the ways in which neo-liberal policies and austerity measures have contributed to a workplace culture in which workers expressed feeling replaceable, devalued, and in precarious situations.  Cutbacks to services and staffing, crushing workload and increasingly complex client situations contribute to the sense of being overwhelmed experienced by workers.  Addressing experiences of compassion fatigue and vicarious trauma requires a paradigm shift from exclusively individual responsibility and towards an understanding of the broader systemic context and organizational responsibility (Antonopoulou, 2017; Mathieu, 2012; van Dernoot Lipsky, 2009). Organizational strategies to support worker wellbeing are shown to be significant factors in addressing and preventing compassion fatigue and vicarious trauma, ultimately preventing burnout and staff turnover.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Are physical activity and exercise associated with cardiometabolic health in early pregnancy?

contributor:
Atkinson, Stephanie
Medical Sciences

subject: exercise

subject: pregnancy

subject: physical activity

subject: cardiometabolic health

subject: maternal health

subject: inflammation

subject: physical activity recommendations

subject: SOGC/CSEP Clinical Practice Guidelines for Exercise in Pregnancy

subject: accelerometer

subject: PARmed-X for Pregnancy

subject: step count

abstract:
Background: Physical activity (PA) is an important component of a healthy pregnancy and has consistently been associated with improved weight management and a reduced risk of pregnancy complications. While the percentage of pregnant women meeting PA guidelines internationally is alarmingly low, no such data exists for the Canadian population. PA in pregnancy may also be a useful intervention for preventing and
managing cardiometabolic dysfunction, but research in pregnancy is limited.
Objectives: 1) To describe the PA and exercise habits of women in early pregnancy and assess the percentage of women meeting SOGC/CSEP guidelines for exercise in pregnancy; 2) To determine the association of PA with maternal cardiometabolic health in early pregnancy.
Study Design: Maternal blood samples, and PA, dietary, and adiposity measures were collected from a subset of women in early pregnancy (12 – 17 wk gestation) upon enrollment in the Be Healthy in Pregnancy RCT. Fasted blood samples were analyzed for glucose, triglycerides, insulin, leptin, adiponectin and C-reactive protein (CRP). Self-reported and objectively measured PA were assessed using the PARmed-X for Pregnancy
and an accelerometer. PA was quantified by three parameters: daily step count, energy expenditure (kcal/day) and meeting the SOGC/CSEP recommendations.
Results: For the 198 participants of age 31 ± 4 years; BMI 25.4 ± 4.7kg/m2; at 13 ± 2 wk gestation (mean ± SD), 19.2% reported not exercising in early pregnancy. Approximately half of participants met the minimum SOGC/CSEP recommendation (15 min, 3x/wk), but only 14.2% met the preferred SOGC/CSEP recommendation (30 min, 4x/wk). Meeting the preferred recommendation was associated with lower CRP. Daily step count and energy expenditure (kcal/day) were not significantly associated with glucose, triglycerides, insulin, leptin, adiponectin or CRP. Percent body fat and a higher diet quality were associated with some of the cardiometabolic biomarkers.
Conclusion: In a healthy pregnant cohort, while the majority had PA below
recommendations, measured PA was not associated with most cardiometabolic biomarkers thus cardiometabolic risk in early pregnancy was low.

abstract: Thesis

abstract: Master of Science (MSc)


title: Decision Game: A Serious Gaming Approach to Understanding Household Flood Risk Mitigation Decision-Making

contributor:
Yiannakoulias, Niko
Geography and Earth Sciences

subject: Flood Risk Mitigation Serious Games Decision Making Insurance

abstract:
Household flood risk mitigation is an important component of Integrated Flood Risk Management. Voluntary household decisions about whether or not to structurally mitigate or insure can directly and indirectly influence vulnerability to the flooding of a community. Serious games can augment existing data collection methods in the flood risk context by operating in the space in between stated and revealed preference, through observing decisions as opposed to asking abstract hypothetical questions, while allowing for complete control over experimental conditions.

We look to answer the question of which individual and contextual factors contribute to the decision to mitigate against floods. We gather household decision-making data using a serious game role-play experiment named the Decision Game. Participants spent about 20 minutes making decisions about where to live and how to distribute limited income, given geographical information, including flood risk, about the city. We use a generalized linear mixed modelling approach to analyze the data. Among other findings, we see that experiencing an in-game flood had a strong positive effect, compared to a much weaker effect of a participant having experienced a real-life flood; our key observation is that incentivizing flood risk mitigation should be done quickly following a flood event. We find that real-life low-income individuals were no less likely to implement in-game mitigation measures than their higher-income counterparts, suggesting that subsidies to address an income barrier may be an effective method of encouraging low-income household mitigation.

We apply the model to a case study of Calgary, Alberta finding that the insurance market could maintain cross-subsidization after a flood, making insuring higher risk areas more feasible. Moreover, we find that Calgarian policymakers should be encouraged to limit subsidy coverage to high-risk areas to avoid inefficient use of funds in low-risk areas which were projected to have the clear majority of program uptake.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: We develop a research tool to help understand what drives people to protect themselves against flooding. This tool is a computer-based role-playing game experiment in which people take on the role of a homeowner tasked with choosing where to live and how to distribute their income. We log the decisions that people make in the game and use statistical analysis to figure out which factors are important in driving the decisions to insure against floods and to invest in protective structural measures. We find that experiencing a flood in the game has the largest positive effect on these decisions. The results of the model are used to inform a case study where we investigate potential outcomes of policy decisions in Calgary, Alberta. The development of this research tool and the findings contributes to optimizing policies to improve flood risk management through household interventions.


title: INTRODUCING ASPECTS INTO SOFTWARE ARCHITECTURES BY GRAPH TRANSFORMATION

contributor:
Kahl, Wolfram
Maibaum, Tom
Computing and Software

subject:
ASPECT INTRODUCTION
DIAGRAM TRANSFORMATION
GRAPH TRANSFORMATION
SOFTWARE ARCHITECTURE

abstract:
While aspect-oriented programming (AOP) addresses the introduction of “aspects” at the code level, we argue that addressing this at the level of software architecture is conceptually and methodologically more adequate, since many aspects, that is, “crosscutting concerns”, are formulated already in the requirements, and therefore can be dealt with in a more controlled manner in the “earlier” phase of software architecture design.

We use the precise concept of software architectures organised as diagrams over a category of component specifications, where the architecture semantics are defined as a colimit specification (Fiadeiro and Maibaum, 1992). The diagram structure suggests aspect introduction via an appropriate variant of graph transformation. Singlepushout rewriting in categories of total homomorphisms has already been used previously for different kinds of “enrichment” transformations; we identify “zigzag-path homomorphisms” as producing a category where many practically useful aspect introductions turn out to be such single-pushout transformations, and present the relevant theorems concerning pushout existence and pushout construction.

Practical aspect introduction (e.g., privacy) always breaks some properties (e.g., “message can be read in transit”); therefore, aspect introduction transformations cannot be designed to be semantics preserving. Our special categorical setting enables selective reasoning about property preservation in the transformed specifications, and property introduction from the introduced aspects. This method enables us to detect and resolve both conflicts and undesirable emergent behaviors that arise from aspect introduction or interaction.

We have developed tool support to introduce and analyze aspects at the system architecture level through zigzag graph transformation. The implementation is based on Hets, an initiative of Mossakowski et al. (2007) and consists of two key parts: the language development and the zigzag transformation. The development of the MFLogic language is based on the specification language Casl (Astesiano et al., 2002) and uses the logic introduced by Fiadeiro and Maibaum (1992). Besides parsing, syntactic and static semantics correctness checking, the language inclusion in Hets opens the door for automatic property preservation analysis and conflict detection. The main contribution of the tool support in Hets is the automatic aspect introduction and the “result architecture” generation by applying our zigzag graph transformation.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Autophagy and Muscle Dysfunction in Lysosomal Storage Diseases

title: Autophagy and Myogenic Differentiation in Lysosomal Storage Diseases

contributor:
Igdoura, Suleiman
Biology

subject: Lysosomes, LSD, autophagy, myogenesis, lysosomal storage diseases, myogenic differentiation

abstract: Lysosomal storage diseases (LSDs) are metabolic diseases which occur as a result of a deficiency of one of the essential lysosomal enzymes, called glycohydrolases. A mutation in the gene encoding one of these enzymes leads to an accumulation of unwanted substrates, resulting in a variety of clinical manifestations. A common symptom found in LSDs is skeletal muscle dysfunction, which includes muscle weakness, atrophy and loss of muscle mass. The genes for lysosomal hydrolases are well characterized; however, much less is known about how mutations in these genes affect the cell and lead to the muscle dysfunction observed. One pathway of interest is autophagy; it has been shown to be essential for maintenance of skeletal muscles. This study sought to investigate the impact of LSDs on autophagy and how this may potentiate muscle dysfunction. We utilized in-vivo and in-vitro models of Sialidosis, Sandhoff Disease, and GM1-Gangliosidosis in order to assess autophagy and its impact on myogenic differentiation in skeletal muscles. Our results demonstrated that autophagy is induced upstream (ULK1 phosphorylation) but is inhibited at the autophagosome to lysosome fusion (p62 upregulation) in LSDs. We also found that myoblast fusion and myogenic differentiation are impaired. We conclude that blocking autophagy impairs myogenic differentiation, which potentiates the muscle dysfunction observed in LSDs. This work highlights autophagy as a new pathway of interest and possible therapeutic target to alleviate muscle dysfunction in LSDs, and other similar neurodegenerative diseases.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Lysosomal storage diseases (LSDs) occur because of a deficiency of lysosomal glycohydrolases. A common symptom found in LSDs is skeletal muscle dysfunction. Little is known about how a deficiency of these enzymes leads to the clinical manifestations observed. However, one pathway of interest is autophagy. This study sought to investigate the impact of LSDs on autophagy and how this may potentiate muscle dysfunction. We utilized in-vivo and in-vitro models of LSDs to assess autophagy and its impact on myogenic differentiation in skeletal muscles. We demonstrated that autophagy is induced and blocked, and that myoblast fusion and myogenic differentiation is impaired. We concluded that the induction and block of autophagy impairs myogenic differentiation, which potentiates muscle dysfunction.


title: Social, Cultural, and Ecological Systems' Influence on Community Health and Wellbeing.

contributor:
Doubleday, Nancy
Health Policy

subject:
community health and wellbeing
social, cultural, and ecological system
community-based research
Nunaut

abstract:
An individual’s health is influenced by more than just the health care system, but also in large part by the social determinants of health. People exist within broader social, cultural, and ecological systems which influence their health outcomes through the social determinants of health. This doctoral dissertation examines social, cultural, and ecological systems to understand several factors that support and hinder community health and wellbeing to inform future policy. This dissertation incorporates a mix of methodological approaches across four interrelated research studies to better understand direct and indirect factors influencing community health and wellbeing. In doing so, this thesis is divided into four research chapters.
Study 1 consists of a community-based research project that examines how food security, cultural continuity, and community health and wellbeing are connected through the sharing of harvested country food in Chesterfield Inlet, Nunavut, Canada. Based on this understanding we can demonstrate how climate change and increased shipping along the inlet affects the community as a result of changes in marine mammals and harvesting activities.
Study 2 presents a logistic regression that models how cultural continuity variables impact self-rated health for participants living in Inuit Nunangat in Canada. This model uses the Arctic Supplement questions of the Aboriginal Peoples Survey to compare measures of cultural continuity to traditional measures based on government services. This study demonstrates an important link between cultural continuity and self-rated health for Inuit living in Inuit Nunangat.
iv
Study 3 contains a case study of different implementation successes and challenges of Locally Managed Marine Areas globally. These cases are used to understand how community member involvement as stakeholders in marine resource decision-making not only aligns with existing local and Indigenous ways of management, but also can enhance biodiversity as well as local livelihoods.
Finally, Study 4 uses ontology engineering methods to represent the results from the first three studies. This study demonstrates how this novel method can be used to illustrate the interconnectedness of results from different disciplines using diverse data sources and through the creation of different scenarios.
Taken together, these studies provide timely insights regarding the ways policy can support or hinder efforts to improve community health and wellbeing and adapt to climate changes.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The goal of this doctoral dissertation was to develop a better understanding of how social, cultural, and ecological systems impact community health and wellbeing in various contexts. Findings indicate climate and shipping changes impact Chesterfield Inlet, Nunavut through the relationship between food security, cultural continuity, and community health and wellbeing. Relatedly, harvesting activities, access to country food, satisfaction in Inuit governance, and community involvement all increase the probability that an Inuk living in the Arctic has good or great self-rated health. Additionally, Locally Managed Marine Areas, an approach to marine resources management that includes community members as key stakeholders, not only aligns with existing local and Indigenous management practices, but can also support biodiversity and increased catch of various species. Finally, by representing these research results in a single model called an ontology, we can make educated guesses about how these different studies are interconnected. The insights gained from this work can be adopted by decision- makers to create supports for and remove barriers to improved community health and wellbeing and community efforts to adapt to changes.