VictorJuiz/thesis huggingface dataset:
Fatigue and Mechanical Damage Propagation in Automotive PEM Fuel Cells
Keywords: Cohesive Elements
Damage Propagation
Fatigue
Finite Element Modeling
Polymer Electrolyte Membrane Fuel Cell
Vibration

Polymer electrolyte membrane (PEM) fuel cells are generally exposed to high magnitude road-induced vibrations and impact loads, frequent humidity-temperature loading cycles, and freeze/thaw stresses when employed in automotive applications. The resultant mechanical stresses can play a significant role in the evolution of mechanical defects in the membrane electrode assembly (MEA). The focus of this research is to investigate fatigue challenges due to humidity-temperature (hygrothermal) cycles and vibrations and their effects on damage evolution in PEM fuel cells. To achieve this goal, this thesis is divided into three parts that provide insight into damage propagation in the MEA under i) hygrothermal cycles, ii) external applied vibrations, and iii) a combination of both to simulate realistic automotive conditions. A finite element damage model based on cohesive zone theory was developed to simulate the propagation of micro-scale defects (cracks and delaminations) in the MEA under fuel cell operating conditions. It was found that the micro-defects can propagate to critical states under start-up and shut-down cycles, prior to reaching the desired lifespan of the fuel cell. The simultaneous presence of hygrothermal cycles and vibrations severely intensified damage propagation and resulted in considerably large defects within 75% of the fuel cell life expectancy. However, the order of generated damage was found to be larger under hygrothermal cycles than vibrations. Under hygrothermal cycles, membrane crack propagation was more severe compared to delamination propagation. Conversely, the degrading influence of vibrations was more significant on delaminations. The presence of an anode/cathode channel offset under the combined loadings lead to a 2.5-fold increase in the delamination length compared to the aligned-channel case. The developed model can be used to investigate the damage behaviour of current materials employed in fuel cells as well as to evaluate the alternative materials for the next generation of fuel cell development.
Epistemic Representation in Science and Beyond
Keywords: information
models
representation

In this dissertation, I define epistemic representations to be tools for gaining information about aspects of the target systems they represent, which I call as phenomena of interest. I ask: in virtue of what is one vehicle of representation, rather than another, selected when the user's aim is to learn about such a phenomenon? I argue that examining the nature of epistemic representation promises to be more fruitful than the present debate about scientific representation. I look at two sorts of contexts in which epistemic representations are used: those in which little or nothing is known about the phenomenon of interest, and those in which this phenomenon is already relatively well understood. To see how epistemic representations are used in the first sort of context, I examine the histories of the discoveries of protein and DNA structure. I argue that the process of structure determination may be understood as one of successively eliminating possible structures through the consideration and interpretation of pieces of evidence about this structure. I show that consulting stereochemical rules--chemical laws dictating permissible structures--before x-ray diffraction photographs of the molecules was the strategy likeliest to yield the correct structure most efficiently. I argue that the construction of physical molecular models further contributed to the efficiency of this strategy by helping scientists to consider stereochemical rules first and acting as a cognitive aid, enabling the consideration of many such rules at once.When the phenomenon of interest is already fairly well understood, I argue that an epistemic representation is successful to the extent that it contains sufficiently accurate information about the phenomenon and is able to convey it to the user in a way that makes this information readily available to her. A vehicle may qualify as a mere (but not necessarily successful) epistemic representation of its target system only if it is chosen with the aim of faithfully representing the phenomenon of interest. I show that this is a feature that epistemic representation shares with our ordinary notion of interpretation.
In vitro Toxicological Study of Particulate Matter and the Relationship with Physicochemical Properties of Particles
Keywords: Health Effects
In virto
Particulate matter
Physicochemical properties

Numerous epidemiological and toxicological studies have reported substantial evidence linking airborne particulate matter (PM) exposure to adverse health effects. PM-initiated oxidative stress at the cellular level is considered a potential mechanism contributing the pathogenesis of cardiopulmonary diseases. However, there remain major gaps in knowledge about the relationship between toxicity and the physicochemical properties of PM. The main objective of this study was to investigate the effects of different source-related and size-fractionated ambient PM on cellular responses to identify relevant physicochemical properties (e.g., size, composition, and redox activity) of particles that could be responsible for the effects. Another objective was to evaluate whether progressive oxidative stress-induced cellular responses (i.e., activation of antioxidant defence at lower level of oxidative stress, followed by inflammatory response, and ultimately cell death as the stress level increases) represent a potential biological mechanism affecting cells in all size fractions. For this purpose, different source-related Standard Reference Materials (industrial, urban, and diesel PM), and size-fractionated ambient coarse, fine, and ultrafine PM (collected from Toronto, Canada) were tested. A549 cells were exposed to different PM doses for certain duration. After exposure, the cells were analyzed for different biological responses and the responses were then compared with available physicochemical properties of the PM. This study demonstrated that exposure to PM can initiate mass-dependent antioxidant, proinflammatory, and cytotoxic responses. Among the different source and size-related PM, transition metal-enriched industrial and coarse PM exhibited the greatest cytotoxic effect, whereas organic compound-enriched ultrafine PM caused significant induction of antioxidant defence. Correlation analyses with chemical constituents suggested transition metals and organic compounds were associated with the observed biological responses. However, the observed biological responses could not be explained by particle size or composition alone. Both of these properties should be considered when explaining the observed PM toxicity. This study also showed that ultrafine PM initiated the hypothesized progressive biological responses, whereas different biological pathways might be involved in coarse and fine PM. Overall, this study demonstrated that the cellular responses varied substantially after in vitro exposure to PM from different sources and ultrafine PM could be as potent as coarse and fine PM.
Prevalence and Correlates of HIV, Syphilis, Hepatitis B, Hepatitis C Infections and Sexual Behaviours of Men who have Sex with Men in Two Cities in Nigeria
Keywords: Hepatitis B
Hepatitis C
High risk sexual behaviours
HIV
MSM
Nigeria

Globally, men who have sex with men (MSM) continue to be disproportionately affected by the HIV pandemic. However, prior to this study, very little was known about the magnitude and factors that heighten MSM's vulnerabilities to HIV and other STIs in Nigeria. A cross-sectional survey was administered to 1,125 consenting MSM in Lagos and Ibadan recruited through modified respondent driven strategy. Sero-prevalence of HIV, hepatitis B (HBV), hepatitis C (HCV) and syphilis and levels of unprotected anal intercourse (UAI) were determined using data adjusted for network size and unweighted data for the pooled sample. Correlates of HIV, HBV, HCV and UAI were examined using multiple logistic regression analyses. Results revealed relatively young sexually active men who engaged in multiple concurrent sexual relationships with both men and women. More than half of the men self-identified as bisexual, and 44.4% as homosexual. High levels of risky sexual behaviours were demonstrated with over two-thirds of MSM in Ibadan (65.5%) and Lagos (69.7%) reporting UAI with their male partners in the previous 6 months. Correlates of URAI included homosexual identity, older age, lack of social support, and douching. Prevalence of previously undiagnosed HIV infection were four times higher in Lagos 12.7% (95% CI 10.6-15.0), and Ibadan 11.2% (95% CI 5.7-16.2) than the national HIV prevalence among Nigerian men. Prevalence of HBV (10.1% and 18.0%); HCV (2.8% and 4.3%) and current active syphilis (0.03%) infections in Lagos and Ibadan respectively were also high. Correlates of HIV were URAI and UIAI with men and women, condom breakage, homosexual identity, increasing age, employment, sexual activities with non-African white men and internalized homophobia. Bisexual identity, UIAI with male sex partners, and low self-esteem were associated with HBV infection. Correlates of HCV were URAI and reported sex with men who had lower educational status. This study confirms the existence of MSM who engage in risky behaviours with very limited access to appropriate HIV and STI prevention services.
Trade and Economic Growth: A Latin American Perspective
Keywords: Development
Free Trade
Latin America

Although the World Trade Organization has played a significant role in world trade and in the development of world economies it has not been able to evenly distribute the gains from trade across both the developed and developing world. With the effects of the 2008 financial crises still encumbering economic growth for many countries, Mercosur members face serious challenges to accessing world trading markets, attracting foreign direct investment and promoting competition for domestic industries. As such, for Mercosur to recapture the economic growth experienced in the 1990s Mercosur must abandon hopes of achieving success through the special and differential treatment provisions within the WTO and instead pursue a trade liberalization agenda, one which includes negotiating a free trade agreement with the European Union and implementing comparative advantage based structural, social and political reforms.
Sexuality Education in Paraguay: Using Human Rights and International Policies to Define Adolescents' Right to Sexuality Education
Keywords: human rights
Paraguay
policies
sexuality education

This dissertation explores the issue of sexuality education through the lens of international human rights obligations and policy commitments, with a focus on the Paraguayan context. It identifies relevant international human rights instruments and international policy commitments related to sexuality education, and explores their legal and political value. Making use of human rights analytical frameworks, it elaborates on Paraguay's concrete obligations with regards to sexuality education. It argues that standards reveal a clear link between sexuality education and adolescents' enjoyment of their fundamental rights. Taking a substantive equality approach, it argues that the lack of sexuality education policies has a disproportionate effect on certain groups. The dissertation concludes by offering concrete standards for the implementation of sexuality education policies.
Opening the Doré to Proportionality: Discretionary Administrative Decisions and the Charter
Keywords: administrative
constitutional
dore
oakes
review
standard

In Doré v. Barreau du Québec, 2012 SCC 12, the Supreme Court of Canada revisited the debate over how courts should review administrative discretionary decisions implicating Charter rights. In short, the Court held that such decisions should be reviewed using a values-based, administrative law approach focused on proportionality, one that asks whether the decision-maker has properly balanced the relevant Charter values and statutory objectives at issue. This thesis will explore several problematic aspects of Dore's reasoning and implications, and dispute the Court's claim that there is conceptual harmony between the traditional Oakes analysis and its new approach to reviewing the constitutionality of administrative discretionary decisions. In doing so, this thesis will illustrate how the Doré framework subverts the guarantee that the Charter's rights and freedoms are subject only to "such reasonable limits prescribed by law as can be demonstrably justified."
Religious Contentions in Modern Iran, 1881-1941
Keywords: Baha'i
Babi
Shi'i
Azali
Reformist Theologians
Shaykh Hadi Najmabadi
Afghani
Sangalaji
Dolgoruki
Riza Shah
Kharaqani
Russia
Iran
Qajar
Pahlavi

It has been suggested that in mid-twentieth century Iran, anti-Bahā’ism played a seminal role in transforming Iranian Shī‘ī religious piety into the political ideology known as Islamism. This dissertation charts this transformation by offering a historical genealogy of the politicization of anti-Bahā’ism. Using the post-colonial theory of Othering as a theoretical framework, and discourse analysis and microhistory as methodologies, it interrogates a wide range of hitherto neglected primary sources to analyze how Bahā’īs were gradually branded the nation’s internal Other. It tests the thesis it was mainly through the Othering of Bahā’īs that of the two national identities that struggled for supremacy in the decades that immediately followed the Constitutional Revolution, the pendulum swung towards a religious national identity and away from an ethnic-language based national identity (which had been officially dominant in the 1920s and 30s) as the nation approached the midpoint of the twentieth century. The process of Othering the Bahā’īs had at least three components; 1) religious, carried on by the traditionalist theologians; 2) institutional and formal, sanctioned by the state; and 3) political, the result of a joint and gradual process in which Azalīs, former Bahā’īs and reformist theologians all played a role. This process reached its culmination with the widespread publication of The Confessions of Dolgoruki which resulted in a fundamental paradigm shift in the anti-Bahā’ī discourse. With the widespread impression of Bahā’īs as spies of foreign powers, what up to that point constituted a sporadic theme in some anti-Bahā’ī polemics now became the dominant narrative of them all, including those authored by traditionalist clerics. Consequently, as Iran entered the 1940s, the process that would transform Islamic piety to political ideology was well under way.
The Anatomy of an Efficient Synthesis: The Total Synthesis of Agelastatin A and Related Chemistry
Keywords: Total Synthesis
Natural Product
Electrocyclization
Selective acylation
N-Methylurea
Lithium carboxylate coupling

This thesis provides a summary of research conducted towards the total synthesis of agelastatin A since September 2005 in the laboratories of Professor Robert A. Batey at the University of Toronto. The manuscript is divided into four chapters. Chapter one gives an overview of the progression of total synthesis as both science and art, with an emphasis on the importance of efficiency as exemplified through domino and multicomponent reactions. The biological importance of agelastatin A is presented, as well as an overview of its various literature syntheses, with a focus on problematic issues within the numerous end-games utilized. Chapter two describes the construction of the agelastatin core through a domino, multicomponent ring-opening/electrocyclization reaction, which gives trans-4,5-diaminocyclopent-2-enones in good to excellent yields from furfural and secondary amines. Efforts to the core through nitroso-Diels–Alder and aza-Achmatowicz chemistry are also discussed. Chapter three outlines the failed progression of N-protected derivatives of the core to agelastatin A with a focus on palladium-catalyzed deallylations, oxazolidinone ring-openings mediated by aluminum amides or diiodosilane, and amide formation through the coupling of carbamoyl imidazolium salts and lithium carboxylates. The chemistry of trimethylaluminum towards the synthesis of 1,3-diones and the coupling of carbamoyl imidazolium salts with 1,3-diones were also investigated. Chapter four describes the successful synthesis of agelastatin A through the elaboration of an N-deproteced core, providing the shortest published route to the natural product. To achieve this, the first general, neutral amide coupling of lithium 5-bromopyrrole carboxylate was developed, which will prove fruitful for the installation of this key moiety in a number of pyrrole aminoimidazole alkaloids. Also developed was a crystalline chemical equivalent of methyl isocyanate. Its ease of handling and stability should lead to its use over the volatile and toxic methyl isocyanate for fine-chemical industrial processes and small-scale syntheses alike.
Risks Inside and Beyond Institutional Walls: Organisational Responses to Substance Use in Canadian Federal Prisons
Keywords: prisons
substance use
organisations
drug interdiction
risk management
harm reduction

My dissertation examines substance abuse policy and related practices within Canadian federal prisons. I triangulated across three data sources: 16 interviews with former Correctional Service of Canada (CSC) senior administrative officials, former frontline staff, and external stakeholders; publicly available CSC documents; and testimony from a relevant House of Commons Standing Committee study. Thematic analysis was used to examine themes of interest and emergent themes. I attempted to interview current CSC employees, but access was denied. I turn my access experience into a case study and use reputational risk as a conceptual tool, whereby my proposed research is interpreted as a risk to be managed from the organisation’s point of view. I view CSC’s enhanced drug interdiction response through an organisational risk management lens and examine “unintended”, negative effects that have resulted. Five key themes emerged: 1) continued efforts by offenders to bring substances into prisons; 2) climate of tensions and violence; 3) offenders switching substances; 4) health-related harms; and 5) culture of distrusting visitors. I thread through my analysis two divergent framings – a dominant, safety-reaffirming framing versus one that challenges enhanced interdiction. I provide an in-depth account of political barriers that prevent implementation of prison-based harm reduction programs. Four interrelated issues are central to the politics: 1) a narrower definition of harm reduction in corrections; 2) the Conservative government with a tough-on-crime agenda; 3) strong union opposition; and 4) stakeholder perceptions of ongoing constraints. Contributing knowledge as an external researcher is made difficult by an overprotective organisation with formal research access that appears to favour certain kinds of research over potentially critical research. A downside of such protectionism is the curtailment of studying innovative approaches. Viewing CSC as a complex organisation reveals how embedded practices and cultures are resistant to change, even when the traditional response (i.e., zero tolerance) has adverse effects. CSC could be at an impasse in terms of overcoming political and operational logics that align to oppose in-prison harm reduction services. Despite a highly challenging policy environment, future researchers can move forward by asking new questions and devising strategic ways of entering the political-operational dialogue.
Characterizing the Role of the DNA Damage Response in Class switch recombination
Keywords: Class switch recombination
DNA damage response

B cells undergo secondary antibody diversification to elicit an effective immune response. Secondary antibody diversification generates antibodies with high affinity for the cognate antigen, and antibodies of different classes. Different classes of antibodies mediate different effector functions, enabling the humoral response to be fine-tuned to the infection at hand. The different classes are generated by a process called class switch recombination (CSR), which requires the generation and repair of double-stranded DNA breaks (DSBs) at the antibody heavy chain locus, and relies on the 53BP1-dependent DNA damage response (DDR). However, the molecular mechanism and function of DDR in CSR is not fully understood. To characterize the role of DDR in CSR, we first established an in vitro CH12F3-2 mouse B cell line/ RNA interference system and used this system to demonstrate that the DDR factors RNF8 and RN168, play a role in CSR. Using this system, we then developed and conducted a genome-wide screen to identify novel CSR factors, followed by a secondary screen to identify DDR factors among the CSR candidates. Based on this study, we selected one candidate, the Drosophila enhancer of yellow 2 homolog (Eny2), for further characterization. Eny2 is a structural component of the H2B-deubiquitination module of the SAGA complex. We found that Eny2 likely acts downstream of the DSBs generated for CSR, and that Eny2 might act with the SAGA complex in mediating H2B-deubiquitination to facilitate CSR. We also provide evidence that, in addition to its role in CSR, Eny2 is important for H2B-deubiquitination upon irradiation-induced DNA damage, and may be required for optimal DNAPK activation.
Investigation of the Mechanism of Idiosyncratic Drug-induced Liver Injury
Keywords: Idiosyncratic drug reactions
reactive metabolites
immunotoxicology
immune mediated
tolerance
bioactivation
covalent binding
autoimmunity
liver injury
hepatotoxicity
liver failure
animal model
autoantibodies
anti-drug antibodies
adaptation
T helper 17 cells
natural killer cells
interleukin 10

Idiosyncratic drug reactions represent a special problem because of their unpredictable nature, and idiosyncratic drug-induced liver injury (IDILI) is a major reason for drug withdrawal. Our objective was to investigate the mechanism of IDILI caused by isoniazid and amodiaquine. Isoniazid-induced liver injury was believed to be due to bioactivation of N-acetylhydrazine, a metabolite of isoniazid; however, that conclusion was based on a rat model with characteristics very different from isoniazid-induced IDILI in patients. I found that isoniazid is directly bioactivated and covalently binds to hepatic proteins; furthermore, mice are a better model for human isoniazid metabolism than rats. We found that mild isoniazid-induced liver injury in patients is associated with an increase in Th17 cells and IL-10-producing T cells. I also found anti-isoniazid antibodies in the serum of patients with isoniazid-induced liver failure. These results suggest that isoniazid-induced IDILI is immune-mediated rather than metabolic idiosyncrasy as previously believed. Treatment of mice with isoniazid failed to lead to significant liver injury. We postulated that this was because of immune tolerance; however, attempts to develop an animal model using mice with impaired immune tolerance were unsuccessful. Treatment of mice with amodiaquine resulted in mild liver injury that resolved despite continued treatment similar to the more common type of IDILI observed in humans. In this model, liver injury is immune-mediated with the initial injury mediated by natural killer cells, while the resolution of liver injury appears to involve the adaptive immune system because resolution was slower in Rag-/- mice. In summary, my studies have resulted a change in what is considered to be the mechanism of isoniazid-induced IDILI. We have developed an animal model of mild immune-mediated amodiaquine-induced liver injury, but we failed to develop a valid animal model of severe IDILI, most likely because the dominant immune response in the liver is tolerance.