VictorJuiz/thesis huggingface dataset:
Kant's Philosophy of Religion and Climate Change
Keywords: climate change
climate ethics
environmental ethics
Kant
philosophy of religion
religion

This thesis argues that Kant’s Religion within the Boundaries of Mere Reason (1793) may be applied to climate change issues. This thesis makes use of James DiCenso’s interpretation of Kant’s philosophy of religion (2011, 2012), which argues that Kant’s key text on religion conveys a social and political vision. This thesis addresses both traditional religious worldviews and secular political movements engaged in climate politics. It argues for the need to ethically assess these social formations’ evolving responses to the climate crisis. The failure (to date) of religious traditions to adequately address the climate crisis, and possible reasons for this, are addressed. Examples of social formations, ideologies, and religious responses examined include consumerism, environmental theology, religiously motivated climate change denial and dispensationalist theology, as well as the secular climate justice movement. Kant locates the source of many of our problems in the power of choice and determining ground of morality. In this sense, his ethical system is distinct from the neo-Marxist interpretation of “systems of power.” The theory of what DiCenso refers to as “shared representations” of “supersensible” cognition is helpful for understanding the dynamics of belief that inform complex social and political formations. Kant’s philosophy of religion may be of value for those trying to understand how religions and political ideologies that employ powerful symbols and ideals play a role in the unfolding of historical events.
Towards Engineering a Programmable Universal Transcription Activation System
Keywords: Programmable
Protein Engineering
Synthetic Biology
T7 RNA Polymerase
Zinc Finger

Developing the next generation of medical, agricultural and sustainability biotechnology is limited by the complexity of natural biological systems; namely the dynamics and interactions between genetically encoded parts. Synthetic biology seeks to reduce the complexity by replacing natural biological components with simplified, synthetic control systems. Transcription is a major control step for biological systems and thus subject to a number of successful efforts for synthetic regulation, primarily in eukaryotes. These systems, however, rely primarily on host components and thus are still largely entangled in the complex host processes. Additionally, prokaryotes, which represent a large fraction of hosts in industrial biotech, still lack the programmable activation systems of eukaryotes. Furthermore components are not readily transferable between the two, which is important for simplifying design. Thus, we sought to design a programmable transcription activation system in prokaryotes by combining the wealth of information on the strong phage T7 RNA Polymerase (RNAP) with modular and programmable DNA binding proteins. Importantly, T7 RNAP is a self-contained RNAP that interacts minimally with the host and is thus orthogonal. We reasoned that reducing T7 RNAPs natural affinity for DNA would allow for control of initiation through programmable DNA binding proteins (DBPs). We show that indeed, T7 RNAP can be programmed to transcribe synthetic promoters via fusion to programmable DNA binding proteins and this interaction can be tuned with various molecular manipulations of promoter and protein. Furthermore, the set of DBPs can be expanded by replacing the fusion with a split T7 and DBP facilitated through programmable leucine zipper domains. This culminates in T7 RNAPs that are programmable and small molecule inducible.
Maximal Interval Handgrip Exercise for Blood Pressure Modification Among Post-menopausal Women
Keywords: blood pressure
isometric handgrip exercise
post-menopausal women

Handgrip (HG) exercise training reduces resting blood pressure (BP) but is infrequently employed. Common HG protocols prescribe sustained grips at moderate intensities of 20-50% of one’s maximum intensity, an approach that requires real-time force monitoring. This limits exercise accessibility, an especially important consideration for at-risk cohorts (ie. older women) who display low adherence to traditional aerobic exercise options. This research describes the creation and evaluation of a novel HG strategy: the Maximal INTerval (MINT) strategy. MINT is highly accessible, easy to use, and participant-informed. Testing of acute cardiovascular responses to MINT among older women (n=20) with normotension demonstrated moderate BP increases during the exercise bout (systolic BP: 24 ± 3mmHg, diastolic BP: 11 ± 2) that swiftly returned to resting values following exercise cessation. In comparison to a commercially available strategy (ZONA), the MINT intervention took less time to complete and required less exercise effort, yet participants perceived greater exertion. Neither HG intervention produced post-exercise alterations to either resting forearm blood flow or peak reactive flow. The concomitant creation of the MINT grip tool followed stages of new product development with structured focus groups (n=20). The result was a participant-preferred tool with a small grip circumference, slight grip contouring, soft foam covering, and black colour. Finally, the MINT exercise protocol and MINT grip tool were combined and the impact of MINT HG training was assessed via measures of both exercise efficacy and exercise effectiveness. Among a cohort of post-menopausal women (n=17) with a range of resting BPs and various co-morbidities, eight weeks of MINT training effectively reduced resting systolic BP (128 ± 14mmHg to 122 ± 14mmHg), improved sample entropy (a measure of heart rate complexity) (1.36±0.10 to 1.62±0.11), and reduced cardiovascular reactivity to a serial subtraction stressor (21.7 ± 20.5mmHg to 19.0 ± 13.8mmHg, Measures of adherence were high for this at-home handgrip training program (96.9%) with participants indicting high levels of both exercise effort and exercise enjoyment. Collectively, the participant-informed MINT training strategy is a safe, efficacious, and effective exercise option for post-menopausal women to reduce resting blood pressure.
Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging
Keywords: Blood Pool Agent
Contrast Agents
Human Serum Albumin
Magnetic Resonance Imaging
Mn Porphyrin
Targeted Imaging

Magnetic Resonance Imaging (MRI) provides detailed anatomical information and has become indispensable for a wide range of medical applications. To further broaden our diagnostic capabilities, about 40% of clinical MRI scans are performed with the administration of MRI contrast agents (CAs). There are, however, two major limitations to the current clinical CAs which are mainly small Gd-based chelates. 1) They exhibit low relaxivities at high magnetic fields, requiring high dose in modern clinical MRI scanners and 2) the release and accumulation of Gd ions in vivo is correlated with Nephrogenic Systemic Fibrosis (NSF) in some patients with renal dysfunction. These challenges motivate us to develop a new class of CAs using more biocompatible metal species. Paramagnetic Mn-porphyrin (MnP) was the building block of choice as it is stable and exhibits high relaxivities at high fields. This thesis focuses on the development of MnP MRI CAs for blood pool and targeted imaging purposes. In Chapter 2, a water-soluble MnP dimer, MnP2 was designed as a high-relaxivity T1 agent. Preliminary in vivo study of MnP2 showed prolonged blood circulation, desirable for MR angiography (MRA). In Chapter 3, MnP2 was systematically evaluated as a BPA in vitro and in vivo. Using different spectroscopic methods, MnP2 was found to form a tight and non-covalent interaction with HSA. Via a competitive binding study using ligands with known HSA binding site, results suggest MnP2 to be bound in subdomain IB. In Chapter 4, a second generation dimer, m-MnP2 was developed. m-MnP2 exhibited slightly lower relaxivity than MnP2, likely due to its smaller size. The relaxivity of m-MnP2 did not increase upon binding to HSA and is similar to that of the MnP2â HSA complex. This suggests that both CAs are potential BPAs and that the tumbling rate may be excessively slow. (Chapter 5) Towards the goal of active targeted imaging, a versatile covalent protein tagging MnPNCS was synthesized. Successful tagging of multiple MnPs onto HSA was demonstrated and the resulting MnPâ HSA exhibited excellent blood pool properties. Overall, through rational design, the highly sensitive MnPs have shown promise as the next generation Gd-free MRI CAs.
Mass Spectrometry Coupled with Laser Spectroscopy for Probing the Intrinsic Photophysical Properties of Light-Harvesters
Keywords: Chlorophyll
Fluorescence
Gas phase
Ion Spectroscopy
Mass Spectrometry
Porphyrin

In the pockets of proteins and in solution, light-harvesting molecules are subject to a variety of interactions which fine-tune their photophysical properties. This makes it difficult to distinguish which of their photophysical features are intrinsic (due to their structure) versus those that arise out of these specific environmental interactions. Thus, there has been considerable interest in probing the photophysical properties of a number of different light-harvesters, especially porphyrins, in vacuo. A convenient in vacuo approach is through the use of optical spectroscopy combined with ion trapping mass spectrometry. For one, light-harvesters are easily introduced intact into the gas phase using electrospray ionization and can be subsequently isolated based on their mass-to-charge ratio and stored using the capabilities of the ion trap. However, the ion number densities achieved using this method are well below those required to perform conventional absorption measurements. Thus, alternative techniques relying on the measurement of an event occurring in response to photon absorption are employed. These include fluorescence excitation (FE) and photodissociation (PD) action spectroscopy. The work in this dissertation features an evaluation of these commonly employed action spectroscopy techniques and subsequently applies them to investigate the intrinsic photophysical properties of a select series of biologically-significant light-harvesters. Thus, Chapter 2 begins by presenting a back-to-back comparison of the absorption spectrum measured for Rhodamine 100 using FE and PD action spectroscopy. Equipped with this knowledge, PD action spectroscopy is used to characterize the intrinsic spectroscopic features of the well-known porphyrin chlorophyll a (Chla) including when it is adducted with different alkali metal cations. Significantly, this chapter also featured the first report of fluorescence emission from gaseous Chla and demonstrated how it may be â turned offâ via protonation. PD action spectroscopy was also used to characterize a heme-related porphyrin, n-methyl mesoporphyrin IX (NMM), so as to uncover the intrinsic relationship between its charge state and spectroscopic profile. Together, these investigations progress our understanding of how and to what extent environmental interactions are responsible for fine-tuning the photophysical properties of these porphyrins while also specifically highlighting how optical spectroscopy combined with mass spectrometry is a powerful approach for addressing these questions.
Characterizing effects of prebiotics and human milk oligosaccharides on the intestinal epithelial barrier
Keywords: Fructans
Human milk oligosaccharides
Kinome
Necrotizing enterocolitis
Prebiotics

Prebiotics are non-digestible compounds that enhance the growth of certain microbes within the gut microbiota and confer benefits on the host, but whether they can also elicit direct immune-regulatory effects is unknown. This thesis addresses this gap through three specific aims: (1) to characterize the effects of prebiotics on the intestinal epithelial barrier, (2) to delineate the underlying signaling mechanisms underlying barrier- and immune-regulation, and (3) to evaluate the effects of human milk oligosaccharides using relevant models of human disease. In the first part of this thesis, two prebiotics, inulin and short-chain fructooligosaccharides (scFOS), were tested in an in vitro bacterial challenge system with enterohemorrhagic Escherichia coli serotype O157:H7. Inulin and scFOS increased the resistance of Caco-2Bbe1 monolayers, reduced permeability and increased the expression of select tight junction proteins. These changes were associated with the activation of protein kinase C isoform Î´ - a host kinase enzyme that controls multiple cell functions. The second part of this thesis expands on PKCÎ´ signaling and characterizes the global signaling of inulin and scFOS using Caco-2Bbe1 cells. This was performed using a kinome peptide array to profile kinase phosphorylation levels, which revealed several immune pathways and functional networks that were regulated by prebiotics. These findings were then validated in vivo using a neonatal endotoxemia model, which showed that prebiotics dampened intestinal inflammation without altering the composition of gut microbiota. In the third part of this thesis, I demonstrate a unique mechanism whereby HMOs promote barrier function by inducing the production of mucus. This finding was confirmed using a neonatal mouse model of necrotizing enterocolitis (NEC), where HMOs prevented the development of NEC by enhancing intestinal goblet cell production. Taken together, these data demonstrate that prebiotics are not biologically inert. In fact, prebiotics directly trigger host cell signaling to alter epithelial barrier integrity and gut inflammation â indicating previously unrecognized mechanisms of prebiotics and HMOs.
Biogenic-Anthropogenic Interactions in Secondary Organic Aerosol Formation and Health Effects of Atmospheric Organic Aerosol
Keywords: Aerosol Miscibility
Biogenic-anthropogenic Interaction
Health Effects
Secondary Organic Aerosol
Sulfur Dioxide

Secondary organic aerosol (SOA) formed from oxidation of volatile organic compounds (VOCs), comprises a major fraction of atmospheric submicron particulate matter, which is crucial for global climate change and human health. While biogenic VOCs are naturally emitted and cannot be directly controlled, field measurements and satellite observations have shown that biogenic SOA (BSOA) formation correlates well with anthropogenic pollutants and may be anthropogenically controlled. In this work, the formation of the “anthropogenically controllable BSOA” was examined. BSOA from α-pinene ozonolysis was investigated in the presence of laboratory-generated or ambient organic aerosol such as Toronto ambient particles. It is shown that SOA was not equally miscible with all organic species. Aerosol mixing thermodynamics in the atmosphere is composition dependent. Based on laboratory observations, an empirical framework using bulk elemental ratios was developed to predict atmospheric organic miscibility and SOA yield enhancements. Besides organic aerosol, interactions between BSOA formation and SO2 was also examined. Synergistic effects were observed between BSOA formation and SO2 oxidation through Criegee and peroxide chemistry under atmospherically relevant RH conditions. In addition to the physicochemical properties of SOA, health impacts of SOA were examined. An atmospheric simulation reactor (ASR) was developed to investigate the health effects of air pollutants by permitting controlled chronic in vivo exposure of mice to combine particulate and gaseous pollutants at ‘real-life’ concentrations. Results show that daily exposure to SOA from naphthalene photooxidation led to increased airway hyperresponsiveness (AHR) to methacholine in a dose-dependent manner. Multi-pollutant exposures with ozone and/or NO2 in conjunction with a sub-toxic concentration of SOA resulted in additive effects on AHR to methacholine. Inflammatory cell recruitment to the airways was not observed in any of the exposure conditions, indicating the increased AHR was not associated with airway inflammation and may occur through other mechanisms.
Reducing the computational cost of UV reactor performance calculations
Keywords: mixedness
Shannon entropy
UV disinfection
wastewater disinfection

The performance of a UV reactor can be described using the concept of UV dose, which is the product of the residence time of a microbe or particle and the intensity, or fluence rate, of UV light hitting that particle in a reactor. The process to model the reactor performance of a UV reactor, hereby known as the reactor performance process (RPP), consists of three separate models: 1) the computational fluid dynamics (CFD) model: the UV fluid flow field modeling, typically performed using commercial software; 2) the fluence rate model: the physics of the intensity of the UV irradiation; and 3) the reactor performance model: RED, for example, an organism-specific metric for delivered UV dose. The combination of these three models to numerically estimate the UV reactor performance has never been subjected to scrutiny for relevancy, efficiency, nor computational expense. The aim of this thesis was to examine and reduce the computational cost of the RPP and as a result of this work, in certain scenarios, the cost of calculating the reactor performance of a UV reactor was reduced from over 300 billion steps to less than 12,000. This was accomplished by optimizing each of the models of the RPP: by focusing on four key factors in CFD modeling (initial condition, mesh size, time step, and particle tracking), the computational cost of that step was reduced by five times; by systematizing fluence rate model implementation, the computational cost of that step was reduced by at least nine times; by using mixing as a proxy for reactor performance in certain lamp orientations, the computational cost was reduced by over 99%. Further scenarios need to be examined where mixing can be used as a proxy for reactor performance; this optimization offered the best reduction in computational cost. This optimization would reduce the overall computational cost of the RPP for more general UV reactors but also provide a different perspective from which to examine the performance of UV reactors.
The Association of Health Literacy and Self-Efficacy to Cancer Chemotherapy Self-Management Behaviours and Health Service Utilization
Keywords: Cancer
Health Literacy
Neoplasm
Self-Efficacy
Self-Management

Abstract Background Increasing demands on Canadaâ s healthcare system require patients to take on more active roles in their health [1]. Effective self-management has been linked to improved health outcomes; and there is evidence that effective behaviours are linked to health literacy, however, this link has had minimal testing in the cancer context [2, 3]. Firmly establishing this link is important because those aged 65 years and older comprise the majority of the users of the cancer care system, and these individuals are most at risk for inadequate health literacy [4]. As such, the cancer care system may require increased self-management by patients least able to do so and, in doing so, fail to provide adequate care and incur substantial cost [5-7]. Objectives To examine the association between health literacy and cancer chemotherapy self-management behaviours (CSMB) and health service utilization (HSU) and test the hypothesized relationship between self-efficacy and these outcomes. Design Cross-sectional survey. Methods Participants completed a questionnaire package with socio-demographic information and validated measures of health literacy, cancer coping self-efficacy, symptom severity, symptom interference, CSMB score, and HSU. Multivariate modeling using hierarchical linear regression was used to examine the association of health literacy to CSMB health services utilization. Results Education and language spoken at home explained a significant amount of variance (22.5%) in health literacy score. Health literacy was not significantly associated with any of the dependent variables in multivariate analysis. The analyses conducted to explore the association of self-efficacy to CSMB score and HSU showed that self-efficacy contributed to explaining variation in CSMB score but did not contribute significantly to explaining HSU. Conclusion This study provides new knowledge that advances understanding of the association of health literacy and self-efficacy on CSMBs and HSU in the context of cancer care.
The Aesthetics of Redemption in fin de siècle Literature and the Arts
Keywords: Aestheticism
Friedrich Nietzsche
Oscar Wilde
Religion of Art
Secularization
Walter Pater

This dissertation explores a cluster of texts in fin de siècle aestheticism from a Nietzschean perspective, questioning whether their claims about art and life are, at bottom, world-affirming or world-denying. I argue that the aesthetic worldviews of Friedrich Nietzsche, Walter Pater and Oscar Wilde manifest a struggle against Christian (especially Protestant) values, a struggle that, however, periodically and sometimes fatally capitulates to the otherworldliness it seeks to overcome. Chapter 1 delineates the theoretical framework for my investigation. Drawing on the work of Nietzsche and Max Weber, I begin by examining the diverse strains of otherworldliness, some more implicit than others, that run through the aesthetic theories of Arthur Schopenhauer, Richard Wagner, Joris-Karl Huysmans, and Charles Baudelaire. In Chapter 2, I consider the evolution of Nietzsche’s own aesthetic philosophy from his youthful embrace of the Wagnerian Gesamtkunstwerk to his mature view that the Dionysian artist exemplifies the individual who has vanquished all decadent urges to be redeemed from worldly suffering, and is thus able to affirm life through his work. Chapter 3 demonstrates how Pater’s contemplative aestheticism, which originally sets out to counteract the antipathy to the ‘here and now’ associated with ascetic Protestantism, ends up reproducing the hierarchy between the temporal world and a more desirable ‘otherworld.’ In the fourth and final chapter, I suggest that Wilde overcomes the otherworldliness of Paterian aestheticism but only by advancing a secularized version of aesthetic incarnation. This dissertation argues that aestheticism is neither an inevitable offshoot of secularization nor a particular phase of Christian theology, but rather a struggle to work through the complex moral and philosophical dilemmas that arise from the rigorous commitment to valuing life on its own terms.