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Elucidating Mechanisms of Enhanced dsRNA-Nanophytoglycogen Innate Immune Responses in Healthy Human Cells
No full textImmunostimulatory nucleic acids, such as long double-stranded RNA (ds)RNA, can stimulate innate immune responses in a non-sequence specific manner. These molecules are recognized by pattern-recognition receptors in the cytoplasm, endosome, and on the cell surface. Activation leads to the production of mediators of innate immune pathways, including type I interferon and proinflammatory cytokines. Although these receptors are present in all cells, their role in non-immune cells is often overlooked due to their lower level of responsiveness. Nanocarriers can enhance these nucleic acid-mediated responses, allowing for exploration of innate immune pathways in non-immune cells. Nanoparticles as carriers of nucleic acids can improve cellular delivery, protect from nuclease degradation, and concentrate nucleic acids, enabling multivalent cellular presentation for a more potent response. In my thesis, poly inosinic:cytidylic acid (poly I:C), a commonly used dsRNA in pathway research and therapeutics, was delivered to cells using a previously explored carrier, nanophytoglycogen (NDX). Pathways surrounding uptake, signalling molecules, and overall immune responses were explored. Two non-immune human cell lines were used, immortalized human fibroblasts (THF) and embryonic kidney cells (HEK-293). In THF cells, immunofluorescent analysis demonstrated that NDX-delivery significantly enhanced poly I:C uptake and demonstrated the involvement of class A scavenger receptors (SRAs). Lysosomal staining indicated that poly I:C-NDX is present in low-pH vesicles after uptake. THF cells mount an enhanced immune response to poly I:C-NDX compared to poly I:C, measured using qRT-PCR for a classic interferon-stimulated gene, IFIT-1. Using THF cells lacking TLR-3, an endosomal receptor, and the type I interferon receptor, IFNAR, we observed a significant decrease of type I IFN response after treatment with poly I:C-NDX, demonstrating the reliance on these receptors. Knock-down of RIG-I-MDA5 or IPS-1 did not significantly change responses to poly I:C-NDX. HEK-293 cells modified with reporter assays for proinflammatory and type I interferon pathways were used to further explore cytokine outcomes in which cells with or without TLR3-overexpresison were tested. All cells produced both interferon and proinflammatory responses to poly I:C and poly I:C-NDX. Cells overexpressing TLR-3 had a significantly improved response to poly I:C-NDX compared to poly I:C, further indicating its importance in the ability for cells to robustly respond to the nanocarrier. The data from this thesis will contribute to the knowledge base surrounding nanoparticle-mediated dsRNA recognition and innate immune pathway activation in non-immune cells, leading to a better understanding of the fundamental mechanisms of innate immunity in vertebrates and contributing to potential future antiviral and anticancer therapeutics
Last Passage Time and Excursion Theory for Solvable Diffusions with Applications in Mathematical Finance
Get PDFIn this dissertation, we investigate the properties of last passage times and excursion theory in one-dimensional solvable diffusions, emphasizing their applications in financial modeling, particularly in option pricing. We derive closed-form formulas for the marginal distribution of last passage times and their joint distribution with process values, including the maximum and minimum of the process value. The focus is on time-homogeneous diffusions with various boundaries and imposed killing. Employing spectral expansion theory, we derive explicit formulas for distributions of last passage times in common processes such as Drifted Brownian Motion (BM), Squared Bessel (SQB), Ornstein-Uhlenbeck (OU), and Cox-Ingersoll-Ross (CIR) models. By simple mapping techniques, we also derive distributions for Geometric Brownian Motion (GBM) and Constant Elasticity of Variance (CEV) processes. Additionally, by applying a diffusion canonical transformation, we extend our study to multi-parameter families of solvable diffusions with nonlinear local volatility, including the so-called Bessel-K and Unbounded OU (UOU) processes. Our findings are substantiated with numerical calculations to verify accuracy.
The practical application of these theoretical insights is explored in the realm of option pricing. We focus on barrier options related to the last passage time, particularly introducing and analyzing new types of step options. Utilizing our established joint distribution formulas, we compute the initial prices of these options under common asset pricing models, supported by extensive numerical calculations.
An additional novel contribution of this dissertation lies in the exploration of excursion theory. We examine the relationship between last passage time and the first hitting time after a fixed time , deriving general formulas for all solvable diffusions. Our comprehensive analysis extends to related processes, like the excursion process straddling a time and the meander processes, for which we derive formulas for their joint distribution with the last passage time. We apply these formulas to the Brownian Motion case as a validation, successfully recovering known results
What Traces Did They Leave?: The Varied Involvement in Book Culture of Three ‘Conventional’ Premodern Englishwomen
No full textThis thesis discusses English nuns and laywomen\u27s continual direct or indirect involvement in book production in the late Middle Ages and Early Modern period from approximately 1385 to 1600 CE. I define conventional women as women considered socially acceptable during their period who did not deviate overtly from the norm. To do so, I examine three specific case studies: Richard Beauchamp\u27s wives and daughters\u27 roles as patrons, the nuns of Syon Abbey\u27s consumption and production of books, and Elizabeth Pickering, a widow who was one of the first female printers in England. Through these three case studies, I will demonstrate how English women consumed and actively participated in book culture throughout the late Middle Ages and Early Modern period. Demonstrating the breadth of women\u27s engagement in book culture in this period is essential for these sources to provide insight into the level and variety of women\u27s involvement
Corporate Bond ETFs, Bond Liquidity, and ETF Trading Volume
Get PDFThis study investigates the impact of corporate bond ETFs on the liquidity of their underlying securities. By alternatively utilizing panel regressions in levels, in changes, controlling for past liquidity, subsample tests—including periods of market stress and arbitrage—and a novel quasi-natural experiment, this study addresses self-selection and index effect identification issues. The findings indicate that ETFs significantly reduce transaction costs and enhance bond liquidity. Notably, the trading volume of ETFs, which is 6.67 times greater than their arbitrage, appears beneficial
Review of “Part of Life Itself: The War Diary of Lieutenant Leslie H. Miller, CEF” edited by Graham Broad
Get PDFReview of Part of Life Itself: The War Diary of Lieutenant Leslie H. Miller, CEF edited by Graham Broad
No. 29: Translocal Households, Rural-Urban Links and Migrant Food Security in South Africa
No full textThis paper revisits the issue of rural-urban links in post-apartheid South Africa, challenging the assumption that the end of apartheid would lead to rapid urbanization and the dissolution of circular migration. Despite the abolition of influx controls and the significant increase in the urban population from 33% in 1980 to 55% in 2011 among black South Africans, rural-urban ties and flows have proven resilient. The persistence of circular migration is evident in the continuous flow of people, goods, and remittances between urban and rural areas. This paper draws on a survey of over 800 Eastern Cape migrants in Cape Town, conducted in 2022, to explore the dynamics of these connections. The findings highlight the complexity and nuances of post-apartheid migration, revealing that translocal livelihoods and mobilities are still prevalent. The study also examines the significant gender shift in migration patterns, with a notable increase in female migrants. Remittances play a crucial role in supporting rural households, indicating the enduring importance of rural-urban links. The research underscores the need to rethink traditional concepts of urbanisation and consider the broader implications of sustained migrancy for rural and urban development in South Africa
No. 27: Invisible Work, Visible Impacts: Gender, Migrants, and Informal Food Trade amid the COVID-19 Pandemic in the Global South
No full textThis paper examines the abrupt and far-reaching consequences of the COVID-19 pandemic on women engaged in the informal food sector within the Global South. It highlights the deepening effects of the pandemic on food insecurity, gender inequality, and economic disparities. Based on a case study of three groups of women – internal migrants, international migrants, and cross-border traders – engaged in informal food work within and across countries and regions of the Global South, the paper investigates the compounded challenges they face, as well as their exacerbated risks and vulnerabilities. The analysis exposes the complex interplay between gender, migration, and food security through the pandemic. The results also reveal significant gaps in government responses during the pandemic in addressing the specific needs of women in general and female migrant workers in the informal food sector more specifically. By recognizing the important contributions of women and women migrants to food security, the paper makes a case for stronger efforts to support these informal enterprises