ScholarWorks@Georgia State University
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Regulation of Nontypeable Haemophilus influenzae-induced Host Innate Immunity in Lung Epithelium
The host's innate immune response begins with the identification of molecules known as pathogen-associated molecular patterns by a series of germline-encoded pattern-recognition receptors. Retinoic acid-inducible gene I (RIG-I) is one such innate immune receptor that detects viral RNA in the cytosol of cells and is crucial to mount an effective antiviral immune response in the course of viral infections. RIG-I with the adaptor protein mitochondrial antiviral signaling protein (MAVS) leads to the activation of the transcription factors including interferon-regulatory factor 3 (IRF3), IRF7 and nuclear factor-κB (NF-κB), which induce type I and III interferon (IFN), and proinflammatory cytokines. Many studies have demonstrated the crucial role of RIG-I in viral infections such as influenza A virus (IAV) and respiratory syncytial virus (RSV) infections. However, as airway viral infection is frequently followed by bacterial co-infections, the role of RIG-I and how it is regulated in airway epithelium inflammation in mixed viral and bacterial infection remains undefined. Despite the well-known role of viruses in bacterial co-infections, the impact of bacterial infections on viral co-infections remains largely unknown. Therefore, understanding the mechanism of airway bacterial pathogen Nontypeable Haemophilus influenzae (NTHi)-induced RIG-I will help to understand the complex inflammatory signaling pathway and further contribute to the development of new therapies.
In the present study, we showed that NTHi induced RIG-I upregulation in airway epithelial cells. We also demonstrated that NTHi induced RIG-I upregulation by activation of TNF receptor associated factor 6 (TRAF6)-inhibitor of nuclear factor-κB kinase subunit β (IKKβ)-p65 pathway. Interestingly, interleukin-1 receptor-associated kinase M (IRAK-M) negatively regulated NTHi-induced up-regulation of RIG-I via inhibiting the IKKβ-p65 pathway and inflammation. We also confirmed that IKKβ activation is sufficient for RIG-I up-regulation. We showed that p65 phosphorylation at S276 and S536 residues is likely critical for RIG-I up-regulation. We also investigated the role of histone deacetylases (HDACs) as a positive regulator for NTHi-induced RIG-I up-regulation. Along with NTHi-induced RIG-I upregulation, we also confirmed the functional significance of RIG-I by confirming the CXCL10 expression mediated via RIG-I. Thus, our study provides new insights into the regulation of NTHi-induced RIG-I upregulation, which may contribute to the development of a new therapeutic strategy for controlling inflammation in mixed airway infections.
2023-04-12
Recent Submissions
Publication Essays in Financial and Actuarial Risk ModelingThis dissertation comprises three essays that advance the theory and application of risk modeling in financial and actuarial domains. The first chapter introduces the overarching motivation, research themes, and methodological orientation of the dissertation. Particular emphasis is placed on the development of robust statistical tools to address key challenges in empirical finance and insurance risk management, including structural breaks, tail risk, volatility clustering, risk forecasting, and optimal risk-sharing. The second chapter develops a new, distribution-free test for financial contagion, aimed at detecting structural breaks in residual dependence between asset returns during crisis periods. Unlike traditional contagion tests that rely on strong parametric assumptions, the proposed method accommodates heteroscedasticity through a deterministic volatility jump model and leverages block-based variance estimators for valid inference. The resulting test remains robust under time-varying volatility and dependent innovations and outperforms classical benchmarks in both size control and power across a range of simulated and historical crisis episodes, including the COVID-19 and subprime mortgage crises. Chapter 3 addresses the optimal reinsurance retention problem under regulatory frameworks that use Value-at-Risk (VaR) and Expected Shortfall (ES) as capital standards. It revisits the performance and limitations of the traditional stop-loss (SL) contract, demonstrating that SL-optimal solutions under VaR imply unrealistic outcomes such as zero insolvency probability. A generalizable framework is developed using Excess-of-Loss (EoL) reinsurance, where optimal retention is characterized via central limit approximations and distortion risk measures. The framework admits several premium loading principles, including standard deviation and Sharpe ratio principles, and allows for tractable, asymptotically valid estimation procedures. The last chapter proposes a simulation-consistent and distributionally robust method for multi-horizon Value-at-Risk forecasting under ARMA-GARCH models. The approach estimates the gamma-quantile of the maximum return over a fixed horizon. Parameters are estimated via weighted quasi-maximum likelihood, and uncertainty is quantified using a residual-based bootstrap. The methodology is validated through simulation and applied to ten years of asset-level financial returns. Together, these essays contribute new tools and perspectives to the literature on financial contagion, reinsurance optimization, and tail risk forecasting.Publication Working From Home Then Forced to Return: Employing Resource Theory and Social and Economic Exchange to Address Impact on Employee Organizational Commitment and Turnover IntentionsThroughout the documented history of business, there have been ongoing efforts by both employees and employers to influence the balance of social and economic exchanges. Each major shift in process, technology, environment, climate, or leadership creates an opportunity to revisit existing research. Revisiting research helps academic scholars understand its impact on social and economic balance as well as conduct innovative studies. These events allow researchers in the field to examine how employees and employers are adapting and reacting to reset the balance in social and economic exchange. It also allows us to develop ways to provide options for employers and employees to practically navigate these changes successfully. The global Covid-19 pandemic outbreak was one such shift, specifically the need for employees to work from home to protect the health and well-being of all employees. It was also a mandatory requirement for a majority of local, state, and federal agencies to ensure the health of the overall communities, in The United States. During the Covid-19 pandemic, a two-fold symbiotic relationship began to emerge between employers and employees. The first being that, working from home increased the positive perception of employees with added flexibility and increased social and economic benefits. Secondly, employers perceived that there was balance regarding production and culture. However, that swiftly changed and became a perceived imbalance once it was clear that the Covid-19 pandemic was long lasting. Because of this perceived imbalance several large organizations leaders led major initiatives to begin forcing employees to return to the office to work once the Covid-19 pandemic was reduced to endemic. By requiring employees to return to an in-person office working location or face grave penalties, such as job loss, reduced hours, or a hostile work environment was viewed negatively by employees. In turn, this negative viewpoint impacted employee sentiment, commitment, and drove turnover intent up, thus creating a struggle for social and economic exchange. After surveying eight thousand employees, Flex Job survey found that 56% either have or know someone who has or plans to quit a job because of a return-to-work mandate (Battle, 2024). Based on the social and economic exchange theory (Homans, 1958) and (Shore, 2006), as well as resource theory (Thao, 1974,1980), I hypothesize that the collected data will have the potential to assist in creating and developing a collective of resources that can positively impact employ social and economic exchange, drive up commitment, and drive down turnover intent. These resources would be used to help employers offset the negative impacts employees felt when faced with returning to a physical office space. I will better understand employee commitment, turnover, and perceptions when forced to return to the workplace. Using a mixed-method study using qualitative interviews and quantitative surveys, I have attempted to better understand the impacts that the return to the physical office space has on employees and employers. I utilized well developed, valid and reliable surveys to measure organizational commitment, turnover intent, and perceptions of employees by utilizing established prior research and qualitative employee surveying to develop defined resources to measure. The main contribution of this study is the development of insights and applications regarding the positive influence of six known categories of resources to offset the negative impact return to work has had on the social and economic exchange. The research surveyed U.S. based individuals who worked at home 50% of the time or greater during COVID-19 and were forced back to the office. These findings will help business leaders, managers, and executives make better decisions and establish resource-based programs to keep the social and economic exchange between employee and employer positive when forcing them to return to work. In addition, this research will help scholars continue to evolve social and economic exchange theory and advance our understand of resource usage to maintain positive social and economic exchangePublication Factors affecting Preparedness in Cybersecurity Risk Management among Small and Medium-Sized Enterprise (SME) LeadersSmall and medium-size enterprise (SME) leaders are ignoring the significance of cybersecurity risk management. The statistics for the number of SME organizations becoming victims of cyber-attacks increased significantly in 2025 and beyond. Although most SME leaders perceive themselves as non-targets, cybersecurity remains a key area of focus that all firms, regardless of their size, must confront. The area of concern or problem is that many SME organizations are operating without cybersecurity risk management and are at risk of a cyber-attack. The study's findings indicate that 42.5% of the 259 SME leader survey participants had not made an investment in cybersecurity. To investigate behavioral decisions in SME leaders, this study used the Behavioral Decision Theory (BDT) to understand the cognitive biases and heuristics that influenced the decision making of SME leaders. This was a quantitative study of 259 SME leaders residing in the United States that examined leader risk awareness, leader risk tolerance, and leader decision making (Melbourne Decision Making Questionnaire) to identify factors affecting preparedness in cybersecurity risk management. From a theoretical perspective, the findings expanded the understanding of decision leadership-making in cybersecurity preparedness by demonstrating that risk awareness plays a vital role in predicting preparedness. From a practical standpoint, the results can be used to guide on the activities through which leadership of SMEs can improve their preparedness in terms of cybersecurity.Item Snatch Me Up: A Critical Feminist Discourse Analysis on Black Women’s Motivations for Undergoing Brazilian Butt Lift Surgery(2024-08-07)The present study performed a critical feminist discourse analysis (CFDA) on narrative-style YouTube videos created by Black women while on their Brazilian Butt Lift (BBL) surgery journeys. Specifically, this study aimed to answer the main research question: What are Black women’s motivations for undergoing surgery? Additionally, it takes interest in examining the ways undergoing BBL surgery has impacted individual Black women’s mental health and wellness. Upon coding for the discursive objects “motivations” and “mental health impacts”, the following discourses and counter discourses emerged and were subsequently analyzed using a critical Black feminist theoretical framework: “doing it for me” empowerment discourse versus self-preservation counterdiscourse, postop satisfaction discourse versus postop regret discourse, mental obstacle discourse versus psychological resilience counterdiscourse and support system discourse. Conclusively, this study suggests that Black women’s decision-making and motivations for choosing BBL surgery is a topic of complexity and intricacies which suggest a need for further academic research and analysis.
Item Sisters of Conspiracy: A Feminist Analysis of Evangelical, New Age, and Qanon Movements in Contemporary American Politics.(2023-12-13)This thesis explores the link between New Age ideology, Evangelical Christianity, Qanon and the weaponization of women's body autonomy. It delves into how these factors have brought women into the Qanon conspiracy, leading them to engage in COVID denial, anti-vax movements, spreading medical misinformation, Qanon propaganda, and right-wing beliefs. Employing qualitative data analysis, cyberethnography, and feminist analysis, the research identifies online behavior, shared values, and beliefs in wellness, spiritual, and alt-right spaces through specific hashtags. This thesis focuses on a small set of social media hashtags on Facebook and Instagram between 2016 to 2020, revealing connections and shared agendas between New Age and Conservative religious communities. Remarkably, it uncovers a partnership between the male-dominated alt-right and the female-led New Age community, united by a specific feminized metaphysical language. By highlighting this connection, the research exposes the white supremacist origins of Qanon, discouraging well-intentioned women from joining the movement.
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