University of Illinois at Chicago
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Immune Dysregulation in Inflammatory and Autoimmune Disorders
No full textThe immune system is an incredibly complex array of cells that performs the crucial function of host defense against a variety of foreign substances and pathogens. However, the system does not always function as intended, and dysregulation of the various mechanisms governing the immune response can lead to a variety of disease states. The complexity of immunological regulation makes clinical management of such disorders challenging. Doctors and patients must often balance ample immunological management with a variety of side-effects while combating resistance to treatment.
The studies presented in this work aimed to elucidate various biological mechanisms governing immunological disorders, and to identify potential candidates for treatment targeting. We analyzed the similarities and differences between systemic lupus erythematosus and sarcoidosis, two immunological disorders that can affect virtually any organ system and have a wide array of presentations from mild and well controlled to rampant systemic inflammation and organ damage. We also analyzed the differences between mild and severe cases of COVID-19, a viral disease driven by hyperinflammation that similarly illustrates the destructive power of an unregulated immune response. We then studied the effects of COVID-19 vaccination in sarcoidosis to better understand the interaction of the sarcoidosis patient immune system with new mRNA vaccines. Lastly, we analyzed differences between mild and severe cases of sarcoidosis to characterize how severe disease differs and identify cellular contributors to severe disease. This work finds various imbalances in the regulation of inflammatory processes that drive the diseases studied, enabling further study of targeted treatments
Live Cell and Superresolution Microscopy of Vesicular and Interleukin-2 Transport in Jurkat T Cells
No full textT cells are essential to the immune system driving the adaptive immune response, where they coordinate and communicate with various immune cells through the secretion of pro-inflammatory cytokines, such as interleukin-2 (IL-2). A comprehensive understanding of spatio-temporal regulation of cytokine trafficking in T cells would reveal potential targets for the modulation of cytokine secretion, prompting the development of new therapeutic options. Therefore, through the incorporation of live cell imaging and superresolution microscopy, this dissertation investigates the mechanisms and motor proteins involved in the trafficking of intracellular IL-2 from T cells, using Jurkat T cells, as a model system. The first section explores the dynamics of acidic vesicles stained with a pH sensitive dye, Acridine Orange, following activation with CD3/CD28 Dynabeads. Live cell imaging revealed an increase in acidic vesicle mobility, which appeared to peak with 8 h activation, correlating with the maximum production and secretion of IL-2. The generation of a Jurkat cell line expressing IL-2 fused to EGFP demonstrated the utilization of acidic vesicles in the trafficking of IL-2. The second section investigates the role of actin-associated motor protein, Myosin-VI, on the transport of both acidic vesicles and IL-2. Small molecule inhibition and siRNA mediated knockdown of Myosin-VI increased the dynamics of acidic vesicles in 8 h activated Jurkat T cells, as well as the trafficking of IL-2. The involvement of Myosin-VI in the transport of both acidic vesicles and IL-2 was implicated, suggesting Myosin-VI as a potential therapeutic target for cytokine modulation. The third section of this dissertation unveils the distribution and organization of IL-2, particularly near the cell periphery following in vitro activation. Superresolution microscopy revealed not only an increase in intracellular IL-2 as a function of activation but also an increase in the prevalence of elongated IL-2 clusters along the cell periphery, indicating the packaging of IL-2 at the nanoscale. In conclusion, this dissertation reveals the involvement of acidic vesicles and Myosin-VI on intracellular IL-2 trafficking, as well as the clustering of IL-2 along the periphery of the cell following activation. These findings provide insight into the mechanisms and proteins involved in IL-2 transport within T cells, establishing the groundwork for the exploration of therapeutic targets for the modulation of cytokine trafficking and release
Machine Learning Assisted Analog Circuit Design Automation
No full textUnlike digital integrated circuit design, analog integrated circuit design process generally lacks enough automation and relies heavily on the expertise and intuition of the analog designer. Attempts have been made in the past to automate several aspects of the analog design process, but these techniques never became mainstream due to the complexity of analog design. With the recent advancement of artificial intelligence (AI) and machine learning (ML) techniques, which promise to automate many complex tasks, there is a renewed interest in automating analog design process through AI / ML techniques. With such automation, cost and design time can be significantly reduced and new analog designers can be trained more efficiently. In this research, we develop an ML-based framework for automating analog design optimization at the schematic level
Metabolic Dysfunction-Associated Steatotic Liver Disease and the Role of Persistent Organic Pollutants
No full textSteatotic liver disease (SLD) is the most common liver disease globally. Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased morbidity and mortality, with risks rising alongside disease severity. Many persistent organic pollutants (POPs) have been associated with SLD. This dissertation aimed to generate updated prevalence estimates for SLD and SLD subtypes in the United States (US) adult population and to compare reliability of multiple non-invasive metrics to assess steatosis and fibrosis. Additionally, it set out to evaluate both cross-sectional and longitudinal associations of POPs with MASLD prevalence, incidence and progression among a population of US Hispanic/Latino Adults; a group commonly reporting highest SLD risk. All analyses were conducted in a sex-specific manner a priori, and both traditional as well as experimental chemical mixture methods were applied to examine the POPs-MASLD relationships. The National Health and Nutrition Examination Survey (NHANES) data from the 2017-2020 cycle (Males N=1627, Females N=1611) were used for estimating disease prevalence and assessing tool performance in the general US population. An ancillary study population from the Hispanic Community Health Study / Study of Latinos (HCHS / SOL) was used to explore POPs-MASLD relationships at baseline (Males = 895, Females = 1066) and 6-year follow-up (Males N = 669, Females N = 871). Findings suggest the prevalence of MASLD in the adult US population is higher than many historic estimates, with current projections of 46% of females and 51% of males with MASLD, 5.5% of females and 7% of males likely having metabolic dysfunction-associated steatohepatitis (MASH), specifically. The Fatty Liver Index (FLI) appears to be a reliable non-invasive tool for detection of steatosis, but the choice metric for fibrosis is less clear. The fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) are potentially preferable, particularly in Mexican Americans. Among Hispanics/Latinos at baseline, Males showed consistent positive associations for POPs and prevalence of low risk and increased risk MASLD, FLI score, and FIB-4 score. FLI score was especially strongly positively correlated with POPs in males. Females showed less uniform findings but indicated positive associations for POPs and more severe disease/fibrosis metrics. Upon follow-up, incidence and progression of MASLD was common in both males and females, even among those without traditional risk factors. 18.4% of females and 11.9% of males without MASLD (‘Healthy’) at Visit 1 developed suspected fibrosis at Visit 2 with no evidence of steatosis. Chemical mixture methods showed baseline POPs levels were significantly positively associated with increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) liver enzymes at follow-up among females classified as Low Risk MASLD at Visit 1. In sum, the global burden of MASLD is immense and education and screening are lacking. Performance of non-invasive tools for liver disease detection differs meaningfully by subgroup including race/ethnicity, sex, and reproductive status. This research suggests the FLI is a reliable tool to flag patients in need of further testing and staging for MASLD. However, there is a need to re-evaluate guidance and cut points for non-invasive liver metrics, especially by sex and reproductive status. Females tended to show greater associations between POPs and incidence or progression of MASLD, particularly for progression to a fibrotic state. Menopause is an especially vulnerable time for the liver in females, and POPs may aggravate the progression and/or development of more severe liver disease and fibrosis. The role of hormones along with POPs requires further study, and the drastic change in risk profile from pre- to post-menopausal status for women deserves greater attention
Resolute or Resigned: Follower Reactions to Leader-Follower Ethical Disagreement
No full textExisting research on ethical conflict has demonstrated numerous negative outcomes that employees experience when they face dissensus with other organizational members regarding matters of right and wrong. My research shifts the focus from the consequences employees face following ethical conflict to the processes through which employees cope during ethical conflict. I zoom in on the process of leader–follower ethical conflict to better understand the intrapersonal and interpersonal processes that followers engage to overcome perceptions of ethical disagreement. Across two studies which incorporate a critical incident technique and an experimental vignette method, I investigate the extent to which leader–follower ethical disagreement motivates employee moral agency by inducing moral stress. Further, I investigate individual differences that influence more constructive, versus dysfunctional responses. The results suggest that leader–follower ethical disagreement can be a stressful experience for individuals which motivates ethical voice and job withdrawal. Further, individuals higher in moral self-efficacy are less likely to withdraw in the face of such conflict. By illuminating the processes that unfold during leader–follower ethical conflict, my research advances our understanding of not only how such conflict motivates employee responses but also how organizations may empower employees to facilitate more constructive responses
VA Healthcare: Prioritized Access and Utilization at the Intersections of Race and Ethnicity with Gender
No full textFor U.S. military veterans, access to VA healthcare is determined by laws and policies, and involves military service factors (e.g., medals, POW, exposures), service-connected disabilities (SCDs), and income. To access VA care, veterans are assigned to one of eight priority groups (PGs) whereby veterans with higher SCD ratings, higher need, and/or low income are assigned to higher PGs. The prevalence of SCDs among veterans continues to rise and is higher among some racial and ethnic groups and female veterans. Little is known about how the structure of access to VA care relates to healthcare utilization and differences by race, ethnicity, and gender. Therefore, the purpose of this study was to characterize access to VA health care (PGs), VA healthcare utilization (outpatient care), and intersections of race, ethnicity, and gender, and to determine relationships among these concepts. A secondary analysis of healthcare administrative data from the Weight and Veterans Environment Study was used to perform this study.
In Chapter I, using a cross-sectional descriptive analyses, the characterization of veterans’ PGs and outpatient care by intersections of race and ethnicity with gender is presented. Across race and ethnicity, more female veterans were in the highest PGs (SCD ratings >10%) compared to male counterparts. In contrast, the largest proportion of veterans in the lowest PG (0% rated SCDs or without SCDs and higher income) were non-Hispanic White males. Across intersections, outpatient care use was highest in the PG for catastrophically disabled veterans without SCDs.
Chapter II using longitudinal panel data analyses, relationships among PGs, VA outpatient healthcare use, and intersections of race and ethnicity with gender are presented. Overall, outpatient care use was associated with PGs and intersections of race and ethnicity with gender that also moderated the effect of PGs on outpatient care use with the largest effects within the PG for catastrophically disabled veterans without SCDs.
Findings from this study have implications for policy, practice, and research. Knowledge of structural access and use of VA care can inform interventions to prevent and reduce health-related effects of military service across the life course of veterans
An Interrogation of the “It” Narrative: Contract as Narrator
No full textThis creative dissertation is an exploration of the “IT” narrative genre, a style of literary fiction most often found within the Romantic and Victorian periods. The creative manuscript experiments with the technical considerations when deploying narrative logic of an “inhuman” or “IT” narrator; in this case the narrator is deployed by means of a novel concept: an early 19th century contract of town incorporation and land commerce.
By deploying an “IT” narrator, this manuscript interrogates the possibilities and limitations as found within a non-human narrator that both exists within the story (homodiegetic) as well as outside the story (heterodiegetic), all the while merging the idea of setting as narration. This creative dissertation attempts to profer a story that possesses no main protagonist, no human interiority, and only is accessible to the actions and words of the characters within the confined geospatial space (the boundaries of Fortune and the history contained within incorporation, as defined by the contract). With the narration’s accessibility defined by its very essence, as the story can only describe events in accordance with the rules of the contract, this creative dissertation also explores techniques of narratorial privilege, unreliability of narration, dueling narrators, and how the act of narration defines, or impedes, the contemporary conception of story
Latine Mothers' Experiences with Autism: From Early Concerns to Advocacy and School Engagement
No full textThis phenomenology-informed study explores the lived experiences of ten Latine mothers navigating their children’s autism diagnoses, support systems, and education. Participants shared their perspectives on the diagnostic process, sources of support, and their evolving role as advocates within their families, schools, and communities. Findings reveal that while mothers persistently sought information and assistance, they often encountered systemic barriers, dismissive interactions with professionals, and a lack of culturally responsive resources. Despite these challenges, they demonstrated resilience, leveraging informal networks, peer connections, and self-education to bridge information gaps and advocate for their children. Their advocacy evolved alongside the support they received, emphasizing the critical role of social support in securing equitable access to education and healthcare. These findings highlight the need for accessible and responsive systems to foster trust, strengthen family-school partnerships, and ensure that Latine families receive the comprehensive support necessary for meaningful engagement
A Scoping Review of Medical Education and Care of Patients with Criminal-Legal System Involvement
No full textOver 5 million people in the United States with criminal-legal system involvement (CLSI) pose unique ethical and medical considerations for physicians. Despite the rise of academic medical center partnerships with correctional facilities, no framework to teach learners to navigate the care of patients with CLSI exists. The current literature lacks a clear picture of the motivations, formats, and quality of educational interventions for medical learners providing care to patients with CLSI.
Using the Arksey and O’Malley framework methodology, the authors searched PubMed, Embase, MedEdPORTAL, and Web of Science to identify English-language peer-reviewed studies. Articles were included if they (1) included medical trainees, (2) involved patients with CLSI and (3) had an educational component. Data extracted included the study type, motivations, and relevant stakeholders. For educational intervention studies, the authors also extracted the learner characteristics, format and content, assessment tools, and study quality.
Equity and public health were the most common motivations for CLSI educational interventions. Most published educational interventions were academic health center-correctional facility partnerships featuring clinical rotations among medical schools and residency programs. The most common residency specialties were psychiatry, family medicine, and internal medicine. However, most published CLSI educational interventions relied on exposure to patients with CLSI and lacked explicit curricula or rigorous learner assessments
Barrier Optimization of HgCdTe nBn Infrared Detectors
No full textThis thesis investigates the nBn infrared detecting device structure, specifically those made from HgCdTe grown on CdTe/Si substrates by Molecular Beam Epitaxy (MBE), and the improvement to performance that replacing the alloy barrier layer with a properly designed superlattice can yield. The main impacts that the superlattice barrier imparts on the devices comes from the electron and hole mobilities and the band alignment, specifically through the valence band offset (VBO) and conduction band offset (CBO) between barrier and absorber layers. The research explores the device designs both theoretically, through the use of numerical simulations, and experimentally, though the fabrication and characterization of many device designs. Ultimately it is shown that the biggest improvement given by the superlattice barrier to the devices comes from its impact on the electron effective mass in the barrier (blocking unwanted, electron-mediated dark currents), while maintaining a reasonable VBO and CBO.
The study begins by detailing the relevance of infrared technology. Material selection is crucial for optimizing detector performance, and in the case of the nBn structure, the selection of the barrier layer material is of particular importance. This thesis discusses the development of a superlattice for the barrier as a means to adjust the band alignment and carrier mobilities, potentially overcoming some intrinsic limitations of nBn devices.
The experimental section of the research outlines the processes involved in the growth and fabrication of the devices. Techniques such as Molecular Beam Epitaxy (MBE) are detailed, noting their importance in achieving the desired material properties and device structures. The thesis also discusses the challenges and solutions associated with doping and metallization, critical steps that influence the final device performance.
Characterization methods play a vital role in understanding the operational capabilities of the fabricated devices. Techniques like Fourier Transform Infrared (FTIR) spectroscopy are used to evaluate the spectral response of the detectors, demonstrating their capability as an infrared detector. Other techniques like photoconductive lifetime and dark current measurement were used to help optimize the device fabrication process and diagnose troublesome processes like passivation.
In conclusion, this thesis presents a comprehensive examination of the HgCdTe nBn structure for infrared detection. Several alloy barrier and superlattice barrier devices were fabricated, characterized, and compared. Higher than expected dark currents were seen, but a self consistent explanation, derived from theoretical modeling, of increased Hg in both the alloy barrier and the CdTe layers of the superlattice barrier closely matches the experimental results. The overall higher performance of the superlattice barrier devices also agrees with the theoretical results, indicating that the improved performance was likely due to the increased effective electron mass in the barrier, even with a band alignment similar to the alloy barrier design. This shows the improvement to device performance afforded by the superlattice barrier while retaining the robustness and simplified device fabrication that the nBn device design affords
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