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Investigating the Role of Epidermal Growth Factor Receptor in Abdominal Aortic Aneurysms
No full textThe inability of adult vascular smooth muscle cells (SMCs) to facilitate elastic matrix regeneration and repair renders it extremely difficult to reverse the pathophysiology of abdominal aortic aneurysms (AAAs), which are localized aortic expansions characterized by severe and naturally irreversible elastic fiber degradation by locally overexpressed matrix metalloproteases (MMPs). Such MMP overexpression is an outcome of chronic inflammatory responses initiated by the activation of several medial SMC signaling cascades within the aorta upon multifactorial insults to the vessel wall. Currently, the management of AAAs is limited to risky open or endovascular surgery on large, rupture imminent AAAs. There are no other established drug-based treatments for AAAs, especially to stabilize or reverse small (< 5.5 cm diameter), growing AAAs, and none that can regenerate, or repair degraded elastic matrix structures in the AAA wall. Towards identifying a new therapeutic target, one of the signaling pathways which is not well understood in the context of AAA etiology and pathophysiology is the role of epidermal growth factor receptor (EGFR). In this work, we have identified and established a novel molecular target (EGFR) and its mechanism of action through which the elastic matrix breakdown likely occurs to prompt AAA progression.The overall goal of this dissertation research is to investigate the potential anti-proteolytic and pro-elastogenic benefits that can be achieved by targeting the novel, identified molecular target of EGFR in-vitro. Our results indicate that EGFR plays a significant role in the disease progression within the aneurysmal SMC milieu via the activation through an inflammatory stimulus, namely neutrophil elastase. Activation of EGFR via neutrophil elastase triggers the proteolytic behavior of MMPs, which promotes elastic fiber degradation. Moreover, this work also establishes the efficacy of a cancer drug, afatinib, for the very first time to demonstrate the anti-MMP and elastin regeneration prospects via the effective inhibition of the EGFR pathway in aneurysmal SMCs. Lastly, our studies establish the development, characterization, and release kinetics of afatinib loaded biodegradable and biocompatible polymer nanoparticles. Overall, this body of work provides initial evidence of improved elastic matrix homeostasis and regeneration attainable by targeting the novel EGFR pathway within the AAA inflammatory milieu. This work will help in defining an innovative approach through which the AAA disease progression can be reversed to provide a regenerative stimulus for elastic matrix repair. Additionally, establishing EGFR as a molecular target in the aneurysmal cells will provide an opportunity to develop EGFR-targeted, minimally invasive nanotherapies which can eventually open doors for small AAA repair at an earlier diagnosis stage
Vibrational Spectroscopy as a Probe of O-H and O-D Centers in the Ultra-Wide Bandgap Semiconductor β − Ga2O3
No full text? ? Ga2O3 is an ultra-wide bandgap semiconductor whose properties make it promising for high-power and extreme environment applications. Hydrogen has strong effects on the electrical properties, giving rise to shallow donors and the passivation of deep acceptors. The introduction of hydrogen by annealing in an H2 ambient, proton implantation, and plasma exposure gives rise to both hydrogen and native defects with which it interacts. Low-temperature vibrational spectroscopy is used to investigate the microscopic defect processes that are responsible for the effects that hydrogen and deuterium impurities have on the electrical properties of ? ? Ga2O3. The dominant O-H center at 3436 cm?1 has been assigned to a Ga(1) vacancy with two equivalent hydrogen atoms. Introduction of the deuterium isotope into ? ?Ga2O3 samples yields spectra with significantly higher signal-to-noise and these are focused on throughout these experiments. Investigating the polarization dependence of the vibrational absorption of the VGa(1) ?2D center with a vibrational line at 2546 cm?1 allows for the determination of the principal dielectric axes of ? ? Ga2O3 in the near-infrared. The vibrational transition moment directions are also determined from the polarization dependence of these defects and provide additional information about defect structures. Ion implantation of H+ and D+ produces additional O-H and O-D centers in addition to the dominant VGa(1)?2H(D) defect in ??Ga2O3. The additional defects can be converted into the VGa(1) ? 2H(D) by thermal annealing. O-H and O-D lines that involve deep acceptor impurities have been observed at very similar vibrational frequencies in ? ? Ga2O3 samples annealed in an H2 or D2 ambient. The vibrational properties of these complexes were investigated to differentiate between them and determine their defect structures. Many O-H and O-D vibrational lines have been observed in ? ? Ga2O3 but none had absorption with a component of their polarization with E ? [010], or b axis. Experiments performed for Czochralski grown ? ? Ga2O3 samples annealed in an H2 or D2 ambient have led to the discovery of weak O-D lines at 2475 and 2493 cm?1 with a component of their polarization with E ?[010]. This property is consistent with a structure involving a vacancy at the Ga(2) site. Infrared spectroscopy measurements were used to aid in proposing defect structures involving D trapped at a Ga(2) vacancy. O-D centers in ? ? Ga2O3 evolve upon annealing in an inert ambient and are transformed from one O-D center to another. These reactions are investigated and reveal multiple classes of O-D centers that convert into one another based on their thermal stabilities. The absorption arising from free carriers also allowed the conductivity of ? ? Ga2O3 samples to be monitored as defect reactions occurred. The combination of vibrational spectroscopy and free-carrier absorption allowed for a relationship between conductivity changes caused by hydrogen to specific microscopic defect processes to be proposed. The collection of experiments in this dissertation provides detailed information about defect processes by which hydrogen affects the conductivity of ? ? Ga2O3
Particle-Bed 3D Printing by Selective Binder Activation and Topology Optimization with Genetic Algorithms
No full textTopology optimization and 3D printing attract more and more interests from the analysts and engineers. This dissertation deals with a combined technology involving these two technologies. By using topology optimization, a structure with optimal geometry can be designed automatically according to the pre-defined objectives and constraints. On the other hand, by using concrete 3D printing, this customized structure can be manufactured automatically depending on the unique manufacturing technique in 3D printing. A systematic sensitivity analysis to quantify the influence of constituents and proportions of concrete powder on the compressive strength and dimensional inaccuracy of the product is conducted. Three topology optimization methodologies are proposed to solve: 1) the single, linear material optimization problem, 2) multi-, nonlinear material optimization problem, and 3) the utilization of neural network in topology optimization for reducing the computational cost
Developing A Cold Thermal Energy Storage System (ctess) By Using Phase Change Material (pcm) Encapsulated In Pervious Concrete (pc)
No full textCondensers and cooling towers are commonly used in coal power plants to condense the steam from condenser in a power plant and to recycle the condensed-water into the boiler in a closed-loop system. Cooling tower facilitates are used to release the heat of the warm water flow in the condenser. There are two main types of cooling tower depending on the heat transfer mechanism: wet cooling towers (WCTs) and dry cooling towers (DCTs). This work investigates the development, design, and evaluates an effective pre-cooling system to enhance the performance of a mechanical draft dry cooling system (DCS) for coal power plant applications. The dry pre-cooling system is provided by designing a cold thermal energy storage system (CTESS) which consists of a PCM encapsulated in PC. The research presented in this dissertation focuses on: (1) Examination of the replacement of normal weight aggregates (NWAs) by lightweight aggregates (LWAs) in pervious concrete fabrication, and its impact on mechanical properties, with the aim of developing an optimal concrete mix that balances strength and permeability; (2) Quantification of the pressure drop and thermal properties of pervious concrete as well as the development of an empirical model that predicts the pressure drop in pervious concrete; (3) a feasibility study on the utilization of pervious concrete (PC) incorporating diverse lightweight aggregates (LWAs) and phase change materials (PCM) for dry cooling purposes
Quantum Algorithm Implementations and a Classical Look on Quantum Error Mitigation
No full textQuantum computing holds great potential for reducing the time complexity of many problems in theory. However, there are many gaps waiting to be filled in the implementation. In the first part of this dissertation, we explore the performance and applications of several variational algorithms and a quantum linear solver, the HHL algorithm, on simulators. Specifically, we assess the use of the HHL algorithm in addressing scientific and engineering problems through quantum computing utilizing the NWQSim simulation package on high-performance computing. We demonstrate the influence of several tunable parameters of circuits and algorithms on the final solution in an iterative and a non-iterative numerical method. In the second part of this dissertation, we develop the quantum version of the Generator Coordinate Method. It is a hybrid quantum-classical approach for solving quantum chemistry problems without worrying about the barren plateau and the exactness of the ans\\"{a}tze by building the interconnection between constrained optimization and generalized eigenvalue problems through a unique class of Givens rotations. For practical applications, we propose an adaptive scheme for the robust construction of many-body states using these Givens rotations, with an emphasis on a linear expansion that balances accuracy and efficiency. In the final part of the dissertation, we focus on the unique problem in real quantum computers: quantum noise. To address this, we design a Bayesian inference approach that identifies posterior distributions of individual noise parameters for more elaborate characterization of device errors. Thus, we further improve the accuracy of quantum error mitigation. Our experiments on superconducting quantum computing devices show that our approach provides better error mitigation performance than existing techniques used by the vendor and outperforms the standard Bayesian inference method in some scenarios. In addition, our research on Kalman filter aims to simulate the quantum state evolution inside real quantum computers fully. In several multi-qubit experiments, our method has shown leading performance compared to the noise simulator in a popular software package
Enhanced delivery of antibiotics using outer membrane vesicles
No full textAntibiotic resistance poses an immense global threat to human health, contributing to more than 2.8 million antimicrobial-resistant infections annually in the United States alone. This accounts for over 35,000 annual fatalities and an economic burden exceeding $4.6 billion for treatment. A formidable challenge in combating this issue lies in the intrinsic resistance of bacterial membranes, which restricts antibiotic uptake, thus diminishing their effectiveness. To overcome this challenge, we were inspired by outer membrane vesicles, naturally secreted by gram-negative bacteria, facilitating long-distance delivery of numerous biomolecules to the cytosol of target bacteria. We hypothesize that encapsulating antibiotics in outer membrane vesicles will provide stability and increased delivery to pathogens, resulting in more effective eradication. In this study, we used outer membrane vesicles produced by Escherichia coli JC8031 to augment the delivery of moxifloxacin to a range of both gram-positive and gram-negative pathogens. These included E. coli, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Streptococcus mutans, and Staphylococcus aureus, including clinical isolates exhibiting moxifloxacin resistance. Our findings revealed that antibiotic-loaded outer membrane vesicles exhibited comparable efficacy to free antibiotics in treating gram-negative pathogens and demonstrated superior efficiency in killing gram-positive pathogens. Specifically, when faced with clinical isolates of P. aeruginosa and S. aureus resistant to moxifloxacin, the antibiotics encapsulated in the outer membrane vesicles were much more effective. As we advance our research, future investigations will focus on identifying alternative antibiotics that display more effectiveness against gram-negative bacteria when encapsulated by outer membrane vesicles
Paralyzed Changemakers: An Ethnographic Study of Youth Unemployment from Bududa, Uganda and Petra, Jordan
No full textComparative study on youth unemployment in Bududa, Uganda and Petra, Jordan. Analyzing youth unemployment and neoliberalism\u27s effects through a World Systems Theory approach. Bordieau\u27s concept of agency and structure are employed to further assess the youth experience. Topic covered include youth empowerment strategies, the role of government, movement and migration, social and familial networks, guidance and mentorship, tertiary schools and skill building, higher education, sexual transactional economy, and hustle culture
The Relationship Between Parental Responsiveness and Infant Social-Cognitive Behaviors in Infancy and Toddlers\u27 Joint Attention
No full textJoint attention, also known as joint engagement, is defined as the ability to coordinate attention between a social partner and an object or event of shared interest. Joint attention occupies a central position in children\u27s developmental research and has been shown to be crucial for language development, communication, and other advanced social skills. However, influences on the development of joint attention are not well understood. In this longitudinal honors thesis, we examined in 89 dyads how infant social-cognitive behaviors (i.e., triadic engagement, communicative vocalizations, and face looks) and caregiver responsiveness at 9 to12 months of age was associated with later joint engagement skills at 18 or 24 months old. Results showed that infant social-cognitive behaviors at Time 1 were significantly associated with some aspects of toddler joint engagement at Time 2; however, caregiver responsiveness was not. Future research should continue exploring the effects of individual differences in infancy and caregiver behavior on the development of joint attention in toddlerhood
The Role of Women in the American Eugenics Movement
No full textThis thesis examines the role of women in the American eugenics movement from 1900 to 1945, as well as how ideas about motherhood were manipulated to further eugenic ideals about race and hygiene. This paper analyzes primary sources such as propaganda posters about social hygiene, academic articles written by women, advertisements aimed towards women using eugenic ideology, and more in order to determine the prevalence and impact women had on the American eugenics movement. I conclude that women had a prominent role in all aspects of the American eugenics movement, contrary to how it has often been remembered and recorded by historians
The Design and Implementation of AI Partner in Supporting Foreign Language Teaching and Assessment
No full textWe plan to focus on AI training to improve students\u27 performance on the Oral Proficiency Interview (OPI). We will train the AI on the structure of the OPI using ACTFL proficiency guidelines and design prompts that simulate a natural, contextual target language environment.The existing CFLingo platform supports conversations between Chinese as a Foreign Language (CFL) students and OpenAIs ChatGPT LLM. The platform facilitates a variety of exercises, including debates, roleplays, sentence creation, essay outlining, and essay drafting. We are currently in the process of augmenting the scripts supporting our existing CFLingo platform to use audio as both an input and output as well as text. The existing platform uses OpenAIs GPT-4-Omni LLM, which only uses text for input and output. However there is now an available model, GPT-4-Omni-Audio-Preview that can use audio in addition to text for input and output using the same "chat completions" API end point as the standard 4 Omni model. However, we need to slightly restructure the messages being sent and received by our platform as the model requires additional parameters for audio settings and also returns audio as part of its response.</p