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Structure-Guided Strategies to Combat Antibiotic Resistance
No full textThe PhD research focuses on structure-guided strategies to combat antibiotic resistance. It includes three sub-projects: 1). SEQ-9 overcomes Mtb ribosome methylation and inhibits ribosomal activities. Antibiotics are implemented to cue tuberculosis caused by Mycobacterium to inhibit Mtb ribosomes and prevent downstream cellular activities. However, Mtb cells evolve to escape antibiotic pressure. One strategy Mtb implemented is methylation in certain adenosines, which helps Mtb with antibiotic resistance. Our studies found that a naturally derived molecule, SEQ-9, effectively inhibits the methylated Mtb ribosome. By determining the structures of SEQ-9-bound ribosomes, we concluded that SEQ-9 would undergo conformational changes to accommodate the methylation and still be able to inhibit the ribosome. Our results were part of research supported by multiple labs and a pharmaceutical company, Sanofi R&D, and are published in Cell. 2). An antibody derived from AP205 against Acinetobacter genomospecies 16 cells. This research aims to study the organizational pattern of AP205 and the phage-host relationship. Using Cryo-EM, we obtained high-resolution structures of AP205, the host acceptor, and the AP205-host receptor complex. We designed an antibody-like protein based on the structures, and the protein successfully targeted the host receptor. A collaborator is working on the antibody to illustrate its effects against the host. 3). An ongoing project studying Mtb ClpXP protease complex. Mtb ClpXP protease complex plays an essential role in cellular proteohomeostasis. The complex recognizes unfolded/misfolded proteins and degrades them to prevent abnormal activities. Dysregulation of ClpXP functions can cause detrimental effects on cells. To understand the function of the ClpXP complex, we performed structural analysis on the ClpXP complex and yielded a high-resolution structure. We also observed a structure that has yet to be discovered
Multi-coil Wireless Power Transfer Systems Analysis and Design
No full textWireless power transfer (WPT) technology is growing fast and has been used for various applications. experiencing rapid growth and finding applications across various sectors. Emerging markets, such as consumer electronics, electric vehicles, and medical implants, are actively exploring the integration of wireless power transfer as an energy solution. Numerous studies have advanced proposals for WPT coil designs, resonant circuit designs, and the incorporation of wide bandgap devices into WPT systems. Concurrently, multi-coil WPT systems, employing more than one coil on either the transmitter or the receiver, have gained prominence. Among these, three-phase wireless power transfer systems have demonstrated several advantages and exhibit potential as viable solutions for technical challenges encountered in the industry.
The first research topic revolves around wireless lithium battery charging, a critical component of electric vehicles. The charging process for lithium batteries requires a sequential application of constant current (CC) charging succeeded by constant voltage (CV) charging. This paper presents a novel reconfigurable compensation topology designed for three-phase wireless charging systems. The reconfigurable compensation topology facilitates a seamless transition between the inductor-capacitor-capacitor-parallel (LCC-P) configuration and the inductor-capacitor-capacitor-series (LCC-S) configuration. This enables the output to exhibit CC and CV characteristics, respectively.
The second research topic delves into wireless power transfer for autonomous underwater vehicles (AUVs). Charging AUVs presents unique challenges due to insulation and water leakage issues when submerged. The application of three-phase wireless power transfer encounters complexities, primarily stemming from uncontrollable docking angles leading to rotational misalignment issues. In response to these challenges, a three-phase wireless power transfer coil resistant to rotational misalignment has been proposed, simulated, and tested
Accuracy of Three Digital Impression Techniques for Implant-Fixed Complete Dentures
No full textEvidence comparing accuracy of implant-fixed complete denture (IFCD) impression techniques is unclear. The purpose of this in vitro study was to compare the accuracy of three digital impression techniques for IFCD.
A polyurethane edentulous mandible with four implant analogs served as the master model. A reference scan was made using a laboratory scanner. Test scans (n=10 per group) were made for the three groups: splinted IOS (Group S), non-splinted IOS (Group NS), and photogrammetry (Group PG). All scans were exported in standard tessellation language (STL) format and superimposed to compare linear, angular, and RMS deviations using a three-dimensional metrology software. Statistical analysis was performed using Kruskal-Wallis test for non-normally distributed data (a = 0.05).
No significant difference in overall accuracy was seen between the three groups. No significant difference in accuracy was seen when splinting ISBs. Significant differences in accuracy were seen within each group depending on position in the arch; higher angular deviation was seen at position RM1 in Group PG and Group S (p<.001).
Digital impressions for IFCD using either IOS or PG yielded similar results. Splinting ISBs did not seem to have a beneficial effect on accuracy. All three methods produced clinically acceptable results
Bayesian Optimization of Coupled Systems
No full textThe field of multidisciplinary design optimization (MDO) addresses the complex challenge of optimizing systems characterized by interconnections or couplings, which significantly increases the computational burden for ensuring reliability in optimization outcomes. Particularly, design challenges involving feedback-coupled systems are notorious for their substantial demands on computational resources. In response to this issue, substantial efforts have been directed towards developing surrogate models that accurately replicate the intricate interconnected nature of these systems. Such models promise to drastically reduce computational expenses while maintaining effectiveness. Although Bayesian Optimization (BO) is traditionally celebrated for its efficiency in querying surrogate models, it encounters significant limitations when applied to constructing surrogate models for interconnected systems. Specifically, the black-box nature of BO struggles to capture the complexities of these systems, often necessitating frequent queries to the actual functions for training set updates. This approach, while potentially reliable, results in prohibitive computational costs.
To address these challenges and enhance the efficiency and reliability of optimization in the context of interconnected systems, we propose a novel methodology. This methodology focuses on the construction and querying of interconnected surrogate models, designed to more effectively and efficiently replicate the behavior of the target systems. By overcoming the limitations of traditional black-box models, our approach aims to provide a viable solution to the computational and practical challenges inherent in multidisciplinary design optimization of feedback-coupled systems. This advancement represents a significant leap forward in the pursuit of computationally efficient and reliable optimization techniques for complex, interconnected systems
Characterizing Membrane Protein-Lipid Interactions by Native Mass Spectrometry
No full textNative mass spectrometry (MS) is a powerful tool for quantitatively characterizing protein complexes and the interactions between protein and ligands due to the capability of preserving non-covalent interactions during measurement. However, preserving non-covalent interactions in native MS studies for membrane protein complexes can be challenging. Higher activation energy is usually needed for desolvation and detergent release, resulting in higher charge states on membrane protein, disrupting the tertiary structure and non-covalent interactions. Therefore, reducing the charges carried on membrane protein is crucial for native MS study. A series of distinct charge-reducing molecules, polyamines, were investigated for their application in reducing charges on membrane protein. The results indicate that polyamines exhibit enhanced charge-reduction potency, presenting innovative strategies to modulate charge states and preserve non-covalent interactions during native MS studies.
In addition to discovering charge-reducing molecules, native MS was applied to characterize bacterial ATP-binding cassette (ABC) transporter MsbA, a crucial player in bacteria lipopolysaccharides (LPS) biogenesis, and its interactions with lipids. This study discovered the binding of copper (II) to MsbA that modulates MsbA-lipid interactions, with atomic structure resolved by X-ray crystallography. In addition, the results of this study revealed the conformation-dependent lipid binding affinities of MsbA by native MS, especially for the LPS precursor, 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)2-lipid A (KDL). This finding from native MS guided the structural biology study that resolved a 3.6 ��-resolution structure of MsbA in an open, outward-facing conformation, revealing previously undiscovered KDL binding sites that are important for the functions of MsbA.
This study also explored the thermodynamics of the interactions between MsbA and KDL. Despite identifying two distinct LPS binding sites on MsbA, the thermodynamic basis for the interactions of MsbA-KDL remained unclear. Native MS revealed that KDL binding to MsbA is mainly driven by entropy. Basic residues contribute to the binding of KDL through positive coupling entropy, overcoming unfavorable coupling enthalpy. These findings indicated the effect of solvent reorganization, specifically the desolvation of lipid binding sites and the lipid headgroup, in driving KDL binding to MsbA. This study provides new insights into thermodynamic contributions from residues in membrane proteins to lipid binding
Modulating the Tumor Microenvironment via Plga-Mno2 Nanoparticle Mediated Hypoxia Reduction Leads to Increased Immune Responses Against Bone Metastases
No full textBone metastases result in a stark decrease in survivability in cancer cases, with most treatment options focusing on palliative care. Newer therapies, such as immunotherapies, use the patient���s immune cells to target tumors, sometimes to great effect. Though immunotherapies have been effective against some advanced-stage tumors, there has been limited success with bone metastases. Persistent hypoxia in the bone, necessary to maintain the hematopoietic stem cells, induces an immunosuppressive microenvironment that blunts the activity of cytotoxic immune cells against bone metastases. To address this, we have developed a nanoparticle capable of modulating the bone metastasis microenvironment to improve the antitumoral immune response. In this study, we use manganese dioxide nanoparticles (MnO2 NP) to catalyze the degradation of tumor-produced hydrogen peroxide, thereby generating oxygen. For improved biocompatibility and modulation of oxygen production, the MnO2 NPs were encapsulated into poly lactic-co-glycolic acid (PLGA-MnO2 NPs) to produce particles provide sustained high oxygen tension. The PLGA-MnO2 NPs were biocompatible, reduced hypoxia after penetration into the core of cancer spheroids, and decreased hypoxia-induced factor 1 alpha expression. Reducing hypoxia in the spheroid resulted in a decrease in adenosine, and lactate, immunosuppressive metabolites. Notably, the spheroids��� microenvironment changes enhanced NK cells' cytotoxicity, which obliterated the spheroids. Then, to address chronic hypoxia, we then developed altered the PLGA formulation to create poly lactic(50)-co-glycolic(50) (50:50 PLGA), poly lactic(75)-co-glycolic(25) (75:25 PLGA) and poly lactic acid (PLA) encapsulated MnO2 NPs. We then analyzed the oxygen kinetics due to each polymer type and showed that the 50:50 PLGA-MnO2 NPs exhibited the best short- and long-term control of hypoxia in cancer spheroids and the PLA-MnO2 NPs possessing the slowest O2 generation kinetics. In vivo, the 50:50 PLGA-MnO2 showed greater accumulation in the long bones and pelvis, common sites for bone metastases. The NPs decreased hypoxia in bone metastases and decreased regulatory T cell levels, resulting in enhanced survival of mice with established bone metastases
Characterization of a Hypersonic Turbulent Boundary Layer Using the VENOM Technique
No full textModeling fluctuating flow parameters of high speed laminar and turbulent boundary layers is essential for understanding the thermal loading experienced by vehicles re-entering the atmosphere. Hypersonic turbulent flows in particular are challenging to model due to the strong coupling of velocity and energy which drive heat flux. Experimental data of the relationship between these fluctuating quantities are limited due to the required simultaneous measurements of velocity, temperature, and density. Laser diagnostics have become key to measuring these fundamental parameters in unsteady hypersonic flows due to their non-intrusive nature and ability to provide fluctuating measurements, which can be used to assess current predictive turbulence models.
Mean and instantaneous velocity and temperature measurements using the ���Invisible Ink��� Vibrationally Excited Nitric Oxide Monitoring (VENOM) laser diagnostic are presented to characterize the hypersonic boundary layer above a 2.75 degree half-angle wedge test article. The measurements were performed in the Actively Controlled Expansion (ACE) blow-down wind tunnel under both laminar and turbulent conditions. A double dependent Gaussian fitting velocimetry algorithm was developed to account for laser reflections at the wall, and intensity fluctuations due to turbulent motion. Additionally, rotational temperature profiles were using a thermometry algorithm in conjunction with velocity information extracted from each image. The results demonstrated a uniform laminar flow across the flat plate which broke down to turbulence in response to inserted mechanical trips. Freestream fluctuations compare favorably to previous measurements. The laminar boundary layer fluctuations peak around 12% for the velocimetry results and 20% for the thermometry results. The turbulence fluctuations peaked around 18% and 24% for the velocimetry and thermometry results respectively. Using the laminar results as a baseline for the technique uncertainty, it is estimated the true turbulence fluctuations are on the order of 10���15%. The mean and instantaneous measurements qualitatively agree with previous separate velocity and temperature measurements and simulations. The generated database of instantaneous parameters can be used to directly determine the variable heat flux of the flow over the wedge surface using a constant specific heat model to assess current predictive turbulence models. The current measurements are analysis can also serve as a basis for future multi-component velocity and temperature boundary layer measurements, contributing to a comprehensive understanding of turbulence, a complex 3D phenomenon
Development of a Constant-Volume Bomb Experiment for the Study of Lithium-Ion Battery Thermal Runaway and Its Associated Hazards
No full textLithium-ion battery (LIB) thermal runaway (TR) has increasingly become a serious concern for consumer safety. As a result, many different LIB TR experiments have been developed to study this phenomenon. The present study outlines the development of a LIB TR experiment that seeks to improve upon the preexisting methodologies. The experiment centers around a constant-volume vessel with a programmable heating controller and external gas system to allow for complete control of testing parameters. The results for representative tests of a single cell are presented to illustrate the experiment���s fidelity. Two different LIBs were utilized for these tests which were performed in air at standard ambient conditions and heated at a rate of ~5 ��C /min. The first test was an LG INR18650 cell at 100% state-of-charge (SoC) which had a TR onset temperature of 142 ��C to 175 ��C and produced 0.18 �� 0.004 moles of gas. These values and the composition of the gas were consistent with literature.
The next three tests were performed with Panasonic NCR 18650b cells at 0%, 50%, and 100% SoC. It was found that increasing the SoC of the battery led to increased reactivity and agreed with relevant literature. Particles ejected from these batteries were also characterized using scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD), and x-ray photoelectron spectroscopy (XPS). The 0% SoC battery produced no ejected particles, so the debris was collected from the 50% and 100% tests. Additionally, the particles collected from the 50% test were sieved into the following size ranges: (1) > 212 ��m; (2) 75-212 ��m; (3) 25-75 ��m; and (4) ��� 25 ��m. Qualitative and quantitative sizing of SEM images taken from these samples found particles ranging from the microscale to nanoscale. It was found that approximately 75% of the particles in the ��� 25 ��m were less than 8 ��m. The EDS, XRD, and XPS techniques identified various compounds created from reactions which took place between the different battery components. Future testing efforts seek to further validate the processes developed for this experiment and continue investigating the hazards associated with LIB TR
High-Temperature Ignition of HTPB-Based Mixtures in a Shock Tube
No full textHydroxyl-terminated polybutadiene (HTPB) is a molecule of continued interest within the aerospace community due to its excellent mechanical characteristics and combustibility as a rocket propellant ingredient. Recent developments in the defense and space industry such as the development of solid-fuel ramjets and solid rocket propellants depend on the characterization of HTPB as a fuel. However, much of the transport and thermodynamic data available for HTPB are relatively unknown due to the pyrolysis of HTPB to ethylene and butadiene occurring near the vaporization temperature of HTPB. The time scale of this pyrolysis is on the order of seconds and, therefore, a characterization of HTPB using timescales under one second is necessary. To achieve the sub-second characterization, the High-Pressure Shock Tube (HPST) at the TEES Turbomachinery Laboratory was utilized. A recent development for the HPST is the endwall injector system which utilizes the increase in temperature and pressure of the incident wave of the shock tube to vaporize the liquid fuel prior to the arrival of the post-reflected-shock conditions. The fuel is placed into the barrel of the injector, and the injector is actuated when the incident shock wave arrives at the location of a pressure transducer 2 m upstream from the endwall. The injector subsequently opens and allows 40 psia of air to blow through the fuel meniscus, sending it into the shock tube where it vaporizes upon interacting with the hot gas behind the incident wave. This thesis utilized the endwall injector system to test HTPB in sub-second time frames and record combustion at 2.5- and 4.25-atm conditions over a temperature range of 1230 to 1400 K. Additionally, in-situ additives were synthesized in the HTPB by collaborators at the University of Central Florida to produce HTPB-based mixtures without affecting the mechanical behavior of the fuel. This thesis studied a titania-infused HTPB mixture at a pressure of 4.25 atm and a temperature range of 1230 to 1400 K. Following the experiments of the HTPB based mixtures is a brief overview of the chemical kinetics data currently available on HTPB and current issues in modeling the molecule
Application of Image-based Techniques to Analyze Coastal Flows and to Evaluate Temporal Wetland Changes
No full textCoastal transport processes occurring at the landward edge of tidal and wave action are important for the diversity of coastal ecosystems, determining nutrient fluxes, the dynamics of sediment and marine pollution during tidal mixing, and controlling coastal geomorphology. Understanding these processes requires large-scale field observations over modest spatial domains to fully resolve their governing mechanisms and to validate and update algorithms in existing numerical and laboratory simulations. This dissertation investigates the application of remote sensing techniques based on UAS and satellite imagery to monitor large-scale coastal processes along the Texas coast, particularly focusing on Galveston Bay, TX. First, surface current mapping methods using UAS video sequences are presented to provide a means of practical measurements of ocean surface currents for the effective prediction of tidal mixing exchange dynamics. The main method, introduced by Stre��er et al. (2017), utilizes a two-dimensional space-plus-time Fourier transform of UAS imagery, linked to the Doppler-shifted dispersion relation fitting technique for surface gravity waves. The resulting current fields reveal the flow structures of tidal currents through inlets at Freeport Harbor and Galveston Bay entrance in flexible spatial resolution. Second, satellite images from Sentinel-2 near Galveston Bay inlet are utilized to bridge the knowledge gap between a series of laboratory, numerical, and limited field studies on tidal vortices to observe their large-scale formation and the influence of coastal currents. A classification scheme is introduced to identify two types of vortex flow patterns observed in the satellite imagery. This classification scheme is validated at Galveston Bay using different satellite images from MODIS with a larger dataset. Lastly, shoreline change monitoring at coastal wetlands in Galveston Bay is explored, leveraging geospatial mapping from UAS imagery enhanced by a new georectification technique adapting the particle image velocimetry (PIV) algorithm. A time series of wetland maps, generated using a Structure-from-Motion (SfM) technique, facilitates the computation of shoreline change rates along the observed wetland boundaries. Subsequent statistical analysis of these rates allows for an assessment of the impact of seasonal variations and storm events on short-term wetland evolution