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- Genre: Doctoral Dissertation
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
Mycobacterial infections, as represented by leprosy and tuberculosis, have persisted as human pathogens for millennia. Their environmental counterparts, nontuberculous mycobacteria (NTM), are commodious infectious agents endowed with extensive innate and acquired antimicrobial resistance. The current drug development process selects for antibiotics with high specificity for definitive targets within bacterial metabolic and replication pathways. Because these compounds demonstrate limited efficacy against mycobacteria, novel antimycobacterial agents with unconventional mechanisms of action were identified. Two highly resistant NTMs, Mycobacterium abscessus (Mabs) a rapid-growing respiratory, skin, and soft tissue pathogen, and Mycobacterium ulcerans (MU), the causative agent of Buruli ulcer, were selected as targets. Compounds that indicated antimicrobial activity against other highly resistant pathogens were selected for initial screening. Antimicrobial peptides (AMPs) have demonstrated activity against a variety of bacterial pathogens, including mycobacterial species. Designed antimicrobial peptides (dAMPs), rationally-designed and synthetic contingents, combine iterative features of natural AMPs to achieve superior antimicrobial activity in resistant pathogens. Initial screening identified two dAMPs, RP554 and RP557, with bactericidal activity against Mabs. Clay-associated ions have previously demonstrated bactericidal activity against MU. Synthetic and customizable aluminosilicates have also demonstrated adsorption of bacterial cells and toxins. On this basis, two aluminosilicate materials, geopolymers (GP) and ion-exchange nanozeolites (IE-nZeos), were screened for antimicrobial activity against MU and its fast-growing relative, Mycobacterium marinum (Mmar). GPs demonstrated adsorption of MU cells and mycolactone, a secreted, lipophilic toxin, whereas Cu-nZeos and Ag-nZeos demonstrated antibacterial activity against MU and Mmar. Cumulatively, these results indicate that an integrative drug selection process may yield a new generation of antimycobacterial agents.
ContributorsDermody, Roslyn June (Author) / Haydel, Shelley E (Thesis advisor) / Bean, Heather (Committee member) / Nickerson, Cheryl (Committee member) / Stephanopoulos, Nicholas (Committee member) / Arizona State University (Publisher)
Created2022
Description
The objective of this dissertation is to study the optical and radiative properties of inhomogeneous metallic structures. In the ongoing search for new materials with tunable optical characteristics, porous metals and nanowires provides an extensive design space to engineer its optical response based on the morphology-dependent phenomena.This dissertation firstly discusses the use of aluminum nanopillar array on a quartz substrate as spectrally selective optical filter with narrowband transmission for thermophotovoltaic systems. The narrow-band transmission enhancement is attributed to the magnetic polariton resonance between neighboring aluminum nanopillars. Tuning of the resonance wavelengths for selective filters was achieved by changing the nanopillar geometry. It concludes by showing improved efficiency of Gallium-Antimonide thermophotovoltaic system by coupling the designed filter with the cell.
Next, isotropic nanoporous gold films are investigated for applications in energy conversion and three-dimensional laser printing. The fabricated nanoporous gold samples are characterized by scanning electron microscopy, and the spectral hemispherical reflectance is measured with an integrating sphere. The effective isotropic optical constants of nanoporous gold with varying pore volume fraction are modeled using the Bruggeman effective medium theory.
Nanoporous gold are metastable and to understand its temperature dependent optical properties, a lab-scale fiber-based optical spectrometer setup is developed to characterize the in-situ specular reflectance of nanoporous gold thin films at temperatures ranging from 25 to 500 oC. The in-situ and the ex-situ measurements suggest that the
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specular, diffuse, and hemispherical reflectance varies as a function of temperature due to the morphology (ligament diameter) change observed.
The dissertation continues with modeling and measurements of the radiative properties of porous powders. The study shows the enhanced absorption by mixing porous copper to copper powder. This is important from the viewpoint of scalability to get end products such as sheets and tubes with the requirement of high absorptance that can be produced through three-dimensional printing.
Finally, the dissertation concludes with recommendations on the methods to fabricate the suggested optical filters to improve thermophotovoltaic system efficiencies. The results presented in this dissertation will facilitate not only the manufacturing of materials but also the promising applications in solar thermal energy and optical systems.
ContributorsRamesh, Rajagopalan (Author) / Wang, Liping (Thesis advisor) / Azeredo, Bruno (Thesis advisor) / Phelan, Patrick (Committee member) / Yu, Hongbin (Committee member) / Rykaczewski, Konrad (Committee member) / Arizona State University (Publisher)
Created2022
Description
Mycobacterium tuberculosis (Mtb), the etiological agent of the tuberculosis disease, is estimated to infect one-fourth of the human population and is responsible for 1.5 million deaths annually. The increased emergence of bacterial resistance to clinical interventions highlights the lack in development of novel antimicrobial therapeutics. Prototypical bacterial two-component systems (TCS) allow for sensing of extracellular stimuli and relay thereof to create a transcriptional response. The prrAB TCS is essential for viability in Mtb, presenting itself as an attractive novel drug target. In Mtb, PrrAB is involved in the adaptation to the intra-macrophage environment and recent work implicates PrrAB in the dosR-dependent hypoxia adaptation. This work defines a direct molecular and regulatory connection between Mtb PrrAB and the dosR-dependent hypoxia response. Using electrophoretic mobility shift assays combined with surface plasmon resonance, the Mtb dosR gene is established as a specific target of PrrA, corroborated by fluorescence reporter assays demonstrating a regulatory relationship. Considering the scarce understanding of prrAB essentiality in nontuberculous mycobacteria and the presence of multiple prrAB orthologs in Mycobacterium smegmatis and Mycobacterium abscessus, CRISPR interference was utilized to evaluate the essentiality of PrrAB beyond Mtb. prrAB was found to be inessential for viability in M. smegmatis yet required for in vitro growth. Conversely, M. abscessus prrAB repression led to enhanced in vitro growth. Diarylthiazole-48 (DAT-48) displayed decreased selectivity against M. abscessus but demonstrated enhanced intrinsic activity upon prrAB repression in M. abscessus. Lastly, to aid in the rapid determination of mycobacterial drug susceptibility and the detection of mycobacterial heteroresistance, the large volume scattering imaging (LVSim) platform was adapted for mycobacteria. Using LVSim, Mtb drug susceptibility was detected phenotypically within 6 hours, and clinically relevant mycobacterial heteroresistance was detected phenotypically within 10 generations. The data generated in these studies provide insight into the essential role of PrrAB in Mtb and its involvement in the dosR-dependent hypoxia adaptation, advance the understanding of mycobacterial PrrAB essentiality and PrrAB-associated mycobacterial growth dependency. These studies further establish molecular and mechanistic connection between PrrAB and DAT-48 in Mtb and M. abscessus and develop a rapid phenotypic drug susceptibility testing platform for mycobacteria.
ContributorsHaller, Yannik Alex (Author) / Haydel, Shelley E (Thesis advisor) / Bean, Heather (Committee member) / Nickerson, Cheryl (Committee member) / Plaisier, Christopher (Committee member) / Acharya, Abhinav (Committee member) / Arizona State University (Publisher)
Created2023
Description
Energy storage technologies are essential to overcome the temporal variability in renewable energy. The primary aim of this thesis is to develop reactor solutions to better analyze the potential of thermochemical energy storage (TCES) using non-stoichiometric metal oxides, for the multi-day energy storage application. A TCES system consists of a reduction reactor and an insulated MOx storage bin. The reduction reactor heats (to ~ 1100 °C) and partially reduces the MOx, thereby adding sensible and chemical energy (i.e., charging it) under reduced pO2 environments (~10 Pa). Inert gas removes the oxygen generated during reduction. The storage bin holds the hot and partially reduced MOx (typically particles) until it is used in an energy recovery device (i.e., discharge). Irrespective of the reactor heat source (here electrical), or the particle-inert gas flows (here countercurrent), the thermal reduction temperature and inert gas (here N2) flow minimize when the process approaches reversibility, i.e., operates near equilibrium. This study specifically focuses on developing a reduction reactor based on the theoretical considerations for approaching reversibility along the reaction path. The proposed Zigzag flow reactor (ZFR) is capable of thermally reducing CAM28 particles at temperatures ~ 1000 °C under an O2 partial pressure ~ 10 Pa. The associated analytical and numerical models analyze the reaction equilibrium under a real (discrete) reaction path and the mass transfer kinetic conditions necessary to approach equilibrium. The discrete equilibrium model minimizes the exergy destroyed in a practical reactor and identifies methods of maximizing the energy storage density () and the exergetic efficiency. The mass transfer model analyzes the O2 N2 concentration boundary layers to recommend sizing considerations to maximize the reactor power density. Two functional ZFR prototypes, the -ZFR and the -ZFR, establish the proof of concept and achieved a reduction extent, Δδ = 0.071 with CAM28 at T~950 °C and pO2 = 10 Pa, 7x higher than a previous attempt in the literature. The -ZFR consistently achieved > 100 Wh/kg during >10 h. runtime and the -ZFR displayed an improved = 130 Wh/kg during >5 h. operation with CAM28. A techno-economic model of a grid-scale ZFR with an associated storage bin analyzes the cost of scaling the ZFR for grid energy storage requirements. The scaled ZFR capital costs contribute < 1% to the levelized cost of thermochemical energy storage, which ranges from 5-20 ¢/kWh depending on the storage temperature and storage duration.
ContributorsGhotkar, Rhushikesh (Author) / Milcarek, Ryan (Thesis advisor) / Ermanoski, Ivan (Committee member) / Phelan, Patrick (Committee member) / Wang, Liping (Committee member) / Wang, Robert (Committee member) / Arizona State University (Publisher)
Created2023
Description
A well-insulated dark conventional rooftop can be hotter than any other urban surface, including pavements. Since rooftops cover around 20 – 25% of most urban areas, their role in the urban heat island effect is significant. In general, buildings exchange heat with the surroundings in three ways: heat release from the cooling/heating system, air exchange associated with exfiltration and relief air, and heat transfer between the building envelope and surroundings. Several recent studies show that the building envelope generates more heat release into the environment than any other building component.Current advancements in material science have enabled the development of materials and coatings with very high solar reflectance and thermal emissivity, and that can alter their radiative properties based on surface temperature. This dissertation is an effort to quantify the impact of recent developments in such technologies on urban air. The current study addresses three specific unresolved topics: 1) the relative importance of rooftop solar reflectance and thermal emissivity, 2) the role of rooftop radiative properties in different climates, and 3) the impact of temperature-adaptive exterior materials/coatings on building energy savings and urban cooling. The findings from this study show that the use of rooftop materials with solar reflectance above 0.9 maintain the surface temperature below ambient air temperature most of the time, even when the materials have conventional thermal emissivity (0.9). This research has demonstrated that for hot cities, rooftops with high solar reflectance and thermal emittance maximize building energy savings and always cool the surrounding air. For moderate climate regions, high solar reflectance and low thermal emittance result in the greatest building energy cost savings. This combination of radiative properties cools the air during the daytime and warms it at night. Finally, this research found that temperature-adaptive materials could play a significant role in reducing utility costs for poorly insulated buildings, but that they heat the surrounding air in the winter, irrespective of the rooftop insulation.
Through the detailed analysis of building façade radiative properties, this dissertation offers climate-specific design guidance that can be used to simultaneously optimize energy costs while minimizing adverse warming of the surrounding environment.
ContributorsPrem Anand Jayaprabha, Jyothis Anand (Author) / Sailor, David (Thesis advisor) / Phelan, Patrick (Thesis advisor) / Huang, Huei-Ping (Committee member) / Wang, Liping (Committee member) / Yeom, Dongwoo Jason (Committee member) / Arizona State University (Publisher)
Created2022
Description
Siloxane, a common contaminant present in biogas, is known for adverse effects on cogeneration prime movers. In this work, the solid oxide fuel cell (SOFC) nickel-yttria stabilized zirconia (Ni-YSZ) anode degradation due to poisoning by siloxane was investigated. For this purpose, experiments with different fuels, different deposition substrate materials, different structure of contamination siloxane (cyclic and linear) and entire failure process are conducted in this study. The electrochemical and material characterization methods, such as Electrochemical Impedance Spectroscopy (EIS), Scanning Electron Microscope- Wavelength Dispersive Spectrometers (SEM-WDS), X-ray Photoelectron Spectroscopy (XPS), X-ray Diffraction (XRD), and Raman spectroscopy, were applied to investigate the anode degradation behavior. The electrochemical characterization results show that the SOFCs performance degradation caused by siloxane contamination is irreversible under bio-syngas condition. An equivalent circuit model (ECM) is developed based on electrochemical characterization results. Based on the Distribution of Relaxation Time (DRT) method, the detailed microstructure parameter changes are evaluated corresponding to the ECM results. The results contradict the previously proposed siloxane degradation mechanism as the experimental results show that water can inhibit anode deactivation. For anode materials, Ni is considered a major factor in siloxane deposition reactions in Ni-YSZ anode. Based on the results of XPS, XRD and WDS analysis, an initial layer of carbon deposition develops and is considered a critical process for the siloxane deposition reaction. Based on the experimental results in this study and previous studies about siloxane deposition on metal oxides, the proposed siloxane deposition process occurs in stages consisting of the siloxane adsorption, initial carbon deposition, siloxane polymerization and amorphous silicon dioxide deposition.
ContributorsTian, Jiashen (Author) / Milcarek, Ryan J. (Thesis advisor) / Muhich, Christopher (Committee member) / Wang, Liping (Committee member) / Phelan, Patrick (Committee member) / Nian, Qiong (Committee member) / Arizona State University (Publisher)
Created2022
Description
Polarization detection and control techniques play essential roles in various applications, including optical communication, polarization imaging, chemical analysis, target detection, and biomedical diagnosis. Conventional methods for polarization detection and polarization control require bulky optical systems. Flat optics opens a new way for ultra-compact, lower-cost devices and systems for polarization detection and control. However, polarization measurement and manipulating devices with high efficiency and accuracy in the mid-infrared (MIR) range remain elusive. This dissertation presented design concepts and experimental demonstrations of full-Stokes parameters detection and polarization generation devices based on chip-integrated plasmonic metasurfaces with high performance and record efficiency. One of the significant challenges for full-Stokes polarization detection is to achieve high-performance circular polarization (CP) filters. The first design presented in this dissertation is based on the direct integration of plasmonic quarter-wave plate (QWP) onto gold nanowire gratings. It is featured with the subwavelength thickness (~500nm) and extinction ratio around 16. The second design is based on the anisotropic thin-film interference between two vertically integrated anisotropic plasmonic metasurfaces. It provides record high efficiency (around 90%) and extinction ratio (>180). These plasmonic CP filters can be used for circular, elliptical, and linear polarization generation at different wavelengths. The maximum degree of circular polarization (DOCP) measured from the sample achieves 0.99998.
The proposed CP filters were integrated with nanograting-based linear polarization (LP) filters on the same chip for single-shot polarization detection. Full-Stokes measurements were experimentally demonstrated with high accuracy at the single wavelength using the direct subtraction method and over a broad wavelength range from 3.5 to 4.5mm using the Mueller matrix method. This design concept was later expanded to a pixelized array of polarization filters. A full-Stokes imaging system was experimentally demonstrated based on integrating a metasurface with pixelized polarization filters arrays and an MIR camera.
ContributorsBai, Jing (Author) / Yao, Yu (Thesis advisor) / Balanis, Constantine A. (Committee member) / Wang, Liping (Committee member) / Zhang, Yong-Hang (Committee member) / Arizona State University (Publisher)
Created2021
Description
In this dissertation, two types of passive air freshener products from Henkel, the wick-based air freshener and gel-based air freshener, are studied for their wicking mechanisms and evaporation performances.The fibrous pad of the wick-based air freshener is a porous medium that absorbs fragrance by capillary force and releases the fragrance into the ambient air. To investigate the wicking process, a two-dimensional multiphase flow numerical model using COMSOL Multiphysics is built. Saturation and liquid pressure inside the pad are solved. Comparison between the simulation results and experiments shows that evaporation occurs simultaneously with the wicking process. The evaporation performance on the surface of the wicking pad is analyzed based on the kinetic theory, from which the mass flow rate of molecules passing the interface of each pore of the porous medium is obtained. A 3D model coupling the evaporation model and dynamic wicking on the evaporation pad is built to simulate the entire performance of the air freshener to the environment for a long period of time. Diffusion and natural convection effects are included in the simulation. The simulation results match well with the experiments for both the air fresheners placed in a chamber and in the absent of a chamber, the latter of which is subject to indoor airflow.
The gel-based air freshener can be constructed as a porous medium in which the solid network of particles spans the volume of the fragrance liquid. To predict the evaporation performance of the gel, two approaches are tested for gel samples in hemispheric shape. The first approach is the sessile drop model commonly used for the drying process of a pure liquid droplet. It can be used to estimate the weight loss rate and time duration of the evaporation. Another approach is to simulate the concentration profile outside the gel and estimate the evaporation rate from the surface of the gel using the kinetic theory. The evaporation area is updated based on the change of pore size. A 3D simulation using the same analysis is further applied to the cylindrical gel sample. The simulation results match the experimental data well.
ContributorsYuan, Jing (Author) / Chen, Kangping (Thesis advisor) / Herrmann, Marcus (Committee member) / Huang, Huei-Ping (Committee member) / Wang, Liping (Committee member) / Jiao, Yang (Committee member) / Arizona State University (Publisher)
Created2021
Description
The relationships between the properties of materials and their microstructures have been a central topic in materials science. The microstructure-property mapping and numerical failure prediction are critical for integrated computational material engineering (ICME). However, the bottleneck of ICME is the lack of a clear understanding of the failure mechanism as well as an efficient computational framework. To resolve these issues, research is performed on developing novel physics-based and data-driven numerical methods to reveal the failure mechanism of materials in microstructure-sensitive applications.
First, to explore the damage mechanism of microstructure-sensitive materials in general loading cases, a nonlocal lattice particle model (LPM) is adopted because of its intrinsic ability to handle the discontinuity. However, the original form of LPM is unsuitable for simulating nonlinear behavior involving tensor calculation. Therefore, a damage-augmented LPM (DLPM) is proposed by introducing the concept of interchangeability and bond/particle-based damage criteria. The proposed DLPM successfully handles the damage accumulation behavior in general material systems under static and fatigue loading cases.
Then, the study is focused on developing an efficient physics-based data-driven computational framework. A data-driven model is proposed to improve the efficiency of a finite element analysis neural network (FEA-Net). The proposed model, i.e., MFEA-Net, aims to learn a more powerful smoother in a multigrid context. The learned smoothers have good generalization properties, and the resulted MFEA-Net has linear computational complexity. The framework has been applied to efficiently predict the thermal and elastic behavior of composites with various microstructural fields. Finally, the fatigue behavior of additively manufactured (AM) Ti64 alloy is analyzed both experimentally and numerically. The fatigue experiments show the fatigue life is related with the contour process parameters, which can result in different pore defects, surface roughness, and grain structures. The fractography and grain structures are closely observed using scanning electron microscope. The sample geometry and defect/crack morphology are characterized through micro computed tomography (CT). After processing the pixel-level CT data, the fatigue crack initiation and growth behavior are numerically simulated using MFEA-Net and DLPM. The experiments and simulation results provided valuable insights in fatigue mechanism of AM Ti64 alloy.
ContributorsMeng, Changyu (Author) / Liu, Yongming (Thesis advisor) / Hoover, Christian (Committee member) / Li, Lin (Committee member) / Peralta, Pedro (Committee member) / Wang, Liping (Committee member) / Arizona State University (Publisher)
Created2023