Matching Items (144)
Description
The objective of this thesis was to determine whether Zika Virus (ZIKV) can be effectively inactivated by Selective Photonic Disinfection (SEPHODIS) and determine whether key proteins involved in the infection process are preserved, making SEPHODIS a possible source for vaccine development. As of January 2018, there have been 3,720 confirmed cases of Congenital Zika Syndrome in infants, making a Zika Vaccine a high priority (Mitchell, 2018). SEPHODIS is a process that involves prolonged exposure of an object to a pulsing laser which can render it ineffective. Initially, ZIKV was subjected to laser inactivation for 6 hours, then a plaque assay was performed on both laser-treated and control samples. ZIKV was inactivated two-fold? after laser treatment, when compared with control, as indicated by the plaque assay results. Additionally, both samples were submitted to ELISA to evaluate antigenicity with a panel of monoclonal and human sera. As a second control, virus inactivated by formaldehyde (2%) was used. ELISA results showed that antigenicity of some proteins were preserved while others were probably disturbed. However, ELISA results show that ZIKV envelope protein (E-protein), the protein responsible for viral entry into cells, was effectively preserved after laser-treatment, implying that if laser parameters were tweaked to obtain more complete inactivation, then SEPHODIS may be an appropriate source for the development of a vaccine.
ContributorsViafora, Ataiyo Blue (Author) / Johnston, Stephen (Thesis director) / Tsen, Kong-Thon (Committee member) / School of Life Sciences (Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
PD-L1 blockade has shown recent success in cancer therapy and cancer vaccine regimens. One approach for anti-PD-L1 antibodies has been their application as adjuvants for cancer vaccines. Given the disadvantages of such antibodies, including long half-life and adverse events related to their use, a novel strategy using synbodies in place of antibodies can be tested. Synbodies offer a variety of advantages, including shorter half-life, smaller size, and cheaper cost. Peptides that could bind PD-L1 were identified via peptide arrays and used to construct synbodies. These synbodies were tested with inhibition ELISA assays, SPR, and pull down assays. Additional flow cytometry analysis was done to determine the binding specificity of the synbodies to PD-L1 and the ability of those synbodies to inhibit the PD-L1/PD-1 interaction. Although analysis of permeabilized cells expressing PD-L1 indicated that the synbodies could successfully bind PD-L1, those results were not replicated in non-permeabilized cells. Further assays suggested that the binding of the synbodies was non-specific. Other tests were done to see if the synbodies could inhibit the PD-1/PD-L1 interaction. This assay did not yield any conclusive results and further experimentation is needed to determine the efficacy of the synbodies in inhibiting this interaction.
ContributorsMujahed, Tala (Author) / Johnston, Stephen (Thesis director) / Blattman, Joseph (Committee member) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The devastating 2014 Ebola virus outbreak in Western Africa demonstrated the lack of therapeutic approaches available for the virus. Although monoclonal antibodies (mAb) and other molecules have been developed that bind the virus, no therapeutic has shown the efficacy needed for FDA approval. Here, a library of 50 peptide based ligands that bind the glycoprotein of the Zaire Ebola virus (GP) were developed. Using whole virus screening of vesicular stomatitis virus pseudotyped with GP, low affinity peptides were identified for ligand construction. In depth analysis showed that two of the peptide based molecules bound the Zaire GP with <100 nM KD. One of these two ligands was blocked by a known neutralizing mAb, 2G4, and showed cross-reactivity to the Sudan GP. This work presents ligands with promise for therapeutic applications across multiple variants of the Ebola virus.
ContributorsRabinowitz, Joshua Avraam (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Both technological and scientific fields continue to revolutionize in a similar fashion; however, a major difference is that high-tech corporations have found models to continue progressions while still keeping product costs low. The main objective was to identify which, if any, components of certain technological models could be used with the vaccine and pharmaceutical markets to significantly lower their costs. Smartphones and computers were the two main items investigated while the two main items from the scientific standpoint were vaccines and pharmaceuticals. One concept had the ability to conceivably decrease the costs of vaccines and drugs and that was "market competition". If the United States were able to allow competition within the vaccine and drug companies, it would allow for the product prices to be best affected. It would only take a few small companies to generate generic versions of the drugs and decrease the prices. It would force the larger competition to most likely decrease their prices. Furthermore, the PC companies use a cumulative density function (CDF) to effectively divide their price setting in each product cycle. It was predicted that if this CDF model were applied to the vaccine and drug markets, the prices would no longer have to be extreme. The corporations would be able to set the highest price for the wealthiest consumers and then slowly begin to decrease the costs for the middle and lower class. Unfortunately, the problem within the vaccine and pharmaceutical markets was not the lack of innovation or business models. The problem lied with their liberty to choose product costs due to poor U.S. government regulations.
ContributorsCalderon, Gerardo (Author) / Johnston, Stephen (Thesis director) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
ABSTRACT Peptide microarrays may prove to be a powerful tool for proteomics research and clinical diagnosis applications. Fodor et al. and Maurer et al. have shown proof-of-concept methods of light- and electrochemically-directed peptide microarray fabrication on glass and semiconductor microchips respectively. In this work, peptide microarray fabrication based on the abovementioned techniques were optimized. In addition, MALDI mass spectrometry based peptide synthesis characterization on semiconductor microchips was developed and novel applications of a CombiMatrix (CBMX) platform for electrochemically controlled synthesis were explored. We have investigated performance of 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) derivatives as photo-labile protecting group. Specifically, influence of substituents on 4 and 5 positions of phenyl ring of NPPOC group on the rate of photolysis and the yield of the amine was investigated. The results indicated that substituents capable of forming a π-network with the nitro group enhanced the rate of photolysis and yield. Once such properly substituted NPPOC groups were used, the rate of photolysis/yield depended on the nature of protected amino group indicating that a different chemical step during the photo-cleavage process became the rate limiting step. We also focused on electrochemically-directed parallel synthesis of high-density peptide microarrays using the CBMX technology referred to above which uses electrochemically generated acids to perform patterned chemistry. Several issues related to peptide synthesis on the CBMX platform were studied and optimized, with emphasis placed on the reactions of electro-generated acids during the deprotection step of peptide synthesis. We have developed a MALDI mass spectrometry based method to determine the chemical composition of microarray synthesis, directly on the feature. This method utilizes non-diffusional chemical cleavage from the surface, thereby making the chemical characterization of high-density microarray features simple, accurate, and amenable to high-throughput. CBMX Corp. has developed a microarray reader which is based on electro-chemical detection of redox chemical species. Several parameters of the instrument were studied and optimized and novel redox applications of peptide microarrays on CBMX platform were also investigated using the instrument. These include (i) a search of metal binding catalytic peptides to reduce overpotential associated with water oxidation reaction and (ii) an immobilization of peptide microarrays using electro-polymerized polypyrrole.
ContributorsKumar, Pallav (Author) / Woodbury, Neal (Thesis advisor) / Allen, James (Committee member) / Johnston, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
Description
The City of Phoenix Street Transportation Department partnered with the Rob and Melani Walton Sustainability Solutions Service at Arizona State University (ASU) and researchers from various ASU schools to evaluate the effectiveness, performance, and community perception of the new pavement coating. The data collection and analysis occurred across multiple neighborhoods and at varying times across days and/or months over the course of one year (July 15, 2020–July 14, 2021), allowing the team to study the impacts of the surface treatment under various weather conditions.
ContributorsMiddel, Ariane (Author) / Vanos, Jennifer K. (Author) / Hondula, David M. (Author) / Kaloush, Kamil (Author) / Sailor, David (Author) / Medina, Jose R. (Jose Roberto) (Author) / Schneider, Florian (Author) / Ortiz, Johny Cordova (Author) / Campbell, Bill (Author) / Epel, Erin (Contributor) / Rice, Brendan (Contributor) / Garcia, Ruth (Contributor) / Phoenix (Ariz.). Street Transportation Department (Contributor) / City of Phoenix (Funder) / Industrial Development Authority of the County of Maricopa (Funder) / Julie Ann Wrigley Global Institute of Sustainability (Funder) / Arizona State University. Healthy Urban Environments Program (Contributor)
Created2021-09
Description
Particulate Guanylyl Cyclase Receptor A (pGC-A) is an atrial natriuretic peptide receptor, which plays a vital role in controlling cardiovascular, renal, and endocrine functions. The extracellular domain of pGC-A interacts with natriuretic peptides and triggers the intracellular guanylyl cyclase domain to convert GTP to cGMP. To effectively develop a method that can regulate pGC-A, structural information regarding its intact form is necessary. Currently, only the extracellular domain structure of rat pGC-A has been determined. However, structural data regarding the transmembrane domain, as well as functional intracellular domain regions, need to be elucidated.This dissertation presents detailed information regarding pGC-A expression and optimization in the baculovirus expression vector system, along with the first purification method for purifying functional intact human pGC-A. The first in vitro evidence of a purified intact human pGC-A tetramer was detected in detergent micellar solution. Intact pGC-A is currently proposed to function as a homodimer. Upon analyzing my findings and acknowledging that dimer formation is required for pGC-A functionality, I proposed the first tetramer complex model composed of two functional subunits (homodimer). Forming tetramer complexes on the cell membrane increases pGC-A binding efficiency and ligand sensitivity.
Currently, a two-step mechanism has been proposed for ATP-dependent pGC-A signal transduction. Based on cGMP functional assay results, it can be suggested that the binding ligand also moderately activates pGC-A, and that ATP is not crucial for the activation of guanylyl cyclase. Instead, three modulators can regulate different activation levels in intact pGC-A.
Crystallization of purified intact pGC-A was performed to determine its structure. During the crystallization condition screening process, I successfully selected seven promising initial crystallization conditions for intact human pGC-A crystallization. One selected condition led to the formation of excellent needle-shaped crystals. During the serial crystallography diffraction experiment, five diffraction patterns were detected. The highest diffraction resolution spot reached 3 Å.
This work will allow the determination of the intact human pGC-A structure while also providing structural information on the protein signal transduction mechanism. Further structural knowledge may potentially lead to improved drug design. More precise mutation experiments could help verify the current pGC-A signal transduction and activation mechanism.
ContributorsZhang, Shangji (Author) / Fromme, Petra (Thesis advisor) / Johnston, Stephen (Committee member) / Mazor, Yuval (Committee member) / Arizona State University (Publisher)
Created2021
Impacts of Landscape Modifications on Urban Boundary Layer Dynamics in Current and Projected Climate
Description
The planetary boundary layer (PBL) is the lowest part of the troposphere and is directly influenced by surface forcing. Anthropogenic modification from natural to urban environments characterized by increased impervious surfaces, anthropogenic heat emission, and a three-dimensional building morphology, affects land-atmosphere interactions in the urban boundary layer (UBL). Ample research has demonstrated the effect of landscape modifications on development and modulation of the near-surface urban heat island (UHI). However, despite potential implications for air quality, precipitation patterns and aviation operations, considerably less attention has been given to impacts on regional scale wind flow. This dissertation, composed of three peer reviewed manuscripts, fills a fundamental gap in urban climate research, by investigating individual and combined impacts of urbanization, heat adaptation strategies and projected climate change on UBL dynamics.
Paper 1 uses medium-resolution Weather Research and Forecast (WRF) climate simulations to assess contemporary and future impacts across the Conterminous US (CONUS). Results indicate that projected urbanization and climate change are expected to increase summer daytime UBL height in the eastern CONUS. Heat adaptation strategies are expected to reduce summer daytime UBL depth by several hundred meters, increase both daytime and nighttime static stability and induce stronger subsidence, especially in the southwestern US.
Paper 2 investigates urban modifications to contemporary wind circulation in the complex terrain of the Phoenix Metropolitan Area (PMA) using high-resolution WRF simulations. The built environment of PMA decreases wind flow in the evening and nighttime inertial sublayer and produces a UHI-induced circulation of limited vertical extent that modulates the background flow. During daytime, greater urban sensible heat flux dampens the urban roughness-induced drag effect by promoting a deeper, more mixed UBL.
Paper 3 extends the investigation to future scenarios showing that, overall, climate change is expected to reduce wind speed across the PMA. Projected increased soil moisture is expected to intensify katabatic winds and weaken anabatic winds along steeper slopes. Urban development is expected to obstruct nighttime wind flow across areas of urban expansion and increase turbulence in the westernmost UBL.
This dissertation advances the understanding of regional-scale UBL dynamics and highlights challenges and opportunities for future research.
ContributorsBrandi, Aldo (Author) / Georgescu, Matei (Thesis advisor) / Broadbent, Ashley (Committee member) / Moustaoui, Mohamed (Committee member) / Sailor, David (Committee member) / Arizona State University (Publisher)
Created2023
Description
Large-scale cultivation of perennial bioenergy crops (e.g., miscanthus and switch-
grass) offers unique opportunities to mitigate climate change through avoided fossil fuel use and associated greenhouse gas reduction. Although conversion of existing agriculturally intensive lands (e.g., maize and soy) to perennial bioenergy cropping systems has been shown to reduce near-surface temperatures, unintended consequences on natural water resources via depletion of soil moisture may offset these benefits. In the effort of the cross-fertilization across the disciplines of physics-based modeling and spatio-temporal statistics, three topics are investigated in this dissertation aiming to provide a novel quantification and robust justifications of the hydroclimate impacts associated with bioenergy crop expansion. Topic 1 quantifies the hydroclimatic impacts associated with perennial bioenergy crop expansion over the contiguous United States using the Weather Research and Forecasting Model (WRF) dynamically coupled to a land surface model (LSM). A suite of continuous (2000–09) medium-range resolution (20-km grid spacing) ensemble-based simulations is conducted. Hovmöller and Taylor diagrams are utilized to evaluate simulated temperature and precipitation. In addition, Mann-Kendall modified trend tests and Sieve-bootstrap trend tests are performed to evaluate the statistical significance of trends in soil moisture differences. Finally, this research reveals potential hot spots of suitable deployment and regions to avoid. Topic 2 presents spatio-temporal Bayesian models which quantify the robustness of control simulation bias, as well as biofuel impacts, using three spatio-temporal correlation structures. A hierarchical model with spatially varying intercepts and slopes display satisfactory performance in capturing spatio-temporal associations. Simulated temperature impacts due to perennial bioenergy crop expansion are robust to physics parameterization schemes. Topic 3 further focuses on the accuracy and efficiency of spatial-temporal statistical modeling for large datasets. An ensemble of spatio-temporal eigenvector filtering algorithms (hereafter: STEF) is proposed to account for the spatio-temporal autocorrelation structure of the data while taking into account spatial confounding. Monte Carlo experiments are conducted. This method is then used to quantify the robustness of simulated hydroclimatic impacts associated with bioenergy crops to alternative physics parameterizations. Results are evaluated against those obtained from three alternative Bayesian spatio-temporal specifications.
grass) offers unique opportunities to mitigate climate change through avoided fossil fuel use and associated greenhouse gas reduction. Although conversion of existing agriculturally intensive lands (e.g., maize and soy) to perennial bioenergy cropping systems has been shown to reduce near-surface temperatures, unintended consequences on natural water resources via depletion of soil moisture may offset these benefits. In the effort of the cross-fertilization across the disciplines of physics-based modeling and spatio-temporal statistics, three topics are investigated in this dissertation aiming to provide a novel quantification and robust justifications of the hydroclimate impacts associated with bioenergy crop expansion. Topic 1 quantifies the hydroclimatic impacts associated with perennial bioenergy crop expansion over the contiguous United States using the Weather Research and Forecasting Model (WRF) dynamically coupled to a land surface model (LSM). A suite of continuous (2000–09) medium-range resolution (20-km grid spacing) ensemble-based simulations is conducted. Hovmöller and Taylor diagrams are utilized to evaluate simulated temperature and precipitation. In addition, Mann-Kendall modified trend tests and Sieve-bootstrap trend tests are performed to evaluate the statistical significance of trends in soil moisture differences. Finally, this research reveals potential hot spots of suitable deployment and regions to avoid. Topic 2 presents spatio-temporal Bayesian models which quantify the robustness of control simulation bias, as well as biofuel impacts, using three spatio-temporal correlation structures. A hierarchical model with spatially varying intercepts and slopes display satisfactory performance in capturing spatio-temporal associations. Simulated temperature impacts due to perennial bioenergy crop expansion are robust to physics parameterization schemes. Topic 3 further focuses on the accuracy and efficiency of spatial-temporal statistical modeling for large datasets. An ensemble of spatio-temporal eigenvector filtering algorithms (hereafter: STEF) is proposed to account for the spatio-temporal autocorrelation structure of the data while taking into account spatial confounding. Monte Carlo experiments are conducted. This method is then used to quantify the robustness of simulated hydroclimatic impacts associated with bioenergy crops to alternative physics parameterizations. Results are evaluated against those obtained from three alternative Bayesian spatio-temporal specifications.
ContributorsWang, Meng, Ph.D (Author) / Kamarianakis, Yiannis (Thesis advisor) / Georgescu, Matei (Thesis advisor) / Fotheringham, A. Stewart (Committee member) / Moustaoui, Mohamed (Committee member) / Reiser, Mark R. (Committee member) / Arizona State University (Publisher)
Created2018
Description
This thesis examines the synoptic characteristics associated with ozone exceedance events in Arizona during the time period of 2011 to 2013. Finding explanations and sources to the ground level ozone in this state is crucial to maintaining the state’s adherence to federal air quality regulations. This analysis utilizes ambient ozone concentration data, surface meteorological conditions, upper air analyses, and HYSPLIT modeling to analyze the synoptic characteristics of ozone events. Based on these data and analyses, five categories were determined to be associated with these events. The five categories all exhibit distinct upper air patterns and surface conditions conducive to the formation of ozone, as well as distinct potential transport pathways of ozone from different nearby regions. These findings indicate that ozone events in Arizona can be linked to synoptic-scale patterns and potential regional transport of ozone. These results can be useful in the forecasting of high ozone pollution and influential on the legislative reduction of ozone pollution.
ContributorsWood, Jessica (Author) / Cerveny, Randall (Thesis advisor) / Georgescu, Matei (Committee member) / Brazel, Anthony (Committee member) / Arizona State University (Publisher)
Created2016