Matching Items (53)
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
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
Description
The fast pace of global urbanization makes cities the hotspots of population density and anthropogenic activities, leading to intensive emissions of heat and carbon dioxide (CO2), a primary greenhouse gas. Urban climate scientists have been actively seeking effective mitigation strategies over the past decades, aiming to improve the environmental quality for urban dwellers. Prior studies have identified the role of urban green spaces in the relief of urban heat stress. Yet little effort was devoted to quantify their contribution to local and regional CO2 budget. In fact, urban biogenic CO2 fluxes from photosynthesis and respiration are influenced by the microclimate in the built environment and are sensitive to anthropogenic disturbance. The high complexity of the urban ecosystem leads to an outstanding challenge for numerical urban models to disentangling and quantifying the interplay between heat and carbon dynamics.This dissertation aims to advance the simulation of thermal and carbon dynamics in urban land surface models, and to investigate the role of urban greening practices and urban system design in mitigating heat and CO2 emissions. The biogenic CO2 exchange in cities is parameterized by incorporating plant physiological functions into an advanced single-layer urban canopy model in the built environment. The simulation result replicates the microclimate and CO2 flux patterns measured from an eddy covariance system over a residential neighborhood in Phoenix, Arizona with satisfactory accuracy. Moreover, the model decomposes the total CO2 flux from observation and identifies the significant CO2 efflux from soil respiration. The model is then applied to quantify the impact of urban greening practices on heat and biogenic CO2 exchange over designed scenarios. The result shows the use of urban greenery is effective in mitigating both urban heat and carbon emissions, providing environmental co-benefit in cities. Furthermore, to seek the optimal urban system design in terms of thermal comfort and CO2 reduction, a multi-objective optimization algorithm is applied to the machine learning surrogates of the physical urban land surface model. There are manifest trade-offs among ameliorating diverse urban environmental indicators despite the co-benefit from urban greening. The findings of this dissertation, along with its implications on urban planning and landscaping management, would promote sustainable urban development strategies for achieving optimal environmental quality for policy makers, urban residents, and practitioners.
ContributorsLi, Peiyuan (Author) / Wang, Zhihua (Thesis advisor) / Vivoni, Enrique (Committee member) / Huang, Huei-Ping (Committee member) / Myint, Soe (Committee member) / Xu, Tianfang (Committee member) / Arizona State University (Publisher)
Created2021
Description
Concerns, such as global warming, greenhouse gas emissions, and changes in hydrological regimes, have been raised in response to the global ecosystem changes caused by humans. Understanding the ecosystem functions is crucial for assisting stakeholders in formulating viable plans to address the issues for a healthier planet. However, a systematic evaluation of recent environmental changes and current ecosystem status, focusing on terrestrial ecosystem carbon-water trade-off, in the Lower Mekong Basin (LMB) is lacking. This dissertation involves: (1) examining the long-term spatiotemporal patterns of ecosystem conditions in response to gains and losses of the forest; (2) evaluating the current consumptive water use variation across all biome and land use types with remotely sensed evapotranspiration (ET) products; (3) analyzing the trade-off between terrestrial carbon and water stress condition during the photosynthesis process in response to different climatic/ecosystem conditions, and (4) developing a spatial optimization model to effectively determine possible reforestation/afforestation options considering the balance between water conservation and carbon fluxes. These studies were conducted with many recently developed algorithms and satellite imagery. This dissertation makes significant contributions and expands the knowledge of the variation in water consumption and carbon assimilation within the ecosystem when different conditions are present. In addition, the spatial optimization model was applied to the entire region to formulate possible reforestation plans under different water-carbon tradeoff scenarios for the first time. The findings and results of this research can be used to provide constructive suggestions to policymakers, managers, planners, government officials, and any other stakeholders in LMB to formulate policies and guidelines for the environmentally responsible and sustainable development of LMB.
ContributorsLi, Yubin (Author) / Myint, Soe (Thesis advisor) / Tong, Daoqin (Thesis advisor) / Muenich, Rebecca (Committee member) / Schaffer-Smith, Danica (Committee member) / Arizona State University (Publisher)
Created2023
Description
Safe, readily available, and reliable sources of water are an essential component of any municipality’s infrastructure. Phoenix, Arizona, a southwestern city, has among the highest per capita water use in the United States, making it essential to carefully manage its reservoirs. Generally, municipal water bodies are monitored through field sampling. However, this approach is limited spatially and temporally in addition to being costly. In this study, the application of remotely sensed reflectance data from Landsat 7’s Enhanced Thematic Mapper Plus (ETM+) and Landsat 8’s Operational Land Imager (OLI) along with data generated through field-sampling is used to gain a better understanding of the seasonal development of algal communities and levels of suspended particulates in the three main terminal reservoirs supplying water to the Phoenix metro area: Bartlett Lake, Lake Pleasant, and Saguaro Lake. Algal abundances, particularly the abundance of filamentous cyanobacteria, increased with warmer temperatures in all three reservoirs and reached the highest comparative abundance in Bartlett Lake. Prymnesiophytes (the class of algae to which the toxin-producing golden algae belong) tended to peak between June and August, with one notable peak occurring in Saguaro Lake in August 2017 during which time a fish-kill was observed. In the cooler months algal abundance was comparatively lower in all three lakes, with a more even distribution of abundance across algae classes. In-situ data from March 2017 to March 2018 were compared with algal communities sampled approximately ten years ago in each reservoir to understand any possible long-term changes. The findings show that the algal communities in the reservoirs are relatively stable, particularly those of the filamentous cyanobacteria, chlorophytes, and prymnesiophytes with some notable exceptions, such as the abundance of diatoms, which increased in Bartlett Lake and Lake Pleasant. When in-situ data were compared with Landsat-derived reflectance data, two-band combinations were found to be the best-estimators of chlorophyll-a concentration (as a proxy for algal biomass) and total suspended sediment concentration. The ratio of the reflectance value of the red band and the blue band produced reasonable estimates for the in-situ parameters in Bartlett Lake. The ratio of the reflectance value of the green band and the blue band produced reasonable estimates for the in-situ parameters in Saguaro Lake. However, even the best performing two-band algorithm did not produce any significant correlation between reflectance and in-situ data in Lake Pleasant. Overall, remotely-sensed observations can significantly improve our understanding of the water quality as measured by algae abundance and particulate loading in Arizona Reservoirs, especially when applied over long timescales.
ContributorsRussell, Jazmine Barkley (Author) / Neuer, Susanne (Thesis advisor) / Fox, Peter (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2018
Description
The Western Continental United States has a rapidly changing and complex ecosystem that provides valuable resources to a large portion of the nation. Changes in social and environmental factors have been observed to be significantly correlated to usable ground and surface water levels. The assessment of water level changes and their influences on a semi-national level is needed to support planning and decision making for water resource management at local levels. Although many studies have been done in Ground and Surface Water (GSW) trend analysis, very few have attempted determine correlations with other factors. The number of studies done on correlation factors at a semi-national scale and near decadal temporal scale is even fewer. In this study, freshwater resources in GSW changes from 2004 to 2017 were quantified and used to determine if and how environmental and social variables are related to GSW changes using publicly available remotely sensed and census data. Results indicate that mean annual changes of GSW of the study period are significantly correlated with LULC changes related to deforestation, urbanization, environmental trends, as well as social variables. Further analysis indicates a strong correlation in the rate of change of GSW to LULC changes related to deforestation, environmental trends, as well as social variables. GSW slope trend analysis also reveals a negative trend in California, New Mexico, Arizona, and Nevada. Whereas a positive GSW trend is evident in the northeast part of the study area. GSW trends were found to be somewhat consistent in the states of Utah, Idaho, and Colorado, implying that there was no GSW changes over time in these states.
ContributorsReynolds, Ryan (Author) / Myint, Soe (Thesis advisor) / Werth, Susanna (Committee member) / Brazel, Anthony (Committee member) / Arizona State University (Publisher)
Created2018
Description
Soil moisture (θ) is a fundamental variable controlling the exchange of water and energy at the land surface. As a result, the characterization of the statistical properties of θ across multiple scales is essential for many applications including flood prediction, drought monitoring, and weather forecasting. Empirical evidences have demonstrated the existence of emergent relationships and scale invariance properties in θ fields collected from the ground and airborne sensors during intensive field campaigns, mostly in natural landscapes. This dissertation advances the characterization of these relations and statistical properties of θ by (1) analyzing the role of irrigation, and (2) investigating how these properties change in time and across different landscape conditions through θ outputs of a distributed hydrologic model. First, θ observations from two field campaigns in Australia are used to explore how the presence of irrigated fields modifies the spatial distribution of θ and the associated scale invariance properties. Results reveal that the impact of irrigation is larger in drier regions or conditions, where irrigation creates a drastic contrast with the surrounding areas. Second, a physically-based distributed hydrologic model is applied in a regional basin in northern Mexico to generate hyperresolution θ fields, which are useful to conduct analyses in regions and times where θ has not been monitored. For this aim, strategies are proposed to address data, model validation, and computational challenges associated with hyperresolution hydrologic simulations. Third, analyses are carried out to investigate whether the hyperresolution simulated θ fields reproduce the statistical and scaling properties observed from the ground or remote sensors. Results confirm that (i) the relations between spatial mean and standard deviation of θ derived from the model outputs are very similar to those observed in other areas, and (ii) simulated θ fields exhibit the scale invariance properties that are consistent with those analyzed from aircraft-derived estimates. The simulated θ fields are then used to explore the influence of physical controls on the statistical properties, finding that soil properties significantly affect spatial variability and multifractality. The knowledge acquired through this dissertation provides insights on θ statistical properties in regions and landscape conditions that were never investigated before; supports the refinement of the calibration of multifractal downscaling models; and contributes to the improvement of hyperresolution hydrologic modeling.
ContributorsKo, Ara (Author) / Mascaro, Giuseppe (Thesis advisor) / Vivoni, Enrique R. (Thesis advisor) / Myint, Soe (Committee member) / Wang, Zhihua (Committee member) / Muenich, Rebecca (Committee member) / Arizona State University (Publisher)
Created2018