Matching Items (118)
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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

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
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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

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
Yellowstone National Park has a vibrant variety of flora, fauna, and hydrothermal systems all collected together in one large and complex system. Studies have been conducted for at least several decades in order to make sense of this system in ways that may be relevant to other similar geologies around

Yellowstone National Park has a vibrant variety of flora, fauna, and hydrothermal systems all collected together in one large and complex system. Studies have been conducted for at least several decades in order to make sense of this system in ways that may be relevant to other similar geologies around the world. The latest update in this ever-ongoing study involves the collection and analysis of water samples from 2016. These samples have been analyzed for conductivity, pH, temperature, dissolved organic carbon, dissolved inorganic carbon, carbon isotopes, dissolved oxygen, ferrous iron, sulfide, silica, and more. While not many trends were found in this data in regards to dissolved organic carbon values, this is a substantial addition to a growing body of information that could yield more impressive information in times to come. In addition, factors that have yet to analyzed for this 2016 data, such as concentrations of metals and metalloids, may provide some insights when put through a chloride vs sulfate framework to separate out different reaction regions.
ContributorsDoan, Cuong Le (Author) / Shock, Everett (Thesis director) / Gould, Ian (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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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

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
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The ability to find evidence of life on early Earth and other planets is constrained by the current understanding of biosignatures and our ability to differentiate fossils from abiotic mimics. When organisms transition from the living realm to the fossil record, their morphological and chemical characteristics are modified, usually resulting

The ability to find evidence of life on early Earth and other planets is constrained by the current understanding of biosignatures and our ability to differentiate fossils from abiotic mimics. When organisms transition from the living realm to the fossil record, their morphological and chemical characteristics are modified, usually resulting in the loss of information. These modifications can happen during early and late diagenesis and differ depending on local geochemical properties. These post-depositional modifications need to be understood to better interpret the fossil record. Siliceous hot spring deposits (sinters) are of particular interest for biosignature research as they are early Earth analog environments and targets for investigating the presence of fossil life on Mars. As silica-supersaturated fluids flow from the vent to the distal apron, they precipitate non-crystalline opal-A that fossilizes microbial communities at a range in scales (μm-cm). Therefore, many studies have documented the ties between the active microbial communities and the morphological and chemical biosignatures in hot springs. However, far less attention has been placed on understanding preservation in systems with complex mineralogy or how post-depositional alteration affects the retention of biosignatures. Without this context, it can be challenging to recognize biosignatures in ancient rocks. This dissertation research aims to refine our current understanding of biosignature preservation and retention in sinters. Biosignatures of interest include organic matter, microfossils, and biofabrics. The complex nature of hot springs requires a comprehensive understanding of biosignature preservation that is representative of variable chemistries and post-depositional alterations. For this reason, this dissertation research chapters are field site-based. Chapter 2 investigates biosignature preservation in an unusual spring with mixed opal-A-calcite mineralogy at Lýsuhóll, Iceland. Chapter 3 tracks how silica diagenesis modifies microfossil morphology and associated organic matter at Puchuldiza, Chile. Chapter 4 studies the effects of acid fumarolic overprinting on biosignatures in Gunnuhver, Iceland. To accomplish this, traditional geologic methods (mapping, petrography, X-ray diffraction, bulk elemental analyses) were combined with high-spatial-resolution elemental mapping to better understand diagenetic effects in these systems. Preservation models were developed to predict the types and styles of biosignatures that can be present depending on the depositional and geochemical context. Recommendations are also made for the types of deposits that are most likely to preserve biosignatures.
ContributorsJuarez Rivera, Marisol (Author) / Farmer, Jack D (Thesis advisor) / Hartnett, Hilairy E (Committee member) / Shock, Everett (Committee member) / Garcia-Pichel, Ferran (Committee member) / Trembath-Reichert, Elizabeth (Committee member) / Arizona State University (Publisher)
Created2021
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I present results of field and laboratory experiments investigating the habitability of one of Earth’s driest environments: the Atacama Desert. This Desert, along the west coast of South America spanning Perú and Chile, is one of the driest places on Earth and has been exceedingly arid for millions of years.

I present results of field and laboratory experiments investigating the habitability of one of Earth’s driest environments: the Atacama Desert. This Desert, along the west coast of South America spanning Perú and Chile, is one of the driest places on Earth and has been exceedingly arid for millions of years. These conditions create the perfect natural laboratory for assessing life at the extremes of habitability. All known life needs water; however, the extraordinarily dry Atacama Desert is inhabited by well-adapted microorganisms capable of colonizing this hostile environment. I show field and laboratory evidence of an environmental process, water vapor adsorption, that provides a daily, sustainable input of water into the near (3 - 5 cm) subsurface through water vapor-soil particle interactions. I estimate that this water input may rival the yearly average input of rain in these soils (~2 mm). I also demonstrate, for the first time, that water vapor adsorption is dependent on mineral composition via a series of laboratory water vapor adsorption experiments. The results of these experiments provide evidence that mineral composition, and ultimately soil composition, measurably and significantly affect the equilibrium soil water content. This suggests that soil microbial communities may be extremely heterogeneous in distribution depending on the distribution of adsorbent minerals. Finally, I present changes in biologically relevant gasses (i.e., H2, CH4, CO, and CO2) over long-duration incubation experiments designed to assess the potential for biological activity in soils collected from a hyperarid region in the Atacama Desert. These long-duration experiments mimicked typical water availability conditions in the Atacama Desert; in other words, the incubations were performed without condensed water addition. The results suggest a potential for methane-production in the live experiments relative to the sterile controls, and thus, for biological activity in hyperarid soils. However, due to the extremely low biomass and extremely low rates of activity in these soils, the methods employed here were unable to provide robust evidence for activity. Overall, the hyperarid regions of the Atacama Desert are an important resource for researchers by providing a window into the environmental dynamics and subsequent microbial responses near the limit of habitability.
ContributorsGlaser, Donald M (Author) / Hartnett, Hilairy E (Thesis advisor) / Anbar, Ariel (Committee member) / Shock, Everett (Committee member) / Arizona State University (Publisher)
Created2022
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Dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) are crucial nutrients for autotrophic and heterotrophic microbial life, respectively, in hydrothermal systems. Biogeochemical processes that control amounts of DIC and DOC in Yellowstone hot springs can be investigated by measuring carbon abundances and respective isotopic values. A decade and a

Dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) are crucial nutrients for autotrophic and heterotrophic microbial life, respectively, in hydrothermal systems. Biogeochemical processes that control amounts of DIC and DOC in Yellowstone hot springs can be investigated by measuring carbon abundances and respective isotopic values. A decade and a half of field work in 10 regions within Yellowstone National Park and subsequent geochemical lab analyses reveal that sulfate-dominant acidic regions have high DOC (Up to 57 ppm C) and lower DIC (up to 50 ppm C) compared to neutral-chloride regions with low DOC (< 2 ppm C) and higher DIC (up to 100 ppm C). Abundances and isotopic data suggest that sedimentary rock erosion by acidic hydrothermal fluids, fresh snow-derived meteoric water, and exogenous carbon input allowed by local topography may affect DOC levels. Evaluating the isotopic compositions of DIC and DOC in hydrothermal fluids gives insight on the geology and microbial life in the subsurface between different regions. DIC δ13C values range from -4‰ to +5‰ at pH 5-9 and from -10‰ to +3‰ at pH 2-5 with several springs lower than -10‰. DOC δ13C values parkwide range from -10‰ to -30‰. Within this range, neutral-chloride regions in the Lower Geyser Basin have lighter isotopes than sulfate-dominant acidic regions. In hot springs with elevated levels of DOC, the range only varies between -20‰ and -26‰ which may be caused by local exogenous organic matter runoff. Combining other geochemical measurements, such as differences in chloride and sulfate concentrations, demonstrates that some regions contain mixtures of multiple fluids moving through the complex hydrological system in the subsurface. The mixing of these fluids may account for increased levels of DOC in meteoric sulfate-dominant acidic regions. Ultimately, the foundational values of dissolved carbon and their isotopic composition is provided in a parkwide study, so results can be combined with future studies that apply different sequencing analyses to understand specific biogeochemical cycling and microbial communities that occur in individual hot springs.
ContributorsBarnes, Tanner (Author) / Shock, Everett (Thesis advisor) / Meyer-Dombard, D'Arcy (Committee member) / Hartnett, Hilairy (Committee member) / Arizona State University (Publisher)
Created2023
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As air quality standards become more stringent to combat poor air quality, there is a greater need for more effective pollutant control measures and increased air monitoring network coverage. Polluted air, in the form of aerosols and gases, can impact respiratory and cardiovascular health, visibility, the climate, and material weathering.

As air quality standards become more stringent to combat poor air quality, there is a greater need for more effective pollutant control measures and increased air monitoring network coverage. Polluted air, in the form of aerosols and gases, can impact respiratory and cardiovascular health, visibility, the climate, and material weathering. This work demonstrates how traditional networks can be used to study generational events, how these networks can be supplemented with low-cost sensors, and the effectiveness of several control measures. First, an existing network was used to study the effect of COVID-19 travel restrictions on air quality in Maricopa County, Arizona, which would not have been possible without the historical record that a traditional network provides. Although this study determined that decreases in CO and NO2 were not unique to the travel restrictions, it was limited to only three locations due to network sparseness. The second part of this work expanded the traditional NO2 monitoring network using low-cost sensors, that were first collocated with a reference monitor to evaluate their performance and establish a robust calibration. The sensors were then deployed to the field to varying results; their calibration was further improved by cycling the sensors between deployment and reference locations throughout the summer. This calibrated NO2 data, along with volatile organic compound data, were combined to enhance the understanding of ozone formation in Maricopa County, especially during wildfire season. In addition to being in non-attainment for ozone standards, Maricopa County fails to meet particulate matter under 10 μm (PM10) standards. A large portion of PM10 emissions is attributed to fugitive dust that is either windblown or kicked up by vehicles. The third part of this work demonstrated that Enzyme Induced Carbonate Precipitation (EICP) treatments aggregate soil particles and prevent fugitive dust emissions. The final part of the work examined tire wear PM10 emissions, as vehicles are another significant contributor to PM10. Observations showed a decrease in tire wear PM10 during winter with little change when varying the highway surface type.
ContributorsMiech, Jason Andrew (Author) / Herckes, Pierre (Thesis advisor) / Fraser, Matthew P (Committee member) / Shock, Everett (Committee member) / Arizona State University (Publisher)
Created2023
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The prevalence and unique properties of airborne nanoparticles have raised concerns regarding their potential adverse health effects. Despite their significance, the understanding of nanoparticle generation, transport, and exposure remains incomplete. This study first aimed to assess nanoparticle exposure in indoor workplace environments, in the semiconductor manufacturing industry. On-site observations during

The prevalence and unique properties of airborne nanoparticles have raised concerns regarding their potential adverse health effects. Despite their significance, the understanding of nanoparticle generation, transport, and exposure remains incomplete. This study first aimed to assess nanoparticle exposure in indoor workplace environments, in the semiconductor manufacturing industry. On-site observations during tool preventive maintenance revealed a significant release of particles smaller than 30 nm, which subsequent instrumental analysis confirmed as predominantly composed of transition metals. Although the measured mass concentration levels did not exceed current federal limits, it prompted concerns regarding how well filter-based air sampling methods would capture the particles for exposure assessment and how well common personal protective equipment would protect from exposure. To address these concerns, this study evaluated the capture efficiency of filters and masks. When challenged by aerosolized engineered nanomaterials, common filters used in industrial hygiene sampling exhibited capture efficiencies of over 60%. Filtering Facepiece Respirators, such as the N95 mask, exhibited a capture efficiency of over 98%. In contrast, simple surgical masks showed a capture efficiency of approximately 70%. The experiments showed that face velocity and ambient humidity influence capture performance and mostly identified the critical role of mask and particle surface charge in capturing nanoparticles. Masks with higher surface potential exhibited higher capture efficiency towards nanoparticles. Eliminating their surface charge resulted in a significantly diminished capture efficiency, up to 43%. Finally, this study characterized outdoor nanoparticle concentrations in the Phoenix metropolitan area, revealing typical concentrations on the order of 10^4 #/cm3 consistent with other urban environments. During the North American monsoon season, in dust storms, with elevated number concentrations of large particles, particularly in the size range of 1-10 μm, the number concentration of nanoparticles in the size range of 30-100 nm was substantially lower by approximately 55%. These findings provide valuable insights for future assessments of nanoparticle exposure risks and filter capture mechanisms associated with airborne nanoparticles.
ContributorsZhang, Zhaobo (Author) / Herckes, Pierre (Thesis advisor) / Westerhoff, Paul (Committee member) / Shock, Everett (Committee member) / Fraser, Matthew (Committee member) / Arizona State University (Publisher)
Created2023
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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

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