Matching Items (14)
Filtering by

Clear all filters

152192-Thumbnail Image.png
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

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
171906-Thumbnail Image.png
Description
Infrastructure systems are facing non-stationary challenges that stem from climate change and the increasingly complex interactions between the social, ecological, and technological systems (SETSs). It is crucial for transportation infrastructures—which enable residents to access opportunities and foster prosperity, quality of life, and social connections—to be resilient under these non-stationary challenges.

Infrastructure systems are facing non-stationary challenges that stem from climate change and the increasingly complex interactions between the social, ecological, and technological systems (SETSs). It is crucial for transportation infrastructures—which enable residents to access opportunities and foster prosperity, quality of life, and social connections—to be resilient under these non-stationary challenges. Vulnerability assessment (VA) examines the potential consequences a system is likely to experience due to exposure to perturbation or stressors and lack of the capacity to adapt. Post-fire debris flow and heat represent particularly challenging problems for infrastructure and users in the arid U.S. West. Post-fire debris flow, which is manifested with heat and drought, produces powerful runoff threatening physical transportation infrastructures. And heat waves have devastating health effects on transportation infrastructure users, including increased mortality rates. VA anticipates the potential consequences of these perturbations and enables infrastructure stakeholders to improve the system's resilience. The current transportation climate VA—which only considers a single direct climate stressor on the infrastructure—falls short of addressing the wildfire and heat challenges. This work proposes advanced transportation climate VA methods to address the complex and multiple climate stressors and the vulnerability of infrastructure users. Two specific regions were chosen to carry out the progressive transportation climate VA: 1) the California transportation networks’ vulnerability to post-fire debris flows, and 2) the transportation infrastructure user’s vulnerability to heat exposure in Phoenix.
ContributorsLi, Rui (Author) / Chester, Mikhail V. (Thesis advisor) / Middel, Ariane (Committee member) / Hondula, David M. (Committee member) / Pendyala, Ram (Committee member) / Arizona State University (Publisher)
Created2022
161951-Thumbnail Image.png
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

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
156665-Thumbnail Image.png
Description
This dissertation research studies long-term spatio-temporal patterns of surface urban heat island (SUHI) intensity, urban evapotranspiration (ET), and urban outdoor water use (OWU) using Phoenix metropolitan area (PMA), Arizona as the case study. This dissertation is composed of three chapters. The first chapter evaluates the SUHI intensity for PMA using

This dissertation research studies long-term spatio-temporal patterns of surface urban heat island (SUHI) intensity, urban evapotranspiration (ET), and urban outdoor water use (OWU) using Phoenix metropolitan area (PMA), Arizona as the case study. This dissertation is composed of three chapters. The first chapter evaluates the SUHI intensity for PMA using Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) product and a time-series trend analysis to discover areas that experienced significant changes of SUHI intensity between 2000 and 2017. The heating and cooling effects of different urban land use land cover (LULC) types was also examined using classified Landsat satellite images. The second chapter is focused on urban ET and the impacts of urban LULC change on ET. An empirical model of urban ET for PMA was built using flux tower data and MODIS land products using multivariate regression analysis. A time-series trend analysis was then performed to discover areas in PMA that experienced significant changes of ET between 2001 and 2015. The impact of urban LULC change on ET was examined using classified LULC maps. The third chapter models urban OWU in PMA using a surface energy balance model named METRIC (Mapping Evapotranspiration at high spatial Resolution with Internalized Calibration) and time-series Landsat Thematic Mapper 5 imagery for 2010. The relationship between urban LULC types and OWU was examined with the use of very high-resolution land cover classification data generated from the National Agriculture Imagery Program (NAIP) imagery and regression analysis. Socio-demographic variables were selected from census data at the census track level and analyzed against OWU to study their relationship using correlation analysis. This dissertation makes significant contributions and expands the knowledge of long-term urban climate dynamics for PMA and the influence of urban expansion and LULC change on regional climate. Research findings and results can be used to provide constructive suggestions to urban planners, decision-makers, and city managers to formulate new policies and regulations when planning new constructions for the purpose of sustainable development for a desert city.
ContributorsWang, Chuyuan (Author) / Myint, Soe W. (Thesis advisor) / Brazel, Anthony J. (Committee member) / Wang, Zhihua (Committee member) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2018
157538-Thumbnail Image.png
Description

Many coastal cities around the world are becoming increasingly vulnerable to natural disasters, particularly flooding driven by tropical storm and hurricane storm surge – typically the most destructive feature of these storms, generating significant economic damage and loss of life. This increase in vulnerability is driven by the interactions between

Many coastal cities around the world are becoming increasingly vulnerable to natural disasters, particularly flooding driven by tropical storm and hurricane storm surge – typically the most destructive feature of these storms, generating significant economic damage and loss of life. This increase in vulnerability is driven by the interactions between a wide number of complex social and climatic factors, including population growth, irresponsible urban development, a decrease in essential service provision, sea level rise, and changing storm regimes. These issues are exacerbated by the short-term strategic planning that dominates political action and economic decision-making, resulting in many vulnerable coastal communities being particularly unprepared for large, infrequent storm surge events. This lack of preparedness manifests in several ways, but one of the most visible is the lack of comprehensive evacuation and rescue operation plans for use after major storm surge flooding occurs. Typical evacuation or rescue plans are built using a model of a region’s intact road network. While useful for pre-disaster purposes, the immediate aftermath of large floods sees enormous swaths of a given region’s road system flooded, rendering most of these plans largely useless. Post-storm evacuation and rescue requires large amounts of atypical travel through a region (i.e., across non-road surfaces). Traditional road network models (such as those that are used to generate evacuation routes) are unable to conceptualize this type of transportation, and so are of limited utility during post-disaster scenarios. To solve these problems, this dissertation introduces an alternative network conceptualization that preserves important on-network information but also accounts for the possibility of off-network travel during a disaster. Providing this in situ context is necessary to adequately model transportation through a post-storm landscape, one in which evacuees and rescuers are regularly departing from roads and one in which many roads are completely interdicted by flooding. This modeling approach is used to automatically generate routes through a flooded coastal urban area, as well as to identify potentially critical road segments in advance of an actual storm. These tools may help both emergency managers better prepare for large storms, and urban planners in their efforts to mitigate flood damage.

ContributorsHelderop, Edward (Author) / Grubesic, Tony H. (Thesis advisor) / Kuby, Mike (Committee member) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2019
157609-Thumbnail Image.png
Description

Environmental heat is a growing concern in cities as a consequence of rapid urbanization and climate change, threatening human health and urban vitality. The transportation system is naturally embedded in the issue of urban heat and human heat exposure. Research has established how heat poses a threat to urban inhabitants

Environmental heat is a growing concern in cities as a consequence of rapid urbanization and climate change, threatening human health and urban vitality. The transportation system is naturally embedded in the issue of urban heat and human heat exposure. Research has established how heat poses a threat to urban inhabitants and how urban infrastructure design can lead to increased urban heat. Yet there are gaps in understanding how urban communities accumulate heat exposure, and how significantly the urban transportation system influences or exacerbates the many issues of urban heat. This dissertation focuses on advancing the understanding of how modern urban transportation influences urban heat and human heat exposure through three research objectives: 1) Investigate how human activity results in different outdoor heat exposure; 2) Quantify the growth and extent of urban parking infrastructure; and 3) Model and analyze how pavements and vehicles contribute to urban heat.

In the urban US, traveling outdoors (e.g. biking or walking) is the most frequent activity to cause heat exposure during hot periods. However, outdoor travel durations are often very short, and other longer activities such as outdoor housework and recreation contribute more to cumulative urban heat exposure. In Phoenix, parking and roadway pavement infrastructure contributes significantly to the urban heat balance, especially during summer afternoons, and vehicles only contribute significantly in local areas with high density rush hour vehicle travel. Future development of urban areas (especially those with concerns of extreme heat) should focus on ensuring access and mobility for its inhabitants without sacrificing thermal comfort. This may require urban redesign of transportation systems to be less auto-centric, but without clear pathways to mitigating impacts of urban heat, it may be difficult to promote transitions to travel modes that inherently necessitate heat exposure. Transportation planners and engineers need to be cognizant of the pathways to increased urban heat and human heat exposure when planning and designing urban transportation systems.

ContributorsHoehne, Christopher Glenn (Author) / Chester, Mikhail V (Thesis advisor) / Hondula, David M. (Committee member) / Sailor, David (Committee member) / Pendyala, Ram M. (Committee member) / Arizona State University (Publisher)
Created2019
155695-Thumbnail Image.png
Description

The Maricopa County Heat Relief Network (HRN) is an ad-hoc partially self-organized network with some attributes of hierarchical coordination that forms each year to provide heat relief and hydration to residents in need by operating as cooling centers. These HRN organizations are a collection of non-profit, governmental and religious organizations.

The Maricopa County Heat Relief Network (HRN) is an ad-hoc partially self-organized network with some attributes of hierarchical coordination that forms each year to provide heat relief and hydration to residents in need by operating as cooling centers. These HRN organizations are a collection of non-profit, governmental and religious organizations. This dissertation looks at the HRN from a complexity governance perspective and engaged different parts of the network in interviews to learn more about their perspective in delivering heat relief. Further, participatory modeling with a prototype agent based model was done with the HRN coordinating agencies to look for emergent outcomes in the HRN system and learn from their perspective. Chapter one evaluates organizational theory and complexity with climate adaptation, hazard preparedness and resilience in the HRN. Chapter two presents results from interviews with HRN facility managers and evaluates their perspective on how they function to offer heat relief. Chapter three finds that the HRN is a good example of complexity governance when engaged through a participatory agent based modeling approach. Chapter four engages the HRN coordinators in participatory agent based modeling interviews to increase their systems level awareness, learn about their perspective on heat relief delivery, and how the system can be improved. Chapter five looks across the different levels of the HRN investigated, the facility managers and coordinators, for differences and similarities in perspectives. The research conducted in this dissertation shows different levels of systems awareness of the different parts of the HRN and how participatory modeling can be used to increase systems awareness. Results indicate that there was very little horizontal network connection between HRN facility managers and most of the interaction was vertically coordinated indicating opportunities for increased network communication in the future both horizontally and vertically if communication interventions were put in place.

ContributorsUebelherr, Joshua (Author) / Johnston, Erik W., 1977- (Thesis advisor) / Hondula, David M. (Committee member) / Mossberger, Karen (Committee member) / Gerber, Brian (Committee member) / Arizona State University (Publisher)
Created2017
156114-Thumbnail Image.png
Description
Immunosignature is a technology that retrieves information from the immune system. The technology is based on microarrays with peptides chosen from random sequence space. My thesis focuses on improving the Immunosignature platform and using Immunosignatures to improve diagnosis for diseases. I first contributed to the optimization of the immunosignature platform

Immunosignature is a technology that retrieves information from the immune system. The technology is based on microarrays with peptides chosen from random sequence space. My thesis focuses on improving the Immunosignature platform and using Immunosignatures to improve diagnosis for diseases. I first contributed to the optimization of the immunosignature platform by introducing scoring metrics to select optimal parameters, considering performance as well as practicality. Next, I primarily worked on identifying a signature shared across various pathogens that can distinguish them from the healthy population. I further retrieved consensus epitopes from the disease common signature and proposed that most pathogens could share the signature by studying the enrichment of the common signature in the pathogen proteomes. Following this, I worked on studying cancer samples from different stages and correlated the immune response with whether the epitope presented by tumor is similar to the pathogen proteome. An effective immune response is defined as an antibody titer increasing followed by decrease, suggesting elimination of the epitope. I found that an effective immune response usually correlates with epitopes that are more similar to pathogens. This suggests that the immune system might occupy a limited space and can be effective against only certain epitopes that have similarity with pathogens. I then participated in the attempt to solve the antibiotic resistance problem by developing a classification algorithm that can distinguish bacterial versus viral infection. This algorithm outperforms other currently available classification methods. Finally, I worked on the concept of deriving a single number to represent all the data on the immunosignature platform. This is in resemblance to the concept of temperature, which is an approximate measurement of whether an individual is healthy. The measure of Immune Entropy was found to work best as a single measurement to describe the immune system information derived from the immunosignature. Entropy is relatively invariant in healthy population, but shows significant differences when comparing healthy donors with patients either infected with a pathogen or have cancer.
ContributorsWang, Lu (Author) / Johnston, Stephen (Thesis advisor) / Stafford, Phillip (Committee member) / Buetow, Kenneth (Committee member) / McFadden, Grant (Committee member) / Arizona State University (Publisher)
Created2018
158407-Thumbnail Image.png
Description

Interdisciplinary research has highlighted how social-ecological dynamics drive the structure and function of the urban landscape across multiple scales. Land management decisions operate across various levels, from individuals in their backyard to local municipalities and broader political-economic forces. These decisions then scale up and down across the landscape to influence

Interdisciplinary research has highlighted how social-ecological dynamics drive the structure and function of the urban landscape across multiple scales. Land management decisions operate across various levels, from individuals in their backyard to local municipalities and broader political-economic forces. These decisions then scale up and down across the landscape to influence ecological functioning, such as the provisioning of biodiversity. Likewise, people are influenced by, and respond to, their environment. However, there is a lack of integrated research, especially research that considers the spatial and temporal complexities of social-ecological dynamics, to fully understand how people influence ecosystems or how the resulting landscape in turn influences human decision making, attitudes, and well-being.

My dissertation connects these interdisciplinary themes to examine three questions linked by their investigation of the interactions between people and biodiversity: (1) How do the social and spatial patterns within an arid city affect people’s attitudes about their regional desert environment? (2) How are novel communities in cities assembled given the social-ecological dynamics that influence the processes that structure ecological communities? (3) How can we reposition bird species traits into a conservation framework that explains the complexity of the interactions between people and urban bird communities? I found that social-ecological dynamics between people, the environment, and biodiversity are tightly interwoven in urban ecosystems. The regional desert environment shapes people’s attitudes along spatial and social configurations, which holds implications for yard management decisions. Multi-scalar management decisions then influence biodiversity throughout cities, which shifts public perceptions of urban nature. Overall, my research acts as a bridge between social and ecological sciences to theoretically and empirically integrate research focused on biodiversity conservation in complex, social-ecological systems. My goal as a scholar is to understand the balance between social and ecological implications of landscape change to support human well-being and promote biodiversity conservation.

ContributorsAndrade, Riley (Author) / Franklin, Janet (Thesis advisor) / Larson, Kelli L (Thesis advisor) / Hondula, David M. (Committee member) / Lerman, Susannah B (Committee member) / Arizona State University (Publisher)
Created2020
158683-Thumbnail Image.png
Description
This work advances structural and biophysical studies of three proteins important in disease. First protein of interest is the Francisella tularensis outer membrane protein A (FopA), which is a virulence determinant of tularemia. This work describes recombinant expression in Escherichia coli and successful purification of membrane translocated FopA. The purified

This work advances structural and biophysical studies of three proteins important in disease. First protein of interest is the Francisella tularensis outer membrane protein A (FopA), which is a virulence determinant of tularemia. This work describes recombinant expression in Escherichia coli and successful purification of membrane translocated FopA. The purified protein was dimeric as shown by native polyacrylamide gel electrophoresis and small angle X-ray scattering (SAXS) analysis, with an abundance of β-strands based on circular dichroism spectroscopy. SAXS data supports the presence of a pore. Furthermore, protein crystals of membrane translocated FopA were obtained with preliminary X-ray diffraction data. The identified crystallization condition provides the means towards FopA structure determination; a valuable tool for structure-based design of anti-tularemia therapeutics.

Next, the nonstructural protein μNS of avian reoviruses was investigated using in vivo crystallization and serial femtosecond X-ray crystallography. Avian reoviruses infect poultry flocks causing significant economic losses. μNS is crucial in viral factory formation facilitating viral replication within host cells. Thus, structure-based targeting of μNS has the potential to disrupt intracellular viral propagation. Towards this goal, crystals of EGFP-tagged μNS (EGFP-μNS (448-605)) were produced in insect cells. The crystals diffracted to 4.5 Å at X-ray free electron lasers using viscous jets as crystal delivery methods and initial electron density maps were obtained. The resolution reported here is the highest described to date for μNS, which lays the foundation towards its structure determination.

Finally, structural, and functional studies of human Threonine aspartase 1 (Taspase1) were performed. Taspase1 is overexpressed in many liquid and solid malignancies. In the present study, using strategic circular permutations and X-ray crystallography, structure of catalytically active Taspase1 was resolved. The structure reveals the conformation of a 50 residues long fragment preceding the active side residue (Thr234), which has not been structurally characterized previously. This fragment adopted a straight helical conformation in contrast to previous predictions. Functional studies revealed that the long helix is essential for proteolytic activity in addition to the active site nucleophilic residue (Thr234) mediated proteolysis. Together, these findings enable a new approach for designing anti-cancer drugs by targeting the long helical fragment.
ContributorsNagaratnam, Nirupa (Author) / Fromme, Petra (Thesis advisor) / Johnston, Stephen (Thesis advisor) / Van Horn, Wade (Committee member) / Liu, Wei (Committee member) / Arizona State University (Publisher)
Created2020