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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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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
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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
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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
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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
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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
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This study investigated the effect of environmental heat stress on physiological and performance measures during a ~4 mi time trial (TT) mountain hike in the Phoenix metropolitan area. Participants (n = 12; 7M/5F; age 21.6 ± 2.47 [SD]) climbed ‘A’ mountain (~1 mi) four times on a hot day (HOT;

This study investigated the effect of environmental heat stress on physiological and performance measures during a ~4 mi time trial (TT) mountain hike in the Phoenix metropolitan area. Participants (n = 12; 7M/5F; age 21.6 ± 2.47 [SD]) climbed ‘A’ mountain (~1 mi) four times on a hot day (HOT; wet bulb globe temperature [WBGT] = 31.6°C) and again on a moderate day (MOD; WBGT = 19.0°C). Physiological and performance measures were made before and throughout the course of each hike. Mean pre-hike hydration status (urine specific gravity [USG]) indicated that participants began both HOT and MOD trials in a euhydrated state (1.016 ± 0.010 and 1.010 ± 0.008, respectively) and means did not differ significantly between trials (p = .085). Time trial performance was impaired by -11% (11.1 minutes) in the HOT trial (105 ± 21.7 min), compared to MOD (93.9 ± 13.1 min) (p = .013). Peak core temperatures were significantly higher in HOT (38.5 ± 0.36°C) versus MOD (38.0 ± 0.30°C) with progressively increasing differences between trials over time (p < .001). Peak ratings of perceived exertion were significantly higher in HOT (14.2 ± 2.38) compared to MOD (11.9 ± 2.02) (p = .007). Relative intensity (percent of age-predicted maximal heart rate [HR]), estimated absolute intensity (metabolic equivalents [METs]), and estimated energy expenditure (MET-h) were all increased in HOT, but not significantly so. The HOT condition reduced predicted maximal aerobic capacity (CRFp) by 6% (p = .026). Sweat rates differed significantly between HOT (1.38 ± 0.53 L/h) and MOD (0.84 ± 0.27 L/h) (p = .01). Percent body mass loss (PBML) did not differ significantly between HOT (1.06 ± 0.95%) and MOD (0.98 ± 0.84%) (p = .869). All repeated measures variables showed significant between-subjects effects (p < .05), indicating individual differences in response to test conditions. Heat stress was shown to negatively affect physiological and performance measures in recreational mountain hikers. However, considerable variation exists between individuals, and the degree of physiological and performance impairment is probably due, in part, to differences in aerobic fitness and acclimatization status rather than pre- or during-performance hydration status.

ContributorsLinsell, Joshua (Author) / Wardenaar, Floris (Thesis advisor) / Berger, Christopher (Committee member) / Forzani, Erica (Committee member) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2019
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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
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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
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Exertional heat stroke continues to be one of the leading causes of illness and death in sport in the United States, with an athlete’s experienced microclimate varying by venue design and location. A limited number of studies have attempted to determine the relationship between observed wet bulb globe temperature (WBGT)

Exertional heat stroke continues to be one of the leading causes of illness and death in sport in the United States, with an athlete’s experienced microclimate varying by venue design and location. A limited number of studies have attempted to determine the relationship between observed wet bulb globe temperature (WBGT) and WBGT derived from regional weather station data. Moreover, only one study has quantified the relationship between regionally modeled and on-site measured WBGT over different athletic surfaces (natural grass, rubber track, and concrete tennis court). The current research expands on previous studies to examine how different athletic surfaces influence the thermal environment in the Phoenix Metropolitan Area using a combination of fieldwork, modeling, and statistical analysis. Meteorological data were collected from 0700–1900hr across 6 days in June and 5 days in August 2019 in Tempe, Arizona at various Sun Devil Athletics facilities. This research also explored the influence of surface temperatures on WBGT and the changes projected under a future warmer climate. Results indicate that based on American College of Sports Medicine guidelines practice would not be cancelled in June (WBGT≥32.3°C); however, in August, ~33% of practice time was lost across multiple surfaces. The second-tier recommendations (WBGT≥30.1°C) to limit intense exercise were reached an average of 7 hours each day for all surfaces in August. Further, WBGT was calculated using data from four Arizona Meteorological Network (AZMET) weather stations to provide regional WBGT values for comparison. The on-site (field/court) WBGT values were consistently higher than regional values and significantly different (p<0.05). Thus, using regionally-modeled WBGT data to guide activity or clothing modification for heat safety may lead to misclassification and unsafe conditions. Surface temperature measurements indicate a maximum temperature (170°F) occurring around solar noon, yet WBGT reached its highest level mid-afternoon and on the artificial turf surface (2–5PM). Climate projections show that WBGT values are expected to rise, further restricting the amount of practice and games than can take place outdoors during the afternoon. The findings from this study can be used to inform athletic trainers and coaches about the thermal environment through WBGT values on-field.

ContributorsGuyer, Haven Elizabeth (Author) / Vanos, Jennifer K. (Thesis advisor) / Georgescu, Matei (Thesis advisor) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2020