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- Language: English
- Creators: Ira A. Fulton Schools of Engineering
Description
Biomarkers are the cornerstone of modern-day medicine. They are defined as any biological substance in or outside the body that gives insight to the body's condition. Doctors and researchers can measure specific biomarkers to diagnose and treat patients, such as the concentration of hemoglobin Alc and its connection to diabetes. There are a variety of methods, or assays, to detect biomarkers, but the most common assay is enzyme-linked immunosorbent assay (ELISA). A new-generation assay termed mass spectrometric immunoassay (MSIA) can measure proteoforms, the different chemical variations of proteins, and their relative abundance. ELISA on the other hand measures the overall concentration of protein in the sample. Measuring each of the proteoforms of a protein is important because only one or two variations could be biologically significant and/or cause diseases. However, running MSIA is expensive. For this reason, an alternative plate-based MSIA technique was tested for its ability to detect the proteoforms of a protein called apolipoprotein C-III (ApoC-III). This technique combines the protein capturing procedure of ELISA to isolate the protein with detection in a mass spectrometer. A larger amount of ApoC-III present in the body indicates a considerable risk for coronary heart disease. The precision of the assay is determined on the coefficient of variation (CV). A CV value is the ratio of standard deviation in relation to the mean, represented as a percentage. The smaller the percentage, the less variation the assay has, and therefore the more ability it has to detect subtle changes in the biomarker. An accepted CV would be less than 10% for single-day tests (intra-day) and less than 15% for multi-day tests (inter-day). The plate-based MSIA was started by first coating a 96-well round bottom plate with 2.5 micrograms of ApoC-III antibody. Next, a series of steps were conducted: a buffer wash, then the sample incubation, followed by another buffer wash and two consecutive water washes. After the final wash, the wells were filled with a MALDI matrix, then spotted onto a gold plate to dry. The dry gold target was then placed into a MALDI-TOF mass spectrometer to produce mass spectra for each spot. The mass spectra were calibrated and the area underneath each of the four peaks representing the ApoC-III proteoforms was exported as an Excel file. The intra-day CV values were found by dividing the standard deviation by the average relative abundance of each peak. After repeating the same procedure for three more days, the inter-day CVs were found using the same method. After completing the experiment, the CV values were all within the acceptable guidelines. Therefore, the plate-based MSIA is a viable alternative for finding proteoforms than the more expensive MSIA tips. To further validate this, additional tests will need to be conducted with different proteins and number of samples to determine assay flexibility.
ContributorsTieu, Luc (Author) / Borges, Chad (Thesis director) / Nedelkov, Dobrin (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
In recent decades animal agriculture in the U.S. has moved from small, distributed operations to large, Concentrated Animal Feeding Operations (CAFOs). CAFOs are defined by federal regulations based on animal numbers and confinement criteria. Because of the size of these operations, the excessive amount of manure generated is typically stored in lagoons, pits, or barns prior to field application or transport to other farms. Water quality near CAFOs can be impaired through the overflow of lagoons, storm runoff, or lagoon seepage. Assessing water quality impacts of CAFOs in a modeling framework has been difficult because of data paucity. A CAFO lagoon module was developed to assess lagoon overflow risk, groundwater quality, and ammonia emissions of a dairy lagoon. A groundwater quality assessment of a Dairy Lagoon in Lynden Washington was used to calibrate and validate the groundwater quality model. Groundwater down stream of the lagoon was negatively impaired. The long-term effects of this lagoon on water quality were explored as well as the effectiveness of improving the lagoon lining to reduce seepage. This model can be used to improve understanding of the impacts of CAFO lagoon seepage and develop sustainable management practices at the watershed scale for these key components of the agricultural landscape.
ContributorsRudko, Noah (Author) / Muenich, Rebecca (Thesis advisor) / Garcia, Margaret (Committee member) / Xu, Tianfang (Committee member) / Arizona State University (Publisher)
Created2021
Description
Pathogens can proliferate in the built environment and can cause disease outbreaks if water and wastewater are not properly managed. Understanding pathogens that grow in engineered systems is crucial to protecting public health and preventing disease. Using dynamic computational models can reveal mechanistic insights into these systems to aid in understanding risk drivers and determining risk management strategies. The first research chapter of this thesis investigates tradeoffs for reducing the cost associated with Legionnaire’s Disease, hot water scalding, and energy use using a computational framework for evaluating an optimal water heater temperature set point. The model demonstrated that the optimal temperature set point was highly dependent on assumptions made regarding the dose response parameter for a common configuration of an electric water heater in a hospital setting. The optimal temperature was 55°C or 48°C for subclinical vs. clinical severity dose response, respectively, compared with current recommendations of 60°C to kill bacteria and 49°C to prevent scalding and conserve energy.
The second research chapter models the population dynamics of antibiotic-susceptible Escherichia coli (E. coli) and antibiotic-resistant E. coli with a population ecology-exposure assessment model in surface water to quantify the risk of urinary tract infection from recreational swimming activities. Horizontal gene transfer (HGT) was modeled in the environment and the human gastrointestinal tract for several scenarios. HGT was generally not a dominant driver of exposure estimates compared to other factors such as growth and dilution, however, the rank order of factors was scenario-dependent.
The final research chapter models pathogen transport from wastewater treatment plant (WWTP) exposures and assesses the risk to workers based on several exposure scenarios. Case studies were performed to investigate infection risk drivers across different scenarios, including adjustments for the timing of exposure and personal protective equipment. A web application was developed for use by WWTP risk managers to be used with site-specific data.
The proposed modeling frameworks identified risk drivers across several microbial risk scenarios and provide flexible tools for risk managers to use when making water treatment and use decisions for water management plans used for premise plumbing as well as for wastewater treatment practices.
ContributorsHeida, Ashley (Author) / Hamilton, Kerry (Thesis advisor) / Garcia, Margared (Committee member) / Muenich, Rebecca (Committee member) / Wilson, Amanda (Committee member) / Arizona State University (Publisher)
Created2023
Description
Quantifying the interactions among food, energy, and water (FEW) systems is crucial to support integrated policies for the nexus governance. Metropolitan areas are the main consumption and distribution centers of these three resources and, as urbanization continues, their role will become even more central. Despite this, the current understanding of FEW systems in metropolitan regions is limited. In this dissertation, the key factors leading to a more sustainable FEW system are identified in the metropolitan area of Phoenix, Arizona using the integrated WEAP-MABIA-LEAP platform. In this region, the FEW nexus is challenged by dramatic population growth, competition among increasing FEW demand, and limited water availability that could further decrease under climate change. First, it was shown that the WEAP platform allows the reliable simulations of water allocations from supply sources to demand sectors and that agriculture is a key stressor of the nexus, which will require additional groundwater (+83%) and energy (+15%) if cropland area is preserved over the next 50 years. Second, the climate change impacts on the food-water nexus were quantified by applying the WEAP-MABIA model with climate projections up to 2100 from 27 GCMs under different warming levels. It was found that the increases in temperature will lead to higher atmospheric evaporation demand that will, in turn, reduce crop production at a rate of -4.8% per decade. In the last part, the fully integrated WEAP-MABIA-LEAP platform was applied to investigate future scenarios of the FEW nexus in the metropolitan region. Several scenarios targeting each FEW sector were compared through sustainability indicators quantifying availability/consumption, reliability, and productivity of the three resources. Results showed that increasing renewable energy and changing cropping patterns will increase the FEW nexus sustainability compared to business-as-usual conditions. The findings of this dissertation, along with its analytical approach, support policy making towards integrated FEW governance and sustainable development.
ContributorsGuan, Xin (Author) / Mascaro, Giuseppe (Thesis advisor) / White, Dave (Committee member) / Vivoni, Enrique (Committee member) / Muenich, Rebecca (Committee member) / Arizona State University (Publisher)
Created2022
Description
The United States Department of Agriculture provides requirements for a farm operation to become certified organic, but how do these regulations influence nutrient
management on organic farms? There is insufficient evidence to show if the current
regulations on nutrient sourcing and application are feasible and effective. An online
survey was administered to owners and operators of organic farms. Survey respondents
were offered a free soil test as an incentive to participate and to compare their practices
and soil quality. Assessing the current nutrient management under organic regulations
provides information to help assess the sustainability of their nutrient management
practices. Early data suggest that organic farmers may most often be overapplying and
creating legacy sources with this key resource.
ContributorsBonham, Emma Eileen (Author) / Muenich, Rebecca (Thesis advisor) / Zanin, Alaina (Committee member) / Williams, Clinton (Committee member) / Arizona State University (Publisher)
Created2022
Description
Intensified food production on large farms across the world has led to discussions on how to facilitate sustainable policies and practices to reduce nutrient pollution. In Chapter 1, I evaluated the co-variability of agricultural intensification, environmental degradation, and socio-economic indicators throughout the US to explore the potential evidence for the existence of sustainable intensification of agriculture in the US. I identified distinct agro-social-eco regions in the US that provide background for future regional studies of (sustainable intensification) SI in the US and beyond. I observed regions of moderate agricultural intensity and lower environmental degradation within the Great Plains, and regions of high agricultural intensity and higher environmental degradation throughout portions of the Midwest. Insights gained from this study can provide roadmaps for improved sustainable agricultural intensification within the US. In Chapter 2, the study summarized state regulations controlling a key nutrient input - the land application of biosolids from human wastewater treatment and manures from regulated animal feeding operations. Results indicate high variability of both manure and biosolids regulations among the states and stark differences in the regulation of land application of biosolids versus manures. This work can be used to identify opportunities for the strengthening of regulatory frameworks for managing these resources with minimal risk to the environment. In Chapter 3, I combined aspects of the previous chapters to understand the potential impact of specific CAFO land application regulations on nutrient pollution and assess if stricter regulations related to better environmental outcomes. I compared TN AND TP accumulated yields in surface waters across US States with state specific CAFO land application regulations across US Policy scenario tests revealed that more restrictions were associated with higher nutrient levels, indicating reactive policy making and delayed nonpoint source pollution responses. Overall, I found that fostering adaptive capacity and management within delineated agro-social-eco regions will likely facilitate sustainable food systems in the US.
ContributorsRauh, Eleanor (Author) / Muenich, Rebecca (Thesis advisor) / Compton, Jana (Committee member) / Parker, Nathan (Committee member) / Hamilton, Kerry (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
In the recent past, Iraq was considered relatively rich considering its water resources compared to its surroundings. Currently, the magnitude of water resource shortages in Iraq represents an important factor in the stability of the country and in protecting sustained economic development. The need for a practical, applicable, and sustainable river basin management for the Tigris and Euphrates Rivers in Iraq is essential. Applicable water resources allocation scenarios are important to minimize the potential future water crises in connection with water quality and quantity. The allocation of the available fresh water resources in addition to reclaimed water to different users in a sustainable manner is of the urgent necessities to maintain good water quantity and quality.
In this dissertation, predictive water allocation optimization models were developed which can be used to easily identify good alternatives for water management that can then be discussed, debated, adjusted, and simulated in greater detail. This study provides guidance for decision makers in Iraq for potential future conditions, where water supplies are reduced, and demonstrates how it is feasible to adopt an efficient water allocation strategy with flexibility in providing equitable water resource allocation considering alternative resource. Using reclaimed water will help in reducing the potential negative environmental impacts of treated or/and partially treated wastewater discharges while increasing the potential uses of reclaimed water for agriculture and other applications. Using reclaimed water for irrigation is logical and efficient to enhance the economy of farmers and the environment while providing a diversity of crops, especially since most of Iraq’s built or under construction wastewater treatment plants are located in or adjacent to agricultural lands. Adopting an optimization modelling approach can assist decision makers, ensuring their decisions will benefit the economy by incorporating global experiences to control water allocations in Iraq especially considering diminished water supplies.
In this dissertation, predictive water allocation optimization models were developed which can be used to easily identify good alternatives for water management that can then be discussed, debated, adjusted, and simulated in greater detail. This study provides guidance for decision makers in Iraq for potential future conditions, where water supplies are reduced, and demonstrates how it is feasible to adopt an efficient water allocation strategy with flexibility in providing equitable water resource allocation considering alternative resource. Using reclaimed water will help in reducing the potential negative environmental impacts of treated or/and partially treated wastewater discharges while increasing the potential uses of reclaimed water for agriculture and other applications. Using reclaimed water for irrigation is logical and efficient to enhance the economy of farmers and the environment while providing a diversity of crops, especially since most of Iraq’s built or under construction wastewater treatment plants are located in or adjacent to agricultural lands. Adopting an optimization modelling approach can assist decision makers, ensuring their decisions will benefit the economy by incorporating global experiences to control water allocations in Iraq especially considering diminished water supplies.
ContributorsAhmed, Ahmed Abdulrazzaq (Author) / Mays, Larry W. (Thesis advisor) / Fox, Peter (Thesis advisor) / Mascaro, Giuseppe (Committee member) / Muenich, Rebecca (Committee member) / Arizona State University (Publisher)
Created2019
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
Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015