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- Member of: ASU Electronic Theses and Dissertations
- Status: Published
Description
In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
The Chinese Construction Industry has grown to be one of the largest construction markets in the world within the last 10 years. The size of the Chinese Construction Industry is on par with many developed nations, despite it being a developing country. Despite its rapid growth, the productivity and profitability of the Chinese Construction Industry is low compared to similar sized construction industries (United States, United Kingdom, etc.). In addition to the low efficiency of the Chinese Construction Industry, there is minimal documentation available showing the performance of the Chinese Construction Industry (projects completed on time, on budget, and customer satisfaction ratings).
The purpose of this research is to investigate potential solutions that could address the poor efficiency and performance of the Chinese Construction Industry. This research is divided into three phases; first, a literature review to identify countries that have similar construction industries to the Chinese Construction Industry. The second phase is to compare the risks and identify solutions that are proposed to increase the performance of similar construction industries and the Chinese Construction Industry. The third phase is to create a survey from the literature-based information to validate the concepts with the Chinese Construction Industry professionals and stakeholders.
The purpose of this research is to investigate potential solutions that could address the poor efficiency and performance of the Chinese Construction Industry. This research is divided into three phases; first, a literature review to identify countries that have similar construction industries to the Chinese Construction Industry. The second phase is to compare the risks and identify solutions that are proposed to increase the performance of similar construction industries and the Chinese Construction Industry. The third phase is to create a survey from the literature-based information to validate the concepts with the Chinese Construction Industry professionals and stakeholders.
ContributorsChen, Yutian (Author) / Chong, Oswald (Thesis advisor) / Kashiwagi, Dean T. (Committee member) / Badger, Willliam (Committee member) / Arizona State University (Publisher)
Created2020
Description
Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination of simpler behaviors. It is tempting to apply similar idea such that simpler behaviors can be combined in a meaningful way to tailor the complex combination. Such an approach would enable faster learning and modular design of behaviors. Complex behaviors can be combined with other behaviors to create even more advanced behaviors resulting in a rich set of possibilities. Similar to RL, combined behavior can keep evolving by interacting with the environment. The requirement of this method is to specify a reasonable set of simple behaviors. In this research, I present an algorithm that aims at combining behavior such that the resulting behavior has characteristics of each individual behavior. This approach has been inspired by behavior based robotics, such as the subsumption architecture and motor schema-based design. The combination algorithm outputs n weights to combine behaviors linearly. The weights are state dependent and change dynamically at every step in an episode. This idea is tested on discrete and continuous environments like OpenAI’s “Lunar Lander” and “Biped Walker”. Results are compared with related domains like Multi-objective RL, Hierarchical RL, Transfer learning, and basic RL. It is observed that the combination of behaviors is a novel way of learning which helps the agent achieve required characteristics. A combination is learned for a given state and so the agent is able to learn faster in an efficient manner compared to other similar approaches. Agent beautifully demonstrates characteristics of multiple behaviors which helps the agent to learn and adapt to the environment. Future directions are also suggested as possible extensions to this research.
ContributorsVora, Kevin Jatin (Author) / Zhang, Yu (Thesis advisor) / Yang, Yezhou (Committee member) / Praharaj, Sarbeswar (Committee member) / Arizona State University (Publisher)
Created2021
Description
Although Saudi Arabia is moving towards a sustainable future, Existing residential buildings in the country are extremely unsustainable. Therefore, there is a necessity for greening the existing residential building. Mostadam green rating systems was developed by the Saudi ministry of housing in 2019 to address the long-term sustainability vision in residential buildings in the country. By setting Mostadam requirements as an objective of the retrofit process, it will ensure that the building achieve sustainability. However, Mostadam is new and there is a lack of knowledge of implementing its requirements on existing buildings. The aim of this research is to develop a framework to green existing residential buildings in Saudi Arabia to achieve Mostadam energy and water minimum requirements. The framework was developed based on an extensive keyword-based search and an analysis of 92 relevant research. The process starts with assessing the building against the minimum requirements of energy and water of Mostadam. After that, optimization phase is conducted. Building information modelling is used in the optimization phase. Energy and water efficiency optimization measures are identified from the analysed literature. Revit is used in the base model authoring and Green building studio cloud is used to simulate the energy and water efficiency measures. Then, payback period is calculated for all the efficiency measured to assess the decision making. A case study of a villa in Riyadh, Saudi Arabia is provided. result shows that the implemented efficiency measures led to an increment of 37.5% in annual energy savings and 26.1% in the annual water savings. Results shows that the application of the proposed framework supports evaluating energy and water efficiency measures to implement it on the buildings to achieve Mostadam minimum energy and water requirements. Recommendations were made for future work to bridge the knowledge gap.
ContributorsMohamed, Sara Murad (Author) / Sullivan, Kenneth (Thesis advisor) / Chong, Oswald (Committee member) / Hurtado, Kristen (Committee member) / Arizona State University (Publisher)
Created2022
Description
As the construction industry in Saudi Arabia was on its way to thriving again. Their growth was due to the unprecedented volume of planned projects such as large-scale and unique projects. Suddenly, the world was faced with one of the most disrupting events in the last century which had a devastating impact on the construction industry specifically. This paper explores mainly the impact of the COVID-19 pandemic on construction projects in Saudi Arabia. Particularly, this paper explores how the pandemic and its related events contributed to the projects' schedule disturbances. This is because most of the projects rely on manpower and supply chains which were heavily disrupted due to the protective measures. For that, a study was conducted to evaluate the impact on the construction projects in Saudi Arabia, to what extent the schedule projects were affected, and what were the main reasons for the schedule delays. The research relied on a field survey and schedule analysis for 12 projects which resulted in identifying several causes of delays and the delayed durations that the projects in Saudi Arabia were facing. This research allows those in construction fields to identify the main causes of delays in order to avoid or minimize the impact of these issues on future projects.
ContributorsObeid, Muhammad Hasan Hani (Author) / Ariaratnam, Samuel (Thesis advisor) / El Asmar, Mounir (Committee member) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2021
Description
The consequences of failures from large-diameter water pipelines can be severe. Results can include significant property damage, damage to adjacent infrastructure such as roads and bridges resulting in transportation delays or shutdowns, adjacent structural damage to buildings resulting in loss of business, service disruption to a significant number of customers, loss of water, costly emergency repairs, and even loss of life. The American Water Works Association’s (AWWA) 2020 “State of the Water Industry” report states the top issue facing the water industry since 2016 is aging infrastructure, with the second being financing for improvements. The industry must find innovative ways to extend asset life and reduce maintenance expenditures. While are many different assets comprise the drinking water industry, pipelines are a major component and often neglected because they are typically buried. Reliability Centered Maintenance (RCM) is a process used to determine the most effective maintenance strategy for an asset, with the ultimate goal being to establish the required function of the asset with the required reliability at the lowest operations and maintenance costs. The RCM philosophy considers Preventive Maintenance, Predictive Maintenance, Condition Based Monitoring, Reactive Maintenance, and Proactive Maintenance techniques in an integrated manner to increase the probability an asset will perform its designed function throughout its design life with minimal maintenance. In addition to determining maintenance tasks, the timely performance of those tasks is crucial. If performed too late an asset may fail; if performed too early, resources that may be used better elsewhere are expended. Utility agencies can save time and money by using RCM analysis for their drinking water infrastructure. This dissertation reviews industries using RCM, discusses the benefits of an RCM analysis, and goes through a case study of an RCM at a large aqueduct in the United States. The dissertation further discusses the consequence of failure of large diameter water pipelines and proposes a regression model to help agencies determine the optimum time to perform maintenance tasks on large diameter prestressed concrete pipelines using RCM analysis.
ContributorsGeisbush, James R (Author) / Ariaratnam, Samuel T (Thesis advisor) / Grau, David (Committee member) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2024
Description
The world faces significant environmental and social challenges due to high economic development, population growth, industrialization, rapid urbanization, and unsustainable consumption. Global communities are taking the necessary measures to confront these international challenges and applying sustainable development principles across all sectors. Construction is a critical driving instrument of economic activity, and to achieve sustainable development, it is vital to transform conventional construction into a more sustainable model. The research investigated sustainable construction perceptions in Kuwait, a rapidly growing country with a high volume of construction activities. Kuwait has ambitious plans to transition into a more sustainable economic development model, and the construction industry needs to align with these plans. This research aims to identify the characteristics of sustainable construction applications in the Kuwaiti construction market, such as awareness, current perceptions, drivers and barriers, and the construction regulations' impact. The research utilized a qualitative approach to answer research questions and deliver research objectives by conducting eleven Semi-structured interviews with experienced professionals in the Kuwaiti construction market to collect rich data that reflects insights and understandings of the Kuwaiti construction industry. The Thematic analysis of the data resulted in six themes and one sub-theme that presented reflections, insights, and perspectives on sustainable construction perceptions in the Kuwaiti construction market. The research findings reflected poor sustainable construction awareness and poor environmental and social application in the construction industry, the determinant role of construction regulations in promoting sustainable construction. and barriers and drivers to sustainable construction applications. The research concluded with answers to research questions, delivery of research objectives, and an explanation of sustainable construction perceptions in the Kuwaiti construction market.
Contributorsalsalem, mohammad salem (Author) / Duran, Melanie (Thesis advisor) / Chong, Oswald (Committee member) / Sullivan, Kenneth (Committee member) / Grau, David (Committee member) / Arizona State University (Publisher)
Created2023
Description
During the rapid growth of infrastructure projects globally, countries pay high environmental and social costs as a result of the impacts caused from utilizing the traditional open-cut utility installation method that still widely being used in Egypt. For that, it was essential to have alternatives to reduce these environmental impacts and social costs; however, there are some obstacles that prevent the implementation and the realization of these alternatives.This research is conducted mainly to evaluate the environmental impacts of open-cut excavation vs. trenchless technology in Egypt, through two main methodologies. Firstly, a field survey that aims to measure knowledge of people working in the Egyptian construction industry of trenchless technology, and the harms caused from keeping utilizing open-cut for installing all kinds of underground utilities. In addition to investigating the reasons behind not relying on trenchless technology as a safe alternative for open-cut in Egypt.
Furthermore, in order to compare the greenhouse gases emissions resulted from both open-cut vs trenchless technology, a real case study is applied quantifying the amounts of the resulted greenhouse gases from each method. The results show that greenhouse gases emissions generated from open-cut were extremely higher than that of horizontal directional drilling as a trenchless installation method.
ContributorsKhedr, Ahmed Mossad Saeed Hafez (Author) / Ariaratnam, Samuel (Thesis advisor) / El Asmar, Mounir (Committee member) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2023