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Towards a systems biology understanding of metabolic syndrome

Description

This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems…

This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.

ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)

Created2013

Development of the C* fracture test for asphalt concrete mixtures

Description

Laboratory assessment of crack resistance and propagation in asphalt concrete is a difficult task that challenges researchers and engineers. Several fracture mechanics based laboratory tests currently exist; however, these tests and subsequent analysis methods rely on elastic behavior assumptions and do not consider the time-dependent nature of asphalt concrete. The…

Laboratory assessment of crack resistance and propagation in asphalt concrete is a difficult task that challenges researchers and engineers. Several fracture mechanics based laboratory tests currently exist; however, these tests and subsequent analysis methods rely on elastic behavior assumptions and do not consider the time-dependent nature of asphalt concrete. The C* Line Integral test has shown promise to capture crack resistance and propagation within asphalt concrete. In addition, the fracture mechanics based C* parameter considers the time-dependent creep behavior of the materials. However, previous research was limited and lacked standardized test procedure and detailed data analysis methods were not fully presented. This dissertation describes the development and refinement of the C* Fracture Test (CFT) based on concepts of the C* line integral test. The CFT is a promising test to assess crack propagation and fracture resistance especially in modified mixtures. A detailed CFT test protocol was developed based on a laboratory study of different specimen sizes and test conditions. CFT numerical simulations agreed with laboratory results and indicated that the maximum horizontal tensile stress (Mode I) occurs at the crack tip but diminishes at longer crack lengths when shear stress (Mode II) becomes present. Using CFT test results and the principles of time-temperature superposition, a crack growth rate master curve was successfully developed to describe crack growth over a range of test temperatures. This master curve can be applied to pavement design and analysis to describe crack propagation as a function of traffic conditions and pavement temperatures. Several plant mixtures were subjected to the CFT and results showed differences in resistance to crack propagation, especially when comparing an asphalt rubber mixture to a conventional one. Results indicated that crack propagation is ideally captured within a given range of dynamic modulus values. Crack growth rates and C* prediction models were successfully developed for all unmodified mixtures in the CFT database. These models can be used to predict creep crack propagation and the C* parameter when laboratory testing is not feasible. Finally, a conceptual approach to incorporate crack growth rate and the C* parameter into pavement design and analysis was presented.

ContributorsStempihar, Jeffrey (Author) / Kaloush, Kamil (Thesis advisor) / Witczak, Matthew (Committee member) / Mamlouk, Michael (Committee member) / Arizona State University (Publisher)

Created2013

Computational approaches for addressing complexity in biomedicine

Description

The living world we inhabit and observe is extraordinarily complex. From the perspective of a person analyzing data about the living world, complexity is most commonly encountered in two forms: 1) in the sheer size of the datasets that must be analyzed and the physical number of mathematical computations necessary…

The living world we inhabit and observe is extraordinarily complex. From the perspective of a person analyzing data about the living world, complexity is most commonly encountered in two forms: 1) in the sheer size of the datasets that must be analyzed and the physical number of mathematical computations necessary to obtain an answer and 2) in the underlying structure of the data, which does not conform to classical normal theory statistical assumptions and includes clustering and unobserved latent constructs. Until recently, the methods and tools necessary to effectively address the complexity of biomedical data were not ordinarily available. The utility of four methods--High Performance Computing, Monte Carlo Simulations, Multi-Level Modeling and Structural Equation Modeling--designed to help make sense of complex biomedical data are presented here.

ContributorsBrown, Justin Reed (Author) / Dinu, Valentin (Thesis advisor) / Johnson, William (Committee member) / Petitti, Diana (Committee member) / Arizona State University (Publisher)

Created2012

Integrated predictive model for healing and fatigue endurance limit for asphalt concrete

Description

One of the main requirements of designing perpetual pavements is to determine the endurance limit of Hot Mix Asphalt (HMA). The purpose of this study was to validate the endurance limit for HMA using laboratory beam fatigue tests. A mathematical procedure was developed to determine the endurance limit of HMA…

One of the main requirements of designing perpetual pavements is to determine the endurance limit of Hot Mix Asphalt (HMA). The purpose of this study was to validate the endurance limit for HMA using laboratory beam fatigue tests. A mathematical procedure was developed to determine the endurance limit of HMA due to healing that occurs during the rest periods between loading cycles. Relating healing to endurance limit makes this procedure unique compared to previous research projects that investigated these concepts separately. An extensive laboratory testing program, including 468 beam tests, was conducted according to AASHTO T321-03 test procedure. Six factors that affect the fatigue response of HMA were evaluated: binder type, binder content, air voids, test temperature, rest period and applied strain. The endurance limit was determined when no accumulated damage occurred indicating complete healing. Based on the test results, a first generation predictive model was developed to relate stiffness ratio to material properties. A second generation stiffness ratio model was also developed by replacing four factors (binder type, binder content, air voids, and temperature) with the initial stiffness of the mixture, which is a basic material property. The model also accounts for the nonlinear effects of the rest period and the applied strain on the healing and endurance limit. A third generation model was then developed by incorporation the number of loading cycles at different locations along the fatigue degradation curve for each test in order to account for the nonlinearity between stiffness ratio and loading cycles. In addition to predicting endurance limit, the model has the ability to predict the number of cycles to failure at any rest period and stiffness combination. The model was used to predict fatigue relationship curves for tests with rest period and determining the K1, K2, and K3 fatigue cracking coefficients. The three generation models predicted close endurance limit values ranging from 22 to 204 micro strains. After developing the third generation stiffness ratio model, the predicted endurance limit values were integrated in the strain-Nf fatigue relationships as a step toward incorporating the endurance limit in the MEPDG software. The results of this study can be used to design perpetual pavements that can sustain a large number of loads if traffic volumes and vehicle weights are controlled.

ContributorsSouliman, Mena (Author) / Mamlouk, Michael S. (Thesis advisor) / Witczak, Matthew W. (Thesis advisor) / Kaloush, Kamil (Committee member) / Arizona State University (Publisher)

Created2012

Creating to compete: juried exhibitions of Native American painting, 1946-1960

Description

In the middle of the 20th century, juried annuals of Native American painting in art museums were unique opportunities because of their select focus on two-dimensional art as opposed to "craft" objects and their inclusion of artists from across the United States. Their first fifteen years were critical for patronage…

In the middle of the 20th century, juried annuals of Native American painting in art museums were unique opportunities because of their select focus on two-dimensional art as opposed to "craft" objects and their inclusion of artists from across the United States. Their first fifteen years were critical for patronage and widespread acceptance of modern easel painting. Held at the Philbrook Art Center in Tulsa (1946-1979), the Denver Art Museum (1951-1954), and the Museum of New Mexico Art Gallery in Santa Fe (1956-1965), they were significant not only for the accolades and prestige they garnered for award winners, but also for setting standards of quality and style at the time. During the early years of the annuals, the art was changing, some moving away from conventional forms derived from the early art training of the 1920s and 30s in the Southwest and Oklahoma, and incorporating modern themes and styles acquired through expanded opportunities for travel and education. The competitions reinforced and reflected a variety of attitudes about contemporary art which ranged from preserving the authenticity of the traditional style to encouraging experimentation. Ultimately becoming sites of conflict, the museums that hosted annuals contested the directions in which artists were working. Exhibition catalogs, archived documents, and newspaper and magazine articles about the annuals provide details on the exhibits and the changes that occurred over time. The museums' guidelines and motivations, and the statistics on the award winners reveal attitudes toward the art. The institutions' reactions in the face of controversy and their adjustments to the annuals' guidelines impart the compromises each made as they adapted to new trends that occurred in Native American painting over a fifteen year period. This thesis compares the approaches of three museums to their juried annuals and establishes the existence of a variety of attitudes on contemporary Native American painting from 1946-1960. Through this collection of institutional views, the competitions maintained a patronage base for traditional style painting while providing opportunities for experimentation, paving the way for the great variety and artistic progress of Native American painting today.

ContributorsPeters, Stephanie (Author) / Duncan, Kate (Thesis advisor) / Fahlman, Betsy (Thesis advisor) / Mesch, Claudia (Committee member) / Arizona State University (Publisher)

Created2012

Fiber dosage effects in asphalt binders and hot mix asphalt mixtures

Description

The application of fibers and other materials in asphalt mixes has been studied and applied over the past five decades in order to improve pavement performance around the world. This thesis highlights the characteristics and performance properties of modified asphalt mixes using a blend of polypropylene and aramid fibers, The…

The application of fibers and other materials in asphalt mixes has been studied and applied over the past five decades in order to improve pavement performance around the world. This thesis highlights the characteristics and performance properties of modified asphalt mixes using a blend of polypropylene and aramid fibers, The main objective of this study was to evaluate the effect of adding different fiber dosages on the laboratory performance of both asphalt binder and mixture. The laboratory study was conducted on sixteen different dosages and blends of the fibers, with various combinations of polypropylene and aramid, using binder tests as well as hot mix asphalt tests. The binder tests included: penetration, softing point, and Brookfield viscosity tests. The asphalt mixture tests included the dynamic modulus, and indirect tensile strength. The binder test results indicated that the best viscosity - temperature susceptibility performance would be from the blend of three dosages of polypropylene and one dosage of aramid, the dynamic modulus test results also confirmed this finding. Overall, in almost every case, the addition of fibers resulted in an increase in mixture stiffness regardless of fiber content. From the indirect tensile strength results, the polypropylene fibers had less of an effect on post peak failure than the aramid fibers. Overall, the aramid fibers yielded better results than the polypropylene fibers. This study has important implications for the future of pavement design and the prospect of using optimal dosages of polypropylene and aramid fibers in further research to further determine their long-term performance and characteristics used in real world applications.

ContributorsAlrajhi, Ashraf (Author) / Kaloush, Kamil (Thesis advisor) / Mamlouk, Michael (Committee member) / Witzcak, Matthew (Committee member) / Arizona State University (Publisher)

Created2012

Integrated model of the urban continuum with dynamic time-dependent activity-travel microsimulation: framework, prototype, and implementation

Description

The development of microsimulation approaches to urban systems modeling has occurred largely in three parallel streams of research, namely, land use, travel demand and traffic assignment. However, there are important dependencies and inter-relationships between the model systems which need to be accounted to accurately and comprehensively model the urban system.…

The development of microsimulation approaches to urban systems modeling has occurred largely in three parallel streams of research, namely, land use, travel demand and traffic assignment. However, there are important dependencies and inter-relationships between the model systems which need to be accounted to accurately and comprehensively model the urban system. Location choices affect household activity-travel behavior, household activity-travel behavior affects network level of service (performance), and network level of service, in turn, affects land use and activity-travel behavior. The development of conceptual designs and operational frameworks that represent such complex inter-relationships in a consistent fashion across behavioral units, geographical entities, and temporal scales has proven to be a formidable challenge. In this research, an integrated microsimulation modeling framework called SimTRAVEL (Simulator of Transport, Routes, Activities, Vehicles, Emissions, and Land) that integrates the component model systems in a behaviorally consistent fashion, is presented. The model system is designed such that the activity-travel behavior model and the dynamic traffic assignment model are able to communicate with one another along continuous time with a view to simulate emergent activity-travel patterns in response to dynamically changing network conditions. The dissertation describes the operational framework, presents the modeling methodologies, and offers an extensive discussion on the advantages that such a framework may provide for analyzing the impacts of severe network disruptions on activity-travel choices. A prototype of the model system is developed and implemented for a portion of the Greater Phoenix metropolitan area in Arizona to demonstrate the capabilities of the model system.

ContributorsKonduri, Karthik Charan (Author) / Pendyala, Ram M. (Thesis advisor) / Ahn, Soyoung (Committee member) / Kuby, Michael (Committee member) / Kaloush, Kamil (Committee member) / Arizona State University (Publisher)

Created2012

Development of enhanced cylindrical specimen thermal conductivity testing procedure

Description

The current method of measuring thermal conductivity requires flat plates. For most common civil engineering materials, creating or extracting such samples is difficult. A prototype thermal conductivity experiment had been developed at Arizona State University (ASU) to test cylindrical specimens but proved difficult for repeated testing. In this study, enhancements…

The current method of measuring thermal conductivity requires flat plates. For most common civil engineering materials, creating or extracting such samples is difficult. A prototype thermal conductivity experiment had been developed at Arizona State University (ASU) to test cylindrical specimens but proved difficult for repeated testing. In this study, enhancements to both testing methods were made. Additionally, test results of cylindrical testing were correlated with the results from identical materials tested by the Guarded Hot&ndashPlate; method, which uses flat plate specimens. In validating the enhancements made to the Guarded Hot&ndashPlate; and Cylindrical Specimen methods, 23 tests were ran on five different materials. The percent difference shown for the Guarded Hot&ndashPlate; method was less than 1%. This gives strong evidence that the enhanced Guarded Hot-Plate apparatus in itself is now more accurate for measuring thermal conductivity. The correlation between the thermal conductivity values of the Guarded Hot&ndashPlate; to those of the enhanced Cylindrical Specimen method was excellent. The conventional concrete mixture, due to much higher thermal conductivity values compared to the other mixtures, yielded a P&ndashvalue; of 0.600 which provided confidence in the performance of the enhanced Cylindrical Specimen Apparatus. Several recommendations were made for the future implementation of both test methods. The work in this study fulfills the research community and industry desire for a more streamlined, cost effective, and inexpensive means to determine the thermal conductivity of various civil engineering materials.

ContributorsMorris, Derek (Author) / Kaloush, Kamil (Thesis advisor) / Mobasher, Barzin (Committee member) / Phelan, Patrick E (Committee member) / Arizona State University (Publisher)

Created2011

Understanding adaptive behaviors in complex clinical environments

Description

Critical care environments are complex in nature. Fluctuating team dynamics and the plethora of technology and equipment create unforeseen demands on clinicians. Such environments become chaotic very quickly due to the chronic exposure to unpredictable clusters of events. In order to cope with this complexity, clinicians tend to develop ad-hoc…

Critical care environments are complex in nature. Fluctuating team dynamics and the plethora of technology and equipment create unforeseen demands on clinicians. Such environments become chaotic very quickly due to the chronic exposure to unpredictable clusters of events. In order to cope with this complexity, clinicians tend to develop ad-hoc adaptations to function in an effective manner. It is these adaptations or "deviations" from expected behaviors that provide insight into the processes that shape the overall behavior of the complex system. The research described in this manuscript examines the cognitive basis of clinicians' adaptive mechanisms and presents a methodology for studying the same. Examining interactions in complex systems is difficult due to the disassociation between the nature of the environment and the tools available to analyze underlying processes. In this work, the use of a mixed methodology framework to study trauma critical care, a complex environment, is presented. The hybrid framework supplements existing methods of data collection (qualitative observations) with quantitative methods (use of electronic tags) to capture activities in the complex system. Quantitative models of activities (using Hidden Markov Modeling) and theoretical models of deviations were developed to support this mixed methodology framework. The quantitative activity models developed were tested with a set of fifteen simulated activities that represent workflow in trauma care. A mean recognition rate of 87.5% was obtained in automatically recognizing activities. Theoretical models, on the other hand, were developed using field observations of 30 trauma cases. The analysis of the classification schema (with substantial inter-rater reliability) and 161 deviations identified shows that expertise and role played by the clinician in the trauma team influences the nature of deviations made (p<0.01). The results shows that while expert clinicians deviate to innovate, deviations of novices often result in errors. Experts' flexibility and adaptiveness allow their deviations to generate innovative ideas, in particular when dynamic adjustments are required in complex situations. The findings suggest that while adherence to protocols and standards is important for novice practitioners to reduce medical errors and ensure patient safety, there is strong need for training novices in coping with complex situations as well.

ContributorsVankipuram, Mithra (Author) / Greenes, Robert A (Thesis advisor) / Patel, Vimla L. (Thesis advisor) / Petitti, Diana B. (Committee member) / Dinu, Valentin (Committee member) / Smith, Marshall L. (Committee member) / Arizona State University (Publisher)

Created2012

Endurance limit for HMA based on healing phenomenon using viscoelastic continuum damage analysis

Description

Perpetual Pavements, if properly designed and rehabilitated, it can last longer than 50 years without major structural rehabilitation. Fatigue endurance limit is a key parameter for designing perpetual pavements to mitigate bottom-up fatigue cracking. The endurance limit has not been implemented in the Mechanistic Empirical Pavement Design Guide software, currently…

Perpetual Pavements, if properly designed and rehabilitated, it can last longer than 50 years without major structural rehabilitation. Fatigue endurance limit is a key parameter for designing perpetual pavements to mitigate bottom-up fatigue cracking. The endurance limit has not been implemented in the Mechanistic Empirical Pavement Design Guide software, currently known as DARWin-ME. This study was conducted as part of the National Cooperative Highway Research Program (NCHRP) Project 9-44A to develop a framework and mathematical methodology to determine the fatigue endurance limit using the uniaxial fatigue test. In this procedure, the endurance limit is defined as the allowable tensile strains at which a balance takes place between the fatigue damage during loading, and the healing during the rest periods between loading pulses. The viscoelastic continuum damage model was used to isolate time dependent damage and healing in hot mix asphalt from that due to fatigue. This study also included the development of a uniaxial fatigue test method and the associated data acquisition computer programs to conduct the test with and without rest period. Five factors that affect the fatigue and healing behavior of asphalt mixtures were evaluated: asphalt content, air voids, temperature, rest period and tensile strain. Based on the test results, two Pseudo Stiffness Ratio (PSR) regression models were developed. In the first model, the PSR was a function of the five factors and the number of loading cycles. In the second model, air voids, asphalt content, and temperature were replaced by the initial stiffness of the mix. In both models, the endurance limit was defined when PSR is equal to 1.0 (net damage is equal to zero). The results of the first model were compared to the results of a stiffness ratio model developed based on a parallel study using beam fatigue test (part of the same NCHRP 9-44A). The endurance limit values determined from uniaxial and beam fatigue tests showed very good correlation. A methodology was described on how to incorporate the second PSR model into fatigue analysis and damage using the DARWin-ME software. This would provide an effective and efficient methodology to design perpetual flexible pavements.

ContributorsZeiada, Waleed (Author) / Kaloush, Kamil (Thesis advisor) / Witczak, Matthew W. (Thesis advisor) / Zapata, Claudia (Committee member) / Mamlouk, Michael (Committee member) / Arizona State University (Publisher)

Created2012

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