Matching Items (78)
Description
The pathophysiology of Alzheimer’s disease (AD) remains difficult to precisely ascertain in part because animal models fail to fully recapitulate many aspects of the disease and postmortem studies do not allow for the study of the pathophysiology. In vitro models of AD generated with patient derived human induced pluripotent stem cells (hiPSCs) could provide new insight into disease mechanisms. Although many protocols exist to differentiate hiPSCs to neurons, standard practice relies on two-dimensional (2-D) systems, which do not accurately mimic the complexity and architecture of the in vivo brain microenvironment. This research aims to create three-dimensional (3-D) models of AD using hiPSCs, which would enhance the understanding of AD pathophysiology thereby, enabling the generation of effective therapeutics.
ContributorsLundeen, Rachel (Author) / Brafman, David (Thesis advisor) / Kiani, Samira (Committee member) / Ebrahimkhani, Mohammad (Committee member) / Arizona State University (Publisher)
Created2017
Description
Civil infrastructures undergo frequent spatial changes such as deviations between as-designed model and as-is condition, rigid body motions of the structure, and deformations of individual elements of the structure, etc. These spatial changes can occur during the design phase, the construction phase, or during the service life of a structure. Inability to accurately detect and analyze the impact of such changes may miss opportunities for early detections of pending structural integrity and stability issues. Commercial Building Information Modeling (BIM) tools could hardly track differences between as-designed and as-built conditions as they mainly focus on design changes and rely on project managers to manually update and analyze the impact of field changes on the project performance. Structural engineers collect detailed onsite data of a civil infrastructure to perform manual updates of the model for structural analysis, but such approach tends to become tedious and complicated while handling large civil infrastructures.
Previous studies started collecting detailed geometric data generated by 3D laser scanners for defect detection and geometric change analysis of structures. However, previous studies have not yet systematically examined methods for exploring the correlation between the detected geometric changes and their relation to the behaviors of the structural system. Manually checking every possible loading combination leading to the observed geometric change is tedious and sometimes error-prone. The work presented in this dissertation develops a spatial change analysis framework that utilizes spatiotemporal data collected using 3D laser scanning technology and the as-designed models of the structures to automatically detect, classify, and correlate the spatial changes of a structure. The change detection part of the developed framework is computationally efficient and can automatically detect spatial changes between as-designed model and as-built data or between two sets of as-built data collected using 3D laser scanning technology. Then a spatial change classification algorithm automatically classifies the detected spatial changes as global (rigid body motion) and local deformations (tension, compression). Finally, a change correlation technique utilizes a qualitative shape-based reasoning approach for identifying correlated deformations of structure elements connected at joints that contradicts the joint equilibrium. Those contradicting deformations can help to eliminate improbable loading combinations therefore guiding the loading path analysis of the structure.
Previous studies started collecting detailed geometric data generated by 3D laser scanners for defect detection and geometric change analysis of structures. However, previous studies have not yet systematically examined methods for exploring the correlation between the detected geometric changes and their relation to the behaviors of the structural system. Manually checking every possible loading combination leading to the observed geometric change is tedious and sometimes error-prone. The work presented in this dissertation develops a spatial change analysis framework that utilizes spatiotemporal data collected using 3D laser scanning technology and the as-designed models of the structures to automatically detect, classify, and correlate the spatial changes of a structure. The change detection part of the developed framework is computationally efficient and can automatically detect spatial changes between as-designed model and as-built data or between two sets of as-built data collected using 3D laser scanning technology. Then a spatial change classification algorithm automatically classifies the detected spatial changes as global (rigid body motion) and local deformations (tension, compression). Finally, a change correlation technique utilizes a qualitative shape-based reasoning approach for identifying correlated deformations of structure elements connected at joints that contradicts the joint equilibrium. Those contradicting deformations can help to eliminate improbable loading combinations therefore guiding the loading path analysis of the structure.
ContributorsKalasapudi, Vamsi Sai (Author) / Tang, Pingbo (Thesis advisor) / Chong, Oswald (Committee member) / Hjelmstad, Keith (Committee member) / Arizona State University (Publisher)
Created2017
Description
The performance of the Alpha Sprayed Polyurethane Foam (SPF) roofing system is perceived as not an economical option when compared to a 20-year modified bitumen roofing system. Today, the majority of roofs are being replaced, rather than newly installed. The coating manufacturer, Neogard, implemented the Alpha roofing program to identify the best contractors in the industry and to measure their roof performance. The Alpha roof system has shown consistent high performance on over 230 million square feet of surveyed roof. The author proposes to identify if the Alpha roof system is renewable, has proven performance that competes with the traditional modified roofing system, and is a more economical option by evaluating an Alpha roof system installation and the performance of a 29-year-old Alpha roof system. The Dallas Independent School District utilized the Alpha program for William Lipscomb Elementary School in 2016. Dallas Fort Worth Urethane installed the Alpha SPF roof system with high customer satisfaction ratings. This roofing installation showed the value of the Alpha roof system by saving over 20% on costs for the installation and will save approximately 69% of costs on the recoating of the roof in 20 years. The Casa View Elementary School roof system was installed with a Neogard Permathane roof system in 1987. This roof was hail tested with ten drops from 17 feet 9 inches of 1-3/4-inch steel ball (9 out of 10 passed) and four drops from 17 feet 9 inches with a 3-inch diameter steel ball (2 out of 4 passed). The analysis of the passing and failing core samples show that the thickness of the top and base Alpha SPF coating is one of the major differences in a roof passing or failing the FM-SH hail test. Over the 40-year service life, the main difference of purchasing a 61,000 square feet Alpha SPF roof versus modified bitumen roof are savings of approximately $1,067,500. Past hail tests on Alpha SPF roof systems show its cost effectiveness with high customer satisfaction (9.8 out of 10), an over 40-year service life after a $6.00/SF recoat and savings of over $1M for DISD.
ContributorsZulanas, Charles J., IV (Author) / Kashiwagi, Dean T. (Thesis advisor) / Kashiwagi, Jacob S (Thesis advisor) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2017
Description
An in vitro model of Alzheimer’s disease (AD) is required to study the poorly understood molecular mechanisms involved in the familial and sporadic forms of the disease. Animal models have previously proven to be useful in studying familial Alzheimer’s disease (AD) by the introduction of AD related mutations in the animal genome and by the overexpression of AD related proteins. The genetics of sporadic Alzheimer’s is however too complex to model in an animal model. More recently, AD human induced pluripotent stem cells (hiPSCs) have been used to study the disease in a dish. However, AD hiPSC derived neurons do not faithfully reflect all the molecular characteristics and phenotypes observed in the aged cells with neurodegenerative disease. The truncated form of nuclear protein Lamin-A, progerin, has been implicated in premature aging and is found in increasing concentrations as normal cells age. We hypothesized that by overexpressing progerin, we can cause cells to ‘age’ and display the neurodegenerative effects observed with aging in both diseased and normal cells. To answer this hypothesis, we first generated a retrovirus that allows for the overexpression of progerin in AD and non-demented control (NDC) hiPSC derived neural progenitor cells(NPCs). Subsequently, we generated a pure population of hNPCs that overexpress progerin and wild type lamin. Finally, we analyzed the presence of various age related phenotypes such as abnormal nuclear structure and the loss of nuclear lamina associated proteins to characterize ‘aging’ in these cells.
ContributorsRaman, Sreedevi (Author) / Brafman, David (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2017
Description
This dissertation treats a number of related problems in control and data analysis of complex networks.
First, in existing linear controllability frameworks, the ability to steer a network from any initiate state toward any desired state is measured by the minimum number of driver nodes. However, the associated optimal control energy can become unbearably large, preventing actual control from being realized. Here I develop a physical controllability framework and propose strategies to turn physically uncontrollable networks into physically controllable ones. I also discover that although full control can be guaranteed by the prevailing structural controllability theory, it is necessary to balance the number of driver nodes and control energy to achieve actual control, and my work provides a framework to address this issue.
Second, in spite of recent progresses in linear controllability, controlling nonlinear dynamical networks remains an outstanding problem. Here I develop an experimentally feasible control framework for nonlinear dynamical networks that exhibit multistability. The control objective is to apply parameter perturbation to drive the system from one attractor to another. I introduce the concept of attractor network and formulate a quantifiable framework: a network is more controllable if the attractor network is more strongly connected. I test the control framework using examples from various models and demonstrate the beneficial role of noise in facilitating control.
Third, I analyze large data sets from a diverse online social networking (OSN) systems and find that the growth dynamics of meme popularity exhibit characteristically different behaviors: linear, “S”-shape and exponential growths. Inspired by cell population growth model in microbial ecology, I construct a base growth model for meme popularity in OSNs. Then I incorporate human interest dynamics into the base model and propose a hybrid model which contains a small number of free parameters. The model successfully predicts the various distinct meme growth dynamics.
At last, I propose a nonlinear dynamics model to characterize the controlling of WNT signaling pathway in the differentiation of neural progenitor cells. The model is able to predict experiment results and shed light on the understanding of WNT regulation mechanisms.
First, in existing linear controllability frameworks, the ability to steer a network from any initiate state toward any desired state is measured by the minimum number of driver nodes. However, the associated optimal control energy can become unbearably large, preventing actual control from being realized. Here I develop a physical controllability framework and propose strategies to turn physically uncontrollable networks into physically controllable ones. I also discover that although full control can be guaranteed by the prevailing structural controllability theory, it is necessary to balance the number of driver nodes and control energy to achieve actual control, and my work provides a framework to address this issue.
Second, in spite of recent progresses in linear controllability, controlling nonlinear dynamical networks remains an outstanding problem. Here I develop an experimentally feasible control framework for nonlinear dynamical networks that exhibit multistability. The control objective is to apply parameter perturbation to drive the system from one attractor to another. I introduce the concept of attractor network and formulate a quantifiable framework: a network is more controllable if the attractor network is more strongly connected. I test the control framework using examples from various models and demonstrate the beneficial role of noise in facilitating control.
Third, I analyze large data sets from a diverse online social networking (OSN) systems and find that the growth dynamics of meme popularity exhibit characteristically different behaviors: linear, “S”-shape and exponential growths. Inspired by cell population growth model in microbial ecology, I construct a base growth model for meme popularity in OSNs. Then I incorporate human interest dynamics into the base model and propose a hybrid model which contains a small number of free parameters. The model successfully predicts the various distinct meme growth dynamics.
At last, I propose a nonlinear dynamics model to characterize the controlling of WNT signaling pathway in the differentiation of neural progenitor cells. The model is able to predict experiment results and shed light on the understanding of WNT regulation mechanisms.
ContributorsWang, Lezhi (Author) / Lai, Ying-Cheng (Thesis advisor) / Wang, Xiao (Thesis advisor) / Papandreoou-Suppappola, Antonia (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2017
Description
Neurodegenerative diseases such as Alzheimer’s Disease, Parkinson’s Disease and Amyotrophic Lateral Sclerosis are marked by the loss of different types of neurons and glial cells in the central nervous system (CNS). Human Pluripotent Stem Cell (hPSC)-derived Neural Progenitor Cells (hNPCs) have the ability to self-renew indefinitely and to differentiate into various cell types of the CNS. HNPCs can be used in cell based therapies and have the potential to reverse or arrest neurodegeneration and to replace lost neurons and glial cells. However, the lack of completely defined, scalable systems to culture these cells, limits their therapeutic and clinical applications. In a previous study, a completely defined, robust, synthetic peptide- a Vitronectin Derived Peptide (VDP) that supports the long term expansion and differentiation of various embryonic and induced pluripotent stem cell (hESC/hIPSC) derived hNPC lines on two dimensional (2D) tissue culture plates was identified. In this study, the culture of hNPCs was scaled up using VDP coated microcarriers (MC). VDP MC were able to support the long term expansion of hESC and hiPSC derived hNPCs over multiple passages and supported higher fold changes in cell densities, compared to VDP coated 2D surfaces. VDP MC also showed the ability to support the neuronal differentiation of hNPCs, and produced mature neurons expressing several neuronal, neurotransmitter and cortical markers. Additionally, alzheimer’s disease (AD) relevant phenotypes were studied in patient hIPSC derived hNPCs cultured on laminin MC to assess if the MC culture system could be used for disease modelling and drug screening. Finally, a microcarrier based bioreactor system was developed for the large scale expansion of hNPCs, exhibiting more than a five-fold change in cell density and supporting more than 100 million hNPCs in culture. Thus, the development of a xeno-free, scalable system allows hNPC culture under standard and reproducible conditions in quantities required for therapeutic and clinical applications.
ContributorsRajaram Srinivasan, Gayathri (Author) / Brafman, David (Thesis advisor) / Wang, Xiao (Committee member) / Haynes, Karmella (Committee member) / Arizona State University (Publisher)
Created2017
Description
Regulatory agencies, such as the Occupational Safety and Health Administration (OSHA), and the National Institute of Occupational Safety and Health (NIOSH), recognize that decisions regarding occupational health are often economically driven, with worker health only a secondary concern (Ruttenberg, 2014). To investigate the four National Occupational Research Agenda (NORA) long-standing health concerns—welding fumes, crystalline silica, noise, and musculoskeletal disorders—a mixed methods research is conducted. Fourfold structuration, a holistic communication process with roots in indigenous/ancient knowledge, is used to organize data and facilitate making tangible relationships of health to productivity and profits that are abstract and often stated by industries, such as construction, as difficult to quantify. From both construction trade worker and occupational health and safety expert interviews data/codes are developed. For the qualitative method, the codes are organized into a constructivist grounded theory depicting the construction industry with regard to its foundation – profits. A theoretical exercise translating the qualitative codes into potential productivity losses is presented as a way for quantifying the abstract relationships of health to productivity. For the quantitative study, the data/codes are used to develop a comprehensive list of practices, barriers to, and catalysts for addressing health in construction. A significant quantitative finding is that occupational health and safety (OSH) experts are not traditionally involved at the highest levels of the OSHA Hierarchy of Controls, where the greatest opportunity to prevent exposure to health hazards is possible. Organized via a holistic framework, this research emphasizes our primary responsibility to each other as highlighted in recent NIOSH worker health agendas.
ContributorsTello, Linda Marguerite (Author) / Grau, David (Thesis advisor) / Koro-Ljungberg, Mirka (Committee member) / Hanemann, Michael (Committee member) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2017
Description
The past decade has seen a drastic increase in collaboration between Computer Science (CS) and Molecular Biology (MB). Current foci in CS such as deep learning require very large amounts of data, and MB research can often be rapidly advanced by analysis and models from CS. One of the places where CS could aid MB is during analysis of sequences to find binding sites, prediction of folding patterns of proteins. Maintenance and replication of stem-like cells is possible for long terms as well as differentiation of these cells into various tissue types. These behaviors are possible by controlling the expression of specific genes. These genes then cascade into a network effect by either promoting or repressing downstream gene expression. The expression level of all gene transcripts within a single cell can be analyzed using single cell RNA sequencing (scRNA-seq). A significant portion of noise in scRNA-seq data are results of extrinsic factors and could only be removed by customized scRNA-seq analysis pipeline. scRNA-seq experiments utilize next-gen sequencing to measure genome scale gene expression levels with single cell resolution.
Almost every step during analysis and quantification requires the use of an often empirically determined threshold, which makes quantification of noise less accurate. In addition, each research group often develops their own data analysis pipeline making it impossible to compare data from different groups. To remedy this problem a streamlined and standardized scRNA-seq data analysis and normalization protocol was designed and developed. After analyzing multiple experiments we identified the possible pipeline stages, and tools needed. Our pipeline is capable of handling data with adapters and barcodes, which was not the case with pipelines from some experiments. Our pipeline can be used to analyze single experiment scRNA-seq data and also to compare scRNA-seq data across experiments. Various processes like data gathering, file conversion, and data merging were automated in the pipeline. The main focus was to standardize and normalize single-cell RNA-seq data to minimize technical noise introduced by disparate platforms.
Almost every step during analysis and quantification requires the use of an often empirically determined threshold, which makes quantification of noise less accurate. In addition, each research group often develops their own data analysis pipeline making it impossible to compare data from different groups. To remedy this problem a streamlined and standardized scRNA-seq data analysis and normalization protocol was designed and developed. After analyzing multiple experiments we identified the possible pipeline stages, and tools needed. Our pipeline is capable of handling data with adapters and barcodes, which was not the case with pipelines from some experiments. Our pipeline can be used to analyze single experiment scRNA-seq data and also to compare scRNA-seq data across experiments. Various processes like data gathering, file conversion, and data merging were automated in the pipeline. The main focus was to standardize and normalize single-cell RNA-seq data to minimize technical noise introduced by disparate platforms.
ContributorsBalachandran, Parithi (Author) / Wang, Xiao (Thesis advisor) / Brafman, David (Committee member) / Lockhart, Thurmon (Committee member) / Arizona State University (Publisher)
Created2017
Description
Alzheimer’s disease (AD), despite over a century of research, does not have a clearly defined pathogenesis for the sporadic form that makes up the majority of disease incidence. A variety of correlative risk factors have been identified, including the three isoforms of apolipoprotein E (ApoE), a cholesterol transport protein in the central nervous system. ApoE ε3 is the wild-type variant with no effect on risk. ApoE ε2, the protective and most rare variant, reduces risk of developing AD by 40%. ApoE ε4, the risk variant, increases risk by 3.2-fold and 14.9-fold for heterozygous and homozygous representation respectively. Study of these isoforms has been historically complex, but the advent of human induced pluripotent stem cells (hiPSC) provides the means for highly controlled, longitudinal in vitro study. The effect of ApoE variants can be further elucidated using this platform by generating isogenic hiPSC lines through precise genetic modification, the objective of this research. As the difference between alleles is determined by two cytosine-thymine polymorphisms, a specialized CRISPR/Cas9 system for direct base conversion was able to be successfully employed. The base conversion method for transitioning from the ε3 to ε2 allele was first verified using the HEK293 cell line as a model with delivery via electroporation. Following this verification, the transfection method was optimized using two hiPSC lines derived from ε4/ε4 patients, with a lipofection technique ultimately resulting in successful base conversion at the same site verified in the HEK293 model. Additional research performed included characterization of the pre-modification genotype with respect to likely off-target sites and methods of isolating clonal variants.
ContributorsLakers, Mary Frances (Author) / Brafman, David (Thesis advisor) / Haynes, Karmella (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2017
Description
Construction industry performance (schedule, budget, and customer satisfaction) has not improved over the last 20 years. This investigation proposes that academic/industry research using actual project data may have more impact on improving industry performance than traditional survey-based research. The authors utilize the CIB and CIB W117 platforms to proliferate the concept of academic/industry test results to increase the impact on the construction industry. The authors propose to use the existing journal and then share the journal papers on an online platform (ResearchGate.net) ensuring a faster proliferation of the key academic/industry test results into the academic research community. The mechanism of the academic/industry test results will have more of an impact on industry practices than the traditional publication systems, which concentrate on literature reviews and surveys to collect industry opinions and analyze the information to change industry practices. The proliferation of industry research results will create transparency in the construction industry and the academic research community.
ContributorsGastelum, David (Author) / Kashiwagi, Dean T. (Thesis advisor) / Chong, Oswald (Committee member) / Badger, William (Committee member) / Arizona State University (Publisher)
Created2017