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The healthcare system in this country is currently unacceptable. New technologies may contribute to reducing cost and improving outcomes. Early diagnosis and treatment represents the least risky option for addressing this issue. Such a technology needs to be inexpensive, highly sensitive, highly specific, and amenable to adoption in a clinic.

The healthcare system in this country is currently unacceptable. New technologies may contribute to reducing cost and improving outcomes. Early diagnosis and treatment represents the least risky option for addressing this issue. Such a technology needs to be inexpensive, highly sensitive, highly specific, and amenable to adoption in a clinic. This thesis explores an immunodiagnostic technology based on highly scalable, non-natural sequence peptide microarrays designed to profile the humoral immune response and address the healthcare problem. The primary aim of this thesis is to explore the ability of these arrays to map continuous (linear) epitopes. I discovered that using a technique termed subsequence analysis where epitopes could be decisively mapped to an eliciting protein with high success rate. This led to the discovery of novel linear epitopes from Plasmodium falciparum (Malaria) and Treponema palladium (Syphilis), as well as validation of previously discovered epitopes in Dengue and monoclonal antibodies. Next, I developed and tested a classification scheme based on Support Vector Machines for development of a Dengue Fever diagnostic, achieving higher sensitivity and specificity than current FDA approved techniques. The software underlying this method is available for download under the BSD license. Following this, I developed a kinetic model for immunosignatures and tested it against existing data driven by previously unexplained phenomena. This model provides a framework and informs ways to optimize the platform for maximum stability and efficiency. I also explored the role of sequence composition in explaining an immunosignature binding profile, determining a strong role for charged residues that seems to have some predictive ability for disease. Finally, I developed a database, software and indexing strategy based on Apache Lucene for searching motif patterns (regular expressions) in large biological databases. These projects as a whole have advanced knowledge of how to approach high throughput immunodiagnostics and provide an example of how technology can be fused with biology in order to affect scientific and health outcomes.
ContributorsRicher, Joshua Amos (Author) / Johnston, Stephen A. (Thesis advisor) / Woodbury, Neal (Committee member) / Stafford, Phillip (Committee member) / Papandreou-Suppappola, Antonia (Committee member) / Arizona State University (Publisher)
Created2014
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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

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.
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
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Description

Trees serve as a natural umbrella to mitigate insolation absorbed by features of the urban environment, especially building structures and pavements. For a desert community, trees are a particularly valuable asset because they contribute to energy conservation efforts, improve home values, allow for cost savings, and promote enhanced health and

Trees serve as a natural umbrella to mitigate insolation absorbed by features of the urban environment, especially building structures and pavements. For a desert community, trees are a particularly valuable asset because they contribute to energy conservation efforts, improve home values, allow for cost savings, and promote enhanced health and well-being. The main obstacle in creating a sustainable urban community in a desert city with trees is the scarceness and cost of irrigation water. Thus, strategically located and arranged desert trees with the fewest tree numbers possible potentially translate into significant energy, water and long-term cost savings as well as conservation, economic, and health benefits. The objective of this dissertation is to achieve this research goal with integrated methods from both theoretical and empirical perspectives.

This dissertation includes three main parts. The first part proposes a spatial optimization method to optimize the tree locations with the objective to maximize shade coverage on building facades and open structures and minimize shade coverage on building rooftops in a 3-dimensional environment. Second, an outdoor urban physical scale model with field measurement is presented to understand the cooling and locational benefits of tree shade. The third part implements a microclimate numerical simulation model to analyze how the specific tree locations and arrangements influence outdoor microclimates and improve human thermal comfort. These three parts of the dissertation attempt to fill the research gap of how to strategically locate trees at the building to neighborhood scale, and quantifying the impact of such arrangements.

Results highlight the significance of arranging residential shade trees across different geographical scales. In both the building and neighborhood scales, research results recommend that trees should be arranged in the central part of the building south front yard. More cooling benefits are provided to the building structures and outdoor microclimates with a cluster tree arrangement without canopy overlap; however, if residents are interested in creating a better outdoor thermal environment, open space between trees is needed to enhance the wind environment for better human thermal comfort. Considering the rapid urbanization process, limited water resources supply, and the severe heat stress in the urban areas, judicious design and planning of trees is of increasing importance for improving the life quality and sustaining the urban environment.

ContributorsZhao, Qunshan (Author) / Wentz, Elizabeth (Thesis advisor) / Sailor, David (Committee member) / Wang, Zhi-Hua (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Online social media is popular due to its real-time nature, extensive connectivity and a large user base. This motivates users to employ social media for seeking information by reaching out to their large number of social connections. Information seeking can manifest in the form of requests for personal and time-critical

Online social media is popular due to its real-time nature, extensive connectivity and a large user base. This motivates users to employ social media for seeking information by reaching out to their large number of social connections. Information seeking can manifest in the form of requests for personal and time-critical information or gathering perspectives on important issues. Social media platforms are not designed for resource seeking and experience large volumes of messages, leading to requests not being fulfilled satisfactorily. Designing frameworks to facilitate efficient information seeking in social media will help users to obtain appropriate assistance for their needs

and help platforms to increase user satisfaction.

Several challenges exist in the way of facilitating information seeking in social media. First, the characteristics affecting the user’s response time for a question are not known, making it hard to identify prompt responders. Second, the social context in which the user has asked the question has to be determined to find personalized responders. Third, users employ rhetorical requests, which are statements having the

syntax of questions, and systems assisting information seeking might be hindered from focusing on genuine questions. Fouth, social media advocates of political campaigns employ nuanced strategies to prevent users from obtaining balanced perspectives on

issues of public importance.

Sociological and linguistic studies on user behavior while making or responding to information seeking requests provides concepts drawing from which we can address these challenges. We propose methods to estimate the response time of the user for a given question to identify prompt responders. We compute the question specific social context an asker shares with his social connections to identify personalized responders. We draw from theories of political mobilization to model the behaviors arising from the strategies of people trying to skew perspectives. We identify rhetorical questions by modeling user motivations to post them.
ContributorsRanganath, Suhas (Author) / Liu, Huan (Thesis advisor) / Lai, Ying-Cheng (Thesis advisor) / Tong, Hanghang (Committee member) / Vaculin, Roman (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Immunosignature is a technology that retrieves information from the immune system. The technology is based on microarrays with peptides chosen from random sequence space. My thesis focuses on improving the Immunosignature platform and using Immunosignatures to improve diagnosis for diseases. I first contributed to the optimization of the immunosignature platform

Immunosignature is a technology that retrieves information from the immune system. The technology is based on microarrays with peptides chosen from random sequence space. My thesis focuses on improving the Immunosignature platform and using Immunosignatures to improve diagnosis for diseases. I first contributed to the optimization of the immunosignature platform by introducing scoring metrics to select optimal parameters, considering performance as well as practicality. Next, I primarily worked on identifying a signature shared across various pathogens that can distinguish them from the healthy population. I further retrieved consensus epitopes from the disease common signature and proposed that most pathogens could share the signature by studying the enrichment of the common signature in the pathogen proteomes. Following this, I worked on studying cancer samples from different stages and correlated the immune response with whether the epitope presented by tumor is similar to the pathogen proteome. An effective immune response is defined as an antibody titer increasing followed by decrease, suggesting elimination of the epitope. I found that an effective immune response usually correlates with epitopes that are more similar to pathogens. This suggests that the immune system might occupy a limited space and can be effective against only certain epitopes that have similarity with pathogens. I then participated in the attempt to solve the antibiotic resistance problem by developing a classification algorithm that can distinguish bacterial versus viral infection. This algorithm outperforms other currently available classification methods. Finally, I worked on the concept of deriving a single number to represent all the data on the immunosignature platform. This is in resemblance to the concept of temperature, which is an approximate measurement of whether an individual is healthy. The measure of Immune Entropy was found to work best as a single measurement to describe the immune system information derived from the immunosignature. Entropy is relatively invariant in healthy population, but shows significant differences when comparing healthy donors with patients either infected with a pathogen or have cancer.
ContributorsWang, Lu (Author) / Johnston, Stephen (Thesis advisor) / Stafford, Phillip (Committee member) / Buetow, Kenneth (Committee member) / McFadden, Grant (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Immunotherapy has been revitalized with the advent of immune checkpoint blockade

treatments, and neo-antigens are the targets of immune system in cancer patients who

respond to the treatments. The cancer vaccine field is focused on using neo-antigens from

unique point mutations of genomic sequence in the cancer patient for making

personalized cancer vaccines. However,

Immunotherapy has been revitalized with the advent of immune checkpoint blockade

treatments, and neo-antigens are the targets of immune system in cancer patients who

respond to the treatments. The cancer vaccine field is focused on using neo-antigens from

unique point mutations of genomic sequence in the cancer patient for making

personalized cancer vaccines. However, we choose a different path to find frameshift

neo-antigens at the mRNA level and develop broadly effective cancer vaccines based on

frameshift antigens.

In this dissertation, I have summarized and characterized all the potential frameshift

antigens from microsatellite regions in human, dog and mouse. A list of frameshift

antigens was validated by PCR in tumor samples and the mutation rate was calculated for

one candidate – SEC62. I develop a method to screen the antibody response against

frameshift antigens in human and dog cancer patients by using frameshift peptide arrays.

Frameshift antigens selected by positive antibody response in cancer patients or by MHC

predictions show protection in different mouse tumor models. A dog version of the

cancer vaccine based on frameshift antigens was developed and tested in a small safety

trial. The results demonstrate that the vaccine is safe and it can induce strong B and T cell

immune responses. Further, I built the human exon junction frameshift database which

includes all possible frameshift antigens from mis-splicing events in exon junctions, and I

develop a method to find potential frameshift antigens from large cancer

immunosignature dataset with these databases. In addition, I test the idea of ‘early cancer

diagnosis, early treatment’ in a transgenic mouse cancer model. The results show that

ii

early treatment gives significantly better protection than late treatment and the correct

time point for treatment is crucial to give the best clinical benefit. A model for early

treatment is developed with these results.

Frameshift neo-antigens from microsatellite regions and mis-splicing events are

abundant at mRNA level and they are better antigens than neo-antigens from point

mutations in the genomic sequences of cancer patients in terms of high immunogenicity,

low probability to cause autoimmune diseases and low cost to develop a broadly effective

vaccine. This dissertation demonstrates the feasibility of using frameshift antigens for

cancer vaccine development.
ContributorsZhang, Jian (Author) / Johnston, Stephen Albert (Thesis advisor) / Chang, Yung (Committee member) / Stafford, Phillip (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Resilience is emerging as the preferred way to improve the protection of infrastructure systems beyond established risk management practices. Massive damages experienced during tragedies like Hurricane Katrina showed that risk analysis is incapable to prevent unforeseen infrastructure failures and shifted expert focus towards resilience to absorb and recover from adverse

Resilience is emerging as the preferred way to improve the protection of infrastructure systems beyond established risk management practices. Massive damages experienced during tragedies like Hurricane Katrina showed that risk analysis is incapable to prevent unforeseen infrastructure failures and shifted expert focus towards resilience to absorb and recover from adverse events. Recent, exponential growth in research is now producing consensus on how to think about infrastructure resilience centered on definitions and models from influential organizations like the US National Academy of Sciences. Despite widespread efforts, massive infrastructure failures in 2017 demonstrate that resilience is still not working, raising the question: Are the ways people think about resilience producing resilient infrastructure systems?



This dissertation argues that established thinking harbors misconceptions about infrastructure systems that diminish attempts to improve their resilience. Widespread efforts based on the current canon focus on improving data analytics, establishing resilience goals, reducing failure probabilities, and measuring cascading losses. Unfortunately, none of these pursuits change the resilience of an infrastructure system, because none of them result in knowledge about how data is used, goals are set, or failures occur. Through the examination of each misconception, this dissertation results in practical, new approaches for infrastructure systems to respond to unforeseen failures via sensing, adapting, and anticipating processes. Specifically, infrastructure resilience is improved by sensing when data analytics include the modeler-in-the-loop, adapting to stress contexts by switching between multiple resilience strategies, and anticipating crisis coordination activities prior to experiencing a failure.

Overall, results demonstrate that current resilience thinking needs to change because it does not differentiate resilience from risk. The majority of research thinks resilience is a property that a system has, like a noun, when resilience is really an action a system does, like a verb. Treating resilience as a noun only strengthens commitment to risk-based practices that do not protect infrastructure from unknown events. Instead, switching to thinking about resilience as a verb overcomes prevalent misconceptions about data, goals, systems, and failures, and may bring a necessary, radical change to the way infrastructure is protected in the future.
ContributorsEisenberg, Daniel Alexander (Author) / Seager, Thomas P. (Thesis advisor) / Park, Jeryang (Thesis advisor) / Alderson, David L. (Committee member) / Lai, Ying-Cheng (Committee member) / Arizona State University (Publisher)
Created2018
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Description
This dissertation aims to study and understand the effect of nonlinear dynamics and quantum chaos in graphene, optomechanics, photonics and spintronics systems.

First, in graphene quantum dot systems, conductance fluctuations are investigated from the respects of Fano resonances and quantum chaos. The conventional semi-classical theory of quantum chaotic scattering used in

This dissertation aims to study and understand the effect of nonlinear dynamics and quantum chaos in graphene, optomechanics, photonics and spintronics systems.

First, in graphene quantum dot systems, conductance fluctuations are investigated from the respects of Fano resonances and quantum chaos. The conventional semi-classical theory of quantum chaotic scattering used in this field depends on an invariant classical phase-space structure. I show that for systems without an invariant classical phase-space structure, the quantum pointer states can still be used to explain the conductance fluctuations. Another finding is that the chaotic geometry is demonstrated to have similar effects as the disorders in transportations.

Second, in optomechanics systems, I find rich nonlinear dynamics. Using the semi-classical Langevin equations, I demonstrate a quasi-periodic motion is favorable for the quantum entanglement between the optical mode and mechanical mode. Then I use the quantum trajectory theory to provide a new resolution for the breakdown of the classical-quantum correspondences in the chaotic regions.

Third, I investigate the analogs of the electrical band structures and effects in the non-electrical systems. In the photonic systems, I use an array of waveguides to simulate the transport of the massive relativistic particle in a non-Hermitian scenario. A new form of Zitterbewegung is discovered as well as its analytical explanation. In mechanical systems, I use springs and mass points systems to achieve a three band degenerate band structure with a new pair of spatially separated edge states in the Dice lattice. A new semi-metal phase with the intrinsic valley-Hall effect is found.

At last, I investigate the nonlinear dynamics in the spintronics systems, in which the topological insulator couples with a magnetization. Rich nonlinear dynamics are discovered in this systems, especially the multi-stability states.
ContributorsWang, Guanglei (Author) / Lai, Ying-Cheng (Thesis advisor) / Vasileska, Dragica (Committee member) / Ning, Cun-Zheng (Committee member) / Zhao, Yuji (Committee member) / Arizona State University (Publisher)
Created2017
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Description
This dissertation aims to study and understand relevant issues related to the electronic, spin and valley transport in two-dimensional Dirac systems for different given physical settings. In summary, four key findings are achieved.

First, studying persistent currents in confined chaotic Dirac fermion systems with a ring geometry and an applied Aharonov-Bohm

This dissertation aims to study and understand relevant issues related to the electronic, spin and valley transport in two-dimensional Dirac systems for different given physical settings. In summary, four key findings are achieved.

First, studying persistent currents in confined chaotic Dirac fermion systems with a ring geometry and an applied Aharonov-Bohm flux, unusual whispering-gallery modes with edge-dependent currents and spin polarization are identified. They can survive for highly asymmetric rings that host fully developed classical chaos. By sustaining robust persistent currents, these modes can be utilized to form a robust relativistic quantum two-level system.

Second, the quantized topological edge states in confined massive Dirac fermion systems exhibiting a remarkable reverse Stark effect in response to an applied electric field, and an electrically or optically controllable spin switching behavior are uncovered.

Third, novel wave scattering and transport in Dirac-like pseudospin-1 systems are reported. (a), for small scatterer size, a surprising revival resonant scattering with a peculiar boundary trapping by forming unusual vortices is uncovered. Intriguingly, it can persist in arbitrarily weak scatterer strength regime, which underlies a superscattering behavior beyond the conventional scenario. (b), for larger size, a perfect caustic phenomenon arises as a manifestation of the super-Klein tunneling effect. (c), in the far-field, an unexpected isotropic transport emerges at low energies.

Fourth, a geometric valley Hall effect (gVHE) originated from fractional singular Berry flux is revealed. It is shown that gVHE possesses a nonlinear dependence on the Berry flux with asymmetrical resonance features and can be considerably enhanced by electrically controllable resonant valley skew scattering. With the gVHE, efficient valley filtering can arise and these phenomena are robust against thermal fluctuations and disorder averaging.
ContributorsXu, Hongya (Author) / Lai, Ying-Cheng (Thesis advisor) / Bliss, Daniel (Committee member) / Yu, Hongbin (Committee member) / Chen, Tingyong (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Complex dynamical systems are the kind of systems with many interacting components that usually have nonlinear dynamics. Those systems exist in a wide range of disciplines, such as physical, biological, and social fields. Those systems, due to a large amount of interacting components, tend to possess very high dimensionality. Additionally,

Complex dynamical systems are the kind of systems with many interacting components that usually have nonlinear dynamics. Those systems exist in a wide range of disciplines, such as physical, biological, and social fields. Those systems, due to a large amount of interacting components, tend to possess very high dimensionality. Additionally, due to the intrinsic nonlinear dynamics, they have tremendous rich system behavior, such as bifurcation, synchronization, chaos, solitons. To develop methods to predict and control those systems has always been a challenge and an active research area.

My research mainly concentrates on predicting and controlling tipping points (saddle-node bifurcation) in complex ecological systems, comparing linear and nonlinear control methods in complex dynamical systems. Moreover, I use advanced artificial neural networks to predict chaotic spatiotemporal dynamical systems. Complex networked systems can exhibit a tipping point (a “point of no return”) at which a total collapse occurs. Using complex mutualistic networks in ecology as a prototype class of systems, I carry out a dimension reduction process to arrive at an effective two-dimensional (2D) system with the two dynamical variables corresponding to the average pollinator and plant abundances, respectively. I demonstrate that, using 59 empirical mutualistic networks extracted from real data, our 2D model can accurately predict the occurrence of a tipping point even in the presence of stochastic disturbances. I also develop an ecologically feasible strategy to manage/control the tipping point by maintaining the abundance of a particular pollinator species at a constant level, which essentially removes the hysteresis associated with tipping points.

Besides, I also find that the nodal importance ranking for nonlinear and linear control exhibits opposite trends: for the former, large degree nodes are more important but for the latter, the importance scale is tilted towards the small-degree nodes, suggesting strongly irrelevance of linear controllability to these systems. Focusing on a class of recurrent neural networks - reservoir computing systems that have recently been exploited for model-free prediction of nonlinear dynamical systems, I uncover a surprising phenomenon: the emergence of an interval in the spectral radius of the neural network in which the prediction error is minimized.
ContributorsJiang, Junjie (Author) / Lai, Ying-Cheng (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Wang, Xiao (Committee member) / Zhang, Yanchao (Committee member) / Arizona State University (Publisher)
Created2020