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The human gut microbiome is associated with health outcomes including gastrointestinal and metabolic health, autoimmune disease and cancer. However, the role of the microbiome in many disease processes, including in the preterm gastrointestinal tract and female genital tract, has yet to be defined. Further, the diverse community of viruses within

The human gut microbiome is associated with health outcomes including gastrointestinal and metabolic health, autoimmune disease and cancer. However, the role of the microbiome in many disease processes, including in the preterm gastrointestinal tract and female genital tract, has yet to be defined. Further, the diverse community of viruses within the microbiome (the virome) is understudied compared to bacteria. Here, I examine the microbiome and virome in specific disease models that are poorly understood: necrotizing enterocolitis (NEC), discordant HIV shedding in women living with HIV (WHLIV), female genital tract inflammation and gammaherpesvirus infection. Specifically, I examined the gut virome longitudinally in a cohort of preterm infants at risk for NEC; the female genital tract (FGT) microbiome and virome longitudinally in a cohort of WLHIV from Lima, Peru; the FGT virome in women from Phoenix, Arizona with differing levels of genital inflammation and different microbiome compositions; and the gut microbiome in murine gammaherpesvirus 68 (MHV68) infection. Further, I contributed to research responding to the spread of SARS-CoV-2 in Arizona. I found that 1) gut virome beta diversity decreased before NEC onset in preterm infants, suggesting a role for the virome in NEC; 2) FGT microbiome instability was associated with discordant HIV shedding, while FGT virome composition changed in association with ART duration and immune recovery; 3) FGT virome composition was associated with inflammation and microbiome composition; and 4) MHV68 infection outcomes were independent of microbiome perturbation, which may reflect environmental influences. The results of this research advance understanding of the microbiome and virome in these specific disease processes, and support further investigation of the microbiome and virome in preterm infant gastrointestinal health and FGT health, as well as environmental effects in microbiome research.
ContributorsKaelin, Emily (Author) / Lim, Efrem (Thesis advisor) / Varsani, Arvind (Committee member) / Jacobs, Bertram (Committee member) / McFadden, Grant (Committee member) / Rahman, Masmudur (Committee member) / Arizona State University (Publisher)
Created2024
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Description
Arachnids belong to the phylum Arthropoda, the largest phylum in the animal kingdom. Ticks are blood-feeding arachnids that vector numerous pathogens of significant medical and veterinary importance, while scorpions have become a common concern in urban desert cities due to the high level of toxicity in their venom. To date,

Arachnids belong to the phylum Arthropoda, the largest phylum in the animal kingdom. Ticks are blood-feeding arachnids that vector numerous pathogens of significant medical and veterinary importance, while scorpions have become a common concern in urban desert cities due to the high level of toxicity in their venom. To date, viruses associated with arachnids have been under sampled and understudied. Here viral metagenomics was used to explore the diversity of viruses present in ticks and scorpions. American dog ticks (Dermacentor variabilis) and blacklegged ticks (Ixodes scapularis) were collected in Pennsylvania while one hairy scorpion (Hadrurus arizonensis) and four bark scorpions (Centruroides sculpturatus) were collected in Phoenix. Novel viral genomes described here belong to the families Polyomaviridae, Anelloviridae, Genomoviridae, and a newly proposed family, Arthropolviridae.

Polyomaviruses are non-enveloped viruses with a small, circular double-stranded DNA (dsDNA) genomes that have been identified in a variety of mammals, birds and fish and are known to cause various diseases. Arthropolviridae is a proposed family of circular, large tumor antigen encoding dsDNA viruses that have a unidirectional genome organization. Genomoviruses and anelloviruses are ssDNA viruses that have circular genomes ranging in size from 2–2.4 kb and 2.1–3.8 kb, respectively. Genomoviruses are ubiquitous in the environment, having been identified in a wide range of animal, plant and environmental samples, while anelloviruses have been associated with a plethora of animals.

Here, 16 novel viruses are reported that span four viral families. Eight novel polyomaviruses were recovered from bark scorpions, three arthropolviruses were recovered from dog ticks and one arthropolvirus from a hairy scorpion. Viruses belonging to the families Polyomaviridae and Arthropolviridae are highly divergent. This is the first more extensive study of these viruses in arachnids. Three genomoviruses were recovered from both dog and deer ticks and one anellovirus was recovered from deer ticks, which are the first records of these viruses being recovered from ticks. This work highlights the diversity of dsDNA and ssDNA viruses in the arachnid population and emphasizes the importance of performing viral surveys on these populations.
ContributorsSchmidlin, Kara (Author) / Varsani, Arvind (Thesis advisor) / Van Doorslaer, Koenraad (Committee member) / Stenglein, Mark (Committee member) / Arizona State University (Publisher)
Created2019
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Description
The research on the topology and dynamics of complex networks is one of the most focused area in complex system science. The goals are to structure our understanding of the real-world social, economical, technological, and biological systems in the aspect of networks consisting a large number of interacting units and

The research on the topology and dynamics of complex networks is one of the most focused area in complex system science. The goals are to structure our understanding of the real-world social, economical, technological, and biological systems in the aspect of networks consisting a large number of interacting units and to develop corresponding detection, prediction, and control strategies. In this highly interdisciplinary field, my research mainly concentrates on universal estimation schemes, physical controllability, as well as mechanisms behind extreme events and cascading failure for complex networked systems.

Revealing the underlying structure and dynamics of complex networked systems from observed data without of any specific prior information is of fundamental importance to science, engineering, and society. We articulate a Markov network based model, the sparse dynamical Boltzmann machine (SDBM), as a universal network structural estimator and dynamics approximator based on techniques including compressive sensing and K-means algorithm. It recovers the network structure of the original system and predicts its short-term or even long-term dynamical behavior for a large variety of representative dynamical processes on model and real-world complex networks.

One of the most challenging problems in complex dynamical systems is to control complex networks.

Upon finding that the energy required to approach a target state with reasonable precision

is often unbearably large, and the energy of controlling a set of networks with similar structural properties follows a fat-tail distribution, we identify fundamental structural ``short boards'' that play a dominant role in the enormous energy and offer a theoretical interpretation for the fat-tail distribution and simple strategies to significantly reduce the energy.

Extreme events and cascading failure, a type of collective behavior in complex networked systems, often have catastrophic consequences. Utilizing transportation and evolutionary game dynamics as prototypical

settings, we investigate the emergence of extreme events in simplex complex networks, mobile ad-hoc networks and multi-layer interdependent networks. A striking resonance-like phenomenon and the emergence of global-scale cascading breakdown are discovered. We derive analytic theories to understand the mechanism of

control at a quantitative level and articulate cost-effective control schemes to significantly suppress extreme events and the cascading process.
ContributorsChen, Yuzhong (Author) / Lai, Ying-Cheng (Thesis advisor) / Spanias, Andreas (Committee member) / Tepedelenlioğlu, Cihan (Committee member) / Ying, Lei (Committee member) / Arizona State University (Publisher)
Created2016
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Description
The purpose of information source detection problem (or called rumor source detection) is to identify the source of information diffusion in networks based on available observations like the states of the nodes and the timestamps at which nodes adopted the information (or called infected). The solution of the problem can

The purpose of information source detection problem (or called rumor source detection) is to identify the source of information diffusion in networks based on available observations like the states of the nodes and the timestamps at which nodes adopted the information (or called infected). The solution of the problem can be used to answer a wide range of important questions in epidemiology, computer network security, etc. This dissertation studies the fundamental theory and the design of efficient and robust algorithms for the information source detection problem.

For tree networks, the maximum a posterior (MAP) estimator of the information source is derived under the independent cascades (IC) model with a complete snapshot and a Short-Fat Tree (SFT) algorithm is proposed for general networks based on the MAP estimator. Furthermore, the following possibility and impossibility results are established on the Erdos-Renyi (ER) random graph: $(i)$ when the infection duration $<\frac{2}{3}t_u,$ SFT identifies the source with probability one asymptotically, where $t_u=\left\lceil\frac{\log n}{\log \mu}\right\rceil+2$ and $\mu$ is the average node degree, $(ii)$ when the infection duration $>t_u,$ the probability of identifying the source approaches zero asymptotically under any algorithm; and $(iii)$ when infection duration $
In practice, other than the nodes' states, side information like partial timestamps may also be available. Such information provides important insights of the diffusion process. To utilize the partial timestamps, the information source detection problem is formulated as a ranking problem on graphs and two ranking algorithms, cost-based ranking (CR) and tree-based ranking (TR), are proposed. Extensive experimental evaluations of synthetic data of different diffusion models and real world data demonstrate the effectiveness and robustness of CR and TR compared with existing algorithms.
ContributorsZhu, Kai (Author) / Ying, Lei (Thesis advisor) / Lai, Ying-Cheng (Committee member) / Liu, Huan (Committee member) / Shakarian, Paulo (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Conductance fluctuations associated with quantum transport through quantumdot systems are currently understood to depend on the nature of the corresponding classical dynamics, i.e., integrable or chaotic. There are a couple of interesting phenomena about conductance fluctuation and quantum tunneling related to geometrical shapes of graphene systems. Firstly, in graphene quantum-dot

Conductance fluctuations associated with quantum transport through quantumdot systems are currently understood to depend on the nature of the corresponding classical dynamics, i.e., integrable or chaotic. There are a couple of interesting phenomena about conductance fluctuation and quantum tunneling related to geometrical shapes of graphene systems. Firstly, in graphene quantum-dot systems, when a magnetic field is present, as the Fermi energy or the magnetic flux is varied, both regular oscillations and random fluctuations in the conductance can occur, with alternating transitions between the two. Secondly, a scheme based on geometrical rotation of rectangular devices to effectively modulate the conductance fluctuations is presented. Thirdly, when graphene is placed on a substrate of heavy metal, Rashba spin-orbit interaction of substantial strength can occur. In an open system such as a quantum dot, the interaction can induce spin polarization. Finally, a problem using graphene systems with electron-electron interactions described by the Hubbard Hamiltonian in the setting of resonant tunneling is investigated.

Another interesting problem in quantum transport is the effect of disorder or random impurities since it is inevitable in real experiments. At first, for a twodimensional Dirac ring, as the disorder density is systematically increased, the persistent current decreases slowly initially and then plateaus at a finite nonzero value, indicating remarkable robustness of the persistent currents, which cannot be discovered in normal metal and semiconductor rings. In addition, in a Floquet system with a ribbon structure, the conductance can be remarkably enhanced by onsite disorder.

Recent years have witnessed significant interest in nanoscale physical systems, such as semiconductor supperlattices and optomechanical systems, which can exhibit distinct collective dynamical behaviors. Firstly, a system of two optically coupled optomechanical cavities is considered and the phenomenon of synchronization transition associated with quantum entanglement transition is discovered. Another useful issue is nonlinear dynamics in semiconductor superlattices caused by its key potential application lies in generating radiation sources, amplifiers and detectors in the spectral range of terahertz. In such a system, transition to multistability, i.e., the emergence of multistability with chaos as a system parameter passes through a critical point, is found and argued to be abrupt.
ContributorsYing, Lei (Author) / Lai, Ying-Cheng (Thesis advisor) / Vasileska, Dragica (Committee member) / Chen, Tingyong (Committee member) / Yao, Yu (Committee member) / Arizona State University (Publisher)
Created2016
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Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).

AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.

The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.

This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
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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
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
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