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The increased number of novel pathogens that potentially threaten the human population has motivated the development of mathematical and computational modeling approaches for forecasting epidemic impact and understanding key environmental characteristics that influence the spread of diseases. Yet, in the case that substantial uncertainty surrounds the transmission process during a

The increased number of novel pathogens that potentially threaten the human population has motivated the development of mathematical and computational modeling approaches for forecasting epidemic impact and understanding key environmental characteristics that influence the spread of diseases. Yet, in the case that substantial uncertainty surrounds the transmission process during a rapidly developing infectious disease outbreak, complex mechanistic models may be too difficult to be calibrated quick enough for policy makers to make informed decisions. Simple phenomenological models that rely on a small number of parameters can provide an initial platform for assessing the epidemic trajectory, estimating the reproduction number and quantifying the disease burden from the early epidemic phase.

Chapter 1 provides background information and motivation for infectious disease forecasting and outlines the rest of the thesis.

In chapter 2, logistic patch models are used to assess and forecast the 2013-2015 West Africa Zaire ebolavirus epidemic. In particular, this chapter is concerned with comparing and contrasting the effects that spatial heterogeneity has on the forecasting performance of the cumulative infected case counts reported during the epidemic.

In chapter 3, two simple phenomenological models inspired from population biology are used to assess the Research and Policy for Infectious Disease Dynamics (RAPIDD) Ebola Challenge; a simulated epidemic that generated 4 infectious disease scenarios. Because of the nature of the synthetically generated data, model predictions are compared to exact epidemiological quantities used in the simulation.

In chapter 4, these models are applied to the 1904 Plague epidemic that occurred in Bombay. This chapter provides evidence that these simple models may be applicable to infectious diseases no matter the disease transmission mechanism.

Chapter 5, uses the patch models from chapter 2 to explore how migration in the 1904 Plague epidemic changes the final epidemic size.

The final chapter is an interdisciplinary project concerning within-host dynamics of cereal yellow dwarf virus-RPV, a plant pathogen from a virus group that infects over 150 grass species. Motivated by environmental nutrient enrichment due to anthropological activities, mathematical models are employed to investigate the relevance of resource competition to pathogen and host dynamics.
ContributorsPell, Bruce (Author) / Kuang, Yang (Thesis advisor) / Chowell-Puente, Gerardo (Committee member) / Nagy, John (Committee member) / Kostelich, Eric (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2016
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Description
In sub-Saharan Africa, an invasive form of nontyphoidal Salmonella (iNTS) belonging to sequence type (ST)313 has emerged as a major public health concern causing widespread bacteremia and mortality in children with malaria and adults with HIV. Clinically, ST313 pathovars are characterized by the absence of gastroenteritis, which is commonly found

In sub-Saharan Africa, an invasive form of nontyphoidal Salmonella (iNTS) belonging to sequence type (ST)313 has emerged as a major public health concern causing widespread bacteremia and mortality in children with malaria and adults with HIV. Clinically, ST313 pathovars are characterized by the absence of gastroenteritis, which is commonly found in “classical” nontyphoidal Salmonella (NTS), along with multidrug resistance, pseudogene formation, and chromosome degradation. There is an urgent need to understand the biological and physical factors that regulate the disease causing properties of ST313 strains. Previous studies from our lab using dynamic Rotating Wall Vessel (RWV) bioreactor technology and “classical” NTS strain χ3339 showed that physiological fluid shear regulates gene expression, stress responses and virulence in unexpected ways that are not observed using conventional shake and static flask conditions, and in a very different manner as compared to ST313 strain D23580. Leveraging from these findings, the current study was the first to report the effect of fluid shear on the pathogenesis-related stress responses of S. Typhimurium ST313 strain A130, which evolved earlier than D23580 within the ST313 clade. A130 displayed enhanced resistance to acid, oxidative and bile stresses when cultured in the high fluid shear (HFS) control condition relative to the low fluid shear (LFS) condition in stationary phase using Lennox Broth (LB) as the culture medium. The greatest magnitude of the survival benefit conferred by high fluid shear was observed in response to oxidative and acid stresses. No differences were observed for thermal and osmotic stresses. Based on previous findings from our laboratory, we also assessed how the addition of phosphate or magnesium ions to the culture medium altered the acid or oxidative stress responses of A130 grown in the RWV. Addition of either

phosphate or magnesium to the culture medium abrogated the fluid shear-related differences observed for A130 in LB medium for the acid or oxidative stress responses, respectively. Collectively, these findings indicate that like other Salmonella strains assessed thus far by our team, A130 responds to differences in physiological fluid shear, and that ion concentrations can modulate those responses.
ContributorsGutierrez-Jensen, Ami Dave (Author) / Nickerson, Cheryl A. (Thesis advisor) / Barrila, Jennifer (Thesis advisor) / Ott, C. M. (Committee member) / Roland, Kenneth (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Understanding how microorganisms adapt and respond to the microgravity environment of spaceflight is important for the function and integrity of onboard life support systems, astronaut health and mission success. Microbial contamination of spacecraft Environmental Life Support Systems (ECLSS), including the potable water system, are well documented and have caused major

Understanding how microorganisms adapt and respond to the microgravity environment of spaceflight is important for the function and integrity of onboard life support systems, astronaut health and mission success. Microbial contamination of spacecraft Environmental Life Support Systems (ECLSS), including the potable water system, are well documented and have caused major disruption to spaceflight missions. The potable water system on the International Space Station (ISS) uses recycled wastewater purified by multiple processes so it is safe for astronaut consumption and personal hygiene. However, despite stringent antimicrobial treatments, multiple bacterial species and biofilms have been recovered from this potable water system. This finding raises concern for crew health risks, vehicle operations and ECLSS system integrity during exploration missions. These concerns are further heightened given that 1) potential pathogens have been isolated from the ISS potable water system, 2) the immune response of astronauts is blunted during spaceflight, 3) spaceflight induces unexpected alterations in microbial responses, including growth and biofilm formation, antimicrobial resistance, stress responses, and virulence, and 4) different microbial phenotypes are often observed between reductionistic pure cultures as compared to more complex multispecies co-cultures, the latter of which are more representative of natural environmental conditions. To advance the understanding of the impact of microgravity on microbial responses that could negatively impact spacecraft ECLSS systems and crew health, this study characterized a range of phenotypic profiles in both pure and co-cultures of bacterial isolates collected from the ISS potable water system between 2009 and 2014. Microbial responses profiled included population dynamics, resistance to silver, biofilm formation, and in vitro colonization of intestinal epithelial cells. Growth characteristics and antibiotic sensitivities for bacterial strains were evaluated to develop selective and/or differential media that allow for isolation of a pure culture from co-cultures, which was critical for the success of this study. Bacterial co-culture experiments were performed using dynamic Rotating Wall Vessel (RWV) bioreactors under spaceflight analogue (Low Shear Modeled Microgravity/LSMMG) and control conditions. These experiments indicated changes in fluid shear have minimal impact on strain recovery. The antimicrobial efficacy of silver on both sessile co-cultures, grown on 316L stainless steel coupons, and planktonic co-cultures showed that silver did not uniformly reduce the recovery of all strains; however, it had a stronger antimicrobial effect on biofilm cultures than planktonic cultures. The impact of silver on the ability of RWV cultured planktonic and biofilm bacterial co-cultures to colonize human intestinal epithelial cells showed that, those strains which were impacted by silver treatment, often increased adherence to the monolayer. Results from these studies provide insight into the dynamics of polymicrobial community interactions, biofilm formation and survival mechanisms of ISS potable water isolates, with potential application for future design of ECLSS systems for sustainable human space exploration.
ContributorsKing, Olivia G (Author) / Nickerson, Cheryl (Thesis advisor) / Barrila, Jennifer (Committee member) / Ott, C (Committee member) / Yang, Jiseon (Committee member) / Arizona State University (Publisher)
Created2019
Description
The discovery that mechanical forces regulate microbial virulence, stress responses and gene expression was made using log phase cultures of Salmonella Typhimurium (S. Typhimurium) grown under low fluid shear (LFS) conditions relevant to those encountered in the intestine. However, there has been limited characterization of LFS on other growth phases.

The discovery that mechanical forces regulate microbial virulence, stress responses and gene expression was made using log phase cultures of Salmonella Typhimurium (S. Typhimurium) grown under low fluid shear (LFS) conditions relevant to those encountered in the intestine. However, there has been limited characterization of LFS on other growth phases. To advance the growth-phase dependent understanding of the effect of LFS on S. Typhimurium pathogenicity, this dissertation characterized the effect of LFS on the transcriptomic and phenotypic responses in both stationary and lag phase cultures. In response to LFS, stationary phase cultures exhibited alterations in gene expression associated with metabolism, transport, secretion and stress responses (acid, bile salts, oxidative, and thermal stressors), motility, and colonization of intestinal epithelium (adherence, invasion and intracellular survival). Many of these characteristics are known to be regulated by the stationary phase general stress response regulator, RNA polymerase sigma factor S (RpoS), when S. Typhimurium is grown under conventional conditions. Surprisingly, the stationary phase phenotypic LFS stress response to acid and bile salts, colonization of human intestinal epithelial cells, and swimming motility was not dependent on RpoS. Lag phase cultures exhibited intriguing differences in their LFS regulated transcriptomic and phenotypic profiles as compared to stationary phase cultures, including LFS-dependent regulation of gene expression, adherence to intestinal epithelial cells, and high thermal stress. Furthermore, the addition of cell-free conditioned supernatants derived from either stationary phase LFS or Control cultures modulated the gene expression of lag phase cultures in a manner that differed from either growth phase, however, these supernatants did not modulate the phenotypic responses of lag phase cultures. Collectively, these results demonstrated that S. Typhimurium can sense and respond to LFS as early as lag phase, albeit in a limited fashion, and that the lag phase transcriptomic and phenotypic responses differ from those in stationary phase, which hold important implications for the lifecycle of this pathogen during the infection process.
ContributorsFranco, Karla Paola (Author) / Nikerson, Cheryl A (Thesis advisor) / Bean, Heather D (Committee member) / Stout, Valerie (Committee member) / Ott, C Mark (Committee member) / Barrila, Jennifer (Committee member) / Arizona State University (Publisher)
Created2020
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Description

In this paper, we present a Bayesian analysis for the Weibull proportional hazard (PH) model used in step-stress accelerated life testings. The key mathematical and graphical difference between the Weibull cumulative exposure (CE) model and the PH model is illustrated. Compared with the CE model, the PH model provides more

In this paper, we present a Bayesian analysis for the Weibull proportional hazard (PH) model used in step-stress accelerated life testings. The key mathematical and graphical difference between the Weibull cumulative exposure (CE) model and the PH model is illustrated. Compared with the CE model, the PH model provides more flexibility in fitting step-stress testing data and has the attractive mathematical properties of being desirable in the Bayesian framework. A Markov chain Monte Carlo algorithm with adaptive rejection sampling technique is used for posterior inference. We demonstrate the performance of this method on both simulated and real datasets.

ContributorsSha, Naijun (Author) / Pan, Rong (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-08-01
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We describe mechanical metamaterials created by folding flat sheets in the tradition of origami, the art of paper folding, and study them in terms of their basic geometric and stiffness properties, as well as load bearing capability. A periodic Miura-ori pattern and a non-periodic Ron Resch pattern were studied. Unexceptional

We describe mechanical metamaterials created by folding flat sheets in the tradition of origami, the art of paper folding, and study them in terms of their basic geometric and stiffness properties, as well as load bearing capability. A periodic Miura-ori pattern and a non-periodic Ron Resch pattern were studied. Unexceptional coexistence of positive and negative Poisson's ratio was reported for Miura-ori pattern, which are consistent with the interesting shear behavior and infinity bulk modulus of the same pattern. Unusually strong load bearing capability of the Ron Resch pattern was found and attributed to the unique way of folding. This work paves the way to the study of intriguing properties of origami structures as mechanical metamaterials.

ContributorsLv, Cheng (Author) / Krishnaraju, Deepak Shyam (Author) / Konjevod, Goran (Author) / Yu, Hongyu (Author) / Jiang, Hanqing (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-08-07
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Extreme events, a type of collective behavior in complex networked dynamical systems, often can have catastrophic consequences. To develop effective strategies to control extreme events is of fundamental importance and practical interest. Utilizing transportation dynamics on complex networks as a prototypical setting, we find that making the network “mobile” can

Extreme events, a type of collective behavior in complex networked dynamical systems, often can have catastrophic consequences. To develop effective strategies to control extreme events is of fundamental importance and practical interest. Utilizing transportation dynamics on complex networks as a prototypical setting, we find that making the network “mobile” can effectively suppress extreme events. A striking, resonance-like phenomenon is uncovered, where an optimal degree of mobility exists for which the probability of extreme events is minimized. We derive an analytic theory to understand the mechanism of control at a detailed and quantitative level, and validate the theory numerically. Implications of our finding to current areas such as cybersecurity are discussed.

ContributorsChen, Yu-Zhong (Author) / Huang, Zi-Gang (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-08-18
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We develop a completely data-driven approach to reconstructing coupled neuronal networks that contain a small subset of chaotic neurons. Such chaotic elements can be the result of parameter shift in their individual dynamical systems and may lead to abnormal functions of the network. To accurately identify the chaotic neurons may

We develop a completely data-driven approach to reconstructing coupled neuronal networks that contain a small subset of chaotic neurons. Such chaotic elements can be the result of parameter shift in their individual dynamical systems and may lead to abnormal functions of the network. To accurately identify the chaotic neurons may thus be necessary and important, for example, applying appropriate controls to bring the network to a normal state. However, due to couplings among the nodes, the measured time series, even from non-chaotic neurons, would appear random, rendering inapplicable traditional nonlinear time-series analysis, such as the delay-coordinate embedding method, which yields information about the global dynamics of the entire network. Our method is based on compressive sensing. In particular, we demonstrate that identifying chaotic elements can be formulated as a general problem of reconstructing the nodal dynamical systems, network connections and all coupling functions, as well as their weights. The working and efficiency of the method are illustrated by using networks of non-identical FitzHugh–Nagumo neurons with randomly-distributed coupling weights.

ContributorsSu, Riqi (Author) / Lai, Ying-Cheng (Author) / Wang, Xiao (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-07-01
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X-ray tomography has provided a non-destructive means for microstructure characterization in three and four dimensions. A stochastic procedure to accurately reconstruct material microstructure from limited-angle X-ray tomographic projections is presented and its utility is demonstrated by reconstructing a variety of distinct heterogeneous materials and elucidating the information content of different

X-ray tomography has provided a non-destructive means for microstructure characterization in three and four dimensions. A stochastic procedure to accurately reconstruct material microstructure from limited-angle X-ray tomographic projections is presented and its utility is demonstrated by reconstructing a variety of distinct heterogeneous materials and elucidating the information content of different projection data sets. A small number of projections (e.g. 20–40) are necessary for accurate reconstructions via the stochastic procedure, indicating its high efficiency in using limited structural information.

ContributorsLi, Hechao (Author) / Chawla, Nikhilesh (Author) / Jiao, Yang (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-09-01
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Description

Numerous recent investigations have been devoted to the determination of the equilibrium phase behavior and packing characteristics of hard nonspherical particles, including ellipsoids, superballs, and polyhedra, to name but just a few shapes. Systems of hard nonspherical particles exhibit a variety of stable phases with different degrees of translational and

Numerous recent investigations have been devoted to the determination of the equilibrium phase behavior and packing characteristics of hard nonspherical particles, including ellipsoids, superballs, and polyhedra, to name but just a few shapes. Systems of hard nonspherical particles exhibit a variety of stable phases with different degrees of translational and orientational order, including isotropic liquid, solid crystal, rotator and a variety of liquid crystal phases. In this paper, we employ a Monte Carlo implementation of the adaptive-shrinking-cell (ASC) numerical scheme and free-energy calculations to ascertain with high precision the equilibrium phase behavior of systems of congruent Archimedean truncated tetrahedra over the entire range of possible densities up to the maximal nearly space-filling density. In particular, we find that the system undergoes two first-order phase transitions as the density increases: first a liquid–solid transition and then a solid–solid transition. The isotropic liquid phase coexists with the Conway–Torquato (CT) crystal phase at intermediate densities, verifying the result of a previous qualitative study [J. Chem. Phys. 2011, 135, 151101]. The freezing- and melting-point packing fractions for this transition are respectively ϕF = 0.496 ± 0.006 and ϕM = 0.591 ± 0.005.

At higher densities, we find that the CT phase undergoes another first-order phase transition to one associated with the densest-known crystal, with coexistence densities in the range ϕ ∈ [0.780 ± 0.002, 0.802 ± 0.003]. We find no evidence for stable rotator (or plastic) or nematic phases. We also generate the maximally random jammed (MRJ) packings of truncated tetrahedra, which may be regarded to be the glassy end state of a rapid compression of the liquid. Specifically, we systematically study the structural characteristics of the MRJ packings, including the centroidal pair correlation function, structure factor and orientational pair correlation function. We find that such MRJ packings are hyperuniform with an average packing fraction of 0.770, which is considerably larger than the corresponding value for identical spheres (≈ 0.64). We conclude with some simple observations concerning what types of phase transitions might be expected in general hard-particle systems based on the particle shape and which would be good glass formers.

ContributorsChen, Duyu (Author) / Jiao, Yang (Author) / Torquato, Salvatore (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-07-17