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Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not

Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not widely available (positron emission tomography (PET)). And one of the particular neurodegenerative regions is the hippocampus to which the influence of Aβ/tau on has been one of the research projects focuses in the AD pathophysiological progress. In this dissertation, I proposed three novel machine learning and statistical models to examine subtle aspects of the hippocampal morphometry from MRI that are associated with Aβ /tau burden in the brain, measured using PET images. The first model is a novel unsupervised feature reduction model to generate a low-dimensional representation of hippocampal morphometry for each individual subject, which has superior performance in predicting Aβ/tau burden in the brain. The second one is an efficient federated group lasso model to identify the hippocampal subregions where atrophy is strongly associated with abnormal Aβ/Tau. The last one is a federated model for imaging genetics, which can identify genetic and transcriptomic influences on hippocampal morphometry. Finally, I stated the results of these three models that have been published or submitted to peer-reviewed conferences and journals.
ContributorsWu, Jianfeng (Author) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Liang, Jianming (Committee member) / Wang, Junwen (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2022
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Description
This dissertation presents three novel algorithms with real-world applications to genomic oncology. While the methodologies presented here were all developed to overcome various challenges associated with the adoption of high throughput genomic data in clinical oncology, they can be used in other domains as well. First, a network informed feature

This dissertation presents three novel algorithms with real-world applications to genomic oncology. While the methodologies presented here were all developed to overcome various challenges associated with the adoption of high throughput genomic data in clinical oncology, they can be used in other domains as well. First, a network informed feature ranking algorithm is presented, which shows a significant increase in ability to select true predictive features from simulated data sets when compared to other state of the art graphical feature ranking methods. The methodology also shows an increased ability to predict pathological complete response to preoperative chemotherapy from genomic sequencing data of breast cancer patients utilizing domain knowledge from protein-protein interaction networks. Second, an algorithm that overcomes population biases inherent in the use of a human reference genome developed primarily from European populations is presented to classify microsatellite instability (MSI) status from next-generation-sequencing (NGS) data. The methodology significantly increases the accuracy of MSI status prediction in African and African American ancestries. Finally, a single variable model is presented to capture the bimodality inherent in genomic data stemming from heterogeneous diseases. This model shows improvements over other parametric models in the measurements of receiver-operator characteristic (ROC) curves for bimodal data. The model is used to estimate ROC curves for heterogeneous biomarkers in a dataset containing breast cancer and cancer-free specimen.
ContributorsSaul, Michelle (Author) / Dinu, Valentin (Thesis advisor) / Liu, Li (Committee member) / Wang, Junwen (Committee member) / Arizona State University (Publisher)
Created2021
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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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Description

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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Description

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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Description

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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Description

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

Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal

Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to understand the mechanism of interaction.

ContributorsSantander, Javier (Author) / Kilbourne, Jacquelyn (Author) / Park, Jie Yeun (Author) / Martin, Taylor (Author) / Loh, Amanda (Author) / Diaz, Ignacia (Author) / Rojas, Robert (Author) / Segovia, Cristopher (Author) / DeNardo, Dale (Author) / Curtiss, Roy (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2014-08-01
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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
Description

Background: Styrene is an important building-block petrochemical and monomer used to produce numerous plastics. Whereas styrene bioproduction by Escherichia coli was previously reported, the long-term potential of this approach will ultimately rely on the use of hosts with improved industrial phenotypes, such as the yeast Saccharomyces cerevisiae.

Results: Classical metabolic evolution was first

Background: Styrene is an important building-block petrochemical and monomer used to produce numerous plastics. Whereas styrene bioproduction by Escherichia coli was previously reported, the long-term potential of this approach will ultimately rely on the use of hosts with improved industrial phenotypes, such as the yeast Saccharomyces cerevisiae.

Results: Classical metabolic evolution was first applied to isolate a mutant capable of phenylalanine over-production to 357 mg/L. Transcription analysis revealed up-regulation of several phenylalanine biosynthesis pathway genes including ARO3, encoding the bottleneck enzyme DAHP synthase. To catalyze the first pathway step, phenylalanine ammonia lyase encoded by PAL2 from A. thaliana was constitutively expressed from a high copy plasmid. The final pathway step, phenylacrylate decarboxylase, was catalyzed by the native FDC1. Expression of FDC1 was naturally induced by trans-cinnamate, the pathway intermediate and its substrate, at levels sufficient for ensuring flux through the pathway. Deletion of ARO10 to eliminate the competing Ehrlich pathway and expression of a feedback-resistant DAHP synthase encoded by ARO4[subscript K229L] preserved and promoted the endogenous availability precursor phenylalanine, leading to improved pathway flux and styrene production. These systematic improvements allowed styrene titers to ultimately reach 29 mg/L at a glucose yield of 1.44 mg/g, a 60% improvement over the initial strain.

Conclusions: The potential of S. cerevisiae as a host for renewable styrene production has been demonstrated. Significant strain improvements, however, will ultimately be needed to achieve economical production levels.

ContributorsMcKenna, Rebekah (Author) / Thompson, Brian (Author) / Pugh, Shawn (Author) / Nielsen, David (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-08-21