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Description
Neural tissue is a delicate system comprised of neurons and their synapses, glial cells for support, and vasculature for oxygen and nutrient delivery. This complexity ultimately gives rise to the human brain, a system researchers have become increasingly interested in replicating for artificial intelligence purposes. Some have even gone so far as to use neuronal cultures as computing hardware, but utilizing an environment closer to a living brain means having to grapple with the same issues faced by clinicians and researchers trying to treat brain disorders. Most outstanding among these are the problems that arise with invasive interfaces. Optical techniques that use fluorescent dyes and proteins have emerged as a solution for noninvasive imaging with single-cell resolution in vitro and in vivo, but feeding in information in the form of neuromodulation still requires implanted electrodes. The implantation process of these electrodes damages nearby neurons and their connections, causes hemorrhaging, and leads to scarring and gliosis that diminish efficacy. Here, a new approach for noninvasive neuromodulation with high spatial precision is described. It makes use of a combination of ultrasound, high frequency acoustic energy that can be focused to submillimeter regions at significant depths, and electric fields, an effective tool for neuromodulation that lacks spatial precision when used in a noninvasive manner. The hypothesis is that, when combined in a specific manner, these will lead to nonlinear effects at neuronal membranes that cause cells only in the region of overlap to be stimulated. Computational modeling confirmed this combination to be uniquely stimulating, contingent on certain physical effects of ultrasound on cell membranes. Subsequent in vitro experiments led to inconclusive results, however, leaving the door open for future experimentation with modified configurations and approaches. The specific combination explored here is also not the only untested technique that may achieve a similar goal.
ContributorsNester, Elliot (Author) / Wang, Yalin (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2022
Description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) that emerged from a zoonotic host at the end of 2019 and caused a public health crisis. In this collection of studies, Nicotiana benthamiana plants are used to set the foundation for producing monoclonal antibodies (mAbs) with homogeneous glycosylation to neutralize SARS-CoV-2 and potentially address the immunopathology often observed with severe COVID-19. Specifically, a mAb against the human interleukin (IL)-6 receptor (sarilumab) was generated and evaluated in vitro for its potential to reduce IL-6 signaling that has been shown to be associated with more severe cases of COVID-19. Furthermore, multiple mAbs that bind to the receptor-binding domain (RBD) of SARS-CoV-2 and efficiently neutralize the virus were developed using plant-based expression. Several of these mAbs are from different classes of RBD-binding mAbs that have distinct binding sites from one another. Several mAbs from different classes showed synergy in neutralizing the ancestral strain of SARS-CoV-2 and a smaller subset showed synergy when tested against the highly mutated Omicron (B.1.1.529) variant. Of interest, a novel RBD-binding mAb, termed 11D7, that was raised against the ancestral strain and derived from a hybridoma, appears to have an epitope on the RBD that contributes more synergy to a mAb combination that efficiently neutralizes the B.1.1.529 variant of SARS-CoV-2. This epitope was partially mapped by competitive binding and shows that it overlaps with another known antibody that binds a cryptic, distal epitope, away from the receptor binding site, giving insight into the potential mechanism by which 11D7 neutralizes SARS-CoV-2, as well as potentially allowing it to resist SARS-CoV-2 immune evasion more efficiently. Furthermore, this mAb carries a highly homogeneous glycan pattern when expressed in N. benthamiana, that may contribute to enhanced effector function and provides a tool to elucidate the precise role of crystallizable fragment (Fc)-mediated protection in SARS-CoV-2 infection. Ultimately, these studies provide evidence of the utility of plant-made mAbs to be used as cocktail members, giving clarity to the use of less potent mAbs as valuable cocktail components which will spur further investigations into how mAbs with unique epitopes work together to efficiently neutralize SARS-CoV-2.
ContributorsJugler, Collin (Author) / Chen, Qiang (Thesis advisor) / Lake, Douglas (Committee member) / Steele, Kelly (Committee member) / Mason, Hugh (Committee member) / Arizona State University (Publisher)
Created2022
Description
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
Description
Structural Magnetic Resonance Imaging analysis is a vital component in the study of Alzheimer’s Disease pathology and several techniques exist as part of the existing research conducted. In particular, volumetric approaches in this field are known to be beneficial due to the increased capability to express morphological characteristics when compared to manifold methods. To aid in the improvement of the field, this paper aims to propose an intrinsic volumetric conic system that can be applied to bounded volumetric meshes to enable a more effective study of subjects. The computation of the metric involves the use of heat kernel theory and conformal parameterization on genus-0 surfaces extended to a volumetric domain. Additionally, this paper also explores the use of the ’TetCNN’ architecture on the classification of hippocampal tetrahedral meshes to detect features that correspond to Alzheimer’s indicators. The model tested was able to achieve remarkable results with a measured classification accuracy of above 90% in the task of differentiating between subjects diagnosed with Alzheimer’s and normal control subjects.
ContributorsGeorge, John Varghese (Author) / Wang, Yalin (Thesis advisor) / Hansford, Dianne (Committee member) / Gupta, Vikash (Committee member) / Arizona State University (Publisher)
Created2023
Description
Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically approved to treat only 10 out of the greater than 200 known pathogenic human viruses. Additionally, as obligate intracellular parasites, many virus functions are intimately coupled with host cellular processes. As such, the development of a clinically relevant antiviral is challenged by the limited number of clear targets per virus and necessitates an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. Therefore, a means to develop virus- or strain-specific antivirals without detailed insight into each idiosyncratic biochemical mechanism may aid in the development of antivirals against a larger swath of pathogens. Such an approach will tremendously benefit from having the specific molecular recognition of viral species as the lowest barrier. Here, I modify a nanobody (anti-green fluorescent protein) that specifically recognizes non-essential epitopes (glycoprotein M-pHluorin chimera) presented on the extra virion surface of a virus (Pseudorabies virus strain 486). The nanobody switches from having no inhibitory properties (tested up to 50 μM) to ∼3 nM IC50 in in vitro infectivity assays using porcine kidney (PK15) cells. The nanobody modifications use highly reliable bioconjugation to a three-dimensional wireframe deoxyribonucleic acid (DNA) origami scaffold. Mechanistic studies suggest that inhibition is mediated by the DNA origami scaffold bound to the virus particle, which obstructs the internalization of the viruses into cells, and that inhibition is enhanced by avidity resulting from multivalent virus and scaffold interactions. The assembled nanostructures demonstrate negligible cytotoxicity (<10 nM) and sufficient stability, further supporting their therapeutic potential. If translatable to other viral species and epitopes, this approach may open a new strategy that leverages existing infrastructures – monoclonal antibody development, phage display, and in vitro evolution - for rapidly developing novel antivirals in vivo.
ContributorsPradhan, Swechchha (Author) / Hariadi, Rizal (Thesis advisor) / Hogue, Ian (Committee member) / Varsani, Arvind (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2022
Description
Communicating with computers through thought has been a remarkable achievement in recent years. This was made possible by the use of Electroencephalography (EEG). Brain-computer interface (BCI) relies heavily on Electroencephalography (EEG) signals for communication between humans and computers. With the advent ofdeep learning, many studies recently applied these techniques to EEG data to perform various tasks like emotion recognition, motor imagery classification, sleep analysis, and many more.
Despite the rise of interest in EEG signal classification, very few studies have explored the MindBigData dataset, which collects EEG signals recorded at the stimulus of seeing a digit and thinking about it. This dataset takes us closer to realizing the idea of mind-reading or communication via thought. Thus classifying these signals into the respective digit that the user thinks about is a challenging task. This serves as a motivation to study this dataset and apply existing deep learning techniques to study it.
Given the recent success of transformer architecture in different domains like Computer Vision and Natural language processing, this thesis studies transformer architecture for EEG signal classification. Also, it explores other deep learning
techniques for the same. As a result, the proposed classification pipeline achieves comparable performance with the existing methods.
ContributorsMuglikar, Omkar Dushyant (Author) / Wang, Yalin (Thesis advisor) / Liang, Jianming (Committee member) / Venkateswara, Hemanth (Committee member) / Arizona State University (Publisher)
Created2021
Description
Statistical Shape Modeling is widely used to study the morphometrics of deformable objects in computer vision and biomedical studies. There are mainly two viewpoints to understand the shapes. On one hand, the outer surface of the shape can be taken as a two-dimensional embedding in space. On the other hand, the outer surface along with its enclosed internal volume can be taken as a three-dimensional embedding of interests. Most studies focus on the surface-based perspective by leveraging the intrinsic features on the tangent plane. But a two-dimensional model may fail to fully represent the realistic properties of shapes with both intrinsic and extrinsic properties. In this thesis, severalStochastic Partial Differential Equations (SPDEs) are thoroughly investigated and several methods are originated from these SPDEs to try to solve the problem of both two-dimensional and three-dimensional shape analyses. The unique physical meanings of these SPDEs inspired the findings of features, shape descriptors, metrics, and kernels in this series of works. Initially, the data generation of high-dimensional shapes, here, the tetrahedral meshes, is introduced. The cerebral cortex is taken as the study target and an automatic pipeline of generating the gray matter tetrahedral mesh is introduced. Then, a discretized Laplace-Beltrami operator (LBO) and a Hamiltonian operator (HO) in tetrahedral domain with Finite Element Method (FEM) are derived. Two high-dimensional shape descriptors are defined based on the solution of the heat equation and Schrödinger’s equation. Considering the fact that high-dimensional shape models usually contain massive redundancies, and the demands on effective landmarks in many applications, a Gaussian process landmarking on tetrahedral meshes is further studied. A SIWKS-based metric space is used to define a geometry-aware Gaussian process. The study of the periodic potential diffusion process further inspired the idea of a new kernel call the geometry-aware convolutional kernel. A series of Bayesian learning methods are then introduced to tackle the problem of shape retrieval and classification. Experiments of every single item are demonstrated. From the popular SPDE such as the heat equation and Schrödinger’s equation to the general potential diffusion equation and the specific periodic potential diffusion equation, it clearly shows that classical SPDEs play an important role in discovering new features, metrics, shape descriptors and kernels. I hope this thesis could be an example of using interdisciplinary knowledge to solve problems.
ContributorsFan, Yonghui (Author) / Wang, Yalin (Thesis advisor) / Lepore, Natasha (Committee member) / Turaga, Pavan (Committee member) / Yang, Yezhou (Committee member) / Arizona State University (Publisher)
Created2021
Description
Cities in the Global South face rapid urbanization challenges and often suffer an acute lack of infrastructure and governance capacities. Smart Cities Mission, in India, launched in 2015, aims to offer a novel approach for urban renewal of 100 cities following an area‐based development approach, where the use of ICT and digital technologies is particularly emphasized. This article presents a critical review of the design and implementation framework of this new urban renewal program across selected case‐study cities. The article examines the claims of the so‐called “smart cities” against actual urban transformation on‐ground and evaluates how “inclusive” and “sustainable” these developments are. We quantify the scale and coverage of the smart city urban renewal projects in the cities to highlight who the program includes and excludes. The article also presents a statistical analysis of the sectoral focus and budgetary allocations of the projects under the Smart Cities Mission to find an inherent bias in these smart city initiatives in terms of which types of development they promote and the ones it ignores. The findings indicate that a predominant emphasis on digital urban renewal of selected precincts and enclaves, branded as “smart cities,” leads to deepening social polarization and gentrification. The article offers crucial urban planning lessons for designing ICT‐driven urban renewal projects, while addressing critical questions around inclusion and sustainability in smart city ventures.`
ContributorsPraharaj, Sarbeswar (Author)
Created2021-05-07
Description
Graph matching is a fundamental but notoriously difficult problem due to its NP-hard nature, and serves as a cornerstone for a series of applications in machine learning and computer vision, such as image matching, dynamic routing, drug design, to name a few. Although there has been massive previous investigation on high-performance graph matching solvers, it still remains a challenging task to tackle the matching problem under real-world scenarios with severe graph uncertainty (e.g., noise, outlier, misleading or ambiguous link).In this dissertation, a main focus is to investigate the essence and propose solutions to graph matching with higher reliability under such uncertainty. To this end, the proposed research was conducted taking into account three perspectives related to reliable graph matching: modeling, optimization and learning. For modeling, graph matching is extended from typical quadratic assignment problem to a more generic mathematical model by introducing a specific family of separable function, achieving higher capacity and reliability. In terms of optimization, a novel high gradient-efficient determinant-based regularization technique is proposed in this research, showing high robustness against outliers. Then learning paradigm for graph matching under intrinsic combinatorial characteristics is explored. First, a study is conducted on the way of filling the gap between discrete problem and its continuous approximation under a deep learning framework. Then this dissertation continues to investigate the necessity of more reliable latent topology of graphs for matching, and propose an effective and flexible framework to obtain it. Coherent findings in this dissertation include theoretical study and several novel algorithms, with rich experiments demonstrating the effectiveness.
ContributorsYu, Tianshu (Author) / Li, Baoxin (Thesis advisor) / Wang, Yalin (Committee member) / Yang, Yezhou (Committee member) / Yang, Yingzhen (Committee member) / Arizona State University (Publisher)
Created2021
Description
Graph matching is a fundamental but notoriously difficult problem due to its NP-hard nature, and serves as a cornerstone for a series of applications in machine learning and computer vision, such as image matching, dynamic routing, drug design, to name a few. Although there has been massive previous investigation on high-performance graph matching solvers, it still remains a challenging task to tackle the matching problem under real-world scenarios with severe graph uncertainty (e.g., noise, outlier, misleading or ambiguous link).In this dissertation, a main focus is to investigate the essence and propose solutions to graph matching with higher reliability under such uncertainty. To this end, the proposed research was conducted taking into account three perspectives related to reliable graph matching: modeling, optimization and learning. For modeling, graph matching is extended from typical quadratic assignment problem to a more generic mathematical model by introducing a specific family of separable function, achieving higher capacity and reliability. In terms of optimization, a novel high gradient-efficient determinant-based regularization technique is proposed in this research, showing high robustness against outliers. Then learning paradigm for graph matching under intrinsic combinatorial characteristics is explored. First, a study is conducted on the way of filling the gap between discrete problem and its continuous approximation under a deep learning framework. Then this dissertation continues to investigate the necessity of more reliable latent topology of graphs for matching, and propose an effective and flexible framework to obtain it. Coherent findings in this dissertation include theoretical study and several novel algorithms, with rich experiments demonstrating the effectiveness.
ContributorsYu, Tianshu (Author) / Li, Baoxin (Thesis advisor) / Wang, Yalin (Committee member) / Yang, Yezhou (Committee member) / Yang, Yingzhen (Committee member) / Arizona State University (Publisher)
Created2021