Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item Dynamics, Networks, and Information: Methods for Nonlinear Interactions in Biological Systems(2021) Milzman, Jesse; Levy, Doron; Lyzinski, Vince; Mathematics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In this dissertation, we investigate complex, non-linear interactions in biological systems.This work is presented as two independent projects. The mathematics and biology in each differ, yet there is a unity in that both frameworks are interested in biological responses that cannot be reduced to linear causal chains, nor can they be expressed as an accumulation of binary interactions. In the first part of this dissertation, we use mathematical modeling to study tumor-immune dynamics at the cellular scale.Recent work suggests that LSD1 inhibition reduces tumor growth, increases T cell tumor infiltration, and complements PD1/PDL1 checkpoint inhibitor therapy. In order to elucidate the immunogenic effects of LSD1 inhibition, we create a delay differential equation model of tumor growth under the influence of the adaptive immune response in order to investigate the anti-tumor cytotoxicity of LSD1-mediated T cell dynamics. We fit our model to the B16 mouse model data from Sheng et al. [DOI:10.1016/j.cell.2018.05.052] Our results suggest that the immunogenic effect of LSD1 inhibition accelerates anti-tumor cytoxicity. However, cytotoxicity does not seem to account for the slower growth observed in LSD1 inhibited tumors, despite evidence suggesting immune-mediation of this effect. In the second part, we consider the partial information decomposition (PID) of response information within networks of interacting nodes, inspired by biomolecular networks.We specifically study the potential of PID synergy as a tool for network inference and edge nomination. We conduct both numeric and analytic investigations of the $\Imin$ and $\Ipm$ PIDs, from [arXiv:1004.2515] and [DOI:10.3390/e20040297], respectively. We find that the $I_\text{PM}$ synergy suffers from issues of non-specificity, while $I_{\text{min}}$ synergy is specific but somewhat insensitive. In the course of our work, we extend the $I_\text{PM}$ and $I_{\text{min}}$ PIDs to continuous variables for a general class of noise-free trivariate systems. The $I_\text{PM}$ PID does not respect conditional independence, while$I_{\text{min}}$ does, as demonstrated through asymptotic analysis of linear and non-linear interaction kernels. The technical results of this chapter relate the analytic and information-theoretic properties of our interactions, by expressing the continuous PID of noise-free interactions in terms of the partial derivatives of the interaction kernel.Item Emergent behaviors in adaptive dynamical networks with applications to biological and social systems(2021) Alexander, Brandon Marc; Girvan, Michelle; Applied Mathematics and Scientific Computation; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In this thesis, we consider three network-based systems, focusing on emergent behaviors resulting from adaptive dynamical features. In our first investigation, we create a model for gene regulatory networks in which the network topology evolves over time to avoid instability of the regulatory dynamics. We consider and compare different rules of competitive edge addition that use topological and dynamical information from the network to determine how new network links are added. We find that aiming to keep connected components small is more effective at preventing widespread network failure than limiting the connections of genes with high sensitivity (i.e., potential for high variability across conditions). Finally, we compare our results to real data from several species and find a trend toward disassortativity over evolutionary time that is similar to our model for structure-based selection. In our second investigation, we introduce a bidirectional coupling between a phase synchronization model and a cascade model to produce our `sync-contagion' model. The sync-contagion model is well-suited to describe a system in which a contagious signal alerts individuals to realign their orientations, where `orientation' can be in the literal sense (such as a school of fish escaping the threat of a predator) or a more abstract sense (such as a `political orientation' that changes in response to a hot topic). We find that success in realigning the population towards some desired target orientation depends on the relative strengths of contagion spread and synchronization coupling. In our third and final investigation, we attempt to forecast the complex infection dynamics of the COVID-19 pandemic through a data-driven reservoir computing approach. We focus our attention on forecasting case numbers in the United States at the national and state levels. Despite producing adequate short-term predictions, we find that a simple reservoir computing approach does not perform significantly better than a linear extrapolation. The biggest challenge is the lack of data quantity normally required for machine learning success. We discuss methods to augment our limited data, such as through a `library-based' method or a hybrid modeling approach.Item Enabling Graph Analysis Over Relational Databases(2019) Xirogiannopoulos, Konstantinos; Deshpande, Amol; Computer Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Complex interactions and systems can be modeled by analyzing the connections between underlying entities or objects described by a dataset. These relationships form networks (graphs), the analysis of which has been shown to provide tremendous value in areas ranging from retail to many scientific domains. This value is obtained by using various methodologies from network science-- a field which focuses on studying network representations in the real world. In particular "graph algorithms", which iteratively traverse a graph's connections, are often leveraged to gain insights. To take advantage of the opportunity presented by graph algorithms, there have been a variety of specialized graph data management systems, and analysis frameworks, proposed in recent years, which have made significant advances in efficiently storing and analyzing graph-structured data. Most datasets however currently do not reside in these specialized systems but rather in general-purpose relational database management systems (RDBMS). A relational or similarly structured system is typically governed by a schema of varying strictness that implements constraints and is meticulously designed for the specific enterprise. Such structured datasets contain many relationships between the entities therein, that can be seen as latent or "hidden" graphs that exist inherently inside the datasets. However, these relationships can only typically be traversed via conducting expensive JOINs using SQL or similar languages. Thus, in order for users to efficiently traverse these latent graphs to conduct analysis, data needs to be transformed and migrated to specialized systems. This creates barriers that hinder and discourage graph analysis; our vision is to break these barriers. In this dissertation we investigate the opportunities and challenges involved in efficiently leveraging relationships within data stored in structured databases. First, we present GraphGen, a lightweight software layer that is independent from the underlying database, and provides interfaces for graph analysis of data in RDBMSs. GraphGen is the first such system that introduces an intuitive high-level language for specifying graphs of interest, and utilizes in-memory graph representations to tackle the problems associated with analyzing graphs that are hidden inside structured datasets. We show GraphGen can analyze such graphs in orders of magnitude less memory, and often computation time, while eliminating manual Extract-Transform-Load (ETL) effort. Second, we examine how in-memory graph representations of RDBMS data can be used to enhance relational query processing. We present a novel, general framework for executing GROUP BY aggregation over conjunctive queries which avoids materialization of intermediate JOIN results, and wrap this framework inside a multi-way relational operator called Join-Agg. We show that Join-Agg can compute aggregates over a class of relational and graph queries using orders of magnitude less memory and computation time.Item STABILITY AND SCALING OF NEURONAL AVALANCHES AND THEIR RELATIONSHIP TO NEURONAL OSCILLATIONS(2019) Miller, Stephanie Regina; Roy, Rajarshi; Biophysics (BIPH); Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The generation of cortical dynamics in awake mammals is not yet fully understood. However, it is known that neurons leverage distinct organizational schemes to achieve behavior and cognitive function, and that this precise spatiotemporal organization may go awry in illness. In 2003, a form of scale-free synchrony termed “neuronal avalanches” was first observed by Beggs & Plenz in cultured cortical tissue and later confirmed in rodents, nonhuman primates, and humans. In this dissertation, we draw from monkey and rodent studies to demonstrate that neuronal avalanches capture key features of neural population activity and constitute a robust and stable (e.g. self-organized) indicator of balanced excitation and inhibition in cortical networks. We also show for the first time that neuronal avalanches and oscillations co-exist in frontal cortex of nonhuman primates and identify the avalanche temporal shape as a biomarker predicated upon critical systems theory. Finally, we present progress towards characterizing altered avalanche dynamics in a developmental mouse model for schizophrenia using 2-photon calcium imaging in awake animals.