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- Creators: School of Mathematical and Statistical Sciences
- Member of: Theses and Dissertations
- Status: Published
Description
Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Covering subsequences with sets of permutations arises in many applications, including event-sequence testing. Given a set of subsequences to cover, one is often interested in knowing the fewest number of permutations required to cover each subsequence, and in finding an explicit construction of such a set of permutations that has size close to or equal to the minimum possible. The construction of such permutation coverings has proven to be computationally difficult. While many examples for permutations of small length have been found, and strong asymptotic behavior is known, there are few explicit constructions for permutations of intermediate lengths. Most of these are generated from scratch using greedy algorithms. We explore a different approach here. Starting with a set of permutations with the desired coverage properties, we compute local changes to individual permutations that retain the total coverage of the set. By choosing these local changes so as to make one permutation less "essential" in maintaining the coverage of the set, our method attempts to make a permutation completely non-essential, so it can be removed without sacrificing total coverage. We develop a post-optimization method to do this and present results on sequence covering arrays and other types of permutation covering problems demonstrating that it is surprisingly effective.
ContributorsMurray, Patrick Charles (Author) / Colbourn, Charles (Thesis director) / Czygrinow, Andrzej (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Physics (Contributor)
Created2014-12
Description
Currently in synthetic biology only the Las, Lux, and Rhl quorum sensing pathways have been adapted for broad engineering use. Quorum sensing allows a means of cell to cell communication in which a designated sender cell produces quorum sensing molecules that modify gene expression of a designated receiver cell. While useful, these three quorum sensing pathways exhibit a nontrivial level of crosstalk, hindering robust engineering and leading to unexpected effects in a given design. To address the lack of orthogonality among these three quorum sensing pathways, previous scientists have attempted to perform directed evolution on components of the quorum sensing pathway. While a powerful tool, directed evolution is limited by the subspace that is defined by the protein. For this reason, we take an evolutionary biology approach to identify new orthogonal quorum sensing networks and test these networks for cross-talk with currently-used networks. By charting characteristics of acyl homoserine lactone (AHL) molecules used across quorum sensing pathways in nature, we have identified favorable candidate pathways likely to display orthogonality. These include Aub, Bja, Bra, Cer, Esa, Las, Lux, Rhl, Rpa, and Sin, which we have begun constructing and testing. Our synthetic circuits express GFP in response to a quorum sensing molecule, allowing quantitative measurement of orthogonality between pairs. By determining orthogonal quorum sensing pairs, we hope to identify and adapt novel quorum sensing pathways for robust use in higher-order genetic circuits.
ContributorsMuller, Ryan (Author) / Haynes, Karmella (Thesis director) / Wang, Xiao (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
In many systems, it is difficult or impossible to measure the phase of a signal. Direct recovery from magnitude is an ill-posed problem. Nevertheless, with a sufficiently large set of magnitude measurements, it is often possible to reconstruct the original signal using algorithms that implicitly impose regularization conditions on this ill-posed problem. Two such algorithms were examined: alternating projections, utilizing iterative Fourier transforms with manipulations performed in each domain on every iteration, and phase lifting, converting the problem to that of trace minimization, allowing for the use of convex optimization algorithms to perform the signal recovery. These recovery algorithms were compared on a basis of robustness as a function of signal-to-noise ratio. A second problem examined was that of unimodular polyphase radar waveform design. Under a finite signal energy constraint, the maximal energy return of a scene operator is obtained by transmitting the eigenvector of the scene Gramian associated with the largest eigenvalue. It is shown that if instead the problem is considered under a power constraint, a unimodular signal can be constructed starting from such an eigenvector that will have a greater return.
ContributorsJones, Scott Robert (Author) / Cochran, Douglas (Thesis director) / Diaz, Rodolfo (Committee member) / Barrett, The Honors College (Contributor) / Electrical Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05
Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Mortality of 1918 influenza virus was high, partly due to bacteria coinfections. We characterize pandemic mortality in Arizona, which had high prevalence of tuberculosis. We applied regressions to over 35,000 data points to estimate the basic reproduction number and excess mortality. Age-specific mortality curves show elevated mortality for all age groups, especially the young, and senior sparing effects. The low value for reproduction number indicates that transmissibility was moderately low.
ContributorsJenner, Melinda Eva (Author) / Chowell-Puente, Gerardo (Thesis director) / Kostelich, Eric (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Pogonomyrmex californicus (a species of harvester ant) colonies typically have anywhere from one to five queens. A queen can control the ratio of female to male offspring she produces, field research indicating that this ratio is genetically hardwired and does not change over time relative to other queens. Further, a queen has an individual reproductive advantage if she has a small reproductive ratio. A colony, however, has a reproductive advantage if it has queens with large ratios, as these queens produce many female workers to further colony success. We have developed an agent-based model to analyze the "cheating" phenotype observed in field research, in which queens extend their lifespans by producing disproportionately many male offspring. The model generates phenotypes and simulates years of reproductive cycles. The results allow us to examine the surviving phenotypes and determine conditions under which a cheating phenotype has an evolutionary advantage. Conditions generating a bimodal steady state solution would indicate a cheating phenotype's ability to invade a cooperative population.
ContributorsEngel, Lauren Marie Agnes (Author) / Armbruster, Dieter (Thesis director) / Fewell, Jennifer (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Many forms of programmable matter have been proposed for various tasks. We use an abstract model of self-organizing particle systems for programmable matter which could be used for a variety of applications, including smart paint and coating materials for engineering or programmable cells for medical uses. Previous research using this model has focused on shape formation and other spatial configuration problems, including line formation, compression, and coating. In this work we study foundational computational tasks that exceed the capabilities of the individual constant memory particles described by the model. These tasks represent new ways to use these self-organizing systems, which, in conjunction with previous shape and configuration work, make the systems useful for a wider variety of tasks. We present an implementation of a counter using a line of particles, which makes it possible for the line of particles to count to and store values much larger than their individual capacities. We then present an algorithm that takes a matrix and a vector as input and then sets up and uses a rectangular block of particles to compute the matrix-vector multiplication. This setup also utilizes the counter implementation to store the resulting vector from the matrix-vector multiplication. Operations such as counting and matrix multiplication can leverage the distributed and dynamic nature of the self-organizing system to be more efficient and adaptable than on traditional linear computing hardware. Such computational tools also give the systems more power to make complex decisions when adapting to new situations or to analyze the data they collect, reducing reliance on a central controller for setup and output processing. Finally, we demonstrate an application of similar types of computations with self-organizing systems to image processing, with an implementation of an image edge detection algorithm.
ContributorsPorter, Alexandra Marie (Author) / Richa, Andrea (Thesis director) / Xue, Guoliang (Committee member) / School of Music (Contributor) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Many programmable matter systems have been proposed and realized recently, each often tailored toward a particular task or physical setting. In our work on self-organizing particle systems, we abstract away from specific settings and instead describe programmable matter as a collection of simple computational elements (to be referred to as particles) with limited computational power that each perform fully distributed, local, asynchronous algorithms to solve system-wide problems of movement, configuration, and coordination. In this thesis, we focus on the compression problem, in which the particle system gathers as tightly together as possible, as in a sphere or its equivalent in the presence of some underlying geometry. While there are many ways to formalize what it means for a particle system to be compressed, we address three different notions of compression: (1) local compression, in which each individual particle utilizes local rules to create an overall convex structure containing no holes, (2) hole elimination, in which the particle system seeks to detect and eliminate any holes it contains, and (3) alpha-compression, in which the particle system seeks to shrink its perimeter to be within a constant factor of the minimum possible value. We analyze the behavior of each of these algorithms, examining correctness and convergence where appropriate. In the case of the Markov Chain Algorithm for Compression, we provide improvements to the original bounds for the bias parameter lambda which influences the system to either compress or expand. Lastly, we briefly discuss contributions to the problem of leader election--in which a particle system elects a single leader--since it acts as an important prerequisite for compression algorithms that use a predetermined seed particle.
ContributorsDaymude, Joshua Jungwoo (Author) / Richa, Andrea (Thesis director) / Kierstead, Henry (Committee member) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Optimal foraging theory provides a suite of tools that model the best way that an animal will <br/>structure its searching and processing decisions in uncertain environments. It has been <br/>successful characterizing real patterns of animal decision making, thereby providing insights<br/>into why animals behave the way they do. However, it does not speak to how animals make<br/>decisions that tend to be adaptive. Using simulation studies, prior work has shown empirically<br/>that a simple decision-making heuristic tends to produce prey-choice behaviors that, on <br/>average, match the predicted behaviors of optimal foraging theory. That heuristic chooses<br/>to spend time processing an encountered prey item if that prey item's marginal rate of<br/>caloric gain (in calories per unit of processing time) is greater than the forager's<br/>current long-term rate of accumulated caloric gain (in calories per unit of total searching<br/>and processing time). Although this heuristic may seem intuitive, a rigorous mathematical<br/>argument for why it tends to produce the theorized optimal foraging theory behavior has<br/>not been developed. In this thesis, an analytical argument is given for why this<br/>simple decision-making heuristic is expected to realize the optimal performance<br/>predicted by optimal foraging theory. This theoretical guarantee not only provides support<br/>for why such a heuristic might be favored by natural selection, but it also provides<br/>support for why such a heuristic might a reliable tool for decision-making in autonomous<br/>engineered agents moving through theatres of uncertain rewards. Ultimately, this simple<br/>decision-making heuristic may provide a recipe for reinforcement learning in small robots<br/>with little computational capabilities.
ContributorsCothren, Liliaokeawawa Kiyoko (Author) / Pavlic, Theodore (Thesis director) / Brewer, Naala (Committee member) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05