Matching Items (17)
Filtering by
- All Subjects: Cancer
- Creators: School of Mathematical and Statistical Sciences
- Member of: Theses and Dissertations
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
The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a tumor, as a tumor cannot grow larger than 1-2 mm3 without developing its own blood supply. Vascular disrupting agents, such as iodocombstatin, a derivative of combretastatin, can be used to effectively cut off the blood supply to a growing neoplasm, effectively inhibiting the supply of oxygen and nutrients needed for cell division Thus, VDAs have a very important implication in terms of the future of chemotherapy. A prodrug, defined as an agent that is inactive in the body until metabolized to yield the drug itself, was synthesized by combining iodocombstatin with a β-glucuronide linker. The prodrug is theoretically hydrolyzed in the body to afford the active drug by β-glucuronidase, an enzyme that is produced five times as much by cancer cells as by normal cells. This effectively creates a “magic-bullet” form of chemotherapy, known as Direct Enzyme Prodrug Therapy (DEPT).
ContributorsClark, Caroline Marie (Author) / Pettit, George Robert (Thesis director) / Melody, Noeleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the cells of multicellular organisms which arises when the cell is subjected to an unusual amount of stress. Since this default phenotype is similar across cell types and even organisms, it seems it must be an evolutionarily ancestral phenotype. We take a phylostratigraphical approach, but systematically add species divergence time data to estimate gene ages numerically and use these ages to investigate the ages of genes involved in cancer. We find that ancient disease-recessive cancer genes are significantly enriched for DNA repair and SOS activity, which seems to imply that a core component of cancer development is not the regulation of growth, but the regulation of mutation. Verification of this finding could drastically improve cancer treatment and prevention.
ContributorsOrr, Adam James (Author) / Davies, Paul (Thesis director) / Bussey, Kimberly (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
Magnetic resonance imaging (MRI) data of metastatic brain cancer patients at the Barrow Neurological Institute sparked interest in the radiology department due to the possibility that tumor size distributions might mimic a power law or an exponential distribution. In order to consider the question regarding the growth trends of metastatic brain tumors, this thesis analyzes the volume measurements of the tumor sizes from the BNI data and attempts to explain such size distributions through mathematical models. More specifically, a basic stochastic cellular automaton model is used and has three-dimensional results that show similar size distributions of those of the BNI data. Results of the models are investigated using the likelihood ratio test suggesting that, when the tumor volumes are measured based on assuming tumor sphericity, the tumor size distributions significantly mimic the power law over an exponential distribution.
ContributorsFreed, Rebecca (Co-author) / Snopko, Morgan (Co-author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / WPC Graduate Programs (Contributor) / School of Accountancy (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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
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
Over time, tumor treatment resistance inadvertently develops when androgen de-privation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects of hormone therapy, the clinician may opt to cyclically alternates the patient’s treatment on and off. This method,known as intermittent ADT, is an alternative to continuous ADT that improves the patient’s quality of life while testosterone levels recover between cycles. In this paper,we explore the response of intermittent ADT to metastasized prostate cancer by employing a previously clinical data validated mathematical model to new clinical data from patients undergoing Abiraterone therapy. This cell quota model, a system of ordinary differential equations constructed using Droop’s nutrient limiting theory, assumes the tumor comprises of castration-sensitive (CS) and castration-resistant (CR)cancer sub-populations. The two sub-populations rely on varying levels of intracellular androgen for growth, death and transformation. Due to the complexity of the model,we carry out sensitivity analyses to study the effect of certain parameters on their outputs, and to increase the identifiability of each patient’s unique parameter set. The model’s forecasting results show consistent accuracy for patients with sufficient data,which means the model could give useful information in practice, especially to decide whether an additional round of treatment would be effective.
ContributorsBennett, Justin Klark (Author) / Kuang, Yang (Thesis director) / Kostelich, Eric (Committee member) / Phan, Tin (Committee member) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05