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Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into

Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.

ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in

The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in a single fly that would allow for simultaneous expression of the oncogene and, in <br/>the surrounding cells, other genes of interest. This system would help establish Drosophila as a <br/>more versatile and reliable model organism for cancer research. Furthermore, pilot studies were <br/>performed, using elements of the final proposed system, to determine if tumor growth is possible <br/>in the center of the disc, which oncogene produces the best results, and if oncogene expression <br/>induced later in development causes tumor growth. Three different candidate genes were <br/>investigated: RasV12, PvrACT, and Avli.

ContributorsSt Peter, John Daniel (Author) / Harris, Rob (Thesis director) / Varsani, Arvind (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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The colossal global counterfeit market and advances in cryptography including quantum computing supremacy have led the drive for a class of anti-counterfeit tags that are physically unclonable. Dendrites, previously considered an undesirable side effect of battery operation, have promise as an extremely versatile version of such tags, with their fundamental

The colossal global counterfeit market and advances in cryptography including quantum computing supremacy have led the drive for a class of anti-counterfeit tags that are physically unclonable. Dendrites, previously considered an undesirable side effect of battery operation, have promise as an extremely versatile version of such tags, with their fundamental nature ensuring that no two dendrites are alike and that they can be read at multiple magnification scales. In this work, we first pursue a simulation for electrochemical dendrites that elucidates fundamental information about their growth mechanism. We then translate these results into physical dendrites and demonstrate methods of producing a hash from these dendrites that is damage-tolerant for real-world verification. Finally, we explore theoretical curiosities that arise from the fractal nature of dendrites. We find that uniquely ramified dendrites, which rely on lower ion mobility and conductive deposition, are particularly amenable to wavelet hashing, and demonstrate that these dendrites have strong commercial potential for securing supply chains at the highest level while maintaining a low price point.

ContributorsSneh, Tal (Author) / Kozicki, Michael (Thesis director) / Gonzalez-Velo, Yago (Committee member) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Pelvic Circumferential Compression Devices (PCCDs), an important medical device when caring for patients with pelvic fractures, play a crucial role in the stabilization and reduction of the fracture. During pelvic fracture cases, control of internal bleeding through access to the femoral artery is of utmost importance. Current designs of PCCDs

Pelvic Circumferential Compression Devices (PCCDs), an important medical device when caring for patients with pelvic fractures, play a crucial role in the stabilization and reduction of the fracture. During pelvic fracture cases, control of internal bleeding through access to the femoral artery is of utmost importance. Current designs of PCCDs do not allow vital access to this artery and in attempts to gain access, medical professionals and emergency care providers choose to cut into the PCCDs or place them in suboptimal positions with unknown downstream effects. We researched the effects on surface pressure and the overall pressure distribution created by the PCCDs when they are modified or placed incorrectly on the patient. In addition, we investigated the effects of those misuses on pelvic fracture reduction, a key parameter in stabilizing the patient during critical care. We hypothesized that incorrectly placing or modifying the PCCD will result in increased surface pressure and decreased fracture reduction. Our mannequin studies show that for SAM Sling and T-POD, surface pressure increases if a PCCD is incorrectly placed or modified, in support of our hypothesis. However, opposite results occurred for the Pelvic Binder, where the correctly placed PCCD had higher surface pressure when compared to the incorrectly placed or modified PCCD. Additionally, pressure distribution was significantly affected by the modification of the PCCDs. The cadaver lab measurements show that modifying or incorrectly placing the PCCDs significantly limits their ability to reduce the pelvic fracture. These results suggest that while modifying or incorrectly placing PCCDs allows access to the femoral artery, there are potentially dangerous effects to the patient including increased surface pressures and limited fracture reduction.

ContributorsConley, Ian Patrick (Co-author) / Ryder, Madison (Co-author) / Vernon, Brent (Thesis director) / Bogert, James (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
To supplement lectures, various resources are available to students; however, little research has been done to look systematically at which resources studies find most useful and the frequency at which they are used. We have conducted a preliminary study looking at various resources available in an introductory material science course

To supplement lectures, various resources are available to students; however, little research has been done to look systematically at which resources studies find most useful and the frequency at which they are used. We have conducted a preliminary study looking at various resources available in an introductory material science course over four semesters using a custom survey called the Student Resource Value Survey (SRVS). More specifically, the SRVS was administered before each test to determine which resources students use to do well on exams. Additionally, over the course of the semester, which resources students used changed. For instance, study resources for exams including the use of homework problems decreased from 81% to 50%, the utilization of teaching assistant for exam studying increased from 25% to 80%, the use of in class Muddiest Points for exam study increased form 28% to 70%, old exams and quizzes only slightly increased for exam study ranging from 78% to 87%, and the use of drop-in tutoring services provided to students at no charge decreased from 25% to 17%. The data suggest that students thought highly of peer interactions by using those resources more than tutoring centers. To date, no research has been completed looking at courses at the department level or a different discipline. To this end, we adapted the SRVS administered in material science to investigate resource use in thirteen biomedical engineering (BME) courses. Here, we assess the following research question: "From a variety of resources, which do biomedical engineering students feel addresses difficult concept areas, prepares them for examinations, and helps in computer-aided design (CAD) and programming the most and with what frequency?" The resources considered include teaching assistants, classroom notes, prior exams, homework problems, Muddiest Points, office hours, tutoring centers, group study, and the course textbook. Results varied across the four topical areas: exam study, difficult concept areas, CAD software, and math-based programming. When preparing for exams and struggling with a learning concept, the most used and useful resources were: 1) homework problems, 2) class notes and 3) group studying. When working on math-based programming (Matlab and Mathcad) as well as computer-aided design, the most used and useful resources were: 1) group studying, 2) engineering tutoring center, and 3) undergraduate teaching assistants. Concerning learning concepts and exams in the BME department, homework problems and class notes were considered some of the highest-ranking resources for both frequency and usefulness. When comparing to the pilot study in MSE, both BME and MSE students tend to highly favor peer mentors and old exams as a means of studying for exams at the end of the semester1. Because the MSE course only considered exams, we cannot make any comparisons to BME data concerning programming and CAD. This analysis has highlighted potential resources that are universally beneficial, such as the use of peer work, i.e. group studying, engineering tutoring center, and teaching assistants; however, we see differences by both discipline and topical area thereby highlighting the need to determine important resources on a class-by-class basis as well.
ContributorsMalkoc, Aldin (Author) / Ankeny, Casey (Thesis director) / Krause, Stephen (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Current studies in Multiple Myeloma suggest that patient tumors and cell lines cluster separately based on gene expression profiles. Hyperdiploid patients are also extremely underrepresented in established human myeloma cell lines (HMCLs). This suggests that the average HMCL model system does not accurately represent the average myeloma patient. To investigate

Current studies in Multiple Myeloma suggest that patient tumors and cell lines cluster separately based on gene expression profiles. Hyperdiploid patients are also extremely underrepresented in established human myeloma cell lines (HMCLs). This suggests that the average HMCL model system does not accurately represent the average myeloma patient. To investigate this question we performed a combined CNA and SNV evolutionary comparison between four myeloma tumors and their established HMCLs (JMW-1, VP-6, KAS-6/1-KAS-6/2 and KP-6). We identified copy number changes shared between the tumors and their cell lines (mean of 74 events - 59%), those unique to patients (mean of 21.25 events - 17%), and those only in the cell lines (mean of 30.75 events \u2014 24%). A relapse sample from the JMW-1 patient showed 58% similarity to the primary diagnostic tumor. These data suggest that, on the level of copy number abnormalities, HMCLs show equal levels of evolutionary divergence as that observed within patients. By exome sequencing, patient tumors were 71% similar to their representative HMCLs, with ~12.5% and ~16.5% of SNVs unique to the tumors and HMCLs respectively. The HMCLs studied appear highly representative of the patient from which they were derived, with most differences associated with an enrichment of sub-populations present in the primary tumor. Additionally, our analysis of the KP-6 aCGH data showed that the patient's hyperdiploid karyotype was maintained in its respective HMCL. This discovery confirms the establishment and validation of a novel and potentially clinically relevant hyperdiploid HMCL that could provide a major advance in our ability to understand the pathogenesis and progression of this prominent patient population.
ContributorsBenard, Brooks Avery (Author) / Keats, Jonathan (Thesis director) / Anderson, Karen (Committee member) / Jelinek, Diane (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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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

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
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Description
Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define

Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define cancer genomes in patient samples. By isolating tumor cells from normal cells, and enriching distinct clonal populations, clinically relevant genomic aberrations that drive disease can be identified in patients in vivo. An in-depth analysis of clonal architecture and tumor heterogeneity was performed in a stage II chemoradiation-naïve breast cancer from a sixty-five year old patient. DAPI-based DNA content measurements and DNA content-based flow sorting was used to to isolate nuclei from distinct clonal populations of diploid and aneuploid tumor cells in surgical tumor samples. We combined DNA content-based flow cytometry and ploidy analysis with high-definition array comparative genomic hybridization (aCGH) and next-generation sequencing technologies to interrogate the genomes of multiple biopsies from the breast cancer. The detailed profiles of ploidy, copy number aberrations and mutations were used to recreate and map the lineages present within the tumor. The clonal analysis revealed driver events for tumor progression (a heterozygous germline BRCA2 mutation converted to homozygosity within the tumor by a copy number event and the constitutive activation of Notch and Akt signaling pathways. The highlighted approach has broad implications in the study of tumor heterogeneity by providing a unique ultra-high resolution of polyclonal tumors that can advance effective therapies and clinical management of patients with this disease.
ContributorsLaughlin, Brady Scott (Author) / Ankeny, Casey (Thesis director) / Barrett, Michael (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School for the Science of Health Care Delivery (Contributor)
Created2015-05
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Description
The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be

The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be highly beneficial. In this research, the biomarker neuron-specific enolase (Enolase-2, eno2), a marker of small-cell lung cancer, was detected at varying concentrations using electrochemical impedance spectroscopy in order to develop a mathematical model of predicting protein expression based on a measured impedance value at a determined optimum frequency. The extent of protein expression would indicate the possibility of the patient having small-cell lung cancer. The optimum frequency was found to be 459 Hz, and the mathematical model to determine eno2 concentration based on impedance was found to be y = 40.246x + 719.5 with an R2 value of 0.82237. These results suggest that this approach could provide an option for the development of small-cell lung cancer screening utilizing electrochemical technology.
ContributorsEvans, William Ian (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
The action/adventure game Grad School: HGH is the final, extended version of a BME Prototyping class project in which the goal was to produce a zombie-themed game that teaches biomedical engineering concepts. The gameplay provides fast paced, exciting, and mildly addicting rooms that the player must battle and survive through,

The action/adventure game Grad School: HGH is the final, extended version of a BME Prototyping class project in which the goal was to produce a zombie-themed game that teaches biomedical engineering concepts. The gameplay provides fast paced, exciting, and mildly addicting rooms that the player must battle and survive through, followed by an engineering puzzle that must be solved in order to advance to the next room. The objective of this project was to introduce the core concepts of BME to prospective students, rather than attempt to teach an entire BME curriculum. Based on user testing at various phases in the project, we concluded that the gameplay was engaging enough to keep most users' interest through the educational puzzles, and the potential for expanding this project to reach an even greater audience is vast.
ContributorsNitescu, George (Co-author) / Medawar, Alexandre (Co-author) / Spano, Mark (Thesis director) / LaBelle, Jeffrey (Committee member) / Guiang, Kristoffer (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05