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- Creators: Harrington Bioengineering Program
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
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 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
Description
Motor behavior is prone to variable conditions and deviates further in disorders affecting the nervous system. A combination of environmental and neural factors impacts the amount of uncertainty. Although the influence of these factors on estimating endpoint positions have been examined, the role of limb configuration on endpoint variability has been mostly ignored. Characterizing the influence of arm configuration (i.e. intrinsic factors) would allow greater comprehension of sensorimotor integration and assist in interpreting exaggerated movement variability in patients. In this study, subjects were placed in a 3-D virtual reality environment and were asked to move from a starting position to one of three targets in the frontal plane with and without visual feedback of the moving limb. The alternating of visual feedback during trials increased uncertainty between the planning and execution phases. The starting limb configurations, adducted and abducted, were varied in separate blocks. Arm configurations were setup by rotating along the shoulder-hand axis to maintain endpoint position. The investigation hypothesized: 1) patterns of endpoint variability of movements would be dependent upon the starting arm configuration and 2) any differences observed would be more apparent in conditions that withheld visual feedback. The results indicated that there were differences in endpoint variability between arm configurations in both visual conditions, but differences in variability increased when visual feedback was withheld. Overall this suggests that in the presence of visual feedback, planning of movements in 3D space mostly uses coordinates that are arm configuration independent. On the other hand, without visual feedback, planning of movements in 3D space relies substantially on intrinsic coordinates.
ContributorsRahman, Qasim (Author) / Buneo, Christopher (Thesis director) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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 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
Cerebral aneurysms, also known as intracranial aneurysms, are sac-like lesions in the arteries of the brain that can rupture to cause subarachnoid hemorrhaging, damaging and killing brain cells. Metal coil embolization has been traditionally used to occlude and treat cerebral aneurysms to limited success, but polymer embolization has been suggested, because it can provide a greater fraction of occlusion. One such polymer with low cytotoxicity is poly(propylene glycol)diacrylate (PPODA) crosslinked via Michael-type addition with pentaerythritol tetrakis(3-mercaptopropionate) (QT). This study was performed to examine the behavior of PPODA-QT gel in vitro under pulsatile flow emulating physiological conditions. An idealized cerebral aneurysm flow model was designed based on geometries associated with an increase in rupture risk. Pressure was monitored at the apex of the aneurysm dome for varied flow rates and polymer filling fractions of 32.4, 78.2, and 100%. The results indicate that the amount of PPODA-QT deployed into the aneurysm decreases the peak-to-peak oscillation in pressure at the aneurysm wall by an inverse proportion. The 32.4 and 78.2% treatments did not significantly decrease the mean pressure applied to the aneurysm dome, but the 100% treatment greatly reduced it by diverting flow. This study indicates that the maximum filling fraction after swelling of PPODA-QT polymer should be deployed into the aneurysmal sac for treatment.
ContributorsWorkman, Christopher David (Author) / Vernon, Brent (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
This thesis explores the task of creating industry-based marketing materials to assist academic programs in their recruitment of high school and community college students. With consistent reductions to public university budgets there is an increasing pressure on academic programs to raise their student enrollment figures, as student count is often cited as one of the most important statistics when making budget decisions. Many academic programs are ill-equipped to perform this task, however, as their personnel are not trained as recruiters, but rather as professors and industry professionals; furthermore, the university-level recruitment staff faces the impossible task of advertising every department's recruitment message. The Del E. Webb School of Construction has embarked upon a journey to create industry-based marketing materials to aid them in their recruitment efforts. Construction management (CM) has traditionally been viewed as a technology major relegated to vocational students and those not fit for baccalaureate programs. In recent years that perception has changed, however, as the industry has become increasingly complex and CM programs actively work to recruit students. In an attempt to increase that recruitment, the Del E. Webb School has created marketing materials that are signature to the program featuring the world's most widely-used building material, concrete, to create a keepsake for prospective students. This keepsake comes in the form of concrete replicas of the new ASU Pitchfork logo. These pitchforks are small and designed to be mass produced so that they can be handed out at recruitment events either on campus or in local schools. The Del E. Webb School had previously experimented with flexible rubber molds and flowable mixtures, such that the models could be easily cast and rapidly demolded and reset for casting. There were issues, however, as those pitchforks did not meet desired level of quality and were difficult to reproduce. This thesis thus describes an experimental program examining different casting and demolding regimens in an attempt to find the optimal way to create the pitchforks on a consistent basis. Following this, an operations manual for how to create the pitchforks was created in order to ensure that successive cohorts of construction students can reproduce the pitchforks in preparation for the School's annual recruitment events.
ContributorsErnzen, John Alexander (Author) / Wiezel, Avi (Thesis director) / Rogers, James (Committee member) / Barrett, The Honors College (Contributor) / Division of Educational Leadership and Innovation (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Motor behavior is prone to variable conditions and deviates further in disorders affecting the nervous system. A combination of environmental and neural factors impacts the amount of uncertainty. Although the influence of these factors on estimating endpoint positions have been examined, the role of limb configuration on endpoint variability has been mostly ignored. Characterizing the influence of arm configuration (i.e. intrinsic factors) would allow greater comprehension of sensorimotor integration and assist in interpreting exaggerated movement variability in patients. In this study, subjects were placed in a 3-D virtual reality environment and were asked to move from a starting position to one of three targets in the frontal plane with and without visual feedback of the moving limb. The alternating of visual feedback during trials increased uncertainty between the planning and execution phases. The starting limb configurations, adducted and abducted, were varied in separate blocks. Arm configurations were setup by rotating along the shoulder-hand axis to maintain endpoint position. The investigation hypothesized: 1) patterns of endpoint variability of movements would be dependent upon the starting arm configuration and 2) any differences observed would be more apparent in conditions that withheld visual feedback. The results indicated that there were differences in endpoint variability between arm configurations in both visual conditions, but differences in variability increased when visual feedback was withheld. Overall this suggests that in the presence of visual feedback, planning of movements in 3D space mostly uses coordinates that are arm configuration independent. On the other hand, without visual feedback, planning of movements in 3D space relies substantially on intrinsic coordinates.
ContributorsRahman, Qasim (Author) / Buneo, Christopher (Thesis director) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance, and cell culture growth assays were used to characterize the physical, magnetic, and cytotoxic properties of candidate nanoprobes. The nanoprobes displayed thermosensitve MR properties with decreasing relaxivity with temperature. Future work will be focused on generating and characterizing photo-active analogues of the nanoprobes that could be used for both treatment of tissues and assessment of therapy.
ContributorsHussain, Khateeb Hyder (Author) / Kodibagkar, Vikram (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05
Description
Improving medical aerosols is the multifaceted objective that is the overarching theme of this work. This thesis is the culmination of many hours of academic research. It details the current mechanical and physiological obstacles of state of the art drug inhalation technology, as well as provides a detailed guide of the experimental set up, procedure, analysis and background for the charge neutralization experiments performed by the author. The findings of this research are that inhalation devices need to become personalized; meaning adjustable flow rates, particle sizes, and charge levels. To improve the efficiency of lung deposition they could use MRI to take advantage of 3D modeling software to make transport models of an individual patient's lungs. This model would allow an engineer to calculate the air velocity in each passage of the respiratory system and would account for any pulmonary obstructions that would completely alter the deposition pattern from the average healthy patient. With the velocity profile of the lung a doctor could formulate an aerosol with the perfect attributed for the most targeted delivery. For the experiments performed in this work the following results were obtained. The ionization of air by polonium 210 alpha particles is dependent on the distance from the alpha emitting source and the strength of the electric field. Furthermore discharge of aerosol droplets is possible through volume conduction however the mass of the polonium 210 isotope must be proportional to the ionization current demand.
ContributorsKotin, Matthew Aaron (Author) / Towe, Bruce (Thesis director) / Caplan, Michael (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Brain-computer interface technology establishes communication between the brain and a computer, allowing users to control devices, machines, or virtual objects using their thoughts. This study investigates optimal conditions to facilitate learning to operate this interface. It compares two biofeedback methods, which dictate the relationship between brain activity and the movement of a virtual ball in a target-hitting task. Preliminary results indicate that a method in which the position of the virtual object directly relates to the amplitude of brain signals is most conducive to success. In addition, this research explores learning in the context of neural signals during training with a BCI task. Specifically, it investigates whether subjects can adapt to parameters of the interface without guidance. This experiment prompts subjects to modulate brain signals spectrally, spatially, and temporally, as well differentially to discriminate between two different targets. However, subjects are not given knowledge regarding these desired changes, nor are they given instruction on how to move the virtual ball. Preliminary analysis of signal trends suggests that some successful participants are able to adapt brain wave activity in certain pre-specified locations and frequency bands over time in order to achieve control. Future studies will further explore these phenomena, and future BCI projects will be advised by these methods, which will give insight into the creation of more intuitive and reliable BCI technology.
ContributorsLancaster, Jenessa Mae (Co-author) / Appavu, Brian (Co-author) / Wahnoun, Remy (Co-author, Committee member) / Helms Tillery, Stephen (Thesis director) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor)
Created2014-05
Description
Sickle Cell Disease (SCD) is a prevalent genetic disease in Africa, and specifically in Kenya. The lack of available relevant disease education and screening mean that most don't understand the importance of getting testing and many children die before they can get prophylactic care. This project was designed to address the lack of knowledge with supplemental educational materials to be partnered with an engineering capstone project that provides a low cost diagnostic test.
ContributorsShawver, Jamie Christine (Author) / Caplan, Michael (Thesis director) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05