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- Creators: Harrington Bioengineering Program
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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 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
DescriptionMy main goal for my thesis is in conjunction with the research I started in the summer of 2010 regarding the creation of a TBI continuous-time sensor. Such goals include: characterizing the proteins in sensing targets while immobilized, while free in solution, and while in free solution in the blood.
ContributorsHaselwood, Brittney (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2011-12
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
Batman is one of the most iconic characters in the history of popular culture. Ever since his creation in 1939, the character and his stories have gone through several changes. In my thesis, I explore and analyze the character within the nearly 20-year period in which he went through the most significant changes (1968-1986). Overall, these changes can be summarized as a shift from a lighthearted superhero consistently placed in campy situations to a dark and brooding vigilante who brutally dispatches his enemies. While analyzing the different versions of this character in this period of time, I reference the conclusions of two scholars: Travis Langley and Chuck Tate. Langley wrote a general psychological analysis of Batman by considering the essential characteristics of the character found in all forms of media. Tate concluded that Batman only uses hostile aggression for the sake of deriving pleasure form the pain he causes to criminals. After analyzing the comics as my primary sources, I have concluded that the general findings of Tate and Langley actually ignore the subtle details of changes in the humanity and self-awareness of the character through time. The lighthearted version of Batman in the late 60's is actually a self-obsessed narcissist, but as time passes, the darker mood of the character can be attributed to an increased acknowledgment of the destructive nature of his unique lifestyle. As the character grows more accepting of himself and his own reasons for continuing this lifestyle, his motivations become less self-centered. Overall, the central change of the character throughout time can be traced back to the status of his inner conflict between normal, human desires and the pure desire for constant vengeance.
ContributorsRivera-Passapera, Hiram Alfonso (Author) / Martin, Thomas (Thesis director) / Miller, April (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Humans rely on a complex interworking of visual, tactile and proprioceptive feedback to accomplish even the most simple of daily tasks. These senses work together to provide information about the size, weight, shape, density, and texture of objects being interacted with. While vision is highly relied upon for many tasks, especially those involving accurate reaches, people can typically accomplish common daily skills without constant visual feedback, instead relying on tactile and proprioceptive cues. Amputees using prosthetic hands, however, do not currently have access to such cues, making these tasks impossible. This experiment was designed to test whether vibratory haptic cues could be used in replacement of tactile feedback to signal contact for a size discrimination task. Two experiments were run in which subjects were asked to identify changes in block size between consecutive trials using wither physical or virtual blocks to test the accuracy of size discrimination using tactile and haptic feedback, respectively. Blocks randomly increased or decreased in size in increments of 2 to 12 mm between trials for both experiments. This experiment showed that subjects were significantly better at determining size changes using tactile feedback than vibratory haptic cues. This suggests that, while haptic feedback can technically be used to grasp and discriminate between objects of different sizes, it does not lend the same level of input as tactile cues.
ContributorsOlson, Markey Cierra (Author) / Helms-Tilley, Stephen (Thesis director) / Buneo, Christopher (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
In order to address infant respiratory distress syndrome, this study attempts to develop and characterize a textile strain gauge fabricated with stainless steel, wool, elastic, and tencel. Faire Isle knitted patterns are investigated in order to create channels of conductivity for a linear sensor. The effect linear yarn density on linearity and sensitivity and hysteresis of the sensors is also investigated for sensor optimization. It was found that there was a significant difference between the patterned and non-patterned samples. The patterned sensors were found to have a lower range of resistance than the non-patterned sensors and a smaller average standard of deviation between measurements. The 7 tension, lower linear yarn density, elastic patterned sample was the only sample to not exhibit hysteresis after three trials as well as have a linear range from 11.5cm to 13cm where the sensor behaves in accordance with a linear transfer function.
ContributorsBrown, Shannon (Co-author) / Irimata, Lisa (Co-author) / LaBelle, Jeffrey (Thesis director) / Hanson, Erika (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Inflammation is part of the body’s response to invading pathogens, injury, and a wide range of diseases. Although inflammation is paramount to maintain a healthy immune system, unregulated inflammation can aggravate chronic conditions or cause severe, acute pathologies. Pyroptosis, a caspase-1-dependent, pro-inflammatory cell death that results in the release of IL-1β and IL-18, has been implicated in propagating an inflammatory response in the body. Pyroptosis has been shown to result from the activation of the NLRP3 inflammasome. Furthermore, multiple reports have demonstrated that intracellular potassium efflux and spleen tyrosine kinase (Syk) activity are both essential for facilitating the assembly of the NLRP3 inflammasome and proper processing and release of IL-1β and IL-18. The focus of this thesis was to determine the relationship between intracellular potassium efflux and Syk during key regulatory events in the activation of the NLRP3 inflammasome by identifying their effect on pro-inflammatory cytokine release, inflammasome assembly, mitochondrial reactive oxygen species (mROS) generation, and cell death. Both inhibiting potassium efflux from occurring and deactivating Syk significantly reduced the amount of pro-inflammatory cytokine released (70-100% reduction), the number of inflammasomes assembled (60-80% reduction), the amount of mROS generation, and the quantity of cell death (50-90% reduction). Moreover, it was discovered that potassium efflux was required for Syk activation, but Syk activation had no effect on potassium efflux. Their relationship proved to be unidirectional. This study provides the first demonstration of ion flux-dependent regulation of kinase activation in the NLRP3 inflammasome pathway and provides support for targeting ion regulation mechanisms and Syk kinase activity to manipulate macrophage-mediate inflammatory processes.
ContributorsRao, Mounica Yarlagadda (Author) / Meldrum, Deirdre R. (Thesis director) / Ankeny, Casey (Committee member) / Glenn, Honor (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2015-05
Description
This research investigates the whether dietary and nutritional treatments will improve some of the symptoms of autism. This treatment includes a combination of 6 nutritional and dietary treatments, which are vitamins/minerals, essential fatty acids, Epsom salts, carnitine, digestive enzymes, and healthy gluten-free, casein-free diet. 55 participants were involved in this study; 28 participants are in the Treatment Group and 27 participants in the Delayed Group. Data from the PDD-BI form, the ADOS form, the CARS form and the professional SAS form will be used in this thesis project for analyses. Factors analyzed are age, gender and severity [initial professional SAS data] and then correlating these factors with data from PDD-BI (autism composite score and each subscale), ADOS and CARS. The data analyses show that changing the dietary and nutritional needs of children/adults with autism improves the symptoms of autism (as rated by the PDD-BI) by approximately 22% in the treatment group vs. 3% in the non-treatment group, p<0.001. Overall, these results also suggest that the treatment is equally beneficial for males and females of varying age (young children to adult) and of all severity levels.
ContributorsLee, Chiao May (Author) / Adams, James B. (Thesis director) / Pollard, Elena (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Statistics are rising for adults who are overweight and/or obese, putting them at higher risk of developing serious health problems. Eating fewer portions of vegetable than the daily-recommended amounts contributes to this increase with. College students, being more susceptible to weight gain as they are transitioning from childhood to adulthood. Previous studies demonstrated that children ate more vegetables when repeatedly paired with a low-fat dip compared to when served plain. The current study examined whether this effect was also successful in college-aged subjects. A total of 148 (55 males, 91 females) college-aged students from an introductory psychology class at Arizona State University (Tempe, AZ) participated in the study. Subjects were randomly assigned to receive cauliflower or broccoli (raw) either served plain or with low-fat ranch dressing. Subjects showed a greater preference for and consumption of the vegetable plain that was previously given with dip than without dip. These findings suggest that serving vegetables with low-fat ranch dip two times can increase the liking and consumption of vegetables in college students.
ContributorsKim, Sophia L. (Author) / Phillips, Elizabeth Capaldi (Thesis director) / Bajaj, Devina (Committee member) / Cohen, Adam (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Antibiotics, bacteria, and the continuing trend of antibiotic resistance increasing in various bacteria strains is a complex and multifaceted set of relationships explored in this thesis. Examining a variety of published literature in various sectors of influence, including the social, medical, and economic divisions, this thesis examined the core factors and combined them into a set of recommendations for future progress. In this way, the subject of antibiotic resistance in bacteria begins with an evaluation of the history then continued into an analysis of the economic factors, a social understanding of the subject, a medical evaluation of current procedure, and a concluding framework and general set of recommendations for future use. Ultimately, these factors require a multifaceted approach in order to combat the numerous factors and contributions to emerging antibiotic resistance in bacteria both in the United States of America and around the world.
ContributorsMurphy, Emily Ann (Author) / Chhetri, Netra (Thesis director) / Ankeny, Casey (Committee member) / Hamburg, Robert (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Life Sciences (Contributor)
Created2015-05