Matching Items (19)

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Clonal Analysis of a Human Breast Cancer

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

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.

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  • 2015-05

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POTASSIUM EFFLUX DRIVES SYK-MEDIATED REGULATION OF INFLAMMASOME ACTIVITY IN MOUSE MACROPHAGES

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

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.

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  • 2015-05

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The Ethics of Brain-Computer Interfaces

Description

The development of computational systems known as brain-computer interfaces (BCIs) offers the possibility of allowing individuals disabled by neurological disorders such as Amyotrophic Lateral Sclerosis (ALS) and ischemic stroke the

The development of computational systems known as brain-computer interfaces (BCIs) offers the possibility of allowing individuals disabled by neurological disorders such as Amyotrophic Lateral Sclerosis (ALS) and ischemic stroke the ability to perform relatively complex tasks such as communicating with others and walking. BCIs are closed-loop systems that record physiological signals from the brain and translate those signals into commands that control an external device such as a wheelchair or a robotic exoskeleton. Despite the potential for BCIs to vastly improve the lives of almost one billion people, one question arises: Just because we can use brain-computer interfaces, should we? The human brain is an embodiment of the mind, which is largely seen to determine a person's identity, so a number of ethical and philosophical concerns emerge over current and future uses of BCIs. These concerns include privacy, informed consent, autonomy, identity, enhancement, and justice. In this thesis, I focus on three of these issues: privacy, informed consent, and autonomy. The ultimate purpose of brain-computer interfaces is to provide patients with a greater degree of autonomy; thus, many of the ethical issues associated with BCIs are intertwined with autonomy. Currently, brain-computer interfaces exist mainly in the domain of medicine and medical research, but recently companies have started commercializing BCIs and providing them at affordable prices. These consumer-grade BCIs are primarily for non-medical purposes, and so they are beyond the scope of medicine. As BCIs become more widespread in the near future, it is crucial for interdisciplinary teams of ethicists, philosophers, engineers, and physicians to collaborate to address these ethical concerns now before BCIs become more commonplace.

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  • 2016-05

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Assessment of Concept Mapping in a Biomaterials Class

Description

Concept maps are teaching tools used to encourage students to utilize active learning strategies and to take responsibility for their own learning. The purpose of this two-semester study is to

Concept maps are teaching tools used to encourage students to utilize active learning strategies and to take responsibility for their own learning. The purpose of this two-semester study is to evaluate the use of concept maps in a junior-level Biomaterials classroom. The maps are assessed based on students' attitude, achievement, and persistence. No significant correlation was determined between concept map score and achievement (correlation coefficient = 0.1739 in the first semester, 0.2208 in the first set of the second semester, and 0.0829 in the second set of the second semester), though further studies should be completed to support the effects of concept mapping. Statistically significant increases in student attitude regarding concept mapping cost, interest, and utility between the two semesters were found (p = 0.013, p = 0.105, p = 0.002, p = 0.083 overall). Persistence was moderately high throughout the entire study (98% in the first semester and 100% in the second semester).

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  • 2016-05

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Assessment of Student Responses to Various Resources Offered in Biomedical Engineering and Materials Science Courses

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

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.

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  • 2016-05

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Stereotypical Analysis of Wind Instruments in College-Level Concert Band

Description

The purpose of this study is to analyze the stereotypes surrounding four wind instruments (flutes, oboes, clarinets, and saxophones), and the ways in which those stereotypes propagate through various levels

The purpose of this study is to analyze the stereotypes surrounding four wind instruments (flutes, oboes, clarinets, and saxophones), and the ways in which those stereotypes propagate through various levels of musical professionalism in Western culture. In order to determine what these stereotypes might entail, several thousand social media and blog posts were analyzed, and direct quotations detailing the perceived stereotypical personality profiles for each of the four instruments were collected. From these, the three most commonly mentioned characteristics were isolated for each of the instrument groups as follows: female gender, femininity, and giggliness for flutists, intelligence, studiousness, and demographics (specifically being an Asian male) for clarinetists, quirkiness, eccentricity, and being seen as a misfit for oboists, and overconfidence, attention-seeking behavior, and coolness for saxophonists. From these traits, a survey was drafted which asked participating college-aged musicians various multiple choice, opinion scale, and short-answer questions that gathered how much they agree or disagree with each trait describing the instrument from which it was derived. Their responses were then analyzed to determine how much correlation existed between the researched characteristics and the opinions of modern musicians. From these results, it was determined that 75% of the traits that were isolated for a particular instrument were, in fact, recognized as being true in the survey data, demonstrating that the stereotypes do exist and seem to be widely recognizable across many age groups, locations, and levels of musical skill. Further, 89% of participants admitted that the instrument they play has a certain stereotype associated with it, but only 38% of people identify with that profile. Overall, it was concluded that stereotypes, which are overwhelmingly negative and gendered by nature, are indeed propagated, but musicians do not appear to want to identify with them, and they reflect a more archaic and immature sense that does not correlate to the trends observed in modern, professional music.

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  • 2016-05

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Acanthamoeba Prevalence in a Simulated Reclaimed Water Distribution System

Description

With dwindling water resources due to drought and other pressures, water utilities are seeking to tap into alternative water sources as a means to improve water sustainability. Reclaimed water consists

With dwindling water resources due to drought and other pressures, water utilities are seeking to tap into alternative water sources as a means to improve water sustainability. Reclaimed water consists of treated wastewater and is widely used for non-potable purposes, such as irrigation, both agricultural and recreational. However, the reclaimed water distribution system can be subject to substantial regrowth of microorganisms, including opportunistic pathogens, even following rigorous disinfection. Factors that can influence regrowth include temperature, organic carbon levels, disinfectant type, and the time transported (i.e., water age) in the system. One opportunistic pathogen (OP) that is critical to understanding microbial activity in both reclaimed and drinking water distribution systems is Acanthamoeba. In order to better understand the potential for this amoeba to proliferate in reclaimed water systems and influence other OPs, a simulated reclaimed water distribution system was studied. The objective of this study was to compare the prevalence of Acanthamoeba and one of its endosymbionts, Legionella, across varying assimilable organic carbon (AOC) levels, temperatures, disinfectants, and water ages in a simulated reclaimed water distribution system. The results of the study showed that cooler temperatures, larger water age, and chlorine conditions yielded the lowest detection of Acanthamoeba gene copies per mL or cm2 for bulk water and biofilm samples, respectively.

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  • 2016-12

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Investigation of Student Achievement and Attitude about a Flipped Classroom Using Linked Lecture Videos in Biomedical Engineering

Description

Flipped classrooms invert the traditional teaching methods and deliver the lecture online outside of the classroom. An increase in technology accessibility is increasing the prevalence of this teaching technique in

Flipped classrooms invert the traditional teaching methods and deliver the lecture online outside of the classroom. An increase in technology accessibility is increasing the prevalence of this teaching technique in universities. In this study, we aim to address some of the uncertainties of a flipped classroom by implementing a new lecture format in Transport Phenomena. Transport Phenomena is a junior level biomedical engineering course originally flipped in Spring 2013. Since transitioning to a flipped classroom, students have been required to watch 75-minute lectures outside of class where the instructor covered key concepts and examples using paper and marker on a document camera. In class, students then worked in groups to solve problems with instructor and teaching assistant feedback. Students also completed self-graded homework with the opportunity to earn lost points back by discussing fundamental misconceptions. We are introducing re-formatted mini lectures that contain the same content broken down as well as example problems worked out in a tutorial technique instead of traditional solving method. The purpose of this study is to determine the effectiveness of newly created mini lectures with integrated questions and links in terms of student achievement and attitude [interest, utility, and "cost" (time, effort, and emotion)].

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  • 2016-12

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Synthesis of Dual Layered Microparticles for Tunable Delayed Release Profile

Description

The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in

The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.

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  • 2015-05

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Antibiotic Resistance in Bacteria: Public, Economic, and Medical Perspectives

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

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.

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  • 2015-05