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Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. These vesicles play an important role in cellular communication by virtue of their protein, RNA, and lipid content, which can be transferred among cells. Peripheral blood is a rich source

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. These vesicles play an important role in cellular communication by virtue of their protein, RNA, and lipid content, which can be transferred among cells. Peripheral blood is a rich source of circulating EVs. An analysis of EVs in peripheral blood could provide access to unparalleled amounts of biomarkers of great diagnostic, prognostic as well as therapeutic value. In the current study, a plasma EV enrichment method based on pluronic co-polymer was first established and characterized. Plasma EVs from breast cancer patients were then enriched, profiled and compared to non-cancer controls. Proteins signatures that contributed to the prediction of cancer samples from non-cancer controls were created by a random-forest based cross-validation approach. We found that a large portion of these signatures were related to breast cancer aggression. To verify such findings, KIAA0100, one of the features identified, was chosen for in vitro molecular and cellular studies in the breast cancer cell line MDA-MB-231. We found that KIAA0100 regulates cancer cell aggression in MDA-MB-231 in an anchorage-independent manner and is particularly associated with anoikis resistance through its interaction with HSPA1A. Lastly, plasma EVs contain not only individual proteins, but also numerous molecular complexes. In order to measure millions of proteins, isoforms, and complexes simultaneously, Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT) platform was applied. ADAPT employs an enriched library of single-stranded oligodeoxynucleotides to profile complex biological samples, thus achieving a deep coverage of system-wide, native biomolecules. Profiling of EVs from breast cancer patients was able to obtain a prediction AUC performance of 0.73 when compared biopsy-positive cancer patient to healthy controls and 0.64 compared to biopsy-negative controls and such performance was not associated with the physical breast condition indicated by BIRAD scores. Taken together, current research demonstrated the potential of profiling plasma EVs in searching for therapeutic targets as well as diagnostic signatures.
ContributorsZhong, Zhenyu (Author) / Spetzler, David (Thesis advisor) / Yan, Hao (Thesis advisor) / Lake, Douglas (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2018
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Description
A high voltage plasma arc can be created and sustained in air by subjecting the gases to an electric field with high voltage potential, causing ionization. The internal energy of the ionized gases can be transferred to corresponding pressure waves when the matter involved switches between the gaseous and plasma

A high voltage plasma arc can be created and sustained in air by subjecting the gases to an electric field with high voltage potential, causing ionization. The internal energy of the ionized gases can be transferred to corresponding pressure waves when the matter involved switches between the gaseous and plasma states. By pulse-width modulating a transformer driving signal, the transfer of internal electrical energy to resonating pressure waves may be controlled. Audio wave input to the driver signal can then be modulated into the carrier wave and be used to determine the width of each pulse in the plasma, thus reconstructing the audio signal as pressure, or sound waves, as the plasma arc switches on and off. The result will be the audio waveform resonating out of the plasma arc as audible sound, and thus creating a plasma loudspeaker. Theory of operation was tested through construction of a plasma arc speaker, and resultant audio playback was analyzed. This analysis confirmed accurate reproduction of audio signal in audible sound.
ContributorsBoehringer, Brian Thomas (Author) / Roedel, Ronald (Thesis director) / Huffman, James (Committee member) / Barrett, The Honors College (Contributor) / Electrical Engineering Program (Contributor)
Created2014-05