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- All Subjects: Clarinet and piano music
Description
Despite the wealth of folk music traditions in Portugal and the importance of the clarinet in the music of bandas filarmonicas, it is uncommon to find works featuring the clarinet using Portuguese folk music elements. In the interest of expanding this type of repertoire, three new works were commissioned from three different composers. The resulting works are Seres Imaginarios 3 by Luis Cardoso; Delirio Barroco by Tiago Derrica; and Memória by Pedro Faria Gomes. In an effort to submit these new works for inclusion into mainstream performance literature, the author has recorded these works on compact disc. This document includes interview transcripts with each composer, providing first-person discussion of each composition, as well as detailed biographical information on each composer. To provide context, the author has included a brief discussion on Portuguese folk music, and in particular, the role that the clarinet plays in Portuguese folk music culture.
ContributorsFerreira, Wesley (Contributor) / Spring, Robert S (Thesis advisor) / Bailey, Wayne (Committee member) / Gardner, Joshua (Committee member) / Hill, Gary (Committee member) / Schuring, Martin (Committee member) / Solis, Theodore (Committee member) / Arizona State University (Publisher)
Created2013
Description
Glioblastoma (GBM) is the most common primary brain tumor with an incidence of approximately 11,000 Americans. Despite decades of research, average survival for GBM patients is a modest 15 months. Increasing the extent of GBM resection increases patient survival. However, extending neurosurgical margins also threatens the removal of eloquent brain. For this reason, the infiltrative nature of GBM is an obstacle to its complete resection. We hypothesize that targeting genes and proteins that regulate GBM motility, and developing techniques that safely enhance extent of surgical resection, will improve GBM patient survival by decreasing infiltration into eloquent brain regions and enhancing tumor cytoreduction during surgery. Chapter 2 of this dissertation describes a gene and protein we identified; aquaporin-1 (aqp1) that enhances infiltration of GBM. In chapter 3, we describe a method for enhancing the diagnostic yield of GBM patient biopsies which will assist in identifying future molecular targets for GBM therapies. In chapter 4 we develop an intraoperative optical imaging technique that will assist identifying GBM and its infiltrative margins during surgical resection. The topic of this dissertation aims to target glioblastoma infiltration from molecular and cellular biology and neurosurgical disciplines. In the introduction we; 1. Provide a background of GBM and current therapies. 2. Discuss a protein we found that decreases GBM survival. 3. Describe an imaging modality we utilized for improving the quality of accrued patient GBM samples. 4. We provide an overview of intraoperative contrast agents available for neurosurgical resection of GBM, and discuss a new agent we studied for intraoperative visualization of GBM.
ContributorsGeorges, Joseph F (Author) / Feuerstein, Burt G (Thesis advisor) / Smith, Brian H. (Thesis advisor) / Van Keuren-Jensen, Kendall (Committee member) / Deviche, Pierre (Committee member) / Bennett, Kevin (Committee member) / Arizona State University (Publisher)
Created2014
Description
Cells live in complex environments and must be able to adapt to environmental changes in order to survive. The ability of a cell to survive and thrive in a changing environment depends largely on its ability to receive and respond to extracellular signals. Initiating with receptors, signal transduction cascades begin translating extracellular signals into intracellular messages. Such signaling cascades are responsible for the regulation of cellular metabolism, cell growth, cell movement, transcription, translation, proliferation and differentiation. This dissertation seeks to dissect and examine critical signaling pathways involved in the regulation of proliferation in neural stem cells (Chapter 2) and the regulation of Glioblastoma Multiforme pathogenesis (GBM; Chapter 3). In Chapter 2 of this dissertation, we hypothesize that the mTOR signaling pathway plays a significant role in the determination of neural stem cell proliferation given its control of cell growth, metabolism and survival. We describe the effect of inhibition of mTOR signaling on neural stem cell proliferation using animal models of aging. Our results show that the molecular method of targeted inhibition may result in differential effects on neural stem cell proliferation as the use of rapamycin significantly reduced proliferation while the use of metformin did not. Abnormal signaling cascades resulting in unrestricted proliferation may lead to the development of brain cancer, such as GBM. In Chapter 3 of this dissertation, we hypothesize that the inhibition of the protein kinase, aPKCλ results in halted GBM progression (invasion and proliferation) due to its central location in multiple signaling cascades. Using in-vitro and in-vivo models, we show that aPKCλ functions as a critical node in GBM signaling as both cell-autonomous and non-cell-autonomous signaling converge on aPKCλ resulting in pathogenic downstream effects. This dissertation aims to uncover the molecular mechanisms involved in cell signaling pathways which are responsible for critical cellular effects such as proliferation, invasion and transcriptional regulation.
ContributorsKusne, Yael (Author) / Sanai, Nader (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Tran, Nhan (Committee member) / Hammer, Ronald (Committee member) / Narayanan, Vinodh (Committee member) / Shapiro, Joan (Committee member) / Arizona State University (Publisher)
Created2014
ContributorsBurton, Charlotte (Performer) / ASU Library. Music Library (Publisher)
Created2018-04-08
ContributorsDruesedow, Elizabeth (Performer) / ASU Library. Music Library (Publisher)
Created2018-04-07
Description
Achieving effective drug concentrations within the central nervous system (CNS) remains one of the greatest challenges for the treatment of brain tumors. The presence of the blood-brain barrier and blood-spinal cord barrier severely restricts the blood-to-CNS entry of nearly all systemically administered therapeutics, often leading to the development of peripheral toxicities before a treatment benefit is observed. To circumvent systemic barriers, intrathecal (IT) injection of therapeutics directly into the cerebrospinal fluid (CSF) surrounding the brain and spinal cord has been used as an alternative administration route; however, its widespread translation to the clinic has been hindered by poor drug pharmacokinetics (PK), including rapid clearance, inadequate distribution, as well as toxicity. One strategy to overcome the limitations of free drug PK and improve drug efficacy is to encapsulate drug within nanoparticles (NP), which solubilize hydrophobic molecules for sustained release in physiological environments. In this thesis, we will develop NP delivery strategies for brain tumor therapy in two model systems: glioblastoma (GBM), the most common and deadly malignant primary brain tumor, and medulloblastoma, the most common pediatric brain tumor. In the first research chapter, we developed 120 nm poly(lactic acid-co-glycolic acid) NPs encapsulating the chemotherapy, camptothecin, for intravenous delivery to GBM. NP encapsulation of camptothecin was shown to reduce the drug’s toxicity and enable effective delivery to orthotopic GBM. To build off the success of intravenous NP, the second research chapter explored the utility of 100 nm PEGylated NPs for use with IT administration. Using in vivo imaging and ex vivo tissue slices, we found the NPs were rapidly transported by the convective forces of the CSF along the entire neuraxis and were retained for over 3 weeks. Based on their wide spread delivery and prolonged circulation, we examine the ability of the NPs to localize with tumor lesions in a leptomeningeal metastasis (LM) model of medulloblastoma. NPs administered to LM bearing mice were shown to penetrate into LM mets seeded within the meninges around the brain. These data show the potential to translate our success with intravenous NPs for GBM to improve IT chemotherapy delivery to LM.
ContributorsHouseholder, Kyle Thomas (Author) / Sirianni, Rachael W. (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Caplan, Michael (Committee member) / Wechsler-Reya, Robert (Committee member) / Arizona State University (Publisher)
Created2018
Description
Imaging analysis of local drug delivery is important because in both studies involving chemotherapy targeted toward glioblastoma and antimicrobial addressing infection, the drug concentration and distribution are unknown. There are a variety of studies focused on the local delivery of drug to a targeted location, but we are presenting a way of quantifying the concentration of the drug and the distribution of the drug during a period of time. This study aims to do that by utilizing Materialise Mimics to analyze the MRI images of local drug delivery in glioblastoma in canines and antimicrobial gel in rabbit femurs. The focus of the technique is to register the anatomy in T1-weighted spin echo images to the drug delivery in T2 flow attenuated inversion recovery (FLAIR) images in order to see where the drug went and did not go relative to the anatomical part. Both studies focus on addressing effective volumes of drug to a designated anatomical area, in which the delivery can be difficult as it involves bypassing the blood brain barrier in the first study and achieving effective volumes while preventing toxicity to the kidneys in the second study. The goal of this project lies in determining the drug volumes and location for the specified duration and anatomical part.
ContributorsJehng, Hope (Author) / Caplan, Michael (Thesis director) / Sirianni, Rachael (Committee member) / Chemical Engineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor with a median prognosis of 14 months. Human hairless protein (HR) is a 130 kDa nuclear transcription factor that plays a critical role in skin and hair function but was found to be highly expressed in neural tissue as well. The expression of HR in GBM tumor cells is significantly decreased compared to the normal brain tissue and low levels of HR expression is associated with shortened patient survival. We have recently reported that HR is a DNA binding phosphoprotein, which binds to p53 protein and p53 responsive element (p53RE) in vitro and in intact cells. We hypothesized that HR can regulate p53 downstream target genes, and consequently affects cellular function and activity. To test the hypothesis, we overexpressed HR in normal human embryonic kidney HEK293 and GBM U87MG cell lines and characterized these cells by analyzing p53 target gene expression, viability, cell-cycle arrest, and apoptosis. The results revealed that the overexpressed HR not only regulates p53-mediated target gene expression, but also significantly inhibit cell viability, induced early apoptosis, and G2/M cell cycle arrest in U87MG cells, compared to mock groups. Translating the knowledge gained from this research on the connections between HR and GBM could aid in identifying novel therapies to circumvent GBM progression or improve clinical outcome.
ContributorsBrook, Lemlem Addis (Author) / Blattman, Joseph (Thesis director) / Hsieh, Jui-Cheng (Committee member) / Goldstein, Elliott (Committee member) / Harrington Bioengineering Program (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and is linked to poor survival in affected patients due to its invasive and aggressive nature. The potential role of sexual dimorphism in GBM outcomes has long been overlooked. Notably, males and females differ in tumor behavior across many cancers1, which may be attributable to differences in genetic makeup and physiology, and in GBM there is a difference in incidence rate between males and females. The aim of the study was to investigate sex differences in GBM patients and compare median survival outcomes (OS) and progression-free survival outcomes (PFS) between sexes based on tumor location, laterality, age, tumor volume, and extent of resection. Patients who received standard-of-care (Stupp protocol) consisting of surgical intervention, concomitant chemoradiation, and 6 cycles of adjuvant temozolomide (TMZ) were included in this study to investigate sex differences in tumor characteristics (n = 216; males: n = 129, females: n = 87). Pre-surgical MRIs, specifically T1Gd sequences, were analyzed to determine tumor laterality and location. The patient cohort was divided into two groups indicating the extent of resection (EOR) they received: Gross Total Resection (GTR) and Subtotal Resection (STR). Additionally, the patient cohort was split into three age groups (Group I: 18-29, Group II: 30-49, and Group III: >50). Analyses were done using independent t-test and Cox proportional hazard modeling to determine which variables affect patient survival. The log-rank test was utilized to compare differences in survival rate in Kaplan-Meier analysis.
Overall, our results suggest that female patients receiving standard-of-care may have a better prognosis than male patients. There was a significant difference in OS and PFS in females showing an increase in survival. Additionally, survival was significantly different between sexes following resection, with female patients receiving STR or GTR having longer OS and PFS than males. The difference in median OS between sexes is more pronounced among younger patients. Among five different brain locations, female patients who possess a frontal lobe tumor may live longer than male patients. The apparent difference in OS for patients living >1000 days in the Kaplan-Meier plot warrants further investigation in a larger cohort. Following tumor resection, female patients with a frontal lobe tumor may survive longer in comparison to male patients. Comparing brain hemispheres, patients who possessed a tumor on the left may survive longer. Investigating tumor location and tumor laterality, our results suggests that female patients with a left frontal lobe tumor show a significant survival advantage in comparison to females who possess a right frontal lobe tumor.
ContributorsLorence, Julia (Author) / Swanson, Kristin (Thesis director) / Massey, Susan Christine (Committee member) / Rubin, Joshua (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / School of Life Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Tumor associated microglia-and-macrophages (TAMS) may constitute up to 30% of the composition of glioblastoma. Through mechanisms not well understood, TAMS are thought to aid the progression and invasiveness of glioblastoma. In an effort to investigate properties of TAMS in the context of glioblastoma, I utilized data from a PDGF-driven rat model of glioma that highly resembles human glioblastoma. Data was collected from time-lapse microscopy of slice cultures that differentially labels glioma cells and also microglia cells within and outside the tumor microenvironment. Here I show that microglia localize in the tumor and move with greater speed and migration than microglia outside the tumor environment. Following previous studies that show microglia can be characterized by certain movement distributions based on environmental influences, in this study, the majority of microglia movement was characterized by a power law distribution with a characteristic power law exponent lower than outside the tumor region. This indicates that microglia travel at greater distances within the tumor region than outside of it.
ContributorsJuliano, Joseph Dominic (Author) / Kostelich, Eric (Thesis director) / Nagy, John (Committee member) / Swanson, Kristin (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-12