Music therapy plays an integral role in end-of-life care, positively impacting emotional, social, physical, cognitive and spiritual health. The purpose of this integrative review was to collect and compile studies (N= 55) between 2000 and 2016 on the topic of music therapy interventions in end-of-life care, in order to provide both music therapy students and therapists access to the most recent and commonly used music therapy interventions and goals. Results of the integrative literature review indicate that the most common intervention for all age groups in end-of-life care is songwriting and composition, with the most common therapeutic goal being emotional expression and catharsis. Details of music therapy interventions, goals and song details are written in tables for readers to refer to as a guide. Further research is needed with each specific age group and setting, in order to provide refined results beyond what is revealed through this review. Additionally, evaluating therapeutic outcomes of the interventions and goals obtained through this integrative review is another step that can be taken for future research.

Proteomics is the science of understanding the dynamic protein content of an organism's cells (its proteome), which is one of the largest current challenges in biology. Computational proteomics is an active research area that involves in-silico methods for the analysis of high-throughput protein identification data. Current methods are based on a technology called tandem mass spectrometry (MS/MS) and suffer from low coverage and accuracy, reliably identifying only 20-40% of the proteome. This dissertation addresses recall, precision, speed and scalability of computational proteomics experiments. This research goes beyond the traditional paradigm of analyzing MS/MS experiments in isolation, instead learning priors of protein presence from the joint analysis of various systems biology data sources. This integrative `systems' approach to protein identification is very effective, as demonstrated by two new methods. The first, MSNet, introduces a social model for protein identification and leverages functional dependencies from genome-scale, probabilistic, gene functional networks. The second, MSPresso, learns a gene expression prior from a joint analysis of mRNA and proteomics experiments on similar samples. These two sources of prior information result in more accurate estimates of protein presence, and increase protein recall by as much as 30% in complex samples, while also increasing precision. A comprehensive suite of benchmarking datasets is introduced for evaluation in yeast. Methods to assess statistical significance in the absence of ground truth are also introduced and employed whenever applicable. This dissertation also describes a database indexing solution to improve speed and scalability of protein identification experiments. The method, MSFound, customizes a metric-space database index and its associated approximate k-nearest-neighbor search algorithm with a semi-metric distance designed to match noisy spectra. MSFound achieves an order of magnitude speedup over traditional spectra database searches while maintaining scalability. / text

Oligonucleotides enable many biotechnological applications; however they are easily degraded by nucleases. Many nucleotides modified at the 2’ position are degraded at decreased rates which improves oligonucleotide utility. Most applications of oligonucleotides rely on enzymatic synthesis. Unfortunately, native DNA polymerases do not recognize most useful modified nucleotide substrates. Directed evolution has been used to identify mutants of Taq DNA polymerase I (Taq) that recognize substrates with 2’ modifications. While mutant enzymes capable of modified nucleotide addition have been identified, to date, all of these enzymes are limited by their inability to synthesize full length modified DNA. Despite considerable efforts to evolve new activity there has been little work done to quantitatively characterize these evolved enzymes. This thesis work presents efforts to synthesize modified primers that will help comparatively and quantitatively characterize three enzymes previously evolved to recognize 2’ modified substrates. Using the methods developed in this thesis project, our lab will be able to characterize the relationship between the number of modified nucleotides in the primer terminus and the rate of modified and unmodified nucleotide addition. Future work will identify key enzymatic steps that limit extension in these enzymes with implications for the future design of Taq mutants capable of synthesizing long 2’ modified oligonucleotides.

Approximately 1 in 11 births in the United States are preterm (gestation). Within the United States, there are huge racial disparities for risk of preterm birth, an issue understudied and rarely addressed by research in the field. There is a wealth of biological knowledge surrounding pregnancy and labor, but causes for preterm birth are poorly understood. A genetic factor that has been shown to play a key role in many biological processes crucial to a healthy pregnancy and timely labor is microRNA (miRNA). MiRNA have an active role in the regulation of various tissues, especially developing tissues like those found in the placenta and uterus. Additionally, oxidative stress has been shown essential to placental development and the initiation of labor. Here, a study is proposed that aims to address the effect of oxidative stress on myometrial miRNA expression, specifically the miR-200 family and miR-199/214 cluster. This work also underscores the importance of addressing racial disparities with regards to preterm labor during research, while bringing up ethical considerations for conducting such research. The thesis will conclude with an outline of the many considerations vital for discussing the research and analysis of preterm birth disparities using a feminist, antiracist, queer self-reflexive analysis.

Thermoplastische Kunststoffe werden zur Steigerung der mechanischen Eigenschaften häufig mit Kurzfasern verstärkt, wodurch sich jedoch eine anisotrope Eigenschaftscharakteristik einstellt. Dies führt oftmals zu ungewohntem Werkstoff- und Bauteilverhalten. Die Fertigungsparameter und -randbedingungen im Spritzgießprozess besitzen einen großen Einfluss auf lokale Faserorientierungen, wovon auch die globalen Bauteileigenschaften abhängen. Für eine werkstoffgerechte Auslegung von derartigen Bauteilen sind tiefgreifende Verständnisse über die mechanischen, thermischen und rheologischen Eigenschaften sowie die Kopplung von Spritzgieß- und Bauteilsimulation unerlässlich. Diese sogenannte integrative Simulation wird am Beispiel eines Strukturbauteiles aufgezeigt.

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Fluvastatin, the HMG-CoA reductase inhibitor known for its role in the treatment of hypercholesterolemia and cardiovascular disease, has more recently been shown to play a role in the immune response. Given the critical role that mast cells play in allergy and inflammatory diseases such as asthma, which effects one third of America’s population, we assessed the effect of fluvastatin on mast cell and basophils function. We demonstrate that fluvastatin downregulated IgE-mediated cytokine production. Additionally, in vivo studies showed that fluvastatin suppressed IgE-mediated anaphylaxis. Interestingly, the effects of fluvastatin showed dependence on genetic background, as C57BL/6 mast cells were sensitive, while 129/Sv mast cells were resistant to fluvastatin. Characterizing the role of fluvastatin on mast cells may prove to be therapeutically important.

The field of epigenetics is gaining popularity and speed, due in part to its capability to answer lingering questions about the root cause of certain diseases. Epigenetics plays a crucial role in regulation of the cell and cell survival, particularly by cytosine methylation. It remains controversial if DNMT’s which facilitate methylation are present in mammalian mitochondria and what the functional significance they may have on modification of mitochondrial DNA. CRISPR-Cas9 technology enabled genome editing to remove the MTS (mitochondrial targeting sequence) from DNMT1 of HCT116 cells, purposefully minimizing effects on nuclear cytosine methylation, while exclusively impacting mitochondrial modification. Removal of the DNMT1 MTS did not completely prevent the localization of this enzyme to the mitochondria according to immunoblot analysis. As well, deletion of the MTS in DNMT1 revealed only a small decline in transcription; not until removal of DNMT3B did we see a two-fold decrease in transcription from mitochondrial protein coding genes. No significant decline in transcription occurred when a DNMT3B knockout also lost the MTS of DNMT1; this study is evidencing that DNMT3B is possibly the more significant methyltransferase in the mitochondria. Our aim from this study and future research is to clearly characterize which enzymes in the mitochondria are controlling cytosine modifications and to understand the mechanistic complexities that accompany cause and consequence of epigenetic modifications.

Correct species identification is fundamental to all areas of biology, but particularly the policy related areas of conservation and fisheries management. To enable guidelines to be developed for environmental management and conservation, such identifications need links to studies of the evolutionary history, biological factors and environmental influences driving species divergence and population dynamics for the target species. This study concerns two genera of gadiform fish, Muraenolepis and Macrourus, found in southern temperate and Antarctic waters, with a single species, Macrourus berglax, present in the North Atlantic. With similar distribution patterns to toothfish species, Dissostichus eleginoides and D. mawsoni, they are a major food source and by-catch of the toothfish fishery. Both are slow growing and long lived, with different evolutionary histories, life expectancies and strategies for reproduction. For both genera, the accuracy of morphological keys, number of described species and their distribution is under debate. This study has identified specimens to species level using both morphological and genetic techniques, redefining the range for morphological features and taxonomic keys. For Muraenolepis, this has clarified confusion over Mu. marmoratus and Mu. microps being a single species, confirmed some mis-identification from sexual dimorphism and provided genetic evidence for the recently described species Mu. evseenkoi. For Macrourus, this work has identified a new species, now named Ma. caml, and found that Ma. holotrachys and Ma. berglax are genetically identical, raising the question of bipolar distribution or recent divergence. The low level of genetic variation within both species suggests a recent evolution and expansion into Antarctic waters. Similar geographic species limits imply common processes influencing divergence, with the oceanographic fronts as potential barriers. Further investigation of niche overlap and fine scale population structure are required to fully understand the processes driving speciation and provide the underlying data required for fisheries management.

In the yeast Saccharomyces cerevisiae, the IME4 methyltransferase, interacts genetically with methyl binding protein, Pho92, to affect the expression of PHO regulon target genes. Cells mutant in IME4 or PHO92 show increases in the RNA abundance of PHO regulon target genes. The increase in the RNA abundance of the PHO regulon target genes is not additive in the cells double mutant in IME4 and PHO92. Hence, Ime4 and Pho92 interact in a single pathway in PHO regulon. Surprisingly, cells overexpressing IME4 and MUM2 shows increase in some PHO regulon target genes, indicating that IME4 affects the PHO regulon target genes through multiple mechanisms in different conditions. A promoter swap experiment revealed that one of the PHO regulon mRNAs that codes for phosphatase, PHO5, is a direct target of Ime4. Further experiments are required to examine whether the same is true for all PHO regulon mRNAs.