Conceptualizations of Quality of Life in Geriatric Medicine: Utilizing Quality of Life as a Measure of Effectiveness of Care

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), 2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Anya Plutynsk

Flexural Behaviour of Precast Concrete Slabs Reinforced with Hollow Composite Systems

Precast concrete solid slabs have been used extensively in the building industry. Solid reinforced concrete (RC) slabs are heavy in weight and use significant amount of materials to manufacture. Hollow-core RC slabs are now being manufactured to minimise the weight and the usage of materials. However, the hollow-core creates some issues as they are prone to collapse and shear failure. There is therefore a need to stabilise the hollow-core for a more effective precast concrete slab system. A hollow composite reinforcing system has recently been developed to create hollow-core in RC slabs. This composite system has four flanges to bond more effective in concrete. It is the aim of this project to determine the effectiveness of this hollow composite reinforcing system in enhancing the flexural behaviour of concrete slabs. The flexural behaviour of three slabs with different section configuration was investigated under 4- point static bending. The first slab has a solid cross section, the second with a hollow-core created by providing 3 pieces of PVC of 60 mm internal diameter, and the third one reinforced with 3 pieces of hollow composite reinforcement systems. All slabs have an overall thickness of 175 mm thick and reinforced with 12 mm diameter steel bars at the top and bottom spaced at 150 mm on centres. The results demonstrated that the solid and hollow slab behaved similarly due to the compressive stress in the concrete is above the voids. On the other hand, the slab reinforced with hollow composite systems has twice the capacity to that of solid RC slabs. This indicates that the thickness of this slab can be further reduced to carry the same load carried by solid RC slabs but at significantly lower weight and lesser material usage. Theoretical evaluation following the AS3600 and the simplified Fibre Model Analysis can accurately predict the capacity of the slabs. Overall, this study demonstrated that the SR60 FRP reinforcement is a beneficial technology and is suitable for hollow precast concrete slabs. It could make concrete slabs much lighter and more cost effective than solid and traditional hollow slabs

The Evolution of Violin Technique from Monteverdi to Paganini

The purpose of this thesis is to show through the presentation and analysis of authoritative information, and opinions drawn from the information and analysis, the development of violin technique from its basic rudiments as an accompanying instrument to the plane of a brilliant solo instrument, a position it still maintains today. This thesis aims to deal exclusively with the technical evolution of the violin. Many books on the history of the violin have been written, but none have dealt exclusively with the technical evolution of this instrument, and it is hoped that the materials in this thesis will constitute a contribution to this field

Establishment of Histone Modifications after Chromatin Assembly

Every cell has to duplicate its entire genome during S-phase of the cell cycle. After replication, the newly synthesized DNA is rapidly assembled into chromatin. The newly assembled chromatin ‘matures’ and adopts a variety of different conformations. This differential packaging of DNA plays an important role for the maintenance of gene expression patterns and has to be reliably copied in each cell division. Posttranslational histone modifications are prime candidates for the regulation of the chromatin structure. In order to understand the maintenance of chromatin structures, it is crucial to understand the replication of histone modification patterns. To study the kinetics of histone modifications in vivo, we have pulse-labeled synchronized cells with an isotopically labeled arginine (15N4) that is 4 Da heavier than the naturally occurring 14N4 isoform. As most of the histone synthesis is coupled with replication, the cells were arrested at the G1/S boundary, released into S-phase and simultaneously incubated in the medium containing heavy arginine, thus labeling all newly synthesized proteins. This method allows a comparison of modification patterns on parental versus newly deposited histones. Experiments using various pulse/chase times show that particular modifications have considerably different kinetics until they have acquired a modification pattern indistinguishable from the parental histones

Global Regulation of Nucleotide Biosynthetic Genes by c-Myc

The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP) coupled with pair-end ditag sequencing analysis (ChIP-PET) revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated.Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2) on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA) and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis.Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis

Isolation of chromosome clusters from metaphase-arrested HeLa cells

We have developed a simplified approach for the isolation of metaphase chromosomes from HeLa cells. In this method, all the chromosomes from a cell remain together in a bundle which we call a “metaphase chromosome cluster”. Cells are arrested to 90–95% in metaphase, collected by centrifugation, extracted with non-ionic detergent in a low ionic strength buffer at neutral pH, and homogenised to strip away the cytoskeleton. The chromosome clusters which are released can then be isolated in a crude state by pelleting or they can be purified away from nearly all the interphase nuclei and cytoplasmic debris by banding in a Percoll TM density gradient. — This procedure has the advantages that it is quick and easy, metaphase chromatin is recovered in high yield, and Ca ++ is not needed to stabilise the chromosomes. Although the method does not yield individual chromosomes, it is nevertheless very useful for both structural and biochemical studies of mitotic chromatin. The chromosome clusters also make possible biochemical and structural studies of what holds the different chromosomes together. Such information could be useful in improving chromosome isolation procedures and for understanding suprachromosomal organisation of the nucleus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47359/1/412_2004_Article_BF00327351.pd

Acetylation of core histones in response to HDAC inhibitors is diminished in mitotic HeLa cells

Histone acetylation is a key modification that regulates chromatin accessibility. Here we show that treatment with butyrate or other histone deacetylase (HDAC) inhibitors does not induce histone hyperacetylation in metaphase-arrested HeLa cells. When compared to similarly treated interphase cells, acetylation levels are significantly decreased in all four core histones and at all individual sites examined. However, the extent of the decrease varies, ranging from only slight reduction at H3K23 and H4K12 to no acetylation at H3K27 and barely detectable acetylation at H4K16. Our results show that the bulk effect is not due to increased or butyrate-insensitive HDAC activity, though these factors may play a role with some individual sites. We conclude that the lack of histone acetylation during mitosis is primarily due to changes in histone acetyltransferases (HATs) or changes in chromatin. The effects of protein phosphatase inhibitors on histone acetylation in cell lysates suggest that the reduced ability of histones to become acetylated in mitotic cells depends on protein phosphorylation