The seven symphonies of Arnold Bax, written between 1921 and 1939, are the climax of a fruitful career of music composition. This study investigates the determinants of form in these works, considers some of the formal problems, and makes a correlation between form and style. The two primary formal determinants are thematic organization and textural formation. Other factors, such as rhythm, dynamics, timbre, register, and harmony, act on the thematic and textural process in a secondary way. Tonality sometimes plays an important formal role and is discussed in conjunction with thematicism and texture. Harmony, though an important aspect of Bax's style, frequently has an ornamental rather than structural significance. For the sake of generalization and comparison, formal patterns of individual movements are outlined. Formal patterns are described by simple diagrams of how themes appear in a movement as defined by textural formation. In some cases, these bear a resemblance to traditional formal models, though in an individual way. Formal patterns serve to show that Bax has definite formal shapes in mind. Bax, however, does not artificially impose these patterns on the music; instead, they arise from Bax's need for creative expression. A conclusion of this study is that textural-thematic contrast and variation are fundamental to the form and style of Bax's symphonies. Contrast, especially, is vital to Bax's romantic aesthetic, and variation is largely responsible for the variety of textural change and the evolution of thematic ideas. The Second Symphony is analyzed in some detail. In that work, a cyclical use of themes and motives provides an interesting study. Contrast and variation are very pervasive and result in a very individual and satisfying formal design.

Thesis (Ph.D.)--Kent State University, 2008. / Title from PDF t.p. (viewed Dec. 10, 2009). Advisor: Theodore Albrecht. Keywords: Bax, Tintagel, symphonic poem, British music. Includes bibliographical references (p. 207-213).

Thesis (M.A.)--University of Wisconsin--Madison, 1970. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The upregulation of apoptosis is a hallmark of several neurodegenerative disorders including ischemic stroke. In neurons, as in other cell types, Bax and tBid are critical regulators of the intrinsic pathway upstream of mitochondrial outer membrane permeabilization (MOMP) and caspase activation. The characterization of the molecular events that occur during the early stages is therefore extremely important from a therapeutic standpoint. Here I show that two independent genetic pilot screens looking for novel regulators of Bax activation identified a common hit in the E3 ubiquitin ligase Trim17. Knockdown of Trim17 was found to protect against tBid-induced death in primary cortical neurons and allowed for the maintenance of mitochondrial function and oxidative phosphorylation under this apoptotic stress. The RING-domain of Trim17 was found to interact with Opa1 in mouse brain extracts. Furthermore, Opa1 co-immunoprecipitated with exogenously expressed full-length Trim17 from HEK293 cells. Knockdown of Trim17 in neurons increased Opa1 protein levels under steady-state conditions. These results suggest that Trim17 regulates Bax-dependent apoptosis in neurons via the modulation of Opa1 levels.

The upregulation of apoptosis is a hallmark of several neurodegenerative disorders including ischemic stroke. In neurons, as in other cell types, Bax and tBid are critical regulators of the intrinsic pathway upstream of mitochondrial outer membrane permeabilization (MOMP) and caspase activation. The characterization of the molecular events that occur during the early stages is therefore extremely important from a therapeutic standpoint. Here I show that two independent genetic pilot screens looking for novel regulators of Bax activation identified a common hit in the E3 ubiquitin ligase Trim17. Knockdown of Trim17 was found to protect against tBid-induced death in primary cortical neurons and allowed for the maintenance of mitochondrial function and oxidative phosphorylation under this apoptotic stress. The RING-domain of Trim17 was found to interact with Opa1 in mouse brain extracts. Furthermore, Opa1 co-immunoprecipitated with exogenously expressed full-length Trim17 from HEK293 cells. Knockdown of Trim17 in neurons increased Opa1 protein levels under steady-state conditions. These results suggest that Trim17 regulates Bax-dependent apoptosis in neurons via the modulation of Opa1 levels.

RBBP6 (retinoblastoma binding protein 6) is a 250-kDa multifunctional protein that interacts with both p53 and pRb and has been implicated in mRNA processing. It has also been identified as an E3 ubiquitin ligase due to the presence of a RING finger domain and also assumed to have a regulatory role of p53 due to the presence p53BD through MdM2, although no substrate has been identified up to now. RBBP6 gene mutants are reported to be resistant to apoptosis inducers, which led to a belief that mutation of this gene might result in the development of lung cancer. Earlier localization and expression studies have shown that RBBP6 expression and apoptosis levels are indirectly proportional. The purpose of this study is to establish the expressional pattern of the RBBP6 gene in lung cancer at both mRNA and protein levels. The objective is also to characterize the role of this gene and apoptosis in diverse lung diseases. An understanding of the role of RBBP6 in the development of lung diseases may lead to insights into developing new therapeutic measures for those lung diseases in which apoptosis plays a prominent part. This thesis elucidate the possible role of RBBP6 in lung cancer and apoptosis, to establish tissue distribution and expression levels of RBBP6 at protein and mRNA levels in lung cancer by immunocytochemistry (ICC), in situ hybridization (ISH) and confirm findings by quantitative RT-PCR. RBBP6 mRNA transcripts were expressed in the cytoplasm of normal and tumour lung epithelium. In general, expression was highest in the cytoplasm of welldifferentiated carcinoma and invasive carcinoma that showed signs of cells undergoing mitosis. Immunolabelling results further showed high level of expression in all lung cancer types except in Small and large cell carcinomas. The immunolabeling were confirmed by ISH experiments and RT-PCR. In relation to p53, RBBP6 mRNA expression was higher in lung cancer cell lines that had p53 silenced and apoptosis induced by TRAIL and camptothecin. There was no notable change in the levels of p53 expression following RBBP6 silencing and apoptosis induction. However, there was a little correlation between RBBP6 expression and apoptosis levels in both lung cancer tissues by TUNEL and lung cancer cell line following apoptosis induction by TRAIL. The ratio of Bax/Bcl-2 was seen to be upregulated following p53 and RBBP6 silencing after apoptosis induction. The most common mutation notable after RBBP6 DNA sequencing was point mutations where only single nucleotide was mutated and mostly they were observed in lung cancer tissues. This was the first demonstration that RBBP6 is expressed in lung cancers. Because of the ubiquitin-like nature of the protein and its localized up-regulation and corresponding proapoptotic activity in lung cancer cells, it is possible that further characterization of this gene could lead to its manipulation as a diagnostic marker and a potential therapeutic target for cancer treatment.

Oxaliplatin as an effective chemotherapeutic agent in FOLFOX regimens is using to treat colorectal cancer. In this study we investigate cytotoxicity of Oxaliplatin as single chemotherapeutic agent toHCT116P53+/- to identify molecular mechanism of Oxaliplatin action in induction of apoptosis pathway. Oxaliplatin exposure to HCT116P53+/- colorectal cell lines with deficiency of mismatch repair characteristic resulted to decrease the number of viable cells through apoptosis. Effective Oxaliplatin concentrations (IC50) which inhibit 50% of cell viability were determined using XTT method. Standard curve and time-dependent assay performed to confirm IC50 concentration. Western blot analysis demonstrated relocalization of Bax to mitochondria and induction of intrinsic apoptosis pathway resulted Oxaliplatin exposure. Inactivation of Bax in HCT116P53+/- will result significant reduction in number of viable cells following treatment with Oxaliplatin

During neural development, nearly 50% of all newly generated neurons undergo cell death after making provisional contact with their target cells. The functional consequences of eliminating this neuronal cell death are not known. Bax, a pro-apoptotic protein, is required for cell death in many neural regions. A null mutation of the Bax gene in mice has been shown to increase overall cell number and eliminate the sex differences in neuron number in the anteroventral periventricular nucleus (AVPV) and the principal nucleus of the bed nucleus of the stria terminalis (BNSTp). The aim of my Master’s thesis was to study male and female sexual behaviors and motor behavior in Bax -/- mice and their wild-type siblings. Animals were gonadectomized in adulthood and provided with ovarian hormones or with testosterone for tests of female and male sexual behaviors, respectively. Wild-type mice exhibited a sex difference in feminine sexual behavior, with high lordosis scores in females and low scores in males. This sex difference was eliminated by Bax deletion, with very low receptivity exhibited by both male and female Bax -/- mice. Male sexual behavior was not sexually dimorphic among wild-type mice, but mounts and pelvic thrusts were nearly absent in Bax -/- mice of both sexes. The knockouts did not display deficient motor strength or performance at low speeds on a RotaRod apparatus compared to wild type mice. At high speeds, however, Bax -/- animals exhibited impairments on the RotaRod. Therefore, developmental cell death may be required for exhibition of male and female sexual behaviors, and for coordination of relatively difficult motor tasks.

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