Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xxxii, 311 p.; also includes graphics (some col.). Includes bibliographical references (p. 287-311). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--University of Wisconsin--Madison, 1962. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 182-186).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1958. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 58-61).

Thesis (doctoral)--Rijksuniversiteit te Utrecht.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 1997. / Vita. Includes bibliographical references (leaves 121-129).

Thesis (M.A..)--Marshall University, 2009. / Title from document title page. Includes abstract. Document formatted into pages: contains v, 33 p. Includes bibliographical references p. 33

Thesis (doctoral)--Rijksuniversiteit te Utrecht.

Thesis (M.A.) / Systemic sclerosis (SSc) is a clinically heterogenous chronic fibrotic disease which affects skin and internal organs. While the pathogenesis of SSc remains unknown, the hallmark of both localized and diffuse SSc in the skin is the replacement of normal dermal architecture with excessive deposition of collagen and other connective tissue macromolecules. Progressive replacement of tissue architecture by collagen-rich extracellular matrix (ECM) results in functional impairment of affected organs. Fibrotic damage to these affected organs accounts for much of the morbidity and mortality concomitant with SSc, particularly in the lungs. Myofibroblasts are the primary ECM-secreting cells during wound healing and fibrosis. Myocardin-related transcription factor A (MRTF-A), is an important regulator of myofibroblast differentiation, depending on serum response factor (SRF) for smooth muscle actin (SMA) and Sp1 in the regulation of collagen gene expression. MRTF-A continually shuttles between the nucleus and cytoplasm in unstimulated cells. Signals of stress, mechanical force, and migration control MRTF-A movement by a mechanism in which Rho-activated cytoskeletal actin polymerization induces its relocation from the cytoplasm to the nucleus. The major hypothesis in this thesis is that MRTF-A is dysregulated (impairment of a physiological regulatory mechanisms) and/or activated in SSc patients in part through transforming growth factor beta (TGF-β). To test this hypothesis, immunohistochemistry using MRTF-A antibodies was performed on SSc patient skin lesions and healthy control skin. Staining was observed in the epidermis, epidermal structures, vasculature and dermis of SSc and healthy control skin. In the epidermal layer of patients with SSc, there was significantly more nuclear localization of MRTF-A then in normal controls. Prominent staining is also present in endothelial, perivascular and some perivascular inflammatory cells of SSc patients. Perivascular staining was not seen in healthy controls. Interestingly, there was some accumulation of nuclear MRTF-A in areas typical of myofibroblasts in SSc skin, but this staining is not as striking as vascular staining. TGF-β activates MRTF-A in a cell-specific manner. As SSc typically begins within the skin, human dermal fibroblasts (HDF) were grown in culture. HDFs synthesize and secrete collagen to a greater extent when compared to human lung fibroblasts (IMR90 cells). Treatment with TGF-β enhances cytoplasmic localization of MRTF-A at 4-8 hours in HDFs and prolongs nuclear localization. Transgenic mouse lung cells were isolated from an MRTF-A loss-of-function mouse carrying the 3.6 kb proximal promoter of the rat COL1A1 gene driving topaz green fluorescent protein (GFP) (pOB3.6COLGFPtpz). Since angiotensin II (ANG II) may enhance TGF-β response or collagen transcription directly, wild type (WT) and MRTF-A knockout (KO) cells were treated with ANG II and TGF-β. Quantification of collagen transcription by GFP fluorescence and protein synthesis by Western and secretion by Sircol analysis revealed collagen gene expression is consistently lower in KO fibroblasts compared to WT. Total percentage of fluorescent KO cells were consistently lower in comparison to WT cells as well. KO cells do not respond to TGF-β or ANG II treatment, whereas TGF-β increased collagen gene expression by WT cells, but not KO cells. Furthermore, treatment with ANG II did not up-regulate transcription in WT mouse lung fibroblasts. However, TGF-β receptor kinase 1 (TβR-1) inhibitor SB431542 attenuated collagen transcription in both WT and KO fibroblasts regardless of treatment suggesting that the receptor is active with or without MRTF-A possibly with an endogenous ligand produced by these cells. The activation of MRTF-A is an important protein regulating collagen synthesis and may potentially serve as a therapeutic target in future treatments of fibrotic disease such as SSc.

This dissertation explores talk in an undergraduate seminar context. Research design was informed by an interpretive, ethnomethodological approach to understanding talk as a situated activity. A series of <i>student-led seminars</i> were audio recorded; students and staff were interviewed and post-seminar group debriefing sessions were held. The data was subsequently transcribed and analysed using a functional systemic linguistics and discourse analysis approach. Analysis identified structural and linguistic elements of seminar talk and links between language, identity, power and status was explored through an analysis of the discursive processes at work in the seminar events. An heuristic model of the seminar as a socio-pedagogic space, a site of hegemonic struggle, was used to aid concept development. A number of issues emerged within an interpretative framework of the cognitive, interpersonal and textual elements of seminar talk. In the analysis of the textual meta-function of seminars, how complexity is achieved and how conversational moves are patterned, seminars appear to constitute a hybrid talk variety, a highly unusual textual form in which participants need to learn how to participate. Tensions were found between the social and the cognitive elements of seminars. Student participants tend to use the seminar to achieve social effects, identifying and maintaining interpersonal relationships. The collaborative discourse strategies they employ constrain other opportunities for achieving educational outcomes. The learning which does take place is more likely to be related to personal and skills development than to learning about the academic subject. Students deployed a range of heteroglossic discursive strategies to practice their skills in forming ideas, marshalling evidence and constructing argument. The discursive practices of seminar events foreground tensions between socially situated identities. The research identifies a number of areas for improving practice including: enhanced specification of seminar processes and outcomes; embedding opportunities for preparation and critical reflection; teaching the subject of communication and foregrounding understandings of the discursive practices at work in seminars so as to empower individual learners.