LTBP-1 is a large extracellular glycoprotein that is a component of the large latent TGF-β complex. The extracellular sequestration of latent TGF-β in the extracellular matrix (ECM) is fundamental to the regulation of TGF-β bioavailability and activity. LTBP-1 is described to contribute to the regulation of TGF-β bioavailability through mediating the extracellular sequestration of newly secreted latent TGF-β with fibrillin microfibrils in the ECM. However it is not well understood how LTBP-1, and thus latent TGF-β, becomes deposited into the ECM. Previous work by our group suggested that LTBP-1 interactions with the glycosaminoglycan heparan sulphate (HS) at the cell-matrix interface might facilitate the association of LTBP-1 with fibrillin microfibrils. Using recombinant LTBP-1 fragments and mutants, LTBP-1 interaction with HS have been fine-mapped. Deposition of a LTBP-1 HS-binding mutant, and of LTBP-1 when HS was depleted, was studied in cell cultures; findings presented here demonstrate that HS may not be critical for the deposition of LTBP-1 into the ECM. Contributions of fibrillin and fibronectin to LTBP-1 deposition were investigated, and data presented here support published findings that fibrillin is not always required for LTBP-1 deposition. In addition, the dependency of LTBP-1 deposition upon fibronectin was suggested to differ between different cell types (epithelial and mesenchymal). How LTBP-1 may be stabilised within the ECM through crosslinking by tissue transglutaminase was investigated using recombinant fragments and cell culture studies. Tissue transglutaminase was found to promote the extracellular incorporation of LTBP-1, and novel cross-links within LTBP-1, and between LTBP-1 and fibrillin-1, but not LTBP-1 and fibronectin, were identified. Additionally, results indicated that LTBP-1 was present in extremely high molecular weight assemblies in the ECM of cultured fibroblasts. Collectively, these results have contributed to current knowledge of how LTBP-1 becomes deposited into the ECM. They indicate that the deposition of LTBP-1 is not underpinned by HS, may be cell type-specific, and that LTBP-1 may potentially self-assemble extracellularly into homotypic structures that may associate with fibrillin microfibrils.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19570号 / 医博第4077号 / 新制||医||1013(附属図書館) / 32606 / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 秀一, 教授 開 祐司, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

As part of the Federal Highway Administration's Long-Term Bridge Performance Program, Live Load and Dynamic tests were conducted. A long-term monitoring plan was developed and presented for the Utah Pilot Bridge based on Live Load and Dynamic tests. As one of seven pilot bridges, the Utah Pilot Bridge is one of the first bridges used to initiate the LTBP Program. A formal permit approval process, with the Utah Department of Transportation, was followed to gain permission to conduct the tests and install long-term instrumentation. Analysis provided good results for each test completed, with a summary of test results presented. A Finite Element Model was created and refined based off test data. Instrumentation was installed and checked to ensure quality data was streaming to the collection site.

Modeling of chloride-induced deterioration of bridge decks by using Fick's Second Law of diffusion was performed. The objective of this study is to select suitable input parameters for the model to estimate the service life of bridge decks. Five bridge decks, one in each of the following states, Virginia, Florida, New Jersey, New York, and Minnesota were evaluated. Data collection process involved visual inspections, damage surveys, corrosion testing including continuity, one-point resistivity, four-point resistivity, half-cell potentials, and three-electrode linear polarization, reinforcement cover depths, chloride samples. The Virginia bridge deck was built with epoxy-coated reinforcement as top reinforcement mat and black bar as the bottom mat. The Florida bridge is a segmental prestressed box girder structure built with black bar. The New Jersey bridge deck was overlaid with latex modified concrete. The New York bridge deck, which was built in 1990, is six inch concrete topping over prestressed adjacent box beams structure with epoxy-coated bar in the negative moment area. The Minnesota bridge was rebuilt in 1984. The deck was rebuilt with epoxy coated reinforcing steel in the top and bottom mats. The probabilistic Fickian model requires reinforcement cover depths, surface chloride concentration, chloride initiation concentration, and diffusion coefficients as input parameters. The chloride initiation concentration was input via parametric bootstrapping, while the other parameters were input as simple bootstrapping. Chloride initiation concentration was determined from the chloride concentration at the reinforcement bar depths. The modeling results showed that the deterioration of the Virginia bridge deck was corrosion controlled and the bridge will undergo increasingly severe damage in the future. Florida bridge deck is not undergoing corrosion and will not experience corrosion damage within 100 years. New Jersey bridge deck's service life has been most likely extended by the overlay. Deterioration of the New York bridge was not corrosion controlled, but was related to longitudinal cracking of the topping at match lines of adjacent box beams. Minnesota bridge deck is delaminated and contained a large number of cracks that should be included in service life modeling; otherwise the service life estimate is underestimated. In addition to service life corrosion performance modeling, analyses were conducted on the relationships and interrelations of resistivity, corrosion potential, corrosion current and chloride at the reinforcing bar depth. / Ph. D.