13 research outputs found

    Life-cycle costing of metallic structures

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    Structural material selection has traditionally been based on Initial material cost. However, growing pressure on the construction industry to consider the longer-term financial and environmental implications of projects is encouraging a more holistic view. Thus, materials with higher initial costs, but which offer cost savings over the life cycle of a structure, are gaining increasing recognition. The life-cycle costs of structures of two such metallic materials, namely aluminium alloy and stainless steel, are compared with those of ordinary structural carbon steel in the present study. Two structural applications - a typical office building and a bridge - are analysed, while offshore applications are briefly discussed. The ratio of initial material cost per tonne was assumed to be 1.0:2.5:4.0 (carbon steel:aluminium alloy:stainless steel). Following a preliminary structural design to current European design standards taking due account of the material densities and structural properties (principally strength and stiffness), it was found that on an initial cost basis, carbon steel offers the most competitive solution for both the building and the bridge. However, considering the additional life-cycle costs including maintenance costs, end-of-life costs and the residual value of the structure (appropriately discounted to present values), the results indicate that carbon steel offers the most competitive life-cycle solution for the office building but delivers the most expensive life-cycle solution for the bridge. Overall, it is concluded that on a whole-life basis aluminium alloy and stainless steel may offer more competitive solutions than carbon steel for bridges and exposed areas of building structures

    Deficiency of FLCN in Mouse Kidney Led to Development of Polycystic Kidneys and Renal Neoplasia

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    The Birt–Hogg–Dubé (BHD) disease is a genetic cancer syndrome. The responsible gene, BHD, has been identified by positional cloning and thought to be a novel tumor suppressor gene. BHD mutations cause many types of diseases including renal cell carcinomas, fibrofolliculomas, spontaneous pneumothorax, lung cysts, and colonic polyps/cancers. By combining Gateway Technology with the Ksp-Cre gene knockout system, we have developed a kidney-specific BHD knockout mouse model. BHDflox/flox/Ksp-Cre mice developed enlarged kidneys characterized by polycystic kidneys, hyperplasia, and cystic renal cell carcinoma. The affected BHDflox/flox/Ksp-Cre mice died of renal failure at approximate three weeks of age, having blood urea nitrogen levels over tenfold higher than those of BHD flox/+/Ksp-Cre and wild-type littermate controls. We further demonstrated that these phenotypes were caused by inactivation of BHD and subsequent activation of the mTOR pathway. Application of rapamycin, which inhibits mTOR activity, to the affected mice led to extended survival and inhibited further progression of cystogenesis. These results provide a correlation of kidney-targeted gene inactivation with renal carcinoma, and they suggest that the BHD product FLCN, functioning as a cyst and tumor suppressor, like other hamartoma syndrome–related proteins such as PTEN, LKB1, and TSC1/2, is a component of the mTOR pathway, constituting a novel FLCN-mTOR signaling branch that regulates cell growth/proliferation

    Transgenic nematodes as biosensors for metal stress in soil pore water samples

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    Caenorhabditis elegans strains carrying stress-reporter green fluorescent protein transgenes were used to explore patterns of response to metals. Multiple stress pathways were induced at high doses by most metals tested, including members of the heat shock, oxidative stress, metallothionein (mtl) and xenobiotic response gene families. A mathematical model (to be published separately) of the gene regulatory circuit controlling mtl production predicted that chemically similar divalent metals (classic inducers) should show additive effects on mtl gene induction, whereas chemically dissimilar metals should show interference. These predictions were verified experimentally; thus cadmium and mercury showed additive effects, whereas ferric iron (a weak inducer) significantly reduced the effect of mercury. We applied a similar battery of tests to diluted samples of soil pore water extracted centrifugally after mixing 20% w/w ultrapure water with air-dried soil from an abandoned lead/zinc mine in the Murcia region of Spain. In addition, metal contents of both soil and soil pore water were determined by ICP-MS, and simplified mixtures of soluble metal salts were tested at equivalent final concentrations. The effects of extracted soil pore water (after tenfold dilution) were closely mimicked by mixtures of its principal component ions, and even by the single most prevalent contaminant (zinc) alone, though other metals modulated its effects both positively and negatively. In general, mixtures containing similar (divalent) metal ions exhibited mainly additive effects, whereas admixture of dissimilar (e.g. trivalent) ions often resulted in interference, reducing overall levels of stress-gene induction. These findings were also consistent with model predictions

    Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

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