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101.
M Harmsen TA Oosterlaken C Tangerman H Snippe CA Kraaijeveld 《Canadian Metallurgical Quarterly》1993,43(2):137-146
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) is the rate limiting step in the mevalonate pathway that produces isoprenoids and cholesterol. Inhibitors of HMG-CoA reductase are teratogenic in vivo and induce neural tube defects in rat embryo culture, effects which appear unrelated to cholesterol deficiency. This study is the first to localize HMG-CoA reductase mRNA by in situ hybridization (ISH). Expression of reductase mRNA was examined in post-implantation rat embryos, and for control purposes in rat liver and UT-1 cells, using a digoxigenin-11 (dig-11) labelled cRNA probe. Eighteen-day fetal liver showed heavy but patchy hybridization, and adult rat liver showed strong hybridization only on some periportal hepatocytes, which was absent in livers of fasted animals. UT-1 cells stimulated to overexpress HMG-CoA reductase mRNA were strongly positive with the same probe. Control hybridizations with sense strand RNA probe, or with cRNA probe on pre-RNased tissue were negative. Strong hybridization signal for HMG-CoA reductase mRNA was observed in all tissues of the post-implantation rat embryo, from egg cylinder to 30 somite stages (7 to 12 days). Heavy signal was noted in primitive ectoderm and neural tube. The wide embryonic and extraembryonic distribution and abundance of HMG-CoA reductase mRNA may reflect developmental requirements for products of the mevalonate pathway, e.g., isoprenoids for post-translational farnesylation of p21ras. 相似文献
102.
X Meng X Lu Z Li ED Green H Massa BJ Trask CA Morris MT Keating 《Canadian Metallurgical Quarterly》1998,103(5):590-599
Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS. 相似文献
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In this paper techniques are developed and compared that increase the inferential power of tableau systems for classical first-order logic. The mechanisms are formulated in the framework of connection tableaux, which is an amalgamation of the connection method and the tableau calculus, and a generalization of model elimination. Since connection tableau calculi are among the weakest proof systems with respect to proof compactness, and the (backward) cut rule is not suitable for the first-order case, we study alternative methods for shortening proofs. The techniques we investigate are the folding-up and the folding-down operations. Folding up represents an efficient way of supporting the basic calculus, which is top-down oriented, with lemmata derived in a bottom-up manner. It is shown that both techniques can also be viewed as controlled integrations of the cut rule. To remedy the additional redundancy imported into tableau proof procedures by the new inference rules, we develop and apply an extension of the regularity condition on tableaux and the mechanism of anti-lemmata which realizes a subsumption concept on tableaux. Using the framework of the theorem prover SETHEO, we have implemented three new proof procedures that overcome the deductive weakness of cut-free tableau systems. Experimental results demonstrate the superiority of the systems with folding up over the cut-free variant and the one with folding down.Work supported by the Deutsche Forschungsgemeinschaft and the Esprit Basic Research Action 6471 Medlar II. 相似文献
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It is a demanding and time-consuming task to construct the side window mechanism of a car such that the deflections along the seals are minimized. The reason for this is that the window surface S delivered by the stylist, will in general not be movable in a proper way: It is required that the surface tightly moves along the seals. Deflections will necessarily occur no matter how much effort the engineer invests. This article describes how to find a spatial motion that minimizes seal deflection for some given automobile side window surface. Necessary but acceptable modification of the stylist’s surface S is also addressed, as well as the lifting mechanism design. It is argued that our systematic approach offers considerable savings compared to the prevailing trial-and-error approach. 相似文献
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The peculiarities of meteorological wind potential in alpine settings compared to flatland and offshore sites are studied. Four data sources are used: Global reanalysis ERA40 from ECMWF, long‐term stations in the Tyrolean Alps, spatially dense measurements near the best site and Doppler sodar wind profiles. Due to the decrease of density with height, alpine sites suffer from a nearly linear decrease of harvestable power with altitude, which is more than offset by the increase of wind speed at altitudes above 1.5 km MSL. ERA40 data show higher potential on the northern than on the southern side of the Alps. The best locations are not isolated peaks but ridges within wide orographic channels. The best potential sites in the Tyrolean part of the Alps have median wind speeds of up to 7.1 m s?1 and extractable potentials between 2900 and 1600 kWh per year and per square meter of rotor area. The profile of horizontal wind speed at ridge sites is often not logarithmic but approximately constant within the height of a wind turbine due to a (nearly) complete absence of upwind fetch. Also, the turbulence intensity is independent of height. Icing can cause considerable downtimes. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
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