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Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors 总被引:5,自引:0,他引:5
Al-Tassan N Chmiel NH Maynard J Fleming N Livingston AL Williams GT Hodges AK Davies DR David SS Sampson JR Cheadle JP 《Nature genetics》2002,30(2):227-232
Inherited defects of base excision repair have not been associated with any human genetic disorder, although mutations of the genes mutM and mutY, which function in Escherichia coli base excision repair, lead to increased transversions of G:C to T:A. We have studied family N, which is affected with multiple colorectal adenomas and carcinoma but lacks an inherited mutation of the adenomatous polyposis coli gene (APC) that is associated with familial adenomatous polyposis. Here we show that 11 tumors from 3 affected siblings contain 18 somatic inactivating mutations of APC and that 15 of these mutations are G:C-->A transversions--a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the human homolog of mutY, MYH, showed that the siblings were compound heterozygotes for the nonconservative missense variants Tyr165Cys and Gly382Asp. These mutations affect residues that are conserved in mutY of E. coli (Tyr82 and Gly253). Tyrosine 82 is located in the pseudo-helix-hairpin-helix (HhH) motif and is predicted to function in mismatch specificity. Assays of adenine glycosylase activity of the Tyr82Cys and Gly253Asp mutant proteins with 8-oxoG:A and G:A substrates show that their activity is reduced significantly. Our findings link the inherited variants in MYH to the pattern of somatic APC mutation in family N and implicate defective base excision repair in predisposition to tumors in humans. 相似文献
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Here we report the discovery of a small-bodied (approximately 1.8 m) predatory dinosaur from the Late Cretaceous (Maastrichtian) of Madagascar. Masiakasaurus knopfleri, gen. et sp. nov., represented by several skull elements and much of the postcranial skeleton, is unique in being the only known theropod with a highly procumbent and distinctly heterodont lower dentition. Such a derived dental morphology is otherwise unknown among dinosaurs. Numerous skeletal characteristics indicate that Masiakasaurus is a member of Abelisauroidea, an enigmatic clade of Gondwanan theropods. Previously, small-bodied abelisauroids were known only from Argentina. The occurrence of Masiakasaurus on Madagascar suggests that small-bodied abelisauroids, like their larger-bodied counterparts, were more cosmopolitan, radiating throughout much of Gondwana and paralleling the diversification of small coelurosaur theropods in Laurasia. 相似文献
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目的:观察外用中药制剂对小鼠乳腺增生的预防作用并探讨其机理。方法:采用苯甲酸雌二醇腹腔注射造模,分对照组、模型组与预防组。模型组与预防组腹腔注射苯甲酸雌二醇,隔天1次,并且预防组小鼠乳房涂抹百麦外用中药制剂,每天1次,共30天;对照组小鼠腹腔注射生理盐水,隔天1次,共30 d。测定各组小鼠体重变化,乳晕及乳头直径变化,血清雌激素(E2)、孕激素(P)指标,并取小鼠第二对乳房组织病理切片检查。结果:预防组与模型组小鼠体重、乳晕及乳头直径比较均有显著性差异(P0.05);预防组与模型组比较,E2水平明显降低(P0.05),P水平明显升高(P0.05);预防组小鼠增生的乳腺小叶、腺泡数、腺泡腔直径、导管直径以及胞浆面积较模型组降低。结论:百麦外用中药制剂具有预防乳腺增生的作用,其机理可能是通过抑制血清雌二醇水平而实现。 相似文献
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摩擦非线性环节的特性、建模与控制补偿综述 总被引:42,自引:0,他引:42
首先介绍了机械伺服系统中摩擦非线性环节的动态、静态特性的研究成果和目前常用的几种摩擦模型 ,讨论了摩擦非线性环节对伺服系统的动态性能和静态性能的影响 ,以及摩擦非线性环节导致的极限环振荡、低速爬行等现象。然后对有关摩擦补偿方法方面的研究成果进行了总结 ,介绍了传统的摩擦补偿方法和基于智能控制理论的摩擦补偿方法方面的研究成果。最后 ,展望了该领域今后的发展方向。 相似文献
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网络的带宽抖动和数据传输错误是影响视频传输的重要原因。该文提出了一种新的多参考帧图像预测的视频编码算法,即多参考预测链,使视频具有时域可扩展性和抗错性解决网络的这两个潜在问题。该算法中P帧之间的参考预测关系构成多条链状结构,使视频具有时域可扩展性。链间的不相关性使每个链可独立解码,从而增强了码流抗错性。该算法采用R-D框架动态的管理预测关系链,从而适合网络带宽的变化而获得最佳的终端视觉效果。仿真实验表明,采用多参考预测链编码的码流时域可扩展性的应用非常可行,且表现出较高的抗错性。 相似文献
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Bit-depth scalability is a new research field in the on-going scalable extension of the H.264/AVC (SVC) video coding standard. The key point is to accurately predict the enhancement layer, whose bit depth is 10 or more, from the 8 bit base layer. An improved inter-layer prediction scheme for bit-depth scalability was developed that ensures compatibility with the standard and improves the encoding efficiency. The scheme uses a “perfect” 8 bit picture with an adaptive neighbor filter whose coefficients are optimized by minimizing the block distortion between the 8 bit reconstructed picture and the “perfect” picture to achieve a more precise 10 bit prediction based on the filtered picture. Double arithmetic precision is used to further improve the encoding efficiency. Experimental results show that the scheme outperforms the recent joint video team (JVT) proposal in the joint scalable video model (JSVM). 相似文献
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研究了三层对角回归神经网络(DRNN)用于直流电动机实时控制的方法.首先采用动态反传算法训练神经网络以辨识直流电动机的逆模型,然后将这一训练后的网络作为前馈控制器与常规反馈控制器一起输出控制电压,以控制系统跟踪位置或速度指令.该算法简单、计算量小,适于实时控制.仿真结果表明了该方法的有效性. 相似文献
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飞行转台Backstepping与神经网络并行控制 总被引:1,自引:2,他引:1
阐述了飞行仿真转台的Backstepping设计方法及步骤。在Backstepping鲁棒控制的基础上,提出了一种Backstepping鲁棒控制和神经网络并行控制的方案,以Backstepping鲁棒控制为主控制器,神经网络进行动态误差补偿。Backstepping鲁棒控制克服了对象的不确定性,保障系统的鲁棒性;神经网络可以进一步提高系统的跟踪精度。仿真表明,这种方法实现了Backstepping鲁棒控制和神经网络控制的完美结合,很适合高精度飞行仿真转台系统的鲁棒控制。 相似文献
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Efferent control of the carotid body chemoreceptor 总被引:3,自引:0,他引:3