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1.
String theorists are certain that they are practicing physicists. Yet, some of their recent critics deny this. This paper argues that this conflict is really about who holds authority in making rational judgment in theoretical physics. At bottom, the conflict centers on the question: who is a proper physicist? To illustrate and understand the differing opinions about proper practice and identity, we discuss different appreciations of epistemic virtues and explanation among string theorists and their critics, and how these have been sourced in accounts of Einstein's biography. Just as Einstein is claimed by both sides, historiography offers examples of both successful and unsuccessful non-empirical science. History of science also teaches that times of conflict are often times of innovation, in which novel scholarly identities may come into being. At the same time, since the contributions of Thomas Kuhn historians have developed a critical attitude towards formal attempts and methodological recipes for epistemic demarcation and justification of scientific practice. These are now, however, being considered in the debate on non-empirical physics.  相似文献   
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We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.  相似文献   
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Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum.   总被引:39,自引:0,他引:39  
K Sandvig  O Garred  K Prydz  J V Kozlov  S H Hansen  B van Deurs 《Nature》1992,358(6386):510-512
Shiga toxin and some other protein toxins that act on targets in the cytosol have previously been shown to enter the trans-Golgi network. Transport by this route may be necessary for translocation of the toxin to the cytosol and for intoxication, but it is not known whether the enzymatically active part of the toxins actually enters the cytosol from the trans-Golgi network. It has been suggested that such toxins are transported in a retrograde manner to the endoplasmic reticulum and that translocation occurs in this organelle, but retrograde transport of endocytosed material beyond the trans-Golgi network has never been demonstrated. Here we show that in butyric acid-treated A431 cells endocytosed Shiga toxin is not only transported to the trans-Golgi network, but also to all Golgi stacks, to the endoplasmic reticulum and to the nuclear envelope. Furthermore, butyric acid sensitizes the cells to Shiga toxin, which is consistent with the possibility that retrograde transport is required for translocation of the toxin to the cytosol.  相似文献   
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基于神经网络的企业信用等级评估   总被引:32,自引:2,他引:30  
企业信用等级评估是金融领域重要的问题,论文采用人工神经网络模型研究企业信用等级的评估问题,按照企业样本在信用等级的分布状况来抽样,然后,根据企业样本性质的不同,将其分为制造业和非制造业两大类,利用偏相关分析方法建立了企业信用评级的指标体系,此外,还介绍了几种企业信用评级常用的评估模型,并将神经网络评估模型的性能和其他的信用评估模型作了比较,实验结果表明神经网络模型具有更好的预测准确性。  相似文献   
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管理系统的最经济控制问题   总被引:1,自引:0,他引:1  
依据最经济控制问题的概念及其对无确定性数学模型系统分析存在的局限性,对现代管理系统最经济控制问题,提出了在满足系统基本要求前提下。实现控制功能及品质与控制成本比最佳或最划算的模型定义,并对管理系统的可靠性、ABC管理法、WSR方法论等方面的可靠性成本、运行成本和最佳收益等最经济控制问题进行了研究.  相似文献   
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Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.  相似文献   
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During the past few years, several methods have been developed for the detection of specific nucleic acid sequences by in situ hybridization using non-radioactive labels such as fluorochromes, cytochemically detectable enzymes and electron-dense markers. These methods are preferable to autoradiography in terms of speed of performance and topological resolution. Their limited sensitivity, however, has so far restricted their use to the detection of repeated sequences. Here we report single gene detection with a procedure using 2-acetylaminofluorene (AAF)-modified probes, immunoperoxidase cytochemistry and reflection-contrast microscopy. We confirmed the autoradiographic data on the localization of the human thyroglobulin (Tg) gene to the distal end of the long arm of chromosome 8. A mixture of cosmid cHT2-derived subclones of the 3' part of the Tg gene, 22.3 kilobase pairs (kbp) in total, was used as a hybridization probe. This procedure can be used to map other unique sequences, if genomic clones are available from which clones with an appropriate amount of inserts can be isolated.  相似文献   
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