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A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.  相似文献   
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The Academic Journal Ranking Problem consists in formulating a formal assessment of scientific journals. An outcome variable must be constructed that allows valid journal comparison, either as a set of tiers (ordered classes) or as a numerical index. But part of the problem is also to devise a procedure to get this outcome, that is, how to get and use relevant data coming from expert opinions or from citations database. We propose a novel approach to the problem that applies fuzzy cluster analysis to peer reviews and opinion surveys. The procedure is composed of two steps: the first is to collect the most relevant qualitative assessments from international organizations (for example, the ones available in the Harzing database) and, as inductive analysis, to apply fuzzy clustering to determine homogeneous journal classes; the second deductive step is to determine the hidden logical rules that underlies the classification, using a classification tree to reproduce the same patterns of the first step.  相似文献   
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