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151.
It has been and still is commonly believed by geologists and historians of geology alike that geological theory is an extrapolation from the empirical knowledge of the geology of a region. Abraham Gottlob Werner (1749–1817), whose theory concerning the origin of basalt and the minor role of volcanoes and the major role of water in the history of the earth's crust was eventually proven wrong in some respects, is usually cited as the prime example of a geologist who had not ventured beyond the confines of his native region, Saxony, and had developed a universal geological theory based almost entirely on his observations of that region. In this essay I show that the geology of Saxony played a relatively unimportant role in the development of Werner's universal geological theory; that he became a neptunist before he had closely examined the geology of Saxony; and that his explanation of the history of the earth's crust was as reasonable, if not more reasonable, than the explanations brought forth by those of his contemporaries who opposed his views.  相似文献   
152.
Many members of the nudix hydrolase family exhibit considerable substrate multispecificity and ambiguity, which raises significant issues when assessing their functions in vivo and gives rise to errors in database annotation. Several display low antimutator activity when expressed in bacterial tester strains as well as some degree of activity in vitro towards mutagenic, oxidized nucleotides such as 8-oxo-dGTP. However, many of these show greater activity towards other nucleotides such as ADP-ribose or diadenosine tetraphosphate (Ap4A). The antimutator activities have tended to gain prominence in the literature, whereas they may in fact represent the residual activity of an ancestral antimutator enzyme that has become secondary to the more recently evolved major activity after gene duplication. Whether any meaningful antimutagenic function has also been retained in vivo requires very careful assessment. Then again, other examples of substrate ambiguity may indicate as yet unexplored regulatory systems. For example, bacterial Ap4A hydrolases also efficiently remove pyrophosphate from the 5′ termini of mRNAs, suggesting a potential role for Ap4A in the control of bacterial mRNA turnover, while the ability of some eukaryotic mRNA decapping enzymes to degrade IDP and dIDP or diphosphoinositol polyphosphates (DIPs) may also be indicative of new regulatory networks in RNA metabolism. DIP phosphohydrolases also degrade diadenosine polyphosphates and inorganic polyphosphates, suggesting further avenues for investigation. This article uses these and other examples to highlight the need for a greater awareness of the possible significance of substrate ambiguity among the nudix hydrolases as well as the need to exert caution when interpreting incomplete analyses.  相似文献   
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How can new drug lead suggestions beinferred from neurophysiological models? This paperaddresses this question based on a case study ofresearch into Parkinson's disease at the GroningenUniversity Department of Pharmacy. It is argued thatneurophysiological box-and-arrow models can beunderstood as qualitative differential equationmodels. An inference task is defined to helpunderstand and possibly aid the discovery andexplanation of new drug lead suggestions.  相似文献   
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Summary Lithium, which is used routinely in the treatment of mania, is composed of two stable isotopes, lithium-7 (92.58%) and lithium-6 (7.42%). Usually there is minimal physiological or biochemical differentiation between isotopes of an element, but lithium is an exception. Data derived from a variety of biochemical and behavioral experiments are reviewed to support this idea. Additionally, the clinical implications of this work are presented.  相似文献   
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