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Histone demethylases play a critical role in mammalian gene expression by removing methyl groups from lysine residues in degree- and site-specific manner. To specifically interrogate members and isoforms of this class of enzymes, we have developed demethylase variants with an expanded active site. The mutant enzymes are capable of performing lysine demethylation with wild-type proficiency, but are sensitive to inhibition by cofactor-competitive molecules embellished with a complementary steric “bump”. The selected inhibitors show more than 20-fold selectivity over the wild-type demethylase, thus overcoming issues typical to pharmacological and genetic approaches. The mutant–inhibitor pairs are shown to act on a physiologically relevant full-length substrate. By engineering a conserved amino acid to achieve member-specific perturbation, this study provides a general approach for studying histone demethylases in diverse cellular processes.  相似文献   
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Large deformations of soft materials can give rise to the development of various elastic instabilities. The phenomenon is associated with a sudden and dramatic change in structure morphologies. The underlying mechanism is crucial for the formation of complex morphologies in biology. Moreover, the concept of instability-induced pattern transformations is promising for designing novel materials with switchable functions and properties. In this paper, we review the state of the art in elastic instability phenomena in soft materials. We start by considering the classical buckling in beam-based structure lattice designs. Then, we discuss the instability-induced microstructure transformations in soft porous materials, and heterogeneous multiphase and fiber composites. Next, the mechanisms – often involving the post-buckling consideration – leading to the wrinkling and folding, creasing, fringe, and fingering are discussed.  相似文献   
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Wireless Personal Communications - Face is the most commonly used biometric these days due to its wide potential in numerous security applications. Spoofing attack is a fierce risk for security of...  相似文献   
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A methodology is proposed to reduce the cost and capital intensity of small-scale chemical processes by creating new opportunities for economies of numbers through standardizing the equipment designs across multiple processes. We depart from asynchronous design of single-processes and adopt a common-functionality based simultaneous design of multiple processes that use similar unit operations. A generalized cost function is used to appropriately balance the trade-offs between economies of scale and economies of numbers. An optimization-based framework for design standardization is developed and illustrated using two case studies. The first involves the simultaneous synthesis of methanol and ammonia processes, and the second addresses the optimal synthesis of multi-column natural gas liquid (NGL) fractionation processes for different natural gas sources. We observe that considerable reduction in capital intensity of small-scale processes is possible through equipment standardization.  相似文献   
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