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101.
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Bone is a composite material in which collagen fibrils form a scaffold for a highly organized arrangement of uniaxially oriented apatite crystals. In the periodic 67 nm cross-striated pattern of the collagen fibril, the less dense 40-nm-long gap zone has been implicated as the place where apatite crystals nucleate from an amorphous phase, and subsequently grow. This process is believed to be directed by highly acidic non-collagenous proteins; however, the role of the collagen matrix during bone apatite mineralization remains unknown. Here, combining nanometre-scale resolution cryogenic transmission electron microscopy and cryogenic electron tomography with molecular modelling, we show that collagen functions in synergy with inhibitors of hydroxyapatite nucleation to actively control mineralization. The positive net charge close to the C-terminal end of the collagen molecules promotes the infiltration of the fibrils with amorphous calcium phosphate (ACP). Furthermore, the clusters of charged amino acids, both in gap and overlap regions, form nucleation sites controlling the conversion of ACP into a parallel array of oriented apatite crystals. We developed a model describing the mechanisms through which the structure, supramolecular assembly and charge distribution of collagen can control mineralization in the presence of inhibitors of hydroxyapatite nucleation.  相似文献   
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This paper introduces a new method for safety analysis which modifies, automates and integrates a number of classical safety analysis techniques to address some of the problems currently encountered in complex safety assessments. The method enables the analysis of a complex programmable electronic system from the functional level through to low levels of its hardware and software implementation. In the course of the assessment, the method integrates design and safety analysis and harmonises hardware safety analysis with the hazard analysis of software architectures. It also introduces an algorithm for the synthesis of fault trees, which mechanises and simplifies a large and traditionally problematic part of the assessment, the development of fault trees. In this paper, we present the method and discuss its application on a prototypical distributed brake-by-wire system for cars. We argue that the method can help us rationalise and simplify an inherently creative and difficult task and therefore gain a consistent and meaningful picture of how a complex programmable system behaves in conditions of failure.  相似文献   
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Instabilities can introduce highly non‐linear effects into structural problems. The instabilities, not clearly associated with a change in a parameter, result in a stochastic variation of the responses. This process variation can be distinguished from the effects of the parameter variation by mapping the response variation onto a predictable space and a residual space, where the predictable space contains the possible effects of the parameter variation, and the residual space contains the process effects. This study discusses the sources (mechanics) of the response variation in this class of problems, the use of response surfaces to distinguish between effects driven by design variable changes and bifurcations, and the visualization of unstable zones in the structure. Analytical problems, a headform impact problem, and an occupant safety study clarify the use of the proposed methodology. Copyright © 2005 John Wiley & Sons, Ltd.  相似文献   
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Mechatronik is a combination from Mechanics and electronic and can be defined as a special view and method of engineering. The main difference compared with the traditional way of mechanical and electronic design is the other way of specification and engineering. Interfaces and specification are focused on different blocks and modules on a functional way, independent how it is realized. The results are not only new innovative solutions with better usage of the modern control possibilities. Also for the interfacing, installation and support this way of engineering give many advantages and possibilities for cost reduction. This paper shows on dry vacuum pumps and systems in the chemical and pharmaceutical industry the actual solutions which are available to use these advantages.  相似文献   
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The underlying molecular mechanism and their general effect on the replication capacity of HIV 1 drug-resistance-associated mutations is often poorly understood. To elucidate the effect of two such mutations located in a region with a high density of spicing regulatory elements on the HIV-1-splicing outcome, bioinformatic predictions were combined with transfection and infection experiments. Results show that the previously described R263K drug-resistance-associated integrase mutation has additionally a severe effect on the ESE2b splicing regulatory element (SRE) in exon 2b, which causes loss of SD2b recognition. This was confirmed by an R263R silent mutation with a similar predicted effect on the exon 2b SRE. In contrast, a V260I mutation and its silent counterpart with a lower effect on ESS2b did not exhibit any differences in the splicing pattern. Since HIV-1 highly relies on a balanced splicing reaction, changes in the splicing outcome can contribute to changes in viral replication and might add to the effect of escape mutations toward antiviral drugs. Thus, a classification of mutations purely addressing proteins is insufficient.  相似文献   
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Biodegradable porous calcium phosphate (CaP) ceramics are widely used as synthetic graft substitutes for bone regeneration, owing to their chemical and structural similarity to bone and associated bioactivity in terms of bone-bonding, osteoconductive, and even osteoinductive properties. Nevertheless, the intrinsic brittleness and poor processability of porous CaP ceramics strongly impair their clinical applicability. Herein, a biphasic calcium phosphate (BCP) sponge is developed that consists of a self-supporting network of seamlessly interwoven hydroxyapatite nanowires and β-tricalcium phosphate nanofibers and possesses a highly interconnected porous structure with open cell geometry and ultrahigh porosity. Owing to its unique properties, the ceramic sponge can be easily processed into various shapes and dimensions, such as cylindrical scaffolds and thin, flexible membranes. Moreover, the BCP sponge can be introduced into a bone defect in a compacted or folded state from a syringe and, upon wetting, expand to its original shape, thereby filling the cavity. The nanofibrous sponge gradually degrades in vitro and rapidly mineralizes when immersed in simulated body fluid. Moreover, it adsorbs significantly more proteins than a conventional porous BCP ceramic. Finally, the nanofibrous sponge supports the attachment, proliferation, and osteogenic differentiation of human mesenchymal stromal cells comparable to the conventional porous BCP ceramic.  相似文献   
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