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91.
92.
Current therapies for common types of cancer such as renal cell cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal cancer cells through activation of calcium‐permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (?)‐englerin A. This compound was found to be a highly efficient, fast‐acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high‐affinity extracellular (?)‐englerin A binding site may open up novel opportunities for drug discovery aimed at renal cancer.  相似文献   
93.
The incorporation of non‐proteinogenic amino acids represents a major challenge for the creation of functionalized proteins. The ribosomal pathway is limited to the 20–22 proteinogenic amino acids while nonribosomal peptide synthetases (NRPSs) are able to select from hundreds of different monomers. Introduced herein is a fusion‐protein‐based design for synthetic tRNA‐aminoacylation catalysts based on combining NRPS adenylation domains and a small eukaryotic tRNA‐binding domain (Arc1p‐C). Using rational design, guided by structural insights and molecular modeling, the adenylation domain PheA was fused with Arc1p‐C using flexible linkers and achieved tRNA‐aminoacylation with both proteinogenic and non‐proteinogenic amino acids. The resulting aminoacyl‐tRNAs were functionally validated and the catalysts showed broad substrate specificity towards the acceptor tRNA. Our strategy shows how functional tRNA‐aminoacylation catalysts can be created for bridging the ribosomal and nonribosomal worlds. This opens up new avenues for the aminoacylation of tRNAs with functional non‐proteinogenic amino acids.  相似文献   
94.
This paper presents an efficient two nodes finite element with six degrees of freedom per node, capable to model the total behaviour of a helical spring. The formulation, which includes the shear deformation effects, is based on the assumed forces hybrid approach. The resultant forces approximation verifies exactly the resultant equilibrium equations. The developed model proves its accuracy compared with other elements. This element permits to get the distribution of different stresses along the spring and through the wire surface by only one element.  相似文献   
95.
In this Note we study the effects of the temperature modulation, applied at the horizontal boundaries, on the onset of convection of a horizontal liquid Maxwellian layer. It is assumed that the temperature imposed features a steady component and a time dependent component. To analyse the effect of the temperature modulation, the study is restricted to a linear stability analysis. Thus the Floquet theory and a technique of converting a boundary value problem to an initial value problem are used to solve the system of equations corresponding to the onset of convection. Results obtained may be used to characterize the influence of modulation effects and that of the viscoelastic nature of liquid on the critical Rayleigh number. To cite this article: B. Oukada et al., C. R. Mecanique 334 (2006).  相似文献   
96.
An acoustic numerical code based on Ligthill's analogy is combined with large-eddy simulations techniques in order to evaluate the noise emitted by subsonic (M=0.7) and supersonic (M=1.4) round jets. We show first that, for centerline Mach number M=0.9 and Reynolds number Re=3.6×103, acoustic intensities compare satisfactorily with experimental data of the literature in terms of levels and directivity. Afterwards, high Reynolds number (Re=3.6×104) free and forced jets at Mach 0.7 and 1.4 are studied. Numerical results show that the jet noise intensity depends on the nature of the upstream mixing layer. Indeed, the subsonic jet is 4 dB quieter than the free jet when acting on this shear layer by superposing inlet varicose and flapping perturbations at preferred and first subharmonic frequency, respectively. The maximal acoustic level of the supersonic jet is, on the other hand, 3 dB lower than the free one with a flapping upstream perturbation at the second subharmonic. The results reported in this paper confirm previous works presented in the literature demonstrating that jet noise may be modified according to the inlet conditions. To cite this article: M. Maidi, C. R. Mecanique 334 (2006).  相似文献   
97.
A method improving the evaluation of the stress intensity factor by hybridization of two weight functions is presented and applied to embedded elliptical cracks under various loadings. The hybridization consists in using one or the other function in the zone of the crack where it is the most efficient. The delimitation of the two zones is achieved after optimizing the axes ratio and the curvature radius of the crack. During this optimization we seek to reduce the effects of the singularities present in the weight functions as well as to take better into account the influence of the ellipse curvature. To cite this article: B. El Khalil Hachi et al., C. R. Mecanique 334 (2006).  相似文献   
98.
99.
We consider the following system of fractional differential equations where is the Riemann‐Liouville fractional derivative of order α,f,g : [0,1] × [0, ∞ ) × [0, ∞ ) → [0, ∞ ). Sufficient conditions are provided for the existence of positive solutions to the considered problem. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   
100.
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