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We consider stochastic reaction-diffusion dynamics involved in the formation of a trimeric protein receptor complex, where diffusion is modulated by the presence of small, fixed membrane microdomains. Compartmentalisation of cell membrane signalling proteins may optimise signal transduction but previous modelling work suggests that signalling is only augmented if microdomains are highly mobile. Using a Gillespie algorithm-based spatial numerical simulation, we examine the effect of the presence, size and total coverage of microdomains, which either slow protein diffusion or trap proteins at their boundary. We examine scenarios where protein-protein interactions take place within microdomains, and also where interactions are favoured at the microdomain boundary. This model is motivated by the formation of the high-affinity receptor for the cytokine IL-2. Proliferation requires a threshold number of bound receptors, but pleiotropic effects of IL-2 on other cell types means that high ligand concentrations are undesirable. Hence, optimising T cell sensitivity to IL-2 is essential. In agreement with earlier models, we find that small microdomain sizes result in the greatest augmentation in receptor formation, but that static microdomains can also confer an increased sensitivity in the case of heterotrimeric receptor complex formation. 相似文献
144.
Henderson WA 《The journal of physical chemistry. B》2006,110(26):13177-13183
Phase diagrams are reported for glyme mixtures with simple lithium salts. The glymes studied include monoglyme (DME), diglyme, triglyme, and tetraglyme. The lithium salts include LiBETI, LiAsF6, LiI, LiClO4, LiBF4, LiCF3SO3, LiBr, LiNO3, and LiCF3CO2. The phase diagrams clearly illustrate how solvate formation and thermophysical properties are dictated by the ionic association strength of the salt (i.e., the properties of the anions) and chain length of the solvating molecules. This information provides critical predictive capabilities for solvate formation and ionic interactions common in organometallic reagents and battery electrolytes. 相似文献
145.
Metzger A Diller DJ Lin TH Henderson I Webb ML 《Combinatorial chemistry & high throughput screening》2006,9(5):351-358
Screening of more than 2 million compounds comprising 41 distinct encoded combinatorial libraries revealed a novel structural class of p38 mitogen-activated protein (MAP) kinase inhibitors. The methodology used for screening large encoded combinatorial libraries combined with the statistical interpretation of screening results is described. A strong preference for a particular triaminotriazine aniline amide was discovered based on biological activity observed in the screening campaign. Additional screening of a focused follow-up combinatorial library yielded data expanding the unique combinatorial SAR and emphasizing an extraordinary preference for this particular building block and structural class. The preference is further highlighted when the p38 inhibitor data set is compared to data obtained for a panel of other kinases. 相似文献
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Extremal point properties are examined for the boundary value problem x(n) + ? n-2 i=0 Ai(t)x(i) = 0, x(i)(0) = x(n-2)(T) = 0, 0?i?n-2, where the Ai's, a characterization for the first extremal point is given in terms of the existence of a solution which is positive with respect to a cone in a Banach space. Also, an existence theorem is obtained for a related nonlinear problem 相似文献
148.
In this article, we investigate some classes of semilinear impulsive functional differential inclusions with infinite delay. It is assumed that the linear part is possibly neither densely defined nor it satisfies the Hille–Yosida condition on a Banach space, namely the extrapolated space. Our approach is based on the theory of extrapolation spaces combined with a recent Frigon nonlinear alternative for multivalued admissible contractions in Fréchet spaces. 相似文献
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