Traditionally,parameter design is carried out prior to tolerance design. However, this two-step design strategy cannot guarantee optimal robustness for products' quality. The proposed integrated robust design meth...Traditionally,parameter design is carried out prior to tolerance design. However, this two-step design strategy cannot guarantee optimal robustness for products' quality. The proposed integrated robust design method determined the optimal parameter and tolerance simultaneously by calculating the maximum tolerance region,thereby improving the quality of products. In addition,the proposed method did not need uncertainty analysis to obtain the maximum tolerance region,so that the calculation cost could be decreased. And the method avoided the difficulty of gaining costtolerance function as maximum tolerance region represented both demand of cost and robust. Finally,an amplifier circuit case was conducted for verification purpose. Based on the results, the proposed approach could provide robust solution with optimal maximum tolerance region.展开更多
Let G be a non-abelian group and let l2(G) be a finite dimensional Hilbert space of all complex valued functions for which the elements of G form the (standard) orthonormal basis. In our paper we prove results concern...Let G be a non-abelian group and let l2(G) be a finite dimensional Hilbert space of all complex valued functions for which the elements of G form the (standard) orthonormal basis. In our paper we prove results concerning G-decorrelated decompositions of functions in l2(G). These G-decorrelated decompositions are obtained using the G-convolution either by the irreducible characters of the group G or by an orthogonal projection onto the matrix entries of the irreducible representations of the group G. Applications of these G-decorrelated decompositions are given to crossover designs in clinical trials, in particular the William’s 6×3?design with 3 treatments. In our example, the underlying group is the symmetric group S3.展开更多
In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of...In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.展开更多
基金National Natural Science Foundation of China(No.61304218)
文摘Traditionally,parameter design is carried out prior to tolerance design. However, this two-step design strategy cannot guarantee optimal robustness for products' quality. The proposed integrated robust design method determined the optimal parameter and tolerance simultaneously by calculating the maximum tolerance region,thereby improving the quality of products. In addition,the proposed method did not need uncertainty analysis to obtain the maximum tolerance region,so that the calculation cost could be decreased. And the method avoided the difficulty of gaining costtolerance function as maximum tolerance region represented both demand of cost and robust. Finally,an amplifier circuit case was conducted for verification purpose. Based on the results, the proposed approach could provide robust solution with optimal maximum tolerance region.
文摘Let G be a non-abelian group and let l2(G) be a finite dimensional Hilbert space of all complex valued functions for which the elements of G form the (standard) orthonormal basis. In our paper we prove results concerning G-decorrelated decompositions of functions in l2(G). These G-decorrelated decompositions are obtained using the G-convolution either by the irreducible characters of the group G or by an orthogonal projection onto the matrix entries of the irreducible representations of the group G. Applications of these G-decorrelated decompositions are given to crossover designs in clinical trials, in particular the William’s 6×3?design with 3 treatments. In our example, the underlying group is the symmetric group S3.
基金supported by SIP-IPN,CONACYT (CB-168116)FIS/IMSS (FIS/IMSS/PROT/G11-2/1013)
文摘In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.
