Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which l...Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.展开更多
This paper describes the synthesis of robust and non-fragile H∞ state feedback controllers for a class of uncertain jump linear systems with Markovian jumping parameters and state multiplicative noises. Under the ass...This paper describes the synthesis of robust and non-fragile H∞ state feedback controllers for a class of uncertain jump linear systems with Markovian jumping parameters and state multiplicative noises. Under the assumption of a complete access to the norm-bounds of the system uncertainties and controller gain variations, sufficient conditions on the existence of robust stochastic stability and γ-disturbance attenuation H∞ property are presented. A key feature of this scheme is that the gain matrices of controller are only based on It, the observed projection of the current regime rt.展开更多
Fragile X syndrome(FXS)is the most prevalent inherited intellectual disability,resulting from a loss of fragile X mental retardation protein(FMRP).Patients with FXS suffer lifelong cognitive disabilities,but the funct...Fragile X syndrome(FXS)is the most prevalent inherited intellectual disability,resulting from a loss of fragile X mental retardation protein(FMRP).Patients with FXS suffer lifelong cognitive disabilities,but the function of FMRP in the adult brain and the mechanism underlying age-related cognitive decline in FXS is not fully understood.Here,we report that a loss of FMRP results in increased protein synthesis of histone acetyltransferase EP300 and ubiquitinationmediated degradation of histone deacetylase HDAC1 in adult hippocampal neural stem cells(NSCs).Consequently,FMRPdeficient NSCs exhibit elevated histone acetylation and age-related NSC depletion,leading to cognitive impairment in mature adult mice.Reducing histone acetylation rescues both neurogenesis and cognitive deficits in mature adult FMRPdeficient mice.Our work reveals a role for FMRP and histone acetylation in cognition and presents a potential novel ther⁃apeutic strategy for treating adult FXS patients.展开更多
Considering the design problem of non-fragile decentralized H∞ controller with gain variations, the dynamic feedback controller by measurement feedback for uncertain linear systems is constructed and studied. The par...Considering the design problem of non-fragile decentralized H∞ controller with gain variations, the dynamic feedback controller by measurement feedback for uncertain linear systems is constructed and studied. The parameter uncertainties are considered to be unknown but norm bounded. The design procedures are investigated in terms of positive definite solutions to modify algebraic Riccati inequalities. Using information exchange among local controllers, the designed non-fragile decentralized H∞ controllers guarantee that the uncertain closed-loop linear systems are stable and with H∞ -norm bound on disturbance attenuation. A sufficient condition that there are such non-fragile H∞ controllers is obtained by algebraic Riccati inequalities. The approaches to solve modified algebraic Riccati inequalities are carried out preliminarily. Finally, a numerical example to show the validity of the proposed approach is given.展开更多
The design problem of non-fragile estimator is addressed for a class of perturbed linear continuous systems. The perturbations occur on the plant and estimator parameters. The estimator designed should force the error...The design problem of non-fragile estimator is addressed for a class of perturbed linear continuous systems. The perturbations occur on the plant and estimator parameters. The estimator designed should force the error system to achieve the desired decay rate and force the steady error variance less than the specified upper bound irrelevancy of the admissible plant perturbations and estimator perturbations. Consistency problem of the decay rate with the variance upper bound is first considered via linear matrix inequality (LMI) approach. The solution of the estimator parameter under specifications to be consistent is then discussed. The consistency condition of specifications and estimator parameter solution are transformed to feasible or minimum problems subject to a set of LMI respectively. The method is illustrated by a numerical example.展开更多
文摘Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.
基金Supported by National Natural Science Foundation of P. R. China (60274012)
文摘This paper describes the synthesis of robust and non-fragile H∞ state feedback controllers for a class of uncertain jump linear systems with Markovian jumping parameters and state multiplicative noises. Under the assumption of a complete access to the norm-bounds of the system uncertainties and controller gain variations, sufficient conditions on the existence of robust stochastic stability and γ-disturbance attenuation H∞ property are presented. A key feature of this scheme is that the gain matrices of controller are only based on It, the observed projection of the current regime rt.
基金Supported by the Funds for Creative Research Groups of China 60521003）, the State Key Program of National Natural Science of ina （60534010）, National Natural Science Foundation of China （60674021）, the Funds of Ph.D. Program of Ministry of Eduction, China （20060145019）, and the 111 Project （B08015）
文摘过滤有限的词长度(FWL ) 为线性分离时间的系统影响的问题的 nonfragile H 在这份报纸被调查。要设计的过滤器被假定与添加剂获得变化，它在过滤器实现上反映 FWL 效果。结构化的顶点隔板的一个观点被建议处理这个问题并且利用了以一套线性矩阵不平等(LMI ) 为 nonfragile H 过滤器设计开发足够的条件。设计使扩充系统变为 asymptotically 稳定并且保证 H 变细水平不到规定水平。一个数字例子被给说明建议方法的效果。
基金Supported by National Basic Research Program of China （973 Program） （2009CB320604）, the State Key Program of National Natural Science Foundation of China （60534010）, National Natural Science Foundation of China （60674021）, the Funds for Creative Research Groups of China （60821063）, the 111 Project （B08015）, and the Funds of Doctoral Program of Ministry of Education, China （20060145019）
文摘Fragile X syndrome(FXS)is the most prevalent inherited intellectual disability,resulting from a loss of fragile X mental retardation protein(FMRP).Patients with FXS suffer lifelong cognitive disabilities,but the function of FMRP in the adult brain and the mechanism underlying age-related cognitive decline in FXS is not fully understood.Here,we report that a loss of FMRP results in increased protein synthesis of histone acetyltransferase EP300 and ubiquitinationmediated degradation of histone deacetylase HDAC1 in adult hippocampal neural stem cells(NSCs).Consequently,FMRPdeficient NSCs exhibit elevated histone acetylation and age-related NSC depletion,leading to cognitive impairment in mature adult mice.Reducing histone acetylation rescues both neurogenesis and cognitive deficits in mature adult FMRPdeficient mice.Our work reveals a role for FMRP and histone acetylation in cognition and presents a potential novel ther⁃apeutic strategy for treating adult FXS patients.
基金the National Natural Science Foundation of China (60674019).
文摘Considering the design problem of non-fragile decentralized H∞ controller with gain variations, the dynamic feedback controller by measurement feedback for uncertain linear systems is constructed and studied. The parameter uncertainties are considered to be unknown but norm bounded. The design procedures are investigated in terms of positive definite solutions to modify algebraic Riccati inequalities. Using information exchange among local controllers, the designed non-fragile decentralized H∞ controllers guarantee that the uncertain closed-loop linear systems are stable and with H∞ -norm bound on disturbance attenuation. A sufficient condition that there are such non-fragile H∞ controllers is obtained by algebraic Riccati inequalities. The approaches to solve modified algebraic Riccati inequalities are carried out preliminarily. Finally, a numerical example to show the validity of the proposed approach is given.
文摘The design problem of non-fragile estimator is addressed for a class of perturbed linear continuous systems. The perturbations occur on the plant and estimator parameters. The estimator designed should force the error system to achieve the desired decay rate and force the steady error variance less than the specified upper bound irrelevancy of the admissible plant perturbations and estimator perturbations. Consistency problem of the decay rate with the variance upper bound is first considered via linear matrix inequality (LMI) approach. The solution of the estimator parameter under specifications to be consistent is then discussed. The consistency condition of specifications and estimator parameter solution are transformed to feasible or minimum problems subject to a set of LMI respectively. The method is illustrated by a numerical example.
