As competition in the market for discrete part prod uc ts gets harder and harder the requirements for extreme manufacturing operati on efficiencies get increasingly accentuated. Therefore requirements for well behaved...As competition in the market for discrete part prod uc ts gets harder and harder the requirements for extreme manufacturing operati on efficiencies get increasingly accentuated. Therefore requirements for well behaved manufacturing operation control get more and more significant. The purpose of the paper is to establish a framework for development of formal m ethods for design of systems for simultaneous control of continuous manufacturin g task processes and resource allocation of discrete part manufacturing. In the paper states which are needed for feedback control of continuous manufact uring task processes are defined and an example is presented. States which are necessary for feedback control of distribution of manufacturing resources are defined. The definition is based on the states defined for feedba ck control of the continuous processes of discrete part manufacturing tasks. An exemple is presented. Based on use of the state variables two types of equations are described, the pu rpose of which it is to represent the constraints to which control of the manufa cturing system is subject. Characteristic instances of the equations are presen ted. Methods for design of systems which can control continuous tasks are presented. Methods for design of systems which can control resource allocation are presente d. Methods for design of systems which can simultaneously control continuous tas k processes and resource allocation as the resource allocation is subject to con tinuos task execution constraints are presented.展开更多
OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research...OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research⁃es have reported that hypoglycosylation ofα-DG is associated with the pathophysiology of diseas⁃es,especially muscular dystrophy,but little is known about major depressive disorder(MDD).Like-acetylglucosaminyl transferase(Large)is a key enzyme for glycosylation ofα-DG,which mainly modifies two points in the middle domain ofα-DG:Thr-317 and Thr-319.Glycosylatedα-DG(GLY-α-DG)can bind with high affinity to extracellular matrix(ECM)molecules that con⁃tain laminin globular(LG)domains,including per⁃lecan,agrin and neurexin.Agrin is mainly derived from neurons rather than glial cells.In cultured hippocampal neurons,it was found that agrin could regulate the homeostatic plasticity of inhibi⁃tory neurons by acting on GLY-α-DG.Mdx mice are transgenetic models for the investigation of Duchenne muscular dystrophy.Many studies have shown that the expression of GLY-α-DG in the peripheral and brain tissues of Mdx mice is significantly down-regulated.Mdx mice show cognitive impairment and high levels of anxiety.In this study,we employed chronic social defeat stress(CSDS)to establish an animal model of depression and detected the expression of GLY-α-DG among the brain areas associated with the pathophysiology of depression.METHODS So⁃cial interaction test(SIT)and sucrose preference test(SPT)were used to evaluate depressive-like behavior.Open field(OF)and elevated plus maze(EPM)test were used to determine the anxiety-like behavior of Mdx mice.Novelty-sup⁃pressed feeding test(NSFT)forced swim test(FST)and tail suspension test(TST)were used to detect the depressive-like behavior of Mdx mice.Novel object recognition test(NOR)was applied to evaluate the cognition of Mdx mice.Subthreshold social defeat stress was used to explore the susceptibility to stress in Mdx mice.Stereotactic infusion of agrin into the ventral hippocampus(vHip),FST and TST were used to investigate the antidepressant effects of agrin.Adeno-associated virus(AAV)-mediated overex⁃pression techniques,behavior tests and whole-cell path-clamp technique were conducted to determine the impact of Large overexpression on CSDS susceptible mice.RESULTS The expres⁃sion ofα-DG and GLY-α-DG were significantly decreased in the vHip of CSDS susceptible mice.Mdx mice showed decreased expression of GLY-α-DG and increased anxiety-like behav⁃iors.Mdx mice displayed some depressive-like behaviors,and the susceptibility to stress was significantly increased.Downregulation of the expressionα-DG in the vHip by lentivirus increased the susceptibility to stress.Administra⁃tion of agrin to CSDS susceptible mice exerted antidepressant effects,and this effect could par⁃tially sustain for a week.The expression of Large was decreased in vHip.Overexpression of Large through AAV-Large reversed the depressive-like behaviors and restored the decreased frequency and amplitude of mIPSC.CONCLUSION GLY-α-DG and its glycosylase are significantly decreased in CSDS susceptible mice.Adminis⁃tration of agrin and overexpression of Large displays antidepressant effect,which may be related to its promotion of inhibitory synaptic transmission.展开更多
文摘As competition in the market for discrete part prod uc ts gets harder and harder the requirements for extreme manufacturing operati on efficiencies get increasingly accentuated. Therefore requirements for well behaved manufacturing operation control get more and more significant. The purpose of the paper is to establish a framework for development of formal m ethods for design of systems for simultaneous control of continuous manufacturin g task processes and resource allocation of discrete part manufacturing. In the paper states which are needed for feedback control of continuous manufact uring task processes are defined and an example is presented. States which are necessary for feedback control of distribution of manufacturing resources are defined. The definition is based on the states defined for feedba ck control of the continuous processes of discrete part manufacturing tasks. An exemple is presented. Based on use of the state variables two types of equations are described, the pu rpose of which it is to represent the constraints to which control of the manufa cturing system is subject. Characteristic instances of the equations are presen ted. Methods for design of systems which can control continuous tasks are presented. Methods for design of systems which can control resource allocation are presente d. Methods for design of systems which can simultaneously control continuous tas k processes and resource allocation as the resource allocation is subject to con tinuos task execution constraints are presented.
文摘OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research⁃es have reported that hypoglycosylation ofα-DG is associated with the pathophysiology of diseas⁃es,especially muscular dystrophy,but little is known about major depressive disorder(MDD).Like-acetylglucosaminyl transferase(Large)is a key enzyme for glycosylation ofα-DG,which mainly modifies two points in the middle domain ofα-DG:Thr-317 and Thr-319.Glycosylatedα-DG(GLY-α-DG)can bind with high affinity to extracellular matrix(ECM)molecules that con⁃tain laminin globular(LG)domains,including per⁃lecan,agrin and neurexin.Agrin is mainly derived from neurons rather than glial cells.In cultured hippocampal neurons,it was found that agrin could regulate the homeostatic plasticity of inhibi⁃tory neurons by acting on GLY-α-DG.Mdx mice are transgenetic models for the investigation of Duchenne muscular dystrophy.Many studies have shown that the expression of GLY-α-DG in the peripheral and brain tissues of Mdx mice is significantly down-regulated.Mdx mice show cognitive impairment and high levels of anxiety.In this study,we employed chronic social defeat stress(CSDS)to establish an animal model of depression and detected the expression of GLY-α-DG among the brain areas associated with the pathophysiology of depression.METHODS So⁃cial interaction test(SIT)and sucrose preference test(SPT)were used to evaluate depressive-like behavior.Open field(OF)and elevated plus maze(EPM)test were used to determine the anxiety-like behavior of Mdx mice.Novelty-sup⁃pressed feeding test(NSFT)forced swim test(FST)and tail suspension test(TST)were used to detect the depressive-like behavior of Mdx mice.Novel object recognition test(NOR)was applied to evaluate the cognition of Mdx mice.Subthreshold social defeat stress was used to explore the susceptibility to stress in Mdx mice.Stereotactic infusion of agrin into the ventral hippocampus(vHip),FST and TST were used to investigate the antidepressant effects of agrin.Adeno-associated virus(AAV)-mediated overex⁃pression techniques,behavior tests and whole-cell path-clamp technique were conducted to determine the impact of Large overexpression on CSDS susceptible mice.RESULTS The expres⁃sion ofα-DG and GLY-α-DG were significantly decreased in the vHip of CSDS susceptible mice.Mdx mice showed decreased expression of GLY-α-DG and increased anxiety-like behav⁃iors.Mdx mice displayed some depressive-like behaviors,and the susceptibility to stress was significantly increased.Downregulation of the expressionα-DG in the vHip by lentivirus increased the susceptibility to stress.Administra⁃tion of agrin to CSDS susceptible mice exerted antidepressant effects,and this effect could par⁃tially sustain for a week.The expression of Large was decreased in vHip.Overexpression of Large through AAV-Large reversed the depressive-like behaviors and restored the decreased frequency and amplitude of mIPSC.CONCLUSION GLY-α-DG and its glycosylase are significantly decreased in CSDS susceptible mice.Adminis⁃tration of agrin and overexpression of Large displays antidepressant effect,which may be related to its promotion of inhibitory synaptic transmission.
