The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great cha...The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.展开更多
International cooperation is vital for the polar regions.China’s past polar cooperation has tended to focus on intergovernmental and bilateral mechanisms rather than regional cooperation.However,regional and subregio...International cooperation is vital for the polar regions.China’s past polar cooperation has tended to focus on intergovernmental and bilateral mechanisms rather than regional cooperation.However,regional and subregional cooperation is playing an increasing role in the polar regions with the rapid development of geopolitics and global climate change.Involvement in three subregional polar organizations—the Asian Forum for Polar Sciences(AFoPS),the Pacific Arctic Group(PAG),and the China-Nordic Arctic Research Center(CNARC)—in the last two decades reflects China’s improved skills and flexibility in participating in international polar cooperation and represents an exercise in the“win-win”principle under China’s Arctic policy.This paper presents a review of the development of polar subregional cooperation,examines China’s participation in three of subregional organizations and provides feasible suggestions for China’s future engagement with these organizations.展开更多
Impact processes between flexible bodies often lead to local stress concentration and wave propagation of high frequency. Therefore, the modeling of flexible multibody systems involving impact should consider the loca...Impact processes between flexible bodies often lead to local stress concentration and wave propagation of high frequency. Therefore, the modeling of flexible multibody systems involving impact should consider the local plastic deformation and the strict requirements of the spatial discretization. Owing to the nonlinearity of the stiffness matrix, the reduction of the element number is extremely important. For the contact-impact problem, since different regions have different requirements regarding the element size, a new subregion mesh method is proposed to reduce the number of the unnecessary elements. A dynamic model for flexible multibody systems with elastic-plastic contact impact is established based on a floating frame of reference formulation and complete Lagrange incremental nonlinear finite-element method to investigate the effect of the elastic-plastic deformation as well as spatial discretization. Experiments on the impact between two bodies are carried out to validate the correctness of the elastic-plastic model. The proposed formulation is applied to a slider-crank system with elastic-plastic impact.展开更多
The general features of the seasonal suuface heat budget in the tropical western Pacific Ocean,20°S-20°N, western boundary-160°E, were documented by Qu (1995) using a high-resolution generalcirculation ...The general features of the seasonal suuface heat budget in the tropical western Pacific Ocean,20°S-20°N, western boundary-160°E, were documented by Qu (1995) using a high-resolution generalcirculation model (GCM, Semtner & Chervin,1992) ard existing observations.Close inspection of thesmaller areas, with the whole region further partitioned into six parts, showed different mechanisms balancethe seasonal surface heat budget in different parts of the region The results of study on five subregionsare detailed in this article. In the equatorial (3°S - 3°N) aed North Equatorial Countercurrent(3°N-9°N) region, the surface the flux the does not change significantly throughout the year, so the surface heat content is determined largely by vertical motion near the equator and roughly helf due to horizontal and halfdue to vertical circulation in the region of the North Equatorial Countercurrent(NECC). In the othersubregions (9°N-20°N, 20°S -11°S aed 11°S -3°S ), however, in addition to ocean展开更多
In this paper, the solution to the structure consisting of a bead and a board is given as a result of the application of the subregion function method which was suggested in ref. [1]. The same problem is also computed...In this paper, the solution to the structure consisting of a bead and a board is given as a result of the application of the subregion function method which was suggested in ref. [1]. The same problem is also computed with finite element method. The comparison between the two results shows that the application of the subregion function in the method of weighted residuals is practical and effective, especially for solving compound structures.展开更多
We present a class of preconditioners for the linear systems resulting from a finite element or discontinuous Galerkin discretizations of advection-dominated problems.These preconditioners are designed to treat the ca...We present a class of preconditioners for the linear systems resulting from a finite element or discontinuous Galerkin discretizations of advection-dominated problems.These preconditioners are designed to treat the case of geometrically localized stiffness,where the convergence rates of iterative methods are degraded in a localized subregion of the mesh.Slower convergence may be caused by a number of factors,including the mesh size,anisotropy,highly variable coefficients,and more challenging physics.The approach taken in this work is to correct well-known preconditioners such as the block Jacobi and the block incomplete LU(ILU)with an adaptive inner subregion iteration.The goal of these preconditioners is to reduce the number of costly global iterations by accelerating the convergence in the stiff region by iterating on the less expensive reduced problem.The tolerance for the inner iteration is adaptively chosen to minimize subregion-local work while guaranteeing global convergence rates.We present analysis showing that the convergence of these preconditioners,even when combined with an adaptively selected tolerance,is independent of discretization parameters(e.g.,the mesh size and diffusion coefficient)in the subregion.We demonstrate significant performance improvements over black-box preconditioners when applied to several model convection-diffusion problems.Finally,we present performance results of several variations of iterative subregion correction preconditioners applied to the Reynolds number 2.25×10^(6)fluid flow over the NACA 0012 airfoil,as well as massively separated flow at 30°angle of attack.展开更多
The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippoca...The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.展开更多
基金supported by the Distinguished Professor Project of Liaoning Province.
文摘The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.
文摘International cooperation is vital for the polar regions.China’s past polar cooperation has tended to focus on intergovernmental and bilateral mechanisms rather than regional cooperation.However,regional and subregional cooperation is playing an increasing role in the polar regions with the rapid development of geopolitics and global climate change.Involvement in three subregional polar organizations—the Asian Forum for Polar Sciences(AFoPS),the Pacific Arctic Group(PAG),and the China-Nordic Arctic Research Center(CNARC)—in the last two decades reflects China’s improved skills and flexibility in participating in international polar cooperation and represents an exercise in the“win-win”principle under China’s Arctic policy.This paper presents a review of the development of polar subregional cooperation,examines China’s participation in three of subregional organizations and provides feasible suggestions for China’s future engagement with these organizations.
基金supported by the National Natural Science Foundation of China (Grants 11132007, 11272203)
文摘Impact processes between flexible bodies often lead to local stress concentration and wave propagation of high frequency. Therefore, the modeling of flexible multibody systems involving impact should consider the local plastic deformation and the strict requirements of the spatial discretization. Owing to the nonlinearity of the stiffness matrix, the reduction of the element number is extremely important. For the contact-impact problem, since different regions have different requirements regarding the element size, a new subregion mesh method is proposed to reduce the number of the unnecessary elements. A dynamic model for flexible multibody systems with elastic-plastic contact impact is established based on a floating frame of reference formulation and complete Lagrange incremental nonlinear finite-element method to investigate the effect of the elastic-plastic deformation as well as spatial discretization. Experiments on the impact between two bodies are carried out to validate the correctness of the elastic-plastic model. The proposed formulation is applied to a slider-crank system with elastic-plastic impact.
基金This study was supported by the Australial CSIRO Division of Oceanographythe National Natural Science Foundation of China (No.49176255)
文摘The general features of the seasonal suuface heat budget in the tropical western Pacific Ocean,20°S-20°N, western boundary-160°E, were documented by Qu (1995) using a high-resolution generalcirculation model (GCM, Semtner & Chervin,1992) ard existing observations.Close inspection of thesmaller areas, with the whole region further partitioned into six parts, showed different mechanisms balancethe seasonal surface heat budget in different parts of the region The results of study on five subregionsare detailed in this article. In the equatorial (3°S - 3°N) aed North Equatorial Countercurrent(3°N-9°N) region, the surface the flux the does not change significantly throughout the year, so the surface heat content is determined largely by vertical motion near the equator and roughly helf due to horizontal and halfdue to vertical circulation in the region of the North Equatorial Countercurrent(NECC). In the othersubregions (9°N-20°N, 20°S -11°S aed 11°S -3°S ), however, in addition to ocean
文摘In this paper, the solution to the structure consisting of a bead and a board is given as a result of the application of the subregion function method which was suggested in ref. [1]. The same problem is also computed with finite element method. The comparison between the two results shows that the application of the subregion function in the method of weighted residuals is practical and effective, especially for solving compound structures.
文摘We present a class of preconditioners for the linear systems resulting from a finite element or discontinuous Galerkin discretizations of advection-dominated problems.These preconditioners are designed to treat the case of geometrically localized stiffness,where the convergence rates of iterative methods are degraded in a localized subregion of the mesh.Slower convergence may be caused by a number of factors,including the mesh size,anisotropy,highly variable coefficients,and more challenging physics.The approach taken in this work is to correct well-known preconditioners such as the block Jacobi and the block incomplete LU(ILU)with an adaptive inner subregion iteration.The goal of these preconditioners is to reduce the number of costly global iterations by accelerating the convergence in the stiff region by iterating on the less expensive reduced problem.The tolerance for the inner iteration is adaptively chosen to minimize subregion-local work while guaranteeing global convergence rates.We present analysis showing that the convergence of these preconditioners,even when combined with an adaptively selected tolerance,is independent of discretization parameters(e.g.,the mesh size and diffusion coefficient)in the subregion.We demonstrate significant performance improvements over black-box preconditioners when applied to several model convection-diffusion problems.Finally,we present performance results of several variations of iterative subregion correction preconditioners applied to the Reynolds number 2.25×10^(6)fluid flow over the NACA 0012 airfoil,as well as massively separated flow at 30°angle of attack.
基金supported by the National Natural Science Foundation of China (30825014,81061120529,30970814,81371488,91132727 and 30830046)the Key Program for Clinical Medicine and Science and Technology,Jiangsu Provincial Clinical Medical Research Center,China (BL2013025)
文摘The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.
