The urban transit fare structure and level can largely affect passengers’travel behavior and route choices.The commonly used transit fare policies in the present transit network would lead to the unbalanced transit a...The urban transit fare structure and level can largely affect passengers’travel behavior and route choices.The commonly used transit fare policies in the present transit network would lead to the unbalanced transit assignment and improper transit resources distribution.In order to distribute transit passenger flow evenly and efficiently,this paper introduces a new distance-based fare pattern with Euclidean distance.A bi-level programming model is developed for determining the optimal distance-based fare pattern,with the path-based stochastic transit assignment(STA)problem with elastic demand being proposed at the lower level.The upper-level intends to address a principal-agent game between transport authorities and transit enterprises pursing maximization of social welfare and financial interest,respectively.A genetic algorithm(GA)is implemented to solve the bi-level model,which is verified by a numerical example to illustrate that the proposed nonlinear distance-based fare pattern presents a better financial performance and distribution effect than other fare structures.展开更多
An algorithm is proposed in this paper for solving two-dimensional bi-level linear programming problems without making a graph. Based on the classification of constraints, algorithm removes all redundant constraints, ...An algorithm is proposed in this paper for solving two-dimensional bi-level linear programming problems without making a graph. Based on the classification of constraints, algorithm removes all redundant constraints, which eliminate the possibility of cycling and the solution of the problem is reached in a finite number of steps. Example to illustrate the method is also included in the paper.展开更多
Considering the decision-making variables of the capacities of branch roads and the optimization targets of lowering the saturation of arterial roads and the reconstruction expense of branch roads, the bi-level progra...Considering the decision-making variables of the capacities of branch roads and the optimization targets of lowering the saturation of arterial roads and the reconstruction expense of branch roads, the bi-level programming model for reconstructing the branch roads was set up. The upper level model was for determining the enlarged capacities of the branch roads, and the lower level model was for calculating the flows of road sections via the user equilibrium traffic assignment method. The genetic algorithm for solving the bi-level model was designed to obtain the reconstruction capacities of the branch roads. The results show that by the bi-level model and its algorithm, the optimum scheme of urban branch roads reconstruction can be gained, which reduces the saturation of arterial roads apparently, and alleviates traffic congestion. In the data analysis the arterial saturation decreases from 1.100 to 0.996, which verifies the micro-circulation transportation's function of urban branch road network.展开更多
In silico approaches for metabolites optimization have been derived from the flood of sequenced and annotated genomes. However, there exist still numerous degrees of freedom in terms of optimization algorithm approach...In silico approaches for metabolites optimization have been derived from the flood of sequenced and annotated genomes. However, there exist still numerous degrees of freedom in terms of optimization algorithm approaches that can be exploited in order to enhance yield of processes which are based on biological reactions. Here, we propose an evolutionary approach aiming to suggest different mutant for augmenting ethanol yield using glycerol as substrate in Escherichia coli. We found that this algorithm, even though is far from providing the global optimum, is able to uncover genes that a global optimizer would be incapable of. By over-expressing accB, eno, dapE, and accA mutants in ethanol production was augmented up to 2 fold compared to its counterpart E. coli BW25113.展开更多
Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and ...Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence.展开更多
Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site....Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.展开更多
Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutic...Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.展开更多
Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c...Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.展开更多
Stochastic unit commitment is one of the most powerful methods to address uncertainty. However, the existingscenario clustering technique for stochastic unit commitment cannot accurately select representative scenario...Stochastic unit commitment is one of the most powerful methods to address uncertainty. However, the existingscenario clustering technique for stochastic unit commitment cannot accurately select representative scenarios,which threatens the robustness of stochastic unit commitment and hinders its application. This paper providesa stochastic unit commitment with dynamic scenario clustering based on multi-parametric programming andBenders decomposition. The stochastic unit commitment is solved via the Benders decomposition, which decouplesthe primal problem into the master problem and two types of subproblems. In the master problem, the committedgenerator is determined, while the feasibility and optimality of generator output are checked in these twosubproblems. Scenarios are dynamically clustered during the subproblem solution process through the multiparametric programming with respect to the solution of the master problem. In other words, multiple scenariosare clustered into several representative scenarios after the subproblem is solved, and the Benders cut obtainedby the representative scenario is generated for the master problem. Different from the conventional stochasticunit commitment, the proposed approach integrates scenario clustering into the Benders decomposition solutionprocess. Such a clustering approach could accurately cluster representative scenarios that have impacts on theunit commitment. The proposed method is tested on a 6-bus system and the modified IEEE 118-bus system.Numerical results illustrate the effectiveness of the proposed method in clustering scenarios. Compared withthe conventional clustering method, the proposed method can accurately select representative scenarios whilemitigating computational burden, thus guaranteeing the robustness of unit commitment.展开更多
Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinea...Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinear and combinatorial nature of the HEN problem,it is not easy to find solutions of high quality for large-scale problems.The reinforcement learning(RL)method,which learns strategies through ongoing exploration and exploitation,reveals advantages in such area.However,due to the complexity of the HEN design problem,the RL method for HEN should be dedicated and designed.A hybrid strategy combining RL with mathematical programming is proposed to take better advantage of both methods.An insightful state representation of the HEN structure as well as a customized reward function is introduced.A Q-learning algorithm is applied to update the HEN structure using theε-greedy strategy.Better results are obtained from three literature cases of different scales.展开更多
Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conv...Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems.In this study,a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model(ROM)and probabilistic programming.The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems.Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering.A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution.The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty.Then,a slope case was employed to demonstrate the performance of the developed framework.The results prove that the proposed framework provides a scientific,feasible,and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.展开更多
Genetic Programming (GP) is an important approach to deal with complex problem analysis and modeling, and has been applied in a wide range of areas. The development of GP involves various aspects, including design of ...Genetic Programming (GP) is an important approach to deal with complex problem analysis and modeling, and has been applied in a wide range of areas. The development of GP involves various aspects, including design of genetic operators, evolutionary controls and implementations of heuristic strategy, evaluations and other mechanisms. When designing genetic operators, it is necessary to consider the possible limitations of encoding methods of individuals. And when selecting evolutionary control strategies, it is also necessary to balance search efficiency and diversity based on representation characteristics as well as the problem itself. More importantly, all of these matters, among others, have to be implemented through tedious coding work. Therefore, GP development is both complex and time-consuming. To overcome some of these difficulties that hinder the enhancement of GP development efficiency, we explore the feasibility of mutual assistance among GP variants, and then propose a rapid GP prototyping development method based on πGrammatical Evolution (πGE). It is demonstrated through regression analysis experiments that not only is this method beneficial for the GP developers to get rid of some tedious implementations, but also enables them to concentrate on the essence of the referred problem, such as individual representation, decoding means and evaluation. Additionally, it provides new insights into the roles of individual delineations in phenotypes and semantic research of individuals.展开更多
In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed metho...In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.展开更多
This paper presents a new dimension reduction strategy for medium and large-scale linear programming problems. The proposed method uses a subset of the original constraints and combines two algorithms: the weighted av...This paper presents a new dimension reduction strategy for medium and large-scale linear programming problems. The proposed method uses a subset of the original constraints and combines two algorithms: the weighted average and the cosine simplex algorithm. The first approach identifies binding constraints by using the weighted average of each constraint, whereas the second algorithm is based on the cosine similarity between the vector of the objective function and the constraints. These two approaches are complementary, and when used together, they locate the essential subset of initial constraints required for solving medium and large-scale linear programming problems. After reducing the dimension of the linear programming problem using the subset of the essential constraints, the solution method can be chosen from any suitable method for linear programming. The proposed approach was applied to a set of well-known benchmarks as well as more than 2000 random medium and large-scale linear programming problems. The results are promising, indicating that the new approach contributes to the reduction of both the size of the problems and the total number of iterations required. A tree-based classification model also confirmed the need for combining the two approaches. A detailed numerical example, the general numerical results, and the statistical analysis for the decision tree procedure are presented.展开更多
This study embarks on a comprehensive examination of optimization techniques within GPU-based parallel programming models,pivotal for advancing high-performance computing(HPC).Emphasizing the transition of GPUs from g...This study embarks on a comprehensive examination of optimization techniques within GPU-based parallel programming models,pivotal for advancing high-performance computing(HPC).Emphasizing the transition of GPUs from graphic-centric processors to versatile computing units,it delves into the nuanced optimization of memory access,thread management,algorithmic design,and data structures.These optimizations are critical for exploiting the parallel processing capabilities of GPUs,addressingboth the theoretical frameworks and practical implementations.By integrating advanced strategies such as memory coalescing,dynamic scheduling,and parallel algorithmic transformations,this research aims to significantly elevate computational efficiency and throughput.The findings underscore the potential of optimized GPU programming to revolutionize computational tasks across various domains,highlighting a pathway towards achieving unparalleled processing power and efficiency in HPC environments.The paper not only contributes to the academic discourse on GPU optimization but also provides actionable insights for developers,fostering advancements in computational sciences and technology.展开更多
This paper presents an adaptive path planner for unmanned aerial vehicles (UAVs) to adapt a real-time path search procedure to variations and fluctuations of UAVs’ relevant performances, with respect to sensory cap...This paper presents an adaptive path planner for unmanned aerial vehicles (UAVs) to adapt a real-time path search procedure to variations and fluctuations of UAVs’ relevant performances, with respect to sensory capability, maneuverability, and flight velocity limit. On the basis of a novel adaptability-involved problem statement, bi-level programming (BLP) and variable planning step techniques are introduced to model the necessary path planning components and then an adaptive path planner is developed for the purpose of adaptation and optimization. Additionally, both probabilistic-risk-based obstacle avoidance and performance limits are described as path search constraints to guarantee path safety and navigability. A discrete-search-based path planning solution, embedded with four optimization strategies, is especially designed for the planner to efficiently generate optimal flight paths in complex operational spaces, within which different surface-to-air missiles (SAMs) are deployed. Simulation results in challenging and stochastic scenarios firstly demonstrate the effectiveness and efficiency of the proposed planner, and then verify its great adaptability and relative stability when planning optimal paths for a UAV with changing or fluctuating performances.展开更多
Home health care(HHC)includes a wide range of healthcare services that are performed in customers'homes to help them recover.With the constantly increasing demand for health care,HHC policymakers are eager to addr...Home health care(HHC)includes a wide range of healthcare services that are performed in customers'homes to help them recover.With the constantly increasing demand for health care,HHC policymakers are eager to address routing and scheduling problems from the perspective of optimization.In this paper,a bi-level programming model for HHC routing and scheduling problems with stochastic travel times is proposed,in which the degree of satisfaction with the visit time is simultaneously considered.The upper-level model is formulated for customer assignment with the aim of minimizing the total operating cost,and the lower-level model is formulated as a routing problem to maximize the degree of satisfaction with the visit time.Consistent with Stackelberg game decision-making,the trade-off relationship between these two objectives can be achieved spontaneously so as to reach an equilibrium state.A three-stage hybrid algorithm combining an iterated local search framework,which uses a large neighborhood search procedure as a sub-heuristic,a set-partitioning model,and a post-optimization method is developed to solve the proposed model.Numerical experiments on a set of instances including 10 to 100 customers verify the effectiveness of the proposed model and algorithm.展开更多
The distributed hybrid processing optimization problem of non-cooperative targets is an important research direction for future networked air-defense and anti-missile firepower systems. In this paper, the air-defense ...The distributed hybrid processing optimization problem of non-cooperative targets is an important research direction for future networked air-defense and anti-missile firepower systems. In this paper, the air-defense anti-missile targets defense problem is abstracted as a nonconvex constrained combinatorial optimization problem with the optimization objective of maximizing the degree of contribution of the processing scheme to non-cooperative targets, and the constraints mainly consider geographical conditions and anti-missile equipment resources. The grid discretization concept is used to partition the defense area into network nodes, and the overall defense strategy scheme is described as a nonlinear programming problem to solve the minimum defense cost within the maximum defense capability of the defense system network. In the solution of the minimum defense cost problem, the processing scheme, equipment coverage capability, constraints and node cost requirements are characterized, then a nonlinear mathematical model of the non-cooperative target distributed hybrid processing optimization problem is established, and a local optimal solution based on the sequential quadratic programming algorithm is constructed, and the optimal firepower processing scheme is given by using the sequential quadratic programming method containing non-convex quadratic equations and inequality constraints. Finally, the effectiveness of the proposed method is verified by simulation examples.展开更多
Cell replacement therapy has long been proposed as a treatment for the damaged nervous system.One of the most challenging aspects of such a strategy,however,is finding sources of donor cells for transplantation.Autolo...Cell replacement therapy has long been proposed as a treatment for the damaged nervous system.One of the most challenging aspects of such a strategy,however,is finding sources of donor cells for transplantation.Autologous neural cells are rarely an option as every cell in the nervous system has a defined function that would be lost if that cell was to be removed.One possibility would be sourcing precursor or differentiated cells from fetal tissues;however,aside from ethical issues,heterologous cells are at risk of immunological rejection in the long term.Methodological improvements over the past 15 years have led to the possibility that autologous non-neural cells could be used for cell transplantation through their conversion into neural derivatives.展开更多
Introduction:Ever since the discovery of neural stem cells(NSCs)in the adult mammalian brain,scientists have been trying to decipher which signals govern their turnover and lineage commitment to generate neurons and g...Introduction:Ever since the discovery of neural stem cells(NSCs)in the adult mammalian brain,scientists have been trying to decipher which signals govern their turnover and lineage commitment to generate neurons and glia.Understanding their role in nervous tissue homeostasis can provide new insights into the etiology of several neurological disorders,and might one day be turned to our advantage to promote endogenous brain injury repair.Others and we have identified thyroid hormone(TH)as a key factor transcriptionally regulating NSC behavior in the largest niche of the adult mammalian brain:the subventricular zone(SVZ).展开更多
基金the Humanities and Social Science Foundation of the Ministry of Education of China(Grant No.20YJCZH121).
文摘The urban transit fare structure and level can largely affect passengers’travel behavior and route choices.The commonly used transit fare policies in the present transit network would lead to the unbalanced transit assignment and improper transit resources distribution.In order to distribute transit passenger flow evenly and efficiently,this paper introduces a new distance-based fare pattern with Euclidean distance.A bi-level programming model is developed for determining the optimal distance-based fare pattern,with the path-based stochastic transit assignment(STA)problem with elastic demand being proposed at the lower level.The upper-level intends to address a principal-agent game between transport authorities and transit enterprises pursing maximization of social welfare and financial interest,respectively.A genetic algorithm(GA)is implemented to solve the bi-level model,which is verified by a numerical example to illustrate that the proposed nonlinear distance-based fare pattern presents a better financial performance and distribution effect than other fare structures.
文摘An algorithm is proposed in this paper for solving two-dimensional bi-level linear programming problems without making a graph. Based on the classification of constraints, algorithm removes all redundant constraints, which eliminate the possibility of cycling and the solution of the problem is reached in a finite number of steps. Example to illustrate the method is also included in the paper.
基金Project(2006CB705507) supported by the National Basic Research and Development Program of ChinaProject(20060533036) supported by the Specialized Research Foundation for the Doctoral Program of Higher Education of China
文摘Considering the decision-making variables of the capacities of branch roads and the optimization targets of lowering the saturation of arterial roads and the reconstruction expense of branch roads, the bi-level programming model for reconstructing the branch roads was set up. The upper level model was for determining the enlarged capacities of the branch roads, and the lower level model was for calculating the flows of road sections via the user equilibrium traffic assignment method. The genetic algorithm for solving the bi-level model was designed to obtain the reconstruction capacities of the branch roads. The results show that by the bi-level model and its algorithm, the optimum scheme of urban branch roads reconstruction can be gained, which reduces the saturation of arterial roads apparently, and alleviates traffic congestion. In the data analysis the arterial saturation decreases from 1.100 to 0.996, which verifies the micro-circulation transportation's function of urban branch road network.
基金the support of the National BioResource Project(NIG,Japan):E.coli Strain for kindly providing us with the Keio Collection using for our experimental sectionAlso this work is funded by Vicerrectoria de investigaciones at Universidad de los Andes.
文摘In silico approaches for metabolites optimization have been derived from the flood of sequenced and annotated genomes. However, there exist still numerous degrees of freedom in terms of optimization algorithm approaches that can be exploited in order to enhance yield of processes which are based on biological reactions. Here, we propose an evolutionary approach aiming to suggest different mutant for augmenting ethanol yield using glycerol as substrate in Escherichia coli. We found that this algorithm, even though is far from providing the global optimum, is able to uncover genes that a global optimizer would be incapable of. By over-expressing accB, eno, dapE, and accA mutants in ethanol production was augmented up to 2 fold compared to its counterpart E. coli BW25113.
基金supported in part by the National Natural Science Foundation of China(62222301, 62073085, 62073158, 61890930-5, 62021003)the National Key Research and Development Program of China (2021ZD0112302, 2021ZD0112301, 2018YFC1900800-5)Beijing Natural Science Foundation (JQ19013)。
文摘Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence.
基金supported by the patient organizations“Verticale”(to YNG and FEP).
文摘Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.
基金funded by grants from the Novo Nordisk Foundation (NNF18OC0052699) (M.S.H.) and NNF18OC0055047 (M.F.)the Region of Southern Denmark (ref: 18/17553 (M.S.H.))+3 种基金Odense University Hospital (ref: A3147) (M.F.)a faculty fellowship from the University of Southern Denmark (K.M.), the Lundbeck Foundation (ref: R335-2019-2195) (K.M.and A.R.)an Academy of Medical Sciences Springboard Award supported by the British Heart Foundation, Diabetes UK, the Global Challenges Research Fund, the Government Department of Business, Energy and Industrial Strategy and the Wellcome Trust (ref: SBF004 | 1034, C.M.G)a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 224155/Z/21/Z to C.M.G.).
文摘Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.
基金supported by Canada First Research Excellence Fund,Medicine by Design(to CMM)。
文摘Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.
基金the Science and Technology Project of State Grid Corporation of China,Grant Number 5108-202304065A-1-1-ZN.
文摘Stochastic unit commitment is one of the most powerful methods to address uncertainty. However, the existingscenario clustering technique for stochastic unit commitment cannot accurately select representative scenarios,which threatens the robustness of stochastic unit commitment and hinders its application. This paper providesa stochastic unit commitment with dynamic scenario clustering based on multi-parametric programming andBenders decomposition. The stochastic unit commitment is solved via the Benders decomposition, which decouplesthe primal problem into the master problem and two types of subproblems. In the master problem, the committedgenerator is determined, while the feasibility and optimality of generator output are checked in these twosubproblems. Scenarios are dynamically clustered during the subproblem solution process through the multiparametric programming with respect to the solution of the master problem. In other words, multiple scenariosare clustered into several representative scenarios after the subproblem is solved, and the Benders cut obtainedby the representative scenario is generated for the master problem. Different from the conventional stochasticunit commitment, the proposed approach integrates scenario clustering into the Benders decomposition solutionprocess. Such a clustering approach could accurately cluster representative scenarios that have impacts on theunit commitment. The proposed method is tested on a 6-bus system and the modified IEEE 118-bus system.Numerical results illustrate the effectiveness of the proposed method in clustering scenarios. Compared withthe conventional clustering method, the proposed method can accurately select representative scenarios whilemitigating computational burden, thus guaranteeing the robustness of unit commitment.
基金The financial support provided by the Project of National Natural Science Foundation of China(U22A20415,21978256,22308314)“Pioneer”and“Leading Goose”Research&Development Program of Zhejiang(2022C01SA442617)。
文摘Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinear and combinatorial nature of the HEN problem,it is not easy to find solutions of high quality for large-scale problems.The reinforcement learning(RL)method,which learns strategies through ongoing exploration and exploitation,reveals advantages in such area.However,due to the complexity of the HEN design problem,the RL method for HEN should be dedicated and designed.A hybrid strategy combining RL with mathematical programming is proposed to take better advantage of both methods.An insightful state representation of the HEN structure as well as a customized reward function is introduced.A Q-learning algorithm is applied to update the HEN structure using theε-greedy strategy.Better results are obtained from three literature cases of different scales.
基金The authors gratefully acknowledge the support from the National Natural Science Foundation of China(Grant No.42377174)the Natural Science Foundation of Shandong Province,China(Grant No.ZR2022ME198)the Open Research Fund of State Key Laboratory of Geomechanics and Geotechnical Engineering,Institute of Rock and Soil Mechanics,Chinese Academy of Sciences(Grant No.Z020006).
文摘Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems.In this study,a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model(ROM)and probabilistic programming.The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems.Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering.A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution.The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty.Then,a slope case was employed to demonstrate the performance of the developed framework.The results prove that the proposed framework provides a scientific,feasible,and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.
文摘Genetic Programming (GP) is an important approach to deal with complex problem analysis and modeling, and has been applied in a wide range of areas. The development of GP involves various aspects, including design of genetic operators, evolutionary controls and implementations of heuristic strategy, evaluations and other mechanisms. When designing genetic operators, it is necessary to consider the possible limitations of encoding methods of individuals. And when selecting evolutionary control strategies, it is also necessary to balance search efficiency and diversity based on representation characteristics as well as the problem itself. More importantly, all of these matters, among others, have to be implemented through tedious coding work. Therefore, GP development is both complex and time-consuming. To overcome some of these difficulties that hinder the enhancement of GP development efficiency, we explore the feasibility of mutual assistance among GP variants, and then propose a rapid GP prototyping development method based on πGrammatical Evolution (πGE). It is demonstrated through regression analysis experiments that not only is this method beneficial for the GP developers to get rid of some tedious implementations, but also enables them to concentrate on the essence of the referred problem, such as individual representation, decoding means and evaluation. Additionally, it provides new insights into the roles of individual delineations in phenotypes and semantic research of individuals.
基金supported by the National Science Fund for Distinguished Young Scholars (62225303)the Fundamental Research Funds for the Central Universities (buctrc202201)+1 种基金China Scholarship Council,and High Performance Computing PlatformCollege of Information Science and Technology,Beijing University of Chemical Technology。
文摘In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.
文摘This paper presents a new dimension reduction strategy for medium and large-scale linear programming problems. The proposed method uses a subset of the original constraints and combines two algorithms: the weighted average and the cosine simplex algorithm. The first approach identifies binding constraints by using the weighted average of each constraint, whereas the second algorithm is based on the cosine similarity between the vector of the objective function and the constraints. These two approaches are complementary, and when used together, they locate the essential subset of initial constraints required for solving medium and large-scale linear programming problems. After reducing the dimension of the linear programming problem using the subset of the essential constraints, the solution method can be chosen from any suitable method for linear programming. The proposed approach was applied to a set of well-known benchmarks as well as more than 2000 random medium and large-scale linear programming problems. The results are promising, indicating that the new approach contributes to the reduction of both the size of the problems and the total number of iterations required. A tree-based classification model also confirmed the need for combining the two approaches. A detailed numerical example, the general numerical results, and the statistical analysis for the decision tree procedure are presented.
文摘This study embarks on a comprehensive examination of optimization techniques within GPU-based parallel programming models,pivotal for advancing high-performance computing(HPC).Emphasizing the transition of GPUs from graphic-centric processors to versatile computing units,it delves into the nuanced optimization of memory access,thread management,algorithmic design,and data structures.These optimizations are critical for exploiting the parallel processing capabilities of GPUs,addressingboth the theoretical frameworks and practical implementations.By integrating advanced strategies such as memory coalescing,dynamic scheduling,and parallel algorithmic transformations,this research aims to significantly elevate computational efficiency and throughput.The findings underscore the potential of optimized GPU programming to revolutionize computational tasks across various domains,highlighting a pathway towards achieving unparalleled processing power and efficiency in HPC environments.The paper not only contributes to the academic discourse on GPU optimization but also provides actionable insights for developers,fostering advancements in computational sciences and technology.
基金the National Natural Science Foundation of China(No.60904066)
文摘This paper presents an adaptive path planner for unmanned aerial vehicles (UAVs) to adapt a real-time path search procedure to variations and fluctuations of UAVs’ relevant performances, with respect to sensory capability, maneuverability, and flight velocity limit. On the basis of a novel adaptability-involved problem statement, bi-level programming (BLP) and variable planning step techniques are introduced to model the necessary path planning components and then an adaptive path planner is developed for the purpose of adaptation and optimization. Additionally, both probabilistic-risk-based obstacle avoidance and performance limits are described as path search constraints to guarantee path safety and navigability. A discrete-search-based path planning solution, embedded with four optimization strategies, is especially designed for the planner to efficiently generate optimal flight paths in complex operational spaces, within which different surface-to-air missiles (SAMs) are deployed. Simulation results in challenging and stochastic scenarios firstly demonstrate the effectiveness and efficiency of the proposed planner, and then verify its great adaptability and relative stability when planning optimal paths for a UAV with changing or fluctuating performances.
基金funded by the National Natural Science Foundation of China under Grant NSFCProj.71771070,71831006,71801065 and 71932005.
文摘Home health care(HHC)includes a wide range of healthcare services that are performed in customers'homes to help them recover.With the constantly increasing demand for health care,HHC policymakers are eager to address routing and scheduling problems from the perspective of optimization.In this paper,a bi-level programming model for HHC routing and scheduling problems with stochastic travel times is proposed,in which the degree of satisfaction with the visit time is simultaneously considered.The upper-level model is formulated for customer assignment with the aim of minimizing the total operating cost,and the lower-level model is formulated as a routing problem to maximize the degree of satisfaction with the visit time.Consistent with Stackelberg game decision-making,the trade-off relationship between these two objectives can be achieved spontaneously so as to reach an equilibrium state.A three-stage hybrid algorithm combining an iterated local search framework,which uses a large neighborhood search procedure as a sub-heuristic,a set-partitioning model,and a post-optimization method is developed to solve the proposed model.Numerical experiments on a set of instances including 10 to 100 customers verify the effectiveness of the proposed model and algorithm.
基金supported by the National Natural Science Foundation of China (61903025)the Fundamental Research Funds for the Cent ral Universities (FRF-IDRY-20-013)。
文摘The distributed hybrid processing optimization problem of non-cooperative targets is an important research direction for future networked air-defense and anti-missile firepower systems. In this paper, the air-defense anti-missile targets defense problem is abstracted as a nonconvex constrained combinatorial optimization problem with the optimization objective of maximizing the degree of contribution of the processing scheme to non-cooperative targets, and the constraints mainly consider geographical conditions and anti-missile equipment resources. The grid discretization concept is used to partition the defense area into network nodes, and the overall defense strategy scheme is described as a nonlinear programming problem to solve the minimum defense cost within the maximum defense capability of the defense system network. In the solution of the minimum defense cost problem, the processing scheme, equipment coverage capability, constraints and node cost requirements are characterized, then a nonlinear mathematical model of the non-cooperative target distributed hybrid processing optimization problem is established, and a local optimal solution based on the sequential quadratic programming algorithm is constructed, and the optimal firepower processing scheme is given by using the sequential quadratic programming method containing non-convex quadratic equations and inequality constraints. Finally, the effectiveness of the proposed method is verified by simulation examples.
基金supported by projects NDG09/014 and Proyecto VEXEM(to CLP),European Social Fund,YEI,(Nos.PEJ16/MED/AI-1153 and PEJD-2018-PRE/SAL-8532)of the Community of Madrid,SpainSAF-2016-78666-R,CP19-0010,and PID 2020-113014RB-I00 funded by MCIN/AEI/10.13039/501100011033(to JARN).
文摘Cell replacement therapy has long been proposed as a treatment for the damaged nervous system.One of the most challenging aspects of such a strategy,however,is finding sources of donor cells for transplantation.Autologous neural cells are rarely an option as every cell in the nervous system has a defined function that would be lost if that cell was to be removed.One possibility would be sourcing precursor or differentiated cells from fetal tissues;however,aside from ethical issues,heterologous cells are at risk of immunological rejection in the long term.Methodological improvements over the past 15 years have led to the possibility that autologous non-neural cells could be used for cell transplantation through their conversion into neural derivatives.
基金supported by the European Union’s Horizon 2020 contract ATHENA(grant No.666869)ENDpoiNTs(grant No.825759)+1 种基金supported by the European Thyroid Association(ETA)the Fondation pour la Recherche Médicale(FRM grant No.SPF201909009111)。
文摘Introduction:Ever since the discovery of neural stem cells(NSCs)in the adult mammalian brain,scientists have been trying to decipher which signals govern their turnover and lineage commitment to generate neurons and glia.Understanding their role in nervous tissue homeostasis can provide new insights into the etiology of several neurological disorders,and might one day be turned to our advantage to promote endogenous brain injury repair.Others and we have identified thyroid hormone(TH)as a key factor transcriptionally regulating NSC behavior in the largest niche of the adult mammalian brain:the subventricular zone(SVZ).