An improved genetic algorithm(IGA) based on a novel selection strategy to handle nonlinear programming problems is proposed.Each individual in selection process is represented as a three-dimensional feature vector whi...An improved genetic algorithm(IGA) based on a novel selection strategy to handle nonlinear programming problems is proposed.Each individual in selection process is represented as a three-dimensional feature vector which is composed of objective function value,the degree of constraints violations and the number of constraints violations.It is easy to distinguish excellent individuals from general individuals by using an individuals' feature vector.Additionally,a local search(LS) process is incorporated into selection operation so as to find feasible solutions located in the neighboring areas of some infeasible solutions.The combination of IGA and LS should offer the advantage of both the quality of solutions and diversity of solutions.Experimental results over a set of benchmark problems demonstrate that IGA has better performance than other algorithms.展开更多
A penalized interior point approach for constrained nonlinear programming is examined in this work.To overcome the difficulty of initialization for the interior point method,a problem equivalent to the primal problem ...A penalized interior point approach for constrained nonlinear programming is examined in this work.To overcome the difficulty of initialization for the interior point method,a problem equivalent to the primal problem via incorporating an auxiliary variable is constructed.A combined approach of logarithm barrier and quadratic penalty function is proposed to solve the problem.Based on Newton's method,the global convergence of interior point and line search algorithm is proven.Only a finite number of iterations is required to reach an approximate optimal solution.Numerical tests are given to show the effectiveness of the method.展开更多
Converting the balance equation of the branch of a mine ventilation network into an equivalent nonlinearprogramming problem,this paper proves that the total sum of the energy loss in every branch will be a minimumwhen...Converting the balance equation of the branch of a mine ventilation network into an equivalent nonlinearprogramming problem,this paper proves that the total sum of the energy loss in every branch will be a minimumwhen the airflow distribution in the networks is in a balanced state.The energy means of solving the networkequations by nodal methods is also noted,and a theorem for the unique existence of the solution for a networkbalance equation is give.An example is used to explain these conclusions.展开更多
In this paper, on the basis of the logarithmic barrier function and KKT conditions , we propose a combined homotopy infeasible interior-point method (CHIIP) for convex nonlinear programming problems. For any convex no...In this paper, on the basis of the logarithmic barrier function and KKT conditions , we propose a combined homotopy infeasible interior-point method (CHIIP) for convex nonlinear programming problems. For any convex nonlinear programming, without strict convexity for the logarithmic barrier function, we get different solutions of the convex programming in different cases by CHIIP method.展开更多
Planning for water quality management is important for facilitating sustainable socio-economic development;however, the planning is also complicated by a variety of uncertainties and nonlinearities. In this study, an ...Planning for water quality management is important for facilitating sustainable socio-economic development;however, the planning is also complicated by a variety of uncertainties and nonlinearities. In this study, an interval-parameter fuzzy robust nonlinear programming (IFRNP) model was developed for water quality management to deal with such difficulties. The developed model incorporated interval nonlinear programming (INP) and fuzzy robust programming (FRP) methods within a general optimization framework. The developed IFRNP model not only could explicitly deal with uncertainties represented as discrete interval numbers and fuzzy membership functions, but also was able to deal with nonlinearities in the objective function.展开更多
In this paper a new approach for obtaining an approximation global optimum solution of zero-one nonlinear programming (0-1 NP) problem which we call it Parametric Linearization Approach (P.L.A) is proposed. By using t...In this paper a new approach for obtaining an approximation global optimum solution of zero-one nonlinear programming (0-1 NP) problem which we call it Parametric Linearization Approach (P.L.A) is proposed. By using this approach the problem is transformed to a sequence of linear programming problems. The approximately solution of the original 0-1 NP problem is obtained based on the optimum values of the objective functions of this sequence of linear programming problems defined by (P.L.A).展开更多
We propose an exact penalty approach for solving mixed integer nonlinear programming (MINLP) problems by converting a general MINLP problem to a finite sequence of nonlinear programming (NLP) problems with only contin...We propose an exact penalty approach for solving mixed integer nonlinear programming (MINLP) problems by converting a general MINLP problem to a finite sequence of nonlinear programming (NLP) problems with only continuous variables. We express conditions of exactness for MINLP problems and show how the exact penalty approach can be extended to constrained problems.展开更多
One of the most important issues in numerical calculations is finding simple roots of nonlinear equations. This topic is one of the oldest challenges in science and engineering. Many important problems in engineering,...One of the most important issues in numerical calculations is finding simple roots of nonlinear equations. This topic is one of the oldest challenges in science and engineering. Many important problems in engineering, to achieve the result need to solve a nonlinear equation. Thus, the formulation of a recursive relationship with high order of convergence and low time complexity is very important. This paper provides a modification to the Weerakoon-Fernando and Parhi-Gupta methods. It is shown that, in each iterate, the improved method requires three evaluations of the function and two evaluations of the first derivatives of function. The proposed with the Kou et al., Neta, Parhi-Gupta, Thukral and Mir et al. methods have been applied to a collection of 12 test problem. The results show that proposed approach significantly reduces the number of function calls when compared to the above methods. The numerical examples show that the proposed method is more efficiency than other methods in this class, such as sixth-order method of Parhi-Gupta or eighth-order method of Mir et al. and Thukral. We show that the order of convergence the proposed method is 9 and also, the modified method has the efficiency of .展开更多
In this paper,we improve the algorithm proposed by T.F.Colemen and A.R.Conn in paper [1]. It is shown that the improved algorithm is possessed of global convergence and under some conditions it can obtain locally supp...In this paper,we improve the algorithm proposed by T.F.Colemen and A.R.Conn in paper [1]. It is shown that the improved algorithm is possessed of global convergence and under some conditions it can obtain locally supperlinear convergence which is not possessed by the original algorithm.展开更多
A universal numerical approach for nonlinear mathematic programming problems is presented with an application of ratios of first-order differentials/differences of objective functions to constraint functions with resp...A universal numerical approach for nonlinear mathematic programming problems is presented with an application of ratios of first-order differentials/differences of objective functions to constraint functions with respect to design variables. This approach can be efficiently used to solve continuous and, in particular, discrete programmings with arbitrary design variables and constraints. As a search method, this approach requires only computations of the functions and their partial derivatives or differences with respect to design variables, rather than any solution of mathematic equations. The present approach has been applied on many numerical examples as well as on some classical operational problems such as one-dimensional and two-dimensional knap-sack problems, one-dimensional and two-dimensional resource-distribution problems, problems of working reliability of composite systems and loading problems of machine, and more efficient and reliable solutions are obtained than traditional methods. The present approach can be used without limitation of modeling scales of the problem. Optimum solutions can be guaranteed as long as the objective function, constraint functions and their first-order derivatives/differences exist in the feasible domain or feasible set. There are no failures of convergence and instability when this approach is adopted.展开更多
An exact augmented Lagrangian function for the nonlinear nonconvex programming problems with inequality constraints was discussed. Under suitable hypotheses, the relationship was established between the local unconstr...An exact augmented Lagrangian function for the nonlinear nonconvex programming problems with inequality constraints was discussed. Under suitable hypotheses, the relationship was established between the local unconstrained minimizers of the augmented Lagrangian function on the space of problem variables and the local minimizers of the original constrained problem. Furthermore, under some assumptions,the relationship was also established between the global solutions of the augmented Lagrangian function on some compact subset of the space of problem variables and the global solutions of the constrained problem. Therefore, from the theoretical point of view, a solution of the inequality constrained problem and the corresponding values of the Lagrange multipliers can be found by the well-known method of multipliers which resort to the unconstrained minimization of the augmented Lagrangian function presented.展开更多
By redefining the multiplier associated with inequality constraint as a positive definite function of the originally-defined multiplier, say, u2_i, i=1, 2, ..., m, nonnegative constraints imposed on inequality constra...By redefining the multiplier associated with inequality constraint as a positive definite function of the originally-defined multiplier, say, u2_i, i=1, 2, ..., m, nonnegative constraints imposed on inequality constraints in Karush-Kuhn-Tucker necessary conditions are removed. For constructing the Lagrange neural network and Lagrange multiplier method, it is no longer necessary to convert inequality constraints into equality constraints by slack variables in order to reuse those results dedicated to equality constraints, and they can be similarly proved with minor modification. Utilizing this technique, a new type of Lagrange neural network and a new type of Lagrange multiplier method are devised, which both handle inequality constraints directly. Also, their stability and convergence are analyzed rigorously.展开更多
In this paper,we propose a primal-dual interior point method for solving general constrained nonlinear programming problems.To avoid the situation that the algorithm we use may converge to a saddle point or a local ma...In this paper,we propose a primal-dual interior point method for solving general constrained nonlinear programming problems.To avoid the situation that the algorithm we use may converge to a saddle point or a local maximum,we utilize a merit function to guide the iterates toward a local minimum.Especially,we add the parameterεto the Newton system when calculating the decrease directions.The global convergence is achieved by the decrease of a merit function.Furthermore,the numerical results confirm that the algorithm can solve this kind of problems in an efficient way.展开更多
A new preamble structure and design method for orthogonal frequency division multiplexing(OFDM)systems is described,which results a two-symbol long training preamble.The preamble contains four parts,the first part is ...A new preamble structure and design method for orthogonal frequency division multiplexing(OFDM)systems is described,which results a two-symbol long training preamble.The preamble contains four parts,the first part is the same as the third,and the four parts are calculated by using nonlinear programming(NLP)model such that the moving correlation of the preamble results a steep rectangular-like pulse of certain width,whose step-down indicates the timing offset.Simulation results in AWGN channel are given to evaluate the perf o rmance of the proposed preamble design.展开更多
In this paper we present a homotopy continuation method for finding the Karush-Kuhn-Tucker point of a class of nonlinear non-convex programming problems. Two numerical examples are given to show that this method is ef...In this paper we present a homotopy continuation method for finding the Karush-Kuhn-Tucker point of a class of nonlinear non-convex programming problems. Two numerical examples are given to show that this method is effective.It should be pointed out that we extend the results of Lin et al.(see Appl.Math.Comput., 80(1996),209-224) to a broader class of non-convex programming problems.展开更多
Dear Editor,This letter concerns the parameter tuning problem for nonlinear satellite buffer networks with communication delays, aiming to optimize their stability properties under L_(1)-gain. We first model the satel...Dear Editor,This letter concerns the parameter tuning problem for nonlinear satellite buffer networks with communication delays, aiming to optimize their stability properties under L_(1)-gain. We first model the satellite buffer networks by a nonlinear time-delay positive system and propose a novel characterization under which the nonlinear system is asymptotically stable with a prescribed L_(1)-induced performance.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
基金supported by the National Natural Science Foundation of China (60632050)National Basic Research Program of Jiangsu Province University (08KJB520003)
文摘An improved genetic algorithm(IGA) based on a novel selection strategy to handle nonlinear programming problems is proposed.Each individual in selection process is represented as a three-dimensional feature vector which is composed of objective function value,the degree of constraints violations and the number of constraints violations.It is easy to distinguish excellent individuals from general individuals by using an individuals' feature vector.Additionally,a local search(LS) process is incorporated into selection operation so as to find feasible solutions located in the neighboring areas of some infeasible solutions.The combination of IGA and LS should offer the advantage of both the quality of solutions and diversity of solutions.Experimental results over a set of benchmark problems demonstrate that IGA has better performance than other algorithms.
基金supported by the National Natural Science Foundation of China (Grant No.10771133)the Shanghai Leading Academic Discipline Project (Grant Nos.J50101, S30104)
文摘A penalized interior point approach for constrained nonlinear programming is examined in this work.To overcome the difficulty of initialization for the interior point method,a problem equivalent to the primal problem via incorporating an auxiliary variable is constructed.A combined approach of logarithm barrier and quadratic penalty function is proposed to solve the problem.Based on Newton's method,the global convergence of interior point and line search algorithm is proven.Only a finite number of iterations is required to reach an approximate optimal solution.Numerical tests are given to show the effectiveness of the method.
文摘Converting the balance equation of the branch of a mine ventilation network into an equivalent nonlinearprogramming problem,this paper proves that the total sum of the energy loss in every branch will be a minimumwhen the airflow distribution in the networks is in a balanced state.The energy means of solving the networkequations by nodal methods is also noted,and a theorem for the unique existence of the solution for a networkbalance equation is give.An example is used to explain these conclusions.
文摘In this paper, on the basis of the logarithmic barrier function and KKT conditions , we propose a combined homotopy infeasible interior-point method (CHIIP) for convex nonlinear programming problems. For any convex nonlinear programming, without strict convexity for the logarithmic barrier function, we get different solutions of the convex programming in different cases by CHIIP method.
文摘Planning for water quality management is important for facilitating sustainable socio-economic development;however, the planning is also complicated by a variety of uncertainties and nonlinearities. In this study, an interval-parameter fuzzy robust nonlinear programming (IFRNP) model was developed for water quality management to deal with such difficulties. The developed model incorporated interval nonlinear programming (INP) and fuzzy robust programming (FRP) methods within a general optimization framework. The developed IFRNP model not only could explicitly deal with uncertainties represented as discrete interval numbers and fuzzy membership functions, but also was able to deal with nonlinearities in the objective function.
文摘In this paper a new approach for obtaining an approximation global optimum solution of zero-one nonlinear programming (0-1 NP) problem which we call it Parametric Linearization Approach (P.L.A) is proposed. By using this approach the problem is transformed to a sequence of linear programming problems. The approximately solution of the original 0-1 NP problem is obtained based on the optimum values of the objective functions of this sequence of linear programming problems defined by (P.L.A).
文摘We propose an exact penalty approach for solving mixed integer nonlinear programming (MINLP) problems by converting a general MINLP problem to a finite sequence of nonlinear programming (NLP) problems with only continuous variables. We express conditions of exactness for MINLP problems and show how the exact penalty approach can be extended to constrained problems.
文摘One of the most important issues in numerical calculations is finding simple roots of nonlinear equations. This topic is one of the oldest challenges in science and engineering. Many important problems in engineering, to achieve the result need to solve a nonlinear equation. Thus, the formulation of a recursive relationship with high order of convergence and low time complexity is very important. This paper provides a modification to the Weerakoon-Fernando and Parhi-Gupta methods. It is shown that, in each iterate, the improved method requires three evaluations of the function and two evaluations of the first derivatives of function. The proposed with the Kou et al., Neta, Parhi-Gupta, Thukral and Mir et al. methods have been applied to a collection of 12 test problem. The results show that proposed approach significantly reduces the number of function calls when compared to the above methods. The numerical examples show that the proposed method is more efficiency than other methods in this class, such as sixth-order method of Parhi-Gupta or eighth-order method of Mir et al. and Thukral. We show that the order of convergence the proposed method is 9 and also, the modified method has the efficiency of .
文摘In this paper,we improve the algorithm proposed by T.F.Colemen and A.R.Conn in paper [1]. It is shown that the improved algorithm is possessed of global convergence and under some conditions it can obtain locally supperlinear convergence which is not possessed by the original algorithm.
文摘A universal numerical approach for nonlinear mathematic programming problems is presented with an application of ratios of first-order differentials/differences of objective functions to constraint functions with respect to design variables. This approach can be efficiently used to solve continuous and, in particular, discrete programmings with arbitrary design variables and constraints. As a search method, this approach requires only computations of the functions and their partial derivatives or differences with respect to design variables, rather than any solution of mathematic equations. The present approach has been applied on many numerical examples as well as on some classical operational problems such as one-dimensional and two-dimensional knap-sack problems, one-dimensional and two-dimensional resource-distribution problems, problems of working reliability of composite systems and loading problems of machine, and more efficient and reliable solutions are obtained than traditional methods. The present approach can be used without limitation of modeling scales of the problem. Optimum solutions can be guaranteed as long as the objective function, constraint functions and their first-order derivatives/differences exist in the feasible domain or feasible set. There are no failures of convergence and instability when this approach is adopted.
文摘An exact augmented Lagrangian function for the nonlinear nonconvex programming problems with inequality constraints was discussed. Under suitable hypotheses, the relationship was established between the local unconstrained minimizers of the augmented Lagrangian function on the space of problem variables and the local minimizers of the original constrained problem. Furthermore, under some assumptions,the relationship was also established between the global solutions of the augmented Lagrangian function on some compact subset of the space of problem variables and the global solutions of the constrained problem. Therefore, from the theoretical point of view, a solution of the inequality constrained problem and the corresponding values of the Lagrange multipliers can be found by the well-known method of multipliers which resort to the unconstrained minimization of the augmented Lagrangian function presented.
文摘By redefining the multiplier associated with inequality constraint as a positive definite function of the originally-defined multiplier, say, u2_i, i=1, 2, ..., m, nonnegative constraints imposed on inequality constraints in Karush-Kuhn-Tucker necessary conditions are removed. For constructing the Lagrange neural network and Lagrange multiplier method, it is no longer necessary to convert inequality constraints into equality constraints by slack variables in order to reuse those results dedicated to equality constraints, and they can be similarly proved with minor modification. Utilizing this technique, a new type of Lagrange neural network and a new type of Lagrange multiplier method are devised, which both handle inequality constraints directly. Also, their stability and convergence are analyzed rigorously.
文摘In this paper,we propose a primal-dual interior point method for solving general constrained nonlinear programming problems.To avoid the situation that the algorithm we use may converge to a saddle point or a local maximum,we utilize a merit function to guide the iterates toward a local minimum.Especially,we add the parameterεto the Newton system when calculating the decrease directions.The global convergence is achieved by the decrease of a merit function.Furthermore,the numerical results confirm that the algorithm can solve this kind of problems in an efficient way.
基金supported by the National Natural Science Foundation of China under Grant No. 60501018
文摘A new preamble structure and design method for orthogonal frequency division multiplexing(OFDM)systems is described,which results a two-symbol long training preamble.The preamble contains four parts,the first part is the same as the third,and the four parts are calculated by using nonlinear programming(NLP)model such that the moving correlation of the preamble results a steep rectangular-like pulse of certain width,whose step-down indicates the timing offset.Simulation results in AWGN channel are given to evaluate the perf o rmance of the proposed preamble design.
文摘In this paper we present a homotopy continuation method for finding the Karush-Kuhn-Tucker point of a class of nonlinear non-convex programming problems. Two numerical examples are given to show that this method is effective.It should be pointed out that we extend the results of Lin et al.(see Appl.Math.Comput., 80(1996),209-224) to a broader class of non-convex programming problems.
基金supported by the National Natural Science Foundation of China (61903258)Guangdong Basic and Applied Basic Research Foundation (2022A1515010234)+1 种基金Project of Department of Education of Guangdong Province (2022KTSCX105, 2023ZDZX4046)Shenzhen Natural Science Fund (Stable Support Plan Program 20231122121608001)。
文摘Dear Editor,This letter concerns the parameter tuning problem for nonlinear satellite buffer networks with communication delays, aiming to optimize their stability properties under L_(1)-gain. We first model the satellite buffer networks by a nonlinear time-delay positive system and propose a novel characterization under which the nonlinear system is asymptotically stable with a prescribed L_(1)-induced performance.
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This work was 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.))+6 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.)Academy of Medical Sciences Springboard Award supported by the British Heart Foundation,Diabetes UKthe Global Challenges Research Fundthe 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.
