Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin a...The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.展开更多
This paper presents a new composite nonlinear bilateral control method based on the nonlinear disturbance observer(NDOB) for teleoperation systems with external disturbances. By introducing the estimations of NDOB and...This paper presents a new composite nonlinear bilateral control method based on the nonlinear disturbance observer(NDOB) for teleoperation systems with external disturbances. By introducing the estimations of NDOB and systems' nominal nonlinear dynamics into controller design, a NDOB based composite nonlinear bilateral controller is constructed to attenuate the influence of disturbance and uncertain nonlinearities. As compared with the existing bilateral control methods which usually achieve force haptic(i.e., contact force tracking)through a passive way, the newly proposed method has two major merits: 1) asymptotical convergence of both position and force tracking errors is guaranteed;2) disturbance influence on force tracking error dynamics is rejected through the direct feedforward compensation of disturbance estimation. Simulations on a nonlinear teleoperation system are carried out and the results validate the effectiveness of the proposed controller.展开更多
In this paper, the problem of making an input-delay system with saturating actuators finite-time stable by virtue of digital control is investigated. A digital state feedback controller and digital observer-controller...In this paper, the problem of making an input-delay system with saturating actuators finite-time stable by virtue of digital control is investigated. A digital state feedback controller and digital observer-controller compensator are designed for two cases: when the state of the input-delay system are available or when it is unavailable. Sufficient conditions which guarantee finite-time stability of a closed-loop input-delay system are given and the proof procedure is presented in a heuristic way by constructing appropriate comparison functions. The condition can be transformed into the intersection of two curves satisfying some constraints, which reveals the relationship between designed parameters clearly. Finally, simulation results are presented to validate the method proposed in this paper.展开更多
In networked robot manipulators that deeply integrate control, communication and computation, the controller design needs to take into consideration the limited or costly system resources and the presence of disturban...In networked robot manipulators that deeply integrate control, communication and computation, the controller design needs to take into consideration the limited or costly system resources and the presence of disturbances/uncertainties. To cope with these requirements, this paper proposes a novel dynamic event-triggered robust tracking control method for a onedegree of freedom(DOF) link manipulator with external disturbance and system uncertainties via a reduced-order generalized proportional-integral observer(GPIO). By only using the sampled-data position signal, a new sampled-data robust output feedback tracking controller is proposed based on a reduced-order GPIO to attenuate the undesirable influence of the external disturbance and the system uncertainties. To save the communication resources, we propose a discrete-time dynamic event-triggering mechanism(DETM), where the estimates and the control signal are transmitted and computed only when the proposed discrete-time DETM is violated. It is shown that with the proposed control method, both tracking control properties and communication properties can be significantly improved. Finally, simulation results are shown to demonstrate the feasibility and efficacy of the proposed control approach.展开更多
The subjects of ecological compensation involve the nation, society, development enterprises of wa-ter-energy resources, as well as the location of resource itself. This paper systematically studies on how to make “w...The subjects of ecological compensation involve the nation, society, development enterprises of wa-ter-energy resources, as well as the location of resource itself. This paper systematically studies on how to make “water energy sources market compensation policy”, “the economic compensation policy for relevant interest subjects” and “the ecological compensation policy of basin ecological water.” So, it is necessary to exert the complementary function between market compensation and government compensation by the means of economic compensation and to establish the ecological compensation policy of basin ecological water, which is beneficial to coordinating the stakeholders’ interests of cross-region or inter-basin. And it is important and significant to establish constantly perfected ecological compensation policy among the micro subjects on water energy resources development, so as to coordinate interest relationships among various subjects and finally reach the aim of sustainable use of water energy resources and environmental protection as possible.展开更多
The lower-mobility parallel mechanism has been widely used in the engineering field due to its numerous excellent characteristics.However,little work has been devoted to the actuator selection and placement that best ...The lower-mobility parallel mechanism has been widely used in the engineering field due to its numerous excellent characteristics.However,little work has been devoted to the actuator selection and placement that best satisfy the system's functional requirements during concept design.In this study,a unified approach for synthesizing the actuation spaces of both rigid and flexure parallel mechanisms has been presented,and all possible combinations of inputs could be obtained,laying a theoretical foundation for the subsequent optimization of inputs.According to the linear independence of actuation space and constraint space of the lower-mobility parallel mechanism,a general expression of actuation spaces in the format of screw systems is deduced,a unified synthesis process for the lower-mobility parallel mechanism is derived,and the efficiency of the method is validated with two selective examples based on screw theory.This study presents a theoretical framework for the input selection problems of parallel mechanisms,aiming to help designers select and place actuators in a correct and even optimal way after the configuration design.展开更多
Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly inve...Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.展开更多
Pointing mechanism is widely used in aerospace field,and its pointing accuracy and stability have high requirements.The pointing mechanism will be affected by external interference when it works.In order to eliminate ...Pointing mechanism is widely used in aerospace field,and its pointing accuracy and stability have high requirements.The pointing mechanism will be affected by external interference when it works.In order to eliminate the impact of interference forces on the output accuracy of the mechanism,firstly,this paper proposes a design method for highprecision pointing mechanisms based on interference separation,aiming at the high-precision pointing requirements of pointing mechanisms.Based on the screw theory,a synthesis method for inner compensation mechanisms has been proposed.And a new type of double-layer parallel mechanism has been designed to compensate for interference forces.Then,the kinematics and dynamics of the mechanism are carried out.An evaluation index for compensating external interference forces is proposed.The interference compensation analysis is conducted for the pointing mechanism.The correctness of the proposed interference force compensation coefficient is verified.Finally,in order to find the optimal solution for the workspace and interference force compensation coefficient of the pointing mechanism,multi-objective optimization design of the structural parameters of the mechanism was carried out based on the particle swarm optimization algorithm.This provides a theoretical basis for the prototype design of the subsequent double-layer parallel mechanism.This double-layer parallel mechanism combines the advantages of large load-bearing capacity,large workspace,and high output accuracy.It can be better applied in the aerospace field where high-precision pointing and force interference compensation are integrated.展开更多
Dear Editor,This letter is concerned with the role of recurrent neural networks(RNNs)on the controller design for a class of nonlinear systems.Inspired by the architectures of RNNs,the system states are stacked accord...Dear Editor,This letter is concerned with the role of recurrent neural networks(RNNs)on the controller design for a class of nonlinear systems.Inspired by the architectures of RNNs,the system states are stacked according to the dynamic along with time while the controller is represented as the neural network output.To build the bridge between RNNs and finite-time controller,a novel activation function is imposed on RNNs to drive the convergence of states at finite-time and propel the overall control process smoother.Rigorous stability proof is briefly provided for the convergence of the proposed finite-time controller.At last,a numerical simulation example is presented to illustrate the efficiency of the proposed strategy.Neural networks can be classified as static(feedforward)and dynamic(recurrent)nets[1].The former nets do not perform well in dealing with training data and using any information of the local data structure[2].In contrast to the feedforward neural networks,RNNs are constituted by high dimensional hidden states with dynamics.展开更多
The problem of fault-tolerant control is discussed for the longitudinal model of an airbreathing hypersonic vehicle （AHV） with actuator faults and external disturbances. Firstly, a fault-tolerant control strategy is...The problem of fault-tolerant control is discussed for the longitudinal model of an airbreathing hypersonic vehicle （AHV） with actuator faults and external disturbances. Firstly, a fault-tolerant control strategy is presented for the longitudinal model of an AHV, which guarantees that velocity and altitude track their reference trajectories at an exponential convergence rate. However, this method needs to know the minimum value of the actuator efficiency factor and the upper bound of the external disturbances, which makes it not easy to implement. Then an improved adaptive fault-tolerant control scheme is proposed, where two adaptive laws are employed to estimate the upper bound of the external disturbances and the minimum value of the actuator efficiency factor, respectively. Secondly, the problem of designing a control scheme with control constraints is further considered, and a new adaptive fault-tolerant control strategy with input saturation is designed to guarantee that velocity and altitude track their reference trajectories. Finally, simulation results are given to show the effectiveness of the proposed methods.展开更多
In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units an...In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units and high stifness is proposed based on screw theory. Firstly, a new criterion for the full decoupled of PMs is presented that the reciprocal product of the transmission wrench screw matrix and the output twist screw matrix of PMs is a diagonal matrix, and all elements on the main diagonal are nonzero constants. The forms of the transmission wrench screws are determined by the criterion. Secondly, the forms of the actuated and unactuated screws can be obtained according to their relationships with the transmission wrench screws. The basic decoupled limbs are generated by combination of the above actuated and unactuated screws. Finally, a closed-loop units construction method is investigated to apply the decoupled mechanisms in a better way on the high stifness occasion. The closed-loop units are constructed in the basic decoupled limbs to generate a high-stifness fully decoupled 3T PM. Kinematic and stifness analyses show that the Jacobian matrix is a diagonal matrix, and the stifness is obviously higher than that of the coupling mechanisms, which verifes the correctness of the proposed synthesis method. The mechanism synthesized by this method has a good application prospect in vehicle durability test platform.展开更多
The speed regulation problem with only speed measurement is investigated in this paper for a permanent magnet direct current(DC)motor driven by a buck converter.By lumping all unknown matched/unmatched disturbances an...The speed regulation problem with only speed measurement is investigated in this paper for a permanent magnet direct current(DC)motor driven by a buck converter.By lumping all unknown matched/unmatched disturbances and uncertainties together,the traditional active disturbance rejection control(ADRC)approach provides an intuitive solution for the problem under consideration.However,for such a higher-order disturbed system,the increase of poles for the extended state observer(ESO)therein will lead to drastically growth of observer gains,which causes severe noise amplification.This paper aims to propose a new model-based disturbance rejection controller for the converter-driven DC motor system using output-feedback.Instead of estimating lumped disturbances directly,a new observer is constructed to estimate the desired steady state of control signal as well as errors between the real states and their desired steady-state responses.Thereafter,a controller with only speed measurement is proposed by utilizing the estimates.The performance of the proposed method is tested through experiments on dSPACE.It is further shown via numerical calculations and experimental results that the poles of the observer within the proposed control approach can be largely increased without significantly increasing magnitude of the observer gains.展开更多
The global adaptive set stabilization problem of the attitude of a rigid spacecraft is addressed in this paper. Two different cases are considered. First, by using adaptive backstepping method, the authors design a gl...The global adaptive set stabilization problem of the attitude of a rigid spacecraft is addressed in this paper. Two different cases are considered. First, by using adaptive backstepping method, the authors design a global adaptive control law for the attitude control system with unknown inertia matrix such that the attitude and the angular velocities can be globally asymptotically stabilized to a set consisting of two equilibria. And then, based on the obtained backstepping adaptive law, the authors consider the case that the angular velocities are not measurable. By introducing an auxiliary state, a semi-global adaptive set stabilization law without angular velocity measurements is also designed. It is rigorously proved that, for the two cases, both of the closed loop systems satisfy the set stability. The effectiveness of the proposed methods is verified by simulation results.展开更多
The yellow fever virus(YFV)is a life-threatening human pathogen.Owing to the lack of available therapeutics,non-vaccinated individuals are at risk.Here,we isolated eight human monoclonal antibodies that neutralize YFV...The yellow fever virus(YFV)is a life-threatening human pathogen.Owing to the lack of available therapeutics,non-vaccinated individuals are at risk.Here,we isolated eight human monoclonal antibodies that neutralize YFV infection.Five recognized overlapping epitopes and exhibited potent neutralizing activity.Two(YD6 and YD73)were ultra-potent and conferred complete protection against the lethal challenge of YFV as both prophylactics and therapeutics in a mouse model.Crystal structures revealed that YD6 engaged the YFV envelope protein in both pre-and post-fusion states,suggesting viral inhibition by a“double-lock”mechanism.The recognition determinants for YD6 and YD73 are clustered at the premembrane(prM)-binding site.Notably,antibodies targeting this site were present in minute traces in YFV-infected individuals but contributed significantly to neutralization,suggesting a vulnerable supersite of YFV.We provide two promising candidates for immunotherapy against YFV,and the supersite represents an ideal target for epitope-based vaccine design.展开更多
The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in hum...The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions.展开更多
In order to dissect amyotrophic lateral sclerosis(ALS),a multigenic,multifactorial,and progressive neurodegenerative disease with heterogeneous clinical presentations,researchers have generated numerous animal models ...In order to dissect amyotrophic lateral sclerosis(ALS),a multigenic,multifactorial,and progressive neurodegenerative disease with heterogeneous clinical presentations,researchers have generated numerous animal models to mimic the genetic defects.Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics.However,most genetically modified rodent models lack overt pathological features,imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms.Recent studies using large animals,including pigs and non-human primates,have uncovered important events that resemble neurodegeneration in patients’brains but could not be produced in small animals.Here we describe common features as well as discrepancies among these models,highlighting new insights from these models.Furthermore,we will discuss how to make rodent models more capable of recapitulating important pathological features based on the important pathogenic insights from large animal models.展开更多
In addressing the challenges of short-range spacecraft docking in the presence of obstacles and disturbances,it is critical to integrate guidance and motion control to ensure autonomous and reliable operation.Traditio...In addressing the challenges of short-range spacecraft docking in the presence of obstacles and disturbances,it is critical to integrate guidance and motion control to ensure autonomous and reliable operation.Traditional methods that separate these two layers often struggle with accurately tracking predefined paths,increasing the risk of collisions.In light of this,a proposed scheme integrating guidance and control in an organic manner has been put forth.This scheme employs the rapidly-exploring random trees(RRT)algorithm within the guidance layer to generate a collision-avoidance trajectory for the control layer,efficiently navigating the spacecraft towards its target.Then the control layer implements a second-order output-constrained controller by adding a power integrator and a novel barrier Lyapunov function(BLF)together,to guarantee that the tracking error of the predefined trajectory remains bounded and the system asymptotically converges to the target.To account for tracking errors,obstacle radii are expanded during path planning through a dilation constant.Based on theoretical derivation and simulation experiments,the effectiveness and advancement of the proposed method are validated.展开更多
In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease(PD).However,difficulty in detecting end...In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease(PD).However,difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1.Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains.CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology.Importantly,PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival.Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.展开更多
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
基金supported by the National Natural Science Foundation of China,Nos.32070534(to WY),32370567(to WY),82371874(to XL),81830032(to XL),82071421(to SL)Key Field Research and Development Program of Guangdong Province,No.2018B030337001(to XL)+2 种基金Guangzhou Key Research Program on Brain Science,No.202007030008(to XL)Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(to XL)Guangdong Basic and Applied Basic Research Foundation,Nos.2022A1515012301(to WY),2023B1515020031(to WY).
文摘The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.
基金supported in part by the National Natural Science Foundation of China(61573099,61633003,61750110525,61903192)Fundamental Research Funds for the Central Universities(2242016R30011)+5 种基金Graduate Innovation Program of Jiangsu Province(KYLX15-0114)Scientific Research Foundation of Graduate School of Southeast University(YBJJ1561)Open Project Program of Ministry of EducationKey Laboratory of Measurement and Control of School of Computer Science and Engineering(CSE) MCCSE2017A01,MCCSE2019A01)Chinese Scholarship CouncilNewton Fund by the British Council
文摘This paper presents a new composite nonlinear bilateral control method based on the nonlinear disturbance observer(NDOB) for teleoperation systems with external disturbances. By introducing the estimations of NDOB and systems' nominal nonlinear dynamics into controller design, a NDOB based composite nonlinear bilateral controller is constructed to attenuate the influence of disturbance and uncertain nonlinearities. As compared with the existing bilateral control methods which usually achieve force haptic(i.e., contact force tracking)through a passive way, the newly proposed method has two major merits: 1) asymptotical convergence of both position and force tracking errors is guaranteed;2) disturbance influence on force tracking error dynamics is rejected through the direct feedforward compensation of disturbance estimation. Simulations on a nonlinear teleoperation system are carried out and the results validate the effectiveness of the proposed controller.
基金supported by the National Natural Science Foundation of China(61773216)Natural Science Foundation of Jiangsu Province of China(BK20171386)
文摘In this paper, the problem of making an input-delay system with saturating actuators finite-time stable by virtue of digital control is investigated. A digital state feedback controller and digital observer-controller compensator are designed for two cases: when the state of the input-delay system are available or when it is unavailable. Sufficient conditions which guarantee finite-time stability of a closed-loop input-delay system are given and the proof procedure is presented in a heuristic way by constructing appropriate comparison functions. The condition can be transformed into the intersection of two curves satisfying some constraints, which reveals the relationship between designed parameters clearly. Finally, simulation results are presented to validate the method proposed in this paper.
基金supported in part by the National Natural Science Foundation of China(61473080,61573099,61973080,61750110525,61633003)。
文摘In networked robot manipulators that deeply integrate control, communication and computation, the controller design needs to take into consideration the limited or costly system resources and the presence of disturbances/uncertainties. To cope with these requirements, this paper proposes a novel dynamic event-triggered robust tracking control method for a onedegree of freedom(DOF) link manipulator with external disturbance and system uncertainties via a reduced-order generalized proportional-integral observer(GPIO). By only using the sampled-data position signal, a new sampled-data robust output feedback tracking controller is proposed based on a reduced-order GPIO to attenuate the undesirable influence of the external disturbance and the system uncertainties. To save the communication resources, we propose a discrete-time dynamic event-triggering mechanism(DETM), where the estimates and the control signal are transmitted and computed only when the proposed discrete-time DETM is violated. It is shown that with the proposed control method, both tracking control properties and communication properties can be significantly improved. Finally, simulation results are shown to demonstrate the feasibility and efficacy of the proposed control approach.
文摘The subjects of ecological compensation involve the nation, society, development enterprises of wa-ter-energy resources, as well as the location of resource itself. This paper systematically studies on how to make “water energy sources market compensation policy”, “the economic compensation policy for relevant interest subjects” and “the ecological compensation policy of basin ecological water.” So, it is necessary to exert the complementary function between market compensation and government compensation by the means of economic compensation and to establish the ecological compensation policy of basin ecological water, which is beneficial to coordinating the stakeholders’ interests of cross-region or inter-basin. And it is important and significant to establish constantly perfected ecological compensation policy among the micro subjects on water energy resources development, so as to coordinate interest relationships among various subjects and finally reach the aim of sustainable use of water energy resources and environmental protection as possible.
基金Supported by National Natural Science Foundation of China(Grant No.51775475).
文摘The lower-mobility parallel mechanism has been widely used in the engineering field due to its numerous excellent characteristics.However,little work has been devoted to the actuator selection and placement that best satisfy the system's functional requirements during concept design.In this study,a unified approach for synthesizing the actuation spaces of both rigid and flexure parallel mechanisms has been presented,and all possible combinations of inputs could be obtained,laying a theoretical foundation for the subsequent optimization of inputs.According to the linear independence of actuation space and constraint space of the lower-mobility parallel mechanism,a general expression of actuation spaces in the format of screw systems is deduced,a unified synthesis process for the lower-mobility parallel mechanism is derived,and the efficiency of the method is validated with two selective examples based on screw theory.This study presents a theoretical framework for the input selection problems of parallel mechanisms,aiming to help designers select and place actuators in a correct and even optimal way after the configuration design.
基金supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200)National Natural Science Foundation of China (32170981,82371874,82394422,82171244,82071421,82271902)+1 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001)。
文摘Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.
基金Supported by the National Natural Science Foundation of China(52275032)the Natural Science Foundation of Hebei Province(E2022203077)+1 种基金the Hebei Provincial Science and Technology Plan(22371801D)the Hebei Provincial Science and Technology Research and Development Program-Central Guidance for Local Science and Technology Development Fund(246Z1818G).
文摘Pointing mechanism is widely used in aerospace field,and its pointing accuracy and stability have high requirements.The pointing mechanism will be affected by external interference when it works.In order to eliminate the impact of interference forces on the output accuracy of the mechanism,firstly,this paper proposes a design method for highprecision pointing mechanisms based on interference separation,aiming at the high-precision pointing requirements of pointing mechanisms.Based on the screw theory,a synthesis method for inner compensation mechanisms has been proposed.And a new type of double-layer parallel mechanism has been designed to compensate for interference forces.Then,the kinematics and dynamics of the mechanism are carried out.An evaluation index for compensating external interference forces is proposed.The interference compensation analysis is conducted for the pointing mechanism.The correctness of the proposed interference force compensation coefficient is verified.Finally,in order to find the optimal solution for the workspace and interference force compensation coefficient of the pointing mechanism,multi-objective optimization design of the structural parameters of the mechanism was carried out based on the particle swarm optimization algorithm.This provides a theoretical basis for the prototype design of the subsequent double-layer parallel mechanism.This double-layer parallel mechanism combines the advantages of large load-bearing capacity,large workspace,and high output accuracy.It can be better applied in the aerospace field where high-precision pointing and force interference compensation are integrated.
文摘Dear Editor,This letter is concerned with the role of recurrent neural networks(RNNs)on the controller design for a class of nonlinear systems.Inspired by the architectures of RNNs,the system states are stacked according to the dynamic along with time while the controller is represented as the neural network output.To build the bridge between RNNs and finite-time controller,a novel activation function is imposed on RNNs to drive the convergence of states at finite-time and propel the overall control process smoother.Rigorous stability proof is briefly provided for the convergence of the proposed finite-time controller.At last,a numerical simulation example is presented to illustrate the efficiency of the proposed strategy.Neural networks can be classified as static(feedforward)and dynamic(recurrent)nets[1].The former nets do not perform well in dealing with training data and using any information of the local data structure[2].In contrast to the feedforward neural networks,RNNs are constituted by high dimensional hidden states with dynamics.
基金supported by the National Natural Science Foundation of China(9101600461125306+2 种基金61203011)the Program for New Century Excellent Talents in University (NCET-10-0328)the Natural Science Foundation of Jiangsu Province(BK2012327)
文摘The problem of fault-tolerant control is discussed for the longitudinal model of an airbreathing hypersonic vehicle （AHV） with actuator faults and external disturbances. Firstly, a fault-tolerant control strategy is presented for the longitudinal model of an AHV, which guarantees that velocity and altitude track their reference trajectories at an exponential convergence rate. However, this method needs to know the minimum value of the actuator efficiency factor and the upper bound of the external disturbances, which makes it not easy to implement. Then an improved adaptive fault-tolerant control scheme is proposed, where two adaptive laws are employed to estimate the upper bound of the external disturbances and the minimum value of the actuator efficiency factor, respectively. Secondly, the problem of designing a control scheme with control constraints is further considered, and a new adaptive fault-tolerant control strategy with input saturation is designed to guarantee that velocity and altitude track their reference trajectories. Finally, simulation results are given to show the effectiveness of the proposed methods.
基金Supported by National Natural Science Foundation of China(Grant No.52275032)Key Project of Hebei Provincial Natural Science Foundation of China(Grant No.E2022203077)Hebei Provincial Key Research and Development Plan of China(Grant No.202230808010057).
文摘In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units and high stifness is proposed based on screw theory. Firstly, a new criterion for the full decoupled of PMs is presented that the reciprocal product of the transmission wrench screw matrix and the output twist screw matrix of PMs is a diagonal matrix, and all elements on the main diagonal are nonzero constants. The forms of the transmission wrench screws are determined by the criterion. Secondly, the forms of the actuated and unactuated screws can be obtained according to their relationships with the transmission wrench screws. The basic decoupled limbs are generated by combination of the above actuated and unactuated screws. Finally, a closed-loop units construction method is investigated to apply the decoupled mechanisms in a better way on the high stifness occasion. The closed-loop units are constructed in the basic decoupled limbs to generate a high-stifness fully decoupled 3T PM. Kinematic and stifness analyses show that the Jacobian matrix is a diagonal matrix, and the stifness is obviously higher than that of the coupling mechanisms, which verifes the correctness of the proposed synthesis method. The mechanism synthesized by this method has a good application prospect in vehicle durability test platform.
基金supported in part by the Natural Science Foundation of China(61973080,61973081)by the Aviation Key Laboratory of Science and Technology on Aero Electromechanical System Integration(201928069002)the Key R&D Plan of Jiangsu Province(BE2020082-4)。
文摘The speed regulation problem with only speed measurement is investigated in this paper for a permanent magnet direct current(DC)motor driven by a buck converter.By lumping all unknown matched/unmatched disturbances and uncertainties together,the traditional active disturbance rejection control(ADRC)approach provides an intuitive solution for the problem under consideration.However,for such a higher-order disturbed system,the increase of poles for the extended state observer(ESO)therein will lead to drastically growth of observer gains,which causes severe noise amplification.This paper aims to propose a new model-based disturbance rejection controller for the converter-driven DC motor system using output-feedback.Instead of estimating lumped disturbances directly,a new observer is constructed to estimate the desired steady state of control signal as well as errors between the real states and their desired steady-state responses.Thereafter,a controller with only speed measurement is proposed by utilizing the estimates.The performance of the proposed method is tested through experiments on dSPACE.It is further shown via numerical calculations and experimental results that the poles of the observer within the proposed control approach can be largely increased without significantly increasing magnitude of the observer gains.
基金This research is supported by the National Nature Science Foundation of China under Grant Nos. 60504007 and 61074013, Open Foundation of Key Laboratory of Micro-Inertial Instruments and Navigation Technology, Ministry of Education under Grant No. 201004, Initial Research Fund of Highly Specialized Personnel from Jiangsu University under Grant No. 10JDGll2, and 973 Sub-project under Grant No. 2009CB724002.
文摘The global adaptive set stabilization problem of the attitude of a rigid spacecraft is addressed in this paper. Two different cases are considered. First, by using adaptive backstepping method, the authors design a global adaptive control law for the attitude control system with unknown inertia matrix such that the attitude and the angular velocities can be globally asymptotically stabilized to a set consisting of two equilibria. And then, based on the obtained backstepping adaptive law, the authors consider the case that the angular velocities are not measurable. By introducing an auxiliary state, a semi-global adaptive set stabilization law without angular velocity measurements is also designed. It is rigorously proved that, for the two cases, both of the closed loop systems satisfy the set stability. The effectiveness of the proposed methods is verified by simulation results.
基金Y.Chen and Z.Yang(Institute of Biophysics,CAS)for technical help with Biacore T100 and Octet RED96,and J.Jia(Institute of Biophysics,CAS)and T.Zhao(Institute of Microbiology,CAS)for technical support during BD FACSAria III and CaliburmanipulationX.Lu(Tianjin Institute of Industrial Biotechnology,CAS)for providing pET 21a-YFV-sE plasmid.This work was supported by the National Key R&D Program of China(2021YFA1300803,2021YFC2300200)+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(grant nos.XDB29040201,XDB37030204)National Natural Science Foundation of China(grant nos.31970854,32090014,81830050,81991494).L.Dai is supported by Youth Innovation Promotion Association CAS(2018113).
文摘The yellow fever virus(YFV)is a life-threatening human pathogen.Owing to the lack of available therapeutics,non-vaccinated individuals are at risk.Here,we isolated eight human monoclonal antibodies that neutralize YFV infection.Five recognized overlapping epitopes and exhibited potent neutralizing activity.Two(YD6 and YD73)were ultra-potent and conferred complete protection against the lethal challenge of YFV as both prophylactics and therapeutics in a mouse model.Crystal structures revealed that YD6 engaged the YFV envelope protein in both pre-and post-fusion states,suggesting viral inhibition by a“double-lock”mechanism.The recognition determinants for YD6 and YD73 are clustered at the premembrane(prM)-binding site.Notably,antibodies targeting this site were present in minute traces in YFV-infected individuals but contributed significantly to neutralization,suggesting a vulnerable supersite of YFV.We provide two promising candidates for immunotherapy against YFV,and the supersite represents an ideal target for epitope-based vaccine design.
基金supported by the National Science and Technology Major Project(2016ZX10004222)the Sanming Project of Medicine in Shenzhen(ZDSYS201504301534057)+6 种基金the Key specialized fund for infectious diseases in Shenzhen City(No.201161)the intramural special grant for influenza virus research from the Chinese Academy of Sciences(KJZD-EW-L09 and KJZD-EWL15)the Shenzhen Science and Technology Research and Development Project(JCYJ20160427151920801 and JCYJ20160427153238750)G.F.G.is a leading principal investigator of the National Natural Science Foundation of China(NSFC)Innovative Research Group(81621091)supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS)(2017122)G.W.is the recipient of a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research(CIHR)the President’s International Fellowship Initiative from the CAS
文摘The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions.
基金supported by the National Natural Science Foundation of China(32270564,81830032,82071421)Department of Science and Technology of Guangdong Province(2021ZT09Y007,2018B030337001)+2 种基金Guangzhou Key Research Program on Brain Science(202007030008)Guangdong Basic and Applied Basic Research(2023A1515010811,2022A1515011205)the Fundamental Research Funds for the Central Universities(21622113).
文摘In order to dissect amyotrophic lateral sclerosis(ALS),a multigenic,multifactorial,and progressive neurodegenerative disease with heterogeneous clinical presentations,researchers have generated numerous animal models to mimic the genetic defects.Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics.However,most genetically modified rodent models lack overt pathological features,imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms.Recent studies using large animals,including pigs and non-human primates,have uncovered important events that resemble neurodegeneration in patients’brains but could not be produced in small animals.Here we describe common features as well as discrepancies among these models,highlighting new insights from these models.Furthermore,we will discuss how to make rodent models more capable of recapitulating important pathological features based on the important pathogenic insights from large animal models.
基金supported by the National Natural Science Foundation of China under Grant 62025302.
文摘In addressing the challenges of short-range spacecraft docking in the presence of obstacles and disturbances,it is critical to integrate guidance and motion control to ensure autonomous and reliable operation.Traditional methods that separate these two layers often struggle with accurately tracking predefined paths,increasing the risk of collisions.In light of this,a proposed scheme integrating guidance and control in an organic manner has been put forth.This scheme employs the rapidly-exploring random trees(RRT)algorithm within the guidance layer to generate a collision-avoidance trajectory for the control layer,efficiently navigating the spacecraft towards its target.Then the control layer implements a second-order output-constrained controller by adding a power integrator and a novel barrier Lyapunov function(BLF)together,to guarantee that the tracking error of the predefined trajectory remains bounded and the system asymptotically converges to the target.To account for tracking errors,obstacle radii are expanded during path planning through a dilation constant.Based on theoretical derivation and simulation experiments,the effectiveness and advancement of the proposed method are validated.
文摘In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease(PD).However,difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1.Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains.CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology.Importantly,PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival.Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.
