Planning in lexical-prior-free environments presents a fundamental challenge for evaluating whether large language models(LLMs)possess genuine structural reasoning capabilities beyond lexical memorization.When predica...Planning in lexical-prior-free environments presents a fundamental challenge for evaluating whether large language models(LLMs)possess genuine structural reasoning capabilities beyond lexical memorization.When predicates and action names are replaced with semantically irrelevant random symbols while preserving logical structures,existing direct generation approaches exhibit severe performance degradation.This paper proposes a symbol-agnostic closed-loop planning pipeline that enables models to construct executable plans through systematic validation and iterative refinement.The system implements a complete generate-verify-repair cycle through six core processing components:semantic comprehension extracts structural constraints,language planner generates text plans,symbol translator performs structure-preserving mapping,consistency checker conducts static screening,Stanford Research Institute Problem Solver(STRIPS)simulator executes step-by-step validation,and VAL(Validator)provides semantic verification.A repair controller orchestrates four targeted strategies addressing typical failure patterns including first-step precondition errors andmid-segment statemaintenance issues.Comprehensive evaluation on PlanBench Mystery Blocksworld demonstrates substantial improvements over baseline approaches across both language models and reasoning models.Ablation studies confirm that each architectural component contributes non-redundantly to overall effectiveness,with targeted repair providing the largest impact,followed by deep constraint extraction and stepwise validation,demonstrating that superior performance emerges from synergistic integration of these mechanisms rather than any single dominant factor.Analysis reveals distinct failure patterns betweenmodel types—languagemodels struggle with local precondition satisfaction while reasoning models face global goal achievement challenges—yet the validation-driven mechanism successfully addresses these diverse weaknesses.A particularly noteworthy finding is the convergence of final success rates across models with varying intrinsic capabilities,suggesting that systematic validation and repair mechanisms play a more decisive role than raw model capacity in lexical-prior-free scenarios.This work establishes a rigorous evaluation framework incorporating statistical significance testing and mechanistic failure analysis,providingmethodological contributions for fair assessment and practical insights into building reliable planning systems under extreme constraint conditions.展开更多
Abstract Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Con- ventional antidepressants take at least several weeks to achieve a therapeutic response and this la...Abstract Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Con- ventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hin- dered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N- methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast- acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concem. In this review, we focus on the limitations of ketamine, including neurotoicity, cognitive dysfunction, adverse events associated with mental status, psy- chotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associ- ated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine （esketamine） and R-ketamine, are also discussed. R-ketamine has greater antidepressantactions than S-ketamine, without ketamine-related side- effects. Future treatment strategies should consider using R- ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term keta- mine use.展开更多
Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system.While the spleen may influence neuropathic pain,its role has been poorly understood.This study demonstrates that the spleen...Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system.While the spleen may influence neuropathic pain,its role has been poorly understood.This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis(BNST)-paraventricular nucleus of the hypothalamus(PVN)neural circuit in a chronic constriction injury(CCI)mouse model.Splenectomy,splenic denervation,or splenic sympathectomy significantly increased the mechanical withdrawal threshold(MWT)and reduced macrophage infiltration in the dorsal root ganglia(DRG)of CCI mice.Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain.Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT;these effects were reversed by splenectomy,splenic denervation,or sympathectomy.These findings underscore the critical role of the spleen,regulated by the BNST-PVN circuit,in neuropathic pain.展开更多
Ketamine is a noncompetitive N-methyl-D-aspartate receptor （NMDAR） antagonist that has attracted wide- spread attention for its rapid-onset antidepressant effects, especially in individuals with treatment-resistant ...Ketamine is a noncompetitive N-methyl-D-aspartate receptor （NMDAR） antagonist that has attracted wide- spread attention for its rapid-onset antidepressant effects, especially in individuals with treatment-resistant depres- sion and suicidal ideation [1-3]. Compared with the tra- ditional antidepressants that take weeks, if not months, to benefit patients and are associated with a high rate of relapse, ketamine exerts its antidepressant effects within several hours. These clinical benefits can last for 2 weeks after a single injection [1, 2, 4]. However, ketamine still has limited clinical application, psychotomimetic side-effects and liability of abuse. A recent paper in Nature [5] showed that the ketamine metabolite enantiomer （2R,6R）-hydroxynorketamine （HNK） has rapid and sustained antidepressant effects without the side-effects associated with ketamine, such as abuse potential. The discovery of （R）-ketamine is a land- mark in the field of depression. Investigations of its mechanism of action will inspire the development of a new展开更多
This paper proposes a system for stable ladder climbing of the human-sized four-limbed robot“WAREC-1”,including the following 3 components:(a)Whole-body motion planning;(b)Rung recognition system and(c)Reaction forc...This paper proposes a system for stable ladder climbing of the human-sized four-limbed robot“WAREC-1”,including the following 3 components:(a)Whole-body motion planning;(b)Rung recognition system and(c)Reaction force adjustment.These 3 components guarantee appropriate ladder climbing motion,successful rung grub and proper reaction force distribution at contact points throughout the climbing motion,respectively.With this system,(1)Stable ladder climbing in 2-point contact gait by a human-sized robot and(2)Successful and stable climbing of an irregular ladder(with a higher or inclined rung)in both 3-point and 2-point contact gait with the capability of recognizing the target rung and the corresponding motion planning are realized,which have rarely been realized by former studies.Finally,experiment results and data of the robot ladder climbing are also presented to evaluate the proposed system.展开更多
Stimulus-specific accumulation of second messengers like reactive oxygen species （ROS） and Ca^＋ are central to many signaling and regulation processes in plants. However, mechanisms that govern the reciprocal inter...Stimulus-specific accumulation of second messengers like reactive oxygen species （ROS） and Ca^＋ are central to many signaling and regulation processes in plants. However, mechanisms that govern the reciprocal interrelation of Ca^＋ and ROS signaling are only beginning to emerge. NADPH oxidases of the respiratory burst oxidase homolog （RBOH） family are critical components contributing to the generation of ROS while Calcineurin B-like （CBL） Ca^＋ sensor proteins together with their interacting kinases （CIPKs） have been shown to function in many Ca^＋- signaling processes. In this study, we identify direct functional interactions between both signaling systems. We report that the CBL-interacting pro- tein kinase ClPK26 specifically interacts with the N-terminal domain of RBOHF in yeast two-hybrid analyses and with the full-length RBOHF protein in plant cells. In addition, CIPK26 phosphorylates RBOHF in vitro and co-expression of either CBL1 or CBL9 with CIPK26 strongly enhances ROS production by RBOHF in HEK293T cells. Together, these findings identify a direct interconnection between CBL-ClPK-mediated Ca^＋ signaling and ROS signaling in plants and provide evidence for a synergistic activation of the NADPH oxidase RBOHF by direct Ca^＋-binding to its EF-hands and Ca2＋-induced phospho-rylation by CBL1/9-ClPK26 complexes.展开更多
基金supported by the Information,Production and Systems Research Center,Waseda University,and partly supported by the Future Robotics Organization,Waseda Universitythe Humanoid Robotics Institute,Waseda University,under the Humanoid Project+1 种基金the Waseda University Grant for Special Research Projects(grant numbers 2024C-518 and 2025E-027)was partly executed under the cooperation of organization between Kioxia Corporation andWaseda University.
文摘Planning in lexical-prior-free environments presents a fundamental challenge for evaluating whether large language models(LLMs)possess genuine structural reasoning capabilities beyond lexical memorization.When predicates and action names are replaced with semantically irrelevant random symbols while preserving logical structures,existing direct generation approaches exhibit severe performance degradation.This paper proposes a symbol-agnostic closed-loop planning pipeline that enables models to construct executable plans through systematic validation and iterative refinement.The system implements a complete generate-verify-repair cycle through six core processing components:semantic comprehension extracts structural constraints,language planner generates text plans,symbol translator performs structure-preserving mapping,consistency checker conducts static screening,Stanford Research Institute Problem Solver(STRIPS)simulator executes step-by-step validation,and VAL(Validator)provides semantic verification.A repair controller orchestrates four targeted strategies addressing typical failure patterns including first-step precondition errors andmid-segment statemaintenance issues.Comprehensive evaluation on PlanBench Mystery Blocksworld demonstrates substantial improvements over baseline approaches across both language models and reasoning models.Ablation studies confirm that each architectural component contributes non-redundantly to overall effectiveness,with targeted repair providing the largest impact,followed by deep constraint extraction and stepwise validation,demonstrating that superior performance emerges from synergistic integration of these mechanisms rather than any single dominant factor.Analysis reveals distinct failure patterns betweenmodel types—languagemodels struggle with local precondition satisfaction while reasoning models face global goal achievement challenges—yet the validation-driven mechanism successfully addresses these diverse weaknesses.A particularly noteworthy finding is the convergence of final success rates across models with varying intrinsic capabilities,suggesting that systematic validation and repair mechanisms play a more decisive role than raw model capacity in lexical-prior-free scenarios.This work establishes a rigorous evaluation framework incorporating statistical significance testing and mechanistic failure analysis,providingmethodological contributions for fair assessment and practical insights into building reliable planning systems under extreme constraint conditions.
基金supported by the National Natural Science Foundation of China(81371489)the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development.AMED
文摘Abstract Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Con- ventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hin- dered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N- methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast- acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concem. In this review, we focus on the limitations of ketamine, including neurotoicity, cognitive dysfunction, adverse events associated with mental status, psy- chotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associ- ated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine （esketamine） and R-ketamine, are also discussed. R-ketamine has greater antidepressantactions than S-ketamine, without ketamine-related side- effects. Future treatment strategies should consider using R- ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term keta- mine use.
基金supported by the National Natural Science Foundation of China(82201549)the Hubei Provincial Natural Science Foundation of China(220100579)the Guangdong Basic and Applied Basic Research Foundation(2021B1515120050 and 2023A1515110107).
文摘Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system.While the spleen may influence neuropathic pain,its role has been poorly understood.This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis(BNST)-paraventricular nucleus of the hypothalamus(PVN)neural circuit in a chronic constriction injury(CCI)mouse model.Splenectomy,splenic denervation,or splenic sympathectomy significantly increased the mechanical withdrawal threshold(MWT)and reduced macrophage infiltration in the dorsal root ganglia(DRG)of CCI mice.Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain.Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT;these effects were reversed by splenectomy,splenic denervation,or sympathectomy.These findings underscore the critical role of the spleen,regulated by the BNST-PVN circuit,in neuropathic pain.
文摘Ketamine is a noncompetitive N-methyl-D-aspartate receptor （NMDAR） antagonist that has attracted wide- spread attention for its rapid-onset antidepressant effects, especially in individuals with treatment-resistant depres- sion and suicidal ideation [1-3]. Compared with the tra- ditional antidepressants that take weeks, if not months, to benefit patients and are associated with a high rate of relapse, ketamine exerts its antidepressant effects within several hours. These clinical benefits can last for 2 weeks after a single injection [1, 2, 4]. However, ketamine still has limited clinical application, psychotomimetic side-effects and liability of abuse. A recent paper in Nature [5] showed that the ketamine metabolite enantiomer （2R,6R）-hydroxynorketamine （HNK） has rapid and sustained antidepressant effects without the side-effects associated with ketamine, such as abuse potential. The discovery of （R）-ketamine is a land- mark in the field of depression. Investigations of its mechanism of action will inspire the development of a new
基金This research was funded by ImPACT TRC Program of Council for Science,Technology and Innovation(Cabinet Office,Government of Japan)This study was conducted with the support of Research Institute for Science and Engineering,Waseda University+3 种基金Future Robotics Organization,Waseda University,and as a part of the humanoid project at the Humanoid Robotics Institute,Waseda UniversityThis research was also partially supported by SolidWorks Japan K.KDYDEN Corporationand KITO Corporation whom we thank for their financial and technical support.
文摘This paper proposes a system for stable ladder climbing of the human-sized four-limbed robot“WAREC-1”,including the following 3 components:(a)Whole-body motion planning;(b)Rung recognition system and(c)Reaction force adjustment.These 3 components guarantee appropriate ladder climbing motion,successful rung grub and proper reaction force distribution at contact points throughout the climbing motion,respectively.With this system,(1)Stable ladder climbing in 2-point contact gait by a human-sized robot and(2)Successful and stable climbing of an irregular ladder(with a higher or inclined rung)in both 3-point and 2-point contact gait with the capability of recognizing the target rung and the corresponding motion planning are realized,which have rarely been realized by former studies.Finally,experiment results and data of the robot ladder climbing are also presented to evaluate the proposed system.
文摘Stimulus-specific accumulation of second messengers like reactive oxygen species （ROS） and Ca^＋ are central to many signaling and regulation processes in plants. However, mechanisms that govern the reciprocal interrelation of Ca^＋ and ROS signaling are only beginning to emerge. NADPH oxidases of the respiratory burst oxidase homolog （RBOH） family are critical components contributing to the generation of ROS while Calcineurin B-like （CBL） Ca^＋ sensor proteins together with their interacting kinases （CIPKs） have been shown to function in many Ca^＋- signaling processes. In this study, we identify direct functional interactions between both signaling systems. We report that the CBL-interacting pro- tein kinase ClPK26 specifically interacts with the N-terminal domain of RBOHF in yeast two-hybrid analyses and with the full-length RBOHF protein in plant cells. In addition, CIPK26 phosphorylates RBOHF in vitro and co-expression of either CBL1 or CBL9 with CIPK26 strongly enhances ROS production by RBOHF in HEK293T cells. Together, these findings identify a direct interconnection between CBL-ClPK-mediated Ca^＋ signaling and ROS signaling in plants and provide evidence for a synergistic activation of the NADPH oxidase RBOHF by direct Ca^＋-binding to its EF-hands and Ca2＋-induced phospho-rylation by CBL1/9-ClPK26 complexes.
