Due to the small size,active mobility,and intrinsic softness,miniature soft robots hold promising po-tentials in reaching the deep region inside living bodies otherwise inaccessible with compelling agility,adaptabilit...Due to the small size,active mobility,and intrinsic softness,miniature soft robots hold promising po-tentials in reaching the deep region inside living bodies otherwise inaccessible with compelling agility,adaptability and safety.Various materials and actuation strategies have been developed for creating soft robots,among which,ferromagnetic soft materials that self-actuate in response to external magnetic fields have attracted worldwide attention due to their remote controllability and excellent compatibil-ity with biological tissues.This review presents comprehensive and systematic research advancements in the design,fabrication,and applications of ferromagnetic soft materials for miniature robots,providing in-sights into their potential use in biomedical fields and beyond.The programming strategies of ferromag-netic soft materials are summarized and classified,including mold-assisted programming,3D printing-assisted programming,microassembly-assisted programming,and magnetization reprogramming.Each approach possesses unique advantages in manipulating the magnetic responsiveness of ferromagnetic soft materials to achieve outstanding actuation and deformation performances.We then discuss the biomedi-cal applications of ferromagnetic soft material-based soft robots(e.g.,minimally invasive surgery,targeted delivery,and tissue engineering),highlighting their potentials in revolutionizing biomedical technologies.This review also points out the current challenges and provides insights into future research directions,which we hope can serve as a useful reference for the development of next-generation adaptive miniature robots.展开更多
G protein coupled receptor kinase 2 (GRK2) is a kinase that regulates cardiac signaling activity. Inhibiting GRK2 is a promising mechanism for the treatment of heart failure (HF). Further development and optimization ...G protein coupled receptor kinase 2 (GRK2) is a kinase that regulates cardiac signaling activity. Inhibiting GRK2 is a promising mechanism for the treatment of heart failure (HF). Further development and optimization of inhibitors targeting GRK2 are highly meaningful. Therefore, in order to design GRK2 inhibitors with better performance, the most active molecule was selected as a reference compound from a data set containing 4-pyridylhydrazone derivatives and triazole derivatives, and its scaffold was extracted as the initial scaffold. Then, a powerful optimization-based framework for de novo drug design, guided by binding affinity, was used to generate a virtual molecular library targeting GRK2. The binding affinity of each virtual compound in this dataset was predicted by our developed deep learning model, and the designed potential compound with high binding affinity was selected for molecular docking and molecular dynamics simulation. It was found that the designed potential molecule binds to the ATP site of GRK2, which consists of key amino acids including Arg199, Gly200, Phe202, Val205, Lys220, Met274 and Asp335. The scaffold of the molecule is stabilized mainly by H-bonding and hydrophobic contacts. Concurrently, the reference compound in the dataset was also simulated by docking. It was found that this molecule also binds to the ATP site of GRK2. In addition, its scaffold is stabilized mainly by H-bonding and π-cation stacking interactions with Lys220, as well as hydrophobic contacts. The above results show that the designed potential molecule has similar binding modes to the reference compound, supporting the effectiveness of our framework for activity-focused molecular design. Finally, we summarized the interaction characteristics of general GRK2 inhibitors and gained insight into their molecule-target binding mechanisms, thereby facilitating the expansion of lead to hit compound.展开更多
In this study,an inverse design framework was established to find lightweight honeycomb structures(HCSs)with high impact resistance.The hybrid HCS,composed of re-entrant(RE)and elliptical annular re-entrant(EARE)honey...In this study,an inverse design framework was established to find lightweight honeycomb structures(HCSs)with high impact resistance.The hybrid HCS,composed of re-entrant(RE)and elliptical annular re-entrant(EARE)honeycomb cells,was created by constructing arrangement matrices to achieve structural lightweight.The machine learning(ML)framework consisted of a neural network(NN)forward regression model for predicting impact resistance and a multi-objective optimization algorithm for generating high-performance designs.The surrogate of the local design space was initially realized by establishing the NN in the small sample dataset,and the active learning strategy was used to continuously extended the local optimal design until the model converged in the global space.The results indicated that the active learning strategy significantly improved the inference capability of the NN model in unknown design domains.By guiding the iteration direction of the optimization algorithm,lightweight designs with high impact resistance were identified.The energy absorption capacity of the optimal design reached 94.98%of the EARE honeycomb,while the initial peak stress and mass decreased by 28.85%and 19.91%,respectively.Furthermore,Shapley Additive Explanations(SHAP)for global explanation of the NN indicated a strong correlation between the arrangement mode of HCS and its impact resistance.By reducing the stiffness of the cells at the top boundary of the structure,the initial impact damage sustained by the structure can be significantly improved.Overall,this study proposed a general lightweight design method for array structures under impact loads,which is beneficial for the widespread application of honeycomb-based protective structures.展开更多
Chiral metamaterials are manmade structures with extraordinary mechanical properties derived from their special geometric design instead of chemical composition.To make the mechanical deformation programmable,the non-...Chiral metamaterials are manmade structures with extraordinary mechanical properties derived from their special geometric design instead of chemical composition.To make the mechanical deformation programmable,the non-uniform rational B-spline(NURBS)curves are taken to replace the traditional ligament boundaries of the chiral structure.The Neural networks are innovatively inserted into the calculation of mechanical properties of the chiral structure instead of finite element methods to improve computational efficiency.For the problem of finding structure configuration with specified mechanical properties,such as Young’s modulus,Poisson’s ratio or deformation,an inverse design method using the Neural network-based proxy model is proposed to build the relationship between mechanical properties and geometric configuration.To satisfy some more complex deformation requirements,a non-homogeneous inverse design method is proposed and verified through simulation and experiments.Numerical and test results reveal the high computational efficiency and accuracy of the proposed method in the design of chiral metamaterials.展开更多
Advanced programmable metamaterials with heterogeneous microstructures have become increasingly prevalent in scientific and engineering disciplines attributed to their tunable properties.However,exploring the structur...Advanced programmable metamaterials with heterogeneous microstructures have become increasingly prevalent in scientific and engineering disciplines attributed to their tunable properties.However,exploring the structure-property relationship in these materials,including forward prediction and inverse design,presents substantial challenges.The inhomogeneous microstructures significantly complicate traditional analytical or simulation-based approaches.Here,we establish a novel framework that integrates the machine learning(ML)-encoded multiscale computational method for forward prediction and Bayesian optimization for inverse design.Unlike prior end-to-end ML methods limited to specific problems,our framework is both load-independent and geometry-independent.This means that a single training session for a constitutive model suffices to tackle various problems directly,eliminating the need for repeated data collection or training.We demonstrate the efficacy and efficiency of this framework using metamaterials with designable elliptical holes or lattice honeycombs microstructures.Leveraging accelerated forward prediction,we can precisely customize the stiffness and shape of metamaterials under diverse loading scenarios,and extend this capability to multi-objective customization seamlessly.Moreover,we achieve topology optimization for stress alleviation at the crack tip,resulting in a significant reduction of Mises stress by up to 41.2%and yielding a theoretical interpretable pattern.This framework offers a general,efficient and precise tool for analyzing the structure-property relationships of novel metamaterials.展开更多
Online programming platforms are popular in programming education.However,there has been no research investigating students’real opinions and expectations of the error feedback mechanisms,leaving educators without a ...Online programming platforms are popular in programming education.However,there has been no research investigating students’real opinions and expectations of the error feedback mechanisms,leaving educators without a solid data foundation when attempting to improve the error feedback mechanisms.This paper makes a survey of 834 students across various programming courses and investigates student perceptions of error feedback mechanisms on online programming platforms.It explores the effectiveness of existing feedback,student satisfaction,and preferences for potential improvements,focusing on automatic error localization and program repair mechanisms.Results reveal a significant portion of students are dissatisfied with current feedback due to its limited informativeness.Students also express a clear demand for stronger feedback mechanisms,such as error localization and repair hints.Nevertheless,they prefer feedback that subtly guides them toward solutions,rather than providing direct and explicit answers,valuing the opportunity to enhance their debugging skills.The findings suggest a need for balanced,educational-focused feedback mechanisms that aid learning while promoting independent problem-solving.展开更多
Purpose-Interface management is the process of managing communications,responsibilities and coordination of project parties,phases or physical entities which are dependent on one another.Interface management is a cruc...Purpose-Interface management is the process of managing communications,responsibilities and coordination of project parties,phases or physical entities which are dependent on one another.Interface management is a crucial part of managing any construction project-but particularly important for high-speed railway projects that often have several contractual parties and stakeholders,very long project timelines and huge upfront cost overlays.This paper discusses how various project interfaces were managed during the design and construction of the civil engineering infrastructure for the High Speed Two(HS2)project in the United Kingdom.Design/methodology/approach-The paper uses the case study methodology.Key interfaces on the HS2 project are grouped into various categories and the paper discusses how they were managed within the Area North Integrated Project Team(IPT)of the HS2 project made up of contractor Balfour Beatty VINCI(BBV),the Mott MacDonald SYSTRA Design Joint Venture(DJV)and client HS2 Ltd.3 different case studies drawn from across the IPT are used,each of them highlighting different interfaces and how these interfaces were managed.Findings-The paper shows how innovative technical designs and modern methods of construction were used to address some of the unique and peculiar challenges of designing a brand-new railway in the United Kingdom.Addressing the contrasting and often competing requirements of different stakeholders,coupled with challenging physical constraints of the very limited land available for the project and the use of a rarely used Act of Parliament in the delivery of the project required different approach to interface management.Collaboration and proactive stakeholder engagement are necessary for successful interface management on megaprojects.The authors posit that adopting an integrated approach to engineering and construction management is an essential ingredient for the successful delivery of high-speed railway projects.Originality/value-With many high-speed railway projects around the world coming up in the next few years,understanding the context and challenges for each country will help engineering and design managers adopt appropriate approaches for their projects.The lessons learned on the HS2 project are also transferable to other mega infrastructure projects with complex project interfaces.展开更多
Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disruptin...Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.展开更多
Against the backdrop of escalating global climate change and energy crises,the resource utilization of carbon dioxide(CO_(2)),a major greenhouse gas,has become a crucial pathway for achieving carbon peaking and carbon...Against the backdrop of escalating global climate change and energy crises,the resource utilization of carbon dioxide(CO_(2)),a major greenhouse gas,has become a crucial pathway for achieving carbon peaking and carbon neutrality goals.The hydrogenation of CO_(2)to methanol not only enables carbon sequestration and recycling,but also provides a route to produce high value-added fuels and basic chemical feedstocks,holding significant environmental and economic potential.However,this conversion process is thermodynamically and kinetically limited,and traditional catalyst systems(e.g.,Cu/ZnO/Al_(2)O_(3))exhibit inadequate activity,selectivity,and stability under mild conditions.Therefore,the development of novel high-performance catalysts with precisely tunable structures and functionalities is imperative.Metal-organic frameworks(MOFs),as crystalline porous materials with high surface area,tunable pore structures,and diverse metal-ligand compositions,have the great potential in CO_(2)hydrogenation catalysis.Their structural design flexibility allows for the construction of well-dispersed active sites,tailored electronic environments,and enhanced metal-support interactions.This review systematically summarizes the recent advances in MOF-based and MOF-derived catalysts for CO_(2)hydrogenation to methanol,focusing on four design strategies:(1)spatial confinement and in situ construction,(2)defect engineering and ion-exchange,(3)bimetallic synergy and hybrid structure design,and(4)MOF-derived nanomaterial synthesis.These approaches significantly improve CO_(2)conversion and methanol selectivity by optimizing metal dispersion,interfacial structures,and reaction pathways.The reaction mechanism is further explored by focusing on the three main reaction pathways:the formate pathway(HCOO*),the RWGS(Reverse Water Gas Shift reaction)+CO*hydrogenation pathway,and the trans-COOH pathway.In situ spectroscopic studies and density functional theory(DFT)calculations elucidate the formation and transformation of key intermediates,as well as the roles of active sites,metal-support interfaces,oxygen vacancies,and promoters.Additionally,representative catalytic performance data for MOFbased systems are compiled and compared,demonstrating their advantages over traditional catalysts in terms of CO_(2)conversion,methanol selectivity,and space-time yield.Future perspectives for MOF-based CO_(2)hydrogenation catalysts will prioritize two main directions:structural design and mechanistic understanding.The precise construction of active sites through multi-metallic synergy,defect engineering,and interfacial electronic modulation should be made to enhance catalyst selectivity and stability.In addition,advanced in situ characterization techniques combined with theoretical modeling are essential to unravel the detailed reaction mechanisms and intermediate behaviors,thereby guiding rational catalyst design.Moreover,to enable industrial application,challenges related to thermal/hydrothermal stability,catalyst recyclability,and cost-effective large-scale synthesis must be addressed.The development of green,scalable preparation methods and the integration of MOF catalysts into practical reaction systems(e.g.,flow reactors)will be crucial for bridging the gap between laboratory research and commercial deployment.Ultimately,multi-scale structure-performance optimization and catalytic system integration will be vital for accelerating the industrialization of MOF-based CO_(2)-to-methanol technologies.展开更多
The electrochemical oxidation of biomass-derived platform molecule 5-hydroxymethylfurfural(HMF)represents a crucial pathway for green transformation into high-value chemicals,yet its reaction pathway selectivity,effic...The electrochemical oxidation of biomass-derived platform molecule 5-hydroxymethylfurfural(HMF)represents a crucial pathway for green transformation into high-value chemicals,yet its reaction pathway selectivity,efficiency,and catalyst stability are strongly dependent on the electrolyte pH environment.Under alkaline conditions,high OH−concentration facilitates preferential aldehyde group oxidation and efficient deprotonation,enabling highly efficient synthesis of 2,5-furandicarboxylic acid,but simultaneously induces HMF self-degradation and complicates product separation.As pH decreases,the reaction mechanism shifts toward enhanced hydroxymethyl oxidation,leading to intermediate accumulation(such as 5-hydroxymethyl-2-furancarboxylic acid,2,5-diformylfuran,and 5-formyl-2-furancarboxylic acid)with challenging selectivity control and significantly slowed reaction kinetics.This review comprehensively examines the systematic differences in HMF oxidation pathways and surface catalytic mechanisms across the full pH range from alkaline to acidic conditions.Addressing the distinct reaction characteristics and core challenges in alkaline,near-neutral,and acidic media,we systematically evaluate design strategies for high-efficiency electrocatalysts and explore reactor design aspects.Future research should focus on process integration(with tailored reactor design)for energy consumption reduction in alkaline systems,targeted synthesis of diverse oxidation products in near-neutral systems,and innovative catalyst development for acidic systems,thereby advancing the efficiency,selectivity,and practical application of HMF electrooxidation technologies across the entire pH spectrum through synergistic optimization of catalyst,reactor,and process.展开更多
In mixture experiments,the observed response is determined by the relative proportions of the components,consequently rendering the experimental region a simplex.This paper focuses primarily on the optimal designs of ...In mixture experiments,the observed response is determined by the relative proportions of the components,consequently rendering the experimental region a simplex.This paper focuses primarily on the optimal designs of mixture experiments that involve process variables.Prior research has extensively delved into optimal orthogonal block designs for some classic mixture models with process variables.Based on the framework of general blending models,this paper proposes a class of symmetric linear mixture models,which can be regarded as a generalization of many existing ones.Under the orthogonal blocking conditions,orthogonal block designs are devised through Latin squares in the presence of process variables.TheD-,A-,and E-optimality criteria are utilized to obtain optimal designs at the boundary of the simplex in the case of 3 components.As the values of the exponents change,numerically derived optimal design points are presented to illustrate the pattern of their variations,and to verify the consistency of the results with previous research on some specific symmetric general blending models.展开更多
Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 str...Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.展开更多
In this paper,we provide a comprehensive examination of the evolution of graphics Application Programming Interfaces(APIs).We begin by exploring traditional graphics APIs,elucidating their distinct features and inhere...In this paper,we provide a comprehensive examination of the evolution of graphics Application Programming Interfaces(APIs).We begin by exploring traditional graphics APIs,elucidating their distinct features and inherent challenges.This sets the stage for a detailed exploration of modern graphics APIs,with a focus on four critical design principles.These principles are further analyzed through specific case studies and categorical examinations.The paper then introduces MoerEngine,a bespoke rendering engine,as a practical case to demonstrate the real-world application of these modern principles in software engineering.In conclusion,the study offers insights into the potential future trajectory of graphics APIs,spotlighting emerging design patterns and technological innovations.It also ventures to predict the development trends and capabilities of next-generation graphics APIs.展开更多
To systematically elucidate the central role of the cardiac autonomic nervous system(ANS)in maintaining cardiovascular homeostasis,analyze the pathological mechanisms underlying its dysregulation,integrate multidiscip...To systematically elucidate the central role of the cardiac autonomic nervous system(ANS)in maintaining cardiovascular homeostasis,analyze the pathological mechanisms underlying its dysregulation,integrate multidisciplinary research findings from the U.S.stimulating peripheral nerves to alleviate disease symptoms(SPARC)program,and evaluate the unique advantages and current limitations of acupuncture in modulating cardiac ANS function,ultimately proposing novel strategies for the prevention and treatment of cardiovascular diseases.A systematic literature review was conducted to synthesize current knowledge on the fundamental regulatory mechanisms of the cardiac ANS,the SPARC program's innovative contributions to neuroanatomy and neural pathway mapping,as well as clinical and experimental evidence supporting acupuncture's modulation of the ANS.The SPARC program has made significant progress in elucidating the anatomical organization and neural circuitry of the cardiac ANS through interdisciplinary collaboration,offering novel insights and methodological frameworks for studying cardiac autonomic regulation.Acupuncture,as a cornerstone of traditional medicine,has demonstrated both specificity and multi-target regulatory effects on the cardiac ANS through clinical and experimental studies.However,challenges remain,including an incomplete mechanistic understanding,technical limitations in research methodologies,and difficulties in translating findings into clinical practice.Future research on acupuncture should build upon its inherent strengths while advancing its integration with modern scientific and technological approaches.Strengthening interdisciplinary collaboration and leveraging artificial intelligence can open new frontiers in mechanistic exploration and technological innovation.These efforts will facilitate the internationalization of acupuncture research and contribute innovative perspectives and therapeutic strategies for cardiovascular disease prevention and treatment.展开更多
Memristors have emerged as a transformative technology in the realm of electronic devices,offering unique advantages such as fast switching speeds,low power consumption,and the ability to sensor-memory-compute.The app...Memristors have emerged as a transformative technology in the realm of electronic devices,offering unique advantages such as fast switching speeds,low power consumption,and the ability to sensor-memory-compute.The applications span across non-volatile memory,neuromorphic computing,hardware security,and beyond,prompting memristors to become a versatile solution for next-generation computing and data storage systems.Despite enormous potential of memristors,the transition from laboratory prototypes to large-scale applications is challenging in terms of material stability,device reproducibility,and array scalability.This review systematically explores recent advancements in high-performance memristor technologies,focusing on performance enhancement strategies through material engineering,structural design,pulse protocol optimization,and algorithm control.We provide an in-depth analysis of key performance metrics tailored to specific applications,including non-volatile memory,neuromorphic computing,and hardware security.Furthermore,we propose a co-design framework that integrates device-level optimizations with operational-level improvements,aiming to bridge the gap between theoretical models and practical implementations.展开更多
Compact size,high brightness,and wide field of view(FOV)are key requirements for long-wave infrared imagers used in military surveillance or night navigation.However,to meet the imaging requirements of high resolution...Compact size,high brightness,and wide field of view(FOV)are key requirements for long-wave infrared imagers used in military surveillance or night navigation.However,to meet the imaging requirements of high resolution and wide FOV,infrared optical systems often adopt complex optical lens groups,which will increase the size and weight of the optical system.In this paper,a strategy based on wavefront coding(WFC)is proposed to design a compact wide-FOV infrared imager.A cubic phase mask is inserted into the pupil plane of the infrared imager to correct the aberration.The simulated results show that,the WFC infrared imager has good imaging quality in a wide FOV of±16°.In addition,the WFC infrared imager achieves compactness with its 40 mm×40 mm×40 mm size.A fast focal ratio of 1 combined with an entrance pupil diameter of 25 mm ensures brightness.This work is of significance for designing a compact wide-FOV infrared imager.展开更多
基金the National Key R&D Program of China(No.2023YFE0208700)National Natural Sci-ence Foundation of China(No.92163109 and 52072095)+7 种基金Shenzhen Science and Technology Program(No.RCJC20231211090000001,GXWD20231129101105001)the National Natural Science Foundation of China(No.52205590)the Natural Science Foundation of Jiangsu Province(No.BK20220834)the Start-up Research Fund of Southeast University(No.RF1028623098)the State Key Laboratory of Robotics and Systems(HIT)(No.SKLRS-2024-KF-11)National Natural Science Foundation of China(No.52202348)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515011491)Shenzhen Science and Technology Program(Nos.GXWD20220818224716001,KJZD20231023100302006).
文摘Due to the small size,active mobility,and intrinsic softness,miniature soft robots hold promising po-tentials in reaching the deep region inside living bodies otherwise inaccessible with compelling agility,adaptability and safety.Various materials and actuation strategies have been developed for creating soft robots,among which,ferromagnetic soft materials that self-actuate in response to external magnetic fields have attracted worldwide attention due to their remote controllability and excellent compatibil-ity with biological tissues.This review presents comprehensive and systematic research advancements in the design,fabrication,and applications of ferromagnetic soft materials for miniature robots,providing in-sights into their potential use in biomedical fields and beyond.The programming strategies of ferromag-netic soft materials are summarized and classified,including mold-assisted programming,3D printing-assisted programming,microassembly-assisted programming,and magnetization reprogramming.Each approach possesses unique advantages in manipulating the magnetic responsiveness of ferromagnetic soft materials to achieve outstanding actuation and deformation performances.We then discuss the biomedi-cal applications of ferromagnetic soft material-based soft robots(e.g.,minimally invasive surgery,targeted delivery,and tissue engineering),highlighting their potentials in revolutionizing biomedical technologies.This review also points out the current challenges and provides insights into future research directions,which we hope can serve as a useful reference for the development of next-generation adaptive miniature robots.
基金supported by the National Natural Science Foundation of China Excellent Young Scientist Fund(22422801)the National Natural Science Foundation of China General Project(22278053)+1 种基金the National Natural Science Foundation of China General Project(22078041)Dalian High-level Talents Innovation Support Program(2023RQ059).
文摘G protein coupled receptor kinase 2 (GRK2) is a kinase that regulates cardiac signaling activity. Inhibiting GRK2 is a promising mechanism for the treatment of heart failure (HF). Further development and optimization of inhibitors targeting GRK2 are highly meaningful. Therefore, in order to design GRK2 inhibitors with better performance, the most active molecule was selected as a reference compound from a data set containing 4-pyridylhydrazone derivatives and triazole derivatives, and its scaffold was extracted as the initial scaffold. Then, a powerful optimization-based framework for de novo drug design, guided by binding affinity, was used to generate a virtual molecular library targeting GRK2. The binding affinity of each virtual compound in this dataset was predicted by our developed deep learning model, and the designed potential compound with high binding affinity was selected for molecular docking and molecular dynamics simulation. It was found that the designed potential molecule binds to the ATP site of GRK2, which consists of key amino acids including Arg199, Gly200, Phe202, Val205, Lys220, Met274 and Asp335. The scaffold of the molecule is stabilized mainly by H-bonding and hydrophobic contacts. Concurrently, the reference compound in the dataset was also simulated by docking. It was found that this molecule also binds to the ATP site of GRK2. In addition, its scaffold is stabilized mainly by H-bonding and π-cation stacking interactions with Lys220, as well as hydrophobic contacts. The above results show that the designed potential molecule has similar binding modes to the reference compound, supporting the effectiveness of our framework for activity-focused molecular design. Finally, we summarized the interaction characteristics of general GRK2 inhibitors and gained insight into their molecule-target binding mechanisms, thereby facilitating the expansion of lead to hit compound.
基金the financial supports from National Key R&D Program for Young Scientists of China(Grant No.2022YFC3080900)National Natural Science Foundation of China(Grant No.52374181)+1 种基金BIT Research and Innovation Promoting Project(Grant No.2024YCXZ017)supported by Science and Technology Innovation Program of Beijing institute of technology under Grant No.2022CX01025。
文摘In this study,an inverse design framework was established to find lightweight honeycomb structures(HCSs)with high impact resistance.The hybrid HCS,composed of re-entrant(RE)and elliptical annular re-entrant(EARE)honeycomb cells,was created by constructing arrangement matrices to achieve structural lightweight.The machine learning(ML)framework consisted of a neural network(NN)forward regression model for predicting impact resistance and a multi-objective optimization algorithm for generating high-performance designs.The surrogate of the local design space was initially realized by establishing the NN in the small sample dataset,and the active learning strategy was used to continuously extended the local optimal design until the model converged in the global space.The results indicated that the active learning strategy significantly improved the inference capability of the NN model in unknown design domains.By guiding the iteration direction of the optimization algorithm,lightweight designs with high impact resistance were identified.The energy absorption capacity of the optimal design reached 94.98%of the EARE honeycomb,while the initial peak stress and mass decreased by 28.85%and 19.91%,respectively.Furthermore,Shapley Additive Explanations(SHAP)for global explanation of the NN indicated a strong correlation between the arrangement mode of HCS and its impact resistance.By reducing the stiffness of the cells at the top boundary of the structure,the initial impact damage sustained by the structure can be significantly improved.Overall,this study proposed a general lightweight design method for array structures under impact loads,which is beneficial for the widespread application of honeycomb-based protective structures.
基金supported by the National Natural Science Foundation of China(grant numbers 11972287 and 12072266)the State Key Laboratory of Structural Analysis,Optimization and CAE Software for Industrial Equipment(GZ23106)+1 种基金the National Key Laboratory of Aircraft Configuration Design(No.2023-JCJQ-LB-070)the Fundamental Research Funds for the Central Universities.
文摘Chiral metamaterials are manmade structures with extraordinary mechanical properties derived from their special geometric design instead of chemical composition.To make the mechanical deformation programmable,the non-uniform rational B-spline(NURBS)curves are taken to replace the traditional ligament boundaries of the chiral structure.The Neural networks are innovatively inserted into the calculation of mechanical properties of the chiral structure instead of finite element methods to improve computational efficiency.For the problem of finding structure configuration with specified mechanical properties,such as Young’s modulus,Poisson’s ratio or deformation,an inverse design method using the Neural network-based proxy model is proposed to build the relationship between mechanical properties and geometric configuration.To satisfy some more complex deformation requirements,a non-homogeneous inverse design method is proposed and verified through simulation and experiments.Numerical and test results reveal the high computational efficiency and accuracy of the proposed method in the design of chiral metamaterials.
基金supported by the National Natural Science Foundation of China (Grant Nos.12102021,12372105,12172026,and 12225201)the Fundamental Research Funds for the Central Universities and the Academic Excellence Foundation of BUAA for PhD Students.
文摘Advanced programmable metamaterials with heterogeneous microstructures have become increasingly prevalent in scientific and engineering disciplines attributed to their tunable properties.However,exploring the structure-property relationship in these materials,including forward prediction and inverse design,presents substantial challenges.The inhomogeneous microstructures significantly complicate traditional analytical or simulation-based approaches.Here,we establish a novel framework that integrates the machine learning(ML)-encoded multiscale computational method for forward prediction and Bayesian optimization for inverse design.Unlike prior end-to-end ML methods limited to specific problems,our framework is both load-independent and geometry-independent.This means that a single training session for a constitutive model suffices to tackle various problems directly,eliminating the need for repeated data collection or training.We demonstrate the efficacy and efficiency of this framework using metamaterials with designable elliptical holes or lattice honeycombs microstructures.Leveraging accelerated forward prediction,we can precisely customize the stiffness and shape of metamaterials under diverse loading scenarios,and extend this capability to multi-objective customization seamlessly.Moreover,we achieve topology optimization for stress alleviation at the crack tip,resulting in a significant reduction of Mises stress by up to 41.2%and yielding a theoretical interpretable pattern.This framework offers a general,efficient and precise tool for analyzing the structure-property relationships of novel metamaterials.
基金supported by the National Natural Science Foundation of China under Grant No.92582204,No.62577007,and No.62177003the Fundamental Research Funds for the Central Universities under Grant No.JKF-2025011975129.
文摘Online programming platforms are popular in programming education.However,there has been no research investigating students’real opinions and expectations of the error feedback mechanisms,leaving educators without a solid data foundation when attempting to improve the error feedback mechanisms.This paper makes a survey of 834 students across various programming courses and investigates student perceptions of error feedback mechanisms on online programming platforms.It explores the effectiveness of existing feedback,student satisfaction,and preferences for potential improvements,focusing on automatic error localization and program repair mechanisms.Results reveal a significant portion of students are dissatisfied with current feedback due to its limited informativeness.Students also express a clear demand for stronger feedback mechanisms,such as error localization and repair hints.Nevertheless,they prefer feedback that subtly guides them toward solutions,rather than providing direct and explicit answers,valuing the opportunity to enhance their debugging skills.The findings suggest a need for balanced,educational-focused feedback mechanisms that aid learning while promoting independent problem-solving.
文摘Purpose-Interface management is the process of managing communications,responsibilities and coordination of project parties,phases or physical entities which are dependent on one another.Interface management is a crucial part of managing any construction project-but particularly important for high-speed railway projects that often have several contractual parties and stakeholders,very long project timelines and huge upfront cost overlays.This paper discusses how various project interfaces were managed during the design and construction of the civil engineering infrastructure for the High Speed Two(HS2)project in the United Kingdom.Design/methodology/approach-The paper uses the case study methodology.Key interfaces on the HS2 project are grouped into various categories and the paper discusses how they were managed within the Area North Integrated Project Team(IPT)of the HS2 project made up of contractor Balfour Beatty VINCI(BBV),the Mott MacDonald SYSTRA Design Joint Venture(DJV)and client HS2 Ltd.3 different case studies drawn from across the IPT are used,each of them highlighting different interfaces and how these interfaces were managed.Findings-The paper shows how innovative technical designs and modern methods of construction were used to address some of the unique and peculiar challenges of designing a brand-new railway in the United Kingdom.Addressing the contrasting and often competing requirements of different stakeholders,coupled with challenging physical constraints of the very limited land available for the project and the use of a rarely used Act of Parliament in the delivery of the project required different approach to interface management.Collaboration and proactive stakeholder engagement are necessary for successful interface management on megaprojects.The authors posit that adopting an integrated approach to engineering and construction management is an essential ingredient for the successful delivery of high-speed railway projects.Originality/value-With many high-speed railway projects around the world coming up in the next few years,understanding the context and challenges for each country will help engineering and design managers adopt appropriate approaches for their projects.The lessons learned on the HS2 project are also transferable to other mega infrastructure projects with complex project interfaces.
基金financially supported by Ministerio de Ciencia e Innovación projects SAF2017-82736-C2-1-R to MTMFin Universidad Autónoma de Madrid and by Fundación Universidad Francisco de Vitoria to JS+2 种基金a predoctoral scholarship from Fundación Universidad Francisco de Vitoriafinancial support from a 6-month contract from Universidad Autónoma de Madrida 3-month contract from the School of Medicine of Universidad Francisco de Vitoria。
文摘Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.
基金Supported by the National Key Research and Development Program of China(2023YFB4104500,2023YFB4104502)the National Natural Science Foundation of China(22138013)the Taishan Scholar Project(ts201712020).
文摘Against the backdrop of escalating global climate change and energy crises,the resource utilization of carbon dioxide(CO_(2)),a major greenhouse gas,has become a crucial pathway for achieving carbon peaking and carbon neutrality goals.The hydrogenation of CO_(2)to methanol not only enables carbon sequestration and recycling,but also provides a route to produce high value-added fuels and basic chemical feedstocks,holding significant environmental and economic potential.However,this conversion process is thermodynamically and kinetically limited,and traditional catalyst systems(e.g.,Cu/ZnO/Al_(2)O_(3))exhibit inadequate activity,selectivity,and stability under mild conditions.Therefore,the development of novel high-performance catalysts with precisely tunable structures and functionalities is imperative.Metal-organic frameworks(MOFs),as crystalline porous materials with high surface area,tunable pore structures,and diverse metal-ligand compositions,have the great potential in CO_(2)hydrogenation catalysis.Their structural design flexibility allows for the construction of well-dispersed active sites,tailored electronic environments,and enhanced metal-support interactions.This review systematically summarizes the recent advances in MOF-based and MOF-derived catalysts for CO_(2)hydrogenation to methanol,focusing on four design strategies:(1)spatial confinement and in situ construction,(2)defect engineering and ion-exchange,(3)bimetallic synergy and hybrid structure design,and(4)MOF-derived nanomaterial synthesis.These approaches significantly improve CO_(2)conversion and methanol selectivity by optimizing metal dispersion,interfacial structures,and reaction pathways.The reaction mechanism is further explored by focusing on the three main reaction pathways:the formate pathway(HCOO*),the RWGS(Reverse Water Gas Shift reaction)+CO*hydrogenation pathway,and the trans-COOH pathway.In situ spectroscopic studies and density functional theory(DFT)calculations elucidate the formation and transformation of key intermediates,as well as the roles of active sites,metal-support interfaces,oxygen vacancies,and promoters.Additionally,representative catalytic performance data for MOFbased systems are compiled and compared,demonstrating their advantages over traditional catalysts in terms of CO_(2)conversion,methanol selectivity,and space-time yield.Future perspectives for MOF-based CO_(2)hydrogenation catalysts will prioritize two main directions:structural design and mechanistic understanding.The precise construction of active sites through multi-metallic synergy,defect engineering,and interfacial electronic modulation should be made to enhance catalyst selectivity and stability.In addition,advanced in situ characterization techniques combined with theoretical modeling are essential to unravel the detailed reaction mechanisms and intermediate behaviors,thereby guiding rational catalyst design.Moreover,to enable industrial application,challenges related to thermal/hydrothermal stability,catalyst recyclability,and cost-effective large-scale synthesis must be addressed.The development of green,scalable preparation methods and the integration of MOF catalysts into practical reaction systems(e.g.,flow reactors)will be crucial for bridging the gap between laboratory research and commercial deployment.Ultimately,multi-scale structure-performance optimization and catalytic system integration will be vital for accelerating the industrialization of MOF-based CO_(2)-to-methanol technologies.
基金supported by the National Key R&D Program of China(2023YFA1507400)the National Natural Science Foundation of China(Grant No.22325805,22441010,22408203)+2 种基金Beijing Natural Science Foundation(Grant No.JQ22003)the Haihe Laboratory of Sustainable Chemical Transformations(24HHWCSS00007)Tsinghua University Dushi Program,and Sinopec Group(PR20232572).
文摘The electrochemical oxidation of biomass-derived platform molecule 5-hydroxymethylfurfural(HMF)represents a crucial pathway for green transformation into high-value chemicals,yet its reaction pathway selectivity,efficiency,and catalyst stability are strongly dependent on the electrolyte pH environment.Under alkaline conditions,high OH−concentration facilitates preferential aldehyde group oxidation and efficient deprotonation,enabling highly efficient synthesis of 2,5-furandicarboxylic acid,but simultaneously induces HMF self-degradation and complicates product separation.As pH decreases,the reaction mechanism shifts toward enhanced hydroxymethyl oxidation,leading to intermediate accumulation(such as 5-hydroxymethyl-2-furancarboxylic acid,2,5-diformylfuran,and 5-formyl-2-furancarboxylic acid)with challenging selectivity control and significantly slowed reaction kinetics.This review comprehensively examines the systematic differences in HMF oxidation pathways and surface catalytic mechanisms across the full pH range from alkaline to acidic conditions.Addressing the distinct reaction characteristics and core challenges in alkaline,near-neutral,and acidic media,we systematically evaluate design strategies for high-efficiency electrocatalysts and explore reactor design aspects.Future research should focus on process integration(with tailored reactor design)for energy consumption reduction in alkaline systems,targeted synthesis of diverse oxidation products in near-neutral systems,and innovative catalyst development for acidic systems,thereby advancing the efficiency,selectivity,and practical application of HMF electrooxidation technologies across the entire pH spectrum through synergistic optimization of catalyst,reactor,and process.
基金supported by the National Natural Science Foundation of China[grant numbers 12071329,12471246].
文摘In mixture experiments,the observed response is determined by the relative proportions of the components,consequently rendering the experimental region a simplex.This paper focuses primarily on the optimal designs of mixture experiments that involve process variables.Prior research has extensively delved into optimal orthogonal block designs for some classic mixture models with process variables.Based on the framework of general blending models,this paper proposes a class of symmetric linear mixture models,which can be regarded as a generalization of many existing ones.Under the orthogonal blocking conditions,orthogonal block designs are devised through Latin squares in the presence of process variables.TheD-,A-,and E-optimality criteria are utilized to obtain optimal designs at the boundary of the simplex in the case of 3 components.As the values of the exponents change,numerically derived optimal design points are presented to illustrate the pattern of their variations,and to verify the consistency of the results with previous research on some specific symmetric general blending models.
基金The National Natural Science Foundation of China[72174184]provided policy and financialsupport for this research.
文摘Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.
基金supported by ZTE Industry-University-Institute Cooperation Funds under Grant No.IA20230921014。
文摘In this paper,we provide a comprehensive examination of the evolution of graphics Application Programming Interfaces(APIs).We begin by exploring traditional graphics APIs,elucidating their distinct features and inherent challenges.This sets the stage for a detailed exploration of modern graphics APIs,with a focus on four critical design principles.These principles are further analyzed through specific case studies and categorical examinations.The paper then introduces MoerEngine,a bespoke rendering engine,as a practical case to demonstrate the real-world application of these modern principles in software engineering.In conclusion,the study offers insights into the potential future trajectory of graphics APIs,spotlighting emerging design patterns and technological innovations.It also ventures to predict the development trends and capabilities of next-generation graphics APIs.
基金supported by the National Natural Science Foundation of China(82174513)Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ-JQ2023003).
文摘To systematically elucidate the central role of the cardiac autonomic nervous system(ANS)in maintaining cardiovascular homeostasis,analyze the pathological mechanisms underlying its dysregulation,integrate multidisciplinary research findings from the U.S.stimulating peripheral nerves to alleviate disease symptoms(SPARC)program,and evaluate the unique advantages and current limitations of acupuncture in modulating cardiac ANS function,ultimately proposing novel strategies for the prevention and treatment of cardiovascular diseases.A systematic literature review was conducted to synthesize current knowledge on the fundamental regulatory mechanisms of the cardiac ANS,the SPARC program's innovative contributions to neuroanatomy and neural pathway mapping,as well as clinical and experimental evidence supporting acupuncture's modulation of the ANS.The SPARC program has made significant progress in elucidating the anatomical organization and neural circuitry of the cardiac ANS through interdisciplinary collaboration,offering novel insights and methodological frameworks for studying cardiac autonomic regulation.Acupuncture,as a cornerstone of traditional medicine,has demonstrated both specificity and multi-target regulatory effects on the cardiac ANS through clinical and experimental studies.However,challenges remain,including an incomplete mechanistic understanding,technical limitations in research methodologies,and difficulties in translating findings into clinical practice.Future research on acupuncture should build upon its inherent strengths while advancing its integration with modern scientific and technological approaches.Strengthening interdisciplinary collaboration and leveraging artificial intelligence can open new frontiers in mechanistic exploration and technological innovation.These efforts will facilitate the internationalization of acupuncture research and contribute innovative perspectives and therapeutic strategies for cardiovascular disease prevention and treatment.
基金supported by the National Key R&D Project from the Minister of Science and Technology(2024YFA1211500)the National Natural Science Foundation of China(Grant Nos.62304130,62405158 and 62574123)+1 种基金the Shanghai youth science and technology star project(24QA2702800)Shanghai Key Laboratory of Chips and Systems for Intelligent Connected Vehicle。
文摘Memristors have emerged as a transformative technology in the realm of electronic devices,offering unique advantages such as fast switching speeds,low power consumption,and the ability to sensor-memory-compute.The applications span across non-volatile memory,neuromorphic computing,hardware security,and beyond,prompting memristors to become a versatile solution for next-generation computing and data storage systems.Despite enormous potential of memristors,the transition from laboratory prototypes to large-scale applications is challenging in terms of material stability,device reproducibility,and array scalability.This review systematically explores recent advancements in high-performance memristor technologies,focusing on performance enhancement strategies through material engineering,structural design,pulse protocol optimization,and algorithm control.We provide an in-depth analysis of key performance metrics tailored to specific applications,including non-volatile memory,neuromorphic computing,and hardware security.Furthermore,we propose a co-design framework that integrates device-level optimizations with operational-level improvements,aiming to bridge the gap between theoretical models and practical implementations.
文摘Compact size,high brightness,and wide field of view(FOV)are key requirements for long-wave infrared imagers used in military surveillance or night navigation.However,to meet the imaging requirements of high resolution and wide FOV,infrared optical systems often adopt complex optical lens groups,which will increase the size and weight of the optical system.In this paper,a strategy based on wavefront coding(WFC)is proposed to design a compact wide-FOV infrared imager.A cubic phase mask is inserted into the pupil plane of the infrared imager to correct the aberration.The simulated results show that,the WFC infrared imager has good imaging quality in a wide FOV of±16°.In addition,the WFC infrared imager achieves compactness with its 40 mm×40 mm×40 mm size.A fast focal ratio of 1 combined with an entrance pupil diameter of 25 mm ensures brightness.This work is of significance for designing a compact wide-FOV infrared imager.
