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High-throughput and intelligent design of potential GRK2 inhibitor candidates using deep learning and mathematical programming methods
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作者 Yujing Zhao Qilei Liu +3 位作者 Jian Du Qingwei Meng Liang Sun Lei Zhang 《Chinese Journal of Chemical Engineering》 2025年第8期11-22,共12页
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
关键词 mathematical modeling Optimal design Product design GRK2 mathematical programmingmethod Binding affinity
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Combining reinforcement learning with mathematical programming:An approach for optimal design of heat exchanger networks
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作者 Hui Tan Xiaodong Hong +4 位作者 Zuwei Liao Jingyuan Sun Yao Yang Jingdai Wang Yongrong Yang 《Chinese Journal of Chemical Engineering》 SCIE EI CAS CSCD 2024年第5期63-71,共9页
Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinea... Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinear and combinatorial nature of the HEN problem,it is not easy to find solutions of high quality for large-scale problems.The reinforcement learning(RL)method,which learns strategies through ongoing exploration and exploitation,reveals advantages in such area.However,due to the complexity of the HEN design problem,the RL method for HEN should be dedicated and designed.A hybrid strategy combining RL with mathematical programming is proposed to take better advantage of both methods.An insightful state representation of the HEN structure as well as a customized reward function is introduced.A Q-learning algorithm is applied to update the HEN structure using theε-greedy strategy.Better results are obtained from three literature cases of different scales. 展开更多
关键词 Heat exchanger network Reinforcement learning mathematical programming Process design
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Glia-to-neuron reprogramming to the rescue?
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作者 Jack W.Hickmott Cindi M.Morshead 《Neural Regeneration Research》 SCIE CAS 2025年第5期1395-1396,共2页
Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c... Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state. 展开更多
关键词 programming PASSING proof
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Neurocircuit regeneration by extracellular matrix reprogramming
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作者 Shengzhang Su Ian N.Levasseur Kimberly M.Alonge 《Neural Regeneration Research》 SCIE CAS 2025年第8期2300-2301,共2页
The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functio... The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases. 展开更多
关键词 MATRIX programming
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Safe flight corridor constrained sequential convex programming for efficient trajectory generation of fixed-wing UAVs 被引量:2
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作者 Jing SUN Guangtong XU +2 位作者 Zhu WANG Teng LONG Jingliang SUN 《Chinese Journal of Aeronautics》 2025年第1期537-550,共14页
Generating dynamically feasible trajectory for fixed-wing Unmanned Aerial Vehicles(UAVs)in dense obstacle environments remains computationally intractable.This paper proposes a Safe Flight Corridor constrained Sequent... Generating dynamically feasible trajectory for fixed-wing Unmanned Aerial Vehicles(UAVs)in dense obstacle environments remains computationally intractable.This paper proposes a Safe Flight Corridor constrained Sequential Convex Programming(SFC-SCP)to improve the computation efficiency and reliability of trajectory generation.SFC-SCP combines the front-end convex polyhedron SFC construction and back-end SCP-based trajectory optimization.A Sparse A^(*)Search(SAS)driven SFC construction method is designed to efficiently generate polyhedron SFC according to the geometric relation among obstacles and collision-free waypoints.Via transforming the nonconvex obstacle-avoidance constraints to linear inequality constraints,SFC can mitigate infeasibility of trajectory planning and reduce computation complexity.Then,SCP casts the nonlinear trajectory optimization subject to SFC into convex programming subproblems to decrease the problem complexity.In addition,a convex optimizer based on interior point method is customized,where the search direction is calculated via successive elimination to further improve efficiency.Simulation experiments on dense obstacle scenarios show that SFC-SCP can generate dynamically feasible safe trajectory rapidly.Comparative studies with state-of-the-art SCP-based methods demonstrate the efficiency and reliability merits of SFC-SCP.Besides,the customized convex optimizer outperforms off-the-shelf optimizers in terms of computation time. 展开更多
关键词 Fixed-wing unmanned aerial vehicle Efficient trajectory planning Safe flight corridor Sequential convex programming Customized convex optimizer
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Journal of Mathematical Research with Applications Guide for Authors
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《Journal of Mathematical Research with Applications》 2025年第5期F0003-F0003,共1页
Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Appli... Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Applied Mathematics,is a home for original research papers of the highest quality in all areas of mathematics with applications.The target audience comprises:pure and applied mathematicians,graduate students in broad fields of sciences and technology,scientists and engineers interested in mathematics. 展开更多
关键词 academic journal applied mathematics MATHEMATICS mathematical research research papers pure mathematics journal overview china society industrial applied mathematics
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Journal of Mathematical Research with Applications Guide for Authors
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《Journal of Mathematical Research with Applications》 2025年第3期F0003-F0003,共1页
Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Appli... Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Applied Mathematics,is a home for original research papers of the highest quality in all areas of mathematics with applications.The target audience comprises:pure and applied mathematicians,graduate students in broad felds of sciences and technology,scientists and engineers interested in mathematics. 展开更多
关键词 applied mathematics MATHEMATICS mathematical research research papers pure mathematics journal overview
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Journal of Mathematical Research with Applications Guide for Authors
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《Journal of Mathematical Research with Applications》 2025年第4期F0003-F0003,共1页
Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Appli... Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Applied Mathematics,is a home for original research papers of the highest quality in all areas of mathematics with applications.The target audience comprises:pure and applied mathematicians,graduate students in broad fields of sciences and technology,scientists and engineers interested in mathematics. 展开更多
关键词 academic journal applied mathematics MATHEMATICS mathematical research research papers pure mathematics journal overview china society industrial applied mathematics
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Journal of Mathematical Research with Applications Guide for Authors
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《Journal of Mathematical Research with Applications》 2025年第2期F0003-F0003,共1页
Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Appli... Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Applied Mathematics,is a home for original research papers of the highest quality in all areas of mathematics with applications.The target audience comprises:pure and applied mathematicians,graduate students in broad fields of sciences and technology,scientists and engineers interested in mathematics. 展开更多
关键词 journal overview applied mathematics academic journal mathematical research research papers pure mathematics
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Journal of Mathematical Research with Applications Guide for Authors
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《Journal of Mathematical Research with Applications》 2025年第1期F0003-F0003,共1页
Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Appli... Journal overview:Journal of Mathematical Research with Applications(JMRA),formerly Journal of Mathematical Research and Exposition(JMRE)created in 1981,one of the transactions of China Society for Industrial and Applied Mathematics,is a home for original research papers of the highest quality in all areas of mathematics with applications.The target audience comprises:pure and applied mathematicians,graduate students in broad fields of sciences and technology,scientists and engineers interested in mathematics. 展开更多
关键词 mathematical MATHEMATICS INTERESTED
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Evaluation of Integer Programming Solvers to Improve the Efficiency of Individual Work Planning
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作者 Keiichi Takahashi 《Open Journal of Modelling and Simulation》 2025年第1期51-64,共14页
This study proposes a novel approach to optimizing individual work schedules for book digitization using mixed-integer programming (MIP). By leveraging the power of MIP solvers, we aimed to minimize the overall digiti... This study proposes a novel approach to optimizing individual work schedules for book digitization using mixed-integer programming (MIP). By leveraging the power of MIP solvers, we aimed to minimize the overall digitization time while considering various constraints and process dependencies. The book digitization process involves three key steps: cutting, scanning, and binding. Each step has specific requirements and limitations such as the number of pages that can be processed simultaneously and potential bottlenecks. To address these complexities, we formulate the problem as a one-machine job shop scheduling problem with additional constraints to capture the unique characteristics of book digitization. We conducted a series of experiments to evaluate the performance of our proposed approach. By comparing the optimized schedules with the baseline approach, we demonstrated significant reductions in the overall processing time. In addition, we analyzed the impact of different weighting schemes on the optimization results, highlighting the importance of identifying and prioritizing critical processes. Our findings suggest that MIP-based optimization can be a valuable tool for improving the efficiency of individual work schedules, even in seemingly simple tasks, such as book digitization. By carefully considering specific constraints and objectives, we can save time and leverage resources by carefully considering specific constraints and objectives. 展开更多
关键词 Mixed Integer programming Scheduling Optimization Work Planning Book Scanning Gantt Chart
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Research on Human-Computer Collaboration Paradigm in AIGC-Empowered High-Level Language Programming Courses
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作者 Hongyuan Wang Baokai Zu +2 位作者 Yafang Li Wanting Zhu Hongli Chen 《Journal of Contemporary Educational Research》 2025年第5期285-289,共5页
With the rapid development of artificial intelligence technology,AIGC(Artificial Intelligence-Generated Content)has triggered profound changes in the field of high-level language programming courses.This paper deeply ... With the rapid development of artificial intelligence technology,AIGC(Artificial Intelligence-Generated Content)has triggered profound changes in the field of high-level language programming courses.This paper deeply explored the application principles,advantages,and limitations of AIGC in intelligent code generation,analyzed the new mode of human-computer collaboration in high-level language programming courses driven by AIGC,discussed the impact of human-computer collaboration on programming efficiency and code quality through practical case studies,and looks forward to future development trends.This research aims to provide theoretical and practical guidance for high-level language programming courses and promote innovative development of high-level language programming courses under the human-computer collaboration paradigm. 展开更多
关键词 Human-computer collaboration AIGC High-level language programming Intelligence programming Efficiency improvement
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A 28 nm 576K RRAM-based computing-in-memory macro featuring hybrid programming with area efficiency of 2.82 TOPS/mm^(2)
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作者 Siqi Liu Songtao Wei +7 位作者 Peng Yao Dong Wu Lu Jie Sining Pan Jianshi Tang Bin Gao He Qian Huaqiang Wu 《Journal of Semiconductors》 2025年第6期112-119,共8页
Computing-in-memory(CIM)has been a promising candidate for artificial-intelligent applications thanks to the absence of data transfer between computation and storage blocks.Resistive random access memory(RRAM)based CI... Computing-in-memory(CIM)has been a promising candidate for artificial-intelligent applications thanks to the absence of data transfer between computation and storage blocks.Resistive random access memory(RRAM)based CIM has the advantage of high computing density,non-volatility as well as high energy efficiency.However,previous CIM research has predominantly focused on realizing high energy efficiency and high area efficiency for inference,while little attention has been devoted to addressing the challenges of on-chip programming speed,power consumption,and accuracy.In this paper,a fabri-cated 28 nm 576K RRAM-based CIM macro featuring optimized on-chip programming schemes is proposed to address the issues mentioned above.Different strategies of mapping weights to RRAM arrays are compared,and a novel direct-current ADC design is designed for both programming and inference stages.Utilizing the optimized hybrid programming scheme,4.67×programming speed,0.15×power saving and 4.31×compact weight distribution are realized.Besides,this macro achieves a normalized area efficiency of 2.82 TOPS/mm2 and a normalized energy efficiency of 35.6 TOPS/W. 展开更多
关键词 computing-in-memory on-chip programming scheme hybrid programming resistive random access memory matrix-vector-multiplication acceleration
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Adapting High-Level Language Programming(C Language)Education in the Era of Large Language Models
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作者 Baokai Zu Hongyuan Wang +1 位作者 Hongli Chen Yafang Li 《Journal of Contemporary Educational Research》 2025年第5期264-269,共6页
With the widespread application of large language models(LLMs)in natural language processing and code generation,traditional High-Level Language Programming courses are facing unprecedented challenges and opportunitie... With the widespread application of large language models(LLMs)in natural language processing and code generation,traditional High-Level Language Programming courses are facing unprecedented challenges and opportunities.As a core programming language for computer science majors,C language remains irreplaceable due to its foundational nature and engineering adaptability.This paper,based on the rapid development of large model technologies,proposes a systematic reform design for C language teaching,focusing on teaching objectives,content structure,teaching methods,and evaluation systems.The article suggests a teaching framework centered on“human-computer collaborative programming,”integrating prompt training,AI-assisted debugging,and code generation analysis,aiming to enhance students’problem modeling ability,programming expression skills,and AI collaboration literacy. 展开更多
关键词 Large language models(LLMs) High-level language programming C language Human-computer collaborative programming
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Reprogramming induced neurons from olfactory ensheathing glial cells: A feasible approach for spinal cord injury repair
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作者 Javier Sierra María Portela-Lomba +1 位作者 Diana Simón M.Teresa Moreno-Flores 《Neural Regeneration Research》 2026年第1期296-297,共2页
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
关键词 INJURY feasible programming
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From flying dreams to programming pioneer
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作者 孙启禄 《疯狂英语(新读写)》 2025年第7期24-27,76,共5页
More than seventy years before airplanes were invented,a twelve⁃year⁃old girl named Ada Lovelace dreamed of flying.She studied birds and experimented with materials to make wings,even writing a guide called Flyology.B... More than seventy years before airplanes were invented,a twelve⁃year⁃old girl named Ada Lovelace dreamed of flying.She studied birds and experimented with materials to make wings,even writing a guide called Flyology.But her curiosity didnt stop there. 展开更多
关键词 GUIDE flyology ada lovelace programming pioneer FLYING
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AI-Enabled Computer Programming Course Teaching Reform
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作者 Yao Dai 《Journal of Electronic Research and Application》 2025年第3期90-96,共7页
With the rapid development of modern science and technology,the era of artificial intelligence has quietly come.Against the background of the new era,students’learning needs,learning resource acquisition methods,teac... With the rapid development of modern science and technology,the era of artificial intelligence has quietly come.Against the background of the new era,students’learning needs,learning resource acquisition methods,teachers’teaching concepts,teaching tools,and so on have changed significantly.How to carry out teaching reform based on this change has become one of the important issues facing educators,and the same is true for the teaching of computer programming courses.This paper focuses on the teaching reform of AI-enabled computer programming courses,analyzes its basic problems,and puts forward corresponding reform countermeasures to provide a useful reference for front-line teachers. 展开更多
关键词 AI Computer programming
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Mathematical principle and engineering application of end-mining technology with non-pillar
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作者 Jianyong Qiao Zhiqiang Wang +1 位作者 Tingzhao Li Yun Zhao 《Earth Energy Science》 2025年第1期85-97,共13页
To ameliorate the difficulties of on-site dynamic disaster control in the end-mining stage of traditional mining engineering,this paper introduces the mathematical research and engineering application of the end-minin... To ameliorate the difficulties of on-site dynamic disaster control in the end-mining stage of traditional mining engineering,this paper introduces the mathematical research and engineering application of the end-mining technology system with non-pillar in mines(ETSNM)in recent years.The petal warning criterion for the stability of the surrounding rock of the roadway at the end-mining stage was obtained by studying the inverse problem of the petal theorem.A conformal mathematical model of the end-mining stage was established using the conformal mapping method,and the limit theorem of the peak point of mine pressure(LTPPMP)in the end-mining stage was demonstrated.Based on the cross-fusion of the above basic mathematical theory and the LTPPMP,a new ETSNM model was proposed,which includes no coal pillar,no dedicated retracement roadways,and fast retracement equipment(NNF).The mathematical principles of engineering technology for height control,speed limit,and roof cutting in the end-mining stage with non-pillar were revealed.The scientific and application values of the ETSNM were confirmed through engineering applications.Based on this,a new non-pillar control technology for dynamic disasters in the end-mining stage was proposed.The above research will play an active role in promoting the engineering application of ETSNM driven by mathematical theory. 展开更多
关键词 NON-PILLAR End-mining technology mathematical principle Engineering application Dynamic disaster
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Study on Improving the Teaching Effect of Mathematical Methods for Physics Using Manim Animation Technology
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作者 Yong Niu Linhao Wang +1 位作者 Ying Wang Pan Wang 《Journal of Contemporary Educational Research》 2025年第10期215-222,共8页
With the development of educational digitalization,how to effectively apply digital animation technology to traditional classroom teaching has become an urgent problem to be solved.This study explores the application ... With the development of educational digitalization,how to effectively apply digital animation technology to traditional classroom teaching has become an urgent problem to be solved.This study explores the application of Manim in the course of Mathematical Methods for Physics.Taking the visualization of Fourier series,complex numbers,and other content as examples,it improves students’understanding of complex and abstract mathematical physics concepts through dynamic and visual teaching methods.The teaching effect shows that Manim helps to enhance students’learning experience,improve teaching efficiency and effectiveness,and has a positive impact on students’active learning ability.The research in this paper can provide references and inspiration for the educational digitalization of higher education. 展开更多
关键词 Manim mathematical methods for physics Educational digitalization Animation visualization
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Enhancing the data processing speed of a deep-learning-based three-dimensional single molecule localization algorithm (FD-DeepLoc) with a combination of feature compression and pipeline programming
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作者 Shuhao Guo Jiaxun Lin +1 位作者 Yingjun Zhang Zhen-Li Huang 《Journal of Innovative Optical Health Sciences》 2025年第2期150-160,共11页
Three-dimensional(3D)single molecule localization microscopy(SMLM)plays an important role in biomedical applications,but its data processing is very complicated.Deep learning is a potential tool to solve this problem.... Three-dimensional(3D)single molecule localization microscopy(SMLM)plays an important role in biomedical applications,but its data processing is very complicated.Deep learning is a potential tool to solve this problem.As the state of art 3D super-resolution localization algorithm based on deep learning,FD-DeepLoc algorithm reported recently still has a gap with the expected goal of online image processing,even though it has greatly improved the data processing throughput.In this paper,a new algorithm Lite-FD-DeepLoc is developed on the basis of FD-DeepLoc algorithm to meet the online image processing requirements of 3D SMLM.This new algorithm uses the feature compression method to reduce the parameters of the model,and combines it with pipeline programming to accelerate the inference process of the deep learning model.The simulated data processing results show that the image processing speed of Lite-FD-DeepLoc is about twice as fast as that of FD-DeepLoc with a slight decrease in localization accuracy,which can realize real-time processing of 256×256 pixels size images.The results of biological experimental data processing imply that Lite-FD-DeepLoc can successfully analyze the data based on astigmatism and saddle point engineering,and the global resolution of the reconstructed image is equivalent to or even better than FD-DeepLoc algorithm. 展开更多
关键词 Real-time data processing feature compression pipeline programming
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