Multiphase flow simulation is critical in science and engineering but incurs high computational costs due to complex field discontinuities and the need for high-resolution numerical meshes. While Neural Operators (NOs) offer an efficient alternative for solving Partial Differential Equations (PDEs), they struggle with two core challenges unique to multiphase systems: spectral bias caused by spatial heterogeneity at phase interfaces, and the persistent scarcity of expensive, high-resolution field data. This work introduces the Interface Information Aware Neural Operator (IANO), a novel architecture that mitigates these issues by leveraging readily obtainable interface data (e.g., topology and position). Interface data inherently contains the high-frequency features not only necessary to complement the physical field data, but also help with spectral bias. IANO incorporates an interface-aware function encoding mechanism to capture dynamic coupling, and a geometry-aware positional encoding method to enhance spatial fidelity for pointwise super-resolution. Empirical results across multiple multiphase flow cases demonstrate that IANO achieves significant accuracy improvements (up to ~10%) over existing NO baselines. Furthermore, IANO exhibits superior generalization capabilities in low-data and noisy settings, confirming its utility for practical, data-efficient AI-based multiphase flow simulations.

Accurate and efficient simulations of physical phenomena governed by partial differential equations (PDEs) are important for scientific and engineering progress. While traditional numerical solvers are powerful, they are often computationally expensive. Recently, data-driven methods have emerged as alternatives, but they frequently suffer from error accumulation and limited physical consistency, especially in multiphysics and complex geometries. To address these challenges, we propose PEGNet, a Physics-Embedded Graph Network that incorporates PDE-guided message passing to redesign the graph neural network architecture. By embedding key PDE dynamics like convection, viscosity, and diffusion into distinct message functions, the model naturally integrates physical constraints into its forward propagation, producing more stable and physically consistent solutions. Additionally, a hierarchical architecture is employed to capture multi-scale features, and physical regularization is integrated into the loss function to further enforce adherence to governing physics. We evaluated PEGNet on benchmarks, including custom datasets for respiratory airflow and drug delivery, showing significant improvements in long-term prediction accuracy and physical consistency over existing methods.

With the rise of 3D Gaussian Splatting (3DGS), a variety of digital watermarking techniques, embedding either 1D bitstreams or 2D images, are used for copyright protection. However, the robustness of these watermarking techniques against potential attacks remains underexplored. This paper introduces the first universal black-box attack framework, the Group-based Multi-objective Evolutionary Attack (GMEA), designed to challenge these watermarking systems. We formulate the attack as a large-scale multi-objective optimization problem, balancing watermark removal with visual quality. In a black-box setting, we introduce an indirect objective function that blinds the watermark detector by minimizing the standard deviation of features extracted by a convolutional network, thus rendering the feature maps uninformative. To manage the vast search space of 3DGS models, we employ a group-based optimization strategy to partition the model into multiple, independent sub-optimization problems. Experiments demonstrate that our framework effectively removes both 1D and 2D watermarks from mainstream 3DGS watermarking methods while maintaining high visual fidelity. This work reveals critical vulnerabilities in existing 3DGS copyright protection schemes and calls for the development of more robust watermarking systems.

Providing explainable molecular property predictions is critical for many scientific domains, such as drug discovery and material science. Though transformer-based language models have shown great potential in accurate molecular property prediction, they neither provide chemically meaningful explanations nor faithfully reveal the molecular structure-property relationships. In this work, we develop a framework for explainable molecular property prediction based on language models, dubbed as Lamole, which can provide chemical concepts-aligned explanations. We take a string-based molecular representation - Group SELFIES - as input tokens to pre-train and fine-tune our Lamole, as it provides chemically meaningful semantics. By disentangling the information flows of Lamole, we propose considering both self-attention weights and gradients for better quantification of each chemically meaningful substructure's impact on the model's output. To make the explanations more faithful to the structure-property relationship, we then carefully craft a marginal loss to explicitly optimize the explanations to align with the chemists' annotations. We bridge the manifold hypothesis with the elaborated marginal loss to prove that the loss can align the explanations with the tangent space of the data manifold, leading to concept-aligned explanations. Experimental results over eight datasets demonstrate Lamole can achieve comparable prediction accuracy and boost the explanation accuracy by up to 14.3%, being the state-of-the-art in explainable molecular property prediction. To further illustrate the actionable utility of the explanations derived from Lamole, we integrated the framework with an evolutionary algorithm. This integration established an interpretable optimization pipeline for molecular editing, demonstrating that Lamole functions beyond simple post-hoc analysis but serves as a practical guide for molecule discovery.

4D content generation aims to create dynamically evolving 3D content that responds to specific input objects such as images or 3D representations. Current approaches typically incorporate physical priors to animate 3D representations, but these methods suffer from significant limitations: they not only require users lacking physics expertise to manually specify material properties but also struggle to effectively handle the generation of multi-material composite objects. To address these challenges, we propose Phys4DGen, a novel 4D generation framework that integrates multi-material composition perception with physical simulation. The framework achieves automated, physically plausible 4D generation through three innovative modules: first, the 3D Material Grouping module partitions heterogeneous material regions on 3D representations' surfaces via semantic segmentation; second, the Internal Physical Structure Discovery module constructs the mechanical structure of object interiors; finally, we distill physical prior knowledge from multimodal large language models to enable rapid and automatic material properties identification for both objects' surfaces and interiors. Experiments on both synthetic and real-world datasets demonstrate that Phys4DGen can generate high-fidelity 4D content with physical realism in open-world scenarios, significantly outperforming state-of-the-art methods.

Traditional Chinese medicine (TCM) utilizes intricate herbal formulations that exemplify the principles of compatibility and synergy. However, the rapid proliferation of herbal data has resulted in redundant information, complicating the understanding of their potential mechanisms. To address this issue, we first established a comprehensive database that encompasses 992 herbs, 18 681 molecules, and 2168 targets. Consequently, we implemented a multi-network strategy based on a core information screening method to elucidate the highly intertwined relationships among the targets of various herbs and to refine herbal target information. Within a non-redundant network framework, separation and overlap analysis demonstrated that the networking of herbs preserves essential clinical information, including their properties, meridians, and therapeutic classifications. Furthermore, two notable trends emerged from the statistical analyses of classical TCM formulas: the separation of herbs and the overlap between herbs and diseases. This phenomenon is termed the herbal combination model (HCM), validated through statistical analyses of two representative case studies: the common cold and rheumatoid arthritis. Additionally, in vivo and in vitro experiments with the new formula YanChuanQin (YanHuSuo-Corydalis Rhizoma, ChuanWu-Aconiti Radix, and QinJiao-Gentianae Macrophyllae Radix) for acute gouty arthritis further support the HCM. Overall, this computational method provides a systematic network strategy for exploring herbal combinations in complex and poorly understood diseases from a non-redundant perspective.

Evolutionary multitasking (EMT) is an emerging research direction within the evolutionary computation community, attempting to concurrently solve multiple optimization tasks by exploiting the underlying synergies between the tasks. Recently, numerous explicit transfer strategies have been developed for enhancing positive transfer among optimization tasks. Nevertheless, most of these methods conduct knowledge transfer by transferring the best solutions from a source task to the target task, while ignoring the proper use of information from the target task in solution selection. As a result, the transferred solutions could not well adapt to the target task, thus limiting the effectiveness of knowledge transfer across tasks. To address this issue, this paper proposes a solution selection method based on the lower confidence bound (LCB) for EMT, which is designed by leveraging task-specific information of both source and target tasks. With the proposed LCB metric, a number of high-quality solutions that could be more helpful for the target task can be selected and transferred to enhance positive transfer in EMT. To verify the effectiveness of the proposed approach, the solution selection method is embedded into several existing EMT algorithms and then evaluated on the single-objective multitasking benchmarks, the multiobjective multitasking benchmark, and a real-world application. The obtained results confirmed the generality and efficacy of the proposed solution selection approach.

Recommendation system (RS) is an important information filtering tool in nowadays digital era. With the growing concern on privacy, deploying RSs in a federated learning (FL) manner emerges as a promising solution, which can train a high-quality model on the premise that the server does not directly access sensitive user data. Nevertheless, some malicious clients can deduce user data by analyzing the uploaded model parameters. Even worse, some Byzantine clients can also send contaminated data to the server, causing blockage or failure of model convergence. In addition, most existing researches on federated recommendation algorithms only focus on unimodality learning, ignoring the assistance of multiple modality data to promote recommendation accuracy. Therefore, this article designs an FL-based privacy-preserving multimodal RS framework. To distinguish various modality data, an attention mechanism is introduced, wherein different weight ratios are assigned to various modal features. To further strengthen the privacy, local differential privacy (LDP) and personalized FL strategies are designed to identify malicious clients and bolster the resilience against Byzantine attacks. Finally, two multimodal datasets are established to verify the effectiveness of the proposed algorithm. The superiority of our proposed techniques is confirmed by the simulation results.

While graph neural networks (GNNs) have become the de facto standard for graph-based node classification, they impose a strong assumption on the availability of sufficient labeled samples. This assumption restricts the classification performance of prevailing GNNs on many real-world applications suffering from low-data regimes. Specifically, features extracted from scarce labeled nodes could not provide sufficient supervision for the unlabeled samples, leading to severe overfitting. We point out that leveraging subgraphs to capture long-range dependencies can augment the node representation, thus alleviating the low-data regime. To this end, we present a novel self-supervised learning (SSL) framework, called multiview subgraph neural networks (Muse), for handling the long-range dependencies. In particular, we propose an information theory-based identification mechanism to identify two types of subgraphs from the views of input space and latent space, respectively. The former is to capture the local structure of the graph, while the latter captures the long-range dependencies among nodes. By fusing these two views of subgraphs, the learned representations can preserve the topological properties of the graph at large, including the local structure and long-range dependencies, thus maximizing their expressiveness. Theoretically, we provide the generalization error bound to show the effectiveness of capturing complementary information from multiview subgraphs. Empirically, we show a proof-of-concept of Muse on canonical node classification problems on graph data.

In recent years, machine learning algorithms, especially deep learning, have shown promising prospects in solving Partial Differential Equations (PDEs). However, as the dimension increases, the relationship and interaction between variables become more complex, and existing methods are difficult to provide fast and interpretable solutions for high-dimensional PDEs. To address this issue, we propose a genetic programming symbolic regression algorithm based on transfer learning and automatic differentiation to solve PDEs. This method uses genetic programming to search for a mathematically understandable expression and combines automatic differentiation to determine whether the search result satisfies the PDE and boundary conditions to be solved. To overcome the problem of slow solution speed caused by large search space, we propose a transfer learning mechanism that transfers the structure of one-dimensional PDE analytical solution to the form of high-dimensional PDE solution. We tested three representative types of PDEs, and the results showed that our proposed method can obtain reliable and human-understandable real solutions or algebraic equivalent solutions of PDEs, and the convergence speed is better than the compared methods. Code of this project is at https://github.com/grassdeerdeer/HD-TLGP.

A plethora of fair graph neural networks (GNNs) have been proposed to promote algorithmic fairness for high-stake real-life contexts. Meanwhile, explainability is generally proposed to help machine learning practitioners debug models by providing human-understandable explanations. However, seldom work on explainability is made to generate explanations for fairness diagnosis in GNNs. From the explainability perspective, this paper explores the problem of what subgraph patterns cause the biased behavior of GNNs, and what actions could practitioners take to rectify the bias? By answering the two questions, this paper aims to produce compact, diagnostic, and actionable explanations that are responsible for discriminatory behavior. Specifically, we formulate the problem of generating diagnostic and actionable explanations as a multi-objective combinatorial optimization problem. To solve the problem, a dedicated multi-objective evolutionary algorithm is presented to ensure GNNs' explainability and fairness in one go. In particular, an influenced nodes-based gradient approximation is developed to boost the computation efficiency of the evolutionary algorithm. We provide a theoretical analysis to illustrate the effectiveness of the proposed framework. Extensive experiments have been conducted to demonstrate the superiority of the proposed method in terms of classification performance, fairness, and interpretability.

While image-to-text models have demonstrated significant advancements in various vision-language tasks, they remain susceptible to adversarial attacks. Existing white-box attacks on image-to-text models require access to the architecture, gradients, and parameters of the target model, resulting in low practicality. Although the recently proposed gray-box attacks have improved practicality, they suffer from semantic loss during the training process, which limits their targeted attack performance. To advance adversarial attacks of image-to-text models, this paper focuses on a challenging scenario: decision-based black-box targeted attacks where the attackers only have access to the final output text and aim to perform targeted attacks. Specifically, we formulate the decision-based black-box targeted attack as a large-scale optimization problem. To efficiently solve the optimization problem, a three-stage process \textit{Ask, Attend, Attack}, called \textit{AAA}, is proposed to coordinate with the solver. \textit{Ask} guides attackers to create target texts that satisfy the specific semantics. \textit{Attend} identifies the crucial regions of the image for attacking, thus reducing the search space for the subsequent \textit{Attack}. \textit{Attack} uses an evolutionary algorithm to attack the crucial regions, where the attacks are semantically related to the target texts of \textit{Ask}, thus achieving targeted attacks without semantic loss. Experimental results on transformer-based and CNN+RNN-based image-to-text models confirmed the effectiveness of our proposed \textit{AAA}.

Graph meta-learning has become a preferable paradigm for graph-based node classification with long-tail distribution, owing to its capability of capturing the intrinsic manifold of support and query nodes. Despite the remarkable success, graph meta-learning suffers from severe performance degradation when training on graph data with structural noise. In this work, we observe that the structural noise may impair the smoothness of the intrinsic manifold supporting the support and query nodes, leading to the poor transferable priori of the meta-learner. To address the issue, we propose a new approach for graph meta-learning that is robust against structural noise, called Proxy subgraph-based Manifold Calibration method (Pro-MC). Concretely, a subgraph generator is designed to generate proxy subgraphs that can calibrate the smoothness of the manifold. The proxy subgraph compromises two types of subgraphs with two biases, thus preventing the manifold from being rugged and straightforward. By doing so, our proposed meta-learner can obtain generalizable and transferable prior knowledge. In addition, we provide a theoretical analysis to illustrate the effectiveness of Pro-MC. Experimental results have demonstrated that our approach can achieve state-of-the-art performance under various structural noises.

To reduce the delay and network congestion for content delivery in wireless networks, proactive caching scheme has attracted lots of attentions from both academia and industry. However, traditional caching prediction methods require to collect user data in a centralized server, which is becoming unreliable and impractical due to regulatory restrictions. To circumvent this issue, deploying caching prediction system in a federated learning (FL) fashion becomes a promising solution. However, there still exist privacy risks, and even worse, the FL is vulnerable to low-cost attacks. To solve this problem, a novel federated prediction system (FPS) is studied to provide high robustness and privacy. Firstly, to keep a balance between further enhancing privacy protection and alleviating the performance degradation caused by additional protection schemes, we propose an edge-assisted, robust and privacy-preserving FPS framework based on the local differential privacy (LDP) scheme. Secondly, to mitigate the impact of heterogeneous data, we add a regularization term to the local loss function. Furthermore, an attention-based aggregation scheme is proposed to defend against Byzantine attacks during the training process. Finally, the experiment results are provided to show the superiority of our proposed algorithm in terms of prediction accuracy and robustness.

Deep learning enhanced Internet of Things (IoT) is advancing the transformation toward smart manufacturing. Intelligent robot guidance is one of the most potential deep learning + IoT applications in the manufacturing industry. However, low costs, efficient computing, and extremely high localization accuracy are mandatory requirements for vision robot guidance, particularly in operational factories. Therefore, in this work, a low-cost edge computing-based IoT system is developed based on an innovative fine-grained attention model (FGAM). FGAM integrates a deep-learning-based attention model to detect the region of interest (ROI) and an optimized conventional computer vision model to perform fine-grained localization concentrating on the ROI. Trained with only 100 images collected from real production line, the proposed FGAM has shown superior performance over multiple benchmark models when validated using operational data. Eventually, the FGAM-based edge computing system has been deployed on a welding robot in a real-world factory for mass production. After the assembly of about 6000 products, the deployed system has achieved averaged overall process and transmission time down to 200 ms and overall localization accuracy up to 99.998%.

Large-scale multiobjective optimization problems (LSMOPs) are characterized as optimization problems involving hundreds or even thousands of decision variables and multiple conflicting objectives. To solve LSMOPs, some algorithms designed a variety of strategies to track Pareto-optimal solutions (POSs) by assuming that the distribution of POSs follows a low-dimensional manifold. However, traditional genetic operators for solving LSMOPs have some deficiencies in dealing with the manifold, which often results in poor diversity, local optima, and inefficient searches. In this work, a generative adversarial network (GAN)-based manifold interpolation framework is proposed to learn the manifold and generate high-quality solutions on the manifold, thereby improving the optimization performance of evolutionary algorithms. We compare the proposed approach with several state-of-the-art algorithms on various large-scale multiobjective benchmark functions. The experimental results demonstrate that significant improvements have been achieved by the proposed framework in solving LSMOPs.

Computation offloading via device-to-device communications can improve the performance of mobile edge computing by exploiting the computing resources of user devices. However, most proposed optimization-based computation offloading schemes lack self-adaptive abilities in dynamic environments due to time-varying wireless environment, continuous-discrete mixed actions, and coordination among devices. The conventional reinforcement learning based approaches are not effective for solving an optimal sequential decision problem with continuous-discrete mixed actions. In this paper, we propose a hierarchical deep reinforcement learning (HDRL) framework to solve the joint computation offloading and resource allocation problem. The proposed HDRL framework has a hierarchical actor-critic architecture with a meta critic, multiple basic critics and actors. Specifically, a combination of deep Q-network (DQN) and deep deterministic policy gradient (DDPG) is exploited to cope with the continuous-discrete mixed action spaces. Furthermore, to handle the coordination among devices, the meta critic acts as a DQN to output the joint discrete action of all devices and each basic critic acts as the critic part of DDPG to evaluate the output of the corresponding actor. Simulation results show that the proposed HDRL algorithm can significantly reduce the task computation latency compared with baseline offloading schemes.

Deep learning-enhanced Internet of Things (IoT) plays a pivot role in advancing the transformation toward smart manufacturing, and an essential component in many smart manufacturing IoT systems is the quality inspection. However, challenges, such as expensive data labeling, innumerable types of defects, and high costs for iterative optimization, hinder the industrial applicability of previous visual surface quality inspection methods. In this article, we present an edge-computing-enabled IoT system based on an innovative hybrid learning method for visual surface quality inspection using only few labeled data and minimum iterative optimization efforts. Our hybrid learning method first employs a deep neural network to synthesize global representations of real-world industrial images, which are subsequently analyzed via an unsupervised clustering algorithm for anomaly detection. Besides, enhancement strategies, such as fine-tuning and data augmentation, are proposed to improve the robustness against the noisy data set and support low-cost inference in multiple edge devices for manufacturing operation. On a holdout data set collected from real-world factories, our method achieves classification accuracies between 90% and 98%, outperforming the benchmark method by 7%–12%. Moreover, this hybrid learning method demonstrates the effectiveness in detecting new types of surface defects and achieves test recalls between 86% and 97%, outperforming the benchmark method by 11%–34%.

Dynamic multiobjective optimization problems (DMOPs) are characterized by optimization functions that change over time in varying environments. The DMOP is challenging because it requires the varying Pareto-optimal sets (POSs) to be tracked quickly and accurately during the optimization process. In recent years, transfer learning has been proven to be one of the effective means to solve dynamic multiobjective optimization. However, the negative transfer will lead the search of finding the POS to a wrong direction, which greatly reduces the efficiency of solving optimization problems. Minimizing the occurrence of negative transfer is thus critical for the use of transfer learning in solving DMOPs. In this article, we propose a new individual-based transfer learning method, called an individual transfer-based dynamic multiobjective evolutionary algorithm (IT-DMOEA), for solving DMOPs. Unlike existing approaches, it uses a presearch strategy to filter out some high-quality individuals with better diversity so that it can avoid negative transfer caused by individual aggregation. On this basis, an individual-based transfer learning technique is applied to accelerate the construction of an initial population. The merit of the IT-DMOEA method is that it combines different strategies in maintaining the advantages of transfer learning methods as well as avoiding the occurrence of negative transfer; thereby greatly improving the quality of solutions and convergence speed. The experimental results show that the proposed IT-DMOEA approach can considerably improve the quality of solutions and convergence speed compared to several state-of-the-art algorithms based on different benchmark problems.

Many real-world optimization problems involve multiple objectives, constraints, and parameters that may change over time. These problems are often called dynamic multiobjective optimization problems (DMOPs). The difficulty in solving DMOPs is the need to track the changing Pareto-optimal front efficiently and accurately. It is known that transfer learning (TL)-based methods have the advantage of reusing experiences obtained from past computational processes to improve the quality of current solutions. However, existing TL-based methods are generally computationally intensive and thus time consuming. This article proposes a new memory-driven manifold TL-based evolutionary algorithm for dynamic multiobjective optimization (MMTL-DMOEA). The method combines the mechanism of memory to preserve the best individuals from the past with the feature of manifold TL to predict the optimal individuals at the new instance during the evolution. The elites of these individuals obtained from both past experience and future prediction will then constitute as the initial population in the optimization process. This strategy significantly improves the quality of solutions at the initial stage and reduces the computational cost required in existing methods. Different benchmark problems are used to validate the proposed algorithm and the simulation results are compared with state-of-the-art dynamic multiobjective optimization algorithms (DMOAs). The results show that our approach is capable of improving the computational speed by two orders of magnitude while achieving a better quality of solutions than existing methods.

Dynamic multiobjective optimization problems (DMOPs) are optimization problems with multiple conflicting optimization objectives, and these objectives change over time. Transfer learning-based approaches have been proven to be promising; however, a slow solving speed is one of the main obstacles preventing such methods from solving real-world problems. One of the reasons for the slow running speed is that low-quality individuals occupy a large amount of computing resources, and these individuals may lead to negative transfer. Combining high-quality individuals, such as knee points, with transfer learning is a feasible solution to this problem. However, the problem with this idea is that the number of high-quality individuals is often very small, so it is difficult to acquire substantial improvements using conventional transfer learning methods. In this article, we propose a knee point-based transfer learning method, called KT-DMOEA, for solving DMOPs. In the proposed method, a trend prediction model (TPM) is developed for producing the estimated knee points. Then, an imbalance transfer learning method is proposed to generate a high-quality initial population by using these estimated knee points. The advantage of this approach is that the seamless integration of a small number of high-quality individuals and the imbalance transfer learning technique can greatly improve the computational efficiency while maintaining the quality of the solution. The experimental results and performance comparisons with some chosen state-of-the-art algorithms demonstrate that the proposed design is capable of significantly improving the performance of dynamic optimization.

When dynamic multi-objective optimization evolutionary algorithms (DMOEA) are used to solve real world problems, these are not only required to be able to find the Pareto-Optimal Set (POS) quickly, but also the results obtained can be easily used by decision makers. The classic DMOEAs have much room for improvement in both aspects. Recently, the transfer learning based DMOEAs have been proved that these methods can significantly improve the quality of the solution, but there are still too many individuals in the POS obtained by these algorithms. The resulting problems are twofold: this not only consumes a lot of computing resources to those solutions that will not be used, but also makes it more difficult for decision makers to choose. In this paper, we proposed a dynamic multiobjective optimization evolutionary algorithm which combines knee solutions with transfer learning method, and the feature of the proposed method is that it only outputs a very small number of solutions, which can greatly improve the efficiency of decisionmaking. The proposed algorithm divides the whole decision space into different subspaces, and find a local knee solutions in each subspace, then a transfer learning framework, Tr-DMOEA, is used to predict the knee solutions of the optimization problem at the next moment by using the local knee solutions and a global knee solution. The experimental results show the effectiveness of our design.

Optical character rcecognition (OCR) is a process of converting images of typed, handwritten or printed text into machine-encoded one. In recent years, the methods represented by deep learning have greatly improved the performance of OCR systems, but the main challenges of such systems are 1) to accurately perform text detection in complex scenes and 2) to identify and set the optimal parameters to optimize the performance of the system. In this paper, we propose an OCR method based on Neural Architecture Search technique, called AutOCR. The characteristic of the proposed method is the automatic design of text detection framework using an evolutionary computation neural architecture search method. This design can not only accurately recognize the text in a complex environment, but also avoid the process of experts participating in parameter adjustment. We compared it with different methods, and the experimental results proved the effectiveness of our method.

Designing maximally selective ligands that act on individual drug targets with high binding affinity has been the central dogma of drug discovery and development for the past two decades. However, many low-affinity drugs that aim for several targets at the same time are found more effective than the high-affinity binders when faced with complex disease conditions, such as cancers, Alzheimer's disease and cardiovascular diseases. The aim of this study was to appreciate the importance and reveal the features of weak-binding drugs and propose an integrated strategy for discovering them. Weak-binding drugs can be characterized by their high dissociation rates and transient interactions with their targets. In addition, network topologies and dynamics parameters involved in the targets of weak-binding drugs also influence the effects of the drugs. Here, we first performed a dynamics analysis for 33 elementary subgraphs to determine the desirable topology and dynamics parameters among targets. Then, by applying the elementary subgraphs to the mitogen-activated protein kinase (MAPK) pathway, several optimal target combinations were obtained. Combining drug-target interaction prediction with molecular dynamics simulation, we got two potential weak-binding drug candidates, luteolin and tanshinone IIA, acting on these targets. Further, the binding affinity of these two compounds to their targets and the anti-inflammatory effects of them were validated through in vitro experiments. In conclusion, weak-binding drugs have real opportunities for maximum efficiency and may show reduced adverse reactions, which can offer a bright and promising future for new drug discovery.

This study introduces a novel learning algorithm for spiking neurons, called CCDS, which is able to learn and reproduce arbitrary spike patterns in a supervised fashion allowing the processing of spatiotemporal information encoded in the precise timing of spikes. Unlike the Remote Supervised Method (ReSuMe), synapse delays and axonal delays in CCDS are variants which are modulated together with weights during learning. The CCDS rule is both biologically plausible and computationally efficient. The properties of this learning rule are investigated extensively through experimental evaluations in terms of reliability, adaptive learning performance, generality to different neuron models, learning in the presence of noise, effects of its learning parameters and classification performance. Results presented show that the CCDS learning method achieves learning accuracy and learning speed comparable with ReSuMe, but improves classification accuracy when compared to both the Spike Pattern Association Neuron (SPAN) learning rule and the Tempotron learning rule. The merit of CCDS rule is further validated on a practical example involving the automated detection of interictal spikes in EEG records of patients with epilepsy. Results again show that with proper encoding, the CCDS rule achieves good recognition performance.

This study introduces a new Generalized Leaky Integrate-and-Fire (GLIF) neuron model with variable leaking resistor and bias current in order to reproduce accurately the membrane voltage dynamics of a biological neuron. The accuracy of this model is ensured by adjusting its parameters to the statistical properties of the Hodgkin-Huxley model outputs; while the speed is enhanced by introducing a Generalized Exponential Moving Average method that converts the parameterized kernel functions into pre-calculated lookup tables based on an analytic solution of the dynamic equations of the GLIF model.