Identification of parallel medicinal chemistry protocols to expand branched amine design space.

α-Branched heteroaryl amines are prevalent motifs in drugs and are typically prepared through C-N bond formation. In contrast, C-C bond-forming approaches to branched amines may dramatically expand available chemical space but are rarely pursued in parallel format due to a lack of established library protocols. Methods for the synthesis of α-branched heteroaryl amines via aldimine addition have been evaluated for compatibility with parallel synthesis. In situ activation of aliphatic carboxylic acids as redox-active esters enables Zn-mediated decarboxylative radical imine addition to access aliphatic-branched heterobenzylic amines. In situ activation of (hetero)aryl bromides via Li-halogen exchange enables heteroaryl-lithium addition to imines to access (hetero)benzhydryl amines. Condensation of heteroaryl amines with heteroaryl aldehydes provides aldimines which may be intercepted with aryl Grignard reagents to provide modular access to (hetero)benzhydryl amines. These protocols minimize synthetic step count and maximize accessible design space, enhancing access to α-branched heteroaryl amines for medicinal chemistry.

Multimodal Human-Exoskeleton Interface for Lower Limb Movement Prediction Through a Dense Co-Attention Symmetric Mechanism.

A challenging task for the biological neural signal-based human-exoskeleton interface is to achieve accurate lower limb movement prediction of patients with hemiplegia in rehabilitation training scenarios. The human-exoskeleton interface based on single-modal biological signals such as electroencephalogram (EEG) is currently not mature in predicting movements, due to its unreliability. The multimodal human-exoskeleton interface is a very novel solution to this problem. This kind of interface normally combines the EEG signal with surface electromyography (sEMG) signal. However, their use for the lower limb movement prediction is still limited-the connection between sEMG and EEG signals and the deep feature fusion between them are ignored. In this article, a Dense con-attention mechanism-based Multimodal Enhance Fusion Network (DMEFNet) is proposed for predicting lower limb movement of patients with hemiplegia. The DMEFNet introduces the con-attention structure to extract the common attention between sEMG and EEG signal features. To verify the effectiveness of DMEFNet, an sEMG and EEG data acquisition experiment and an incomplete asynchronous data collection paradigm are designed. The experimental results show that DMEFNet has a good movement prediction performance in both within-subject and cross-subject situations, reaching an accuracy of 82.96 and 88.44%, respectively.

MCSNet: Channel Synergy-Based Human-Exoskeleton Interface With Surface Electromyogram.

The human-robot interface (HRI) based on biological signals can realize the natural interaction between human and robot. It has been widely used in exoskeleton robots recently to help predict the wearer's movement. Surface electromyography (sEMG)-based HRI has mature applications on the exoskeleton. However, the sEMG signals of paraplegic patients' lower limbs are weak, which means that most HRI based on lower limb sEMG signals cannot be applied to the exoskeleton. Few studies have explored the possibility of using upper limb sEMG signals to predict lower limb movement. In addition, most HRIs do not consider the contribution and synergy of sEMG signal channels. This paper proposes a human-exoskeleton interface based on upper limb sEMG signals to predict lower limb movements of paraplegic patients. The interface constructs an channel synergy-based network (MCSNet) to extract the contribution and synergy of different feature channels. An sEMG data acquisition experiment is designed to verify the effectiveness of MCSNet. The experimental results show that our method has a good movement prediction performance in both within-subject and cross-subject situations, reaching an accuracy of 94.51 and 80.75%, respectively. Furthermore, feature visualization and model ablation analysis show that the features extracted by MCSNet are physiologically interpretable.

Channel Synergy-based Human-Robot Interface for a Lower Limb Walking Assistance Exoskeleton.

The human-robot interface (HRI) based on surface electromyography(sEMG) can realize the natural interaction between human and robot. It has been widely used in exoskeleton robots recently to help predict the wearer's movement. The sEMG signal of the paraplegic patients' lower limbs is weak. How to achieve accurate prediction of the lower limb movement of patients with paraplegia has always been the focus of attention in the field of HRI. Few studies have explored the possibility of using upper limb sEMG signals to predict lower limb movement. In addition, most HRIs do not consider the contribution and synergy of sEMG signal channels. This paper proposes a human-exoskeleton interface based on upper limb sEMG signals to predict lower limb movements of paraplegic patients. The interface constructs a channel synergy-based network (MCSNet) to extract the contribution and synergy of different feature channels. An sEMG data acquisition experiment is designed to verify the effectiveness of MCSNet. The experimental results show that our method has a good movement prediction performance in both within-subject and cross-subject situations, reaching an accuracy of 94.51% and 80.75% respectively.

Data-Driven Optimal Assistance Control of a Lower Limb Exoskeleton for Hemiplegic Patients.

More recently, lower limb exoskeletons (LLE) have gained considerable interests in strength augmentation, rehabilitation, and walking assistance scenarios. For walking assistance, the LLE is expected to control the affected leg to track the unaffected leg's motion naturally. A critical issue in this scenario is that the exoskeleton system needs to deal with unpredictable disturbance from the patient, and the controller has the ability to adapt to different wearers. To this end, a novel data-driven optimal control (DDOC) strategy is proposed to adapt different hemiplegic patients with unpredictable disturbances. The interaction relation between two lower limbs of LLE and the leg of patient's unaffected side are modeled in the context of leader-follower framework. Then, the walking assistance control problem is transformed into an optimal control problem. A policy iteration (PI) algorithm is utilized to obtain the optimal controller. To improve the online adaptation to different patients, an actor-critic neural network (AC/NN) structure of the reinforcement learning (RL) is employed to learn the optimal controller on the basis of PI algorithm. Finally, experiments both on a simulation environment and a real LLE system are conducted to verify the effectiveness of the proposed walking assistance control method.