Brain-computer interfaces (BCIs) provide a direct pathway from the brain to external devices and have demonstrated great potential for assistive and rehabilitation technologies. Endogenous BCIs based on electroencephalogram (EEG) signals, such as motor imagery (MI) BCIs, can provide some level of control. However, mastering spontaneous BCI control requires the users to generate discriminative and stable brain signal patterns by imagery, which is challenging and is usually achieved over a very long training time (weeks/months). Here, we propose a human-machine joint learning framework to boost the learning process in endogenous BCIs, by guiding the user to generate brain signals towards an optimal distribution estimated by the decoder, given the historical brain signals of the user. To this end, we firstly model the human-machine joint learning process in a uniform formulation. Then a human-machine joint learning framework is proposed: 1) for the human side, we model the learning process in a sequential trial-and-error scenario and propose a novel ``copy/new'' feedback paradigm to help shape the signal generation of the subject toward the optimal distribution; 2) for the machine side, we propose a novel adaptive learning algorithm to learn an optimal signal distribution along with the subject's learning process. Specifically, the decoder reweighs the brain signals generated by the subject to focus more on ``good'' samples to cope with the learning process of the subject. Online and psuedo-online BCI experiments with 18 healthy subjects demonstrated the advantages of the proposed joint learning process over co-adaptive approaches in both learning efficiency and effectiveness.

The central problem in cryo-electron microscopy (cryo-EM) is to recover the 3D structure from noisy 2D projection images which requires estimating the missing projection angles (poses). Recent methods attempted to solve the 3D reconstruction problem with the autoencoder architecture, which suffers from the latent vector space sampling problem and frequently produces suboptimal pose inferences and inferior 3D reconstructions. Here we present an improved autoencoder architecture called ACE (Asymmetric Complementary autoEncoder), based on which we designed the ACE-EM method for cryo-EM 3D reconstructions. Compared to previous methods, ACE-EM reached higher pose space coverage within the same training time and boosted the reconstruction performance regardless of the choice of decoders. With this method, the Nyquist resolution (highest possible resolution) was reached for 3D reconstructions of both simulated and experimental cryo-EM datasets. Furthermore, ACE-EM is the only amortized inference method that reached the Nyquist resolution.

Structure-based drug design, i.e., finding molecules with high affinities to the target protein pocket, is one of the most critical tasks in drug discovery. Traditional solutions, like virtual screening, require exhaustively searching on a large molecular database, which are inefficient and cannot return novel molecules beyond the database. The pocket-based 3D molecular generation model, i.e., directly generating a molecule with a 3D structure and binding position in the pocket, is a new promising way to address this issue. Herein, we propose VD-Gen, a novel pocket-based 3D molecular generation pipeline. VD-Gen consists of several carefully designed stages to generate fine-grained 3D molecules with binding positions in the pocket cavity end-to-end. Rather than directly generating or sampling atoms with 3D positions in the pocket like in early attempts, in VD-Gen, we first randomly initialize many virtual particles in the pocket; then iteratively move these virtual particles, making the distribution of virtual particles approximate the distribution of molecular atoms. After virtual particles are stabilized in 3D space, we extract a 3D molecule from them. Finally, we further refine atoms in the extracted molecule by iterative movement again, to get a high-quality 3D molecule, and predict a confidence score for it. Extensive experiment results on pocket-based molecular generation demonstrate that VD-Gen can generate novel 3D molecules to fill the target pocket cavity with high binding affinities, significantly outperforming previous baselines.