Computational protein design (CPD) refers to the use of computational methods to design proteins. Traditional methods relying on energy functions and heuristic algorithms for sequence design are inefficient and do not meet the demands of the big data era in biomolecules, with their accuracy limited by the energy functions and search algorithms. Existing deep learning methods are constrained by the learning capabilities of the networks, failing to extract effective information from sparse protein structures, which limits the accuracy of protein design. To address these shortcomings, we developed an Efficient attention-based Models for Computational Protein Design using amino acid microenvironment (EMOCPD). It aims to predict the category of each amino acid in a protein by analyzing the three-dimensional atomic environment surrounding the amino acids, and optimize the protein based on the predicted high-probability potential amino acid categories. EMOCPD employs a multi-head attention mechanism to focus on important features in the sparse protein microenvironment and utilizes an inverse residual structure to optimize the network architecture. The proposed EMOCPD achieves over 80% accuracy on the training set and 68.33% and 62.32% accuracy on two independent test sets, respectively, surpassing the best comparative methods by over 10%. In protein design, the thermal stability and protein expression of the predicted mutants from EMOCPD show significant improvements compared to the wild type, effectively validating EMOCPD's potential in designing superior proteins. Furthermore, the predictions of EMOCPD are influenced positively, negatively, or have minimal impact based on the content of the 20 amino acids, categorizing amino acids as positive, negative, or neutral. Research findings indicate that EMOCPD is more suitable for designing proteins with lower contents of negative amino acids.

In the drug discovery process, the low success rate of drug candidate screening often leads to insufficient labeled data, causing the few-shot learning problem in molecular property prediction. Existing methods for few-shot molecular property prediction overlook the sample selection bias, which arises from non-random sample selection in chemical experiments. This bias in data representativeness leads to suboptimal performance. To overcome this challenge, we present a novel method named contextual representation anchor Network (CRA), where an anchor refers to a cluster center of the representations of molecules and serves as a bridge to transfer enriched contextual knowledge into molecular representations and enhance their expressiveness. CRA introduces a dual-augmentation mechanism that includes context augmentation, which dynamically retrieves analogous unlabeled molecules and captures their task-specific contextual knowledge to enhance the anchors, and anchor augmentation, which leverages the anchors to augment the molecular representations. We evaluate our approach on the MoleculeNet and FS-Mol benchmarks, as well as in domain transfer experiments. The results demonstrate that CRA outperforms the state-of-the-art by 2.60% and 3.28% in AUC and $\Delta$AUC-PR metrics, respectively, and exhibits superior generalization capabilities.

The use of autonomous systems in medical evacuation (MEDEVAC) scenarios is promising, but existing implementations overlook key insights from human-robot interaction (HRI) research. Studies on human-machine teams demonstrate that human perceptions of a machine teammate are critical in governing the machine's performance. Here, we present a mixed factorial design to assess human perceptions of a MEDEVAC robot in a simulated evacuation scenario. Participants were assigned to the role of casualty (CAS) or bystander (BYS) and subjected to three within-subjects conditions based on the MEDEVAC robot's operating mode: autonomous-slow (AS), autonomous-fast (AF), and teleoperation (TO). During each trial, a MEDEVAC robot navigated an 11-meter path, acquiring a casualty and transporting them to an ambulance exchange point while avoiding an idle bystander. Following each trial, subjects completed a questionnaire measuring their emotional states, perceived safety, and social compatibility with the robot. Results indicate a consistent main effect of operating mode on reported emotional states and perceived safety. Pairwise analyses suggest that the employment of the AF operating mode negatively impacted perceptions along these dimensions. There were no persistent differences between casualty and bystander responses.

We address the question of how to successively add new knowledge to an LLM whilst retaining previously-added knowledge. We consider two settings, semi-cooperative and fully-cooperative. Overall, LoRA performs better in most cases than full-fine tuning of all parameters when both new knowledge acquisition and retention of old, including recent, knowledge are taken into account. In the semi-cooperative setting, where datasets are not available after training, MOE mixing, model merging, and LoRA-based orthogonal subspace sequential learning, using a small weight on the orthogonality term, perform well. In the fully-cooperative setting where datasets remain available, joint training and sequential training with replay are both effective approaches with LoRA training generally preferable to full fine-tuning. The codes needed to reproduce the results are provided in an open source repository.

With high-dimensional state spaces, visual reinforcement learning (RL) faces significant challenges in exploitation and exploration, resulting in low sample efficiency and training stability. As a time-efficient diffusion model, although consistency models have been validated in online state-based RL, it is still an open question whether it can be extended to visual RL. In this paper, we investigate the impact of non-stationary distribution and the actor-critic framework on consistency policy in online RL, and find that consistency policy was unstable during the training, especially in visual RL with the high-dimensional state space. To this end, we suggest sample-based entropy regularization to stabilize the policy training, and propose a consistency policy with prioritized proximal experience regularization (CP3ER) to improve sample efficiency. CP3ER achieves new state-of-the-art (SOTA) performance in 21 tasks across DeepMind control suite and Meta-world. To our knowledge, CP3ER is the first method to apply diffusion/consistency models to visual RL and demonstrates the potential of consistency models in visual RL. More visualization results are available at https://jzndd.github.io/CP3ER-Page/.

This paper aims at developing novel shuffling gradient-based methods for tackling two classes of minimax problems: nonconvex-linear and nonconvex-strongly concave settings. The first algorithm addresses the nonconvex-linear minimax model and achieves the state-of-the-art oracle complexity typically observed in nonconvex optimization. It also employs a new shuffling estimator for the "hyper-gradient", departing from standard shuffling techniques in optimization. The second method consists of two variants: semi-shuffling and full-shuffling schemes. These variants tackle the nonconvex-strongly concave minimax setting. We establish their oracle complexity bounds under standard assumptions, which, to our best knowledge, are the best-known for this specific setting. Numerical examples demonstrate the performance of our algorithms and compare them with two other methods. Our results show that the new methods achieve comparable performance with SGD, supporting the potential of incorporating shuffling strategies into minimax algorithms.

Recent analysis on the training dynamics of Transformers has unveiled an interesting characteristic: the training loss plateaus for a significant number of training steps, and then suddenly (and sharply) drops to near--optimal values. To understand this phenomenon in depth, we formulate the low-rank matrix completion problem as a masked language modeling (MLM) task, and show that it is possible to train a BERT model to solve this task to low error. Furthermore, the loss curve shows a plateau early in training followed by a sudden drop to near-optimal values, despite no changes in the training procedure or hyper-parameters. To gain interpretability insights into this sudden drop, we examine the model's predictions, attention heads, and hidden states before and after this transition. Concretely, we observe that (a) the model transitions from simply copying the masked input to accurately predicting the masked entries; (b) the attention heads transition to interpretable patterns relevant to the task; and (c) the embeddings and hidden states encode information relevant to the problem. We also analyze the training dynamics of individual model components to understand the sudden drop in loss.

Large-scale foundation models have demonstrated exceptional performance in language and vision tasks. However, the numerous dense matrix-vector operations involved in these large networks pose significant computational challenges during inference. To address these challenges, we introduce the Block-Level Adaptive STructured (BLAST) matrix, designed to learn and leverage efficient structures prevalent in the weight matrices of linear layers within deep learning models. Compared to existing structured matrices, the BLAST matrix offers substantial flexibility, as it can represent various types of structures that are either learned from data or computed from pre-existing weight matrices. We demonstrate the efficiency of using the BLAST matrix for compressing both language and vision tasks, showing that (i) for medium-sized models such as ViT and GPT-2, training with BLAST weights boosts performance while reducing complexity by 70% and 40%, respectively; and (ii) for large foundation models such as Llama-7B and DiT-XL, the BLAST matrix achieves a 2x compression while exhibiting the lowest performance degradation among all tested structured matrices. Our code is available at https://github.com/changwoolee/BLAST.

Reinforcement learning (RL) has achieved outstanding success in complex robot control tasks, such as drone racing, where the RL agents have outperformed human champions in a known racing track. However, these agents fail in unseen track configurations, always requiring complete retraining when presented with new track layouts. This work aims to develop RL agents that generalize effectively to novel track configurations without retraining. The naive solution of training directly on a diverse set of track layouts can overburden the agent, resulting in suboptimal policy learning as the increased complexity of the environment impairs the agent's ability to learn to fly. To enhance the generalizability of the RL agent, we propose an adaptive environment-shaping framework that dynamically adjusts the training environment based on the agent's performance. We achieve this by leveraging a secondary RL policy to design environments that strike a balance between being challenging and achievable, allowing the agent to adapt and improve progressively. Using our adaptive environment shaping, one single racing policy efficiently learns to race in diverse challenging tracks. Experimental results validated in both simulation and the real world show that our method enables drones to successfully fly complex and unseen race tracks, outperforming existing environment-shaping techniques. Project page: http://rpg.ifi.uzh.ch/env_as_policy/index.html

A new tool could improve the one-on-one tutoring sometimes used to supplement class instruction in these schools, by letting tutors tap into more experienced teachers' expertise during virtual sessions. It's been in chaos for the best part of five years, and the problems just keep piling up.