Daily Papers

Designing biological sequences that satisfy multiple, often conflicting, functional and biophysical criteria remains a central challenge in biomolecule engineering. While discrete flow matching models have recently shown promise for efficient sampling in high-dimensional sequence spaces, existing approaches address only single objectives or require continuous embeddings that can distort discrete distributions. We present Multi-Objective-Guided Discrete Flow Matching (MOG-DFM), a general framework to steer any pretrained discrete-time flow matching generator toward Pareto-efficient trade-offs across multiple scalar objectives. At each sampling step, MOG-DFM computes a hybrid rank-directional score for candidate transitions and applies an adaptive hypercone filter to enforce consistent multi-objective progression. We also trained two unconditional discrete flow matching models, PepDFM for diverse peptide generation and EnhancerDFM for functional enhancer DNA generation, as base generation models for MOG-DFM. We demonstrate MOG-DFM's effectiveness in generating peptide binders optimized across five properties (hemolysis, non-fouling, solubility, half-life, and binding affinity), and in designing DNA sequences with specific enhancer classes and DNA shapes. In total, MOG-DFM proves to be a powerful tool for multi-property-guided biomolecule sequence design.

Large language models (LLMs) are increasingly deployed in multi-turn dialogue settings, but their behavior is still bottlenecked by fixed context windows and naive memory strategies. Replaying the full conversation at every turn is simple but expensive, while static summarization or recency-only heuristics often erase safety-critical user details. We present Adaptive Focus Memory (AFM), a dynamic context manager that assigns each past message one of three fidelity levels -- FULL, COMPRESSED, or PLACEHOLDER -- based on semantic similarity to the current query, half-life recency weighting, and importance classification. AFM packs messages chronologically under a strict token budget, preferring high fidelity for the most relevant turns while aiming to preserve a cheap trace of the dialogue. In a safety-oriented benchmark involving a user with a severe peanut allergy planning a trip to Thailand, AFM retains the allergy across both short and medium-length conversations, matches the safety performance of naive replay, and cuts average token usage by 66% relative to a replay baseline. We release a modular Python implementation of AFM designed for OpenAI-compatible APIs and offline operation, enabling practitioners to reduce inference cost without sacrificing safety or factual continuity in the evaluated scenario.

Accurate prediction of atomistic, thermodynamic, and kinetic properties from molecular structures underpins materials innovation. Existing computational and experimental approaches lack the scalability required to efficiently navigate chemical space. Scientific foundation models trained on large unlabeled datasets offer a path toward exploring chemical space across diverse application domains. Here we develop MIST, a family of molecular foundation models with up to an order of magnitude more parameters and data than prior works. Trained using a novel tokenization scheme that comprehensively captures nuclear, electronic, and geometric information, MIST learns from a diverse range of molecules. MIST models have been fine-tuned to predict more than 400 structure -- property relationships and match or exceed state-of-the-art performance across benchmarks spanning physiology, electrochemistry, and quantum chemistry. We demonstrate the ability of these models to solve real-world problems across chemical space, including multiobjective electrolyte solvent screening, olfactory perception mapping, isotope half-life prediction, stereochemical reasoning for chiral organometallic compounds, and binary and multi-component mixture property prediction. Probing MIST models using mechanistic interpretability methods reveals identifiable patterns and trends not explicitly present in the training data, suggesting that the models learn generalizable scientific concepts. We formulate hyperparameter-penalized Bayesian neural scaling laws and use them to reduce the computational cost of model development by an order of magnitude. The methods and findings presented here represent a significant step toward accelerating materials discovery, design, and optimization using foundation models and provide valuable guidance for training compute-optimal scientific foundation models.

Designing sequences that satisfy multiple, often conflicting, objectives is a central challenge in therapeutic and biomolecular engineering. Existing generative frameworks largely operate in continuous spaces with single-objective guidance, while discrete approaches lack guarantees for multi-objective Pareto optimality. We introduce AReUReDi (Annealed Rectified Updates for Refining Discrete Flows), a discrete optimization algorithm with theoretical guarantees of convergence to the Pareto front. Building on Rectified Discrete Flows (ReDi), AReUReDi combines Tchebycheff scalarization, locally balanced proposals, and annealed Metropolis-Hastings updates to bias sampling toward Pareto-optimal states while preserving distributional invariance. Applied to peptide and SMILES sequence design, AReUReDi simultaneously optimizes up to five therapeutic properties (including affinity, solubility, hemolysis, half-life, and non-fouling) and outperforms both evolutionary and diffusion-based baselines. These results establish AReUReDi as a powerful, sequence-based framework for multi-property biomolecule generation.

In recent years, researchers tend to pre-train ever-larger language models to explore the upper limit of deep models. However, large language model pre-training costs intensive computational resources and most of the models are trained from scratch without reusing the existing pre-trained models, which is wasteful. In this paper, we propose bert2BERT, which can effectively transfer the knowledge of an existing smaller pre-trained model (e.g., BERT_BASE) to a large model (e.g., BERT_LARGE) through parameter initialization and significantly improve the pre-training efficiency of the large model. Specifically, we extend the previous function-preserving on Transformer-based language model, and further improve it by proposing advanced knowledge for large model's initialization. In addition, a two-stage pre-training method is proposed to further accelerate the training process. We did extensive experiments on representative PLMs (e.g., BERT and GPT) and demonstrate that (1) our method can save a significant amount of training cost compared with baselines including learning from scratch, StackBERT and MSLT; (2) our method is generic and applicable to different types of pre-trained models. In particular, bert2BERT saves about 45% and 47% computational cost of pre-training BERT_BASE and GPT_BASE by reusing the models of almost their half sizes. The source code will be publicly available upon publication.