Designing protein sequences of both high fitness and novelty is a challenging task in data-efficient protein engineering. Exploration beyond wild-type neighborhoods often leads to biologically implausible sequences or relies on surrogate models that lose fidelity in novel regions. Here, we propose PROSPERO, an active learning framework in which a frozen pre-trained generative model is guided by a surrogate updated from oracle feedback. By integrating fitness-relevant residue selection with biologically-constrained Sequential Monte Carlo sampling, our approach enables exploration beyond wild-type neighborhoods while preserving biological plausibility. We show that our framework remains effective even when the surrogate is misspecified. PROSPERO consistently outperforms or matches existing methods across diverse protein engineering tasks, retrieving sequences of both high fitness and novelty.

Stochastic optimal control methods often struggle in complex non-convex landscapes, frequently becoming trapped in local optima due to their inability to learn from historical trajectory data. This paper introduces Memory-Augmented Potential Field Theory, a unified mathematical framework that integrates historical experience into stochastic optimal control. Our approach dynamically constructs memory-based potential fields that identify and encode key topological features of the state space, enabling controllers to automatically learn from past experiences and adapt their optimization strategy. We provide a theoretical analysis showing that memory-augmented potential fields possess non-convex escape properties, asymptotic convergence characteristics, and computational efficiency. We implement this theoretical framework in a Memory-Augmented Model Predictive Path Integral (MPPI) controller that demonstrates significantly improved performance in challenging non-convex environments. The framework represents a generalizable approach to experience-based learning within control systems (especially robotic dynamics), enhancing their ability to navigate complex state spaces without requiring specialized domain knowledge or extensive offline training.

The loss landscapes of neural networks contain minima and saddle points that may be connected in flat regions or appear in isolation. We identify and characterize a special structure in the loss landscape: channels along which the loss decreases extremely slowly, while the output weights of at least two neurons, ai and aj, diverge to infinity, and their input weight vectors, wi and wj, become equal to each other. At convergence, the two neurons implement a gated linear unit: aiσ(wi x) + ajσ(wj x) cσ(w x) + (v x)σ (w x). Geometrically, these channels to infinity are asymptotically parallel to symmetry-induced lines of critical points. Gradient flow solvers, and related optimization methods like SGD or ADAM, reach the channels with high probability in diverse regression settings, but without careful inspection they look like flat local minima with finite parameter values. Our characterization provides a comprehensive picture of these quasi-flat regions in terms of gradient dynamics, geometry, and functional interpretation. The emergence of gated linear units at the end of the channels highlights a surprising aspect of the computational capabilities of fully connected layers.

Remote sensing is critical for disaster monitoring, yet existing datasets lack temporal image pairs and detailed textual annotations. While single-snapshot imagery dominates current resources, it fails to capture dynamic disaster impacts over time. To address this gap, we introduce the Remote Sensing Change Caption (RSCC) dataset, a large-scale benchmark comprising 62,351 pre-/post-disaster image pairs (spanning earthquakes, floods, wildfires, and more) paired with rich, human-like change captions. By bridging the temporal and semantic divide in remote sensing data, RSCC enables robust training and evaluation of vision-language models for disaster-aware bi-temporal understanding. Our results highlight RSCC's ability to facilitate detailed disaster-related analysis, paving the way for more accurate, interpretable, and scalable vision-language applications in remote sensing.

Protein language models (PLMs) learn probability distributions over natural protein sequences. By learning from hundreds of millions of natural protein sequences, protein understanding and design capabilities emerge. Recent works have shown that scaling these models improves structure prediction, but does not seem to improve mutation understanding and representation quality for protein function prediction. We introduce PoET-2, a multimodal, retrieval-augmented protein foundation model that incorporates in-context learning of family-specific evolutionary constraints with optional structure conditioning to learn generative distributions over protein sequences. PoET-2 uses a hierarchical transformer encoder that is equivariant to sequence context ordering and a dual decoder architecture with both causal and masked language modeling objectives, allowing PoET-2 to operate in both fully generative and bidirectional representation learning modes. PoET-2 achieves stateof-the-art performance on zero-shot variant effect prediction, excelling at scoring variants with multiple mutations and challenging indel mutations. In supervised settings, PoET-2 embeddings outperform previous methods for learning sequencefunction relationships, especially with small datasets. This work highlights the benefits of combining retrieval augmentation with multimodal, family-centric modeling for advancing protein foundation models. 1

The success of Reinforcement Learning from Human Feedback (RLHF) critically depends on the quality of the reward model. However, while this quality is primarily evaluated through accuracy, it remains unclear whether accuracy fully captures what makes a reward model an effective teacher. We address this question from an optimization perspective. First, we prove that regardless of how accurate a reward model is, if it induces low reward variance, then the RLHF objective suffers from a flat landscape. Consequently, even a perfectly accurate reward model can lead to extremely slow optimization, underperforming less accurate models that induce higher reward variance. We additionally show that a reward model that works well for one language model can induce low reward variance, and thus a flat objective landscape, for another. These results establish a fundamental limitation of evaluating reward models solely based on accuracy or independently of the language model they guide. Experiments using models of up to 8B parameters corroborate our theory, demonstrating the interplay between reward variance, accuracy, and reward maximization rate. Overall, our findings highlight that beyond accuracy, a reward model needs to induce sufficient variance for efficient optimization.

Machine learning models increasingly map biological sequence-fitness landscapes to predict mutational effects. Effective evaluation of these models requires benchmarks curated from empirical data. Despite their impressive scales, existing benchmarks lack topographical information regarding the underlying fitness landscapes, which hampers interpretation and comparison of model performance beyond averaged scores. Here, we introduce GraphFLA, a Python framework that constructs and analyzes fitness landscapes from diverse modalities (DNA, RNA, protein, and beyond.),

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While parameter-efficient fine-tuning methods like low-rank adaptation (LoRA) are standard for large language models, principled estimation of epistemic uncertainty remains challenging. Recent results in the LoRA regime suggest that discrete multi-mode approaches such as deep ensembles offer little benefit over single-mode methods. This contradicts broader observations in deep learning, where ensembling independent optima typically improves generalization, and linking these modes through continuous low-loss valleys further enhances Bayesian model averaging (BMA). Whether such structure exists in the LoRA space and whether it yields functional diversity missed by local or discrete methods has not been studied. We introduce LoRA-Curve, a segmented Bézier curve parameterization in the LoRA space, with two variants: a free configuration that jointly optimizes all control points, and an anchored configuration that connects independently fine-tuned LoRA optima. We prove pathwise continuity and Lipschitz regularity of the loss along the curve and empirically show, across reasoning and classification benchmarks with Qwen2.5 7B, that linear interpolation encounters loss barriers, while our anchored multi-segment curves connect independent optima through continuous low-loss valleys. Combined with flat-minima perturbations and a Jensen-Shannon divergence regularizer, LoRA-Curve yields measurably higher mutual information of the predictive distribution without sacrificing performance, and links continuous parameter-space traversal to functional diversity.

Generative models, including diffusion models, are increasingly used as foundation models and adapted through sequential fine-tuning, making continual learning an essential problem setting. However, continual learning in such generative models remains poorly understood: after a task change, what aspects of the learned distribution are most easily lost, and what replay samples should be prioritized? We address these questions through the modern Hopfield energy. Recent links between modern Hopfield networks (MHNs) and diffusion models allow analyses in MHNs to be transferred to diffusion models. We introduce intrinsic forgetting as an increase in Hopfield energy after the task change. In tractable settings in an MHN, we prove that high-energy, outlier-like samples undergo a larger energy increase than cluster-like samples, implying that samples located in sharp, isolated basins are more forgettable. We further analyze memory replay and show that replay is particularly effective for high-energy samples, enabling an energy-based selection of replay samples. We validate these predictions in experiments on MHNs and two diffusion models under continual-learning settings: Stable Diffusion and a pixel-space DDPM. In these diffusion models, Hopfield energy tracks reconstruction-based forgetting, and replay experiments reveal energy-dependent mitigation of forgetting that is consistent with the MHN analysis.