Protein language models are trained primarily with masked language modeling (MLM), which predicts amino-acid identities at masked positions. We ask whether latent-space prediction can complement these token-level objectives under matched wall-clock budget. Across pretrained and random-init protein sequence encoders at 35--150M parameters, we find that the best protein-JEPA design is not all-position latent prediction but a variant: predicting latent targets only at masked positions, and retaining the MLM cross-entropy. We call this recipe masked-position MLM+JEPA. On a 16-task downstream suite (15 frozen linear probes plus SCOPe-40 zero-shot fold retrieval), under matched wall-clock budgets, this recipe wins more tasks than it loses against MLM-only continuation: 10 wins / 3 losses / 3 ties (hereafter W/L/T) on pretrained ESM2-35M, 11/2/3 on ESM2-150M while results in pretraining from scratch are mixed (6/8/2). Gains are seen for multiple models on 11 of 16 tasks, including stability, \b{eta}β\b{eta}-lactamase fitness, variant effect, intrinsic disorder, remote homology, enzyme classification, and SCOPe-40 fold retrieval. Tasks with more losses than wins are Fluorescence (TAPE) and Peptide-HLA Binding. All-position MLM+JEPA matches MLM-only overall but does not reproduce the masked-position gains. JEPA-only (no MLM) collapses in nearly every experiment. We conclude that JEPA, when combined with MLM, is competitive and can outperform pure MLM in pretraining and continued training, even under matched wall-clock budgets.

We study zeroth-order optimisation under context distributional uncertainty, a setting commonly tackled using Bayesian optimisation (BO). A prevailing strategy to make BO more robust to the complex and noisy nature of data is to employ an ensemble as the surrogate model, thereby mitigating the weaknesses of any single model. In this study, we propose a novel algorithm for Ensemble Distributionally Robust Bayesian Optimisation that remains computationally tractable while managing continuous context. We obtain theoretical sublinear regret bounds, improving current state-of-the-art results. We show that our method's empirical behaviour aligns with its theoretical guarantees.

When applying Bayesian optimization (BO) to scientific workflow, a major yet often overlooked source of uncertainty is the task itself -- namely, what to optimize and how to evaluate it -- which can evolve as evidence accumulates. We introduce Generate-Select-Refine (GSR), a open-ended BO framework that alternates between task generation and task optimization. Starting from a user-provided seed task, GSR generates new tasks in a coarse-to-fine manner while a task-acquisition function schedules optimization. Asymptotically, it concentrates evaluations on the best task, incurring only logarithmic regret overhead relative to single-task BO. We apply GSR to new product development, chemical synthesis scaling, algorithm analysis, and patent repurposing, where it outperforms existing LLM-based optimizers.

Transformer blocks typically combine multi-head attention (MHA) for token mixing with gated MLPs for token-wise feature transformation, yet many choices in their parameterization remain largely empirical. We introduce Causal Energy Minimization (CEM), a framework that recasts Transformer layers as optimization steps on conditional energy functions while explicitly accounting for layer parameterization. Extending prior energy-based interpretations of attention, CEM shows that weight-tied MHA can be derived as a gradient update on an interaction energy, and that a gated MLP with shared up/down projections can be viewed through an element-wise energy. This perspective identifies a design space for Transformer layers that includes within-layer weight sharing, diagonal-plus-low-rank interactions, lightweight preconditioners, and recursive updates. We evaluate CEM-derived layers in language-modeling experiments at the moderate hundred-million-parameter scale. Despite their constrained parameterizations, these layers train stably and can match corresponding Transformer baselines. Overall, our results suggest that CEM provides a useful lens for understanding Transformer layer parameterization, connecting Transformer architectures to energy-based models and motivating further exploration of energy-guided layer designs.

Denoising diffusion models have evolved into a state-of-the-art method for tasks in various fields, such as denoising and generation of images, text generation, or generation of synthetic data for training of other machine learning models. First hitting diffusion models (FHDM) are a particular class of denoising diffusion models with \textit{random} adaptive generation time tailored to generate data on a known manifold. Building on the conditioning framework of Doob's $h$-transform these models leverage the given information on the target data manifold to demonstrate strong performance across tasks while offering distinct features such as time-homogeneous dynamics of the generating process and a reduced average simulation time. Even though the theoretical investigation of standard forward-backward diffusion models has attracted much attention in the recent past, the statistical convergence properties of FHDMs are not yet understood. In this work, we show that, up to logarithmic factors, FHDMs achieve the minimax optimal convergence rate in total variation for spherically supported Sobolev smooth data distributions. In particular, this is the first statistical optimality result for denoising diffusion modelling with random generation time.

Large Language Models often improve accuracy on reasoning tasks by sampling multiple Chain-of-Thought (CoT) traces and aggregating them with majority voting (MV), a test-time technique called self-consistency. When we truncate a CoT partway through and regenerate the remainder, we observe that traces with correct answers reproduce their original answer more often than traces with wrong answers. We use this difference as a reliability signal, prefix consistency, that weights each candidate answer by how often it reappears under regeneration. It requires no access to token log-probabilities or self-rating prompts. Across five reasoning models and four math and science benchmarks, prefix consistency is the best correctness predictor in most settings, and reweighting votes by it reaches Standard MV plateau accuracy at up to 21x fewer tokens (median 4.6x). Our code is available at https://github.com/naoto-iwase/prefix-consistency.

Estimating counterfactual distributions under interventions is central to treatment risk assessment and counterfactual generation tasks. Existing approaches model the counterfactual distribution as a standalone generative target, without exploiting its relationship to the observational data. In this work, we show that under standard assumptions, observational and counterfactual outcome distributions are tightly linked: they have identical support and tail behavior, remain statistically close under weak confounding, and share any features of high-dimensional outcomes which are invariant to confounders. These properties motivate learning counterfactual distributions not from scratch, but via a deconfounding flow from the observational distribution. We formulate this problem via flow-matching and derive a semiparametrically efficient estimator based on a novel efficient influence function correction. We subsequently extend our estimator to target minimal-energy flows in high-dimensions, which we show can be especially simple targets between observational and counterfactual distributions. In experiments, deconfounding flows outperform existing debiased counterfactual distribution estimators, while also mitigating known failure modes of flow-based methods.

Persistence diagrams provide stable, interpretable summaries of geometric and topological structure and are useful for simulation-based inference when low-order statistics miss key information. Yet persistence-based pipelines require hand-chosen filtrations, vectorizations, and compressors, typically without an objective tied to parameter uncertainty. We introduce \textbf{TopoFisher}, a differentiable persistent-homology pipeline that learns topological summaries by maximizing local Gaussian Fisher information. Using simulations near a fiducial parameter, TopoFisher optimizes trainable filtrations, diagram vectorizations, and compressors without posterior samples or supervised regression targets, while retaining stable topological inductive bias. We also give sufficient regularity conditions for the log-determinant Fisher loss to be locally Lipschitz in trainable parameters. Controlled experiments on noisy spirals and Gaussian random fields, where total Fisher information is known, show that TopoFisher recovers much of the available information and outperforms fixed topological vectorizations. Our main results are on weak gravitational lensing, a high-dimensional non-Gaussian cosmological field-inference problem. Learned topological summaries reach higher Fisher information than state-of-the-art cosmological summaries and approach an unconstrained Information Maximising Neural Network baseline with up to $\sim80\times$ fewer parameters. The learned filtrations also generalize better: under simulator shift from lognormal to LPT-based maps it retains most Fisher information, while the neural baseline drops, and in neural posterior estimation they give tighter constraints than the neural baseline, and of state-of-the-art cosmological summaries. These results support Fisher-based topological optimization as a robust, parameter-efficient front end for simulation-based inference.

High-dimensional count data arise in applications such as single-cell RNA sequencing and neural spike trains, where mapping between distributions across successive batches or time points form critical components of data analysis. The recent success of diffusion- and flow-based deep generative models for images, video, and text motivates extending these ideas to count-valued settings, but many existing methods either treat each count as a categorical state or transform counts into a continuous space, neither of which is natural or efficient when the count range is large. We propose count-FM, a flow-matching framework for count data based on a continuous-time birth-death process with local unit jumps. Count-FM learns marginal transitions efficiently in count space through simulation-free training of conditional transition rates, allowing transport between arbitrary count-distributed source and target populations. In simulation, count-FM achieves better sample quality than representative baselines while using substantially fewer parameters. We further apply count-FM to scRNA-seq and neural spike-train data for unconditional generation, transport, and conditional generation. Across these tasks, count-FM yields improved sample quality, greater modeling efficiency, and interpretable transport paths.

Balancing exploration and exploitation is a core challenge in sequential decision-making and black-box optimization. We introduce POETS ($\textbf{Po}$licy $\textbf{E}$nsembles for $\textbf{T}$hompson $\textbf{S}$ampling), a novel framework that bridges uncertainty quantification and policy optimization. Our approach is grounded in the insight that policies trained with Kullback-Leibler (KL) regularization implicitly encode an underlying reward function. Building on this, POETS bypasses the complex, nested process of training an uncertainty-aware reward model and separately fitting a policy to this model. Instead, we directly train a policy ensemble to capture epistemic uncertainty by matching implicitly encoded reward functions to online, bootstrapped data. To overcome the prohibitive compute and memory constraints of ensembling Large Language Models (LLMs), POETS utilizes an efficient architecture: the ensemble shares a pre-trained backbone while maintaining diversity through independent Low-Rank Adaptation (LoRA) branches. Theoretically, we prove that POETS implicitly conducts KL-regularized Thompson sampling and thus inherits strong cumulative regret bounds of ${\mathcal O}(\sqrt{T γ_T})$. Empirically, we demonstrate that POETS achieves state-of-the-art sample efficiency across diverse scientific discovery domains, including protein search and quantum circuit design. Furthermore, it improves the optimization trajectories of reinforcement learning, proving particularly robust in off-policy settings with experience replay or in small dataset regimes.