Rare events such as conformational changes in biomolecules, phase transitions, and chemical reactions are central to the behavior of many physical systems, yet they are extremely difficult to study computationally because unbiased simulations seldom produce them. Transition Path Theory (TPT) provides a rigorous statistical framework for analyzing such events: it characterizes the ensemble of reactive trajectories between two designated metastable states (reactant and product), and its central object--the committor function, which gives the probability that the system will next reach the product rather than the reactant--encodes all essential kinetic and thermodynamic information. We introduce a framework that casts committor estimation as a stochastic optimal control (SOC) problem. In this formulation the committor defines a feedback control--proportional to the gradient of its logarithm--that actively steers trajectories toward the reactive region, thereby enabling efficient sampling of reactive paths. To solve the resulting hitting-time control problem we develop two complementary objectives: a direct backpropagation loss and a principled off-policy Value Matching loss, for which we establish first-order optimality guarantees. We further address metastability, which can trap controlled trajectories in intermediate basins, by introducing an alternative sampling process that preserves the reactive current while lowering effective energy barriers. On benchmark systems, the framework yields markedly more accurate committor estimates, reaction rates, and equilibrium constants than existing methods.

Antibody lead optimization is inherently a multi-objective challenge in drug discovery. Achieving a balance between different drug-like properties is crucial for the development of viable candidates, and this search becomes exponentially challenging as desired properties grow. The ever-growing zoo of sophisticated in silico tools for predicting antibody properties calls for an efficient joint optimization procedure to overcome resource-intensive sequential filtering pipelines. We present BOAT, a versatile Bayesian optimization framework for multi-property antibody engineering. Our `plug-and-play' framework couples uncertainty-aware surrogate modeling with a genetic algorithm to jointly optimize various predicted antibody traits while enabling efficient exploration of sequence space. Through systematic benchmarking against genetic algorithms and newer generative learning approaches, we demonstrate competitive performance with state-of-the-art methods for multi-objective protein optimization. We identify clear regimes where surrogate-driven optimization outperforms expensive generative approaches and establish practical limits imposed by sequence dimensionality and oracle costs.

We study learning to learn for regression problems through the lens of hyperparameter tuning. We propose the Langevin Gradient Descent Algorithm (LGD), which approximates the mean of the posterior distribution defined by the loss function and regularizer of a convex regression task. We prove the existence of an optimal hyperparameter configuration for which the LGD algorithm achieves the Bayes' optimal solution for squared loss. Subsequently, we study generalization guarantees on meta-learning optimal hyperparameters for the LGD algorithm from a given set of tasks in the data-driven setting. For a number of parameters $d$ and hyperparameter dimension $h$, we show a pseudo-dimension bound of $O(dh)$, upto logarithmic terms under mild assumptions on LGD. This matches the dimensional dependence of the bounds obtained in prior work for the elastic net, which only allows for $h=2$ hyperparameters, and extends their bounds to regression on convex loss. Finally, we show empirical evidence of the success of LGD and the meta-learning procedure for few-shot learning on linear regression using a few synthetically created datasets.

Clinical decision-making often involves selecting tests that are costly, invasive, or time-consuming, motivating individualized, sequential strategies for what to measure and when to stop ascertaining. We study the problem of learning cost-optimal sequential decision policies from retrospective data, where test availability depends on prior results, inducing informative missingness. Under a sequential missing-at-random mechanism, we develop a doubly robust Q-learning framework for estimating optimal policies. The method introduces path-specific inverse probability weights that account for heterogeneous test trajectories and satisfy a normalization property conditional on the observed history. By combining these weights with auxiliary contrast models, we construct orthogonal pseudo-outcomes that enable unbiased policy learning when either the acquisition model or the contrast model is correctly specified. We establish oracle inequalities for the stage-wise contrast estimators, along with convergence rates, regret bounds, and misclassification rates for the learned policy. Simulations demonstrate improved cost-adjusted performance over weighted and complete-case baselines, and an application to a prostate cancer cohort study illustrates how the method reduces testing cost without compromising predictive accuracy.

We prove that conditional diffusion models whose reverse kernels are finite Gaussian mixtures with ReLU-network logits can approximate suitably regular target distributions arbitrarily well in context-averaged conditional KL divergence, up to an irreducible terminal mismatch that typically vanishes with increasing diffusion horizon. A path-space decomposition reduces the output error to this mismatch plus per-step reverse-kernel errors; assuming each reverse kernel factors through a finite-dimensional feature map, each step becomes a static conditional density approximation problem, solved by composing Norets' Gaussian-mixture theory with quantitative ReLU bounds. Under exact terminal matching the resulting neural reverse-kernel class is dense in conditional KL.

We show that the maximum expected inner product between a random vector and the standard normal vector over all couplings subject to a mutual information constraint or regularization is equivalent to a truncated integral involving the rate-distortion function, up to universal multiplicative constants. The proof is based on a lifting technique, which constructs a Gaussian process indexed by a random subset of the type class of the probability distribution involved in the information-theoretic inequality, and then applying a form of the majorizing measure theorem.

This paper studies continuous-time stochastic control problems whose controlled states are fully non-Markovian and depend on unknown model parameters. Such problems arise naturally in path-dependent stochastic differential equations, rough-volatility hedging, and systems driven by fractional Brownian motion. Building on the discrete skeleton approach developed in earlier work, we propose a Monte Carlo learning methodology for the associated embedded backward dynamic programming equation. Our main contribution is twofold. First, we construct explicit dominating training laws and Radon--Nikodym weights for several representative classes of non-Markovian controlled systems. This yields an off-model training architecture in which a fixed synthetic dataset is generated under a reference law, while the dynamic programming operators associated with a target model are recovered by importance sampling. Second, we use this structure to design an adaptive update mechanism under parametric model uncertainty, so that repeated recalibration can be performed by reweighting the same training sample rather than regenerating new trajectories. For fixed parameters, we establish non-asymptotic error bounds for the approximation of the embedded dynamic programming equation via deep neural networks. For adaptive learning, we derive quantitative estimates that separate Monte Carlo approximation error from model-risk error. Numerical experiments illustrate both the off-model training mechanism and the adaptive importance-sampling update in structured linear-quadratic examples.

We introduce Multistage Conditional Compositional Optimization (MCCO) as a new paradigm for decision-making under uncertainty that combines aspects of multistage stochastic programming and conditional stochastic optimization. MCCO minimizes a nest of conditional expectations and nonlinear cost functions. It has numerous applications and arises, for example, in optimal stopping, linear-quadratic regulator problems, distributionally robust contextual bandits, as well as in problems involving dynamic risk measures. The naïve nested sampling approach for MCCO suffers from the curse of dimensionality familiar from scenario tree-based multistage stochastic programming, that is, its scenario complexity grows exponentially with the number of nests. We develop new multilevel Monte Carlo techniques for MCCO whose scenario complexity grows only polynomially with the desired accuracy.

We propose a new partial-observability model for online learning problems where the learner, besides its own loss, also observes some noisy feedback about the other actions, depending on the underlying structure of the problem. We represent this structure by a weighted directed graph, where the edge weights are related to the quality of the feedback shared by the connected nodes. Our main contribution is an efficient algorithm that guarantees a regret of $\widetilde{O}(\sqrt{α^* T})$ after $T$ rounds, where $α^*$ is a novel graph property that we call the effective independence number. Our algorithm is completely parameter-free and does not require knowledge (or even estimation) of $α^*$. For the special case of binary edge weights, our setting reduces to the partial-observability models of Mannor and Shamir (2011) and Alon et al. (2013) and our algorithm recovers the near-optimal regret bounds.

Thompson Sampling (TS) has attracted a lot of interest due to its good empirical performance, in particular in the computational advertising. Though successful, the tools for its performance analysis appeared only recently. In this paper, we describe and analyze SpectralTS algorithm for a bandit problem, where the payoffs of the choices are smooth given an underlying graph. In this setting, each choice is a node of a graph and the expected payoffs of the neighboring nodes are assumed to be similar. Although the setting has application both in recommender systems and advertising, the traditional algorithms would scale poorly with the number of choices. For that purpose we consider an effective dimension d, which is small in real-world graphs. We deliver the analysis showing that the regret of SpectralTS scales as d*sqrt(T ln N) with high probability, where T is the time horizon and N is the number of choices. Since a d*sqrt(T ln N) regret is comparable to the known results, SpectralTS offers a computationally more efficient alternative. We also show that our algorithm is competitive on both synthetic and real-world data.