Lead optimization in drug discovery requires efficiently navigating vast chemical space through iterative cycles to enhance molecular properties while preserving structural similarity to the original lead compound. Despite recent advances, traditional optimization methods struggle with sample efficiency-achieving good optimization performance with limited oracle evaluations. Large Language Models (LLMs) provide a promising approach through their in-context learning and instruction following capabilities, which align naturally with these iterative processes. However, existing LLM-based methods fail to leverage this strength, treating each optimization step independently. To address this, we present POLO (Preference-guided multi-turn Optimization for Lead Optimization), which enables LLMs to learn from complete optimization trajectories rather than isolated steps. At its core, POLO introduces Preference-Guided Policy Optimization (PGPO), a novel reinforcement learning algorithm that extracts learning signals at two complementary levels: trajectory-level optimization reinforces successful strategies, while turn-level preference learning provides dense comparative feedback by ranking intermediate molecules within each trajectory. Through this dual-level learning from intermediate evaluation, POLO achieves superior sample efficiency by fully exploiting each costly oracle call. Extensive experiments demonstrate that POLO achieves 84% average success rate on single-property tasks (2.3x better than baselines) and 50% on multi-property tasks using only 500 oracle evaluations, significantly advancing the state-of-the-art in sample-efficient molecular optimization.

A bilevel optimization problem consists of two optimization problems nested as an upper- and a lower-level problem, in which the optimality of the lower-level problem defines a constraint for the upper-level problem. This paper considers Bayesian optimization (BO) for the case that both the upper- and lower-levels involve expensive black-box functions. Because of its nested structure, bilevel optimization has a complex problem definition and, compared with other standard extensions of BO such as multi-objective or constraint settings, it has not been widely studied. We propose an information-theoretic approach that considers the information gain of both the upper- and lower-optimal solutions and values. This enables us to define a unified criterion that measures the benefit for both level problems, simultaneously. Further, we also show a practical lower bound based approach to evaluating the information gain. We empirically demonstrate the effectiveness of our proposed method through several benchmark datasets.

We propose a conversion scheme that turns regret minimizing algorithms into fixed point iterations, with convergence guarantees following from regret bounds. The resulting iterations can be seen as a grand extension of the classical Krasnoselskii--Mann iterations, as the latter are recovered by converting the Online Gradient Descent algorithm. This approach yields new simple iterations for finding fixed points of non-self operators. We also focus on converting algorithms from the AdaGrad family of regret minimizers, and thus obtain fixed point iterations with adaptive guarantees of a new kind. Numerical experiments on various problems demonstrate faster convergence of AdaGrad-based fixed point iterations over Krasnoselskii--Mann iterations.

Vision-based odometry has been widely adopted in autonomous driving owing to its low cost and lightweight setup; however, its performance often degrades in complex outdoor urban environments. To address these challenges, we propose PL-VIWO2, a filter-based visual-inertial-wheel odometry system that integrates an IMU, wheel encoder, and camera (supporting both monocular and stereo) for long-term robust state estimation. The main contributions are: (i) a novel line feature processing framework that exploits the geometric relationship between 2D feature points and lines, enabling fast and robust line tracking and triangulation while ensuring real-time performance; (ii) an SE(2)-constrained SE(3) wheel pre-integration method that leverages the planar motion characteristics of ground vehicles for accurate wheel updates; and (iii) an efficient motion consistency check (MCC) that filters out dynamic features by jointly using IMU and wheel measurements. Extensive experiments on Monte Carlo simulations and public autonomous driving datasets demonstrate that PL-VIWO2 outperforms state-of-the-art methods in terms of accuracy, efficiency, and robustness.