Therapeutic antibodies have been extensively studied in drug discovery and development in the past decades. Antibodies are specialized protective proteins that bind to antigens in a lock-to-key manner. The binding strength/affinity between an antibody and a specific antigen is heavily determined by the complementarity-determining regions (CDRs) on the antibodies. Existing machine learning methods cast in silico development of CDRs as either sequence or 3D graph (with a single chain) generation tasks and have achieved initial success. However, with CDR loops having specific geometry shapes, learning the 3D geometric structures of CDRs remains a challenge. To address this issue, we propose AntibodyFlow, a 3D flow model to design antibody CDR loops. Specifically, AntibodyFlow first constructs the distance matrix, then predicts amino acids conditioned on the distance matrix. Also, AntibodyFlow conducts constraint learning and constrained generation to ensure valid 3D structures. Experimental results indicate that AntibodyFlow outperforms the best baseline consistently with up to 16.0% relative improvement in validity rate and 24.3% relative reduction in geometric graph level error (root mean square deviation, RMSD).

Graph neural networks (GNNs) have emerged as a powerful tool for solving combinatorial optimization problems (COPs), exhibiting state-of-the-art performance in both graph-structured and non-graph-structured domains. However, existing approaches lack a unified framework capable of addressing a wide range of COPs. After presenting a summary of representative COPs and a brief review of recent advancements in GNNs for solving COPs, this paper proposes a unified framework for solving COPs based on GNNs, including graph representation of COPs, equivalent conversion of non-graph structured COPs to graph-structured COPs, graph decomposition, and graph simplification. The proposed framework leverages the ability of GNNs to effectively capture the relational information and extract features from the graph representation of COPs, offering a generic solution to COPs that can address the limitations of state-of-the-art in solving non-graph-structured and highly complex graph-structured COPs.

In this paper, we propose a novel decentralized control method to maintain Line-of-Sight connectivity for multi-robot networks in the presence of Guassian-distributed localization uncertainty. In contrast to most existing work that assumes perfect positional information about robots or enforces overly restrictive rigid formation against uncertainty, our method enables robots to preserve Line-of-Sight connectivity with high probability under unbounded Gaussian-like positional noises while remaining minimally intrusive to the original robots' tasks. This is achieved by a motion coordination framework that jointly optimizes the set of existing Line-of-Sight edges to preserve and control revisions to the nominal task-related controllers, subject to the safety constraints and the corresponding composition of uncertainty-aware Line-of-Sight control constraints. Such compositional control constraints, expressed by our novel notion of probabilistic Line-of-Sight connectivity barrier certificates (PrLOS-CBC) for pairwise robots using control barrier functions, explicitly characterize the deterministic admissible control space for the two robots. The resulting motion ensures Line-of-Sight connectedness for the robot team with high probability. Furthermore, we propose a fully decentralized algorithm that decomposes the motion coordination framework by interleaving the composite constraint specification and solving for the resulting optimization-based controllers. The optimality of our approach is justified by the theoretical proofs. Simulation and real-world experiments results are given to demonstrate the effectiveness of our method.

Sparsity-constraint optimization has wide applicability in signal processing, statistics, and machine learning. Existing fast algorithms must burdensomely tune parameters, such as the step size or the implementation of precise stop criteria, which may be challenging to determine in practice. To address this issue, we develop an algorithm named Sparsity-Constraint Optimization via sPlicing itEration (SCOPE) to optimize nonlinear differential objective functions with strong convexity and smoothness in low dimensional subspaces. Algorithmically, the SCOPE algorithm converges effectively without tuning parameters. Theoretically, SCOPE has a linear convergence rate and converges to a solution that recovers the true support set when it correctly specifies the sparsity. We also develop parallel theoretical results without restricted-isometry-property-type conditions. We apply SCOPE's versatility and power to solve sparse quadratic optimization, learn sparse classifiers, and recover sparse Markov networks for binary variables. The numerical results on these specific tasks reveal that SCOPE perfectly identifies the true support set with a 10--1000 speedup over the standard exact solver, confirming SCOPE's algorithmic and theoretical merits. Our open-source Python package skscope based on C++ implementation is publicly available on GitHub, reaching a ten-fold speedup on the competing convex relaxation methods implemented by the cvxpy library.

We introduce iterative reasoning through energy diffusion (IRED), a novel framework for learning to reason for a variety of tasks by formulating reasoning and decision-making problems with energy-based optimization. IRED learns energy functions to represent the constraints between input conditions and desired outputs. After training, IRED adapts the number of optimization steps during inference based on problem difficulty, enabling it to solve problems outside its training distribution -- such as more complex Sudoku puzzles, matrix completion with large value magnitudes, and pathfinding in larger graphs. Key to our method's success is two novel techniques: learning a sequence of annealed energy landscapes for easier inference and a combination of score function and energy landscape supervision for faster and more stable training. Our experiments show that IRED outperforms existing methods in continuous-space reasoning, discrete-space reasoning, and planning tasks, particularly in more challenging scenarios. Code and visualizations at https://energy-based-model.github.io/ired/

Constrained text generation remains a challenging task, particularly when dealing with hard constraints. Traditional Natural Language Processing (NLP) approaches prioritize generating meaningful and coherent output. Also, the current state-of-the-art methods often lack the expressiveness and constraint satisfaction capabilities to handle such tasks effectively. This paper presents the Constraints First Framework to remedy this issue. This framework considers a constrained text generation problem as a discrete combinatorial optimization problem. It is solved by a constraint programming method that combines linguistic properties (e.g., n-grams or language level) with other more classical constraints (e.g., the number of characters, syllables, or words). Eventually, a curation phase allows for selecting the best-generated sentences according to perplexity using a large language model. The effectiveness of this approach is demonstrated by tackling a new more tediously constrained text generation problem: the iconic RADNER sentences problem. This problem aims to generate sentences respecting a set of quite strict rules defined by their use in vision and clinical research. Thanks to our CP-based approach, many new strongly constrained sentences have been successfully generated in an automatic manner. This highlights the potential of our approach to handle unreasonably constrained text generation scenarios.

Many automated planning methods and formulations rely on suitably designed abstractions or simplifications of the constrained dynamics associated with agents to attain computational scalability. We consider formulations of temporal planning where intervals are associated with both action and fluent atoms, and relations between these are given as sentences in Allen's Interval Logic. We propose a notion of planning graphs that can account for complex concurrency relations between actions and fluents as a Constraint Programming (CP) model. We test an implementation of our algorithm on a state-of-the-art framework for CP and compare it with PDDL 2.1 planners that capture plans requiring complex concurrent interactions between agents. We demonstrate our algorithm outperforms existing PDDL 2.1 planners in the case studies. Still, scalability remains challenging when plans must comply with intricate concurrent interactions and the sequencing of actions.

While the recent Chain-of-Thought (CoT) technique enhances the reasoning ability of large language models (LLMs) with the theory of mind, it might still struggle in handling logical reasoning that relies much on symbolic expressions and rigid deducing rules. To strengthen the logical reasoning capability of LLMs, we propose a novel Symbolic Chain-of-Thought, namely SymbCoT, a fully LLM-based framework that integrates symbolic expressions and logic rules with CoT prompting. Technically, building upon an LLM, SymbCoT 1) first translates the natural language context into the symbolic format, and then 2) derives a step-by-step plan to solve the problem with symbolic logical rules, 3) followed by a verifier to check the translation and reasoning chain. Via thorough evaluations on 5 standard datasets with both First-Order Logic and Constraint Optimization symbolic expressions, SymbCoT shows striking improvements over the CoT method consistently, meanwhile refreshing the current state-of-the-art performances. We further demonstrate that our system advances in more faithful, flexible, and explainable logical reasoning. To our knowledge, this is the first to combine symbolic expressions and rules into CoT for logical reasoning with LLMs. Code is open at https://github.com/Aiden0526/SymbCoT.

In recent years, machine learning (ML) has emerged as a promising avenue for addressing optimization problems like the Travelling Salesman Problem (TSP). ML techniques, particularly those involving neural networks and reinforcement learning, have shown potential in learning heuristics and patterns that can guide the search for optimal routes more efficiently. By leveraging data, ML models can improve the quality of solutions and reduce computation time. One notable approach is the use of heat map-based search, where ML models generate heat maps that highlight promising regions of the solution space. These heat maps are then used to focus the search process, potentially enhancing the efficiency and effectiveness of finding optimal or near-optimal solutions [1]. Recently, the authors of paper [2] (referred to as SoftDist) discussed the neural approach and claimed: Our theoretical and experimental analysis raises doubts about the effectiveness of MLbased heat map generation. In support of this, we demonstrate that a simple baseline method can outperform complex ML approaches in heat map generation. Here, however, we show that the authors in SoftDist misconducted the experiments, leading to an unfair comparison and a flawed conclusion.

One part of complying with norms, rules, and preferences is incorporating constraints (such as knowledge of ethics) into one's goal formulation and planning processing. We explore in a simple domain how the encoding of knowledge in different ethical frameworks influences an agent's goal formulation and planning processing and demonstrate ability of an agent to satisfy and satisfice when its collection of relevant constraints includes a mix of "hard" and "soft" constraints of various types. How the agent attempts to comply with ethical constraints depends on the ethical framing and we investigate tradeoffs between deontological framing and utilitarian framing for complying with an ethical norm. Representative scenarios highlight how performing the same task with different framings of the same norm leads to different behaviors. Our explorations suggest an important role for metacognitive judgments in resolving ethical conflicts during goal formulation and planning.