Academic Intelligence · Curated Daily

Explore the Frontier of Global Academia

AcademicHub aggregates real-time literature from top journals and preprint platforms. Build your personal research radar and let large language models compile cross-disciplinary analysis briefings automatically.

01.
arXiv (CS.AI) 2026-06-24

THEIA: Learning Complete Kleene Three-Valued Logic in a Pure-Neural Modular Architecture

arXiv:2604.11284v5 Announce Type: replace-cross Abstract: We present THEIA, a 2.75M-parameter modular neural architecture that learns the complete Kleene three-valued logic (K3) truth table from task data without external symbolic inference or hand-encoded K3 gate primitives. Across 5 seeds it passes all 39 K3 rules at >99% per-rule accuracy. K3 learnability is not the central finding: Transformer baselines also pass all 39 rules, and flat MLPs match THEIA on Phase-1 accuracy within 0.04pp. The contributions are two properties of the learned system. (1) Uncertainty-verdict asymmetric propagation. THEIA preserves Has-Unknown at every upstream boundary (80.0/91.1/90.8/99.7% across Arith/Order/Set/Logic vs. ~52% majority) while final-verdict decodability stays at or below a 73.4% U-vs-non-U oracle reference under linear and nonlinear probes. Activation patching on non-absorbent T->U cases flips 4,898/4,898 OR and 4,719/4,719 AND pairs across 5 seeds, ruling out residual shortcuts. (2) Reliability spectrum under discretized end-to-end training, on tasks decomposable along the engine boundaries. A mod-3 sequential composition task generalizes from 5- to 500-step evaluation at 99.96+-0.04% (5 seeds). Under identical Gumbel-softmax training, flat MLPs collapse to chance by 50 steps; a 2x2 ResMLP grid reaches >=99% on only 3/20 (config, seed) trials; a pre-LN Transformer reaches 99.24+-0.34%. Straight-through discretization prevents 0.999^500 compounding; the architectural separator is sustaining Phase-1 accuracy under Phase-3 training, where flat MLPs fail. Auxiliary: under per-architecture development defaults (not optimizer-controlled), THEIA reaches 12/12 Kleene coverage 6.5x faster than a parameter-comparable 8L Transformer; this narrows to ~3.6x with Transformer-standard tuning and 4.93x with the same recipe on both. Ratios are config-specific, not asymptotic.

02.
arXiv (quant-ph) 2026-06-17

Einstein-Podolsky-Rosen correlations between mechanical oscillators revealed through SU(1,1) interferometry

arXiv:2606.18202v1 Announce Type: new Abstract: Quantum correlations are essential for achieving quantum advantage in computing, communication and sensing. Moreover, their observation challenges and constrains our fundamental understanding of nature. Mechanical oscillators in the quantum regime provide an appealing platform for preparing and investigating quantum correlations at macroscopic scales. Despite substantial progress, however, continuous-variable quantum correlations stronger than entanglement have not yet been observed in this macroscopic regime. Here, we report the experimental observation of continuous-variable Einstein-Podolsky-Rosen correlations between two spatially-separated mechanical oscillators with an effective mass of $\sim 16 \,\mu g$ each. This is achieved by coupling them to a superconducting qubit which allows for engineering a two-mode squeezing interaction when parametrically driven. Crucially, we show that this interaction can be used to witness quantum correlations through the realization of a mechanical SU(1,1) interferometer. Our results expand the toolbox of operations in circuit quantum acoustodynamics and demonstrate that quantum correlations stronger than entanglement can also be observed in macroscopic systems, thereby shedding light on the boundary between quantum and classical regimes.

03.
arXiv (quant-ph) 2026-06-12

Quantum metrology via partial quantum error correction

arXiv:2605.08341v2 Announce Type: replace Abstract: We introduce a method for error-corrected quantum metrology where only partial quantum error correction (QEC) is needed to suppress local noise and maintain the probe states' super-standard-quantum-limit (super-SQL) sensing performance. This stands in contrast to the existing QEC-assisted sensing schemes in Phys. Rev. Lett. 112, 080801 (2014) and Phys. Rev. Lett. 112, 150802 (2014), where a probe state is encoded into the logical subspace of a quantum code and error correction involves measurements on all checks of the code. Here, we encode the probe states into superpositions of energetically different states of the underlying quantum code. For our probe states, error correction using a subset of checks is enough to suppress noise both before and after phase imprinting. We analyze the tradeoff in noise suppression. For noise parallel to our phase imprinter of weight $l$, we achieve a suppression of $p^\delta$ where $p$ is the noise strength and $\delta = \lfloor (l+1)/2 \rfloor$. We propose an adaptive imprinter weight increasing strategy to maintain super-SQL performance as we scale up the system. In all our examples, checks and phase imprinters are chosen to be local operators avoiding non-local connectivity.

04.
arXiv (CS.LG) 2026-06-11

How Low Can You Go? Active Learning for Sparse Model Discovery in the Ultra-Low-Data Limit

arXiv:2606.12182v1 Announce Type: new Abstract: Identifying the governing equations of complex dynamical systems remains a fundamental challenge across science and engineering. While early approaches relied on empirical data and heuristics, modern data-driven methods offer greater flexibility and fewer assumptions. However, data acquisition in real-world settings is often expensive. This work addresses this challenge by introducing an active learning strategy for dynamics discovery in the ultra-low data limit. Rather than sampling randomly, our method iteratively prioritizes regions that are most informative for model identification. This approach builds on Sparse Identification of Nonlinear Dynamics (SINDy), and utilizes an ensemble extension, E-SINDy, to estimate epistemic uncertainty and guide the sampling for both ordinary and partial differential equations (ODEs/PDEs). For ODEs, an exhaustive analysis is conducted on the Lorenz system across varying data budgets and noise levels. For PDEs, two systems with contrasting dynamical characteristics are examined: the Burgers' equation, where a sharp shock front creates a distinction between informative and uninformative regions, and the Kuramoto-Sivashinsky equation, which presents a more spatially complex sampling landscape. Across all scenarios, the proposed method accurately identifies the governing dynamics with significantly fewer data samples than random sampling.

05.
arXiv (CS.AI) 2026-06-25

EvoAgent: An Evolvable Agent Framework with Skill Learning and Multi-Agent Delegation

arXiv:2604.20133v3 Announce Type: replace Abstract: This paper proposes EvoAgent–an evolvable large language model (LLM) agent framework that integrates structured skill learning with a hierarchical sub-agent delegation mechanism. EvoAgent models skills as multi-file structured capability units equipped with triggering mechanisms and evolutionary metadata, and enables continuous skill generation and optimization through a user-feedback-driven closed-loop process. In addition, by incorporating a three-stage skill matching strategy and a three-layer memory architecture, the framework supports dynamic task decomposition for complex problems and long-term capability accumulation. Experimental results based on real-world foreign trade scenarios demonstrate that, after integrating EvoAgent, GPT5.2 achieves significant improvements in professionalism, accuracy, and practical utility. Under a five-dimensional LLM-as-Judge evaluation protocol, the overall average score increases by approximately 28\%. Further model transfer experiments indicate that the performance of an agent system depends not only on the intrinsic capabilities of the underlying model, but also on the degree of synergy between the model and the agent architecture. Code, data, and documents will be released at https://github.com/Focus-AI-Center/Mentarc-EvoAgent.git.

06.
arXiv (CS.AI) 2026-06-18

Skill-MAS: Evolving Meta-Skill for Automatic Multi-Agent Systems

arXiv:2606.18837v1 Announce Type: cross Abstract: Large Language Model (LLM)-based automatic Multi-Agent Systems (MAS) generation has become a crucial frontier for tackling complex tasks. However, existing methods face a dilemma between model capability and experience retention. Inference-time MAS leverages frozen frontier LLMs but repeats identical searches without learning from past experience. Conversely, Training-time MAS internalizes experience via gradient updates but is constrained by the low capability ceiling of smaller models, and is hard to scale to large frontier LLMs. To bridge this gap, we propose Skill-MAS, a novel third path that decouples experience retention from parametric updates by conceptualizing the high-level orchestration capability as an evolvable Meta-Skill. Skill-MAS refines this architectural knowledge through a closed optimization loop: (1) Multi-Trajectory Rollout samples a behavioral distribution for each task under the current Meta-Skill; and (2) Selective Reflection adaptively selects priority tasks and applies hierarchical contrastive analysis to distill systemic experience into generalizable, strategy-level principles. Extensive experiments across four complex benchmarks and four distinct LLMs demonstrate that Skill-MAS not only achieves remarkable performance gains but also maintains a favorable cost-performance trade-off. Further analysis reveals that the evolved Meta-Skills are highly robust and exhibit strong transferability across unseen tasks and different LLMs.

07.
arXiv (CS.AI) 2026-06-15

From Chatbot to Digital Colleague: The Paradigm Shift Toward Persistent Autonomous AI

arXiv:2606.14502v1 Announce Type: new Abstract: Large Language Models (LLMs) are undergoing a fundamental transformation from conversational generators into integrated AI systems capable of reasoning, action, memory, and self-improvement. We conceptualize this transition as a shift from Chatbot to Digital Colleague: from conversational answers to persistent work. We organize this transition along two tightly coupled dimensions. First, at the cognitive core level, LLMs are advancing from Chatbot-era "fast thinking" systems driven by next-token prediction toward Thinking LLMs that leverage inference-time computation, Chain-of-Thought reasoning, reflection, process supervision, and reinforcement learning to support more deliberate and reliable cognition. Second, at the tool-augmented task execution level, LLMs are progressing from tool-calling Agents that invoke external resources in an ad hoc manner toward OpenClaw-style workstation systems (OpenClaw) equipped with persistent Workspaces, skills, verification loops, and governance. The "Workspace + Skill" paradigm makes episodic tool use colleague-like via state persistence, reusable procedures, task closure, and experience reuse. We examine data construction shifts from instruction-response pairs to State-Action-Observation trajectories and evaluation from static benchmarks to sandboxed, auditable, self-evolving AI ecosystems.

08.
arXiv (math.PR) 2026-06-16

A 0-1 Law for Multifractal Spectra via the HGDS Scale Derivative

arXiv:2606.15850v1 Announce Type: new Abstract: We prove that the multifractal spectrum D(h,omega) of a stochastic process is almost surely deterministic under a scale decorrelation condition on the HGDS scale derivative. The key difficulty is that the pointwise Hölder exponent lives in the germ sigma-algebra, where classical 0-1 laws do not reach. We get around this by working with the geometry accumulation integral G_Lambda, which is a genuine Lebesgue integral over scales and concentrates almost surely. The boundary case – log-correlated fields – is sharp: the variance summability condition fails exactly there.

09.
arXiv (CS.CV) 2026-06-11

MedCTA: A Benchmark for Clinical Tool Agents

To make clinically grounded decisions, medical AI agents are expected to go beyond simple recognition and be capable of tool retrieval, evidence acquisition, and integration. Existing benchmarks largely evaluate isolated perception or single-turn question answering, and therefore provide limited visibility into failures of planning, tool recruitment, and rollout reliability. We introduce MedCTA, a benchmark for evaluating medical tool agents on clinician-validated, step-implicit tasks grounded in realistic multimodal clinical inputs, including radiology images, pathology slides, and reports. MedCTA comprises 107 real-world clinical tasks with clinician-verified executable trajectories over 5 deployed tools, and supports process-aware evaluation of tool selection, argument validity, execution stability, trajectory fidelity, and outcome quality. We benchmark 18 open- and closed-source multimodal models and find that even frontier systems remain brittle in multi-step clinical tool use: autonomous rollouts are dominated by protocol failures, premature stopping, and incorrect tool recruitment, while gold-standard tool routing yields large but still incomplete gains. These results show that strong backbone perception does not translate into reliable agentic behavior in clinical settings. MedCTA provides a rigorous testbed for auditing, diagnosing, and advancing trustworthy medical AI agents. The dataset and evaluation suite are available at https://ivul-kaust.github.io/MedCTA/

10.
Science (Express) 2026-05-21

Observation of quantum vortex core fractionalization and skyrmion formation in a superconductor | Science

Authors: Unknown Author

Magnetic fields can penetrate a superconductor in the form of quantum vortices, which consist of a core singularity with circulating currents. London’s quantization implies that there is one core singularity per quantum of magnetic flux in single-component superconductors. Here, we report signatures of quantum vortex core fractionalization on the potassium-terminated surface of a multiband superconductor KFe 2 As 2 . The observed splitting of single integer-flux vortices into several fractional vortices results in a disparity between the numbers of flux quanta and vortex cores. These fractional vortices often arrange in chains, which calculations show are characterized by a ℂP 2 skyrmionic topological invariant; this constitutes a different type of topological defect: the chiral skyrmion. The disparate natures of integer and fractional vortices comprising skyrmions lead to distinct spectroscopic signatures.

11.
medRxiv (Medicine) 2026-06-24

Uncovering the fitness of endemically circulating Zika virus strains

Zika virus (ZIKV) is an arbovirus that usually causes few symptoms and has circulated endemically in Asia for decades. However, a large outbreak in South America in 2015 uncovered the serious risk of congenital Zika syndrome in infants born from ZIKV infected mothers. It is unknown whether a lineage with distinct pre-existing fitness advantage emerged from Asia to cause the South American outbreak, and whether there is ongoing evolution that can result in future globally fit strains. Here we used 107 sequences from a single setting (Thailand) collected over an 18 year period (2006-2023). We used novel analytical tools to identify distinct lineages that have circulated in the population and estimated their relative epidemiological fitness. We found there have been six lineages circulating sequentially in the country, with regular emergence and replacement of lineages showing higher fitness than their predecessors. We identified 15 lineage-defining amino acid changes, including four well-documented fitness-enhancing mutations, and two UTR substitutions. The lineage that emerged in South America was evolutionarily linked to the highest-fitness lineage in Thailand, carrying seven of our lineage-defining substitutions acquired during endemic circulation there, and subsequently accumulating four additional changes. After the global pandemic, endemic ZIKV in Thailand continued to evolve, with newly emerged lineages showing novel mutations and increased fitness. Our findings have key implications for the monitoring of ZIKV and can help identify the pathway to increased transmissibility of this globally important pathogen.

12.
medRxiv (Medicine) 2026-06-24

Generative AI avatar videos for tobacco prevention on social media: a randomized controlled trial

Short-form video platforms increasingly shape how young audiences encounter health information. Generative artificial intelligence can produce standardized avatar-based messages at scale, but randomized evidence for tobacco prevention is scarce. In this three-arm randomized online intervention study with pre-post assessment, participants aged 16 years or older were assigned to an AI avatar video emphasizing short-term smoking consequences, an AI avatar video presenting long-term cancer-related information matched to an American Cancer Society fact sheet, or the same fact sheet in written form. The primary outcome was post-intervention intention to avoid smoking and secondhand smoke exposure, adjusted for baseline intention. Among 400 randomized participants, 272 had complete data for the primary baseline-adjusted analysis. Intention increased from baseline to post-intervention in all conditions, with no statistically significant between-group differences. These findings support AI avatar videos as a scalable, social-media-compatible format for digital tobacco prevention, while not establishing superiority or equivalence.

13.
arXiv (quant-ph) 2026-06-25

Closed Quantum Boltzmann Bridges: Coherent Revivals, Hidden Microstates, and the Emergence of Classical Two-Time Entropy Conditioning

arXiv:2606.25260v1 Announce Type: new Abstract: The classical Boltzmann Bridge describes entropy histories conditioned on both an initial low-entropy macrostate and a later macrostate. Unlike the usual past-only formulation of the thermodynamic arrow, this two-time conditioning can produce entropy profiles that rise above the final entropy and then decrease toward the imposed endpoint. In this work, we formulate closed quantum analogues of the Boltzmann Bridge using macro-subspace projectors, unitary time evolution, and Boltzmann entropy defined by the dimension of coarse-grained macroscopic sectors. We first study a minimal coherent chamber-qubit model, in which each particle has only a two-state chamber degree of freedom. Although this model is the most direct quantization of the classical two-box system, its bridge entropy profile is dominated by coherent oscillations and revivals rather than classical relaxation. We then introduce a hidden-microstate bridge, in which each chamber sector contains unresolved internal degrees of freedom while the full dynamics remain unitary. Numerical experiments show that increasing the internal Hilbert-space dimension suppresses sample-dependent revival behavior and produces bridge entropy profiles whose sign structure and coarse-grained shape increasingly agree with the classical Boltzmann Bridge. We further use a Random Forest classifier to explore the parameter regime separating revival-dominated quantum behavior from classical-like coarse-grained bridge behavior. These results suggest that classical two-time-conditioned entropy behavior is not recovered by quantizing the chamber variable alone, but can emerge statistically from closed quantum.

14.
medRxiv (Medicine) 2026-06-18

Automated Airways Characterization and Assessment of Cystic Fibrosis from CT Imaging

Background Advancements in medical imaging have enabled non-invasive diagnosis and staging of cystic fibrosis (CF) using CT scans, revealing dilated airways, an increased number of visible airways, and airway generation splits in these patients. However, manual characterization of airways remains time-consuming and challenging due to the numerous structural changes, thereby limiting clinical feasibility. This study aims to develop an automated algorithm to characterize airways from segmented lung CT scans and apply this to a retrospective population. This approach reduces the time required to analyze images and obtain disease-staging results. Methods This framework consists of two stages. The first stage extracts and skeletonizes the airway tree from lung CTs, while the second stage measures lung features, including airway volumes, branch counts, generation splits, diameters, and cross-sectional areas. This permits comprehensive characterization for use in clinical assessment. Results The airways analysis was performed on 169 CT volumes ranging in age from 6 to 18 years of age, revealing substantial differences in detected airway branches, generation splits, and normalized airway volume between the control and CF groups. The framework also measures airway diameters and cross-sectional areas, revealing an increase in the number of small airways in cystic fibrosis patients, due to early bronchiectasis. These findings align with previous research and demonstrate the framework's ability to accurately quantify airway changes in patients with CF. Discussion The framework extracts entire airway trees, facilitating measurements of volume, branch count, diameters, and cross-sectional areas, which change with CF severity and/or treatment. However, partial lung atelectasis can limit the accuracy of airway detection in moderate-to-severe cases. Funding NIA U54 AG054345 and NIA R21 AG07857501

15.
arXiv (CS.AI) 2026-06-24

Efficient Test-time Inference for Generative Planning Models with OCL Search

arXiv:2606.00618v2 Announce Type: replace Abstract: Generative models have emerged as a powerful paradigm for AI planning, yet their performance remains constrained by the training data distribution. One approach is to improve generated solutions during inference by scaling test-time compute. A more efficient alternative is to optimize the inference process itself. In this paper, we show that a modified version of a classical Open-Closed List (OCL) search provides just such an efficient inference procedure. Our algorithm synergizes two learned components: a generative model that performs fast rollouts from intermediate states and a heuristic model that prioritizes among candidate reasoning paths. Key contributions include novel exploration control mechanisms and integration of learned models within the OCL framework. Across multiple combinatorial planning domains, our approach outperforms both neurosymbolic search baselines and classical solvers in computational efficiency and solution quality.

16.
arXiv (CS.CL) 2026-06-16

DoubtProbe: Black-Box Jailbreak Defense via Structural Verification and Semantic Auditing

As large language models (LLMs) are increasingly deployed in user-facing systems, black-box jailbreak defense has become an important practical problem. Existing defenses often rely on known-attack coverage, prompt-level semantic judgment, or local runtime control, yet these paths can become unstable under evolving prompt packaging, expression rewriting, and structure manipulation. We observe that many black-box jailbreaks do not remove the harmful goal, but reorganize the information needed to express and execute it, thereby evading safety alignment while remaining recoverable during generation. Motivated by this observation, we propose DoubtProbe, a dual-branch inference-time defense framework that combines structural verification with semantic auditing and formulates black-box jailbreak defense as consistency checking under controlled transformation. The structural branch extracts a structured representation from the original request, reconstructs the request under representation constraints, and detects information-preservation failures between the original and reconstructed requests; the semantic branch audits the original prompt directly. We evaluate DoubtProbe against representative black-box defenses on jailbreak and benign-request benchmarks, and further test backbone transfer from Qwen2.5-72B to Llama-3.1-70B. Results show that DoubtProbe achieves a stronger and more stable defense-utility trade-off: on Qwen2.5-72B, it reduces the JBB attack success rate from 0.293 to 0.100 and the CodeAttack attack success rate from 0.152 to 0.001, while maintaining false positive rates of 0.022 and 0.016 on AlpacaEval and OR-Bench; the same pattern remains stable on Llama-3.1-70B. These findings show that structural inconsistency signals provide a practical and generalizable basis for black-box jailbreak defense, especially when combined with semantic auditing.

17.
medRxiv (Medicine) 2026-06-24

In-vivo glioma viscosity and fluidity as clinical tumor markers of vimentin expression and collective cell migration

Reduced fluidity and viscosity have been demonstrated as biomechanical hallmarks of in vivo glioblastoma and are increasingly used as radiological imaging markers by magnetic resonance elastography (MRE). However, the biological origin and consequences of this unusual mechanical behavior remain unclear. Here, we show that two mechanisms which promote collective cell migration are present in patient gliomas and can be detected in vivo by MRE-based cerebral tomoelastography. Vimentin-driven extracellular matrix remodeling and cellular elongation, quantified by automated histological readings and nuclear aspect ratio (AR) measurements, correlate with decreased in-vivo tumor fluidity and viscosity. These observations in patients are supported by experiments in tissue-mimicking actin-vimentin gels, which mechanistically link the soft-solid viscoelastic signature of in vivo glioma to vimentin's migration-promoting role and to AR-based observations of cellular elongation in unjammed cancer cell clusters. Taken together, our results suggest in-vivo bulk tumor viscosity as a noninvasive biomechanical marker of collective cell migration and invasiveness in brain tumors.

18.
arXiv (CS.CL) 2026-06-19

DeFrame: Debiasing Large Language Models Against Framing Effects

As large language models (LLMs) are increasingly deployed in real-world applications, ensuring their fair responses across demographics has become crucial. Despite many efforts, an ongoing challenge is hidden bias: LLMs appear fair under standard evaluations, but can produce biased responses outside those evaluation settings. In this paper, we identify framing – differences in how semantically equivalent prompts are expressed (e.g., "A is better than B" vs. "B is worse than A") – as an underexplored contributor to this gap. We first introduce the concept of "framing disparity" to quantify the impact of framing on fairness evaluation. By augmenting fairness evaluation benchmarks with alternative framings, we find that (1) fairness scores vary significantly with framing and (2) existing debiasing methods improve overall (i.e., frame-averaged) fairness, but often fail to reduce framing-induced disparities. To address this, we propose a framing-aware debiasing method that encourages LLMs to be more consistent across framings. Experiments demonstrate that our approach reduces overall bias and improves robustness against framing disparities, enabling LLMs to produce fairer and more consistent responses.

19.
medRxiv (Medicine) 2026-06-22

Building accessible resources to empower communities: the case of the Lupus Mexican Registry

Motivation: Although SLE data in Latin America is increasing, clinical datasets remain difficult to access and interpret, highlighting the need for accessible tools that support data-driven precision medicine, citizen science, and public health initiatives. Results: We developed a user-friendly platform that enables us to explore LupusRGMX data through interactive queries, report generation, statistical modeling, and comprehensive insights. This resource supports community-oriented research, improves the visibility of underrepresented populations in lupus research, and provides a useful tool to enhance data accessibility. Availability and implementation: Developed in R using Shiny and bslib for interactive visualization and interface design. Available at https://github.com/NeuroGenomicsMX/Lupus_App_2.0 and https://lupusrgmx.liigh.unam.mx/shiny/lupus/

20.
arXiv (CS.LG) 2026-06-25

Solving Markov Decision Processes with Future Information via MPC

arXiv:2606.24991v1 Announce Type: cross Abstract: Model Predictive Control (MPC) is widely used in industrial and robotic systems for enforcing constraints and embedding domain knowledge through finite-horizon optimization-based planning. However, despite these strengths, an MPC scheme typically does not yield optimal policies for sequential decision-making problems formulated as Markov Decision Processes (MDPs). Recent combinations of MPC with Reinforcement Learning (RL) alleviate this issue by treating MPC as a parameterized model of the optimal policy of an MDP and adjusting its parameters using data. While these approaches typically consider classical MDPs, many real-world problems include future information–such as forecasts, prices, or reference trajectories–at decision time, which must be included in the MDP state for optimal decision-making. Current MPC-RL approaches do not directly account for this augmented-state structure, raising the question of how to incorporate future information into MPC to obtain an optimal policy. This work establishes the structural requirements under which a parameterized MPC can exactly represent the optimal value functions and policy of an MDP with future information. We further demonstrate that such a parameterized MPC can serve as a structured function approximator, with its parameters learned using RL. The approach is illustrated on a point-mass racing task with future reference information.

21.
Nature (Science) 2026-06-24

Zero-shot design of drug-binding proteins via neural iterative selection−expansion

Authors:

The design of proteins that bind to small molecules has been challenging because it requires simultaneous optimization of the protein sequence, protein structure and ligand conformation1–7. Current deep-learning algorithms have struggled to navigate this landscape, precluding the zero-shot design of binders. Here we show that by combining two neural networks in an iterative design algorithm, small-molecule binding proteins can be created from scratch with high accuracy. We trained a graph neural network—ligand-aware sequence engineering message-passing neural network (LASErMPNN)—to design compatible protein sequences for an input protein backbone and docked ligand. We paired  LASErMPNN with a structure predictor that models a three-dimensional protein–ligand complex for an input protein sequence and ligand identity. The closed-loop iteration of these reciprocal networks optimized sequence–structure–ligand compatibility, and outperformed a comparable design loop using a physics-based energy function. We used our strategy, termed neural iterative selection–expansion (NISE), to design proteins that, using different folds, specifically bind to two chemically distinct small-molecule drugs, exatecan and apixaban, with success rates of 100% and 83%, respectively. The tightest NISE binders had nanomolar-to-picomolar affinities, surpassing those of the next-leading method by 70-fold for exatecan and nearly 10,000-fold for apixaban. LASErMPNN then suggested two amino-acid substitutions that improved the affinity of the tightest exatecan binder by 100-fold without any experimental input. The optimized binder protected the labile lactone ring of exatecan from hydrolysis for days. Our work describes a general recipe for using neural networks to automate the design of small-molecule binding proteins for applications in drug delivery, sensing and catalysis.  By pairing two neural networks in an iterative optimization algorithm, small-molecule binding proteins can be designed from scratch with high accuracy, affinity and success rates, showing promise for applications in drug delivery and sequestration.

22.
arXiv (CS.CV) 2026-06-12

CD-RCM: Generalizable Continuous-Depth Novel View Synthesis for Reflectance Confocal Microscopy

Reflectance confocal microscopy (RCM) provides noninvasive, cellular-resolution "optical biopsies" of human skin in vivo by acquiring en-face images at successive depths, forming a sparse z-stack. Due to optical limitations, these stacks are anisotropic 3D volumes with lateral resolution (0.5 $\mu$m) $\sim$6 times higher compared to axial resolution, which is defined by the optical sectioning (3 $\mu$m), limiting the interpretation of tissue. Our goal is to provide continuous-depth visualization by interpolating intermediate sections and making the 3D volume isotropic. Such a representation permits arbitrary-direction sectioning, including histopathology-like cross-sectional examination, without requiring per-patient optimization. To that end, we introduce the first RCM-specific novel-view synthesis (NVS) approach, CD-RCM, a feedforward model that predicts realistic, unseen depths from sparsely sampled RCM stacks. Classical neural rendering methods focus on reconstruction from surface-level multi-view observations. In contrast to surface-level camera views, RCM can acquire optically sectioned en-face images of tissue beyond the surface up to 200 $\mu$m. However, during visualization of the RCM stacks, observations of the shallower sections (towards the surface) obscure the deeper ones. This unique axial imaging geometry and layer-dependent anatomical organization motivated our development of a tailored architectural and training framework that explicitly accounts for RCM's depth-resolved, occlusive imaging physics. Experiments demonstrate that CD-RCM achieves high-fidelity novel-view synthesis with sub-second inference time.

23.
arXiv (CS.AI) 2026-06-17

Visored: A Controlled-Natural-Language Prover for LLM-Generated Mathematics

arXiv:2606.17581v1 Announce Type: cross Abstract: We present a dependent-type-based prover designed around the way LLMs (and humans) tend to write mathematics, complementing existing systems such as Lean and Rocq. Its core design choices are a surface that imitates mathematical natural language and a rule-driven automation layer that closes the routine steps a textbook would omit, so that an accepted proof can be re-emitted as a checked Lean file. Early experiments suggest that, even without any prover-specific training data, LLMs can learn to use it effectively on the miniF2F benchmark. Lean output excerpts: https://github.com/xiyuzhai-husky-lang/visored/

24.
arXiv (CS.LG) 2026-06-11

NARRAS: Edge-Triggered Distributed Inference for CSI-Based Localization in Vehicular IoT Networks

arXiv:2606.11914v1 Announce Type: cross Abstract: CSI-based localization with spatially distributed antenna arrays exposes a basic resource trade-off. Each array can provide a rich view of the channel, but forwarding observations from all arrays to a fusion center is wasteful when only a few carry useful information, and the shared uplink supports only a limited number of simultaneous transmissions. We let each array decide locally whether its current observation is worth reporting, subject to a budget on the average number of active transmitters. We refer to this abstraction as Edge-Triggered Distributed Inference (ETDI). It captures a broader class of task-oriented communication problems where resource-constrained devices share an access channel for a common inference task. We instantiate ETDI for CSI-based localization, a common scenario in vehicular IoT networks. Spatially distributed remote antenna arrays (RAAs) encode local channel state information (CSI) from user equipment (UE) transmissions into latent features, and the fusion center estimates the UE position from the subset of reported features. We propose NARRAS, a decentralized reporting policy in which each RAA combines a recurrent summary of its recent observations with a memory of the last latent it transmitted. Training controls an explicit activity budget through differentiable activity penalties and validation-calibrated deterministic thresholds, and uses channel-chart regularization to shape the latent geometry. Experiments show that, at comparable uplink activity, NARRAS improves localization accuracy over learned and heuristic sparse-reporting strategies, while dense full-report models remain useful budget-free references. In low-activity regimes, chart regularization further reduces high-percentile localization errors, suggesting that geometry-aware latent representations are more robust under sparse reporting.

25.
arXiv (CS.AI) 2026-06-11

Rule Taxonomy and Evolution in AI IDEs: A Mining and Survey Study

arXiv:2606.12231v1 Announce Type: cross Abstract: The adoption of AI-powered Integrated Development Environments (AI IDEs) has introduced "Rules" as a novel software artifact, allowing developers to persistently inject project-specific constraints and architectural guidelines into the context of Large Language Models (LLMs). Despite their role in aligning AI behavior with developer intent, the taxonomy, evolution, and practical impact of these rules remain largely unexplored. To bridge this gap, we conducted a mixed-methods empirical study on AI IDE rules. By mining 83 open-source projects and extracting 7,310 rules, we established a comprehensive taxonomy comprising 5 primary and 25 secondary categories. We then triangulated these artifacts with survey responses from 99 practitioners. Our analysis identified a contrast between developer priorities and actual configurations: while practitioners rate architectural constraints as highly important, rule files in repositories primarily consist of low-level workflow and code formatting constraints. Furthermore, our analysis of 1,540 rule evolution events revealed that rules are updated frequently. Repository data further indicate that rule evolution is primarily driven by constructive context expansions (29.17%) and enrichments (26.59%). In contrast, surveyed developers reported modifying rules primarily to correct AI errors (77.78%), typically by adding new negative constraints rather than editing existing ones. Finally, an artifact compliance assessment of 160 rule evolution events revealed that updating rules significantly improves the adherence of software artifacts, with the average artifact compliance rate increasing by 22.99% (from 49.14% to 72.13%) following an update. Our study provides empirical insights that can help developers optimize prompting strategies and guide tool builders in designing automated conflict-detection and context-management mechanisms for AI IDEs.