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01.
arXiv (CS.CV) 2026-06-17

Contrastive Action-Image Pre-training for Visuomotor Control

Existing vision encoders for robotics face a fundamental bottleneck: robotic datasets lack the scale necessary for large-scale pre-training. Prior work circumvents this data scarcity by turning to internet-scale image and language data or egocentric human video. While these models show promise, neither paradigm learns from paired vision and action data, which downstream visuomotor control policies require. However, robot trajectories, the most direct source of this paired signal, are not available at pre-training scale, motivating us to extract action signals from abundant human video instead. To this end, we introduce CAIP (Contrastive Action-Image Pre-training), a vision encoder that treats human hand poses from large-scale egocentric video as a proxy for end-effector actions. By extracting 3D hand keypoints, a representation that aligns naturally with downstream robot action spaces, CAIP learns a unified action-image representation through a contrastive objective. Leveraging 32,041 hours of egocentric human video and only 88 hours of robotic manipulation data, CAIP outperforms state-of-the-art vision encoders including DINOv2, SigLIP, MVP, and R3M. Evaluated on a challenging real-world dexterous manipulation setup using Dexmate Vega and Sharpa Wave hands, CAIP yields performance gains of more than 30% on tasks involving folding, pouring, and fine-grained manipulation. Our results show that our method of contrastive action-centric pre-training yields a scalable path to achieving robust visual representations better suited for physical interaction.

02.
medRxiv (Medicine) 2026-06-18

Multicluster measles outbreak with a substantial proportion of modified cases in Tokyo, Japan, January-May 2026

Tokyo experienced a measles outbreak (260 cases) in early 2026 despite elimination status. Adults aged 20-39 years were most affected, and 38% of cases were modified measles, increasing with prior vaccination. Although incidence rose until April, the effective reproduction number; R(t) fell below 1, consistent with outbreak control. Multiple clusters were identified, but many cases lacked epidemiological links, suggesting that modified measles is less likely to be considered in differential diagnosis. Intensive contact tracing and surveillance contributed to limiting transmission.

03.
bioRxiv (Bioinfo) 2026-06-11

Sequence-Based Therapeutic Peptide Classification with Augmented Negative Sampling

Therapeutic peptides offer high target specificity, low toxicity, and the ability to modulate protein-protein interactions, yet experimental functional characterization remains costly and slow. Computational prediction of therapeutic function directly from sequence could accelerate peptide screening and enable generative design pipelines, but requires reliable discrimination between therapeutic and non-therapeutic peptides. Existing multi-label predictors cover few functions, rely on limited datasets, and exhibit high glspl{fpr}, limiting their practical utility. We present a lightweight CNN classifier trained on the most comprehensive therapeutic peptide database to date (54,655 peptides, 48 functional categories). A key contribution is a statistically motivated negative sampling strategy using Markov models to generate diverse synthetic decoys at multiple difficulty levels. When evaluated on this controlled decoy benchmark, the FRP is reduced from over 60% for previous models to 2.1% for our approach. Our fine-tuned five-model ensemble achieves 78.9% Micro F1 and 54.6% Macro F1 while requiring only amino acid sequences as inputs. Analysis using a sparse L1-constrained variant of our model shows that convolutional filters capture conserved functional motifs and statistically improbable non-therapeutic patterns, with downstream layers combining these signals, providing mechanistic evidence that the network learns biologically meaningful structure. In a generalization task on the TPpred-LE benchmark, our model achieves 55.3% Micro F1 and 38.6% Macro F1, comparable to TPpred-LE trained on its native dataset (57.9%/38.1%) while predicting four times more therapeutic functions with four times fewer parameters. Code and models will be made available at https://github.com/terra-quantum-public/tq-therapep-ai.

04.
arXiv (math.PR) 2026-06-17

Full $\Gamma-$expansion for the level-two large deviation rate functionals of non-reversible one-dimensional diffusions with periodic boundary conditions

arXiv:2606.17859v1 Announce Type: new Abstract: Consider the diffusion process \begin{equation*} dX_{\epsilon}(t) = \mss b(X_{\epsilon}(t)) \, dt + \sqrt{2\, \epsilon\, \mss a(X_\epsilon(t))} \, dW_{t}, \end{equation*} on the one-dimensional torus $\bb T = [0,1)$. Here $\epsilon$ is the temperature, $W_{t}$ a Brownian motion on $\bb T$ and $\mss a$, $\mss b$ functions of class $C^{2}(\bb T)$ satisfying further conditions. Denote by $\mss P(\bb T)$ the set of probability measures on $\bb T$ equipped with the weak topology, and by $\ms I_{\epsilon}\colon \mss P(\bb T)\to [0,+\infty)$ the level two large deviation rate functional of the diffusion $X_{\epsilon}(\cdot)$. We derive a full $\Gamma-$expansion of $\ms I_{\epsilon}$, as $\epsilon \to 0$, expressing it as \begin{equation*} \ms I_{\epsilon} = \frac{1}{\epsilon} \;\ms J^{(-1)} \; +\; \ms J^{(0)} \;+\; \sum_{p=1}^{\widehat{\mf q}}\frac{1}{\theta^{(p)}_{\epsilon}}\;\ms J^{(p)}\,, \end{equation*} where $\ms J^{(-1)}$, $\ms J^{(0)}$, $\ms J^{(p)} \colon \mss P(\bb T)\to [0,+\infty]$ represent rate functionals, independent of $\epsilon$, and $\theta^{(p)}_{\epsilon}$ are the time-scales at which the Markov process $X_{\epsilon}(\cdot)$ exhibits a metastable behaviour.

05.
medRxiv (Medicine) 2026-06-15

Dysplasia-Stratified Management of Barrett's Esophagus: An Incidence-Based U.S. Cost-Effectiveness Analysis

Authors:

Background and Aims Barrett's esophagus (BE) is the principal precursor of esophageal adenocarcinoma (EAC), whose incidence has risen sharply in Western countries since the 1960s. Effective, dysplasia stratified surveillance strategies are needed to prevent progression. This study evaluated the cost effectiveness of dysplasia stratified surveillance intervals and endoscopic eradication therapy (EET) across the BE spectrum. Methods We developed an incidence-based Markov state transition model of BE progression calibrated to U.S. epidemiologic data from a healthcare sector perspective over a lifetime horizon. Four hypothetical cohorts of 50-year-old individuals with short segment BE (SSBE), nondysplastic BE (NDBE), low grade dysplasia (LGD), or high-grade dysplasia (HGD) were evaluated. Strategies included no surveillance; surveillance at 1-, 2-, 3-, 4-, 5-, or 10-year intervals; standard or AI assisted endoscopy; non endoscopic screening (sponge, breath, miRNA tests); and EET for LGD and HGD. Outcomes included costs, quality adjusted life years (QALYs), incremental cost effectiveness ratios (ICERs), net monetary benefits (NMBs), EAC cases, and EAC-related deaths. Sensitivity analyses used a willingness to pay threshold of US$100,000 per QALY. Results No surveillance was the most cost-effective strategy for SSBE and NDBE. For LGD, upfront EET was more cost effective than all surveillance strategies, with results sensitive to EAC incidence and recurrence. For HGD, EET was cost saving and yielded the greatest QALYs, with findings robust in 99.9% of simulations. EET prevented 12,614 and 44,295 EAC related deaths per 100,000 individuals with LGD and HGD, respectively. Conclusion Dysplasia-stratified management is essential for optimizing surveillance and treatment strategies in BE. Any degree of dysplasia should receive EET followed by targeted post-treatment monitoring, establishing EET as the central therapeutic pathway for dysplastic BE.

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

OpenClaw-Skill: Collective Skill Tree Search for Agentic Large Language Models

Equipping Large Language Model (LLM) agents with effective skills is crucial for solving complex tasks in real-world systems like OpenClaw. In this work, we aim to develop a framework that automatically constructs such reusable skills to enhance LLMs in tool use, multi-step reasoning, and dynamic environment interaction. To this end, we propose Collective Skill Tree Search (CSTS), a novel tree-search-based skill construction framework that constructs structured, diverse and generalizable tree of skills. The core idea of CSTS is to leverage collective intelligence to jointly search, identify and compose effective skills via two iterative phases: Collective Skill Node Generation (CSN-Gen) and Collective Skill Node Assessment (CSN-Assess). CSN-Gen exploits collective knowledge from multiple models to explore diverse candidate skills for each subtask, enabling comprehensive skill exploration. CSN-Assess employs multiple models as judges to evaluate and select skill nodes with two scoring mechanisms: (1) collective quality scoring that aggregates independent evaluations to produce a robust estimate of skill effectiveness, and (2) collective transferability scoring that explicitly verifies whether a skill generalizes well across different models. With CSTS, we construct a set of comprehensive tree of skills along with skill-augmented training data, enabling models to effectively learn and utilize skills. Besides, we introduce Collective Skill Reinforcement Learning, which actively selects multiple relevant skills from the tree to broaden solution-space exploration, avoid being trapped by a single skill and its resulting homogeneous or suboptimal solutions. As a result, our trained model, OpenClaw-Skill, exhibits outstanding agentic capabilities in long-horizon planning, tool use and generalization over challenging benchmarks.

07.
Nature (Science) 2026-06-10

The Amazon can be saved — with concerted action inside and outside Brazil

Authors: Unknown Author

As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down. As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down.

08.
arXiv (CS.CV) 2026-06-19

CUPID: Reconstructing UV Texture Maps for Interpretable Person-of-Interest Deepfake Detection

Deepfakes targeting a high-profile individual, known as Person-of-Interest (POI), are a threat to modern democracies and societies. Current POI deepfake detection methods still struggle to combine robustness to post-processing, efficiency and interpretability, focal aspects of modern deepfake detectors. In this paper we propose CUPID, a POI video deepfake detector that combines UV texture maps, a facial appearance representation derived from 3D face reconstructions, with the representation learning capabilities of the Masked Autoencoder (MAE). Our method does not require any deepfake videos in its training phase. Moreover, it does not even require to include a specific POI in the training set: the combination of UV texture maps extracted from real video frames and the MAE context-guided reconstruction yields a latent space that captures rich and discriminative facial features also for identities unseen during training. In the testing phase, the embeddings extracted from a query video depicting the POI can be matched against pristine reference videos to assess the video authenticity. Furthermore, operating in the UV space naturally provides an additional layer of interpretability. Specifically, we can extract decoded residual maps that highlight which facial regions of a test video deviate most from the identity representation of the corresponding POI. Experiments on four deepfake datasets show that CUPID outperforms current state of the art on most datasets and achieves the best overall robustness against strong downscaling and compression, providing also substantially faster inference. Our experimental code will be released at https://github.com/polimi-ispl/CUPID.

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

Workflow-GYM: Towards Long-Horizon Evaluation of Computer-use Agentic tasks in Real-World Professional Fields

arXiv:2606.11042v2 Announce Type: replace Abstract: Recent years have witnessed the rapid evolution of AI agents toward handling increasingly complex, real-world tasks. However, existing benchmarks rarely evaluate whether agents can operate graphical user interfaces to complete long-horizon, high-value professional workflows across diverse domains. Current GUI benchmarks still predominantly focus on general-purpose software, relatively simple applications, and short-horizon tasks, leaving it largely unknown whether modern agents can follow user instructions to autonomously operate domain-specific professional software and accomplish economically valuable work in an end-to-end manner. To bridge this gap, we introduce Workflow-GYM, a benchmark for long-horizon GUI tasks centered on professional domains and specialized software environments. Through extensive experiments on state-of-the-art models, we find that even the strongest models achieve only slightly above 30% success rates, highlighting that professional long-horizon GUI workflows remain highly challenging for current GUI agents. Further analysis reveals that current agents struggle to maintain long-horizon workflow consistency, frequently exhibiting workflow stage omission, error propagation, objective drift, and insufficient understanding of professional software environments. Our findings provide important insights into the limitations of current agent systems and suggest key directions for the next generation of GUI-agent research.

10.
arXiv (quant-ph) 2026-06-15

Tensor network manifolds and Riemannian fundamental theorem for tensor networks

arXiv:2606.14613v1 Announce Type: cross Abstract: Tensor networks provide a powerful framework for efficiently representing high-dimensional data and many-body quantum states. Endowing tensor networks with a Riemannian manifold structure provides a natural setting for numerical optimization and analysis. A central feature of tensor networks is their gauge freedom, whose characterisation (captured by so-called fundamental theorems) underlies both their intrinsic structure and the design of numerical algorithms. In this work, we study the interaction between the Riemannian manifold structure and the gauge freedom for several families of tensor networks. Using group actions and Riemannian submersions, we establish a Riemannian fundamental theorem for the tensor network families studied.

11.
Nature (Science) 2026-06-10

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis

Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle. In two human datasets, moderate-to-vigorous physical activity was associated with lower prevalence of non-DNMT3A-driven CH. In atherogenic mice with Jak2V617F or Tet2 loss of function (LOF), but not Trp53 LOF or Dnmt3aR878H CH, uninterrupted sleep or exercise curtails clone expansion. In CH with the Jak2V617F mutation, sleep and exercise reduces clone expansion by selectively reprogramming mutant, but not cohabitant wild type, haematopoietic progenitor cells towards antiproliferative and metabolically healthy phenotypes by tempering bone marrow macrophage–haematopoietic progenitor cell IL-1β signalling. Sleep or exercise also lessens Jak2V617F-driven, Tet2 LOF-driven and Trp53 LOF-driven, but not Dnmt3aR878H-driven, atherosclerosis by locally reprogramming mutant vascular macrophages, independent of peripheral clone dynamics. In Jak2V617F, but not adjacent wild type, aortic macrophages, uninterrupted sleep blunts CLEC4E-dependent inflammasome activation, consequently diminishing lesions. Exercise, meanwhile, activates PAC1+ neurons in the locus coeruleus, raising the levels of peripheral noradrenaline, which signals through adrenergic receptor β2 (ADRβ2) whose expression is preserved by exercise in Jak2V617F, but not cohabitant wild type, aortic macrophages, selectively repressing their inflammatory programming and atherosclerosis. Our findings establish that healthy lifestyles gene-specifically diminish CH and selectively reprogram mutant haematopoietic progenitor cells and macrophages to maintain cardiovascular health. Sleep and exercise can slow clonal haematopoiesis and limit mutant cell-driven atherosclerosis.

12.
arXiv (CS.AI) 2026-06-12

EWAM: An Enhanced World Action Model for Closed-Loop Online Adaptation in Embodied Intelligence

arXiv:2606.12690v1 Announce Type: cross Abstract: In this paper, we propose the Enhanced World Action Model (EWAM), a closed-loop online adaptation architecture built upon a pretrained and fully frozen Cosmos3 backbone network. Evaluated entirely under a zero-shot task protocol, EWAM is centrally focused on reducing the amount of additional deployment data required to adapt to new task layouts. Notably, no extra task-specific demonstration sets were introduced in any of the evaluations, and no fine-tuning was performed on the backbone network. Its performance gains stem entirely from an inference-time co-reasoning mechanism composed of four inserted lightweight neural layers: the Neural Experience Memory Layer located in the intermediate layers of the Diffusion Transformer (DiT) provides task-relevant execution context; the Neural Anomaly Detection Layer after the state prediction head monitors the divergence between predicted and actual states in real time; the Neural Policy Routing Layer dynamically selects direct execution, conservative replanning, or rollback recovery based on the anomaly severity; and the Neural Action Correction Layer refines the generated action chunks using execution diagnostics. Unlike naive feature fusion, the memory, anomaly detection, and correction modules are deeply integrated into the Cosmos3 forward path in a differentiable manner, with only the final routing decision being a discrete supervised one.

13.
arXiv (CS.AI) 2026-06-16

Intelligence Is Not the Bottleneck: Validating an LLM First-Pass Manuscript Score Against Peer-Review Outcomes

arXiv:2606.15887v1 Announce Type: cross Abstract: Large language model (LLM) systems are increasingly proposed to assist peer review, yet most evaluations judge the prose of machine-generated review text, not the validity of the numeric score a system assigns. We validate AIPR, which reads a submitted manuscript and emits five 0-100 quality dimensions and a weighted overall score, against the public decision outcomes of a major machine learning venue. AIPR grades by prompting alone, with no fine-tuning on reviews or decisions. Across 300 ICLR submissions with public decision tiers and reviewer ratings, graded under a frozen pipeline with hypotheses pre-registered before any score met any outcome, the overall score separates rejected from accepted submissions (AUROC 0.82, 95% CI 0.78-0.87), rises monotonically across tiers, and tracks the mean reviewer rating. The signal is strongest where we claim it: the lowest-scoring fifth is rejected far above the base rate, with oral papers absent. The validity comes mostly from the model: a one-paragraph prompt on the same model discriminates almost as well as the full pipeline (the small gap favours the pipeline but does not meet the pre-declared criterion, p = 0.09). What the engineering adds is reliability and a grounded review: AIPR's score barely moves across repeated runs (0.7 vs. 2.8 points within-paper SD) where the bare prompt swings, and the same pass returns a rubric-structured, evidence-grounded review rather than a bare number, with the human keeping the decision.

14.
Nature (Science) 2026-06-09

Good recycling starts at home — and benefits the world

Authors: Unknown Author

New research supports the value of household-level waste separation. But policies must also carefully consider consumer behaviours to maximize the quality of material collected. New research supports the value of household-level waste separation. But policies must also carefully consider consumer behaviours to maximize the quality of material collected.

15.
arXiv (quant-ph) 2026-06-17

Pulse-optimised circuit elements for scalable and noise-resilient quantum chemistry

arXiv:2606.17357v1 Announce Type: new Abstract: Useful chemistry calculations on near-term quantum processors are hindered by current algorithmic runtimes. We develop a methodology to significantly reduce these runtimes. Typically, variational quantum eigensolver (VQE) algorithms are implemented as sequences of primitive gates. Our methodology instead relies on gradient-ascent pulse engineering to construct hardware-tailored pulses for the direct implementation of VQEs. As problem sizes increase, it quickly becomes intractable to optimise a pulse that implements an entire VQE ansatz circuit. However, leading VQEs are constructed in a modular fashion. A problem-tailored VQE is assembled from parameterised circuit elements that simulate hopping between two or four electronic spin orbitals. We show that these circuit elements can be implemented more efficiently using hardware-tailored pulses. We numerically demonstrate our methodology on a silicon spin-qubit quantum processor. We find that common circuit elements, known as single- and double-qubit excitations, can be implemented in less than 289 ns and 927 ns, respectively. Compared with conventional gate-based implementations, our pulse-accelerated qubit excitations provide a scalable approach for faster and therefore more noise-robust quantum chemistry simulations by reducing VQE runtimes by up to a factor of 15.3.

16.
arXiv (CS.CL) 2026-06-11

Teaching Diffusion to Speculate Left-to-Right

Large language models (LLMs) achieve remarkable performance across a wide range of tasks, but their autoregressive decoding process incurs substantial inference costs due to inherently sequential token generation. Speculative decoding addresses this bottleneck by employing a lightweight draft model to propose multiple future tokens that are subsequently verified in parallel by a larger target model. Recent work has demonstrated that diffusion language models are well suited for this setting, as they can generate entire blocks of draft tokens in parallel and thereby alleviate the sequential constraints of autoregressive drafting. A subtlety of this regime is that block-diffusion drafters generate tokens bidirectionally within a block, whereas verification is performed by an autoregressive target model that evaluates tokens in a strictly left-to-right manner, leaving a gap between the symmetric training-time objective and the asymmetric verification-time reward. In this work, we offer an empirical analysis of three training-time interventions that narrow this gap: token positional weighting, a first-error focal loss that targets the position that breaks the accepted prefix within each block, and a chain loss term that substitutes a differentiable surrogate for the expected accepted length. The three interventions act along orthogonal axes (position, block-conditional first error, joint prefix) and compose additively; they are likewise orthogonal to test-time alignment mechanisms such as multi-draft self-selection, with which they can in principle be combined. Across four target models and six reasoning, code, and dialogue benchmarks, the three interventions raise accepted draft length by 21-76% per benchmark over a position-uniform baseline, without adding additional forward passes and without changing the inference pipeline or the rejection-sampling exactness contract.

17.
arXiv (CS.CL) 2026-06-16

Exploring Extrinsic and Intrinsic Properties for Effective Reasoning with Code Interpreter

Reasoning with a Code Interpreter (CI) has emerged as an effective paradigm for enhancing the reasoning capabilities of large language models (LLMs) through executable computation and iterative verification. Despite its growing adoption, the behavioral properties underlying effective code reasoning remain largely underexplored. In this work, we investigate code reasoning from two distinct perspectives inspired by prior studies of natural language reasoning: extrinsic properties, represented by crucial tokens, and intrinsic properties, represented by code-specific cognitive behaviors. Across multiple LLMs, we find that stronger CI reasoning models consistently exhibit a higher prevalence of crucial tokens and cognitive behaviors, particularly verification, backtracking, and backward chaining. Building on these observations, we examine how these properties can be leveraged during both inference and training. At inference time, appending code-specific crucial tokens improves performance on several reasoning capabilities, including mathematical, ordering, and optimization, while yielding limited benefits elsewhere. At training time, augmenting a state-of-the-art framework with code-specific cognitive behaviors improves supervised fine-tuning and reinforcement learning performance in two of three evaluated models. Further analysis shows that these behaviors reduce overthinking in incorrect responses and improve token efficiency, while also revealing factors that limit gains in a certain model. Our findings provide the first systematic characterization of effective reasoning with CI and demonstrate both the potential and limitations of leveraging key properties to improve CI-based reasoning.

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

Beyond Tokenization: Direct Timestep Embedding and Contrastive Alignment for Time-Series Question Answering

Recent advances in large language models (LLMs) have given rise to time-series question answering (TSQA), which formulates time-series analysis as natural-language question answering. However, directly feeding raw numerical series into LLMs suffers from a tokenization bottleneck: Byte Pair Encoding fragments continuous values into unstable tokens whose embeddings lack meaningful metric structure, resulting in the loss of magnitude, scale, and trend information. Prior methods use patch-based encoders that split the series into fixed windows, locking in one granularity that breaks patterns and hides exact timesteps, through a separate module that rarely transfers across datasets with different lengths or sampling rates. To address this challenge, we propose CADE (Contrastive Alignment with Direct Embedding), a novel framework for TSQA built upon two key components: direct timestep embedding and semantic alignment. The proposed framework maps each timestep directly into the LLM embedding space through a point-wise linear encoder and MLP projector, preserving exact index-level access while eliminating the need for patching and padding. To further bridge the semantic gap between time-series and language representations, we introduce a novel one-directional supervised contrastive loss that aligns time-series embeddings with frozen class-name text anchors. Experimental results on the public Time-MQA benchmark demonstrate that our framework consistently improves performance across six TSQA tasks, outperforming both open-source and proprietary LLM baselines.

19.
arXiv (CS.CV) 2026-06-11

TextHOI-3D: Text-to-3D Hand-Object Interaction via Discrete Multi-View Generation and Joint Mesh Optimization

Text-conditioned 3D generation has progressed rapidly for images and isolated objects, but producing a hand-object mesh remains challenging: the output must preserve language semantics, cross-view consistency, object geometry, articulated hand shape, and physically plausible contact. We present TextHOI-3D, a staged framework that uses generated multi-view observations as an explicit interface between text-conditioned visual generation and geometry-aware hand-object recovery. TextHOI-3D learns a compact VQ token space for fixed-camera hand-object observations, predicts multi-view visual tokens from text with a CLIP-conditioned visual autoregressive model, and recovers a unified hand-object mesh through prior initialization, multi-view joint optimization, and anti-penetration refinement. The design separates semantic generation from geometric recovery while keeping both stages connected by a discrete multi-view representation. On HO3D-derived evaluations, the multi-view setting reduces object CD from 17.26 mm to 4.92 mm and penetration volume from 5.3721 cm^3 to 0.2193 cm^3 compared with a single-view counterpart, while improving hand errors and surface F-scores. These results support multi-view visual tokens as an effective intermediate representation for text-driven 3D hand-object mesh creation.

20.
bioRxiv (Bioinfo) 2026-06-11

Combinatorial docking and molecular generation to navigate over 100-billion molecules for prospective ligand discovery

Commercially available make-on-demand libraries now exceed 100 billion compounds, requiring over 50 years to screen on 2,000 CPU cores using conventional docking. We present two complementary approaches to address this challenge. CombiDOCK, a combinatorial docking framework, enables exhaustive screening at the 100-billion scale within 40 days. MINT-Dock, a generative framework, accelerates navigation of this space by integrating CombiDOCK with Monte Carlo Tree Search. Benchmarked on 46 diverse targets, CombiDOCK matched full-molecule docking accuracy, and MINT-Dock achieved a 4,800-fold enrichment over random selection. Compared with prior billion-scale brute-force campaigns against {sigma}2, VMAT2, and VAChT, prospective CombiDOCK screens of the 100-billion-molecule library yielded higher hit rates and more potent ligands, while MINT-Dock achieved comparable outcomes across single- and multi-target objectives with >20-fold computational cost reductions. Docking-predicted poses of the best VAChT-binding compounds were confirmed by cryo-EM structures. These methods provide exhaustive and generative paths for navigating the trillion-molecule frontier of drug discovery.

21.
arXiv (CS.CL) 2026-06-12

Observable Patterns Are Not Explanations: A Causal-Geometric Analysis of Latent Reasoning Models

Latent reasoning models (LRMs) replace explicit chain-of-thought with continuous thoughts. Recent work treats observable latent-state patterns, such as BFS-like frontiers and decodable arithmetic computation, as evidence for internal reasoning mechanisms. Evaluating two LRMs (Coconut and CODI) against controls lacking the proposed recurrence or curriculum, we find these patterns also appear in the controls and do not always causally affect behavior. Causal interventions reveal that latent-thought utilization is not binary but graded, scaling with a thought's causal effect on model behavior. Geometric analyses reveal this effect concentrates in low-rank directions whose step-to-step geometry grows more structured as their behavioral influence increases. Latent thoughts should therefore be treated as hidden computation, not hidden explanation: decodability, attention, or static structure alone cannot establish mechanism. LRM interpretability thus requires matched controls and causal tests.

22.
arXiv (CS.AI) 2026-06-19

One Probe Won't Catch Them All: Towards Targeted Deception Detection

arXiv:2602.01425v2 Announce Type: replace Abstract: Linear probes are a promising approach for monitoring AI systems for deceptive behaviour. Previous work has shown that a linear classifier trained on a contrastive instruction pair and a simple dataset can achieve good performance. However, these probes exhibit notable failures even in straightforward scenarios, including spurious correlations and false positives on non-deceptive responses. In this paper, we demonstrate that deception detection is inherently heterogeneous: while a single universal probe achieves modest improvements (+0.032 AUC), post-hoc oracle analysis reveals substantially higher potential (+0.108 AUC) when probes are matched to specific deception types, and synthetic validation experiments suggest this ceiling is achievable a priori when the deception type is known in advance. Our findings reveal that instruction pairs capture deceptive intent rather than content-specific patterns, explaining why prompt choice dominates probe performance (70.6% of variance). Given this heterogeneity, we conclude that organizations should define their specific threat models and deploy appropriately matched probes rather than seeking a universal deception detector.

23.
arXiv (CS.CV) 2026-06-11

How Auxiliary Reasoning Unleashes GUI Grounding in VLMs

Graphical user interface (GUI) grounding is a fundamental task for building GUI agents. However, general vision-language models (VLMs) struggle with this task due to a lack of specific optimization. We identify a key gap in this paper: while VLMs exhibit significant latent grounding potential, as demonstrated by their performance measured by Pointing Game, they underperform when tasked with outputting explicit coordinates. To address this discrepancy and bypass the high data and annotation costs of current fine-tuning approaches, we propose three zero-shot auxiliary reasoning methods. By providing explicit spatial cues such as axes, grids and labeled intersections as part of the input image, these methods enable VLMs to better articulate their implicit spatial understanding capabilities. We evaluate these methods on four GUI grounding benchmarks across seven open-source and proprietary VLMs. Experimental results show substantial gains from auxiliary reasoning. Mark-Grid Scaffold boosts Gemini-3.1-Pro from 11.72\% under direct inference to 95.20\% on ScreenSpot-v2, achieves state-of-the-art performance on ScreenSpot, and approaches the strongest fine-tuned methods on ScreenSpot-v2 and UI-I2E-Bench. Our code is available at https://github.com/liweim/AuxiliaryReasoning.

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

Closing the Reflection Gap: A Free Calibration Bonus for Agentic RL

Authors:

arXiv:2606.14211v1 Announce Type: new Abstract: LLMs are increasingly deployed as agents that interact with external environments and observe feedback such as execution results, error messages, and tool outputs. A well-functioning agent should be able to leverage this feedback to accurately assess its own performance. Yet we find a persistent reflection gap: LLM agents tend to mis-assess their own outputs after observing concrete environment feedback – even for questions they correctly answered – and standard RL barely helps due to a credit-assignment mismatch. To close this gap, we propose RefGRPO, a simple yet effective fix that augments standard RL algorithms with two key ingredients: a free calibration bonus computed by contrasting the agent's own reflection with the actual outcome (requiring no additional reward model, LLM judge, or external annotation), and a dynamic schedule on its coefficient. Compared to standard RL baselines, our method simultaneously improves reflection calibration (e.g., reduces underconfidence rate $44.4\% \to 7.7\%$) and task accuracy (e.g., $75.1\% \to 76.5\%$) on text-to-SQL across five benchmarks. The resulting calibrated reflection turns the agent into its own verifier grounded in environment feedback, which further enables (i) better self-improvement that uses reflections as pseudo-rewards without outcome supervision, and (ii) more effective test-time selective prediction by committing only to rollouts flagged as correct.

25.
arXiv (quant-ph) 2026-06-12

Simple analytical flux-tuned iSWAP pulses for leakage suppression

arXiv:2606.13052v1 Announce Type: new Abstract: Fast, high-fidelity two-qubit gates are a key requirement for fault-tolerant quantum computation. Tunable coupler architectures provide a flexible approach for implementing entangling gates through flux control with large on-off ratios, but fast flux modulation can induce diabatic transitions and population leakage to non-computational states, limiting gate performance. Here we present an analytical flux control method enabling derivative removal by adiabatic gate ($\Phi$-DRAG) for suppressing leakage in flux tunable two-qubit gates. We show that $\Phi$-DRAG differs fundamentally from conventional microwave implementations and derive modified flux modulation protocols that suppress leakage below $10^{-4}$ for fast entangling gates. The method remains effective across a range of asymmetry between qubit anharmonicities and different circuit parameters, enabling high-fidelity two-qubit gates within the fifteen nanosecond range.