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01.
arXiv (CS.LG) 2026-06-12

Mirror Descent on Riemannian Manifolds

Authors:
Jiaxin Jiang↗Lei Shi↗Jiyuan Tan↗

arXiv:2603.17527v2 Announce Type: replace-cross Abstract: Mirror Descent (MD) is a scalable first-order method widely used in large-scale optimization, with applications in image processing, policy optimization, and neural network training. This paper generalizes MD to optimization on Riemannian manifolds. In particular, we develop a Riemannian Mirror Descent (RMD) framework via reparameterization and further propose a stochastic variant of RMD. We also establish non-asymptotic convergence guarantees for both RMD and stochastic RMD. As an application to the Stiefel manifold, our RMD framework reduces to the Curvilinear Gradient Descent (CGD) method proposed in [26]. Moreover, when specializing the stochastic RMD framework to the Stiefel setting, we obtain a stochastic extension of CGD, which effectively addresses large-scale manifold optimization problems.

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02.
arXiv (CS.LG) 2026-06-17

Finite-Time Queue Peak Laws in Stochastic Networks: Logarithmic Scaling After Geometric Thresholds

Authors:
Hao Liang↗Cheng Tang↗Yunzong Xu↗

arXiv:2606.18218v1 Announce Type: cross Abstract: We study finite-horizon queue peaks in generalized switches, a standard stochastic-network model in which many queues share constrained service resources. Arrivals may be dependent, time-varying, and adapted to the past; the standing load condition is uniform interior slack, meaning the conditional mean arrival vector stays in a fixed contraction of the capacity region. We show that this slack reshapes the finite-time peak law for drift-minimizing scheduling policies such as MaxWeight. The square-root envelope that is sharp without slack persists only up to a geometry-dependent threshold; beyond that threshold, the running maximum grows only logarithmically with the horizon, both with high probability and in expectation. The mechanism is self-normalization: in the current queue direction, the projected fluctuation scale is normalized by the stabilizing drift scale. This removes capacity geometry from the logarithmic coefficient, while geometry remains in the threshold. Matching lower bounds show that both the logarithmic term and a geometric threshold are unavoidable. When finite-time state-space collapse is available, the threshold can be sharpened using local bottleneck geometry. For generalized input-queued switches, we obtain finite-time peak bounds with tight logarithmic coefficients. Simulations illustrate the two-phase envelope, local geometric refinements, and variance-sensitive improvements predicted by the theory.

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03.
arXiv (CS.CL) 2026-06-12

ProPlay: Procedural World Models for Self-Evolving LLM Agents

Authors:
Yijun Ma↗Zehong Wang↗Yiyang Li↗Ziming Li↗Xiaoguang Guo↗Weixiang Sun↗Chuxu Zhang↗Yanfang Ye↗

Self-evolving agents are expected to improve through interaction without external supervision, but this remains difficult in partially observable environments where agents must explore actively, learn from limited feedback, and decide when to trust prior experience. Existing LLM-agent methods often rely on memory or planning modules, yet they rarely close the loop between them to continually refine an internal understanding of environment dynamics. We introduce ProPlay, a procedural world model that supports procedure-level preplay, where agents can rehearse future procedural paths using the learned world knowledge. Rather than representing experience as isolated rules or low-level action constraints, ProPlay abstracts successful trajectories into procedures and organizes them in a procedure graph that captures causal transitions among task stages. Each transition is associated with a reliability record embedding to estimate its task-specific contribution from past outcomes. Before each episode, ProPlay simulates future procedural trajectories over known graph structures as structured soft guidance; after execution, it refines the graph using environment feedback. Experiments on public benchmarks show that ProPlay consistently improves environment understanding and self-evolution capability over strong baselines. Our code has been released in https://github.com/antman9914/proplay.

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04.
arXiv (CS.CV) 2026-06-16

Efficient Reinforcement for Visual-Textual Thinking with Discrete Diffusion Model

Authors:
Yoonjeon Kim↗Yuhta Takida↗Chieh-Hsin Lai↗Eunho Yang↗Yuki Mitsufuji↗

RL-based post-training has been widely adopted to enable interleaved visual and textual reasoning in unified multimodal models capable of both text and image generation. However, most existing approaches are built upon autoregressive (AR) unified models, which require full image regeneration during visual reasoning. In this work, we demonstrate that multimodal discrete diffusion models are effective alternatives to AR models for reinforcement learning in interleaved reasoning, owing to their ability to perform efficient visual rollouts via localized visual editing rather than full image-token regeneration. This reduces rollout computation during GRPO by 26.9\% compared to AR baselines, with minimal performance drop. Despite the improved efficiency, we find that joint reward assignment, which employs a shared reward signal across modalities, introduces cross-modal interference between unrelated image and text token sequences during RL updates. To address this issue, we propose factorized reward assignment, a strategy that assigns rewards independently to text and vision segments. With factorized reward assignment, our RL approach achieves an 11.2% improvement over joint reward assignment and a 38.04% improvement over the base model.

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05.
arXiv (CS.AI) 2026-06-16

Protein Design with Agent Rosetta: A Case Study for Specialized Scientific Agents

Authors:
Jacopo Teneggi↗S. M. Bargeen A. Turzo↗Tanya Marwah↗Alberto Bietti↗P. Douglas Renfrew↗Vikram Khipple Mulligan↗Siavash Golkar↗

arXiv:2603.15952v2 Announce Type: replace Abstract: Large language models (LLMs) are capable of emulating reasoning and using tools, creating opportunities for autonomous agents that execute complex scientific tasks. Protein design provides a natural testbed: although machine learning (ML) methods achieve strong results, these are largely restricted to canonical amino acids and narrow objectives, leaving unfilled need for a generalist tool for broad design pipelines. We introduce Agent Rosetta, an LLM agent paired with a structured environment for operating Rosetta, the leading physics-based heteropolymer design software, capable of modeling non-canonical building blocks and geometries. Agent Rosetta iteratively refines designs to achieve user-defined objectives, combining LLM reasoning with Rosetta's generality. We evaluate Agent Rosetta on design with canonical amino acids, matching specialized models and expert baselines, and with non-canonical residues – where ML approaches fail – achieving comparable performance. Critically, prompt engineering alone often fails to generate Rosetta actions, demonstrating that environment design is essential for integrating LLM agents with specialized software. Our results show that properly designed environments enable LLM agents to make scientific software accessible while matching specialized tools and human experts.

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

Localized Kernel Projection Outlyingness: A Two-Stage Approach for Multi-Modal Outlier Detection

Authors:
Akira Tamamori↗

arXiv:2510.24043v4 Announce Type: replace Abstract: This paper presents Two-Stage LKPLO, a novel multi-stage outlier detection framework that overcomes the coexisting limitations of conventional projection-based methods: their reliance on a fixed statistical metric and their assumption of a single data structure. Our framework uniquely synthesizes three key concepts: (1) a generalized loss-based outlyingness measure (PLO) that replaces the fixed metric with flexible, adaptive loss functions like our proposed SVM-like loss; (2) a global kernel PCA stage to linearize non-linear data structures; and (3) a subsequent local clustering stage to handle multi-modal distributions. Comprehensive 5-fold cross-validation experiments on 10 benchmark datasets, with automated hyperparameter optimization, demonstrate that Two-Stage LKPLO achieves state-of-the-art performance. It significantly outperforms strong baselines on datasets with challenging structures where existing methods fail, most notably on multi-cluster data (Optdigits) and complex, high-dimensional data (Arrhythmia). Furthermore, an ablation study empirically confirms that the synergistic combination of both the kernelization and localization stages is indispensable for its superior performance. This work contributes a powerful new tool for a significant class of outlier detection problems and underscores the importance of hybrid, multi-stage architectures.

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07.
arXiv (CS.AI) 2026-06-16

Learning aligned EEG representations with subject-specific encoders

Authors:
Bruna J. Lopes↗Gabriel Schwartz↗Sylvain Chevallier↗Raphael Y. de Camargo↗Bruno Aristimunha↗

arXiv:2606.16462v1 Announce Type: cross Abstract: Cross-subject EEG decoding promises more training data, but it also exposes neural networks to strong inter-subject distribution shifts. We study whether task supervision and architecture alone can learn subject-aligned representations. We replace a shared EEG encoder with subject-specific encoders followed by a common classifier, and compare this hybrid model with standard EEGNet, AttentionBaseNet, and CTNet baselines with Euclidean Alignment (EA) on four motor-imagery datasets. EA improves shared encoders by recentering subject covariances, but the hybrid encoder largely internalises this role: validation-loss curves and latent-distance analyses change little when EA is removed. Subject-specific heads increase class distinctiveness and place each subject close to its own latent manifold, improving most subjects while leaving a method-sensitive subset. These results support subject-specific encoders as a learned alignment mechanism for EEG decoding and identify head selection for unseen subjects as the remaining bottleneck.

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08.
arXiv (CS.CV) 2026-06-12

From Seeing to Experiencing: Scaling Navigation Foundation Models with Reinforcement Learning

Authors:
Honglin He↗Yukai Ma↗Brad Squicciarini↗Wayne Wu↗Bolei Zhou↗

Navigation foundation models trained on massive web-scale data enable agents to generalize across diverse environments and embodiments. However, these models, which are trained solely on offline data, often lack the capacity to reason about the consequences of their actions or adapt through counterfactual understanding. They thus face significant limitations in real-world urban navigation, where interactive and safe behaviors, such as avoiding obstacles and moving pedestrians, are critical. To tackle these challenges, we introduce the Seeing-to-Experiencing (S2E) learning framework to scale the capability of navigation foundation models with reinforcement learning. S2E combines the strengths of pretraining on offline videos and post-training through reinforcement learning. It maintains the model's generalizability acquired from large-scale real-world videos while enhancing its interactivity through reinforcement learning in simulation environments. Specifically, we introduce two innovations: (1) an Anchor-Guided Distribution Matching strategy for offline pretraining, which stabilizes learning and models diverse motion patterns through anchor-based supervision; and (2) a Residual-Attention Module for reinforcement learning, which obtains reactive behaviors from simulation environments without erasing the model's pretrained knowledge. Moreover, we establish a comprehensive end-to-end evaluation benchmark, NavBench-GS, built on photorealistic 3D Gaussian Splatting reconstructions of real-world scenes that incorporate physical interactions. It can systematically assess the generalizability and safety of navigation foundation models.

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09.
arXiv (CS.CV) 2026-06-17

Complex Layout Classification in the Wild: A Low-Resource Approach with Layout-Preserving Augmentations

Authors:
Sharva Gogawale↗Iddo Hakim↗Gal Grudka↗Mohammad Suliman↗Omer Ventura↗Daria Vasyutinsky-Shapira↗Berat Kurar-Barakat↗Nachum Dershowitz↗

Many digitized corpora suffer from low resources because annotations may be scarce, page scans are noisy and of poor resolution, or layouts are structurally complex in ways that negatively affect the quality of automatic transcription. Developing robust classification models for low-resource languages is inhibited by the lack of large-scale annotated data and by the frequent semantic complexity of page layouts. To this end, we have curated a complex-layout dataset, manually classified into eight distinct layout types based on their separator regions. To overcome data scarcity, we propose a novel training strategy in the form of a CNN-based classifier that employs strong, domain-aware augmentations to improve generalization. We utilize narrow anisotropic Gaussian masking to suppress incidental textual details while preserving essential separations, compelling the model to learn global geometric arrangements. Additionally, we implement reflection-induced label transformations to enrich the training distribution while maintaining label consistency across asymmetric categories. The results demonstrate that layout-specific augmentations can substantially improve page-level layout classification under severe annotation scarcity.

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10.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

Authors:
De la Hoz↗J. F↗Lee↗Y. H↗Tubbs↗J. D↗Meyerson↗Cudic↗Watts↗Feng↗Y.-C. A↗Chen↗…

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

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

Mechanical Field Networks: Structured Neural Dynamics for Multivariate Systems

Authors:
Xingji Cui↗

arXiv:2606.11251v1 Announce Type: new Abstract: Many multivariate dynamical systems are observed only through trajectories, leaving the mechanisms governing their joint dynamics hidden. Existing approaches can impose interpretable dynamics or learn flexible state transitions, yet the resulting interaction structure is typically either specified in advance or left implicit within the learned dynamics. We introduce MF-Net, a recurrent dynamical model that represents all variables in a shared field state and updates this state through a learned relation law. Each variable carries a field component, and these components evolve jointly through a learnable mechanical transition. Here, mechanical refers to the relation-to-motion organization of the transition, where learned relations shape state-dependent flows, field responses, and motion tendencies that move the field state forward. The resulting structure is part of the rollout itself: learned relations influence how the field moves, and the same internal quantities support both forecasting and structural readout. Across known-law interaction systems, chaotic benchmarks, real neural recordings, and ecological time series, MF-Net achieves competitive short- and medium-horizon forecasting while retaining inspectable structural readout. On the 40-dimensional Lorenz–96 testbed, MF-Net achieves an eight-step $R^2$ of $0.798\pm0.018$; across five seeds, its learned relation matrix recovers the local coupling support with a local/nonlocal strength ratio of $19.80\pm1.00$ and Precision@$K$ of $1.000\pm0.000$. MF-Net provides a structure-readable dynamical modeling framework in which learned relations are trained through forward evolution and, on real data, interpreted as functional predictive couplings under appropriate observational limits.

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12.
arXiv (CS.CL) 2026-06-19

CombEval: A Framework for Evaluating Combinatorial Counting in Large Language Models

Authors:
Yuxu Zhou↗Ond\v{r}ej Ku\v{z}elka↗Yuyi Wang↗Yuanhong Wang↗Yi Chang↗

We present CombEval, a dynamic benchmark for evaluating combinatorial counting in large language models. CombEval represents each problem as a typed Cofola specification over entities, combinatorial objects, object dependencies, and constraints, enabling controlled generation of natural-language counting problems with exact solver-verified answers. Unlike static collections, CombEval supports systematic variation of object type, entity scale, constraint count, and reasoning depth. We evaluate 11 LLMs under direct and code-augmented settings and find that models remain brittle on ordered objects, indistinguishable elements, relatively positional constraints, and nested object dependencies. Error analysis further identifies failures in constraint interpretation and counting principles. CombEval provides a diagnostic testbed for studying when and why LLMs fail at combinatorial reasoning. The code and generated benchmark suites are publicly available at \url{https://github.com/YuxuZhou-CN/combination-problem-generation}.

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13.
arXiv (CS.LG) 2026-06-18

Smoothness-Based Derandomization of PAC-Bayes Bounds

Authors:
Alexandre Lemire Paquin↗Brahim Chaib-Draa↗Philippe Gigu\`ere↗

arXiv:2606.19105v1 Announce Type: new Abstract: We study PAC-Bayes derandomization for smooth loss functions. Our goal is to obtain generalization bounds that hold with high probability for deterministic predictors by exploiting smoothness properties of both the loss and the predictor class. We show that passing from the Gibbs predictor to the deterministic predictor at the posterior mean has a precise cost, given by the generalization gap of the Jensen gap class. We control this class through its Rademacher complexity, leading to bounds for deterministic predictors that involve flatness quantities expressed in terms of parameter Jacobians and Hessians of the score map. The framework applies to both bounded and unbounded smooth loss functions, and we specialize the results to linear predictors and smooth neural networks. Finally, the Jacobian and Hessian quantities appearing in the theory motivate a practical regularizer. For BatchNorm networks, we compute this regularizer with respect to effective BatchNorm weights obtained by folding the BatchNorm transformation into the adjacent affine weights. Experiments on CIFAR-10 illustrate the behavior of this regularizer under different batch sizes.

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14.
arXiv (CS.LG) 2026-06-12

Forecasting Is Not Attribution: Localizing Decoder Bypass in Graph-Based Neural Marketing Mix Models

Authors:
Yunbo Wang↗Bolbi Liu↗

arXiv:2606.12687v1 Announce Type: new Abstract: Marketing mix models are used to forecast business outcomes and to attribute those outcomes to marketing channels, but these goals are not equivalent. We study a failure mode in graph-based neural MMM called attribution bypass: a high-capacity decoder can obtain low forecasting error through target autoregression, dense communication, co-movement, context, or latent memory while failing to route counterfactual sensitivity through the graph used as the attribution object. We introduce DICE-MMM as a bounded diagnostic and training framework. We do not claim that observational neural MMM identifies causal effects. Instead, DICE separates three questions often conflated in graph-based MMM: graph recovery, forecasting accuracy, and whether the trained decoder's perturbation-induced influence is graph aligned. Stage 1 trains a graph encoder with a restricted graph-mediated decoder. Stage 2 freezes the selected encoder and trains a graph-safe latent decoder whose cross-node communication must pass through the supplied graph. Decoder use is evaluated with CIG, AR-CIG, and graph-swap tests. Across controlled R/d/T swaps and an external multi-graph rawlog stress test, DICE improves stable graph recovery over CausalMMM. The experiments show that forecasting accuracy is not an attribution certificate: in a sparse-target benchmark, no-graph and full-graph decoders achieve MSE@7 around 0.004 while AR-CIG nAUPRC remains near or below zero, whereas an oracle graph reaches 0.807 +/- 0.129 at comparable MSE. Frozen graph-swap localizes the bottleneck: the same DICE-hard-trained decoder moves from nAUPRC -0.044 +/- 0.006 under learned graph inputs to 0.894 +/- 0.027 with the oracle graph. The contribution is a stress test and failure-localization framework showing that low MSE can hide attribution bypass and that the unresolved bottleneck is graph-support selection, not forecasting or decoder capacity.

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15.
arXiv (CS.AI) 2026-06-19

OnDeFog: Online Decision Transformer under Frame Dropping

Authors:
Daiki Yotsufuji↗Kenta Nishihara↗Shoma Shimizu↗Kento Uchida↗Shinichi Shirakawa↗

arXiv:2606.19721v1 Announce Type: cross Abstract: In challenging real-world reinforcement learning applications, communication delays or sensor failures often cause frame dropping, in which the agent cannot receive the dropped states and associated rewards. To address the performance degradation caused by frame dropping, the Decision Transformer under Random Frame Dropping (DeFog) was developed by incorporating additional mechanisms into the decision transformer to tackle frame dropping. Although DeFog can mitigate performance degradation in frame-dropping environments, since DeFog is an offline learning method, it struggles to effectively generalize to novel states not adequately represented in the training dataset. In this study, we propose OnDeFog, which integrates the mechanisms in DeFog with the online decision transformer (ODT), an online reinforcement learning method that learns policies through direct environmental interaction. Comprehensive experimental evaluation demonstrates that our proposed OnDeFog achieves superior performance compared to ODT in environments characterized by high dropping frame rate and outperforms DeFog on datasets containing a large amount of low-reward data.

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16.
arXiv (CS.LG) 2026-06-12

Graph Reinforcement Learning for Calibration-Aware Quantum Circuit Routing

Authors:
Yash Vardhan Tomar↗Dheeraj Peddireddy↗Vaneet Aggarwal↗

arXiv:2606.12816v1 Announce Type: cross Abstract: Quantum circuit routing is a key step in compiling programs for noisy intermediate-scale quantum processors. Routes that appear efficient by standard overhead metrics can still lose fidelity when they pass through poorly calibrated couplers. We study a calibration-aware graph reinforcement-learning router that uses same-day IBM Heron r2 calibration data to choose hardware-edge SWAPs. We train the policy with proximal policy optimization and evaluate it with exact simulated fidelity across nine Munich Quantum Toolkit (MQT) Bench circuits and three calibration snapshots. Across these evaluations, pooled mean exact fidelity is $0.727$, compared with $0.440$ for SABRE-best20 and $0.481$ for target-aware SABRE. Fidelity gains come with higher routed two-qubit counts and are concentrated in the 5q and 8q circuit families; under the fixed tree action graph, all 10q families favor SABRE-best20. Overall, our results show that calibration-aware learned routing can improve fidelity beyond gate-count-driven compilation.

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

UXBench: Measuring the Actionability of LLM-Generated UX Critiques

Authors:
Wenjie Wang↗Yue Huang↗Zipeng Ling↗Han Bao↗Hang hua↗Xiaonan Luo↗Yu Jiang↗Shiyi Du↗Yuexing Hao↗Xiaomin Li↗Yuchen Ma↗Dianzhuo Wang↗…

arXiv:2606.16262v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly deployed as UX judges that inspect interfaces, diagnose usability problems, and propose repairs. Yet no controlled benchmark measures whether the resulting critiques are reliable and actionable across heterogeneous product surfaces. We introduce UXBench, a benchmark for evaluating LLMs as interaction-grounded UX judges. UXBench comprises local-first runnable web fixtures spanning ten product-surface families, paired with coverage-gated browser exploration that forces models to collect interaction evidence before reporting. Each judge model produces a structured UX report over seven rubric dimensions; report quality is measured by whether a fixed downstream repair agent can improve the interface based on the critique. We evaluate eight frontier models under both an automated repair-lift protocol and a blind human validation study. Results show that UX judging is neither saturated nor one dimensional: models differ meaningfully in report actionability, exhibit distinct rubric-level repair signatures, vary in fixture-level reliability, and trade leadership across surface categories

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18.
arXiv (CS.CV) 2026-06-15

TSA: Temporal Slot Activation for Persistent Object-Centric Video Representation

Authors:
Duc Nguyen↗Sieu Tran↗Hao Vo↗Khoa Vo↗Duy Minh Ho Nguyen↗Nghi D. Q. Bui↗Anh Nguyen↗Long Mai↗Ngan Le↗

Unsupervised video object-centric learning aims to decompose dynamic scenes into temporally persistent entity representations. Existing recurrent video slot-attention methods propagate a fixed set of slots across frames, but typically assume unconditional slot propagation: every slot is updated and decoded at every frame, regardless of whether its corresponding object is visible. We show that this design violates a basic lifecycle requirement for persistent slots: when an object is absent or fully occluded, its slot should preserve its previous state and avoid explaining unrelated visible content. Instead, unconditional propagation creates two failure pathways: update-induced state drift, where current-frame evidence overwrites the absent object's representation, and decoder-induced reconstruction interference, where the inactive slot remains coupled to reconstruction through decoder attention. We propose Temporal Slot Activation (TSA), a mechanism that learns a per-slot, per-frame activation score $\alpha_{k,t} \in (0, 1)$ without visibility supervision. TSA uses this activation as a shared latent control variable for slot lifecycle modeling. When a slot is inactive, TSA anchors its state to the previous slot via activation-gated updating and suppresses its decoder participation through an activation-dependent additive bias on attention logits before softmax normalization. This jointly reduces state drift and reconstruction-driven interference. To improve decisions under partial occlusion and gradual reappearance, TSA further conditions activation prediction on a per-slot temporal memory produced by a Temporal Context Encoder. We evaluate TSA on MOVi-C/E, YT-VIS, and OVIS benchmarks using both standard and tracking-based metrics (FG-ARI, mBO, IDF1, HOTA). TSA consistently improves object decomposition and temporal identity preservation, with large gains on long, heavily occluded videos.

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19.
Nature (Science) 2026-06-10

Lignin to adipic acid in a high-yield chemical and biological redox process

Authors:
Kathryn M. Mains↗

Viable manufacturing pathways to produce bio-based chemicals from renewable feedstocks, such as lignin derived from plant biomass, are needed to decarbonize the chemicals manufacturing sector. Converting the recalcitrant lignin polymer to valuable bioproducts remains a longstanding challenge in biorefining, with the highest reported single-product yield from lignin currently around 20 wt% (refs. 1–4). Most existing lignin depolymerization strategies target aryl–ether bond cleavage, which can produce aromatic monomers in yields of only about 30 wt%, and&nbsp;still as complex mixtures with C–C-linked dimers and oligomers5,6. The recalcitrance of these C–C linkages between aromatic moieties fundamentally limits single-product yields from lignin, prompting the development of strategies to efficiently cleave these C–C bonds3,7–9. Here we show how reductive processing of lignin from poplar accesses a hydrocarbon mixture of alkyl-aromatic monomers and oligomers that is privileged for oxidative conversion to monomeric aromatic carboxylic acids, comprising mostly benzoic acid and phthalic acid isomers in up to 73 wt% monomer yields, using a Co/Mn/Br catalyst. The soil bacterium Pseudomonas putida KT2440 was engineered to convert this mixture of aromatic carboxylic acids to muconolactone, a precursor to bio-based nylons, enabling final adipic acid yields up to 26 wt% (gram adipic acid per gram lignin) with a maximum theoretical yield of 57&nbsp;wt%. This pairing of reductive and oxidative steps with lignin resembles processes in petrochemical refining and shows how lignin may be converted into a single, valuable bioproduct in high yields. A chemical and biological redox process that resembles processes in petrochemical refining is used to convert lignin from poplar into a single, valuable bioproduct, adipic acid, in high yields.

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20.
Nature (Science) 2026-06-10

Mitochondria directly interact with the nuclear pore complex

Authors:
Ivan Menendez-Montes↗

Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5. Here we identify direct interactions between mitochondria and nuclear pores. Using two unbiased proteomic screens, GST pulldown and BioID, we found that VDAC1 was the top mitochondrial candidate that interacts with the filamentous nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knockout,&nbsp;RANBP2 truncation&nbsp;or site-directed mutagenesis of RANBP2–VDAC1 interacting amino acids resulted in reduced mitochondria–nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in the levels of the nuclear phosphoproteome and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. Moreover, deletion of the RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the nuclear pore complex, a phenomenon critical for regulation of nuclear energetics and cellular differentiation. Undoubtedly, additional roles of this interaction remain to be revealed. Mitochondria interact directly with the nuclear pore complex via VDAC1–RANBP2&nbsp;binding to sustain nuclear ATP levels.

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21.
medRxiv (Medicine) 2026-06-18

Automated Airways Characterization and Assessment of Cystic Fibrosis from CT Imaging

Authors:
Chong Chie↗J. A. K. H↗Cooper↗M. L↗Persohn↗S. A↗Burton↗C. P↗Salama↗Territo↗P. R↗

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

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22.
Nature Biotechnology 2026-06-08

Single-cell spatial pharmacobiology for imaging antibody-based therapies in solid tumors

Authors: Unknown Author

We have developed single-cell spatial pharmacobiology (SSP), which combines in situ imaging of a systemically infused fluorescent therapeutic antibody with high-plex spatial proteomics. Applied to head and neck and pancreatic tumors from patients treated in phase 1 trials, SSP revealed marked spatial heterogeneity in antibody delivery and target engagement, which was shaped by conserved stromal barriers.

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23.
arXiv (CS.CV) 2026-06-16

JoyAI-VL-Interaction: Real-Time Vision-Language Interaction Intelligence

Authors:
Dingyu Yao↗Junhao Zhou↗Chenxu Yang↗Chuanyu Qin↗Haowen Hou↗Zheming Liang↗Congcong Wang↗Yuhang Cao↗Shenglong Ye↗Shuai Xie↗Shuhuan Gu↗Haoyang Huang↗…

Many moments in the real world do not wait for a user to ask. A fire starts on a security monitor, an expression flickers across a video call, or a product a viewer wants flashes by in a livestream. Yet today's large models remain mostly turn-based by design: they answer only when addressed, and even video-call apps that appear interactive still operate as question-answer systems, reacting only when polled or prompted. We argue for a different paradigm: a model that is present in the world like a person. It continuously watches what is happening now, decides on its own whether to speak or stay silent, interacts in real time, and delegates to a background model when the problem is hard. To advance interaction models and their adoption across domains, we make two fully open-sourced contributions. First, we release JoyAI-VL-Interaction, an 8B-scale, vision-first VL-interaction model. The model makes the response decision internally, choosing each second to stay silent, respond, or delegate to a background model, and it excels at vision-triggered responsiveness and time awareness. We pair it with a transferable training recipe, from which capabilities we never trained for emerge, such as guiding a shopper through changing app screens or improvising a lecture from a slide deck. Second, we release a complete, deployable system built around that model. The system streams any ongoing video into the model, making it genuinely present in the world. All other components are pluggable, including ASR/TTS modules, memory, visualization UI, and a background brain that can connect to any API or agent. Across six real-world scenarios, human raters prefer JoyAI-VL-Interaction over the in-app video-call assistants of Doubao and Gemini by a wide margin. To our knowledge, this is the first open, vision-driven interaction model released together with its training recipe, data, and complete deployable system.

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24.
medRxiv (Medicine) 2026-06-15

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

Authors:
Kowada↗

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.

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25.
bioRxiv (Bioinfo) 2026-06-15

DAQplugin: Deep Learning based Real-time Model Evaluation Plugin for ChimeraX

Authors:
Terashi↗Zhu↗Kihara↗

Although an increasing number of protein structures are determined by cryogenic electron microscopy (cryo-EM), protein structure modeling frequently suffers from residue misassignments and sequence register shifts, particularly in regions with ambiguous density. Here, we present DAQplugin, a ChimeraX plugin that performs real-time evaluation of protein models against cryo-EM density maps using the deep-learning-based residue-wise model quality (DAQ) score. Unlike existing validation tools that are typically applied after model construction, DAQplugin enables real-time deep-learning-based validation during model building and refinement. To our knowledge, DAQplugin is the first tool that provides real-time deep-learning based validation of protein models for cryo-EM map within an interactive modeling environment. In addition to identifying potential modeling errors, DAQplugin also provides guidance for correcting sequence register shifts by suggesting alternative residue placements along the backbone. The computation in this plugin is designed to run efficiently on general CPUs without requiring GPU hardware. Using DAQplugin, users can perform deep-learning-based validation on standard laptops during interactive model building, model-map fitting, and refinement. DAQplugin is able to facilitate more accurate interpretation of cryo-EM density maps and improve the reliability assessment of protein structure models.

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