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Lightweight Deep Learning Framework for Astrocyte-Centric 3D Reconstruction across Normal and Stress-associated Ultrastructural States
2026-11-10 04:54:30Bowen Deng, Gwang-Jin Jeong, Seulgi Noh, Ji Young Mun, Na Young KimAbstract
The morphology of astrocytes is closely associated with their ability to support and modulate neural circuit functions; however, its reconstruction from volume electron microscopy (vEM) data remains labor-intensive and computationally resource-intensive, placing substantial barriers on its broader adoption and scalability despite the high spatial resolution of vEM. We present AstroSeg-vEM, a lightweight, astrocyte-centric framework for morphology-preserving astrocyte segmentation, 3D reconstruction, and quantitative morphological analysis in vEM images. AstroSeg-vEM combines transformer-based 2D segmentation with dedicated post-processing methods and operates directly on high-resolution EM sections, making it well suited to anisotropic vEM data and downstream proofreading workflows while preserving the full in-plane resolution of the original EM data. Across four mouse hippocampal datasets representing normal and morphologically defined stress-associated astrocyte ultrastructural states, AstroSeg-vEM demonstrates robust performance and generalization, achieving average Dice and weighted Dice values of 0.92 and 0.95, respectively, on a held-out test dataset. Its lightweight architecture enables efficient, high-fidelity reconstruction on consumer-grade hardware, providing a scalable and accessible platform for large-scale astrocyte ultrastructure analysis and future astrocyte-neuron interaction studies.
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https://arxiv.org/abs/2611.13581
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PhyRubric: Rubric-Grounded Diagnostic Evaluation of Physical Commonsense in Text-to-Video Generation
2026-11-10 04:50:38Huiyi Chen, Weitai Kang, Shicheng Fan, Xinshuo Wang, Zhixiang Shen, Yan Yan, Philip S. Yu, Baoxin LiAbstract
As text-to-video (T2V) models are increasingly positioned as world simulators, it is essential to evaluate whether their videos conform to physical commonsense. However, existing benchmarks rely on annotators who rate each video with a single score based on intuition, yielding ratings that are subjective and do not tell which physical principle is violated. We introduce PhyRubric, a rubric-grounded diagnostic framework for evaluating physical commonsense in T2V generation. For each caption, PhyRubric constructs a caption-specific rubric before any video is seen, decomposing the caption into semantic and physical items, and derives scores from item-level verdicts grounded in timestamped evidence. We instantiate this framework as PhyRubric-Bench, which spans 34 categories across five physical domains, and scale it up to PhyRubric-Train with 3,788 videos, on which we fine-tune the open-source PhyRubric-Judge. Empirical results across ten T2V models show that physical commonsense remains far from solved, and that PhyRubric-Judge correlates more closely with human judgments than existing open-source judges while matching the frontier proprietary Gemini 4 Argon. Further analysis provides actionable insights for T2V models.
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https://arxiv.org/abs/2611.13576
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Navigating relational agency in AI feedback musicianship: a diffractive dialogue
2026-11-10 04:20:02Yichen Wang, Charles Patrick Martin, David Gunawan, David CooperAbstract
Musical AI systems behave in non-linear, dynamic ways that exceed the tool-oriented framings inherited from earlier instrument design. Existing frames of control and ensemble interaction do not articulate the entangled, relational agency that emerges when performers work with AI feedback instruments over time. We examine a duet practice with two AI-enabled feedback instruments, Sù and Agentier, in which feedback operates at the inner level of the AI's recurrent processes and the outer loop of musical interaction between performer, instrument, and co-performer. Our work draws on agential realism and a diffractive dialogue methodology to read our independent reflections through one another across five performances, examining how agency is enacted between performers and AI instruments. We find that control and agency are relational and shift across performances; musical textures enact feedback moments of control with performers; reaching a productive feedback environment is itself a shared exploratory act; and performers maintain their instruments through funnelling and injection, developing the skill of navigating agency along a continuous spectrum. Feedback musicianship with AI instruments demands navigation of this relational agency, displacing the leading-versus-responding binary that initially framed our reflections. This work contributes a materially-grounded vocabulary for AI feedback musicianship and a model of human-AI creative collaboration in which mutual agency is worked for through practice rather than designed in.
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URL
https://arxiv.org/abs/2611.13555
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Control-Aware Command Generation for Asynchronous Control and Action Inference with Vision-Based Policies towards Fast Execution
2026-11-10 04:14:23Takayuki Osa, Kazuki OtaAbstract
Vision-based control policies, including vision-language-action models, have enabled robots to perform increasingly complex tasks. However, their execution speed is often limited by the high computational cost of action inference. In this work, we investigate what can be achieved at the control level without modifying the underlying policy learning process. We introduce an asynchronous inference and control framework that enables fast task execution while maintaining smooth and stable robot motions. By formulating the generation of continuous target positions from discontinuous model predictions as a tracking control problem, our method makes asynchronous inference practical for real robots. We further accelerate execution through adaptive action skipping based on the variance of predicted positions. Experiments with Action Chunking Transformer and OpenVLA-OFT on a bimanual robot demonstrate substantial speedups while preserving high task success rates.
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URL
https://arxiv.org/abs/2611.11089
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AgenticConflictLens: From Long Traffic Videos to Verifiable Conflict Evidence
2026-11-10 04:02:51Boshra Khalili, Sonia Moshfeghi, Jinwoo Jang, Andrew W SmythAbstract
Traffic cameras continuously record urban road-user behavior, providing proactive safety evidence beyond crash reports. Yet safety-critical events - conflicts, near misses, unsafe turns, sudden braking, and crosswalk interactions - are rare and brief, buried in hours of routine footage. Existing traffic-video pipelines extract detections, trajectories, and risk scores but process footage uniformly, without adapting to an analyst's query. Vision-language methods improve scene understanding but often lack traffic-specific verification of participant-level conflicts. We introduce AgenticConflictLens, an agentic, query-conditioned framework for efficient, auditable conflict extraction from long fixed-camera traffic videos. Given a natural-language safety query, a Traffic-Aware Controller combines structured traffic memory with specialized conflict-analysis tools to choose where to search, which road users to examine, and which evidence to verify or reject. A coarse-to-fine search retrieves candidate intervals and applies detailed verification selectively. The framework produces conflict records with refined time intervals, participant pairs, semantic regions, trajectories, motion evidence, uncertainty, rejection reasons, and supporting clips. On 96 annotated hours from Bellevue and NYC DOT, AgenticConflictLens achieves the highest conflict-existence F1 and temporal IoU on both datasets: 0.84 F1/0.77 tIoU on Bellevue and 0.80 F1/0.73 tIoU on NYC DOT, while inspecting only 8.7% and 11.9% of video, respectively. These results support scalable, evidence-grounded urban traffic-safety analysis.
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URL
https://arxiv.org/abs/2611.13540
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Distribution Shift Detection in Remote Sensing Imagery using Machine Learning Models
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Remote sensing imagery acquired by Unmanned Aerial Vehicles (UAVs) supports wide range of applications; however, deploying machine learning (ML) models on resource-constrained aerial platforms introduces challenges beyond predictive accuracy, particularly when deployment data differ from the distributions observed during training. Such shifts are common in remote sensing due to geographic, sensor, seasonal, and other visual variations. A practical solution is to equip deployed models with mechanisms that detect emerging distribution shifts and support subsequent responsive actions. This paper presents an empirical case study of three open-source detection tools: (i) Alibi-Detect; (ii) NannyML; and (iii) PyTorch-OOD. Using cross-dataset remote-sensing shifts, we evaluate both detection effectiveness and computational latency of these tools. Our results reveal differences in detection behavior and processing cost across methods and implementations, highlighting trade-offs between detection capability and response-time. These findings motivate further work toward lightweight, and latency-aware monitoring mechanisms for resource-constrained systems.
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URL
https://arxiv.org/abs/2611.13510
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Mobile AI Factory: Building Specialized Language Models for Your Mobile Device
2026-11-10 03:29:29Evan Li, Krishna Deshpande, Wen Cheng, Shyamnath GollakotaAbstract
Small language models (SLMs) running on mobile devices can keep user data private and work without connectivity. But they perform well only when fine-tuned for the target task and sized for the target device, a process that today requires repeated expert tuning. We present {\it Mobile AI Factory}, an agentic system that builds a fine-tuned, quantized SLM for a given task and phone. Given a task specification and a target phone, an orchestrator LLM chooses whether to tune hyperparameters, mine real data, or generate synthetic examples, while fixed rules roll back changes that hurt accuracy. The factory searches from small to large models across base models and quantizations, adapts its accuracy goal as it searches, and uses real measurements of the target phone across inference engines and backends. We evaluate Mobile AI Factory on ten tasks and four Android phones. On an unseen testset, its on-device models outperform two five-shot frontier models on five tasks, by up to 0.34, and match them on three more. Its search comes within 0.03 of exhaustively training all 27 model variants on an entity extraction task, while using 19$\times$ less GPU time. Phone measurements also matter: the best configuration changes across phones. Without phone measurements, Claude Opus 5.5, given the full hardware and model specifications, misses the app's requirements in 25\% of easy and moderate cases and in 60\% of hard ones. Code is available at: this https URL.
Abstract (translated)
URL
https://arxiv.org/abs/2611.13509
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Hand-Object Contact Transition Detection in Egocentric Video
2026-11-10 02:52:29Huy Anh Nguyen, Chang Dong, Feras Dayoub, Minh HoaiAbstract
This paper tackles the task of hand-object contact transition detection in egocentric video, which aims to localize the two temporal boundaries of a contact episode: the moment a hand first establishes contact with an object (touch) and the moment contact is released (release). We propose a unified framework that jointly models the interacting hand and object to accurately localize both transition types. The proposed framework augments hand-centric spatiotemporal representations with object-aware features learned directly from the video and introduces a transition-aware event spotting formulation tailored to contact transitions, without relying on external object or hand-object interaction detectors during inference. To support this task, we present ContactTransition, a dataset comprising 4,021 egocentric videos with 8,498 touch and 8,077 release annotations, together with object-of-interest supervision. Experiments demonstrate that the proposed method consistently outperforms strong two-stage and end-to-end event-spotting baselines on both transition types. Finally, we show that detected contact transitions provide effective temporal anchors for downstream egocentric hand-object reasoning.
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URL
https://arxiv.org/abs/2611.13486
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ExRL: Sample-Efficient Online Adaptation of Long-Chunk Policies via Execution Length Control
2026-11-10 02:44:05Xu Luo, Jiaying Yang, Hao Wu, Junlin Xie, Zijin Hong, Ji Zhang, Lianli Gao, Jingkuan SongAbstract
Predicting long action chunks, often spanning dozens of timesteps, has become a key ingredient in increasingly capable robot policies. In this paper, we find that adapting these long-chunk policies with existing reinforcement learning (RL) methods can require many online samples due to the high dimensionality of the action chunks being optimized, making such adaptation impractical in real-world scenarios where interaction data are costly to collect. Our key insight is to shift adaptation from optimizing actions to optimizing how long to execute each predicted action chunk. This keeps the adaptation space low-dimensional while its expressivity grows with the chunk size. We thus introduce Execution at the Right Length (ExRL), a simple approach which augments the base policy with a lightweight adapter that predicts the execution length of each chunk and is trained using off-policy RL algorithms. Across simulation benchmarks and real-world robotic tasks, ExRL enables sample-efficient adaptation of a diverse range of long-chunk policies with minimal task-specific hyperparameter tuning.
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URL
https://arxiv.org/abs/2611.13482
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Sharp Sample Complexity of KL-Regularized Reinforcement Learning
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KL-regularized reinforcement learning, the objective behind maximum-entropy RL and RL from human feedback, is variational inference in the graphical model of "control as inference": the regularized optimal policy is a posterior over trajectories, and the suboptimality of a policy is $\beta$ times a KL divergence between path measures. However, it is not known how many samples it takes to learn this posterior, even with a generative model. Earlier $1/\epsilon$ guarantees scale with $H^5$ in the effective horizon $H$, and no lower bound for MDPs depends on the temperature $\beta$. In this work, we show that for a discounted MDP with $K$ state-action pairs, the plug-in estimator finds a policy that is $\epsilon$-optimal from every initial state with $\widetilde{O}(KH^3/(\epsilon\max\{\epsilon,\beta\}) + KH)$ samples, and that no algorithm, even one that chooses where to sample, can do with fewer when $\epsilon \lesssim \min\{H, H^2/\beta\}$. For $\epsilon < \beta$ this is a $1/\epsilon$ rate with the same horizon dependence as unregularized RL. We also find the exact asymptotic constant of the plug-in estimator, a Fisher-weighted variance of the estimated soft Q-function. The estimator is locally asymptotically minimax among methods that sample every pair equally often, and we give the allocation of samples that is optimal among adaptive designs. Simulations on small MDPs match the rates and the constants.
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URL
https://arxiv.org/abs/2611.13480
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Off-target posterior mass: A training-free diagnostic for fine-tuning spoken language diarization probes
2026-11-10 01:15:31Zhuoyan Tao, Aditya Kommineni, Shrikanth NarayananAbstract
Spoken Language Diarization (SLD) models provide frame-level language information of a speech recording. SLD modeling pipeline includes feature extraction from pre-trained speech models followed by clustering. Fine-tuning pre-trained speech models has shown performance gains for SLD with its magnitude being dataset dependent. Off-target Posterior Mass (OTPM), computed based on posterior language identification probabilities is proposed as a diagnostic metric to forecast performance gains from SLD fine-tuning. OTPM obtains positive correlation with probe gains, 0.56 on unseen synthetic bilingual data and 0.23 on real-world corpora. These results indicate promising potential of OTPM as a diagnostic metric for SLD.
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URL
https://arxiv.org/abs/2611.13430
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BioMem: Agentic Memory for Biomedical LLM Agents
2026-11-10 01:09:11Mingchen Li, Yongkang Xiao, Rumeng Li, Rui Zhang, Hong YuAbstract
Large language models (LLMs) have demonstrated considerable potential in biomedical applications, while agentic memory systems have emerged as a promising approach to preserving and utilizing information across tasks and interactions. However, a fundamental question remains: how effectively and reliably do these systems retain, retrieve, update, and utilize biomedical information? In this study, we systematically investigate agentic memory in the biomedical domain, focusing on task effectiveness, retrieval quality, information fidelity, and long-term robustness. We evaluate five memory approaches across four LLMs in three representative settings: biomedical knowledge reasoning, clinical prediction, and long-term conversational memory. Our analyses reveal how memory construction, evidence relevance, and conversational history shape downstream biomedical performance, highlighting the distinct challenges of retrieving relevant information, preserving its fidelity, and effectively utilizing it for reasoning. Building on these findings, we introduce Hybrid Memory Retrieval and Utilization (HMRU), a training-free framework that jointly enhances evidence accessibility and task-aware utilization to improve biomedical reasoning and long-term conversational memory. HMRU achieves an average relative improvement of 8.6% across biomedical question-answering and conversational memory benchmarks, with additional gains in selected clinical prediction tasks. It further reduces conversational answer errors by 24.9% and closes 48.0% of the performance gap to full-context inference. Our findings provide a systematic characterization of biomedical agentic memory and practical insights into developing more effective and reliable memory-augmented LLM systems.
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URL
https://arxiv.org/abs/2611.13426
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Prompt2Echo : Text-Prompted Multi-View Echocardiography Segmentation with One Model
2026-11-10 01:08:01Moein Heidari, Alvin Kimbowa, Mahdi Tabatabaei, Afshin Bozorgpour, Sina Ghorbani Kolahi, River Jiang, Wenjin Chen, David J. Foran, Jasmine Grewal, Dorit Merhof, Ilker HacihalilogluAbstract
Automated segmentation in multi-view echocardiography is essential for comprehensive cardiac assessment, yet remains challenging due to substantial anatomical and appearance variability across standard acoustic windows. In this paper, we present P2Echo, a unified framework capable of segmenting diverse cardiac structures across multiple standard echocardiographic views using a single model controlled by structured view-aware text prompts. Unlike recent foundation model adaptations that rely on implicit latent priors, P2Echo explicitly conditions the segmentation process via a novel Dynamic Image-Text Alignment (DyITA) module. DyITA integrates a differentiable routing mechanism and token differential operators to dynamically modulate decoder features according to the requested view and target structure. This allows the network to adaptively switch its processing pathways for different views without architectural changes. Extensive experiments on a large-scale internal dataset (seen during training) and held-out evaluation on three external datasets demonstrate that P2Echo matches or exceeds both view-specific specialists and state-of-the-art universal models at a fraction of their computational cost, offering an efficient, controllable solution for multi-plane cardiac analysis. Code is available at: this https URL.
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URL
https://arxiv.org/abs/2611.13425
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Knowing When to Intervene: Causal Evaluation of AI Agents
2026-11-10 00:34:33Ayush Sawarni, Wenqian Xing, Tijana Zrnic, Ramesh Johari, Vasilis SyrgkanisAbstract
Current evaluations of agentic AI systems primarily rely on benchmarks. However, the static nature of benchmarks makes them uninformative about the value of auditing interventions at deployment time. For reliable deployment, we often need to determine within an agent's trajectory whether or not to intervene, e.g., by verifying the agent's current output or steering it toward different behavior, using either human review or more costly models or time-consuming agentic supervision. The value of such interventions is fundamentally a causal inference question, asking whether the causal effect of such an intervention is beneficial for the final outcome. Estimating this causal effect is particularly challenging due to the dynamic nature of the problem: the impact of an intervention depends on the current context and environment, as well as the agent's future behavior. We develop the first methodologically grounded framework for evaluating the causal effects of randomized interventions within agent trajectories. By leveraging a relatively small dataset of agent trajectories collected under randomized interventions such as verification or screening, we can estimate the dynamic causal effect of a rich class of (contextual) intervention policies. The structural parameters that we estimate can also be used to construct safety leaderboards that capture the risk of various agentic actions, which can be used by practitioners for audit prioritization. Applying our methods to tau-bench Retail, ToolSandbox, and ImpossibleBench, we find that intervention effects vary substantially across agent actions and states. More broadly, our work suggests a rich research agenda at the intersection of causal inference and agentic evaluation, which we believe is essential for the reliable and safe deployment of AI agents in the real world.
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URL
https://arxiv.org/abs/2611.09792
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Living constitutions: Participatory alignment for sovereign foundation models
2026-11-10 00:32:24Stine Lyngs{\o} Beltoft, Jonas Vistrup, Peter Schneider-Kamp, Lukas Galke PoechAbstract
In Constitutional AI, a plain-text "constitution" encodes values and gets incorporated into a model via post-training. However, the procedure for creating such a constitution poses significant challenges: who contributes, who decides which norms are included, and to what extent must the process be participatory or democratic? These challenges can be paralyzing. Yet, we argue that taking action is essential: without a deliberate constitution, sovereign models would risk misalignment or default to norms set by frontier model providers. We propose treating the development of a constitution as an evolving, participatory process akin to citizen science, iteratively drafted, tested, and refined. We therefore formulate five desirable principles: iterative, modular, justifiable, positional, and legitimate. We further argue that such a document must remain responsive not only over time but across the people it governs, and propose that provisions be marked as settled, contested, or underdetermined, so that durable disagreement is recorded in the constitution rather than resolved away. Empirically, we show via agent-based modelling that proposed process for maintaining living constitutions is robust against 50% bad actors among citizens - assuming a share of 75% participants with good intent in the deliberative body. This indicates that the proposed process tolerates a substantial share of adversarial participants.
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URL
https://arxiv.org/abs/2611.13402
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Online-Adaptive Fuzzy Cognitive Maps for Neuro-symbolic Financial Forecasting
2026-11-10 00:05:44Brandon Rodriguez, Abel Deulofeu, Olaoluwa AdigunAbstract
We present a neuro-symbolic framework that pairs online-adaptive Fuzzy Cognitive Maps (FCMs) with long short-term memory (LSTM) networks for financial forecasting. Financial markets exhibit regime shifts and nonlinear dynamics. Existing models often trade off one of these key properties: these models capture temporal patterns but hide causal drivers, or they recover causal graphs that cannot adapt post-training. We close this gap with two frameworks. Framework I constructs an FCM from live dual-source price series and macroeconomic indicators, and adapts its edges online through an error-driven Hebbian rule. We introduce the Asymmetric Additive Residual Fusion method to seamlessly combine the FCM and LSTM predictions under Framework I. Framework II constructs a literature-grounded, LLM-augmented FCM where every edge carries a verifiable citation that gives an auditable map of factor interactions. On NASDAQ Composite data, Framework I matched the performance of the LSTM baseline on state-directional accuracy and outperformed LSTM by 7.6 percentage points on the return-sign accuracy. Framework I outperformed standalone FCM models across both evaluation metrics. The adaptive maps converged to new regimes within 10-15 trading days, and Framework II center-node FCMs scored 68.9% to 85.7% on the state-directional accuracy.
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URL
https://arxiv.org/abs/2611.13388
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Discrete Model-Based Diffusion for Combinatorial Optimization in Multi-Robot Task Allocation
2026-11-09 23:59:47Haejoon Lee, Thomas Marshall Vielmetti, Xinyi Wang, Dimitra PanagouAbstract
Decision making in multi-agent and multi-robot systems often involves discrete decision variables, leading to NP-hard combinatorial optimization problems that must be solved within seconds for near real-time implementation. Denoising diffusion has emerged as a powerful tool for such problems, but existing approaches face a trade-off: Model-Based Diffusion (MBD) incorporates diffusion in sampling-based optimization (SBO) without training but only over continuous spaces, while existing diffusion-based combinatorial solvers operate over discrete spaces but require offline training. To this end, we propose Discrete Model-Based Diffusion (Discrete MBD), a training-free SBO method that directly optimizes discrete variables by approximating categorical reverse transition distributions through Monte Carlo sampling. We establish a finite-step lower bound on the probability of finding a global minimizer and show that this bound converges to one as the number of denoising steps increases. Extensive experiments on generic integer programs and heterogeneous multi-robot coalition formation and scheduling demonstrate that Discrete MBD outperforms SBO baselines in nearly all settings while achieving solution quality competitive with that of mixed-integer programming and reinforcement learning methods at a fraction of their computational cost.
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URL
https://arxiv.org/abs/2611.13382
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No finite rulebook can certify every safe program: an impossibility theorem for gatekeeping AI agents
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An AI assistant writes small programs, and a gatekeeper must decide, from the code alone, whether each one may run. Suppose the rules are fixed: never perform a forbidden action, never let the output depend on a secret, always answer eventually. Can two rulebooks, one listing what is allowed and one listing what is not, both be complete, if every rule must be backed by evidence that a machine can check in finite time? We prove that they cannot. Checkable evidence can only establish what a finite record settles, and ``never'' and ``eventually'' are never settled by a finite record. For prohibitions the failure is one-sided: every violation can be caught by watching, but no safe program can be cleared for good. For confidentiality and responsiveness, neither side can be. We characterise exactly which rules about visible behaviour evidence can confirm, and we show that any sound rulebook of $n$ bits omits a compliant program of about $n$ bits. A time limit makes everything checkable, but only by running the program for essentially the whole limit, so a finite machine is not a feasible one. Finally, we show what a gatekeeper can still guarantee: not a verdict on every program, but a checkable list that contains everything it must allow and nothing it must refuse. Simulations on 2.2 million random programs and on self-referential adversaries show that the obstruction is adversarial rather than typical, and that the one error a longer test never removes is the liveness part of confidentiality.
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URL
https://arxiv.org/abs/2611.13367
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A Technique to Model Product Information and User Reviews
2026-11-09 23:36:38Emna Belguith, Fajrian Yunus, Talel AbdessalemAbstract
Modern e-commerce platforms naturally provide three complementary modalities: textual item descriptions, item images, and user reviews. However, existing multimodal recommendation methods often omit reviews or do not integrate all three modalities within a unified framework. In this paper, we propose MPIUR, a multimodal graph-based recommendation model that encodes reviews in heterogeneous graphs, aligns image and text representations, and adapts collaborative--semantic alignment to item interaction density. Experiments on the Amazon Reviews 2023 Musical Instruments and Baby categories show that MPIUR achieves the best global nDCG@10 and Recall@10 among the evaluated methods on both datasets. It also obtains the best nDCG@10 and Recall@10 on sparse items, indicating that jointly exploiting reviews and multimodal item content is particularly useful when interaction histories are limited.
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URL
https://arxiv.org/abs/2611.13361
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ProTEUS: A mutation-resolved world model for closed-loop protein evolution
2026-11-09 23:19:33Yikun Zhang, Minghao Guo, Guangxue Xu, Peter Yichen Chen, Wojciech Matusik, Wengong Jin, Jingjing Chai, Kaiyi JiangAbstract
Protein engineering requires navigating rugged fitness landscapes, where small sequence changes can produce large functional differences, but experimental screening can only sample a small fraction of sequence space. Thus, a central challenge is to efficiently traverse the large combinatorial space of mutations in silico. We introduce ProTEUS, a mutation-resolved world model for closed-loop protein evolution. Pretrained on deep mutational scanning assays, ProTEUS learns a joint representation of sequence, evolutionary, and structural information using MutationFormer, a mutation-biased attention architecture. Variants are represented as states in this joint latent space, and mutations define actions whose functional consequences are predicted. To support exploration of many mutants, we developed a fast, physics-constrained all-atom predictor that utilizes explicit geometric constraint enforcement to achieve >10 fold increase in speed than AlphaFold3 with guaranteed physical validity. Lastly, ProTEUS refines its prediction and understanding of protein activity through closed loop experimental feedback to guide evolution toward a desired phenotype. ProTEUS surpasses established models in both zero-shot and supervised fine-tuning mutation prediction tasks. We experimentally demonstrate its utility in two closed-loop multi-objective engineering campaigns on aldehyde dehydrogenase and levansucrase, yielding variants with >10 fold higher activity than wild type. ProTEUS provides a world-model framework that connects virtual evaluation of mutational outcomes with experimental learning for efficient protein evolution.
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URL
https://arxiv.org/abs/2611.13348
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