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01.
arXiv (CS.AI) 2026-06-11

Agents All the Way Down; A Methodology for Building Custom AI Agents from Substrate to Production

arXiv:2606.11869v1 Announce Type: cross Abstract: Custom AI agents areagents that live inside their own application, talk to their own data and tools, enforce their own security boundaries, and carry their own brand and audit trail. What separates them from the general-purpose tier is fit, not capability: each is built for one job, by the engineer who will maintain it. No published practice sets out how to build one end to end. The pieces are everywhere (function-calling APIs, the Model Context Protocol, code agents to pair with), but the practice that chains them lives in podcasts, blogs, and leaked system prompts. This paper writes that practice down as a methodology, Agents All the Way Down: two preconditions crossed once and kept, then three practices repeated for the agent's life. The preconditions are (P1) Substrate, the LLM as a software component, framed as tools, then system, then messages under prompt-caching; and (P2) Building blocks: function calling, MCP, CLI orchestration, the liteshell pattern, the agent loop, skills, characters, hooks, and scaffolding. The practices are (P3) prototype with a general-purpose agent; (P4) harvest, fold, and ship the result as a CLI, the Turtle pattern; and (P5) agent-tests-agent, in which a general-purpose agent drives it through behavioural scenarios, a complement to classical testing, not a replacement. The working loop is P3 to P4 to P5 and back, and one corollary falls out for free: multi-agent orchestration is just CLI composition. The methodology is framework-free by construction. It was distilled from the AAC, a custom agent for the open-source LAMB platform, built in about ten days by one developer with an AI pair-programmer and in production . We present it as a transferable practice, independent of any language or framework.

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

Symplectic Transversality and Endpoint Green Estimates for Finite-Horizon Pontryagin Systems

arXiv:2606.17762v1 Announce Type: cross Abstract: We study horizon-uniform local branches of finite-horizon discrete-time Pontryagin boundary value systems after smooth control elimination. The central input is a two-point endpoint inverse for the linearization. We verify this inverse from scaled stable–unstable boundary transversality, prove the associated endpoint-corrected Green estimate, and combine it with weighted contractions to obtain existence, uniqueness, Lipschitz dependence, and first-order expansions with constants independent of the horizon. The framework covers smooth nonlinear endpoint maps, including the original Pontryagin rows that fix the initial state and couple the terminal costate to the terminal state. Symplectic and Riccati criteria verify the inverse hypothesis at the level of the matrix data; in particular, every stabilizable linear-quadratic system with invertible dynamics and definite weights is covered, including noncommuting coupled data. A numerical section illustrates the certificates and the horizon-uniform first-order expansion.

03.
arXiv (CS.CV) 2026-06-16

Geometric Action Model for Robot Policy Learning

Generalist robot policies must follow user instructions while reasoning about how objects, cameras, and robot actions interact in the 3D physical world. Recent vision-language-action models (VLAs) and video world-action models (WAMs) inherit strong semantic or temporal priors from large-scale foundation models, but they still operate primarily on 2D image frames or 2D-derived latent spaces, leaving implicit the 3D geometry required for contact-rich manipulation. We propose the Geometric Action Model (GAM), a language-conditioned manipulation policy that directly repurposes a pretrained geometric foundation model (GFM) as a shared substrate for perception, temporal prediction, and action decoding. GAM splits the GFM at an intermediate layer: the shallow layers serve as an observation encoder, and a causal future predictor inserted at the split layer forecasts future latent tokens conditioned on language, proprioception, and action history. The predicted future tokens are then routed through the remaining GFM blocks for feature propagation and decoding, allowing a single backbone to produce both future geometry and actions. This design equips the GFM with language-conditioned temporal world modeling through minimal architectural modification while preserving its rich geometric priors. Across a broad suite of simulation and real-robot manipulation benchmarks, GAM is more accurate, more robust, faster, and lighter than current foundation-model-scale baselines.

04.
arXiv (CS.LG) 2026-06-15

Operator Calculus for Population-Based Optimization: A Mean-Field Convergence Theory

arXiv:2606.14289v1 Announce Type: cross Abstract: Population-based and distributional optimization methods, from evolution strategies and consensus-based optimization to covariance-matrix adaptation and stochastic gradient methods viewed as distributional dynamics, are widely used for nonconvex or black-box problems, yet their convergence analyses remain fragmented across algorithm-specific techniques. We introduce an operator calculus in which a broad class of such methods, after choosing an appropriate state space and, where necessary, augmenting the state by memory or strategy variables, is described as a composition of three elementary operators (mutation, selection, and recombination) acting on probability measures. Under explicit stability and regularity conditions, the composite operator admits a pre-generator whose continuous-time limit is a transport-reaction-jump (TRJ) PDE that preserves the operator splitting. On this foundation we establish a modular Lyapunov principle. If a state-space Lyapunov function both dissipates under the full generator and controls the relevant search-space gauges, then the state-space Lyapunov functional and the induced search errors decay exponentially. The additive generator structure allows dissipation estimates to be assembled operator by operator, providing a toolkit for certifying convergence of composite mean-field algorithms.

05.
arXiv (CS.LG) 2026-06-17

Tacit Coordination of Large Language Models

arXiv:2601.22184v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) are increasingly deployed in multi-agent settings that require coordination without communication, from human-AI interaction to safety-critical scenarios. Humans often overcome the absence of communication through focal points: salient solutions that naturally stand out to all participants. We present the first large-scale evaluation of how, when, and why focal points emerge in LLMs, comparing their behaviour with humans across cooperative and competitive games, including realistic search and rescue scenarios, demonstrating when focal points enable effective coordination. Across more than 20 open- and closed-source models, we find that LLMs exhibit a remarkable ability to coordinate without communication, often matching or outperforming humans. However, the same models consistently fail in tasks requiring numerical common sense or culturally nuanced notions of salience. We additionally evaluate simple learning-free strategies that substantially improve coordination both among LLMs and between humans and LLMs. Our results reveal striking coordination capabilities, as well as social limitations in modern LLMs, and offer new insight into the latent notions of salience encoded within them. Our findings caution against assuming that LLMs share humans' cultural and perceptual substrate when deployed in coordination settings.

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

Engineering Robustness into Personal Agents with the AI Workflow Store

arXiv:2605.10907v3 Announce Type: replace-cross Abstract: The dominant paradigm for AI agents is an "on-the-fly" loop in which agents synthesize plans and execute actions within seconds or minutes in response to user prompts. We argue that this paradigm short-circuits disciplined software engineering (SE) processes – iterative design, rigorous testing, adversarial evaluation, staged deployment, and more – that have delivered the (relatively) reliable and secure systems we use today. By focusing on rapid, real-time synthesis, are AI agents effectively delivering users improvised prototypes rather than systems fit for high-stakes scenarios in which users may unwittingly apply them? This paper argues for the need to integrate rigorous SE processes into the agentic loop to produce production-grade, hardened, and deterministically-constrained agent *workflows* that substantially outperform the potentially brittle and vulnerable results of on-the-fly synthesis. Doing so may require extra compute and time, and if so, we must amortize the cost of rigor through reuse across a broad user community. We envision an *AI Workflow Store* that consists of hardened and reusable workflows that agents can invoke with far greater reliability and security than improvised tool chains. We outline the research challenges of this vision, which stem from a broader flexibility-robustness tension that we argue requires moving beyond the ``on-the-fly'' paradigm to navigate effectively.

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

MamBOA: State-Space Architecture for Video Recognition

Fine-grained action recognition demands temporal reasoning that general-purpose architectures address through different cost-accuracy tradeoffs: 3D dense operators couple computation to the input volume, while difference-based methods approximate motion through rigid, hand-crafted subtraction of uncontextualized features - each reflecting a deliberate design choice with corresponding limitations in expressiveness or flexibility. We present MamBOA, a backbone-agnostic temporal framework built upon a novel interleaved scan structure that recasts the selective state-space recurrence (S6) as a native motion synthesizer. By interleaving consecutive feature representations extracted from a pretrained backbone into a single alternating sequence, the proposed scan structurally drives the recurrence to encode both temporal observations of each position within a shared hidden state, separated by only a single decay step - rendering the inter-frame transition an intrinsic component of the state dynamics rather than an externally computed quantity. A cascade of dedicated alignment and decoding operations then distills this joint encoding into an explicit motion representation, which a dual-path pooling mechanism adaptively aggregates by balancing attention-driven selection with uniform temporal coverage. The framework interfaces seamlessly with CNN, Transformer, and Mamba backbone families, adding only ~2.1 GFLOPs per feature pair. On Diving48, MamBOA achieves 85.02% Top-1 accuracy with an image-pretrained backbone and 86.24% with a video-pretrained backbone processing the entire video in a single forward pass - demonstrating that structurally induced state-space dynamics constitute a principled and general foundation for motion modeling.

08.
arXiv (CS.LG) 2026-06-18

Structural MRI Synthesis for Alzheimer's Disease via Conditional Diffusion on Anatomical Masks

arXiv:2606.18354v1 Announce Type: cross Abstract: Recent advances in generative machine learning models have significantly improved medical imaging, offering promising solutions for data augmentation, privacy preservation, and improved model generalization. However, synthesizing high-quality structural MRI data for Alzheimer's Disease (AD) remains challenging due to the subtle, region-specific, and progressive anatomical changes associated with neurodegeneration. In this paper, we extend the Med-DDPM conditional diffusion model – originally designed for brain tumor synthesis – to generate 3D structural MRIs specifically tailored to AD. We adopted Med-DDPM due to its established stability and structural fidelity compared to other generative models, which makes it particularly suitable for capturing the subtle anatomical changes characteristic of AD. Our approach conditions the diffusion process on anatomical segmentation masks derived from the ADNI dataset, incorporating key AD-relevant brain structures into the generation process. We systematically evaluate the quality and utility of the synthetic images by training segmentation models on real, synthetic, and hybrid (mixed) datasets. Experimental results demonstrate that segmentation models trained exclusively on synthetic data achieve comparable Dice scores (0.6532) to those trained on real data (0.6513), while exhibiting significantly enhanced recall. Notably, models trained on hybrid datasets (mixing real and synthetic images) outperform both real and synthetic-only baselines, achieving a Dice score of 0.7244. These findings underscore the successful use of conditional diffusion models for generating anatomically accurate, AD-specific synthetic MRIs, and highlight their potential for enhancing training data availability, improving diagnostic accuracy, and promoting research reproducibility in neuroimaging studies.

09.
PLOS Medicine 2026-05-06

Pathways of emergency care for severely ill children in Nigerian and Ugandan hospitals: A process mapping study

作者:

by Rami Subhi, Abiodun Sogbesan, Dan Muramuzi, Mikael Burhin, Ayobami A. Bakare, Adegoke G. Falade, Freddy E. Kitutu, Freddie Ssengooba, Carina King, Sumit Kane, Belinda Dawson-McClaren, Hamish R. Graham, the MOXY-Implementation Research Collaboration Background Child mortality remains high in countries with weak emergency care systems. Facility organisation for paediatric emergency care is heterogeneous and under-described. We examined how hospitals in Uganda and Nigeria are organised to deliver emergency care for neonates and children. Methods and findings We conducted a qualitative, multi-method study in 26 purposively selected secondary and tertiary facilities in Uganda and Nigeria from October 2023 to December 2024. Embedded researchers documented patient pathways, resources for care, and care processes for severely ill children (

10.
Nature (Science) 2026-06-10

Two-component exciton condensates in an electron–hole bilayer

作者:

Macroscopic quantum coherence emerges when bosons condense into a Bose–Einstein condensate (BEC)1–5. Excitons are a long-sought solid-state route to high-temperature BECs with strong interactions, electrical tunability and potentially multicomponent spinor order, but conclusive evidence for equilibrium condensation has remained elusive. Here we report evidence for two-component exciton BECs in MoSe2/hBN/WSe2 electron–hole bilayers6–9 by probing the spin–valley susceptibility of constituent electrons and holes. This heterostructure hosts equilibrium exciton fluids with four spin–valley flavours. Magneto-optical spectroscopy in a dilution refrigerator reveals three exciton condensate phases with distinct flavour polarizations. At zero magnetic field, the many-body ground state is a coherent superposition of two condensed intravalley exciton flavours. Under a magnetic field, the intravalley exciton condensate first switches to a two-component intervalley condensate through a first-order quantum phase transition at a weak critical field and then turns into a fully polarized single-component condensate at high fields. The condensate signatures form a dome in density–temperature space, persisting up to approximately 1.8 K. Our results establish van der Waals electron–hole bilayers as a versatile platform for strongly interacting, multicomponent exciton BECs. Macroscopic quantum coherence arises in two-component exciton Bose–Einstein condensates within MoSe2/hBN/WSe2 electron–hole bilayers, exhibiting distinct spin–valley polarized phases, quantum phase transitions under magnetic fields and stable condensate behaviour up to approximately 1.8 K.

11.
arXiv (CS.CV) 2026-06-12

Efficient, Robust, and Anti-Collusion Fingerprinting of Image Diffusion Models

Model fingerprinting, embedding user-specific identifiers (fingerprints) into generated outputs, has recently emerged as a popular solution to protect the intellectual property rights (IPR) of generative text-to-image (T2I) models and prevent unauthorized redistribution. In this work, we reveal a previously unexplored systematic vulnerability in existing generative model fingerprinting methods: they lack robustness against collusion attacks, where multiple attackers combine their models to remove or obscure the fingerprints. To address this issue, we take the first step towards a robust fingerprinting method for T2I models with anti-collusion capabilities. The proposed method encodes strings of bits, namely fingerprints, into the coefficients of a personalized normalization module (PNM) incorporated into T2I models, so that fingerprints can be reliably recovered from any generated image. To defend against collusion attacks and prevent unauthorized model redistribution, we introduce an anti-collusion mechanism based on lossless function-invariant parameter transformations. This mechanism significantly degrades the image generation quality of colluded models, making them effectively unusable. Moreover, our method allows developers to efficiently create multiple copies of fingerprinted T2I models by reparameterizing the PNM without the need for retraining. We also introduce a worst-case optimization strategy to improve robustness against model-level attacks. Our experiments demonstrate that the proposed method achieves high fidelity and robustness across multiple T2I image generation and editing tasks, with fingerprint extraction accuracy exceeding 99.5%. Compared with existing methods, our method demonstrates, for the first time, a notable proactive robustness to collusion attacks by significantly increasing the FID of colluded models.

12.
arXiv (CS.LG) 2026-06-11

Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

arXiv:2606.08493v2 Announce Type: replace-cross Abstract: Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

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

The Reward Was in Your Data All Along: Correcting Flow Matching with Discriminator-Guided RL

Score- and flow-matching models often rely on preference-based reinforcement learning for two purposes: aligning with subjective preferences and, surprisingly, recovering properties such as visual realism and coherent object structure that matching-based training is intended to learn from the data itself. We argue that this reflects a structural mismatch. Matching losses measure $\ell_2$ regression error on the velocity or score field under training-time marginals, a proxy poorly aligned with the visual and semantic properties that determine sample quality at inference. Given a reward aligned with these properties, RL sidesteps the mismatch by evaluating the model on its own samples and following the reward landscape directly. The challenge is to obtain such a reward without relying on human preferences, which are expensive and conflate data realism with annotator inclinations. We propose Discriminator-Guided RL (DRL). DRL trains a discriminator to separate data from base-model samples in a pretrained representation space and uses its logit as the reward in KL-regularized RL. The pretrained space restricts the discriminator to perceptually meaningful directions, and the logit estimates the log-likelihood ratio between data and model, which is the optimal reward for targeting the data distribution. Across SiT, JiT, REPA, and RAE, DRL reduces guidance-free FID (e.g., $9.38 \to 2.62$ on SiT) and semantic-space FD (e.g., $88.2 \to 19.3$ on DINOv3 for SiT), with consistent gains across all backbones, and improves human-preference rewards without training on them. It also yields a better Pareto frontier between preference reward and image fidelity under subsequent preference-based post-training, increasing alignment while reducing low-level artifacts such as oversaturation and excessive brightness.

14.
arXiv (CS.LG) 2026-06-15

Classification of Astronomical Spectra Using PCA-Compressed Flux and Inverse-Variance Features

arXiv:2606.13978v1 Announce Type: cross Abstract: This paper evaluates a signal-processing and supervised-learning pipeline for classifying SDSS DR17 astronomical spectra into stars, galaxies, and quasars. Each spectrum is represented by its measured flux and inverse-variance information, combining spectral shape with a wavelength-dependent reliability profile. After resampling onto a common logarithmic wavelength grid, the flux and inverse-variance vectors are standardized and separately compressed using principal component analysis. The resulting components are concatenated and used to train several classifiers. The best performance was obtained with the LightGBM gradient-boosting classifier, reaching $94.6\%$ accuracy and $92.1\%$ balanced accuracy on the test set.

15.
bioRxiv (Bioinfo) 2026-06-11

SPARK: A Systems-level Computational Framework for Reconstructing Transcriptomic State Organisation in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) exhibits substantial molecular heterogeneity, which complicates tumour stratification and limits the ability of mutation-centric models to capture tumour behaviour and predict patient outcomes. This study investigates whether coordinated transcriptomic programs can provide a systems-level representation of tumour states. Bulk RNA-sequencing data from the TCGA-LUAD cohort were analysed to reconstruct pathway-level transcriptomic organisation using a stability-optimised network framework (SPARK). This analysis identified eight transcriptomic modules representing coordinated biological processes active across tumours. Module activity scores were subsequently used to derive a composite Transcriptomic Risk Score through elastic-net Cox proportional hazards modelling. The resulting risk score showed a significant association with overall survival in the discovery cohort and improved prognostic discrimination beyond clinical variables. An independent evaluation in the CPTAC-LUAD cohort confirmed the prognostic signal and preserved risk stratification across patient groups. Unsupervised clustering of module activity further revealed three transcriptomic patient groups characterised by distinct biological programs, genomic alteration patterns, and survival outcomes. Single-cell analysis also demonstrated that the identified transcriptomic modules reflect coordinated organisation of the tumour-immune-stromal ecosystem across cellular compartments. Together, these findings suggest that LUAD heterogeneity can be organised into coordinated transcriptomic programs with measurable clinical relevance, providing a systems-level framework for representing tumour molecular states.

16.
arXiv (CS.LG) 2026-06-15

Efficient On-Device Diffusion LLM Inference with Mobile NPU

arXiv:2606.13740v1 Announce Type: new Abstract: Diffusion large language models (dLLMs) accelerate generation by denoising multiple tokens in parallel, making them attractive for latency-sensitive mobile inference. However, repeated denoising introduces substantial computation on smartphones. Mobile neural processing units (NPUs) offer high-throughput dense matrix computation, but efficiently exploiting them remains challenging: token commitment shrinks per-block effective workloads, token revision complicates KV cache reuse, and limited NPU-visible address space incurs costly remapping and data transfer overheads. In this paper, we propose llada.cpp, the first NPU-aware inference framework for accelerating dLLMs on smartphones. llada.cpp aligns block-wise dLLM inference with the execution characteristics of mobile NPUs through three techniques. (1) Multi-Block Speculative Decoding fills the shrinking workload in late-stage current-block decoding with speculative future-block tokens. (2) Dual-Path Progressive Revision keeps committed tokens revisable until stable and refreshes unstable tokens through a CPU-side path without stalling dense NPU execution. (3) Swap-Optimized Memory Runtime compacts NPU-visible address layouts and overlaps data staging with NPU computation to reduce remapping and transfer overheads. We implement llada.cpp as an end-to-end framework and evaluate it across diverse hardware platforms and dLLM workloads. llada.cpp reduces LLaDA-8B generation latency by 17x-42x over the CPU baseline with prefix KV cache reuse, while preserving generation quality.

17.
arXiv (CS.AI) 2026-06-18

Signals of Provenance: Practices & Challenges of Navigating Indicators in AI-Generated Media for Sighted and Blind Individuals

arXiv:2505.16057v2 Announce Type: replace-cross Abstract: AI-Generated (AIG) content has become increasingly widespread by recent advances in generative models and the easy-to-use tools that have significantly lowered the technical barriers for producing highly realistic audio, images, and videos through simple natural language prompts. In response, platforms are adopting provable provenance with platforms recommending AIG to be self-disclosed and signaled to users. However, these indicators may be often missed, especially when they rely solely on visual cues and make them ineffective to users with different sensory abilities. To address the gap, we conducted semi-structured interviews (N=28) with 15 sighted and 13 BLV participants to examine their interaction with AIG content through self-disclosed AI indicators. Our findings reveal diverse mental models and practices, highlighting different strengths and weaknesses of content-based (e.g., title, description) and menu-aided (e.g., AI labels) indicators. While sighted participants leveraged visual and audio cues, BLV participants primarily relied on audio and existing assistive tools, limiting their ability to identify AIG. Across both groups, they frequently overlooked menu-aided indicators deployed by platforms and rather interacted with content-based indicators such as title and comments. We uncovered usability challenges stemming from inconsistent indicator placement, unclear metadata, and cognitive overload. These issues were especially critical for BLV individuals due to the insufficient accessibility of interface elements. We provide practical recommendations and design implications for future AIG indicators across several dimensions.

18.
arXiv (quant-ph) 2026-06-12

Quantum optical photoelectron interferometry

arXiv:2606.13447v1 Announce Type: new Abstract: We present a general theoretical framework for multiphoton processes driven by quantum light fields, establishing a direct link between photon statistics and photoelectron observables. Our results show that the autocorrelation and cross-correlation functions, which quantify the underlying photon statistics, are directly mapped onto the resulting photoelectron spectra. Although our framework is broadly applicable, we demonstrate specifically in the example of reconstruction of attosecond beating by interference of two-photon transitions (RABBIT) the influence of the light statistical properties. In this approach, the amplitude, contrast and phase of the oscillations of the sideband signal as a function of pump-probe delay reveal the quantum nature of light. We analyze these observables across several quantum configurations, including correlated infrared and harmonic modes, as well as the uncorrelated case with non-classical harmonic statistics, thereby establishing a general framework for quantum-light RABBIT spectroscopy. We compare the analytical theory with numerical simulations for the case of classical harmonics and an infrared field in a squeezed coherent state, obtaining excellent agreement. Our results reveal how the interplay between classical and quantum correlations dictates the coherence of the photoemission process, providing a new window into the quantum-optical foundations of attosecond science.

19.
medRxiv (Medicine) 2026-06-18

Intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion (MeVO-TNK): Study rationale and design

Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

20.
arXiv (CS.AI) 2026-06-11

Sparse probes and murky physics: a case study of interpretability challenges in a foundation model for continuum dynamics

arXiv:2606.11657v1 Announce Type: cross Abstract: Generative AI emulators are increasingly used in scientific domains where we already have strong theory, benchmarks, and physical intuition. This raises a central evaluation and interpretability question: when a foundation-style model can reproduce known continuum dynamics, what internal mechanism supports that behavior, is the internal behaviour consistent with known physics, and how does it relate to where the emulator succeeds or fails? We investigate a cross-domain foundation model for continuum dynamics, Walrus by Polymathic, using mechanistic interpretability guided by physical principles. We apply a sparse autoencoder (SAE) to probe a selected layer, and address the practical challenge of triaging a large feature set (over 20,000) using enstrophy as a physically grounded metric. As a deliberately simple testbed, we focus on shear flow and compare feature recruitment across multiple shear-flow setups, i.e. parameter values in the numerical simulation. Across setups we find evidence of piecewise consistency, with subsets of features recurring in similar roles, but this structure is intermittent and does not map cleanly onto standard physical decompositions. In parallel, direct comparisons between numerical simulation and the emulator reveal systematic output-level discrepancies, including regimes where energy/structures become too diffuse or too localized. We connect parts of these discrepancies to changes in specific SAE feature usage. Our work highlights open questions for scientific foundation models: how to robustly prioritize mechanistically meaningful features, how to separate stable structure from analysis artifacts (including single-layer and SAE limitations), and how to use established benchmarks to decide when "different" internal representations are genuinely informative rather than merely effective.

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

Unsafer in Many Turns: Benchmarking and Defending Multi-Turn Safety Risks in Tool-Using Agents

LLM-based agents are becoming increasingly capable, yet their safety lags behind. This creates a gap between what agents can do and should do. This gap widens as agents engage in multi-turn interactions and employ diverse tools, introducing new risks overlooked by existing benchmarks. To systematically scale safety testing into multi-turn, tool-realistic settings, we propose a principled taxonomy that transforms single-turn harmful tasks into multi-turn attack sequences. Using this taxonomy, we construct MT-AgentRisk (Multi-Turn Agent Risk Benchmark), the first benchmark to evaluate multi-turn tool-using agent safety. Our experiments reveal substantial safety degradation: the Attack Success Rate (ASR) increases by 16% on average across open and closed models in multi-turn settings. To close this gap, we propose ToolShield, a training-free, tool-agnostic, self-exploration defense: when encountering a new tool, the agent autonomously generates test cases, executes them to observe downstream effects, and distills safety experiences for deployment. Experiments show that ToolShield effectively reduces ASR by 30% on average in multi-turn interactions. Our code is available at https://github.com/CHATS-lab/ToolShield.

22.
medRxiv (Medicine) 2026-06-22

Rare loss-of-function variants in POLD1, PMS1 and FAN1 modify age at onset of motor symptoms in Huntington's disease

Huntington's disease is a rare neurodegenerative disease whose primary risk factors are inherited expansions of a CAG repeat tract in the HTT gene. Somatic expansion of these tracts leads to neuronal toxicity, neuronal death and clinical disease progression. To identify genetic factors with a major impact on disease onset and progression, we genome sequenced 18,825 individuals for the ENROLL-HD study. Our results show rare inactivating mutations in three genes, all involved in DNA damage repair, are major determinants of age of onset for motor symptoms (n=10,610) and other clinical manifestations. Heterozygote carriers of predicted loss-of-function (pLoF) variants in POLD1 and PMS1 developed motor symptoms an average 20 years (n=3; P=1x10-5) and 7 years (n=6; P=2x10-3) later than non-carriers, respectively. Conversely, heterozygote carriers of pLoF variants in FAN1 (n=30) developed symptoms 10 years earlier (P=2x10-10). Our findings highlight therapeutic strategies and help predict age of onset for at-risk individuals.

23.
arXiv (CS.CV) 2026-06-18

Physics-IQ Verified

Video generative models ( VGMs) have become a new frontier that can be used not just for video generation but for a multitude of downstream tasks, including world modeling. To advance these tasks, a good video model must understand the physical reality of the world. Evaluating this understanding is an emerging field and has led to the Physics-IQ benchmark, which quantifies this explicitly by comparing model-generated videos to real-world videos of physical experiments. In this work, we present a systematic audit of the Physics-IQ benchmark, expose shortcomings and propose three solutions that sharpen how we can measure physical understanding of VGMs. Specifically, we improve prompt and ground-truth quality to reduce the influence of confounding factors and further introduce a sample-level scoring system that weights each sample and metric equally. Our resulting benchmark, Physics-IQ Verified, refines 57.6\% of all samples and improves over 34.8\% of prompts. In a comparison study using six image-to-video generative models, we observe moderate but meaningful ranking changes (Kendall's $\tau = 0.46$). We hope Physics-IQ Verified advances the community by providing a more reliable signal toward physically accurate VGMs. The code for the benchmark can be accessed at https://github.com/google-deepmind/physics-iq-benchmark

24.
medRxiv (Medicine) 2026-06-16

Validating an Early Pregnancy HbA1c as the Screening Test for Gestational Diabetes Mellitus: Findings from PRISMA Pakistan Cohort

Background: Early identification of gestational diabetes mellitus (GDM) is critical to improving maternal and neonatal outcomes, particularly in resource-constrained settings where universal oral glucose tolerance testing (OGTT) is burdensome. We assessed whether early-pregnancy HbA1c alone or combined with common risk factors can predict GDM and reduce the burden of OGTT requirements in a peri-urban cohort in Karachi, Pakistan. Methods: We conducted a secondary analysis of the Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA) Pakistan cohort. Women enrolled before 20 weeks' gestation with available early-pregnancy HbA1c and a 2-hour 75g OGTT at 24 to 28 weeks were included. We externally validated GDM prediction models originally developed in the STRiDE-India cohort. Model performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). We assessed four models: HbA1c alone (Model 1a); age, BMI, and family history of diabetes mellitus (FH DM) (Model 1b); HbA1c combined with age, BMI, and FH DM (Model 2); and an extended model, i.e., Model 2 combined with socioeconomic status, gestational age, parity, systolic and diastolic blood pressure (Model 3). A dual-threshold approach was applied to assess rule-in and rule-out performance. Results: Among 2,489 women, GDM incidence was 7.5% (n=186). Models with a broader set of predictors demonstrated higher AUC values, with Model 2 achieving an AUC of 0.61 (95% CI: 0.57, 0.66). Including additional factors (Model 3) did not further improve predictive ability (AUC: 0.62; 95% CI: 0.58, 0.66). In addition, at predefined thresholds, Model 2 achieved sensitivity of 73.7% (rule-out) and specificity of 83.5% (rule-in), with the potential to reduce OGTT requirements (58.5%). Conclusions: Early-pregnancy risk stratification using HbA1c combined with simple clinical predictors offers a pragmatic approach to streamline GDM screening among high-risk pregnant women. A dual-threshold strategy using Model 2 could reduce reliance on universal OGTT while prioritizing high-risk women for confirmatory testing.

25.
arXiv (CS.CV) 2026-06-19

Efficiently Linking Real Scenes with Synthetic Data Generation for AI-based Cognitive Robotics and Computer Vision Applications

AI vision models are a driving factor for the potential use case scenarios of cognitive robotics within in the industry and household applications. A large array of methods from semantic environment analysis towards 6D and grasping pose estimation have been proposed based on the latest AI achievements. However, such advancements require further strong and efficient methods w.r.t. training data and AI-architectures, which are capable in synergy to tackle current challenges, precision limits, and scalability beyond domain gaps. In this paper, we discuss these current limits and trends in the related state-of-the-art which are challenging those. Further we discuss our current work in progress on bridging the domain gap between simulations and real world applications by linking those in the training data generation.