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01.
arXiv (CS.CV) 2026-06-15

Hierarchical Consistency Learning for Test-time Adaptation in Camouflage Perception

Camouflaged object detection (COD) aims to localize targets that exhibit minimal perceptual differences from backgrounds through physical attributes. Existing methods, constrained by the static train-then-freeze paradigm, suffer from domain rigidity and annotation dependency, limiting their adaptability to scene variations and unseen camouflage patterns. To overcome these, we propose the hierarchical consistency learning (HCL) framework, which integrates test-time adaptation for dynamic representation recalibration. Specifically, we design the hierarchical representation reconstruction (HRR) to alleviate feature entanglement by synergizing spatial reconstruction with dual-stream frequency-domain decomposition, enhancing robustness against appearance homogenization. The pixel and spectrum inference provide structural and contextual priors. We further introduce task affinity guidance (TAG) to propagate knowledge across branches via channel-wise affinity, aligning local discriminative cues and mitigating semantic drift. To ensure semantic invariance, we formulate the prototype consistency calibration (PCC), which aggregates region features into compact prototypes and establishes prototype-feature similarity. This imposes implicit and hierarchical constraints that bridge task and representation gaps. Extensive experiments across four camouflaged and four underwater object benchmarks, under three degradation settings, demonstrate that our method consistently outperforms state-of-the-art approaches, highlighting its robustness and generalization under distribution shifts.

02.
arXiv (CS.LG) 2026-06-18

Starter-Iterator Neural Operator: A Unified Architecture for High-Fidelity Forward and Inverse PDE Problems

arXiv:2606.18305v1 Announce Type: cross Abstract: Operator learning is an emerging interdisciplinary field that integrates machine learning with scientific computing. By mapping infinite-dimensional function spaces, this approach provides an efficient surrogate modeling framework for high-dimensional partial differential equations (PDEs). Compared to traditional numerical solvers, it achieves a superior trade-off between computational complexity and approximation accuracy, demonstrating significant advantages in many-query tasks such as real-time prediction and parameter sweeps. Given the stringent accuracy requirements of both forward simulation and inverse inference, as well as the precision bottlenecks of existing operator learning methods in handling complex boundaries or long-term evolution, we propose the Starter-Iterator Neural Operator (SINO). Our framework reinterprets the initialization strategies and iterative formats of traditional iterative methods through neural networks, establishing an efficient approach for spectral-spatiotemporal collaborative modeling. Specifically, the frequency-domain initialization module captures globally stable low-frequency features, while the time-domain learning module focuses on optimizing local solution residuals, thereby effectively overcoming the inherent limitations of conventional single-domain modeling approaches. Extensive experiments on typical dynamical systems such as the Navier-Stokes equations and acoustic wave equations, as well as practical applications including super-resolution imaging and weather forecasting, demonstrate that SINO achieves outstanding performance in numerical accuracy, generalization capability, and robustness.

03.
arXiv (CS.CL) 2026-06-18

SAGE: Stochastic Prompt Optimization via Agent-Guided Exploration

Context engineering has emerged as a primary lever for improving AI systems without parameter updates. Recent work showing that textual gradients do not function as real gradients motivates treating automatic prompt optimization (APO) as black-box search. We introduce SPO (Stochastic Prompt Optimization), a framework for stochastic search over prompt space, and compare three strategies of increasing sophistication: error-informed random search, a genetic algorithm with evolutionary operators, and SAGE (SPO via Agent-Guided Exploration), a multi-agent pipeline with diagnostic code execution. Across three benchmarks, no single strategy dominates; effectiveness depends on the interaction of landscape structure with error type. We further deploy SAGE on a mental-health chatbot under a continuous optimization paradigm, where it compounds eight cycles of individually-noisy A/B tests into a statistically robust gain in next-day retention. We argue that coupling qualitative diagnosis with quantitative validation is what makes agentic optimization effective for open-ended task-oriented dialogue.

04.
medRxiv (Medicine) 2026-06-17

Silent Manipulation of Mental Health Treatment Recommendations from a Large Language Model

Importance. Large language models (LLMs) increasingly inform mental health decisions by patients and clinicians. Inference-time activation steering can shift model behavior on a target dimension without altering weights or prompts and without disclosure to users, allowing treatment recommendations to be silently changed for commercial or ideological reasons. Objective. To determine whether directional activation steering can shift an open-weights LLM's depression treatment recommendations. Design, Setting, and Participants. This non-human subjects study applied directional activation steering to an open-weights LLM (DeepSeek V4 Flash) responding to 12 depression-advice scenarios (4 favoring medication, 4 favoring avoidance, 4 neutral), generated at 30 amplitudes from -1.5 to +1.5 in 0.1 increments plus an unsteered baseline. Exposures. A single steering direction contrasting antidepressant medication with self-directed approaches (diet, exercise, meditation, dietary supplements), constructed from 16 paired training prompts and applied at the attention output of every transformer block; weights and system prompt were held constant. Main Outcomes and Measures. The extent to which medication and four self-care categories were addressed, scored 0 to 3 by a human-validated LLM rater (Claude Opus 4.7), the medication-versus-self-care balance, and clinician referral, estimated per unit of amplitude using mixed-effects models with a scenario random intercept. Results. Across 372 generations, steering produced a graded, dose-dependent shift in the medication-versus-self-care balance, which declined by 0.32 per unit of amplitude (beta=-0.32; 95% CI, -0.39 to -0.25; P < .001); medication extent fell and self-care extent rose. The shift was largest for scenarios with no stated treatment preference (beta = -0.44; 95% CI, -0.54 to -0.34; P < .001). A clinician referral appeared in 322 of 372 responses (87%) and did not vary with steering amplitude (P = .63). Conclusions and Relevance. In this open-weights LLM providing depression treatment information, inference-time activation steering shifted treatment recommendations without altering weights, prompt structure, or safety outputs, with the largest effect among users expressing no treatment preference. These findings suggest a need for LLM disclosure standards and independent auditing as such models inform clinical decisions.

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

GRACE-DS: a Guarded Reward-guided Agent Correction Environment in Data Science

We introduce GRACE-DS, a Guarded Reward-guided Agent Correction Environment in Data Science for pre-deployment evaluation of LLM-powered AutoML agents. GRACE-DS is a set of evaluation metrics in an isolated environment that can be applied to tabular ML tasks specific to a particular organization. It exposes agents to realistic workflow stages, from planning and data inspection through feature engineering, model development, validation, and code repair to final submission, while hidden executable validators measure not only final predictive performance but also leakage avoidance, reproducibility, protocol validity, correction behavior, and reward alignment. The strongest structured regime, flexible iterative interaction (our approach), achieves higher end-to-end normalized hidden-test quality than single-shot generation, unstructured interaction, and restart-based baselines, while also improving protocol-valid completion. Validated across more than 7,000 episodes, these results establish GRACE-DS as a robust platform for assessing the capacity of LLM-based AutoML agents to execute machine learning workflows under production-like conditions and in accordance with organization-specific requirements.

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

AlignDrive: Aligned Lateral-Longitudinal Planning for End-to-End Autonomous Driving

Practical autonomous driving requires models that generalize by reasoning through spatial-temporal possibilities to exclude unsafe outcomes. While state-of-the-art (SOTA) methods use parallel planning architectures, they fail to explicitly couple speed decisions with agent behavior along the driving path, leading to suboptimal coordination. To address this, we propose a cascaded framework that transforms longitudinal planning from an independent prediction task into a path-conditioned reasoning process. On the model side, we introduce an anchor-based regression design that conditions longitudinal prediction on the lateral drive path, and reformulate longitudinal planning as 1D displacement prediction along the path. This reduces geometric uncertainty and sharpens the model's focus on interaction-driven dynamics. On the data side, we introduce a planning-oriented data augmentation strategy that simulates rare safety-critical events by programmatically inserting agents and relabeling longitudinal targets to enforce collision avoidance. Evaluated on the challenging Bench2Drive benchmark, our method achieves SOTA performance with a driving score of 89.07 and a success rate of 73.18%, demonstrating significantly improved coordination and safety. Further evaluation on Fail2Drive confirms strong generalization to rare edge cases where parallel formulations typically fail. Project page:https://yanhaowu.github.io/AlignDrive/.

07.
arXiv (quant-ph) 2026-06-25

Neural network decoder confidence as a learned proxy for the logical gap

arXiv:2606.08758v2 Announce Type: replace Abstract: To utilize quantum error-correcting codes, a decoder must infer the logical sector from the measured syndrome. Beyond producing a hard logical decision, some decoders provide soft information that estimates the reliability of that decision. For minimum-weight perfect matching (MWPM), a common confidence measure is the complementary, or logical, gap. Here we test whether the logit of a graph neural network (GNN) decoder can act as a learned proxy for the logical gap. Using a pretrained GNN for the rotated surface code under uniform circuit-level noise [Physical Review Research, 7(2):023181, 2025], we compare its soft output with the MWPM complementary gap on the same sampled syndromes. We find that post-selection based on the GNN logit yields a lower logical error rate than one based on the MWPM gap. Shot-by-shot, the signed GNN confidence distribution resembles the signed MWPM gap at low and intermediate values, but assigns higher confidence to many correctly decoded shots. While both scores approximate the posterior log-likelihood ratio, the GNN confidence magnitude is closer to its ideal value. These results show that a neural-network decoder trained only on syndromes and logical labels learns both gap-like discrimination and a quantitative confidence scale, enabling confidence-based post-selection when MWPM gap estimates are unavailable, costly, or poorly matched to the noise model.

08.
medRxiv (Medicine) 2026-06-19

"Us with them": Co-designing a caesarean section consent and debriefing intervention in West Cameroon

Background Women-centred maternity care is a rights issue that determines the use of services. Such care ensures responsiveness to womens needs which is enacted through shared decision-making, review and response. In the West Region of Cameroon, informed consent (IC) and Debriefing for caesarean section (c-section) have been shown to be suboptimal or absent. This paper describes the participatory design of a quality-improvement hospital-based intervention. Methods From February to May 2025, we conducted a co-design process with three groups of stakeholders: 59 post c-section women and community representatives, 78 frontline c-section providers, and 29 directors of public and private hospitals. We followed four phases: planning, conducting, evaluating, and reporting. The conduct phase comprised five all-day workshops with post c-section women and community representatives, followed by five all-day workshops with the c-section providers. Finally, we held an 11th workshop with the hospital directors to scrutinize suggested interventions, evaluate their feasibility, and establish a consensus on their components. We described the intervention using the TIDieR (Template for Intervention Description and Replication) checklist. We documented the co-design process, using open-ended narratives to delineate interventions, and carried out real-time synthesis on visual aids (whiteboards and flipcharts). Intervention feasibility was quantified using a structured ad hoc matrix, while insights on facilitators and barriers were captured through qualitative free-text entries. We coupled data collection with constant comparison and triangulation through contemporaneous field notes, photographic documentation, and thematic mapping of stakeholders perceptions and interactive dynamics. Results Participants perspectives on the co-design were positive, and their motivation were very high although less than 50% reported previous involvement in co-design processes. More than 80% of participants found rated the co-design process as either good or very good. The final intervention comprised four components: (i) an in-service training; (ii) a standard operating procedure including a harmonised consent form and debriefing checklist; (ii) systematic supportive supervision, monitoring & evaluation; and (iv) a routine clinical audit. Each group of stakeholders upheld specific dimensions of the consent and debrief intervention. Post c-section women and community members emphasized emotional support, written discharge advice after debriefing, and zero tolerance of suboptimal consent and debriefing practices. Frontline c-section providers insisted on robust documentation for medico-legal protection. Hospitals Directors emphasized capacity-building and cultural friendliness. All the groups supported womans autonomous decision making. The intervention feasibility was rated high or very high by hospital directors except for the financial, infrastructural and technical domains. Conclusion This co-design process yielded a context-specific, multi-component intervention that was well accepted and deemed feasible across stakeholders. It provides a methodological approach to strengthening informed consent and debriefing as core elements of women-centred, accountable maternity care, and warrants implementation.

09.
arXiv (CS.CL) 2026-06-15

The Linguistics Olympiads: Towards a New Corpus for Linguistics Research?

Linguistics olympiad problems (LOPs) are a category of self-sufficient puzzles consisting of a scaled-down corpus representative of certain linguistic phenomena, from which the solver must deduce a primitive set of rules of the language and then translate a new set of elements. The linguistics olympiads (LOs) have become a worldwide phenomenon with 43 different territories taking part in the International Linguistics Olympiad (IOL) 2025. While the typology and solving strategies of LOPs have been analysed, their scientific facet and connections to academic linguistics have yet to be explored. LOPs are directly connected to many linguistic fields, e.g., linguistic typology, linguistic relativity, and linguistics fieldwork. Recently, LOPs have become a research focus as benchmarks for large language models, thus highlighting their usefulness in computational linguistics. Nevertheless, they have not yet been integrated into mainstream linguistics research. This paper attempts to open new directions of including this particular type of puzzle in academic research by offering a structured evaluation of LOPs as linguistic data sources and proposes criteria for their responsible use in academic research. Starting from a set of over 1800 LOPs, this study critically examines the potential of LOPs as a novel corpus for linguistics research by discussing their strengths and limitations as tools, as well as the areas of linguistics into which these problems could fit. This work forms the foundation for a broader initiative aimed at bridging the gap between LOs and academic linguistics, by establishing a robust theoretical framework for LOPs.

10.
arXiv (CS.CV) 2026-06-12

Skeleton Sparsification and Densification Scale-Spaces

The Hamilton-Jacobi skeleton, also known as the medial axis, is a powerful shape descriptor that represents binary objects in terms of the centres of maximal inscribed discs. Despite its broad applicability, the medial axis suffers from sensitivity to noise: Minor boundary variations can lead to disproportionately large and undesirable expansions of the skeleton. Classical pruning methods mitigate this shortcoming by systematically removing extraneous skeletal branches. This sequential simplification of skeletons resembles the principle of sparsification scale-spaces that embed images into a family of reconstructions from increasingly sparse pixel representations. We combine both worlds by introducing skeletonisation scale-spaces: They leverage sparsification of the medial axis to achieve hierarchical simplification of shapes. Unlike conventional pruning, our framework inherently satisfies key scale-space properties such as hierarchical architecture, controllable simplification, and equivariance to geometric transformations. We provide a rigorous theoretical foundation in both continuous and discrete formulations and extend the concept further with densification. By growing the skeleton successively instead of shrinking it, we allow inverse progression from coarse to fine scales. Densification scale-spaces can even reach beyond the original skeleton to produce overcomplete shape representations with relevancy for practical applications. Through proof-of-concept experiments, we demonstrate the effectiveness of our framework for practical tasks including robust skeletonisation, shape compression, and stiffness enhancement for additive manufacturing.

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

RepWAM: World Action Modeling with Representation Visual-Action Tokenizers

This work presents RepWAM, a representation-centric world action model (WAM) built on representation visual-action tokenizers. Existing WAMs typically inherit reconstruction-oriented video tokenizers from pretrained video generation models. Although these tokenizers preserve visual fidelity, pixel reconstruction alone provides limited guidance for learning instruction-following dynamics that connect future prediction with robot control. To address this, we explore a semantic visual-action latent space for representation-centric world action modeling. Specifically, we train a representation visual-action tokenizer that maps visual inputs into aligned visual and latent action tokens. We then pretrain our WAM to jointly model future visual states and the latent actions that connect them under language instructions, followed by adaptation to real robot trajectories for closed-loop manipulation. Experiments on real-world manipulation tasks and simulation benchmarks show that RepWAM delivers strong performance across diverse manipulation settings, while ablations highlight the value of semantic visual-action tokenization over reconstruction-oriented alternatives. These results establish representation visual-action tokenization as a promising foundation for world action models and a step toward generalist robot policies. Code and weights will be available at https://github.com/wdrink/RepWAM.

12.
arXiv (CS.CL) 2026-06-15

OdysSim: Building Foundation Models for Human Behavior Simulation

Large language models are increasingly deployed as human simulators for interactive evaluation and social simulation. Yet helpfulness-driven post-training pulls them toward a homogeneous, overly agreeable assistant register, creating a behavioral Sim2Real gap. We present OdysSim, the largest open systematic investigation of behavioral foundation models, i.e., models trained to simulate human behavior at scale. We propose SOUL, a taxonomy of five capability axes (CONV, SS, COG, ROLE, EVAL) that unifies 62 datasets and 23 benchmark tasks under one framework. Specifically, we curate the OdysSim corpus (21.4M interactions, 10B tokens, retrofitted with back-generated social contexts), construct the SOUL-Index benchmark, and develop an end-to-end training recipe combining midtraining, task-specific RL, and expert distillation. The resulting open 8B OSim model ranks first or tied-first on 8 of 23 tasks, outperforming any individual frontier model by this count, with the strongest gains on conversational and social tasks. Its outputs are also more human-like in length, formatting, and word choice, and it transfers zero-shot to out-of-distribution user simulation on $\tau$-bench, nearly matching real users on reaction alignment (93.2 vs. 93.5). We further show that LLM-as-judge RL induces reward-hacking patterns, and that our detectors can mitigate them during post-training. Together, our findings suggest that behavioral foundation models require rethinking the LLM training paradigm. We release all artifacts to support future research.

13.
bioRxiv (Bioinfo) 2026-06-18

ScriptManager: a platform for scalable and reproducible high-resolution analysis of genomics datasets

Background: The growing diversity of genomic and epigenomic assays has driven a parallel expansion in data formats, analysis workflows, and figure-generation tools. However, tools for analyzing data and assembling publication-quality figures are often specialized to a specific assay, dramatically limiting their interoperability and reproducibility. Results: We present the v1.0 release of ScriptManager, a Java-based framework for modular and reproducible analysis and visualization workflows of genomics and epigenomics data. Unlike existing tools specialized for individual assay types, ScriptManager provides a unified and extensible framework for cross-assay visualization and workflow reproducibility. The v1.0 release adds novel analytical modules, GUI session logging, automated unit and integration testing, tutorials, and expanded documentation. It also integrates with the broader reproducibility ecosystem through Singularity containers, Anaconda packaging, and Galaxy XML wrappers. We demonstrate ScriptManager's TagPileup scaling from local single-core execution to a 10,305-job analysis distributed across the Open Science Grid (OSG), with the full workload completing in

14.
arXiv (CS.CV) 2026-06-11

Latent Geometric Chords for Query-Efficient Decision-Based Adversarial Attacks

While decision-based black-box adversarial attacks present a severe security threat, current methodologies suffer from fundamental limitations. Pixel-wise attacks frequently introduce unnatural, high-frequency visual artifacts, while latent-space frameworks are confined by the limited search space of low-dimensional manifolds and inherent reconstruction flaws. To resolve these limitations, we propose Latent Geometric Chords (LGC) for Query-Efficient Decision-Based Adversarial Attacks alongside a variant, LGC-H. At its core, LGC navigates decision boundaries by executing a curvature-aware geometric search within a compressed semantic manifold. To guarantee high visual fidelity and circumvent dimensionality bottlenecks, we introduce a Residual-based Adversarial Generation (RAG) mechanism. RAG isolates semantic perturbations as geometric chords and superimposes them directly onto the original source image. RAG substantially resolves baseline reconstruction flaws and effectively doubles the permissible search space dimensions. Experimental results demonstrate that LGC achieves robust cross-dataset transferability and substantially outperforms state-of-the-art baselines. Notably, our method, LGC, minimizes perturbation magnitudes while achieving state-of-the-art visual fidelity–with a Structural Similarity Index Measure (SSIM) exceeding 0.99 and a Learned Perceptual Image Patch Similarity (LPIPS) below 0.01 at 5000 queries–and sustaining high attack success rates under stringent perceptual constraints, successfully compromising adversarially trained robust models. The source code is available at: https://github.com/eihmuekhine/Latent-Geometric-Chords.

15.
arXiv (quant-ph) 2026-06-11

Quantum optimal control of the Dicke manifold in dipolar Rydberg atom arrays

arXiv:2606.02283v2 Announce Type: replace Abstract: The ability to engineer and control quantum states of many-body systems is a central challenge in quantum information science. For a register of $N$ qubits, the full Hilbert space dimension grows exponentially as $2^N$, rendering generic state preparation and control infeasible without exploiting structure or symmetry. A particularly important and physically motivated restriction is to the fully symmetric subspace, spanned by the Dicke states, which are simultaneous eigenstates of collective spin $J=N/2$. Ensembles of Rydberg atoms interacting via electric dipoles in two-dimensional tweezer arrays form a promising platform for achieving such control. However, the finite range of dipole-dipole interactions poses a challenge to generating and controlling the Dicke manifold because the Hamiltonian incurs leakage from the computational subspace. To counteract this leakage, we perform quantum optimal control algorithms on a truncated Hilbert space according to our newly developed method of ``irrep distillation'' (IRD), which captures the process by which the symmetric subspace couples to leakage error-spaces, using only linear-scaling Hilbert dimension. We implement gradient ascent pulse engineering (GrAPE) on control schemes with little or no local addressing, to generate resourceful states like Greenberger-Horne-Zeilinger, Dicke, and extremal quantum states. We benchmark each scheme of IRD-GrAPE for its quantum speed limit (QSL), as well as exactly testing pulse fidelities on small system sizes and predicting fidelities using higher-order IRD on larger systems.

16.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

18.
arXiv (CS.CL) 2026-06-11

Measuring Semantic Progress in Multi-turn Dialogue via Information Gain

Evaluating multi-turn dialogue is challenging because quality emerges across turns rather than within individual responses. We focus on a key dimension of information-seeking dialogue: semantic progress, defined as the accumulation of new, question-relevant, and non-redundant information over the course of a conversation. We formalize semantic progress as question-conditioned uncertainty reduction and introduce an information-theoretic metric that approximates it in embedding space. Our main estimator uses a tractable Gaussian formulation with closed-form updates, while a complementary maximum-entropy argument shows why log-determinant structure arises more broadly when only second-order embedding information is retained. This formulation yields desirable theoretical properties, including monotonicity, additive decomposition of total information gain across turns, and diminishing returns for redundant evidence. Unlike LLM-as-a-judge approaches, our metric requires no autoregressive inference at evaluation time and is fully reproducible for a fixed embedding model. Experiments on MT-Bench, Chatbot Arena, and UltraFeedback show that the proposed metric achieves competitive agreement with human judgments despite targeting only semantic progress, with improved alignment on MT-Bench and UltraFeedback compared to several LLM-based judges. Notably, the method remains effective with lightweight embedding models under CPU-only execution, indicating that semantic progress can be captured without reliance on large model capacity.

19.
Nature (Science) 2026-06-25

How long-term dietary cholesterol can slow down its own clearance by liver cells

作者: 未知作者

Cholesterol carried by low-density lipoprotein (LDL) drives heart disease and is cleared by liver cells expressing the receptor LDLR. A cell-signalling mechanism has been discovered through which high cholesterol promotes the enzyme-mediated degradation of LDLR. Blocking this enzyme restores LDLR levels in liver cells, suggesting a new strategy for treating high cholesterol. Chronic exposure to cholesterol can move the receptor protein LDLR into cells for degradation.

20.
arXiv (quant-ph) 2026-06-15

Experimental violation of a Bell-like inequality for causal order

arXiv:2506.20516v2 Announce Type: replace Abstract: Quantum mechanics is compatible with scenarios where physical processes happen in an indefinite order. In theory, this feature could be detected through violations of inequalities on the observed correlations, analogous to Bell inequalities. However, experimental demonstrations of such violations have been missing until recently due to the complexity of the required setup. Here we report an experimental violation of a Bell-like inequality involving the correlations of four parties, one of which is spacelike separated from the others. Our demonstration employs 3 km fiber spools to simulate spacelike separation, and achieves high-speed operations in photonic time-bin encoding, nanosecond synchronization, and accurate temperature stabilization. These experimental advances enable a violation by 5.7 standard deviations and open a path towards a certification of indefinite order in conditions that guarantee spacelike separation with existing state-of-the-art devices. However, the certification is not device-independent, as it relies on knowledge about the setup to exclude bidirectional signaling–a loophole inherent to implementations in classical acyclic spacetimes, which may be resolved in future quantum-spacetime tests.

21.
arXiv (CS.CV) 2026-06-24

PointVG-R: Internalizing Geometric Reasoning in MLLMs for Precise Pointing Localization via Visual Chain of Thought

Pointing-based visual grounding requires models to precisely locate target objects by deciphering complex spatial relationships between the visual scene and pointing gestures. Traditional methods typically encode input images into static feature representations and perform reasoning primarily within the linguistic domain, often overlooking the rich perceptual cues and explicit spatial geometry inherent in images. In this study, we aim to mitigate the cognitive vulnerability of models in interpreting gestural spatial relations by proposing PointVG-R, a reasoning-guided Multi-modal Large Language Model (MLLM). PointVG-R introduces geometric-aware reasoning for pointing-based grounding, enabling the model to think with images through the strategic integration of Reinforcement Learning (RL) and cold-start data. Specifically, we design a novel geometric reasoning pipeline that simulates the iterative cognitive process humans employ when interpreting pointing gestures. Furthermore, we construct EgoPoint-CoT, a high-quality visual Chain-of-Thought (CoT) dataset featuring detailed reasoning trajectories to guide the model via Supervised Fine-Tuning (SFT) and RL. To address the varying quality of learning signals encountered during training, we further propose an Adaptive Importance Weighting strategy based on Group Variance, which dynamically adjusts reward signals to optimize the learning process. Experimental results demonstrate that PointVG-R achieves SOTA performance, outperforming the baseline by $15.86$ points in mIoU. Extensive ablation studies further validate the efficacy of our proposed modules. Code: https://github.com/lingli1724/PointVG-R.

22.
Nature (Science) 2026-06-24

Small-molecule modulation of β-arrestins

β-Arrestins are multifunctional regulators of G-protein-coupled receptor (GPCR) signalling and orchestrate diverse downstream signalling events and physiological responses across the GPCR superfamily1–3. Although GPCR pharmacology has advanced to target orthosteric and allosteric sites, as well as G proteins and GPCR kinases, direct chemical tools to modulate β-arrestin activities have remained conspicuously absent. Here we report the identification of small-molecule inhibitors that selectively target β-arrestins and delineate their mechanism of action through integrated pharmacological, biochemical, biophysical and structural analyses. These inhibitors disrupt β-arrestin engagement with agonist-activated GPCRs, impairing desensitization, internalization and β-arrestin-dependent physiological functions while sparing G protein–receptor coupling. Cryo-electron microscopy, molecular dynamics simulations and structure-guided mutagenesis reveal that one modulator, Cmpd-5, engages a pocket within the central crest of β-arrestin1 formed by the middle, C and lariat loops, a critical receptor-binding interface, stabilizing a distinct conformation that is incompatible with full β-arrestin–receptor engagement. Together, these findings establish a mechanistic framework for β-arrestin modulation, reveal&nbsp;a novel allosteric site for structure-based drug design, and open new avenues for transducer-targeted, pathway-specific GPCR therapeutic agents. Integrated pharmacological, biochemical, biophysical and structural analyses of small-molecule β-arrestin inhibitors show how they block β-arrestin engagement with activated GPCRs, revealing their mechanism of action and uncovering a previously unrecognized allosteric regulatory site.

23.
arXiv (quant-ph) 2026-06-16

Detecting basis-dependent hardware errors through spatio-temporal quantum steering

arXiv:2606.16451v1 Announce Type: new Abstract: Spatio-temporal quantum steering provides a framework for benchmarking the nonclassicality of general quantum state transfer processes. A central diagnostic is the no-signaling-in-time (NSIT) condition, whose violation can indicate basis-dependent hardware errors. However, finite measurement statistics may also yield apparent violations, thereby obscuring the detection of basis-dependent hardware errors. To address this, we construct a statistical hypothesis test under the null hypothesis that NSIT violations arise solely from statistical fluctuations. Combining the statistical properties of NSIT violation under the null hypothesis with Chebyshev's inequality, we obtain a distribution-free upper bound on the $p$-value without parametric assumptions. We apply this method to two examples. For a single-qubit state-transfer experiment on a superconducting processor, we observe several instances that the NSIT violation is observed and the null hypothesis is simultaneously rejected by a small $p$-value, providing statistical evidence of basis-dependent hardware errors. For a seven-qubit Hayden-Preskill teleportation protocol on IonQ devices, the null hypothesis is also rejected even when the average fidelity exceeds the classical threshold, while the associated nonclassicality measure vanishes. Our results highlight the necessity of statistical hypothesis testing for detecting basis-dependent errors in near-term quantum devices.

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

Sentinel: Decoding Context Utilization via Attention Probing for Efficient LLM Context Compression

Retrieval-augmented generation (RAG) often suffers from long and noisy retrieved contexts. Existing context compression methods typically rely on heuristic relevance estimation or supervised compression models rather than on how LLMs utilize retrieved context during inference. We propose Sentinel, a lightweight sentence-level compression framework that decodes inference-time contextual utilization behaviors from head-wise attention patterns of frozen LLMs. To ground supervision in retrieval-dependent answering behavior, Sentinel trains a lightweight probe using QA examples where the model succeeds only when retrieved context is available. Sentinel performs compression using only a single non-autoregressive forward pass without dedicated compression training or autoregressive scoring. Empirically, we find that effective contextual utilization signals remain accessible even in compact proxy models. On LongBench, Sentinel with a 0.5B proxy model achieves up to 5$\times$ compression while attaining question-answering performance competitive with compression methods built on 7B-scale models. Despite being trained only on English QA data, Sentinel also generalizes effectively to Chinese and out-of-domain settings.

25.
bioRxiv (Bioinfo) 2026-06-11

Viability of engineered AAVs via protein language models

Capsid engineering has greatly improved the performance of recombinant AAV vectors used for gene therapy. One commonly used strategy is the insertion of a short, 7-mer, peptide into surface-exposed loops to modify receptor interactions and enhance cell entry. While effective in receptor retargeting and improved transduction, these insertions might destabilize the capsid protein, hinder assembly, and thus limit production. While previous attempts have used deep mutational scanning and AI to predict which insertions are viable, there is lack in understanding the structural consequences of these peptide insertions at the amino-acid level. Here we combined experiments, deep sequencing and large protein language models to gain insight on the impact of 7-mer insertions on the VR-VIII region. We first characterize the biochemical properties of viable insertions, thus identifying which residues are well tolerated, and which should instead be avoided. We then focus on the nearby context of those insertions, by studying the effect of the linkers, either for highly diverse libraries or for individual variants known for their efficiency. Next, we study the broader context, by extending our analysis to the whole capsid sequence, and identifying regions that can tolerate insertions without long-ranged structural deformations that could affect capsid functionality. We conclude with a cross-serotype comparison and a viability analysis of tens of previously engineered variants. Our work showcases how AI can uncover structure-function rules governing the success of engineered AAV capsids.