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

Pix2Pix-Hybrid: Structure-Guided Conditional Synthesis of Hajj Crowd Images with Multi-Channel Conditioning and Weak Attribute Supervision

Developing accurate crowd-counting models for Hajj pilgrimage scenes remains challenging because domain-specific annotated images are scarce and data collection during large gatherings raises privacy concerns. To address these limitations, this paper proposes Pix2Pix-Hybrid (P2P-H), a hybrid conditional GAN for structure-guided Hajj crowd-image synthesis and data augmentation. P2P-H builds on Pix2Pix and employs a U-Net generator conditioned on eight input channels that jointly encode structural cues (edges and grayscale) and contextual attributes (crowd density and time of day). To capture detailed textures in dense scenes, the framework integrates two multi-scale PatchGAN discriminators operating at different resolutions. The training procedure combines adversarial, perceptual, and feature-matching objectives with adaptive data augmentation and stabilization strategies. The model was trained on 993 real Hajj frames collected from 60 publicly available video sources, with conditioning attributes derived automatically to reduce manual labeling effort. Using this framework, we constructed CrowdH, a synthetic dataset of 10,000 high-resolution Hajj crowd images. Experimental results show that P2P-H improves structure-preserving conditional synthesis quality compared with Pix2Pix and StyleGAN2-ADA baselines and shows favorable transfer to other crowd datasets. To assess downstream utility, we further constructed CrowdH-Mix-469, an annotated mixed real-synthetic dataset comprising 384 real Hajj images and 85 selected synthetic images,and evaluated five crowd-counting models under real-only and real-plus-synthetic training. The selected synthetic data reduced MAE across all five models, with the strongest gain observed for CSRNet.

02.
arXiv (quant-ph) 2026-06-11

Mach's principle in atomic transitions

arXiv:2606.11608v1 Announce Type: new Abstract: We investigate the atomic transition probabilities in atom-mirror set-ups that are in circular motion. In one scenario, the atom is in circular motion inside a static cylindrical mirror. In the other scenario, the cylindrical mirror rotates around its central axis while the atom remains static. We report structural similarity in the atomic transition probabilities between these two cases – these probabilities are equivalent upon interchanging the field frequencies between the two scenarios. We interpret such an observation as a semi-classical phenomenon analogous to the classical Mach's principle.

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

G-IdiomAlign: A Gloss-Pivoted Benchmark for Cross-Lingual Idiom Alignment

Idioms are difficult to transfer across languages due to their non-compositionality and weak surface-form grounding, making literal mappings unreliable. We present G-IdiomAlign, a gloss-pivoted benchmark where each idiom is anchored by an English gloss from Wiktionary. We further construct a high-confidence reference alignment set for reproducible evaluation. G-IdiomAlign supports two protocols: (1) a controlled Multiple-Choice Idiom Equivalence with typed distractors for error attribution; and (2) a Gloss-Contrastive Generation contrasting No-gloss and With-gloss inputs to isolate the effect of an explicit semantic pivot. Across diverse LLMs, a bias to literal translation is a dominant failure mode, especially when the target is a low-resource language. Glosses consistently improve Gloss-Contrastive Generation under an embedding-based semantic proxy, but performance remains modest, indicating substantial headroom in the open output space. Subsequent analysis on Qwen3-8B further suggests that cross-condition differences are concentrated more in attention heads than in layers, while better With-gloss generations coincide with stronger gloss anchoring.

04.
arXiv (CS.LG) 2026-06-17

Statistical Learning from Attribution Sets

arXiv:2602.06276v2 Announce Type: replace Abstract: We address the problem of training conversion prediction models in advertising domains under privacy constraints, where direct links between ad clicks and conversions are unavailable. Motivated by privacy-preserving browser APIs and the deprecation of third-party cookies, we study a setting where the learner observes a sequence of clicks and a sequence of conversions, but can only link a conversion to a set of candidate clicks (an attribution set) rather than a unique source. We formalize this as learning from attribution sets generated by an oblivious adversary equipped with a prior distribution over the candidates. Despite the lack of explicit labels, we construct an unbiased estimator of the population loss from these coarse signals via a novel approach. Leveraging this estimator, we show that Empirical Risk Minimization achieves generalization guarantees that scale with the informativeness of the prior and is also robust against estimation errors in the prior, despite complex dependencies among attribution sets. Simple empirical evaluations on standard datasets suggest our unbiased approach significantly outperforms common industry heuristics, particularly in regimes where attribution sets are large or overlapping.

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

Creative Collision: Directorial Persona Steering and Competition in Large Language Models

Activation steering has emerged as a powerful tool for shaping the behaviour of large language models at inference time, yet most prior work injects a single semantic direction into the residual stream. We study the richer setting in which two semantically opposing steering vectors are superimposed – a regime we call Creative Collision. Concretely, we construct directorial persona vectors for Steven Spielberg (optimistic, redemptive moral valence) and Martin Scorsese (dark, morally ambiguous) via mean-difference activation contrast on curated screenplay-derived corpora, then interpolate between them with a scalar mixing parameter $\alpha \in [0,1]$ and a steering coefficient $\lambda$. Across five evaluation axes – moral valence, generation coherence, surface style, directional dominance, and vector geometry – three principal findings emerge: (i)~Spielberg's representational signature exhibits robust directional dominance, suppressing Scorsese's moral influence across almost the entire interpolation range; (ii)~intermediate collision points paradoxically improve generation coherence relative to pure single-director steering at high $\lambda$; and (iii)~both personas localise maximally to layer~28 of a 40-layer decoder-only transformer, revealing a shared moral-tone substrate. These results illuminate the geometry of competing semantic directions in transformer residual streams and have direct implications for controllable creative generation and value-aligned narrative synthesis.

06.
bioRxiv (Bioinfo) 2026-06-15

AliceDB database and pipeline for identification of natural protein variants based on mass spectrometry measurement data

The natural variation that distinguishes living organisms within a single species is currently being studied intensively, primarily at the genetic level. Unfortunately, studies of natural variants at the level of protein gene products are not very common, mainly due to the lack of appropriate databases and bioinformatics tools. The main research technique used to study proteomes/peptidomes is mass spectrometry (MS). A classic method for interpreting raw mass spectrometry data in proteomic/peptidomic studies involves the use of databases containing representative (canonical) sequences that define the proteome of the organism under study. In this paper, we present the AliceDB database, which contains information on over 7 million natural variants of protein sequences described in the scientific literature for Homo sapiens. The data contained in the AliceDB database can be utilized using widely available and commonly used software for interpreting proteomic data. Test results regarding the use of the AliceDB database for the interpretation of proteomic data indicate that accounting for the presence of natural variants increases both the number and quality of identified proteins. Furthermore, it is easy to identify protein sequence variants that may, for example, be of significance in medicine.

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

QoS-Aware Token Scheduling and Private Data Valuation for Multi-Modal Agentic Networks

arXiv:2606.15573v1 Announce Type: new Abstract: In agentic systems, human-generated data records anchor the value of AI services. Yet cloud compute pipelines centralize processing on remote servers. Data centralization reduces personal data sovereignty and may potentially degrade the quality of service (QoS). Meanwhile, user contributions are diverse in quantity and quality: decentralized records can be biased, noisy, and heterogeneously distributed. To address the data challenge, we study fair token allocation and private data valuation for decentralized and resource-constrained agentic systems. Our approach embeds multi-modal representations in a shared semantic space and releases differentially private (DP) prototypes to preserve utility while reducing semantic leakage. With the DP guarantee, we design a fair token allocation scheme that rewards effective contributions and remains robust to data heterogeneity and AI resource scarcity. Extensive simulations demonstrate improved contribution-based fairness and QoS compared to standard benchmarks. The improved resistance to image reconstruction attacks indicates enhanced privacy for multi-modal personal data.

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

Performance Gap Analysis between Latin and Arabic Scripts HTR

Recent studies have shown that handwritten text recognition (HTR) systems perform worse on Arabic-script datasets than on Latin-script data. However, the reasons for this gap are still not well understood due to the lack of controlled comparisons. In this work, we present a comprehensive study of Arabic and Latin scripts HTR using a unified CRNN model for line-level HTR across nine datasets (including KHATT (Arabic), Muharaf (Arabic), NUST-UHWR (Urdu), PHTD (Persian), IAM (English), READ-2016 (German), and others) and di ferent training sizes (K in {100, 500, 1000, 2000, ..., Kfull}). Our results show the performance gap remains: it is large in low-resource settings, decreases with more data, but remains even at full scale, with a consistent difference of 5-7 CER points. We show that annotation quality matters, as many datasets contain labeling errors. Cleaning reduces error rates and narrows the gap, but does not eliminate it. In addition, we find that a fixed number of training samples provides less effective coverage in Arabic due to higher visual variability, requiring more data to learn similar representations. We compare recognition across datasets in terms of the number of text lines and the number of characters, showing an equivalence trade-off. We compare character frequency distributions across scripts and show that Arabic is significantly more heavy-tailed than Latin. Our error analysis reveals that around 30 percent of substitution errors in Arabic datasets (e.g., KHATT) are caused by confusion between visually similar characters, compared to about 15 percent in Latin-script datasets such as IAM.

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

Exploring Adaptive Masked Reconstruction for Self-Supervised Skeleton-Based Action Recognition

Recently, masked skeleton reconstruction models have emerged as strong action representation learners, driving significant progress in self-supervised skeleton-based action recognition. However, existing state-of-the-art methods must predict an exceedingly large number of spatiotemporal patches, significantly prolonging training time. Besides, by treating all spatiotemporal regions equally during reconstruction, these models are distracted from learning the critical motion patterns that underlie action semantics. To address these challenges, we propose Adaptive Masked Reconstruction (AMR), a faster and stronger pre-training framework. We first decouple the decoder from the encoder, enabling flexible prediction of larger spatiotemporal patches and dramatically reducing reconstruction complexity. Given that larger patches contain more complex information, which is challenging to predict and consequently degrades performance, we accordingly introduce an adaptive guidance module. This module identifies regions of high motion informativeness, guiding the model to focus on the most discriminative parts of each patch and alleviating reconstruction difficulty. Experiments on NTU RGB+D 60, NTU RGB+D 120, and PKU-MMD datasets demonstrate that AMR not only accelerates pre-training substantially but also improves downstream recognition accuracy, surpassing current state-of-the-art approaches.

10.
arXiv (CS.CL) 2026-06-18

Possible or Definite? A Benchmark for Evaluating Diagnostic Uncertainty Preservation in Clinical Text

Large language models (LLMs) are increasingly used for clinical text tasks such as summarization and revision. While most studies evaluate the fluency and coherence of LLM-generated text, whether LLMs correctly preserve diagnostic uncertainty remains underexplored. In clinical practice, phrases such as ``possible pneumonia'' communicate the strength of available evidence and directly guide decisions about follow-up testing and treatment. Altering these uncertainty expressions can change the clinical meaning entirely. In this paper, we systematically evaluated this problem in two steps. First, we constructed a benchmark of 1,200 clinical documents with 9,184 uncertainty annotations across five levels. Second, we evaluated three LLMs on this benchmark. Our results show that (1) LLMs preserve the original uncertainty cues poorly, often less than half the time; (2) LLMs struggle with nuanced distinctions between adjacent levels. This work reveals a failure mode not captured by standard evaluation metrics and provides implications for the safe deployment of LLMs in clinical workflows.

11.
arXiv (CS.AI) 2026-06-15

Scalable Production Scheduling: Linear Complexity via Unified Homogeneous Graphs

arXiv:2604.23841v2 Announce Type: replace-cross Abstract: Efficiently solving the Job Shop Scheduling Problem in real-world industrial applications requires policies that are both computationally lean and topologically robust. While Reinforcement Learning has shown potential in automating dispatching rules, existing models often struggle with a scalability bottleneck caused by quadratic graph complexity or the architectural overhead of heterogeneous layers. We introduce a unified graph framework that employs feature-based homogenization to project distinct node roles into a shared latent space. This allows a standard homogeneous Graph Isomorphism Network to capture complex resource contention with linear complexity, ensuring low-latency inference for large-scale industrial applications. Our empirical results demonstrate that our framework achieves state-of-the-art performance while exhibiting consistent zero-shot generalization. We identify the job-to-machine ratio as the primary driver of policy effectiveness, rather than absolute problem size. Based on this, we propose a hypothesis of structural saturation, demonstrating that policies trained on critically congested instances ($\mathcal{J} \approx \mathcal{M}$) learn scale-invariant resolution strategies. Agents trained at this saturation point internalize invariant conflict-resolution logic, allowing them to treat massive rectangular instances as a sequential concatenation of saturated sub-problems. This approach eliminates the need for expensive scale-specific retraining and prevents overfitting to statistical shortcuts, providing a robust and efficient pathway for deploying RL solutions in dynamic production environments.

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

The Risk Shadow of Principal Component Analysis: When 99.9999% Variance Preservation Causes Catastrophic Decision Errors

arXiv:2606.14533v1 Announce Type: new Abstract: Principal Component Analysis (PCA) preserves variance, not the information needed to detect rare catastrophic events. This paper proves the existence of a {\it Risk Shadow}: PCA can retain over 99.9999 percent of total variance while completely erasing all signal about rare, high-impact failures. When this happens, even the best possible classifier operating on the PCA representation reduces to a constant predictor. The root cause is a fundamental mismatch between variance maximization and tail risk awareness. To break the shadow, we introduce Expectile PCA (ExPCA) and Tail-Preserving PCA (TP-PCA), two methods that reweight the data covariance toward high-impact events. We prove theoretically that ExPCA strictly outperforms PCA in retaining rare-event information, and we validate our claims on synthetic data and a real-world credit card fraud detection benchmark. Our results call for a fundamental rethinking of variance-based dimensionality reduction in high-stakes decisions.

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

Characterizing Brazilian Atlantic Forest Restoration Outcomes with Geospatial AlphaEarth Embeddings

作者:

The Atlantic Forest in Brazil is a critical biodiversity hotspot, yet less than 12-15% of its original cover remains. Although monitoring forest restoration on a large scale is essential, traditional methods are limited by the impracticality of on-the-ground reporting on such a scale and by the saturation of remote-sensing indices such as NDVI. Furthermore, reforestation is a gradual process as opposed to the rapid spectral changes caused by deforestation. In this study, we examine 1,729 restoration sites in S\~ao Paulo, using satellite embeddings from the AlphaEarth Foundation's model to evaluate their effectiveness in characterising early restoration success. We introduce the concept of a 'Reference Trajectory Embedding', defining a metric of restoration success based on cosine similarity to reference sites of mature secondary forest. We observe distinct clusters in embedding space according to different land use and land cover (LULC) types, and we can identify sites with clear change vectors. However, the signal can be noisy, and embeddings may require further fine-tuning to capture and predict site metadata beyond LULC.

14.
arXiv (CS.CL) 2026-06-18

SproutRAG: Attention-Guided Tree Search with Progressive Embeddings for Long-Document RAG

Retrieval-augmented generation (RAG) systems must balance retrieval granularity with contextual coherence, a challenge that existing methods address through LLM-guided chunking, single-level context expansion, or hierarchical summarization. These approaches variously depend on costly LLM calls during indexing or retrieval, limit context aggregation to a single granularity level, or introduce information loss through summarization. We present SproutRAG, an attention-guided hierarchical RAG framework that addresses this trade-off by organizing sentence-level chunks into progressively larger but semantically coherent units, using learned inter-sentence attention to construct a binary chunking tree. Unlike prior approaches that rely on external LLMs, fixed context expansion, or lossy summarization, SproutRAG learns which attention heads and layers best capture semantic document structure, enabling multi-granularity retrieval without additional LLM calls or compressed summaries. At retrieval time, SproutRAG uses hierarchical beam search to retrieve candidates at multiple granularities, capturing multi-sentence relevance beyond flat retrieval. The framework is trained end-to-end with a joint objective that improves both embeddings and tree structure. Experiments across four benchmarks spanning scientific, legal, and open-domain settings demonstrate that SproutRAG improves information efficiency (IE) by 6.1% on average over the strongest baseline. Code is available on https://github.com/AmirAbaskohi/SproutRAG.

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

Bag of Dims: Training-Free Mechanistic Interpretability via Dimension-Level Sign Patterns

arXiv:2606.12629v1 Announce Type: cross Abstract: We show that the standard basis of transformer hidden states already provides a training-free, architecture-general feature basis. Individual dimensions encode semantic content via their signs and confidence via their magnitudes, functioning as independent binary registers. We validate this Bag of Dims framework across three model families (Qwen 3.5-4B, Gemma 3-4B, Mistral 7B) through four progressive experiments. Sign patterns alone carry predictive content: replacing all magnitudes with unity achieves 72-93% top-5 next-token accuracy through the LM head, and pure Hamming scoring without any decoder reaches 80-90% top-4096. These sign patterns organize into semantic features: using a single-token type cache (one forward pass per vocabulary token, no context), we discover 175 categories via per-dimension sign consistency (mean AUC 0.80) from 50 anchors with zero training. A trained probe adds only +0.018 AUC and converges to axis-aligned weights, confirming negligible cross-dimension structure. This structure extends to attention: all 175 categories remain discoverable in K and V projections. On the write side, static FFN weight inspection links 20% of features to individual writer neurons (>0.70 agreement; random controls: 0%), with top-200 neuron coalitions achieving >0.70 agreement on 99.9% of prototypes via majority vote. Fully unsupervised discovery (random seeds, no labels) scales to 1500 features at 100% yield and 99% sparsity across all three models, with pairwise MI of 0.0014 bits confirming low inter-dimension coupling. These results establish that the standard basis already suffices for feature reading throughout the transformer compute pathway, requiring no training, no optimization, and no GPU-days beyond a single forward pass per vocabulary token.

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

The Discrete-Log Clock: How a Transformer Learns Modular Multiplication

arXiv:2606.17399v1 Announce Type: cross Abstract: When small transformers grok modular multiplication, prior work reports that the learned embedding has a "dense" Fourier spectrum requiring all frequencies. This contrasts with modular addition, where only a sparse set of key frequencies suffices. We show this density is an artifact of analyzing in the wrong basis. The natural Fourier transform for multiplication is not the standard additive DFT but the multiplicative character transform, which decomposes functions on the multiplicative group $(\mathbb{Z}/p\mathbb{Z})^*$ into its irreducible representations. Applying this transform to a grokked transformer trained on $a \cdot b \bmod 113$, we find the embedding spectrum becomes highly sparse (Gini coefficient 0.58 vs. 0.07 in the additive basis) with only 4 key frequencies carrying significant energy. Furthermore, 96.9% of MLP neurons are cleanly tuned to a single multiplicative frequency, and neuron activation heatmaps reveal 2D-periodic structure when reordered by the discrete logarithm. These results demonstrate the transformer reduces multiplication to addition in discrete-log space, implementing a "Discrete-Log Clock" algorithm analogous to Nanda et al.'s Clock algorithm for addition. The methodology generalizes: matching the analysis basis to the algebraic structure of the task reveals interpretable structure where standard tools see noise.

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

Fisher Width: A Geometric Measure of Complexity on Statistical Manifolds

作者:

arXiv:2606.18306v1 Announce Type: new Abstract: Gaussian width is a central geometric complexity measure in high-dimensional probability, compressed sensing, convex optimization, and learning theory. It quantifies the average extent of a set along random directions, thereby capturing the effective dimension of constraint sets, hypothesis classes, and descent cones. However, this notion is intrinsically Euclidean. Statistical models instead carry a natural Riemannian geometry induced by the Fisher information metric, where directions are scaled according to statistical distinguishability rather than ambient Euclidean length. We introduce Fisher width, a Fisher-geometric analogue of Gaussian width for statistical manifolds. At a parameter point $\theta$, Fisher width replaces the Euclidean identity by the local metric tensor $G(\theta)^{1/2}$, measuring the Gaussian width of the Fisher-rescaled set. This makes the resulting quantity sensitive to local statistical curvature and invariant under smooth reparameterizations. We develop the basic theory of Fisher width, showing that it retains key structural features of Gaussian width, including concentration, metric perturbation stability, and spectral comparison bounds with the Euclidean baseline, while also capturing anisotropic geometric effects invisible to Euclidean measures. As an application, we prove a generalization bound for Fisher-Lipschitz hypothesis classes and propose computable estimators, which we evaluate empirically on MNIST across three model classes. Fisher width is to statistical manifolds what Gaussian width is to Euclidean convex bodies. This work lays the foundation for studying complexity and learning on curved statistical manifolds.

18.
arXiv (CS.CV) 2026-06-12

SeamEdit: A Black-Box VLM-Agnostic Pipeline for Large-Image Semantic Editing

Semantic region editing for large images must satisfy two requirements at the same time: high generative quality and natural integration with surrounding content. Some related methods rely on white-box models and leave the strong generation capability of closed-source models underexplored. Directly applying closed-source models to tiled editing, however, introduces several failure modes: semantic deformation, canvas-level alignment drift, and visible seam artifacts. This paper presents SeamEdit, a training-free and model-agnostic pipeline that treats any VLM with inpainting capability as a black-box oracle. SeamEdit mitigates these issues through a five-stage post-hoc pipeline: overlay-based tile decomposition, black-box VLM inpainting, geometric and color-consistency correction, seam-risk-based multi-candidate ranking, and dynamic-programming curved seam fusion. The pipeline reduces seam visibility and supports semantic modification of arbitrary tile regions.

19.
medRxiv (Medicine) 2026-06-17

Perceptions of aging well among older adults with heart failure: insights from a qualitative study

Background: Heart failure (HF) is a prevalent and often debilitating cardiovascular condition among older adults, frequently accompanied by multimorbidity, functional limitations, and the need to age in place. Traditional models of successful aging emphasize disease absence and preserved function, yet most individuals with HF live with ongoing symptoms and chronic health challenges. How older adults with HF define aging well, particularly across different socioeconomic contexts, remains underexplored. Objectives: To explore how older adults with HF conceptualize aging well and to identify perceived facilitators and barriers across more and less resourced New York City neighborhoods. Methods: We conducted semi-structured interviews with 20 adults diagnosed with HF residing in Manhattan and Brooklyn neighborhoods classified by 2019 United States Census data. Interviews were guided by Rowe and Kahn's model. Transcripts were analyzed using an inductive-deductive thematic approach and interpreted in alignment with the Healthy People 2030 framework. Results: Participants had a mean age of 69 years; 50% identified as Black and 50% were women. Despite functional limitations, 65% reported aging well. Five themes emerged: maintaining physical function, maintaining cognitive function, sustaining social relationships, avoiding pain, and promoting overall well-being. Avoiding pain and promoting well-being extended beyond traditional models. Neighborhood context shaped priorities, with financial stability emphasized in more affluent areas and social cohesion prioritized in less affluent communities. Conclusions: Older adults with HF frequently perceive themselves as aging well despite chronic illness, reframing successful aging beyond disease avoidance. These findings support a patient-centered, place-informed model of aging well with implications for healthcare delivery and policy.

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

Online Shift Detection and Conformal Adaptation for Deployed Safety Classifiers

arXiv:2606.11949v1 Announce Type: new Abstract: We present an online monitoring system for distributional shift in deployed safety classifiers, using calibrated sequential statistics to detect when a classifier has moved out of distribution. Upon detection, a conformal abstention layer adapts decision thresholds to recover a target error rate epsilon=0.1. In a pre-registered factorial evaluation (4 classifiers x 5 shift conditions x 20 seeds x 2 window sizes, 800 cells), the system achieves 86.6% valid detection (693/800, 95% CI [84.1%, 88.8%]) with mean latency of 39.5 steps. Detection holds across three ground-truth regimes: synthetic onset (86.6%), real temporal jailbreaks (85%, 17/20), and GCG adversarial attacks. Weighted conformal prediction recovers up to 39 pp of lost coverage for DeBERTa (ESS=46/300) but collapses for all other classifiers (ESS~300): logistic density ratio estimation achieves perfect source/target separability in high-dimensional embedding spaces, clipping all importance weights to the floor. DeBERTa shows a gradient from effective correction (paraphrase, ESS=46) to near-total collapse (adversarial suffix, ESS=206). PCA to 32 dimensions breaks the collapse, recovering 33 pp for Llama Guard and 21 pp for ShieldGemma. Variance decomposition reveals classifier (eta^2=0.243), shift type (eta^2=0.237), and their interaction (eta^2=0.185) all contribute substantially to detection latency variance (all p

21.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

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

Phase-Localized Curation Does Not Help: A Negative Result on Per-Phase Metric Selection for Demonstration Filtering

作者:

arXiv:2606.15064v1 Announce Type: new Abstract: Manipulation demonstrations have temporal phase structure, and a natural hypothesis is that demonstration-curation metrics should be applied within phases rather than globally. The idea is to segment each trajectory into phases, score each phase with the metric that is locally most informative, and then aggregate. This follows directly from prior work showing that a single global metric can be the best detector of a defect and yet the worst curator of the resulting policy. We test the per-phase hypothesis on three contact-rich LIBERO pick-and-place tasks with a controlled early-release structural defect, comparing phase-gated curation against the same metrics applied uniformly and against a strong single global metric. Across all three tasks and five random seeds per condition, phase-gated curation is never the best curation strategy, and it is the worst of the three on two of the three tasks (Task 1: 86.0 vs. 92.0 for global; Task 3: 22.7 vs. 48.0 for uniform). We trace the failure to a concrete mechanism. When the defect signal is concentrated in a single phase, rank-aggregating across phases dilutes that signal with uninformative scores from defect-free phases, selecting a worse demonstration subset than simply applying the defect-informative metric everywhere. We further show that the per-phase metric selection does not transfer across tasks, since no phase shares a winning metric between any two tasks, so the selection cannot be reused and must be re-derived per task from a noisy sweep. These results bound a plausible and previously untested method, and they argue that practitioners should prefer identifying a single defect-informative metric over decomposing curation by phase. We release the full pipeline, all metric implementations, and per-seed results.

24.
arXiv (CS.CL) 2026-06-16

Agentic Retrieval and Reinforcement Learned Equation Chains: A Controlled Generation Framework for Complex and Novel Physics Word Problems

Generating high-quality Physics Word Problems (PWPs) that are novel, complex, and solvable remains a challenging and underexplored problem in educational content generation. Existing approaches, many adapted from Math Word Problem (MWP) generation, often produce ambiguous, unsolvable, or structurally simple questions with limited linguistic diversity. We introduce ARVRE (Agentic Retrieval Value Reinforced Equation-chain), a two-stage framework for generating diverse and mathematically valid PWPs. In the first stage, a form of offline temporal-difference learning is used to construct valid chains of physics equations, while an agentic retrieval-augmented generation (RAG) framework dynamically selects topic-specific concepts and vocabulary. This design enables explicit control over problem structure and difficulty. In the second stage, a Large Language Model (LLM) converts the equation chain and retrieved concepts into a natural-language physics question. By grounding generation in valid equation chains, our method preserves mathematical correctness while promoting linguistic diversity and contextual richness. Human and automated evaluations demonstrate that ARVRE generates PWPs that are more complex, novel, and solvable than those produced by existing approaches. These results highlight the potential of combining reinforcement learning, retrieval, and LLMs for reliable generation of educational physics content.

25.
arXiv (CS.CV) 2026-06-12

Quality-Preserving Imperceptible Adversarial Attack on Skeleton-based Human Action Recognition

Adversarial attacks on skeletal human action recognition have received significant attention. However, existing methods typically introduce noise-like perturbations that degrade motion quality post-attack, and thereby are inherently perceptible with recent advancements in S-HAR systems. We discover that this degradation stems from the gap between empirical and true risks during the optimization process of previous adversarial attacks. To address this issue, we propose an attack where adversarial motions are obtained without compromising their motion quality. To minimize the risk gap and preserve motion quality, we propose a distribution-based adversarial attack method without introducing noise-like perturbations. To faithfully evaluate the motion quality, we propose a new metric that aligns with human perception on real-world naturalness. Experiments have been conducted on the state-of-the-art S-HAR methods across two datasets, demonstrating the superiority of our method in both the attack success rate and the post-attack motion quality through qualitative and quantitative analyses. The success of our quality-preserving attack application and distribution-based method raises serious concerns about the robustness of action recognizers, highlighting the need for further enhancements in this domain.