Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (CS.CL) 2026-06-17

Prompt Perturbation for Reliable LLM Evaluation over Comparison Graphs

Evaluating large language models (LLMs) is important for understanding their capabilities, comparing competing systems, and supporting the deployment of reliable models in practice. For open-ended tasks, pairwise evaluation has become a popular paradigm, in which two responses to the same prompt are compared and the resulting judgments are aggregated into an overall ranking. A central challenge of this paradigm is intransitivity: the induced comparison outcomes may fail to support any coherent global ranking. For example, one may observe cyclic preferences such as $A \succ B \succ C \succ A$, or inconsistencies involving ties such as $A \equiv B\equiv C\neq A$. Such contradictions make the resulting leaderboard unstable and challenging to interpret. In this paper, we propose a prompt perturbation framework for improving the consistency of pairwise LLM evaluation. Our approach generates perturbed variants of each prompt, uses the resulting comparison graphs to identify and filter out structurally inconsistent comparison patterns, and then applies standard ranking methods to the filtered comparisons. A key feature of the proposed framework is that graph-level structural consistency is incorporated explicitly into the evaluation pipeline before ranking aggregation. This provides a simple and principled way to reduce cyclic inconsistencies and improve the reliability of LLM rankings.

02.
arXiv (CS.AI) 2026-06-12

Boosting Direct Preference Optimization with Penalization

作者:

arXiv:2606.12505v1 Announce Type: cross Abstract: Offline preference optimization has become a practical substitute for reinforcement learning from human feedback, but pairwise objectives such as Direct Preference Optimization (DPO) and its variants use only the chosen and rejected responses stored in a static dataset. This leaves a useful signal unused: the response that the reference model itself would generate for the same prompt. We propose Direct Preference Optimization with Penalization (DPOP), a simple extension of DPO that augments the base preference loss with a gated penalty on reference-greedy responses. DPOP activates this penalty only when the current policy still assigns a lower likelihood to the preferred response than to the rejected response. On AlpacaEval 2.0, DPOP improves length-controlled win rate over DPO, SimPO, and AlphaDPO on both Llama-3-8b-it and Gemma-2-9b-it, achieving relative gains of 5.3\% and 4.4\% over baselines on the two models, respectively. Ablations further show that a SimNPO-style length-normalized penalty is stronger than NPO and token-level unlikelihood in this setting.

03.
arXiv (CS.CV) 2026-06-11

ERN-Net : Evolving Reason Node-Net for Document Binarization

This paper presents ERN-Net, an Evolving Reason Node-Net for efficient document image binarization. ERN-Net enhances degradation-sensitive regions, such as faint strokes, broken characters, and noisy backgrounds, through evolving reason nodes and multi-scale reasoning. We further compare ResNet-101, ConvNeXt-Tiny, and ConvNeXt-Base, and find that ConvNeXt-Tiny provides the best practical trade-off between accuracy and memory usage. In addition, DIBCO-based pretraining improves binarization performance without increasing model memory consumption, requiring only about 1.5 additional training hours. Experiments on DIBCO-style benchmarks show that ERN-Net is effective under low-data and low-memory settings.

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

SiGnature: Explicit Motion Diffusion for Stylized Semantic Gesture

While recent advances in co-speech gesture generation have achieved impressive rhythmic synchronization, synthesizing gestures that are both semantically meaningful and faithful to a speaker's unique non-verbal style remains an open challenge. Semantic gestures, such as iconic shapes or deictic pointing, are statistically sparse, making them difficult to learn effectively within standard generative models. We present SiGnature, a framework for Stylized and Semantic Gesture generation that reconciles precise semantic control with high-fidelity style preservation. Unlike prevalent methods that rely on entangled latent representations, SiGnature operates in an explicit joint-rotation space. This design enables our core contribution, Joint Motion Integration (JMI), a training-free inference mechanism capable of injecting any external motion sequence, particularly in-the-wild semantic gestures, directly into the diffusion process. JMI automatically identifies the specific ``active joints'' conveying a semantic action and injects them into the generation, while relying on the diffusion backbone to synthesize the remaining body dynamics, including posture and flow, in accordance with the pre-learned style of the target speaker. This allows for the plug-and-play integration of arbitrary motions, including complex semantic gestures, without retraining or introducing the ``Frankenstein'' artifacts typical of cut-and-paste methods. Extensive experiments and perceptual studies demonstrate that SiGnature offers superior semantic motion control while maintaining smooth and natural co-speech gesture generation and preserving the distinct characteristics of the speaker, thereby outperforming state-of-the-art baselines.

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

Stringalign: Moving beyond summary statistics with a transparent Unicode-aware tool for evaluating automatic transcription models

Comparing text strings is crucial when evaluating and understanding the performance of various text processing tasks such as document recognition and audio transcription. With an increasingly complex landscape of AI-based handwritten text recognition (HTR), optical character recognition (OCR) and automatic speech recognition (ASR) models, there is a need for tools that facilitate evaluation in a flexible and reproducible way. This paper presents Stringalign, a Python library designed to simplify the evaluation process for automatic transcription projects and facilitate transparent evaluation. Stringalign's tools to examine and visualise both the rate of errors and the types of errors a model makes, give insights into possible improvements and help inform model selection for a particular task. Widely used string comparison metrics, such as the character and word error rates (CER and WER), although useful, can be ambiguous due to varying definitions of what constitutes a character and a word. Stringalign addresses this challenge by ensuring all preprocessing (i.e. normalisation and tokenisation) is transparent and easily replicable, and by providing tools to move beyond summary statistics and analyse common model errors. Moreover, Stringalign adheres to FAIR (Findable, Accessible, Interoperable, and Reusable) principles for research software while staying lightweight and easy to adapt into researchers existing workflows. In this paper, we discuss challenges with character and word level string comparisons and show through examples that where existing tools can yield opaque and sometimes confusing results, Stringalign provides an easy-to-use and unambiguous alternative.

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

Prototyping an AI-powered Tool for Energy Efficiency in New Zealand Homes

arXiv:2509.05364v2 Announce Type: replace-cross Abstract: Residential buildings contribute significantly to energy use, health outcomes, and carbon emissions. In New Zealand, housing quality has historically been poor, with inadequate insulation and inefficient heating contributing to widespread energy hardship. Recent reforms, including the Warmer Kiwi Homes program, Healthy Homes Standards, and H1 Building Code upgrades, have delivered health and comfort improvements, yet challenges persist. Many retrofits remain partial, data on household performance are limited, and decision-making support for homeowners is fragmented. This study presents the design and evaluation of an AI-powered decision-support tool for residential energy efficiency in New Zealand. The prototype, developed using Python and Streamlit, integrates data ingestion, anomaly detection, baseline modeling, and scenario simulation (e.g., LED retrofits, insulation upgrades) into a modular dashboard. Fifteen domain experts, including building scientists, consultants, and policy practitioners, tested the tool through semi-structured interviews. Results show strong usability (M = 4.3), high value of scenario outputs (M = 4.5), and positive perceptions of its potential to complement subsidy programs and regulatory frameworks. The tool demonstrates how AI can translate national policies into personalized, household-level guidance, bridging the gap between funding, standards, and practical decision-making. Its significance lies in offering a replicable framework for reducing energy hardship, improving health outcomes, and supporting climate goals. Future development should focus on carbon metrics, tariff modeling, integration with national datasets, and longitudinal trials to assess real-world adoption.

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

Dynestyx: A Probabilistic Programming Library for Dynamical Systems

arXiv:2606.16985v1 Announce Type: cross Abstract: State-space models (SSMs) are the standard formalism for Bayesian treatment of dynamical systems, with natural applications in statistics, signal processing, and machine learning. Despite their importance in both theory and application, dynamical systems have proven difficult to incorporate in modern probabilistic programming languages (PPLs), making state-of-the-art methods less accessible to practitioners and introducing friction in following the "Bayesian workflow." We introduce dynestyx, a probabilistic programming library with first-class support for SSMs, including state-of-the-art methods in the estimation of both states and parameters. Through a single, unified interface, users may specify arbitrary priors for discrete-time or continuous-time dynamical systems, perform inference over mixed-effect data, and make state and parameter estimates with principled uncertainty quantification.

08.
arXiv (CS.LG) 2026-06-16

Biarchetype analysis for univariate functional data. An application to macroeconomic financial time series

arXiv:2606.15881v1 Announce Type: cross Abstract: We introduce biarchetype analysis for the first time in the context of univariate functional data. This unsupervised methodology extends archetype analysis by simultaneously identifying archetypal structures across both the cases (countries, in our application) and the temporal argument. Both cases and time points are expressed as mixtures of biarchetypes, yielding a concise and highly interpretable representation of complex functional observations. Although biarchetype analysis is not intended as a clustering technique, it offers superior interpretability compared with biclustering approaches, as it is based on extreme, representative patterns rather than average centroids, thereby enhancing human comprehension. We apply the proposed method to 10-year government bond yields of European countries over the period 2001-2025. The results identify three distinct time regimes (the pre-crisis period, the euro-area sovereign debt crisis, and the post-crisis period), and reveal Germany, Greece, and Hungary as country archetypes.

09.
arXiv (CS.LG) 2026-06-19

Adversarial Dependence Minimization

arXiv:2502.03227v2 Announce Type: replace Abstract: Minimally redundant representations are typically learned by minimizing feature covariance. However, covariance-based methods fail to eliminate all dependencies/redundancies, as linearly uncorrelated variables can still exhibit nonlinear relationships. To address this, we introduce ADM, a differentiable algorithm that minimizes statistical dependence between feature dimensions through an adversarial game: auxiliary networks identify dependencies, while the encoder removes them. We prove that mutual independence is achieved at the global optimum, empirically verify convergence, and study three potential applications: extending PCA to nonlinear decorrelation, improving generalization in image classification, and preventing dimensional collapse in self-supervised learning. By promoting statistically independent representations, ADM paves the way for learning more robust, compressed, and generalizable representations across diverse applications.

10.
arXiv (CS.CL) 2026-06-15

CoRe: A Continuously Reward-Finetuned LLM Query Rewriter for Multi-Stage Context-Aware Relevance in Web-Scale Video Search

LLM-based query rewriters in production face a tension: the training reward must reflect how the rewrite is consumed by the production ranker, yet the training procedure must be cheap enough to support continuous redeployment as data drifts. We present CoRe (Context Relevance), such a system, redeployed weekly for over five months in a major short-video search engine. Our reward uses the deployed multimodal relevance model as its source and a multiplicative ratio form mirroring the production fusion algebra, closing the simulation-production gap that offline reward proxies leave open. A semi-online Mixed Preference Optimization loop makes this reward affordable at multi-million-instance weekly scale: a DPO-style pairwise objective restricts the gradient pass to a small top-k/bottom-k subset of sampled trajectories, and a phase structure reduces trainer/inference-server parameter syncs from per-step to per-phase. An automated promotion gate over reward-like and stability metrics detected and recovered from a real reward-hacking incident in production. Rewriter output is consumed as parallel relevance signals at recall, rawrank, and finerank without displacing the original signals, bounding rewriter-failure blast radius. Online A/B from two sequential production launches, first deploying the rewriter at finerank, then extending consumption to recall and rawrank, delivers statistically significant reductions in change-query rate on rewrite-impacted queries, with all headline relevance and engagement metrics moving in the expected direction.

11.
medRxiv (Medicine) 2026-06-22

Clinical-grade Cuffless Blood Pressure Monitoring via Deep-tissue Diffuse Speckle Pulsatile Flowmetry

Blood pressure (BP) is a vital sign which is measured to diagnose and manage hypertension. However, current methods to measure BP use inflatable cuffs which cause discomfort and limit the frequency at which measurements can be made, or intra-arterial catheters which are invasive and pose infection risks. Here, we propose and evaluate the use of Diffuse Speckle Pulsatile Flowmetry (DSPF) as a cuffless BP measurement method to address these limitations. DSPF is a laser speckle-based technique which simultaneously records blood flow rate and blood volume (i.e. photoplethysmography or PPG) signals from relatively deep vascular tissue. Using information from these signals, we studied DSPFs effectiveness in measuring systolic BP (SBP) and diastolic BP (DBP) through an outpatient study in which 133 patients were recruited, and in measuring beat-to-beat BP waveforms through an inpatient study in which two patients were recruited. In the outpatient study, the DSPF method was able to achieve mean absolute errors (MAEs) of 4.17 mmHg and 2.42 mmHg for SBP and DBP respectively compared to conventional cuff-based methods. It was also able to fulfil the requirements of the AAMI/ESH/ISO 81060-2:2018 standard for BP measurement devices and attain an "A" grade according to the British Hypertension Society grading scheme. For the inpatient study, it produced BP waveforms which had MAEs of 2.35 mmHg and 3.06 mmHg compared to arterial-line measurements for the two patients, respectively. Compared to PPG which has been studied more extensively as a cuffless BP measurement method, we found through ablation studies that DSPF was able to reach significantly lower MAEs and hence better accuracies. DSPF augments the performance of PPG-only methods by leveraging additional information from the blood flow rate signal, and we therefore find it to be a superior cuffless BP measurement method which can potentially be used in outpatient, inpatient, and remote settings.

12.
Nature (Science) 2026-06-17

A prototype differential atom interferometer for fundamental physics

Gravitational waves and ultralight dark matter are among the most compelling frontiers in fundamental physics, motivating proposals for very-long-baseline atom interferometerssuch as AION1, MAGIS2, AICE3 and AEDGE4 that aim to detect at frequencies at which ground-based5 and space-borne6 laser interferometers lose sensitivity. Very-long-baseline atom interferometers look for signals by comparing the quantum phase evolution of widely separated atomic ensembles interrogated by a common laser. However, their performance depends critically on suppressing noise sources, particularly laser phase noise. The experimental validation of such noise rejection remains an important challenge. Here we demonstrate a prototype differential atom interferometer based on the single-photon clock transition of fermionic 87Sr. Thus, we obtain a gradiometer configuration with a species intrinsically suited to kilometre-scale and space-baseline operation. The instrument operates at the standard quantum limit7 with no excess noise beyond atom shot noise. The differential configuration maintains quantum-limited sensitivity in the presence of several radians of artificially injected laser phase noise per shot, which emulates the conditions expected in a very-long-baseline atom interferometer. We also demonstrate the recovery of coherent oscillatory signals across a broad frequency range under fully phase-randomized conditions, a capability that is inaccessible to a single interferometer operating in the same regime. These results provide an experimental validation of the noise-immune measurement principle underlying very-long-baseline atom interferometers and mark an important step towards next-generation quantum sensors for gravitational-wave detection and searches for ultralight dark matter8,9. A prototype differential atom interferometer operates at the standard quantum limit with no excess noise beyond atom shot noise, achieving performance in line with the specifications for future long-baseline atom interferometers.

13.
arXiv (CS.CL) 2026-06-12

G-Long: Graph-Enhanced Memory Management for Efficient Long-Term Dialogue Agents

While Large Language Models (LLMs) have advanced open-domain dialogue systems, maintaining long-term consistency remains a challenge due to inherent limitations in long-context reasoning and the inefficiency of processing extensive raw text. Existing approaches typically rely on either unstructured memory storage, which is prone to information loss, or computationally expensive LLMs that incur high latency. To address these limitations, we propose G-Long, a graph-enhanced framework that utilizes a fine-tuned small Language Model (sLM) for structured triplet extraction and associative retrieval, significantly reducing operational costs. Furthermore, we introduce the novel attention-aware importance scoring mechanism that leverages the intrinsic cross-attention signals of a T5 summarizer to identify salient memories. Extensive experiments across diverse benchmarks demonstrate that G-Long achieves state-of-the-art performance in both response generation and memory retrieval, yielding performance gains of up to 9.8% in response quality on MSC and 40.8% in retrieval recall on LME, while significantly minimizing computational overhead.

14.
medRxiv (Medicine) 2026-06-22

Anterior-superior hypothalamic enlargement as specific marker in episodic migraine: converging evidence from an independent discovery-replication design

Background: Growing evidence implicates the hypothalamus as a key structure in migraine pathophysiology; however, our understanding of its precise role and of the specific nuclei involved remains limited. We combined MRI data from our laboratory with publicly available MRI datasets from OpenNeuro to examine hypothalamic subunit volumes in episodic migraine and assess the specificity of these alterations relative to chronic pain conditions. Methods: Structural MRI combined with an automated atlas-based segmentation algorithm and a discovery-replication design was employed to investigate cross-sectional volumetric differences across 5 bilateral hypothalamic subunits in two independent migraine cohorts: DS1-MIG (DS1-MIG-base, n = 111 patients, n = 35 controls) and DS2-MIG (n = 27 patients, n = 31 controls). The adjusted volumes were compared between groups using MANOVA as an omnibus test, followed by Welch t-tests to test univariate follow-up. Longitudinal volumetric changes were additionally assessed in DS1-MIG participants with available follow-up scans using linear mixed models. To assess the specificity of findings to migraine, the same pipeline was applied to two chronic pain datasets, one including patients with fibromyalgia (DS-FM, n = 33 patients, n = 33 controls) and the other including patients with trigeminal neuralgia (n = 119 patients, n = 55 controls). Results: MANOVA revealed significant multivariate group differences in the discovery and replication migraine cohorts (DS1-MIG-base: = .006; DS2-MIG: = .008). Follow-up univariate analyses identified a consistent enlargement of the left anterior-superior subunit across both cohorts (FDR = .023 in DS1-MIG-base and FDR = .046 in DS2-MIG), representing the only cross-cohort replication finding. Beyond this shared signature, DS2-MIG exhibited additional significant enlargements of the right anterior-inferior and right tubular-inferior subunits. Longitudinal analyses in DS1-MIG showed that hypothalamic subunit volumes remained broadly stable over time within both migraine patients and control participants. No significant volumetric alterations were detected in the fibromyalgia or trigeminal neuralgia cohorts, either in multivariate or univariate analyses, underscoring migraine-specific findings. Conclusions: These findings provide evidence for subunit-specific hypothalamic structural alterations in migraine localized in the left anterior hypothalamic subunit. The stability of these differences over time and their absence in other chronic pain conditions suggest a migraine-specific structural organisation of hypothalamic circuitry.

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

Rotational Symmetry based Object Pose Estimation from Point Clouds in the Absence of Known 3D Models

Object pose estimation is crucial to many industrial applications, with one example being automated spray painting using a robot. However, confidentiality concerns often limit access to high-quality 3D models, posing a significant challenge for point-cloud-based pose estimation. In such scenarios, rotational symmetry, a readily accessible characteristic of many industrial objects, can provide valuable prior information to facilitate pose estimation.In this paper, we propose a method that leverages the rotational symmetry commonly found in industrial objects to address the challenge caused by the absence of 3D models. The object pose is jointly estimated with point cloud refinement through an iterative optimization process. This optimization relies on a rotational symmetry constraint loss. To construct this loss, each 3D point is rotated according to the currently estimated pose, and multiple correspondences are identified using nearest-neighbor search by exploiting the rotational symmetry property. These correspondences are then used to compute the rotational symmetry constraint loss, which iteratively refines both the pose and the point cloud.By explicitly incorporating rotational symmetry into the optimization process, the proposed method achieves robust pose estimation and generalizes well across diverse object types. The proposed method is evaluated on a dataset specifically created for point clouds without known 3D models, consisting of four categories of synthetic objects and one real wheel hub collected from a production line. Experimental results demonstrate that the proposed method achieves performance comparable to methods that rely on known 3D models.

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

Beyond Self-Attention: Sub-Quadratic Vision Transformers for Fast Image Captioning

Image captioning is a challenging and significant task that aims to generate coherent and semantically meaningful textual descriptions for given images. To accomplish this task, it requires a deep understanding of visual content along with the ability to express that understanding in natural language. Despite remarkable progress with transformer-based architectures, existing approaches often suffer from limitations, such as a lack of rich local feature representations and the high computational cost of quadratic self-attention. The proposed model focuses on improving computational efficiency by restructuring the vision transformer architecture. In designing this approach, the standard self-attention mechanism in Vision Transformers is replaced with a probabilistic transformer approach based on a Gaussian Mixture Model (GMM), a soft-clustering technique. Instead of computing pairwise attention among all image patches, the model groups similar patches into a fixed number of clusters using an Expectation-Maximization (EM) algorithm. This clustering-based mechanism reduces the computational complexity from quadratic O(n^2) to linear O(nK), where K

17.
arXiv (CS.CL) 2026-06-19

IHUBERT: Vector-Based Semantic Deduplication and Domain-Balanced Pretraining for Persian Resources

Persian pretrained language models (PLMs) are still limited by the scarcity of large-scale, high-quality pretraining corpora and by insufficient evaluation beyond standard classification and NER tasks. We present IHUBERT, a monolingual Persian PLM trained from scratch with the RoBERTa-base encoder (125M parameters) on a 45 GB curated subset of the Sepahr-Danesh collection (about 7-8B tokens). To improve corpus quality and reduce redundancy, we employ a multi-stage preprocessing pipeline that includes normalization, exact and near-duplicate removal, anonymization, and vector-database-based semantic deduplication for distribution balancing control across domains and registers. We additionally train a 139k-vocabulary BPE tokenizer on the full pretraining corpus to better capture Persian morphology and orthographic variation. IHUBERT is evaluated on seven Persian NLU benchmarks covering NER, sentiment analysis, topic classification, NLI, extractive question answering, and relation extraction, using task-standard metrics (entity-level F1, Macro-F1, EM/F1). IHUBERT achieves its strongest gains on extractive QA, ranking first on both PQuAD (F1 88.3542) and ParsiNLU-RC (F1 49.0987), and attains the best result on FarsTail (Macro-F1 0.8350). On NER and topic classification, it remains competitive (e.g., 0.8308 F1 on ParsTwiNER; 0.7953 Macro-F1 on DigiMag), while relation extraction remains the main remaining gap (0.6684 Macro-F1 on PERLEX). A controlled tokenizer ablation on the IHUBERT pretraining corpus shows that BPE yields slightly lower subword fragmentation than WordPiece at matched vocabulary size, supporting our tokenization design. Overall, IHUBERT advances Persian language modeling through semantically curated large-scale pretraining and broad evaluation across both classification and comprehension-oriented tasks.

18.
arXiv (CS.LG) 2026-06-16

Factorized Neural Operators Decompose Dynamic and Persistent Responses

arXiv:2606.16900v1 Announce Type: new Abstract: Physical systems often exhibit heterogeneous mechanisms, where rapidly evolving dynamics coexist with persistent structures. Capturing such multiscale physical behavior remains challenging for existing neural operators, which typically rely on single dominant inductive bias and therefore couple distinct physical responses into a shared representation. We introduce the Unified Green's Function Framework across domains and propose the Factorized Neural Operators (FaNO), which decompose spectral representations into equivariant dynamic responses and invariant persistent responses, leading to better interpretability and generalization. Mechanistically, we show that the two operator branches spontaneously specialize into distinct physical roles that remain consistent across scales and domains: the equivariant branch captures rapidly varying transient dynamics, whereas the invariant branch extracts coherent persistent structures. This factorized mechanism of FaNO improves prediction accuracy, parameter efficiency and cross-scale generalization across physical systems and domains. In particular, it maintains consistent predictions under long-horizon autoregressive rollout, cross-resolution extrapolation and physical-regime shifts. These findings suggest that scalable physical modeling may benefit from moving beyond single-inductive-bias formulations toward factorized operator representations that better reflect the heterogeneous organization of physical systems, accelerating the reliable deployment of machine learning for scientific computing and discovery.

19.
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.

20.
arXiv (quant-ph) 2026-06-17

Quantum Resources and Wigner Symmetry in Nucleon-Nucleon Scattering from Effective Field Theory

arXiv:2606.17148v1 Announce Type: cross Abstract: We study quantum resources in the spin degrees of freedom, such as entanglement, stabilizer magic, and non-local magic, in low-energy nucleon-nucleon scattering through next-to-leading order in pionless effective field theory. Treating each nucleon spin as a qubit, we calculate the corresponding resource-generating powers of the scattering operator at generic center-of-mass momentum and scattering angle $\Theta$. The analysis retains $S$- and $P$-wave channels generated by two-derivative contact interactions. When the microscopic physics exhibits Wigner's $SU(4)$ spin-flavor symmetry, the neutron-proton amplitude becomes proportional to the spin-space identity operator and therefore generates no new resources after scattering, extending an observation previously made for leading-order $S$-wave scattering. The same-nucleon channel remains resource-generating because constraints from identical particles project out part of the Hilbert space. These results show how enhanced symmetries, partial-wave structure, and resource generation are intertwined in low-energy two-body scattering.

21.
bioRxiv (Bioinfo) 2026-06-22

CellTosg2Sequence: A Unified Text-Omics-Signaling-Graph Large Language Model for Single-Cell Analysis

bioRxivLaTeXUnicodeabstract — In single-cell (sc)-based scientific discovery, text-formatted biomedical prior knowledge and signaling graphs are essential for annotating and interpreting numeric sc-omics data and for generating novel testable hypotheses. A major limitation of existing single-cell large language models (scLLMs) is that they rely on numeric expression data with gene names as the only textual signal, while comprehensive biomedical priors – cellular localization, gene function, disease associations, and signaling interaction patterns – remain absent from the model input. We introduce CellTosg2Sequence, a textual-prior- and signaling-graph-augmented cell-omics-sentence language model. A lightweight heterogeneous graph encoder maps a curated 62,507-node biomedical knowledge graph (KG) into compact virtual tokens that are prepended to each cell sentence, allowing the language model to condition on biological structure with minimal sequence-length overhead. We train CellTosg2Sequence with a three-stage objective: Stage I anchors the KG channel under autoregressive language-model pretraining, leveraging Qwen2.5-32B's own language reasoning for rapid KG alignment; Stage II aligns labels via supervised fine-tuning with KG-anchored InfoNCE; Stage III applies Group Relative Policy Optimization (GRPO) with an ontology-hierarchy reward, enabling free-generation cell-type prediction that generalizes beyond the closed training vocabulary. Across multiple benchmarks and ablation experiments, CellTosg2Sequence outperforms strong baselines. All results are achieved with lightweight LoRA training and a single unified checkpoint.

22.
arXiv (CS.AI) 2026-06-11

Making Models Unmergeable via Scaling-Sensitive Loss Landscape

arXiv:2601.21898v2 Announce Type: replace Abstract: The rise of model hubs has made it easier to access reusable model components, making model merging a practical tool for combining capabilities. Yet, this modularity also creates a governance gap: downstream users can recompose released weights into unauthorized mixtures that bypass safety alignment or licensing terms. Because existing defenses are largely post-hoc and architecture-specific, they provide inconsistent protection across diverse architectures and release formats in practice. To close this gap, we propose Trap$^2$, an architecture-agnostic protection framework that encodes protection into updates during fine-tuning, regardless of whether they are released as adapters or full models. Instead of relying on architecture-dependent approaches, Trap$^2$ uses weight re-scaling as a simple proxy for the merging process. It keeps released weights effective in standalone use, but degrades them under re-scaling that often arises in merging, undermining unauthorized recomposition.

23.
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.

24.
medRxiv (Medicine) 2026-06-16

Physiological Aging of the Respiratory System (PARS): from development to application

Background: Aging has a critical role in lung changes and the outcome of lung disease. Several lung aging equations have been proposed to measure deviation from physiological aging of the respiratory system. In this study, we aimed to develop a single measure of accelerated lung aging and show its application as a measure of lung aging. Method: We used a pre-bronchodilator pulmonary function test (PFT) from NHANES adult participants recruited from 2007 to 2011. We applied Klemera-Dubal Method (KDM) to four PFT measurements, FEV1, FVC, FEF25-75, and PEF, to calculate a measure of lung biological aging. Physiological Aging of the Respiratory System (PARS) was calculated from the residual method vs. chronological age. We tested the construct validity of PARS by measuring its association with risk factors of lung health. The prognostic validity was measured using a survival analysis. Sampling weights were applied to all analyses. Results: In 14,123 adult participants, the mean (SD) of accelerated lung age (PARS) was 0 (8.2) years. Participants with a history of asthma and emphysema had 4- and 10-year higher PARS. Cigarette smoking, lower socioeconomic status, black race, higher serum cadmium, and lower serum selenium and magnesium were associated with higher PARS. During 116 months of follow-up, PARS was associated with a higher mortality (HR = 1.06, 95%CI: 1.05-1.07 per year). Females with higher PARS had a higher risk of death (P for interaction < 0.001). Results were consistent across different subgroups and sensitivity analyses. Conclusion: PARS is a noninvasive lung aging marker and can be applied as a single measure of lung accelerated aging in the adult population. Its strong construct and predictive validity support its future application among different populations with and without lung disease.

25.
arXiv (CS.CV) 2026-06-16

An Extensive Benchmark for Single-round and Multi-round Instruction-based Image Editing

In recent years, there have been notable advancements in the area of instruction-based image editing (IIE), which focuses on the automatic alteration of input images using a model. Nevertheless, assessing the effectiveness of these editing models poses a considerable challenge due to the intricate nature of instructions and the wide variety of edits. To tackle this problem, one urgent task in this domain is the development of a robust evaluation framework that can precisely gauge the quality of editing outcomes and offer valuable benchmarks to guide future improvements. To address this challenge, we present a comprehensive evaluation benchmark named I2EBench2.0, designed for single-round and multi-round assessment of IIE models. I2EBench2.0 has four key features: 1) Evaluation Across Single and Multi-rounds: I2EBench2.0 simultaneously evaluates both single-round and multi-round instruction-based edits, assessing the precision and consistency of the edits. 2) Extensive Evaluation Criteria: I2EBench2.0 encompasses a broad range of criteria, evaluating both high-level and low-level aspects of each IIE model. Specifically, it incorporates 16 dimensions for single-round evaluations and 7 for multi-round evaluations. 3) Alignment with Human Judgment: To ensure our benchmark aligns with human evaluation, we conducted a comprehensive user study for each criterion. 4) Research-driven Insights: By analyzing the strengths and weaknesses of current IIE models across all 16 single-round and 7 multi-round dimensions, we provide critical insights aimed at directing future research in this area. We tested eight recently developed IIE models using I2EBench2.0 and derived academic insights through meticulous comparison and analysis. The related code, dataset, and images generated by all IIE models are available on GitHub: https://github.com/cocoshe/I2EBench.