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01.
arXiv (CS.CL) 2026-06-16

CAF-Gen: A Multi-Agent System for Enriching Argumentation Structures

Formalizing complex reasoning from natural text is one of the central challenges in computational linguistics. It requires systems to understand not just keywords but also the context and complex reasoning embedded in a text. Current Argument Mining (AM) techniques identify basic claims and premises, yet they often struggle to capture the richer structural information required by advanced schemas such as the Carneades Argumentation Framework (CAF), which incorporates features such as premise types, proof standards, and argument schemes. We address this limitation by introducing CAF-Gen, an automated multi-agent framework designed to enrich shallow argument structures into CAF-compliant argument models. By employing an iterative Creator-Reviewer pipeline, a creator agent's output is validated by a critical agent to ensure structural integrity. This multi-agent collaboration is crucial for mitigating the structural instability typical of single-pass generative models. Our experiments demonstrate that the iterative feedback loop improves the quality of the resulting data and achieves strong alignment with the original annotations, while producing structurally richer models. Our findings show that the multi-agent system can overcome the limitations of single-pass generation, providing a robust methodology for the automated modeling of formal argumentation.

02.
arXiv (CS.AI) 2026-06-16

Snyk VulnBench JS 1.0: Can LLMs Find the Same Bugs Twice?

arXiv:2606.15762v1 Announce Type: cross Abstract: We ran 300 repeated vulnerability-finding scans to measure how repeatable agentic large language model (LLM) security review is on the same JavaScript code, prompt, and benchmark harness. The headline result is that LLM security findings were unevenly repeatable: reference-matched findings were stable, but extra model reports varied heavily from run to run. Across 250 model runs, 80 of 161 unique unmatched findings appeared in only one of five identical repetitions, while only 22 appeared in all five. By contrast, when Claude matched a Snyk Code reference finding, the behavior was much more stable: 134 of 158 unique reference-matched findings appeared in all five repetitions. The benchmark also shows complementarity. Models consistently found familiar, high-signal exploit shapes, and in one case surfaced a likely Snyk Code product gap. Snyk Code static application security testing (SAST) was deterministic and better at systematically enumerating repeated data-flow sinks. The results support combining agentic LLM review with deterministic SAST rather than treating either technique as a replacement for the other.

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

Controlled Dynamics Attractor Transformer

arXiv:2606.15207v1 Announce Type: cross Abstract: Transformer architectures have dramatically advanced representation learning and inference in deep models through self-attention mechanisms. In parallel,associative memory (AM) frameworks map representations onto energy landscapes, offering interpretable retrieval mechanisms. However, their continuous-time inference dynamics lack the biological plausibility of classical Continuous Attractor Neural Networks (CANNs). To bridge this gap, we propose Controlled Dynamics Attractor Transformer (CDAT), which couples a mixture von Mises-Fisher (Mo-vMF) attention energy with a Hopfield refinement energy, while augmenting energy descent with a CANN-inspired excitation-inhibition modulation. CDAT instantiates a topology-constrained dynamical system whose couplings encode relational structure among tokens, thereby linking attractor-style dynamics to modern energy-based attention. We further provide a constructive dissipation analysis to formally establish their controlled inference dynamics. Benefiting from these robust and structured dynamics, CDAT achieves state-of-the-art performance across multiple benchmarks in graph anomaly detection and graph classification.

04.
arXiv (CS.CV) 2026-06-24

Training-Time Optical Priors for Wireless Capsule Endoscopy Classification: Hemoglobin-Aware Input Fusion with Cross-Vendor Evaluation

Background. RGB-trained classifiers for wireless capsule endoscopy (WCE) conflate hemoglobin contrast with bile staining and illumination falloff, limiting sensitivity to small-vessel vascular findings such as Lymphangiectasia. We introduce a physics-informed framework that injects an analytic, Monte-Carlo-inspired hemoglobin prior into a standard classifier purely at training time – to our knowledge the first use of an explicit optical light-transport prior in WCE classification. Methods. On Kvasir-Capsule (47,238 frames, 43 patients, 11 evaluable classes; patient-disjoint split) we test, across 6 seeds against an RGB-only EfficientNet-B0 baseline: (i) a 5-channel input-fusion variant feeding the prior P_blood alongside RGB; (ii) a distillation variant that runs on plain 3-channel RGB at inference; and (iii) a three-stream extension adding a temporal Transformer and an autoencoder-residual stream. We replicate across ResNet-18 and ConvNeXt-Tiny and report cross-vendor zero-shot transfer on the public Galar cohort. Results. Input fusion lifts cross-seed macro-AUC 0.760 -> 0.783 (5/6 seeds positive); distillation reaches 0.773; the three-stream model reaches 0.804 (+0.044 over baseline, paired DeLong p < 1e-4). Lymphangiectasia AUC rises 0.238 -> 0.337, sign-consistent across all 6 seeds. A four-variant ablation reveals a parameterization-mechanism boundary: only the spatial-channel form lifts. Cross-vendor zero-shot on Galar retains ~60% of the ConvNeXt-Tiny lift.

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

Gradual Fine-Tuning for Flow Matching Models

arXiv:2601.22495v2 Announce Type: replace Abstract: Fine-tuning flow matching models is a central challenge in settings with limited data, evolving distributions, or computational constraints. While recent work has produced significant advances, particularly in the area of reward-based fine-tuning, current methods fail to demonstrate both theoretical correctness as well as strong empirical results in terms of stability, efficiency, and diversity preservation. In this work, we propose Gradual Fine-Tuning (GFT), a simple yet principled annealing-based framework for fine-tuning flow generative models when only samples from the target distribution are available. For stochastic flows, GFT defines a temperature-controlled sequence of intermediate objectives that smoothly interpolate between the pretrained and target drifts, provably approaching the true target as the temperature approaches zero. We analytically demonstrate that sample generation after GFT can be made substantially more efficient with the use of arbitrary (e.g., optimal transport) couplings, as well as by utilizing few-step inference methods. Empirically, GFT significantly improves convergence stability, while maintaining or improving generation quality, training speed, and generation diversity compared to other fine-tuning methods. Our results position GFT as a simple yet theoretically grounded and practically effective alternative for scalable adaptation of flow matching models under distribution shift.

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

Mitigating Object Hallucinations in LVLMs via Attention Imbalance Rectification

Object hallucination in Large Vision-Language Models (LVLMs) severely compromises their reliability in real-world applications, posing a critical barrier to their deployment in high-stakes scenarios such as autonomous driving and medical image analysis. Through systematic empirical investigation, we identify that the imbalanced attention allocation, both across modalities (i.e., vision and language) and within modalities (among individual tokens), exhibits a strong causal correlation with the occurrence of object hallucination. Leveraging this insight, we introduce a novel concept termed attention imbalance, which not only quantifies the degree of attention disparity but also visually delineates the underlying patterns (e.g., over-attentiveness to irrelevant language tokens or under-attentiveness to discriminative visual features) that drive object hallucination. To mitigate object hallucination, we further propose Attention Imbalance Rectification (AIR), a lightweight decoding-time intervention method that reallocates attention weights and adjusts attention distributions to rectify modality-wise and token-wise imbalances. Extensive evaluations on four mainstream LVLMs and three benchmarks (CHAIR, POPE, and MM-Vet) with seven baselines demonstrate that AIR consistently reduces object hallucination rates, achieving up to a 35.1% reduction compared to the baselines, while improving up to 15.9% of LVLMs' general capability across diverse vision-language tasks.

07.
arXiv (CS.AI) 2026-06-12

GeoNatureAgent Benchmark: Benchmarking LLM Agents for Environmental Geospatial Analysis Across Frontier and Open-Weight Foundation Models

arXiv:2606.12821v1 Announce Type: new Abstract: Environmental scientists spend disproportionate effort on data wrangling rather than analysis, and AI agents that automate geospatial workflows remain unvalidated: no benchmark evaluates agents operating through structured tool calling against real APIs. We introduce the GeoNatureAgent Benchmark, the first benchmark for environmental analysis agents that operate via structured tool calls to a production-style geospatial API. It comprises 93 tasks across 18 categories, covering municipality analysis, multi-turn conversation, spatial reasoning, cross-indicator synthesis, error handling and recovery, ranking, comparison, multilingual understanding, habitat analysis, and task rejection. Tasks are evaluated against an open, self-hostable API serving three environmental indicators across Spain and Portugal via sixteen tools. We evaluate seven LLMs (Claude Sonnet 4, DeepSeek V3.2, GLM-5, Gemini 2.5 Pro, Qwen3-235B, GPT-OSS-120B, Llama 4 Scout) under three temperature-1.0 seeds, reporting capability and per-case cost as orthogonal axes. We find: (1) Claude Sonnet 4 leads at 60.8% +/- 0.8%, followed by DeepSeek V3.2 at 56.3% +/- 3.1%, with no other model above 51%; (2) the cost-accuracy Pareto frontier is occupied mostly by open-weight models, with DeepSeek V3.2 offering 93% of Claude's capability at 11x lower cost ($0.011/case); (3) comparison tasks remain universally unsolved (0% on close-value comparisons), exposing systematic reasoning limits; and (4) structured tool calling against a real API is more discriminative than general-purpose GIS benchmarks, with accuracies 25-35 points lower. We further show extensibility by integrating BigEarthNet V2 land cover for Portugal alongside Spanish CO2 and erosion indicators. The benchmark, harness, and self-hostable API are publicly available.

08.
arXiv (CS.AI) 2026-06-11

When Context Returns: Toward Robust Internalization in On-Policy Distillation

arXiv:2606.11627v1 Announce Type: cross Abstract: Recent work has shown that on-policy distillation can internalize privileged context, such as system prompts or task hints, into a student model so that the context is no longer needed at inference time. Although this approach successfully improves the student's no-context performance, we identify an interesting and previously unstudied phenomenon: in many settings, reintroducing the original privileged context to the distilled student actually degrades its performance, even on instances it already solves correctly without context. We term this context-induced degradation and argue that robust internalization demands not only matching the teacher's context-conditioned behavior, but also remaining stable when the context is reintroduced, a property we call context removability. Motivated by this observation, we propose a lightweight consistency regularizer that first anchors the student's no-context output via stop-gradient, then penalizes the context-conditioned output for deviating from it via forward KL divergence. This simple addition requires only one extra forward pass per training step, yet it effectively mitigates context-induced degradation and, in many cases, even improves no-context performance. Across 12 configurations spanning diverse domains and model families, our method improves context-conditioned accuracy in the majority of settings, reduces context-induced harm in 11 out of 12 settings, and effectively eliminates response-length inflation. A mechanistic case study further confirms that context removability is achieved at the representation level, with hidden states remaining nearly identical regardless of whether the context is present.

09.
arXiv (quant-ph) 2026-06-19

Robust Generation of Topological Biphoton Mode via Adiabatic Passage

arXiv:2606.19786v1 Announce Type: new Abstract: Topological waveguide arrays support robust mode propagation in the presence of fabrication imperfections, providing a significant advantage for on-chip quantum information processing. However, this robustness does not fully extend to nonlinear biphoton generation. Structural disorder can enhance the excitation of non-topological biphoton modes during nonlinear interactions, which degrades the quantum properties of the generated state. To overcome this limitation, we propose an adiabatic passage that connects an isolated site to a topological defect array. By initiating the nonlinear process in a strongly isolated regime, nonlinear coupling to unwanted modes is effectively suppressed, thereby preserving the Schmidt number of the generated state. The subsequent adiabatic connection facilitates the high fidelity transfer of the generated biphoton into the topological biphoton mode. Our numerical simulations demonstrate that, unlike conventional topological structures, the adiabatic scheme maintains both high biphoton fidelity and a unit Schmidt number in the presence of waveguide gap disorder. Furthermore, we show that this robustness extends to path entangled NOON states, achieving a near-unity quantum interference visibility. Our approach provides a practical design strategy for disorder-tolerant integrated quantum photonic devices.

10.
arXiv (quant-ph) 2026-06-24

Crystalline Spectral Form Factors

arXiv:2512.11054v3 Announce Type: replace Abstract: We investigate crystalline-like behavior of the spectral form factor in unitary quantum systems with extremely strong eigenvalue repulsion. Using a low-temperature Coulomb gas as a model of repulsive eigenvalues, we derive the Debye-Waller factor suppressing periodic oscillations of the spectral form factor and estimate the order of its singularities at multiples of the Heisenberg time. We also reproduce this crystalline-like behavior using perturbed permutation circuits and random matrix ensembles associated with Lax matrices. Our results lay a foundation for future studies of quantum systems that exhibit intermediate level statistics between standard random matrix ensembles and permutation circuits.

11.
arXiv (CS.AI) 2026-06-24

CompressKV: Semantic-Retrieval-Guided KV-Cache Compression for Resource-Efficient Long-Context LLM Inference

arXiv:2606.24467v1 Announce Type: new Abstract: Long-context large language model (LLM) inference is increasingly constrained by the memory footprint and decoding cost of key-value (KV) caches, limiting sustainable deployment on resource-constrained hardware. Existing KV cache eviction methods typically apply heuristic token scoring over all heads in GQA-based LLMs. These methods ignore the different functionalities of attention heads, leading to the eviction of critical tokens and thus degrading the performance of LLMs. To address this issue, we propose CompressKV, a resource-efficient KV-cache compression framework for GQA-based LLMs. Instead of aggregating attention scores from all heads, CompressKV identifies Semantic Retrieval Heads (SRHs) that capture both the initial and final tokens of a prompt and semantically important mid-context evidence, and uses them to select tokens whose KV pairs should be retained. Furthermore, CompressKV allocates cache budgets across layers according to offline estimates of layer-wise eviction error. Experiments on LongBench and Needle-in-a-Haystack show that CompressKV consistently outperforms existing KV-cache eviction methods across memory budgets. Notably, it preserves over 97\% of full-cache performance using only 3\% of the KV cache on LongBench question-answering tasks and achieves 90\% accuracy with just 0.7\% KV storage on Needle-in-a-Haystack. These results demonstrate an improved resource–performance trade-off for long-context LLM inference. Our code is publicly available at: https://github.com/TUDa-HWAI/CompressKV

12.
arXiv (CS.AI) 2026-06-16

ToolMenuBench: Benchmarking Tool-Menu Filtering Strategies for Reliable and Efficient LLM Agents

arXiv:2606.15508v1 Announce Type: new Abstract: Tool-augmented large language model agents increasingly operate over large tool libraries, but existing evaluations often focus on whether a model can call a tool correctly rather than how the visible tool menu shapes reliability, efficiency, and safety-relevant risk exposure. We introduce ToolMenuBench, a benchmark for evaluating tool-menu construction in multi-step LLM agents. ToolMenuBench varies tool-menu size, distractor type, state-dependent task structure, and risk exposure, and reports both filter-level and downstream agent metrics, including visible-tool count, risky-tool exposure, task success, wrong-tool calls, premature actions, and token usage. In a controlled evaluation across seven model backends, three tool-menu sizes, six filtering methods, and seven evaluation settings, CMTF improves task success from 32.1% under all-tools exposure to 85.7%, while reducing average token usage by roughly 98%. Causal minimal tool filtering achieves the strongest overall tradeoff, reducing visible tools, wrong-tool calls, premature actions, and risky-tool exposure relative to unfiltered exposure, lexical filtering, state-aware filtering, and broader causal-path baselines. ToolMenuBench provides a reusable evaluation framework for studying the agent-interface problem: which tools should be visible, when they should be visible, and under what cost or risk constraints.

13.
arXiv (CS.AI) 2026-06-24

Prob-BBDM: a Probabilistic Brownian Bridge Diffusion Model for MRI sequence image-to-image translation

arXiv:2606.24313v1 Announce Type: new Abstract: AI-driven image-to-image synthesis is rapidly advancing, with growing applications in medical imaging. Multi-modal image analysis plays a crucial role in optimizing examination quality, yet acquiring multiple imaging modalities in clinical settings remains resource-intensive and time-consuming, especially for 3D imaging. To address this challenge, we propose a novel image-to-image translation model based on Brownian Bridge Diffusion Models (BBDM), which synthesizes magnetic resonance imaging (MRI) sequences from 2D axial slices. Our approach integrates a variational encoder-guided diffusion mechanism, leveraging probabilistic image distributions to enhance synthesis quality. Evaluated on the BraTS 2021 dataset, our Probabilistic-BBDM (Prob-BBDM) achieves superior performance across multiple translation tasks, reaching up to 88.46% SSIM and 26.09 dB PSNR, with consistent improvements over baselines. Notably, our diffusion process requires only 4 steps, making it computationally efficient while maintaining high-quality synthesis. To further validate generalizability, we test Prob-BBDM on an external third-party dataset, demonstrating consistent performance across domains. Additionally, we assess the clinical utility of the synthesized slices by using them as input to a pre-trained segmentation model. Tumor segmentation yields a Dice score of 88.71% and an HD95 of 3.49 mm, confirming that the synthesized slices preserve critical diagnostic information. These results highlight the potential of Prob-BBDM for high-quality, efficient, and generalizable MRI synthesis, offering a promising step toward improved medical image translation.

14.
arXiv (math.PR) 2026-06-18

Stability of Khintchine-type inequalities via log-monotonicity

arXiv:2606.19313v1 Announce Type: new Abstract: We investigate Khintchine-type inequalities for the weighted sums $S=\sum_ka_kX_k$ of independent copies of a symmetric random variable $X$. We show how log-monotonicity of the sequence $r_k(X)=k! \mathbb{E}[X^{2k}]/(2k)!$ implies sharp comparisons between the $L_p$ and $L_2$ norms of $S$ for every even integer $p\geq 2$, extending classic Khintchine-type inequalities and yielding new results in the log-convex setting. We also investigate the stability of our inequalities. Our first stability inequality sharpens the classic inequality by a deviation of the coefficient vector from the coordinate extremizers, while the second quantifies deviation from the Gaussian limit. Our results recover recent stability inequalities for random signs and apply to a broad class of distributions, including type-$\mathscr{L}$ random variables, ultra sub-Gaussian random variables and Gaussian mixtures.

15.
arXiv (math.PR) 2026-06-24

Sparsity-adaptive concentration inequalities for random polynomials

arXiv:2606.24090v1 Announce Type: new Abstract: We prove concentration inequalities for polynomials of independent, sparse $\alpha$-sub-exponential random variables. Specifically, we consider $X_i=\delta_i\xi_i$, where the Bernoulli selectors $\delta_i$ are independent with parameters $p_i$, and the variables $\xi_i$ are independent \(\alpha\)-sub-exponential random variables (not necessarily centered). For any polynomial $f:\mathbb R^n\to\mathbb R $ of degree at most $D$ and any $0

16.
arXiv (CS.AI) 2026-06-19

Emergent Alignment

arXiv:2606.19527v1 Announce Type: new Abstract: Can Large Language Models (LLMs) discern when their own outputs are misaligned with human ethics? And can they self-correct? We endow an LLM with a conscience step that reviews its own reasoning and outputs, and we extend the training loss with an alignment component using Direct Preference Optimization (DPO) to steer the model away from non-ethical outputs. The result is an online technique to align models in a wide range of applications: training, fine-tuning, adversarial prompting, and zero-shot learning. It does not require a weaker or stronger judge, relying instead on a frozen copy of itself. In previous work, the Emergent Misalignment scenario showed a range of emergent unethical behaviors from fine-tuning the model to hack code. Instead, we empirically show how to achieve Emergent Alignment: a single high-level introspective question steers training toward an ethical model under the same code hacking scenario.

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

Evaluating and Enhancing Negation Comprehension in Remote Sensing MLLMs

arXiv:2606.20177v1 Announce Type: cross Abstract: Multimodal Large Language Models (MLLMs) have demonstrated remarkable success in various Remote Sensing (RS) tasks. However, their ability to comprehend negation remains underexplored, limiting deployment in real-world applications where models must explicitly identify what is false or absent, e.g., emergency responders need to locate non-flooded routes for evacuation. To comprehensively study this limitation, we introduce RS-Neg, the first benchmark to evaluate negation understanding across region-level to scene-level tasks. Specifically, we design an automated data generation pipeline for RS imagery, using LLMs to synthesize diverse negation queries, and introduce a dynamic visual focus module for verification. Our evaluation reveals that advanced RS MLLMs struggle with negation, exhibiting hallucinations and substantial performance degradation. To close this gap, we propose NeFo, a novel test-time learning method that explicitly incorporates the logical role of negation into the model optimization. Remarkably, using about 5\% unlabeled test samples, NeFo significantly improves the negation understanding of models and shows strong generalization to unseen tasks. Code and data will be released upon acceptance.

18.
arXiv (CS.AI) 2026-06-24

Entity Resolution via Batched Oracle Queries

arXiv:2606.24407v1 Announce Type: cross Abstract: We consider an oracle that processes a limited batch of records at a time and clusters those that refer to the same real-world entity. We study how to interrogate such an oracle to resolve entities in a dataset whose size is far larger than a single batch, and where no batch is guaranteed to contain all records of any given entity. We aim at a pay-as-you-go approach, to have full control over the costs (the number of oracle consults), while achieving the highest possible recall at every step. We formally cast this problem as batched entity resolution, prove that selecting optimal batches is NP-hard, and provide an optimal solution under a natural condition on entity sizes. Finally, we evaluate our approach on six datasets and show its superiority over state-of-the-art baselines.

19.
PLOS Computational Biology 2026-06-18

A comparison of contact patterns derived from the population structure in agent-based models and empirical contact survey data

Authors:

by Janik Suer, Johannes Ponge, Michael Brüggemann, Jan Pablo Burgard, Vitaly Belik, Bernd Hellingrath, Alejandra Rincón Hidalgo, Andrzej K. Jarynowski, Richard Pastor, Huynh Thi Phuong, Steven Schulz, Ashish Thampi, Chao Xu, Marlli Zambrano, Rafael Mikolajczyk, André Karch, Veronika K. Jaeger, on behalf of the OptimAgent Consortium Agent-based models (ABMs) are powerful tools for simulating disease spread, relying on individual-level interaction rules from which emergent dynamics arise. An important component in ABMs is contact behaviour. To reduce computational complexity, contact behaviour in ABMs is often assumed as random mixing within structurally defined settings (as, e.g., workplaces). with setting composition typically based on empirical data such as census information. However, the validity of this approach to represent contacts remains unclear. To address this gap, we compare the contact structure derived through this approach in a large-scale ABM with empirical contact survey data with respect to age contact matrices for households, schools, workplaces, all remaining contact settings, and all contacts combined (based on difference matrices and sum of squared errors (SSE)). Our results demonstrate that random mixing in settings with known age compositions like households (SSE:0.7(95%CI0.4–0.9)), schools (SSE:0.7(95%CI:0.3–1.1)) and workplaces (SSE:0.5(95%CI:0.2-0.7)), captures basic interaction patterns but fails to account for age-related variation in contact numbers. The largest differences arise for contacts outside these settings (SSE:3.8(95%CI:1.2–6.5)), as ABMs typically use random regional contacts that do not capture age-structured behaviour observed in contact surveys. Applying contact matrices from both approaches to an age-structured compartmental model, leads to noticeable differences in simulated epidemic outcomes regarding reproduction numbers and spreading dynamics between age groups. Our results suggest that naïve approaches to represent contact behaviour in ABMs based on population structure can be valid in settings with defined age-structures while settings with low a priori structure require more advanced methods to represent contact behaviour observed in contact surveys.

20.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

21.
arXiv (CS.CV) 2026-06-16

Learned JPEG Compression for DNN Vision

JPEG, a lossy image compression technique designed for human viewers, has maintained its dominance for decades. However, in the era of artificial intelligence (AI), a substantial portion of image data, often compressed by JPEG, is and will continue to be consumed by deep neural networks (DNNs) instead of humans, thus creating a need to optimize JPEG for DNN inference performance. To this end, we propose learned JPEG compression for DNN vision (J4D), a novel training framework for determining JPEG encoding parameters to minimize compression rate while maximizing DNN inference performance. The major challenge of solving this optimization problem lies in representing the JPEG codec and compression rate in closed form. By incorporating a differentiable soft quantizer based on a probabilistic quantization scheme, we not only obtain a differentiable proxy for the JPEG codec, but are also able to compute the entropy of the coded source analytically, which is a close estimate of the actual compression rate. Equipped with both the differentiable JPEG codec and the information-theoretic rate estimator, we are then able to solve the aforementioned optimization problem with backpropagation. After training, the learned encoding parameters will be subsequently used in actual JPEG encoding based on probabilistic quantization. Extensive experimental results across multiple datasets and DNN architectures demonstrate that J4D consistently and significantly outperforms the default JPEG and other competitive JPEG codecs optimized for DNNs. Notably, compared to the default JPEG, J4D achieves an increase in accuracy by as much as 11.60% at the same rate, or a reduction of compression rate up to 80.05% at the same accuracy. Additionally, with the help of J4D, we show the potential to design universal JPEG encoding parameters for various DNN architectures for the first time.

22.
Nature (Science) 2026-06-10

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

Authors:

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.
Nature (Science) 2026-06-17

The EU needs to back its ambition to end animal testing with cash

Authors: Unknown Author

The European Union has declared that it wants to stop using animals in chemical safety testing. Its goal will need a timeline and a serious funding commitment. The European Union has declared that it wants to stop using animals in chemical safety testing. Its goal will need a timeline and a serious funding commitment.

24.
arXiv (quant-ph) 2026-06-15

Collision models for open quantum systems coupled to finite environments

arXiv:2606.14163v1 Announce Type: new Abstract: We study a system qubit repeatedly interacting with the same environmental qubit, with a reservoir acting on the environment between collisions via a completely positive, trace-preserving map. We show that complete suppression of system–environment correlations uniquely requires a full environmental reset, recovering a semi group dynamics with a time-independent Gorini–Kossakowski–Sudarshan–Lindblad generator, whereas a partial reset yields a continuous transition between Markovian and non-Markovian regimes governed by a single dimensionless relaxation parameter. For a resonant excitation-exchange interaction, we obtain exact closed-form expressions for the Bloch-vector dynamics for both a generalized depolarizing channel and a generalized amplitude-damping channel acting as the reservoir-induced map. Using the Breuer–Laine–Piilo measure and a Choi-matrix CP-divisibility witness, we identify three distinct dynamical regimes across the parameter space: CP-divisible Markovian dynamics, CP-indivisible but P-divisible dynamics, and non-P-divisible non-Markovian dynamics. The boundaries between these regimes, and the structural differences between uniform and anisotropic environmental relaxation, are characterized numerically.

25.
medRxiv (Medicine) 2026-06-12

Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive molecular complexity, profound stromal remodeling, and limited responsiveness to systemic therapies. Although gemcitabine-based regimens remain widely utilized, the molecular pathways that influence treatment-associated biological variation are incompletely understood. The TGF{beta} and JAK/STAT signaling networks are recognized regulators of tumor progression, immune modulation, and therapeutic resistance; however, their genomic architecture in clinically stratified PDAC populations remains poorly defined. Methods: We employed a conversational artificial intelligence-driven analytical framework to investigate TGF{beta} and JAK/STAT pathway alterations in a cohort of 184 PDAC patients. Clinical and molecular data were integrated to generate age- and treatment-stratified cohorts, enabling pathway-level and gene-level analyses according to gemcitabine exposure. Findings generated through AI-assisted interrogation were subsequently evaluated using conventional statistical approaches. Results: TGF{beta} pathway alterations were identified in approximately one-quarter to one-third of tumors across clinical subgroups and demonstrated relatively stable frequencies regardless of age at diagnosis or gemcitabine treatment status. Gene-level analyses revealed that pathway disruption was predominantly driven by recurrent alterations in SMAD4, with additional low-frequency events involving TGFBR1 and TGFBR2. Notably, TGFBR2 mutations were significantly more frequent among late-onset PDAC patients receiving gemcitabine compared with untreated late-onset patients (8.8% vs. 1.4%; p = 0.04), suggesting a potential treatment-associated enrichment. In contrast, JAK/STAT pathway alterations were rare throughout the cohort, with only isolated mutations observed in pathway components including JAK1, JAK2, JAK3, STAT1, STAT3, and related regulatory genes. No significant differences in JAK/STAT alteration frequencies were identified according to age or treatment exposure. Conclusions: TGF{beta} and JAK/STAT pathways exhibit distinct genomic architectures in PDAC. TGF{beta} pathway disruption represents a recurrent feature of disease biology, largely driven by SMAD4 alterations, while TGFBR2 enrichment in gemcitabine-treated late-onset tumors suggests a potential context-specific association worthy of further investigation. Conversely, genomic alterations within the JAK/STAT pathway are uncommon, indicating that pathway activity may be regulated predominantly through non-genomic mechanisms. These findings demonstrate the utility of conversational artificial intelligence agents for rapid, scalable, and clinically contextualized pathway interrogation and support future studies integrating multi-omic data to refine precision medicine strategies in PDAC.