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

Constitutional On-Policy Safe Distillation

arXiv:2606.03089v2 Announce Type: replace-cross Abstract: On-policy self-distillation (OPSD) has emerged as an efficient post-training paradigm by using a teacher conditioned on privileged information to provide dense token-level supervision. Prior work has shown that OPSD can collapse in verifiable reasoning tasks, but safety alignment differs in that it is guided by high-level constitutions rather than explicit target answers, making it a natural setting to revisit dense distillation. However, our pilot study show that safety OPSD still suffers from severe collapse: constitutional conditioning contracts the teacher distribution toward short and overly conservative responses, and Reverse KL further amplifies this contraction into reduced expressiveness. We formalize this effect as geometric leakage under safety boundaries in a non-orthogonal semantic space, where safety pressure transfers into the expressiveness dimension. Based on this analysis, we propose Constitutional On-Policy Safe Distillation (COPSD), which first calibrates the teacher through a Cross-SFT cold-start and then performs constitution-conditioned on-policy distillation. Experiments on 12 benchmarks show that COPSD achieves a consistently stronger safety–helpfulness trade-off than baselines while substantially reducing the safety tax on general reasoning ability.

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

Reinforcing Dual-Path Reasoning in Spatial Vision Language Models

Spatial VLMs have made substantial progress in geometric perception, yet complex spatial reasoning requiring multi-step inference over depth, distance, and scene relations remains challenging. Moreover, different spatial queries call for fundamentally different strategies: some are best addressed through purely linguistic, step-by-step deduction, while others require explicit 3D grounding before quantitative inference. We present Dual-Path Spatial Reasoning via Reinforcement Learning for Spatial VLMs (SR-REAL), a unified framework that equips a spatial VLM with two complementary reasoning paths: Language-Only Reasoning (LOR), which performs step-by-step linguistic deduction, and Detect-Then-Reason (DTR), which detects 3D geometric cues (e.g., centers or bounding boxes) via region tokens before explicit geometric inference. SR-REAL begins with a cold-start supervised fine-tuning stage that constructs LOR and DTR chain-of-thought supervision and exposes a region-to-3D interface, followed by RL that optimizes the policy model with accuracy and format rewards; for DTR, a discrete center-based detection reward further refines geometric alignment. Across diverse spatial benchmarks, SR-REAL significantly outperforms spatial VLM baselines: (i) a single RL-trained model supports both reasoning paths, with DTR excelling in region-aware tasks through precise 3D localization and LOR enhancing general spatial reasoning; (ii) jointly training both paths fosters mutual reinforcement; (iii) high-quality, blended cold-start data is crucial for stable RL optimization; and (iv) the model generalizes across datasets and domains without per-task tuning, demonstrating positive transfer between LOR and DTR.

03.
arXiv (CS.AI) 2026-06-15

Regulating the Machine Contributor: Governance and Policy Alignment in Open Source

arXiv:2606.14594v1 Announce Type: cross Abstract: AI-assisted software development has moved from line-level autocomplete to agents that can plan changes, edit files, and submit pull requests with limited human supervision. Open-source software, however, evolves through a process designed for humans: contributor agreements, codes of conduct, and review norms all assume a legally accountable person who can attest to provenance and answer reviewer questions. Autonomous and semi-autonomous AI contributors strain those assumptions, and the 2025-2026 record of agent-driven incidents, AI-generated nuisance volume, and platform-level shutdowns shows that the gap is operationally consequential. Several open-source organisations have responded with contribution policies, but the result is fragmented, and its alignment with emerging AI governance frameworks (EU AI Act, NIST AI RMF with the UC Berkeley Agentic AI Profile, ISO/IEC 42001 and 23894) is unmapped at the contribution level. We compare policies across six organisations (SymPy, LLVM, matplotlib, OpenInfra, the Apache Software Foundation, and the Linux Foundation) using Most-Similar Systems Design with indicator-based coding and process tracing for SymPy and LLVM. From this we derive a six-dimensional taxonomy (disclosure, responsibility, human oversight, licensing, enforcement, maintainer workload), an ordinal Policy Maturity Score, and a mapping of documented agent incidents onto the dimensions each policy fails to govern. Aligning the dimensions with the regulatory frameworks above identifies overlapping gaps neither side currently closes, and we close by sketching the shape of a harmonised tiered framework and the empirical evaluation needed to calibrate it.

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

A Conservation Law for Equilibrium Propagation and Coupled Learning

arXiv:2606.15444v1 Announce Type: cross Abstract: In this paper we show that the physical learning methods known as coupled learning (CL) and equilibrium propagation (EP) conserve a mass-like quantity in the trainable parameters in the continuous-time, small-nudging limit. We prove that this conservation holds in a broad range of physically relevant settings. We then show that the conservation law constrains the training dynamics in a way that makes convergence reliable in important settings for linear circuits. We conclude by discussing some practical implications of this conservation law.

05.
arXiv (CS.CL) 2026-06-19

CacheWeaver: Cache-Aware Evidence Ordering for Efficient Grounded RAG Inference

Retrieval-Augmented Generation (RAG) improves factual grounding, but it also lengthens prompts and raises prefill cost. Prefix caching in serving engines such as vLLM reduces this cost only when requests share the same token prefix. In grounded generation, however, adjacent queries may retrieve overlapping evidence in different orders, so set overlap does not become reusable prefix overlap. We present CacheWeaver, a lightweight prompt-layer method for cache-aware evidence ordering. The method keeps a prefix tree over recently served evidence sequences and uses a greedy walk to place the most reusable prefix first, while leaving the serving engine and retrieved evidence set unchanged. Across three vLLM configurations, the method lowers median time-to-first-token (TTFT) by about 20-33 percent relative to retrieval-order prefix caching, without hurting answer quality in our QA tests. The greedy policy reaches 97.5 percent of the median TTFT gain from oracle ordering, indicating that most reusable prefix locality can be recovered by a simple scheduling layer between retrieval and inference.

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

EQPO: Equitable Group Relative Policy Optimization for Clinical Reasoning

arXiv:2510.19893v2 Announce Type: replace Abstract: Medical AI systems demonstrated impressive diagnostic performance, yet they routinely show uneven accuracy across demographic groups, disadvantaging underrepresented populations. Although multimodal reasoning foundation models have pushed clinical diagnosis forward, reinforcement learning-based post-training tends to absorb and magnify the biases present in majority-dominated training corpora. We propose Equitable Group Relative Policy Optimization (EQPO), a hierarchical reinforcement learning method that encourages balanced learning across heterogeneous clinical populations by adaptively reweighting samples according to subgroup representation, task difficulty, and data source. As demographic annotations are frequently missing in real-world clinical data, EQPO additionally applies unsupervised clustering to recover latent subpopulations when they are unavailable. On 7 diagnostic benchmarks covering 5 modalities (X-ray, CT, dermoscopy, mammography, ultrasound), EQPO reduces F1 standard deviation by 43.9% and the maximum cross-group F1 gap by 42.7% on QoQ-Med3-8B over vanilla GRPO, and narrows predictive parity gaps by 27.2% on MedGemma-4B over bias-mitigated RL baselines while raising F1 by 12.5% even without any demographic labels. Examining the training trajectory shows that EQPO steadily improves fairness over the course of optimization, in contrast to baseline methods whose fairness degrades as training proceeds, and the discovered implicit groups remain stable and align with masked demographic attributes. We further release EquiMedGemma-4B and EquiQoQ-Med3-8B, equitability-aware clinical VLLMs that attain state-of-the-art accuracy with markedly smaller demographic gaps.

07.
arXiv (CS.AI) 2026-06-17

Learning Red Agent Policy from Observations for Neurosymbolic Autonomous Cyber Agents

arXiv:2606.18223v1 Announce Type: cross Abstract: With sophisticated cyber-attacks becoming increasingly prevalent, modern networks require intelligent autonomous cyber-defense agents trained via Reinforcement Learning (RL). These agents employ neurosymbolic approaches such as behavior trees with learning-enabled components (LECs) to learn, reason, adapt, and implement security rules while maintaining critical operations. However, these autonomous networks are partially observable systems, i.e., the cyber-attacker's (red agent's) actions are not observable, making it difficult for the defender to predict red actions, learn red policies, or assess the attacker's intrusion levels. To address this, we propose a Policy Learning Technique using imitation learning to learn policies for partially observable RL agents with discrete states and discrete actions. We apply this technique in an autonomous cyber environment to predict red agent's actions from network observations and defender actions. Integrated with a neurosymbolic cyber-defense agent, our method effectively handles different red policies and achieves high prediction accuracy across diverse simulated scenarios.

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

CREST: Deployment-Realistic Hardware-in-the-Loop NAS for Embedded Sensing Systems

arXiv:2606.15004v1 Announce Type: cross Abstract: Deploying neural networks on low-power microcontrollers (MCUs) requires selecting model architectures under tight memory, latency, and energy constraints. Existing workflows often simplify this process along one or more axes: static proxy costs such as FLOPs or parameters, treating one MCU as representative, and continuous-inference tests instead of deployed sensing schedules. These assumptions can mis-rank Pareto-front candidates, miss infeasible deployments, and obscure schedule-dependent energy. We present CREST (Cross-platform Runtime Evaluation and Search Tool), a deployment-realistic hardware-in-the-loop (HIL) neural architecture search (NAS) framework for MCU sensing systems. CREST keeps the optimizer, HIL measurement boundary, logging, and replay workflow fixed while exposing workload, model family, target backend, schedule, quantization, and scoring policy as configurable axes. This makes deployment effects experimentally separable within one reusable workflow. We evaluate CREST on inertial odometry and audio classification across three Arm Cortex-M targets. For inertial odometry, measured-energy HIL search reduces median per-inference energy by 41.7% versus FLOPs-based selection and 40.8% versus memory-traffic-based selection at similar error. FLOPs-based selection also chooses infeasible deployments on memory-constrained targets. On the STM32 N657 target, continuous-inference and duty-cycled searches produce different Pareto frontiers. For audio classification, the same application-level policy selects different DS-CNN architectures on different boards, and cross-board replay changes deployment cost substantially. Overall, CREST shows that deployment-realistic MCU NAS must jointly optimize model architecture, target platform, runtime schedule, and deployment policy rather than relying only on static proxy costs or continuous-inference measurements.

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

Geometry-Aware Superpixel Graph Transformer with Metadata for Skin Lesion Classification

Automated skin cancer classification from dermoscopic images remains challenging due to heterogeneous lesion structure, strong intra-class variability, and subtle visual differences between benign and malignant cases. Existing CNN/ViT pipelines typically rely on global or patch-level features and often combine patient metadata via late fusion, which limits spatially grounded multimodal reasoning. We present a novel region-based graph learning framework that explicitly models lesions as graphs of spatially coherent superpixel regions represented as frozen CNN features. To capture fine-grained lesion arrangements, we encode inter-regional geometry as edge attributes and introduce a dedicated metadata context node connected to all regions, providing structured integration of demographic/clinical variables within the same relational space. Node representations are updated using our edge-aware graph transformer followed by attention-driven propagation, and a final graph-level embedding for benign-malignant classification. Experiments on four public benchmarks demonstrate that explicit region-level relational modeling and graph-native multimodal fusion yield consistent gains over the state-of-the-art. Consequently, we establish a new graph-centric perspective in which CNN features are modeled as relational nodes and improved through contextual integration, yielding more expressive and robust classifications.

10.
medRxiv (Medicine) 2026-06-11

Computer Vision Scoring of Figure Copy and Recall

Objective. Figure copy and recall tests are sensitive measures of visuoconstruction and visual episodic memory, but their clinical is constrained by labor-intensive manual scoring. We developed and validated an automated, element-level scoring pipeline using Vertex AI object detection for the tablet-based figure copy and recall tasks in the California Cognitive Assessment Battery (CCAB). The automated scoring pipeline duplicated the scoring procedures used by expert manual raters. Methods. A normative sample of 2,011 community-dwelling adults aged 18-90 completed figure copy and delayed recall trials at baseline, with subsamples retested at 1 day and at 6, 18, and 30 months. Participants completed the drawings with their index finger on a tablet computer with finger position digitized to analyze the speed and timing of individual drawing strokes A convolutional object-detection model trained on the Vertex AI AutoML Vision platform identified each of twelve canonical figure elements in rendered drawings. Separate element presence and location scores were computed after homographically warping drawings onto a canonical template to produce trial-level Element, Location, and Total scores. To compare Vertex and human scores, Vertex AI and expert human raters independently scored 1500 randomly selected drawings to evaluate inter-rater agreement, including a common subset of 100 drawings scored by Vertex AI and all raters. Results. Total scores were virtually indistinguishable (r = 0.966) from human-human agreement (mean r = 0.971) as were Element presence scores (mean r = 0.959 vs. r = 0.963). Location-score agreement (r = 0.951) was slightly below the human-human mean (r = 0.972) due to pixel-level analysis by Vertex AI that was impossible for human raters. The Vertex pipeline showed no preferential advantage for the single expert rater who categorized Elements during training. Automated scores showed strong demographic gradients, age effects on Recall (r = -0.32) were approximately twice those in Copy conditions (r = -0.16). A Memory Cost score (Recall - Copy) showed a monotonic age-related decline from +0.40 z in the youngest subjects to -0.54 z in the oldest. Kinetic analysis revealed that drawing speed and efficiency showed significant age-related changes. Overnight test-retest reliability was high (Recall r = 0.72) and the Recall trial showed a large overnight learning effect ({Delta} = +1.18) that continued with repeated tests up to 30 months ({Delta} = +0.75).

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

EMORSION: Examining the Impact of Audio Parameters on Emotional Responses and Immersion in Film

arXiv:2606.18266v1 Announce Type: cross Abstract: EMORSION is an exploratory proof-of-concept study examining how film audio design shapes audience emotion and immersion in acinema setting. Four film scenes were selected across the horror (2) and drama (2) genres, balanced between mainstream and independent productions. For each scene, multiple alternative audio mixes were created by systematically manipulating three core aspects of audio design, frequency (pitch), dynamics (loudness), and directionality (spatial placement). Three audience groups viewed the scenes, with each group exposed to one manipulated mix alongside a control mix for each scene. Audience responses were assessed through a triangulated multimodal framework combining self-reported emotion and immersion via a questionnaire, physiological measures including heart rate monitoring, and video-based motion tracking. The protocol successfully captured measurable, interpretable differences across audio conditions, indicating that even subtle changes in audio design can shape emotional perception and immersion. Unconventional mixes tended to produce greater variability in audience interpretation, while conventional immersive mixes were associated with stronger cross-audience agreement. These findings establish the feasibility of the EMORSION protocol and motivate larger-scale studies to characterise the role of specific audio parameters in shaping audience experience.

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

Two-Phase Bilevel Search for the Moving-Target Traveling Salesman Problem with Moving Obstacles

arXiv:2606.18730v1 Announce Type: cross Abstract: The Moving-Target Traveling Salesman Problem (MT-TSP) seeks a minimum cost trajectory for an agent that departs from a static depot, visits a set of moving targets, each within one of their assigned time windows, and returns to the depot. In this article, we study the Moving-Target Traveling Salesman Problem with Moving Obstacles (MT-TSP-MO), a generalization of the MT-TSP where the agent trajectory must avoid moving obstacles. We present a Mixed-Integer Conic Programming (MICP) formulation that can be solved using off-the-shelf solvers, as well as a fast and scalable Two-Phase Bilevel Search (TPBS) algorithm that computes high-quality feasible solutions for the problem. We evaluate our approaches against an existing baseline algorithm on a broad range of problem instances with up to 40 targets and 40 obstacles. The results demonstrate that both the proposed methods significantly outperform the baseline with respect to success rates, solution costs, and computation time.

13.
arXiv (CS.CV) 2026-06-11

UI2Code^N: UI-to-Code Generation as Interactive Visual Optimization

UI-to-code aims to translate UI screenshots into executable front-end code. Despite progress with vision-language models (VLMs), most existing methods formulate UI-to-code as a single-pass generation, which mismatches real-world UI development that is inherently iterative and feedback-driven. We reformulate UI-to-code as an interactive visual optimization problem, where code generation is embedded in a closed-loop process of execution, visual inspection, and iterative refinement driven by rendered visual feedback. To address the non-differentiability of visual objectives and the noise of absolute visual evaluators, we propose Relative Visual Policy Optimization (RVPO), a preference-based reinforcement learning method that optimizes relative visual rankings among rendered candidates under execution feedback. We instantiate this paradigm in UI2Code^N, an open-source 9B model trained via continual pre-training, supervised fine-tuning, and reinforcement learning. Experiments demonstrate state-of-the-art performance on UI drafting, UI polishing, and UI editing benchmarks, even outperforming larger models, with performance consistently improving through iterative visual optimization. Our code and models are available at https://github.com/zai-org/UI2Code_N.

14.
arXiv (CS.CV) 2026-06-16

CT-VDETR: Semi-supervised 3D Trauma Detection in Computed Tomography (CT) scans using Dense Vertex Relative Position Encoding

Accurate detection and localization of traumatic injuries in abdominal CT remain challenging because voxel-level annotations are limited and expensive to obtain. We present a label-efficient framework for 3D abdominal trauma detection that combines self-supervised pretraining with semi-supervised transformer-based detection. First, we use Masked Image Modeling (MIM) on 1098 CT volumes to pretrain a 3D U-Net encoder for anatomical representation learning. Next, we adapt V-DETR to dense volumetric CT through a feature adapter that converts the encoder feature grid into a compact token sequence for transformer decoding. The pretrained encoder is then integrated with V-DETR and 3D Vertex Relative Position Encoding (3D V-RPE) to improve the localization of irregularly shaped injuries. Finally, semi-supervised teacher-student consistency regularization leverages 2,000 additional unlabeled volumes during detector training. To the best of our knowledge, this is the first application of a 3D DETR-style detector to the RSNA abdominal trauma detection task. On this benchmark, the proposed method achieves 31.33% test mAP@0.50 using only 78 labeled training volumes, corresponding to a 1.53x improvement over supervised-only training. These results show that combining medical-domain pretraining with semi-supervised learning is an effective strategy for label-scarce 3D medical detection.

15.
arXiv (quant-ph) 2026-06-16

Quantum Algorithm for Open-System Battery Cathodes by Modeling Multiple Strongly Coupled Holstein Polarons with Chain-Mapped Caldeira-Leggett Dynamics

arXiv:2606.16017v1 Announce Type: new Abstract: Cathode lithiation occupies a chemical regime of tightly localized orbitals, narrow bandwidths, and strong electron-lattice coupling. The defining electrochemical observables (open-circuit voltage and differential capacity) are open-system, reservoir-equilibration quantities that closed-Hamiltonian quantum simulation cannot produce, set by exchange with electron, Li$^+$, and phonon baths. We present a fault-tolerant quantum algorithm that recovers them through a unitary chain-mapped Caldeira-Leggett embedding, rendering the baths Trotterizable. The resulting fourth-order Trotter step has a T-gate count polynomial in system size, validating its open-system dynamics against hierarchical equations of motion (HEOM) at strong coupling and the Lindblad limit at weak coupling. For single-carrier olivine LiFePO$_4$, a single voltage anchor on an otherwise DFT-fixed Hamiltonian places the differential-capacity peak within the $\pm5$ mV reproducibility of the experimental plateau. For multi-carrier spinel LiMn$_2$O$_4$, whose $1{:}1$ Mn$^{3+}$/Mn$^{4+}$ filling makes the inter-site Coulomb repulsion dynamically active, the same kernel yields a two-plateau voltage curve with a $125$ mV split, within $17\%$ of the observed $150$ mV. We deliver an end-to-end fault-tolerant resource estimate for such a multi-carrier, three-reservoir observable: $368$ logical qubits and $\sim3\times10^5$ T-gates per step, or $\sim1.7\times10^{12}$ T-gates for a full voltage curve (parallelizable over $\sim10^3$ trajectories), leaving the production-scale dynamical run as a milestone for future hardware. The same kernel reproduces macroscopic quantum coherence, two-band superconductivity, and the Mikheyev-Smirnov-Wolfenstein resonance without modification, placing dynamical battery chemistry and similar Hamiltonians within scope for fault-tolerant quantum simulation.

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

Spectrally Corrected Polynomial Approximation for Quantum Singular Value Transformation

arXiv:2603.03998v2 Announce Type: replace Abstract: Quantum Singular Value Transformation (QSVT) provides a unified framework for applying polynomial functions to the singular values of a block-encoded matrix. QSVT prepares a state proportional to $\bA^{-1}\bb$ with circuit depth $O(d\cdot\mathrm{polylog}(N))$, where $d$ is the polynomial degree of the $1/x$ approximation and $N$ is the size of $\bA$. Current polynomial approximation methods are over the continuous interval $[a,1]$, giving $d = O(\sqrt{\kap}\log(1/\varepsilon))$, and make no use of any properties of $\bA$. We observe here that QSVT solution accuracy depends only on the polynomial accuracy at the eigenvalues of $\bA$. When all $N$ eigenvalues are known exactly, a pure spectral polynomial $p_{S}$ can interpolate $1/x$ at these eigenvalues and achieve unit fidelity at reduced degree. But its practical applicability is limited. To address this, we propose a spectral correction that exploits prior knowledge of $K$ eigenvalues of $\bA$. Given any base polynomial $p_0$, such as Remez, of degree $d_0$, a $K\times K$ linear system enforces exact interpolation of $1/x$ only at these $K$ eigenvalues without increasing $d_0$. The spectrally corrected polynomial $p_{SC}$ preserves the continuous error profile between eigenvalues and inherits the parity of $p_0$. QSVT experiments on the 1D Poisson equation demonstrate up to a $5\times$ reduction in circuit depth relative to the base polynomial, at unit fidelity and improved compliance error. The correction is agnostic to the choice of base polynomial and robust to eigenvalue perturbations up to $10\%$ relative error. Extension to the 2D Poisson equation suggests that correcting a small fraction of the spectrum may suffice to achieve fidelity above $0.999$.

17.
arXiv (CS.CV) 2026-06-15

C-MambaPose: A Physics-Informed Complex Mamba Framework for Cross-Environment WiFi Human Pose Estimation

Human pose estimation (HPE) utilizing wireless WiFi signals has emerged as a promising technology owing to its device-free nature, privacy preservation, and robustness against occlusion and poor lighting. However, existing methods often overlook the physical complex phase information of WiFi signals and fail to generalize across diverse environments due to severe domain shifts. In this paper, we present C-MambaPose, a physics-informed complex-valued Mamba-GraFormer hybrid framework for robust cross-environment WiFi-based 3D HPE. Our framework first sanitizes raw WiFi Channel State Information (CSI) phase errors and constructs a phase-preserving complex-valued representation. We then employ a Spatiotemporal Complex Mamba encoder with a dynamic selective receptive field to capture fine-grained phase dynamics. A cross-attention joint-query mapper maps the unstructured sequence tokens to human joints, which are decoded by a Graph Convolutional Network (GCN) to predict anatomically coherent 3D coordinates. Extensive evaluations on the MM-Fi dataset show that C-MambaPose achieves competitive or superior performance to state-of-the-art baselines across all settings, setting a new state-of-the-art specifically on the challenging cross-environment split, requiring only 3.78 M parameters-an 83.1\% reduction compared to GraphPose-Fi[chen2026graph] and an 85.7\% reduction compared to MetaFi++[zhou2023metafi++], while maintaining a comparable size to DT-Pose[chen2025towards] (which is only 18\% smaller) but achieving significantly superior performance without requiring any pretraining. Our code is publicly available at https://github.com/phucngvinuni/cmampose.git.

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

Style-CCL: Content-Preserving Style Transfer via Curriculum Continual Learning

Content-Preserving Style transfer, given content and style references, remains challenging for Diffusion Transformers (DiTs) due to entangled content and style features. With a reverse triplet synthesis pipeline to build a million-scale training set and a dual-branch Style-Content DiT (SC-DiT) that decouples style and content via separate ROPE embeddings and causal masking, we observe that such a one-stage training paradigm on mixed style categories causes semantic styles to dominate, hindering texture style learning, and harming content preservation. To address these issues, we propose Style-CCL, a Multi-Stage Curriculum Continual Learning framework that trains SC-DiT from semantic (easy) to texture (hard) styles, and from clean to synthetic data, with Random Memory Rehearsal across stages to avoid catastrophic forgetting. Extensive experiments demonstrate that our Style-CCL achieves state-of-the-art performance in three core metrics: style similarity, content consistency, and aesthetic quality.

19.
PLOS Computational Biology 2026-06-22

Beyond the canonical: The role of post-transcriptional regulation in drug-target interaction prediction

by Md Istiaq Ansari, Khandakar Tanvir Ahmed, Debby D. Wang, Kirill Medvedev, Wei Zhang Protein isoforms produced from the same gene through post-transcriptional regulatory mechanisms, such as alternative splicing, can substantially alter protein structure and function, including drug-binding properties. However, most existing drug-target interaction (DTI) and drug-target affinity (DTA) prediction models rely exclusively on a single representative protein sequence per gene, typically the canonical or longest isoform, thereby overlooking the functional diversity introduced by alternative isoforms. This assumption can introduce bias, limit generalizability, and compromise the biological validity of model predictions. In this study, we systematically investigate the impact of protein isoform variation on DTI prediction accuracy. Our results show that substituting the canonical sequence with an alternative isoform often leads to substantial declines in predictive performance. Structural and binding affinity analyses further reveal that these discrepancies are frequently associated with changes in predicted binding-site configurations, which we further examine through controlled perturbations of binding-site residues. These experiments suggest that even subtle alterations in binding regions can lead to inconsistent DTI predictions. Overall, our findings uncover a critical limitation in current DTI modeling frameworks and underscore the importance of incorporating isoform-specific information to better reflect biological reality and improve therapeutic relevance. The codes and datasets are available at https://github.com/compbiolabucf/DTIVariant.

20.
arXiv (CS.CV) 2026-06-15

SAFformer:Improving Spiking Transformer via Active Predictive Filtering

Spiking Neural Networks (SNNs) offer notable advantages in biological plausibility and energy efficiency, making them promising candidates for building low-power Transformers. However, existing Spiking Transformers largely adhere to a passive reactive paradigm, which struggles to focus on task-relevant information and incurs substantial computational overhead when processing redundant visual data. To overcome this fundamental yet underexplored limitation, we propose SAFformer, a novel Spiking Transformer architecture based on an active predictive filtering paradigm. Inspired by the brain's predictive coding mechanism, SAFformer actively suppresses predictable signals and focuses on salient visual features. Extensive experiments show that SAFformer establishes new state-of-the-art performance on CIFAR-10/100 and CIFAR10-DVS. Remarkably, on ImageNet-1K, it achieves 80.44% Top-1 accuracy with only 26.58M parameters and an energy consumption of 5.88 mJ, demonstrating an exceptional balance between accuracy and efficiency.

21.
arXiv (CS.CL) 2026-06-11

Language Shapes Mental Health Evaluations in Large Language Models

Multilingual large language models (LLMs) are increasingly used in socially sensitive mental health contexts, including support chatbots, screening, and content moderation. This raises a reliability question: do semantically equivalent mental health inputs elicit comparable evaluations across languages, or systematic shifts consistent with language-associated social and cultural contexts? We examine this question in an English-Chinese setting with GPT-4o and Qwen3-32B using a two-level framework: construct-level evaluative orientation, measured by psychometric stigma instruments, and decision-level behavior, measured by binary stigma detection and four-class depression severity classification. Across instruments and models, Chinese prompts elicit higher stigma-related scores than English prompts. At the decision level, Chinese prompts reduce sensitivity to stigmatizing content and produce more conservative depression severity judgments, leading to more under-estimation errors. These findings show that prompt language can shift both evaluative orientation and downstream behavior in LLM-based mental health evaluation. They highlight the need to evaluate multilingual LLMs not only for aggregate performance, but also for whether they apply comparable evaluative standards across languages in socially sensitive domains.

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

JailbreakOPT: Tool-Assisted Iterative Jailbreak Prompt Optimization

arXiv:2606.11425v1 Announce Type: cross Abstract: Jailbreak attacks expose persistent safety weaknesses in large language models (LLMs), but existing stateless single-turn methods face a trade-off: hand-crafted prompts are expressive but static, while iterative prompt optimization can adapt but often relies on low-level mutations that require many target queries. We propose JailbreakOPT, a tool-assisted framework for improving iterative single-turn jailbreak prompt optimization. JailbreakOPT organizes diverse atomic jailbreak prompts into an attack tool library and composes them through a unified intra-episode optimization abstraction to generate stronger standalone attack prompts. To reuse experience across attack episodes, JailbreakOPT further frames tool selection as a contextual bandit problem and applies contextual Thompson sampling to guide exploration and exploitation based on past outcomes. Experiments across multiple target LLMs and attack goals show that JailbreakOPT improves attack success rate (ASR) while reducing the number of attacks until success (No.A) compared with atomic single-turn attacks and existing iterative optimization baselines. This paper may contain offensive or harmful content.

23.
arXiv (CS.CL) 2026-06-12

IVIE: A Neuro-symbolic Approach to Incremental and Validated Generation of Interactive Fiction Worlds

Computational creativity in Interactive Fiction faces a fundamental tension: Large Language Models (LLM) may produce creative narratives but struggle with world coherence, while symbolic systems ensure consistency but lack creative flexibility. We present IVIE (Incremental & Validated Interactive Experiences), a neuro-symbolic approach to generating complete and playable interactive fiction worlds from scratch. Building upon PAYADOR's neuro-symbolic framework, IVIE implements a four-stage incremental generation pipeline that delegates creative decisions–setting and character creation, puzzle design–to LLMs while grounding the world state through symbolic validation. The system generates worlds with interconnected locations, functional items, non-player characters, and coherent puzzles, all structured around a central goal-oriented architecture. Human evaluation shows the approach generates immersive, thematically coherent worlds with high player engagement. Results seem to indicate that the neuro-symbolic approach successfully balances flexibility with narrative coherence: symbolic validation grounds LLM generation without eliminating generative freedom. However, challenges remain: LLM inconsistencies occasionally bypass puzzle constraints, and objective validation gaps allow some structurally impossible goals. We identify key design considerations for future neurosymbolic interactive storytelling systems, particularly regarding LLM capabilities and their limitations.

24.
arXiv (quant-ph) 2026-06-11

Machine-learned, finite temperature Fermi-operator expansions suitable for GPUs and AI-hardware

arXiv:2605.08523v2 Announce Type: replace Abstract: We present several finite-temperature recursive Fermi-operator expansion schemes based on the second-order spectral projection (SP2) method. Our approach builds on a previous observation that the electronic structure problem, as formulated through a recursive SP2 expansion, can be mapped onto the architecture of a deep neural network. Using this perspective, we generalize SP2 to finite electronic temperatures by constructing machine learning models that determine optimized recursive expansion coefficients. The same approach is also applied to the prediction of the electronic entropy for fractional occupation numbers. The coefficients are trained for a specified chemical potential and electronic temperature and are not available in closed analytical form. However, by employing an appropriate affine rescaling strategy to the Hamiltonian matrix, we eliminate the need to retrain the model for different temperatures and chemical potentials. Our approach avoids explicit diagonalization and relies solely on highly optimized matrix-matrix multiplication kernels. Compared to state-of-the-art diagonalization, we achieve an order-of-magnitude speedup in the single-particle finite-temperature density matrix calculation for small and moderately sized matrices on modern GPUs and dense matrix multiply units.

25.
arXiv (CS.CL) 2026-06-18

RCEM: Robust Conversational Search EMbedder in Distributional Shift

We propose RCEM, a Robust Conversational search EMbedder that is additionally equipped with LLM's query reformulation capability without losing base model's generalization. Unlike prior conversational dense retrieval approaches that learn direct conversation-to-passage matching, RCEM aligns conversations, prepended by special token, to LLM-rewritten queries, while preserving the original embedding space. The unchanged embedding space automatically maps the rewritten-query to the relevant passages. As a result, RCEM (1) reduces overfitting by simplifying the alignment task from long passages to shorter rewritten queries, (2) eliminates the need for conversation-to-passage relevance labels for training, and (3) maintains its original embedding space that allows conversational queries against indexes built by original embedder without rebuilding them. Extensive experiments show that RCEM consistently outperforms prior approaches, achieving up to 30% improvement under distributional shift.