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01.
arXiv (quant-ph) 2026-06-15

Tantalum as a base material for superconducting integrated circuits

arXiv:2606.13750v1 Announce Type: new Abstract: The performance of superconducting integrated circuits for quantum applications is fundamentally limited by material-related losses. Tantalum, as an emerging material for next-generation quantum circuits, has attracted considerable attention in recent years after demonstrating breakthrough performance in both superconducting microwave resonators and qubits. Concurrently, a growing body of work is devoted to the operation of tantalum-based circuits and related fabrication techniques. This interest is further stimulated by tantalum thin films polymorphism resulting in a variety of its crystalline structure, superconducting properties, coherence, etc. Furthermore, tantalum circuits exhibit distinctive features in cryogenic experiments, which have not been observed in aluminum- or niobium-based ones. In this review, we summarize the recent research of tantalum thin films growth and phase selection mechanisms on various substrates, key aspects of fabrication and performance of superconducting circuit, including a material first-principles theoretical study. In conclusion, we address a number of open issues, including the role of \b{eta}-phase impurities, the effect of hydrofluoric acid solutions on chain characteristics, and the anomalous behavior of {\alpha}-tantalum chains at cryogenic temperatures.

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

A First-Principles Derivation of LLM Policy Optimization: From Expected Reward to GRPO and Its Structural Extensions

arXiv:2606.16733v1 Announce Type: new Abstract: Policy gradient algorithms for language models optimize the same objective $J(\theta) = \mathbb{E}*{\tau \sim p*\theta(\tau)}[R(\tau)]$, which has exactly two factors: the trajectory probability $p_\theta(\tau)$ and the reward $R(\tau)$. Every method from REINFORCE to PPO to GRPO and their descendants modifies one or both factors to address a specific failure in the preceding formulation. Existing surveys organize these methods by domain or chronology, which obscures the rationale behind each design choice and the precise location of its intervention within the gradient estimator. This survey revisits the landscape of LLM policy optimization from $J(\theta)$ on first principles and uses the trajectory side, induced by $p_\theta(\tau)$, and the reward side, induced by $R(\tau)$, as the two axes along which methods are located. It covers the path from REINFORCE and PPO to GRPO, as well as post-GRPO variants, Agentic RL, and GRPO-OPD. The resulting framework is unified, diagnostic, and extensible: it analyzes methods from a shared objective, identifies which side each method modifies and why, and applies the same trajectory and reward axes across these settings. Across these settings, the framework also exposes compound failures that no single-side fix resolves and that therefore require joint design of the trajectory side and the reward side. The boundary cases and coupled failures identified by this map mark where existing solutions run out and provide a principled starting point for designing the next generation of LLM policy optimization algorithms.

03.
medRxiv (Medicine) 2026-06-11

Ferritin across long-term conditions in England: cross-sectional primary care study

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (

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

Future Dynamic 3D Reconstruction: A 3D World Model with Disentangled Ego-Motion

Forecasting the evolution of dynamic environments is crucial for autonomous agents. While generative world models have recently achieved high photorealism in 2D video synthesis by mixing ego-motion and environmental dynamics within the image plane, they exhibit physical inconsistencies, such as morphing or vanishing objects, especially over long time horizons. In this paper, we propose FR3D, a world model that predicts a persistent 3D latent representation for future dynamic 3D reconstruction. Unlike prior works that treat the world as a sequence of image-based features, FR3D explicitly decouples the 3D evolution of the scene from the agent's trajectory, treating the inferred ego-motion as a latent proxy for action. This disentanglement resolves the ambiguities between self-motion and world-motion, ensuring geometric consistency into the future. Furthermore, we introduce a teacher-student distillation strategy that leverages the spatial "common sense" of off-the-shelf foundation models, leading to robust zero-shot generalization. Extensive experiments demonstrate FR3D's strong performance for future dynamic 3D reconstruction from monocular observations across multiple datasets, even 2 seconds into the future. Project page: https://fr3d-wm.github.io.

05.
arXiv (quant-ph) 2026-06-17

Kinematic properties of the Pauli equation

arXiv:2606.17548v1 Announce Type: new Abstract: Based on the Wigner-Vlasov formalism, this paper investigates the kinematic properties of the Pauli equation. It is shown that the probability current associated with the Pauli equation can be represented as a superposition of two currents with certain expansion coefficients. Each of these currents corresponds to a particular component of the spinor. The expansion coefficients effectively serve as weighting functions that determine the probability contribution of the corresponding spinor component. Therefore, each spin projection corresponds to its own probability flux. A new system of the Hamilton-Jacobi equations and also a system of motion equations in electromagnetic fields are obtained, taking into account the interaction between the spin and the magnetic field. To illustrate how these equations can be applied we have investigated the quantum system kinematics in detail using an exact solution of the Pauli equation in the presence of a uniform magnetic field and an asymmetric quadratic potential.

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

TriFlow: Generating Artist-Like 3D Mesh Topology via Nearest-Vertex Vector Fields

We present TriFlow, a new generative approach for producing compact 3D meshes with artist-like triangle topology directly from input geometry conditions such as signed distance fields. Our key insight is to represent mesh topology as a nearest-vertex vector field (NVF) defined over the surface, where each point encodes its association to the nearest triangle vertex in the local barycentric frame. We train a latent flow-matching model to synthesize this field, enabling topology generation conditioned on the input geometry. To extract a coherent mesh, we cluster surface regions using the generated NVF and guide a constrained quadric error metric (QEM) mesh simplification with topology-aware optimization. This yields output meshes that closely match the input geometry while exhibiting structured, artist-like connectivity. Experiments demonstrate that TriFlow achieves stronger generalization and significantly improved topology quality compared to state-of-the-art learning-based approaches, alongside 90% lower Chamfer Distance and an 8x speedup.

07.
arXiv (CS.AI) 2026-06-11

Multimodal Ordinal Modeling of Alzheimer's Disease Severity Using Structural MRI and Clinical Data

arXiv:2606.11794v1 Announce Type: cross Abstract: Neurodegenerative diseases such as Alzheimer's disease (AD) require accurate and scalable tools for assessing disease severity, yet current clinical staging remains time-intensive and prone to variability. We propose an attention-enhanced multimodal machine learning framework with ordinal regression for automated and interpretable AD severity staging. The framework integrates T1-weighted MRI with demographic and genetic variables and compares unimodal and multimodal architectures using ordinal and non-ordinal prediction heads. Models were trained and validated using cohort-stratified splits derived from the ADNI, AIBL, and NIFD datasets. A strictly held-out test set was constructed using subjects excluded from all training, validation, preprocessing, and hyperparameter tuning procedures, with subject-level splitting employed throughout to prevent data leakage. Among unimodal approaches, the T1-weighted MRI model achieved slightly higher adjacent-stage accuracy (0.963) and agreement with clinical staging (QWK 0.444) than the tabular model (QWK 0.433). Integrating imaging, demographic, and genetic information improved overall performance. The multimodal non-ordinal baseline achieved the lowest prediction error (MAE 0.340), whereas the ordinal multimodal model achieved the highest adjacent-stage accuracy (0.970) and strongest agreement with clinical staging (QWK 0.549). These findings indicate that ordinal formulations better capture the ordered structure of the CDR scale and yield predictions more consistent with clinical staging. Explainability analyses using Grad CAM++ and SHAP demonstrated anatomically and clinically plausible model behavior, supporting transparent decision-making. Overall, attention-based multimodal learning with ordinal regression represents a robust, interpretable, and scalable approach for automated AD severity staging and AI-assisted clinical decision support.

08.
arXiv (quant-ph) 2026-06-11

Invariants of Sequential Circuits and Generalized Non-Abelian Statistics

arXiv:2606.11527v1 Announce Type: cross Abstract: Non-invertible symmetries in quantum many-body systems generally give rise to sequential unitary circuits that move symmetry defects. In this paper, we investigate invariants defined by sequences of such circuits, which move non-invertible defects and generate a Berry phase evaluated on quantum states with defects. We show that this Berry phase generally defines an invariant under local deformations, provided that the sequential circuits preserve the locality of those deformations. This invariant also rules out a short-range-entangled state that preserves the non-invertible symmetry, thereby signaling the 't Hooft anomaly of a non-invertible symmetry purely in terms of unitary operators acting on a state. We then apply this framework to loop excitations in three spatial dimensions and identify a new loop excitation in the (3+1)D $\mathbb{D}_4$ topological order, which we dub a non-Abelian fermionic loop. Using the invariant of sequential circuits, we characterize the statistics of non-Abelian fermionic loops. In addition, we find a new (3+1)D mixed topological order with a single non-Abelian fermionic loop, whose long-range entanglement is protected by an invariant of sequential circuits.

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

Deep Learning of Solver-Aware Turbulence Closures from Nudged LES Dynamics

arXiv:2604.23874v3 Announce Type: replace-cross Abstract: The differentiable physics paradigm may be leveraged as an a-posteriori approach for discovering turbulence closure models by embedding a neural network parameterization directly inside the solver and optimizing it given potentially sparse target data. This addresses a key limitation of a-priori learning where direct numerical simulation (DNS) data is used to approximate the subgrid stress with the assumption of a low-pass filter. Closures trained in this a-priori manner frequently lead to unstable deployments due to the mismatch between the assumed filter and the effect of numerical discretizations and coarse-graining. In comparison, while typically stable during deployment, a-posteriori learning incurs high computational costs due to the need to backpropagate through a large eddy simulation (LES) solver. Furthermore, a-posteriori methods are challenging to apply broadly since they require significant modification of existing solvers. Finally, both approaches are limited when generalization is desired across different numerical schemes with their implicit filtering characteristics. In this work, we present a deep-learning approach for turbulence closure modeling built on the continuous data assimilation framework. Our approach enables the a-priori training of closures using sparsely observed DNS data without modifying or differentiating through the LES solver, while preserving stability during deployment for the recovery of invariant statistics. We focus on the model's ability to adapt to different discretizations by explicitly conditioning it on the numerical scheme. We use two- and three-dimensional canonical cases to test our framework and show that the learned correction systematically tracks the discretization error of the coarse solver.

10.
PLOS Computational Biology 2026-06-22

A lactylation- and autophagy-associated prognostic signature reveals LSEC-derived CLEC3B as a novel mediator of hepatocellular carcinoma suppression

作者:

by Youai Song, Yinkuan Ning, Meihui Li, Jianwei Lan, Liangchen Lei, Yufei Han, Zhuo Meng, Binjie Li, Pengpeng Liu, Quanyan Liu The crosstalk between lactylation and autophagy within the hepatocellular carcinoma (HCC) microenvironment is a burgeoning field with profound implications. By integrating multi-omics data from public cohorts, we delineated two molecular subtypes of HCC with divergent clinical outcomes and established a lactylation-autophagy-related prognostic signature. This signature highlighted CLEC3B as a pivotal gene. Subsequent single-cell RNA sequencing and experimental validation unequivocally pinpointed liver sinusoidal endothelial cells (LSECs) as the principal cellular source of CLEC3B, which was significantly downregulated in HCC tissues. Functionally, conditioned media derived from CLEC3B-overexpressing LSECs potently inhibited HCC cell proliferation. Mechanistic investigations revealed that this tumor-suppressive effect was orchestrated through the concurrent suppression of autophagy and diminution of lactylation levels. Our findings position LSEC-secreted CLEC3B as a novel metabolic mediator in HCC, bridging two key pathways in tumor suppression, and endorse its clinical value both as a prognostic indicator and a promising therapeutic target.

11.
arXiv (CS.LG) 2026-06-17

A Closer Look at Failure Modes in Temporal Understanding of Large Audio-Language Models

arXiv:2606.17417v1 Announce Type: cross Abstract: Large Audio Language Models (LALMs) achieve strong performance on a variety of audio understanding tasks but continue to struggle with temporal reasoning, a fundamental capability central to human auditory perception. Understanding the causes of these failures remains challenging as existing benchmarks report performance gaps without probing underlying mechanisms. To address this, we introduce a benchmark with 1,657 questions across three foundational tasks designed specifically for mechanistic analysis. Examining model outputs across varying input settings (behavioral analysis) reveals that models often under-utilize audio when textual cues are available. We also provide the first causal mechanistic analysis of temporal reasoning failures in LALMs. Comparing attention upweighting against scaling, we find that redistributing attention across audio tokens is more effective than increasing audio attention. Targeting task-relevant tokens yields further gains. These findings suggest that modality imbalance alone cannot explain failures. Attention scaling at bottleneck layers improves accuracy from 55.9% to 59.1% without fine-tuning, demonstrating a promising direction for future work.

12.
arXiv (CS.CV) 2026-06-19

Vision-Reasoning-Guided Occlusion Removal from Light Fields

Occlusion-robust scene recovery remains a major challenge in computational imaging, particularly in natural environments where dense foreground vegetation severely limits visibility. We propose a vision-reasoning-guided light field occlusion removal framework that combines the visibility recovery capability of light field integration (LFI) with the semantic reasoning capacity of vision-language models (VLMs). Multi-view observations are first integrated via LFI to suppress foreground occlusions and produce an initial visibility-enhanced representation. A VLM is then incorporated as a conditional semantic prior to restore degraded structures and recover fine details, guided by the observed measurements. To improve recovery consistency and reduce hallucination artifacts, we introduce a multi-sample fusion strategy that aggregates multiple generated hypotheses into a unified estimate. Experimental results on synthetic and real-world datasets demonstrate state-of-the-art performance, achieving the highest average SSIM across four synthetic light field benchmark scenes (4-Syn) and strong generalization across structured and unstructured acquisition settings. These results highlight the effectiveness of combining physical imaging constraints with vision-language reasoning for robust perception under severe occlusion, with applicability to search-and-rescue and exploratory robotic navigation.

13.
arXiv (CS.CV) 2026-06-15

Orchestra-o1: Omnimodal Agent Orchestration

The recent success of agent swarms has shifted the paradigm of large language model (LLM)-based agents from single-agent workflows to multi-agent systems, highlighting the importance of agent orchestration for task decomposition and collaboration. However, existing orchestration frameworks are limited to a narrow set of modalities and struggle to generalize to more complex settings where heterogeneous modalities coexist and interact. This limitation becomes particularly pronounced in omnimodal scenarios, where tasks require the unified understanding and coordination of diverse inputs such as text, image, audio, and video. In this work, we propose Orchestra-o1, an omnimodal agent orchestration framework designed to support efficient agent collaboration across multiple modalities. Orchestra-o1 introduces a unified orchestration mechanism that enables modality-aware task decomposition, online sub-agent specialization, and parallel sub-task execution. This scalable design allows agent systems to effectively tackle complex real-world tasks involving heterogeneous information sources, surpassing the second-best approach by 10.3% accuracy on the OmniGAIA benchmark. Furthermore, we introduce decision-aligned group relative policy optimization (DA-GRPO), an efficient agentic reinforcement learning approach for training Orchestra-o1-8B, which also achieves state-of-the-art performance against all existing open-source omnimodal agents.

14.
arXiv (CS.CV) 2026-06-12

Modality Forcing for Scalable Spatial Generation

Text-to-image (T2I) models contain rich spatial priors. Synthesizing photorealistic, cluttered scenes requires an understanding of geometry, including perspective and relative scale. Prior works adapt T2I models to leverage this prior for depth prediction, but they require dense depth data and involve complex recipes. We propose Modality Forcing, a simple, scalable post-training recipe for joint image-depth generation using a single DiT trained on sparse depth data. Modality Forcing enables conditional and joint generation of image and depth in any permutation by assigning separate noise levels per modality. Per-modality decoders let us train on sparse, real-world depth and achieve strong, generalizable depth prediction. We further show that Modality Forcing inherits the scalability of T2I pre-training: by training a set of T2I models from scratch (370M to 3.3B parameters), we find that larger models trained on more image data produce more accurate depth. Our strongest model is competitive with state-of-the-art monocular depth estimators and reduces AbsRel by 57% relative to existing joint image-depth generative models. These results provide strong evidence that image generation is a scalable pre-training objective for spatial perception. https://modality-forcing.github.io/

15.
arXiv (math.PR) 2026-06-19

Establishing an $\Omega(\sqrt{d})$ complexity lower bound for PDMP samplers and how to break it: a sub-$\sqrt{d}$ algorithm for Gaussian-tailed targets

arXiv:2606.19909v1 Announce Type: cross Abstract: Despite the theoretical appeal of their non-reversibility, to date, no Piecewise Deterministic Markov Process (PDMP) samplers have been developed that scale better than $\mathcal{O}(\sqrt{d})$ in computational complexity with respect to the target dimension $d$. We prove that this is a fundamental limitation by establishing an $\Omega(\sqrt{d})$ lower bound on the algorithmic complexity of PDMP samplers in a standard setup. By relaxing the assumption that the target density must remain invariant at all continuous times, we then demonstrate how to bypass this barrier. Specifically, we introduce a novel PDMP sampling scheme and show that it achieves an empirical complexity of $\mathcal{O}(d^\alpha)$, where $\alpha \in [0.2, 0.3]$ for Gaussian-tailed targets. In addition, this PDMP scheme is locally adaptive in both trajectory length and distance between velocity updates.

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

FFinRED: An Expert-Guided Benchmark Generation and Evaluation Framework for Financial LLM Red-Teaming

arXiv:2606.19887v1 Announce Type: cross Abstract: Existing safety benchmarks target general adversarial scenarios but miss finance-specific risks. Financial LLMs face regulatory compliance violations, fraud facilitation, and systemic trust erosion that require targeted evaluation. We introduce FinRED, an expert-guided red-teaming framework for financial LLM safety evaluation developed with financial experts. FinRED uses a novel two-level taxonomy mapping global standards (e.g., FATF and EU DORA) to threats ranging from regulatory evasion to complex fraud, integrated with a scalable pipeline that converts real financial documents into context-rich red-teaming Behavioral Prompts (seeds) through an expert-defined schema. Rigorous expert validation confirms seed plausibility and realism for meaningful LLM safety evaluation. We also provide an expert-validated, finance-specific rubric that goes beyond disclaimer checks, aligns more closely with human experts than static one-size-fits-all rubrics, and reduces critical false negatives from 28 to 12. Aligned with internationally adopted risk-management and information-security standards (e.g., ISO/IEC 27001), FinRED is deployed in South Korea's Financial Security Institute (FSI) regulatory sandbox for generative AI security evaluation in real financial services. To mitigate dual-use risks, the dataset, generation pipeline, prompt template, and evaluation framework are gated for qualified researchers at https://github.com/selectstar-ai/FinRED-paper and https://huggingface.co/datasets/datumo/FinRED.

17.
arXiv (CS.LG) 2026-06-11

Scaling Laws of Global Weather Models

arXiv:2602.22962v2 Announce Type: replace Abstract: Data-driven models are revolutionizing weather forecasting. To optimize training efficiency and model performance, this paper analyzes empirical scaling laws within this domain. We investigate the relationship between model performance (validation loss) and three key factors: model size ($N$), dataset size ($D$), and compute budget ($C$). Across a range of models, we find that Aurora exhibits the strongest data-scaling behavior: increasing the training dataset by 10x reduces validation loss by up to 3.2x. GraphCast demonstrates the highest parameter efficiency, yet suffers from limited hardware utilization. Our compute-optimal analysis indicates that, under fixed compute budgets, allocating resources to more total training data yields greater performance gains than increasing model size. Furthermore, we analyze model shape and uncover scaling behaviors that differ fundamentally from those observed in language models: weather forecasting models consistently favor increased width over depth. These findings suggest that future weather models should prioritize wider architectures and larger effective training datasets to maximize predictive performance.

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

Grammar-Constrained Decoding Can Jailbreak LLMs into Generating Malicious Code

Large Language Models (LLMs) are increasingly used for code generation, raising concerns that they may be misused to produce malicious code. Meanwhile, Grammar-Constrained Decoding (GCD) has been widely adopted to improve the reliability of LLM-generated code by enforcing syntactic validity. In this paper, we reveal a counterintuitive risk: this reliability-oriented technique can itself become an attack surface. We uncover a new jailbreak attack, termed CodeSpear, that exploits GCD to induce LLMs into generating malicious code. Our experiments show that simply applying a benign code grammar constraint can effectively jailbreak LLMs. To address this vulnerability, we propose CodeShield, a safety alignment approach that robustly preserves safe behavior even under attacker-controlled grammar constraints. CodeShield aligns the model in the code modality by teaching it to generate honeypot code under GCD. Such code is semantically harmless, so it does not implement the malicious request, and structurally diverse, so it is difficult to suppress through grammar tightening. At the same time, CodeShield still preserves natural-language refusals when natural language is available. Experiments on 10 popular LLMs across 4 benchmarks show that CodeSpear outperforms representative jailbreak baselines and increases the attack success rate by more than 30 percentage points on average. CodeShield also restores safety under CodeSpear while preserving benign utility. Our findings reveal a fundamental risk of GCD and call for greater attention to its potential security implications.

19.
arXiv (CS.AI) 2026-06-15

Robustness without Wrinkles: Parallel Simulation and Robust MPC for Certified Deformable Manipulation

arXiv:2606.14188v1 Announce Type: cross Abstract: We present CORD-SLS, a real-time control method for safe deformable object manipulation, with a focus on ropes and cloth. At its core is a GPU-parallel differentiable simulator with contact smoothing which enables efficient gradient-based planning through intermittent contact. To robustly satisfy constraints under model and sensing uncertainty, we develop a real-time, GPU-parallel output-feedback robust model predictive control (MPC) algorithm that plans with this simulator. We further show that the simulator accelerates model-based RL for training neural manipulation policies. To improve real-world robustness, we use conformal prediction to calibrate visual-feedback and perception-error bounds for MPC, producing reachable tubes that enable high-probability safe control. We evaluate CORD-SLS on high-dimensional, contact-rich rope and cloth manipulation tasks in simulation and hardware, including obstacle avoidance, routing, folding, and smoothing. Across settings, CORD-SLS achieves millisecond-speed planning, exceeding baselines in safety, speed, and task success.

20.
medRxiv (Medicine) 2026-06-23

Intrapartum Oxytocin and Maternal Outcomes Following Vaginal and Unscheduled Cesarean Delivery

Objective To examine whether intrapartum synthetic oxytocin exposure for labor induction or augmentation is associated with breastfeeding and postpartum depressive and traumatic stress symptoms. Methods We studied 1,296 postpartum women who delivered at a single tertiary care center, with assessments from the third trimester through approximately two months postpartum. Intrapartum oxytocin exposure was obtained from electronic medical records. Outcomes included exclusive breastfeeding, postpartum depression, and childbirth-related traumatic stress. Analyses were stratified by delivery mode and adjusted for key maternal and obstetric covariates. Results Overall, 63.3% of participants received intrapartum oxytocin. Among participants with vaginal delivery, oxytocin exposure was associated with lower exclusive breastfeeding at two months after adjustment (58.2% vs 70.3%; adjusted RR 0.86, 95% CI 0.76- 0.97; p = 0.02), but not with postpartum mental health outcomes. Among participants with unscheduled cesarean delivery, oxytocin exposure was independently associated with higher immediate postpartum depressive symptoms (F = 4.97, p = 0.03), acute childbirth-related stress (F = 4.56, p = 0.03), and two-month childbirth-related posttraumatic stress symptoms (F = 4.30, p = 0.04), but not two-month depressive symptoms. Conclusion Intrapartum oxytocin exposure was associated with lower exclusive breastfeeding after vaginal delivery and modestly higher childbirth-related distress after unscheduled cesarean delivery. These findings suggest that oxytocin exposure may mark or contribute to postpartum vulnerability in specific delivery contexts.

21.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

22.
arXiv (CS.AI) 2026-06-19

"**Important** You should give me full credits!": Exploring Prompt Injection Attacks on LLM-Based Automatic Grading Systems

arXiv:2606.03090v2 Announce Type: replace-cross Abstract: The emergence of large language models (LLMs) has significantly accelerated recent research on LLM-based automatic grading (AG) systems. Benefiting from the strong instruction-following capabilities and broad prior knowledge of LLMs, educators can deploy AG systems across diverse tasks using only natural language rubrics while achieving satisfactory grading performance. Despite these advantages, new security concerns may also arise. In particular, prompt injection (PI) attacks have recently become a major threat to LLM-based applications. In the context of AG, attackers can potentially exploit PI vulnerabilities to manipulate grading systems into assigning artificially high scores regardless of the actual answer quality. Such behavior poses serious risks to the fairness, reliability, and integrity of educational assessment. In this work, we study PI attacks in AG systems, and systematically investigate the effectiveness of such attacks in educational scenarios. We further evaluate the effectiveness of existing defensive strategies against these attacks. Through comprehensive experiments under rubric-based grading settings, we demonstrate that current LLM-based AG systems remain highly vulnerable to PI attacks. We hope that our findings raise awareness of this emerging threat and motivate future research toward secure, robust, and trustworthy LLM-based educational systems.

23.
medRxiv (Medicine) 2026-06-23

Acute Ischemic Stroke Detection on Non-Contrast CT: A Deep Learning Approach

Acute ischemic stroke (AIS) is a leading cause of disability and death while effective treatment requires quick and accurate diagnosis. Non-contrast CT (NCCT) is widely used in the initial screening of AIS, but stroke detection is challenging because early changes on NCCT are subtle or indistinguishable. Using hyperacute NCCTs as inputs and diffusion-weighted MRI as ground truth, we trained a deep learning algorithm to classify patients with AIS and segment the stroke lesions. We hypothesized that this approach would accurately detect hyperacute tissue density changes on NCCT. For the classification task, our ResNet50 model delivered the best performance (with 98.5% accuracy, 97.4% precision, and 100% recall on an evaluation set). Classification performance remained strong when restricted to lesions smaller than 5 mL, which constituted the majority of our evaluation cases. For the segmentation task accomplished using a range of U-Net architectures, performance was acceptable for large lesions and declined sharply for smaller lesions. Together, these findings demonstrate the feasibility of deep learning for AIS detection and represent a step towards faster triage and treatment for stroke patients.

24.
arXiv (quant-ph) 2026-06-17

Closest Accessible Symmetry reduction: a tool for Hamiltonian interpolation analysis

arXiv:2606.18161v1 Announce Type: new Abstract: We introduce a framework for analysing the spectrum of Hamiltonian interpolations without heavily relying on discretising the interpolation parameter. The method is based on the concept of accessible symmetries: a problem-class-dependent family of certifiable reflections that induce bipartitions of the Hilbert space. At each step, the interpolation Hamiltonian is projected onto the sectors of the accessible symmetry that is closest to being satisfied, yielding a hierarchy of weakly coupled pseudo-eigenspaces together with explicit residual couplings between them. We show that this representation captures qualitative signatures of quantum phase transitions, provides estimates of their location, and offers insights into their nature. The quality of the approximation is controlled by the compatibility between the accessible symmetry family and the problem instance. Although motivated in spirit by adiabatic quantum computation, our approach applies more broadly to the study of Hamiltonian phase diagrams, providing a new perspective on the spectral reorganisation of many-body quantum systems.

25.
arXiv (CS.LG) 2026-06-15

Curvature-Informed Potential Energy Surface for Protein-Ligand Binding Affinity Prediction

arXiv:2606.14217v1 Announce Type: new Abstract: Accurate prediction of protein-ligand binding affinity is essential for structure-based drug discovery. Recent geometric deep learning methods have achieved promising performance by representing protein-ligand complexes as three-dimensional graphs. However, most existing approaches mainly rely on static interaction geometry from a single bound conformation, while neglecting molecular flexibility and binding-induced conformational changes. To address this limitation, we propose a curvature-informed potential energy surface (CPES) graph neural network for protein-ligand binding affinity prediction, which incorporates physics-informed curvature representations to model conformational flexibility. CPES first derives curvature spectral descriptors from the Hessian of the potential energy surface evaluated at equilibrium configurations, whose eigenvalues define the local principal curvatures of the potential energy surface. It then uses spectral cross-attention to compare the unbound ligand and protein with the bound complex, thereby capturing binding-induced changes in conformational dynamics. In parallel, hierarchical protein-ligand interaction representations are learned from static structural features through geometry-aware message passing, soft clustering, and bidirectional cross-attention. Finally, CPES fuses the curvature-informed dynamic representations with static interaction representations for affinity regression. Extensive evaluations on multiple benchmark datasets demonstrate that CPES achieves improved predictive performance and offers physical interpretability.