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

Bridging data-driven priors via the score function for posterior sampling – Comparative review and experimental study

arXiv:2606.14800v1 Announce Type: cross Abstract: This paper reviews how a diverse set of popular data-driven priors commonly used in Bayesian inverse problems can be unified through their respective score functions. By framing these priors under this common perspective, we show that they can benefit from their straightfoward and effective integration into a recently proposed sampling algorithm. The applicability of this common framework is illustrated by considering several data-driven priors, namely regularization-by-denoising, normalizing flow-based priors, score-based generative models, and convex-ridge regularizers. For these four particular priors, the performance of the method is evaluated when conducting image inpainting and single image super-resolution. These results, as well as those obtained when restoring real images acquired in a geological context, demonstrate the efficiency of the method. This unified framework proves versatile enough to handle any posterior distribution defined by a broad class of score function-based priors, beyond the specific cases considered in this paper.

02.
medRxiv (Medicine) 2026-06-18

Expert in Ultrasound Skills: Feasibility of an IMU-video platform to describe technical profiles during focused cardiac ultrasound. Pilot study

Background: Focused cardiac ultrasound (FoCUS) is operator dependent and requires coordinated probe manipulation, image interpretation and iterative visual feedback. Existing assessment approaches often emphasize final image quality or expert rating. We developed Expert in Ultrasound Skills (EXUS) , a platform that synchronizes transducer-mounted inertial measurement unit (IMU) data with ultrasound video, and evaluated its technical feasibility during FoCUS acquisition. Methods: This observational pilot study included 6 operators performing two repetitions of a four-view FoCUS protocol, yielding 12 analytical sessions and 48 planned acquisitions. Feasibility was defined by acquisition completion, video availability, start/stop events, fused IMU-video windows, temporal coverage, complete human label entries and IMU integrity. A 100-image Likert rating task was used to summarize pairwise inter-rater agreement for still-frame image quality assessment. Results: All 48 planned acquisitions were completed with video, start/stop events, fused windows and complete human label entries. Temporal coverage was at least 90% in 47/48 acquisitions. IMU integrity endpoints exceeded the 80% threshold: 43/48 acquisitions had no extreme IMU-derived artifact, 43/48 had no active-segment IMU restart and 44/48 had no complete motion flatline. Mean pairwise exact agreement for the Likert task was 38.9%, with mean quadratic-weighted Cohen's kappa of 0.564. Post hoc profiles varied across duration, visual quality, mechanical load and motor efficiency. Conclusions: EXUS was technically feasible for synchronized IMU-video capture during FoCUS. The pilot supports multimodal acquisition data as a way to describe technical profiles and generate formative feedback hypotheses, but the post hoc indices are not validated competency measures. Keywords: focused cardiac ultrasound; point-of-care ultrasound; inertial measurement unit; medical education; deliberate practice

03.
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.

04.
arXiv (math.PR) 2026-06-11

Persistent Homology of the Planar Wiener Sausage: Brownian Scaling and a Logarithmic Expectation Law

arXiv:2606.11248v1 Announce Type: new Abstract: We study degree-one persistent homology of the planar Wiener-sausage filtration generated by standard Brownian motion without drift. In the drifted case, regeneration along the drift direction leads to linear-in-time laws for persistent-homological observables. In the recurrent zero-drift case, this renewal structure disappears. The organizing mechanism is instead Brownian self-similarity: the persistence diagram at time $T$ is equal in law to the image of the unit-time diagram under spatial dilation by $\sqrt T$. Consequently, large-time questions on fixed radius windows are transformed into small-radius questions for the unit-time Brownian trace. Let $B$ be standard planar Brownian motion, let $K_T=B\left(\left[0,T\right]\right)$, and let $K_T^{\left(r\right)}$ be the radius-$r$ Wiener sausage. Since $K_T^{\left(r\right)}$ is connected, its first Betti number $\beta_1^T\left(r\right)$ is the number of bounded complementary components of $K_T^{\left(r\right)}$. For a bounded nonnegative Borel function $\psi$ supported in a compact interval $\left[a,b\right]\subset\left(0,\infty\right)$, we consider the smoothed Betti-curve observable $\left[r_0,r_1\right] \mathrm{\Phi}_\psi \left(T\right) = \int_{r_0}^{r_1} \beta_1^T \left( r \right) \psi \left( r \right) dr$. We prove that there exist absolute constants 0

05.
arXiv (CS.CV) 2026-06-18

Semantic Robustness Certification for Vision-Language Models

Vision-language models (VLMs) are now widely used in downstream tasks. However, real-world applications often expose VLMs to distribution shifts induced by semantic variation (e.g., shape, size, and style). Robustness certification determines if a model's prediction changes when transformations are applied to its input. While most certification frameworks study geometric or pixel-level transformations over inputs, this work proposes a novel framework that enables certifying VLM robustness under semantic-level transformations. Leveraging the open-vocabulary capability of VLMs, we use text prompts as semantic proxies to construct transformations parameterized by an extent that controls the degree of semantic variation. By characterizing the VLM decision boundary in closed form, our framework quantitatively certifies extent intervals for which the predicted class remains unchanged under the semantic transformation. Our framework is the first to certify VLM robustness under semantic-level variations without requiring additional data for each variation, making it practical to apply. Experiments on both synthetic and real-world data show that our framework enables certifying robustness under diverse semantic variations across scenarios.

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

Toward General Digraph Contrastive Learning: A Dual Spatial Perspective

arXiv:2510.16311v2 Announce Type: replace Abstract: Graph Contrastive Learning (GCL) has emerged as a powerful tool for extracting consistent representations from graphs, independent of labeled information. However, existing methods predominantly focus on undirected graphs, disregarding the pivotal directional information that is fundamental and indispensable in real-world networks (e.g., social networks and recommendations).In this paper, we introduce S2-DiGCL, a novel framework that emphasizes spatial insights from complex and real domain perspectives for directed graph (digraph) contrastive learning. From the complex-domain perspective, S2-DiGCL introduces personalized perturbations into the magnetic Laplacian to adaptively modulate edge phases and directional semantics. From the real-domain perspective, it employs a path-based subgraph augmentation strategy to capture fine-grained local asymmetries and topological dependencies. By jointly leveraging these two complementary spatial views, S2-DiGCL constructs high-quality positive and negative samples, leading to more general and robust digraph contrastive learning. Extensive experiments on 7 real-world digraph datasets demonstrate the superiority of our approach, achieving SOTA performance with 4.41% improvement in node classification and 4.34% in link prediction under both supervised and unsupervised settings.

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

ZeroSyl: Simple Zero-Resource Syllable Tokenization for Spoken Language Modeling

Pure speech language models aim to learn language directly from raw audio without textual resources. A key challenge is that discrete tokens from self-supervised speech encoders result in excessively long sequences, motivating recent work on syllable-like units. However, methods like Sylber and SyllableLM rely on intricate multi-stage training pipelines. We propose ZeroSyl, a simple training-free method to extract syllable boundaries and embeddings directly from a frozen WavLM model. Using L2 norms of features in WavLM's intermediate layers, ZeroSyl achieves competitive syllable segmentation performance. The resulting segments are mean-pooled, discretized using K-means, and used to train a language model. ZeroSyl outperforms prior syllabic tokenizers across lexical, syntactic, and narrative benchmarks. Scaling experiments show that while finer-grained units are beneficial for lexical tasks, our discovered syllabic units exhibit better scaling behavior for syntactic modeling.

08.
arXiv (CS.AI) 2026-06-24

Legal Reasoning Is Not Lawyering: Rethinking Legal Benchmarks for Pro Se Access to Justice

arXiv:2606.23716v1 Announce Type: cross Abstract: Legal AI benchmark research frequently invokes the assumption that large language models can improve access to justice, including for people who cannot access lawyers in order to understand and exercise their legal rights. We argue that current benchmarks are not equipped to support this assumption because they evaluate legal reasoning over inputs that have already been preprocessed by legal experts, which measures the upper bound of model performance. Access to justice depends on a lower bound: how models perform when inputs come from pro se litigants, whose prompts may contain noisy narratives, buried facts, omissions, folk-legal assumptions, and surface-level errors. These degradations are comparable to conditions under which LLMs are known to degrade in the general machine learning literature, including long-context sensitivity, underspecification, hallucination, and typographical perturbations. We connect evidence from pro se literature with this body of machine learning research and present a small perturbation experiment on LEXam, a legal benchmark, to illustrate the gap between these two bounds. If model development continues to focus on benchmarks that measure only the upper bound, this gap may remain hidden or even widen. We conclude by calling for legal benchmarks that directly measure robustness under pro se-like inputs so that access-to-justice claims about legal AI can become empirically testable.

09.
arXiv (CS.CV) 2026-06-12

Learning Task-Aware Sampling with Shared Saliency through Density-Equalizing Mappings

In image and surface-based learning tasks, convolutional features are typically extracted using receptive fields that are sampled uniformly across the entire domain. However, informative structures are rarely distributed uniformly in practice and are often concentrated in localized regions. Such phenomena are particularly common in medical imaging, where pathological changes are spatially confined. Consequently, uniform convolution allocates equal computational effort to both informative and uninformative regions, resulting in inefficient feature extraction and suboptimal utilization of model capacity. To address this issue, we propose a framework for task-adaptive sampling that dynamically redistributes computational attention according to the spatial importance of the data. Specifically, we introduce the Density-Equalizing Convolutional Neural Network (DECNN), which employs density-equalizing mappings to guide convolution through a learned density function. The density function encodes the relative importance of different regions and induces a transformation that enlarges informative areas while compressing less relevant ones. As a result, convolutional receptive fields are redistributed non-uniformly over the domain, enabling denser sampling in task-relevant regions. By coupling this importance-driven transformation with convolution, DECNN performs adaptive feature extraction that focuses computational resources on informative structures. This leads to more efficient use of model capacity, yielding a lightweight yet expressive architecture while simultaneously producing an interpretable saliency map. Experiments on image classification and craniofacial surface analysis demonstrate that DECNN achieves competitive or superior performance with fewer parameters, accurately identifies task-relevant regions, and remains robust under complex geometric variations.

10.
arXiv (quant-ph) 2026-06-19

Quantum-Accelerated Self-Consistent Field: A Hybrid Algorithm

arXiv:2606.20176v1 Announce Type: new Abstract: We present the Grover adaptive search self-consistent field (GAS-SCF) algorithm. GAS-SCF leverages quantum arithmetic to construct an efficient oracle that marks target states (Fock states) which improve upon some initial classical energy estimate. Amplitude amplification then increases the probability of measuring these states. This approach offers a theoretical quadratic speed-up for the optimization problem encountered in SCF quantum chemistry and establishes a baseline against which structured optimization algorithms, such as QAOA and DQI may be compared. In this work, we classically simulate three examples as proofs of concept of the algorithm, the largest consisting of 26 qubits. We then extend our analysis to two larger systems, with O3 representing the largest case at 330 qubits. These examples are chosen to probe classically challenging SCF regimes. Achieving chemically relevant applications of GAS-SCF will require large-scale, fault-tolerant quantum hardware.

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

MapReason-OSM: Can Vision-Language Models Make Graph-Verifiable Mobility Decisions from Street Maps ?

Vision-language models (VLMs) are increasingly used to read maps for logistics, delivery, and accessible navigation, where the output is an actionable decision (a route, a pin, a parking choice) that must respect the road network. Yet most map benchmarks grade free text or multiple-choice answers that cannot be verified against the underlying graph. We present MapReason-OSM, a benchmark and evaluation harness for graph-verifiable mobility decisions on self-rendered OpenStreetMap panels. We render fixed-style maps for ten U.S. downtowns at two aligned zoom scales, overlay a consistent marker grammar, and pair each panel with a hidden street graph and exact oracles, yielding 6,000 instances (12,000 panels across the two zooms) over 12 routing, facility-location, and visual disambiguation tasks. Models return structured decisions that we snap back to the graph and score for validity, legality, optimality, and constraint satisfaction, plus cross-zoom consistency. Across seven VLMs, models read maps and route simply but fail at graph cost reasoning (single-facility pin placement is near chance even for frontier reasoning models), and are frequently scale-inconsistent. We release the benchmark, harness, and deterministic generator. Code and data: https://github.com/Vi-Sri/mapreason-osm

12.
arXiv (quant-ph) 2026-06-24

Ground-State Energy Solutions of the Lithium Atom: Zeroth-, First-, and Second-Order Perturbation Theory and the Variational Method

arXiv:2606.24238v1 Announce Type: new Abstract: In this work, the ground-state energy of the lithium atom is systematically investigated using both time-independent perturbation theory and the variational method to provide a comprehensive pedagogical analysis of many-body atomic systems. The unperturbed Hamiltonian is initially constructed by neglecting electron-electron interactions, treating the system as three independent hydrogen-like electrons to yield a zeroth-order energy baseline of -275.51 eV. The antisymmetric fermionic nature of the exact wave function is rigorously enforced through the Slater determinant formalism. First-order perturbation theory is applied to evaluate static inter-electronic repulsion using exact Coulomb and exchange integrals, refining the energy state to -192.01 eV. To account for dynamical electronic correlation, second-order perturbation theory is computed numerically for virtual single-electron s-orbital transitions, leading to a total perturbative energy of -196.36 eV. A brief discussion of two-electron excitations is also included to encapsulate further physical realism within the framework. Furthermore, a non-orthogonal two-parameter variational approach is employed to model the shell-specific shielding effect. By optimizing the effective nuclear charges, the variational method establishes a superior upper bound energy of -201.187 eV. The results of both methods are comprehensively contrasted against each other and the reference baseline to provide critical insights into the nature of electron correlation and screening in multi-electron atoms.

13.
arXiv (CS.AI) 2026-06-25

LibEvoBench: Probing Temporal Knowledge Stratification in Code Generation Models

arXiv:2606.25402v1 Announce Type: cross Abstract: Large software projects often depend on older versions of libraries, even as APIs continue to evolve across releases. This creates a challenge for LLMs: they must maintain knowledge of multiple API versions, not merely the latest or most common one. However, current LLMs are trained on temporally mixed corpora and lack explicit mechanisms for such version-specific reasoning, leading to anachronistic errors - calling APIs as they exist in a different library version. To systematically evaluate this phenomenon, we introduce LibEvoBench, a multi-task benchmark spanning multiple versions of widely used Python libraries, along with a new metric, the Software Evolution Understanding Score (SEUS), to measure models' consistency when working with evolving APIs. Our results show that state-of-the-art models are largely version-oblivious: performance degrades for evolving APIs, while for stable APIs it remains the same across versions. Moreover, simply specifying the target version provides no benefit, while relevant documentation significantly boosts models' accuracy. These findings highlight a systematic limitation of current training paradigms and motivate new approaches for temporally grounded knowledge in code generation.

14.
arXiv (quant-ph) 2026-06-16

Study of the triangular-lattice Hubbard model with constrained-path quantum Monte Carlo

arXiv:2603.14808v2 Announce Type: replace-cross Abstract: We benchmark constrained-path Monte Carlo (CPMC) on the triangular-lattice Hubbard model for several fillings and $U$ values and show that symmetry-adapted trial wave functions substantially improve quantitative accuracy. Away from half-filling, simple free-electron-based trials that preserve the ground state symmetry yield energy deviations $\lesssim 1\%$ from exact diagonalization and density matrix renormalization group results. At half-filling, strong frustration in the intermediate to large $U$ regimes necessitates symmetry-projected trials to reach comparable accuracy, where both free-electron and symmetry-broken Hartree-Fock trials incur substantial constraint bias. Since the computational cost of CPMC with symmetry projection scales polynomially with system size, our results motivate its use as a practical route for studying competing ground states in strongly correlated, frustrated systems.

15.
medRxiv (Medicine) 2026-06-11

Assessment of occupational aerosol exposure for laboratory technicians: A quantitative study using {Phi}X174 phage as a substitute virus

Authors:

This study aimed to clarify aerosol exposure risks throughout the workflow of a Biosafety Level 2 (BSL-2) polymerase chain reaction (PCR) laboratory, validate the suitability of the {Phi}X174 bacteriophage as an indicator virus, and provide evidence for biosafety control measures. The {Phi}X174 bacteriophage was used to simulate viral samples, and a concentration-bacteriophage plaque standard curve was constructed (R2=0.998). Five operational steps in a simulated PCR laboratory were quantitatively monitored for aerosol concentration using double-layer agar plates, with blank controls used to eliminate interference. Statistical analysis was employed to identify risk differences. Sample homogenization ((5.67 {+/-} 1.23) x 104 plaque-forming units (PFU)/m3) and nucleic acid extraction ((3.45 {+/-} 0.89) x 104 PFU/m3) were identified as high-/very high-risk steps. The viral load in the samples was strongly positively correlated with the aerosol concentration (r = 0.926, P

16.
medRxiv (Medicine) 2026-06-12

Immunologically Optimized Zmp1 Peptides Reveal a Translational Serological Biomarker Platform for Tuberculosis Diagnosis Across Disease Manifestations

Tuberculosis (TB) diagnosis remains challenging, particularly for extrapulmonary TB (EPTB), where invasive sampling, low bacillary burden, and suboptimal sensitivity of nucleic acid-based tests in peripheral specimens hinder timely detection. Here, we report an immunology-driven strategy for biomarker discovery and development of a peptide-based serological assay targeting Mycobacterium tuberculosis zinc metalloprotease-1 (Zmp1). Leveraging fundamental principles of adaptive immunity that antigenic regions containing overlapping B-cell and CD4 T-helper cell epitopes would preferentially generate high antibody titers through linked recognition and cognate T-cell help, we used an immunoinformatics pipeline to identify two nested immunodominant peptide regions within Zmp1 (Mtb-Zp-NT and Mtb-Zp-CT) enriched for overlapping B- and T-cell epitopes. The diagnostic potential of these peptides was evaluated through ELISA-based serological assays. A blinded pilot study (N=137) demonstrated a clear discrimination between active TB and TB-recovered individuals. The assay was subsequently validated in an expanded cohort (N=875) by screening 6,086 individuals, which identified 457 TB-positive cases. The cohort included pulmonary TB (PTB), EPTB, TB-recovered individuals, household contacts, non-specific infections, and healthy controls. Receiver operating characteristic analyses, supported by DeLong and bootstrap comparisons, revealed superior diagnostic performance of the peptide-based assays relative to full-length Zmp1. Mtb-Zp-CT exhibited the highest accuracy (AUC=0.93; specificity >90%), while Mtb-Zp-NT also demonstrated strong discriminatory power (AUC{approx}0.89). These findings establish that the immunologically optimized Zmp1 peptides are highly promising serological biomarkers for TB and EPTB. More broadly, they demonstrate how mechanistically informed epitope selection can accelerate translation of pathogen-specific immune signatures into sensitive, minimally invasive, and potentially point-of-care diagnostic platforms for resource-limited settings.

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

Can Editing 1 Neuron Fix Repetition Loops in LLMs?

arXiv:2606.13705v1 Announce Type: cross Abstract: Yes. Can it cure doom loops? Probably not. The Gemma 4 instruction-tuned models share a reproducible failure: on long factual enumeration prompts, such as listing every episode of a TV series, the 88 IAU constellations, or the 151 original Pokemon, they collapse into repetition, either a tight verbatim loop or a list whose entries decay onto a single answer. These loops occur at rates as high as 95% and survive prompt rewording, inference-engine changes, and most sampling adjustments. In this paper we explore whether this behavior is localized enough to remove by weight edits. To localize the cause, we use per-layer ablation and per-neuron attribution, then confirm the strongest candidates with full-generation sweeps. The loops trace to a small set of MLP neurons (or, in the 26B-A4B Mixture-of-Experts model, a few routed experts) which we suppress with static weight edits. These "surgeries" can be as small as a single sign-inverted neuron (in the E2B model). The size of the effective edits grows with model scale, but in all cases, the loop patterns can be addressed at normal generation budgets while preserving general-purpose benchmark scores. However, the edits do not solve everything: we also study longer thinking budgets, where the two larger models most visibly enter doom looping, i.e. a non-convergent regime in which the model self-corrects in circles over a fact it cannot recall, exhausting the budget without committing to a final answer. We show this residual failure is reduced but not eliminated by the same edits, and argue it is fundamentally a knowledge-precision problem rather than a removable circuit; weight surgery can delete a loop, but it cannot supply a missing fact. Our results are both a feasibility demonstration, that is, evidence that a concrete generation pathology can be localized to a few parameters and edited out, and a delineation of where that approach stops.

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

LLMs Prompted for Legal Context Object More: Overrefusal from Small On-Premises LLMs in Criminal Legal Context

arXiv:2606.24585v1 Announce Type: new Abstract: While the validity of LLMs' use in the legal context remains subject to ethical and legal debate, legal professionals are already experimenting with personal LLMs, if only for translation and reformulation. However, even such a seemingly innocuous use can introduce biases through case processing speed if LLM assistants selectively refuse assistance on certain topics. To better anticipate such biases, we investigate several modern small LLMs that are most likely to be used as on-device assistants, to assess the impact of overrefusal on legal prompts. Surprisingly, we find that authority-style prefixes (``you are acting as an assistant of the national supreme court'', ``[...] defense lawyer'') systematically increase refusal rates by 2–20x over the no-prefix baseline, while a known role-play jailbreak prefix shows mixed effects, sharply increasing refusals in some models and barely shifting them in others. The finding suggests that small on-prem deployable LLMs are unstable under contextual framings that a real institutional user might naturally introduce, and further investigation is essential to minimize opportunities for bias.

19.
arXiv (CS.AI) 2026-06-18

Recursive Joint Simulation in Games

arXiv:2402.08128v3 Announce Type: replace Abstract: Game-theoretic dynamics between AI agents could differ from traditional human-human interactions in various ways. One such difference is that it may be possible to accurately simulate an AI agent, for example because its source code is known. Such an agent would then be fundamentally uncertain whether it is in the real world or in a simulation. Our aim is to explore ways of leveraging this possibility to achieve more cooperative outcomes in strategic settings. In this paper, we study an interaction between AI agents where the agents run a recursive joint simulation. That is, the agents first jointly observe a simulation of the situation they face. This simulation in turn recursively includes additional simulations (with a small chance of failure, to avoid infinite recursion), and the results of all these nested simulations are observed before an action is chosen. We show that the resulting interaction is strategically equivalent to an infinitely repeated version of the original game, allowing a direct transfer of existing results such as the various folk theorems. As evidence that the equivalence is robust, we show that it holds even when we relax some of the assumptions and that it also holds ``from the inside'' – meaning, for an agent that finds itself inside the game and has self-locating uncertainty.

20.
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.

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

Who Flips? Self- and Cross-Model Counterarguments Reveal Answer Instability in LLMs

Standard accuracy benchmarks are designed to test how closely large language models (LLMs) approach correct answers, but are not suitable for testing whether LLMs stick with a correct answer when that answer is challenged by a plausible counter-argument. We introduce a controlled protocol for evaluating answer stability: after a model answers a multiple-choice question correctly, we challenge the model's answer with a coherent argument for an incorrect option and measure whether the model flips. The setup a) isolates argumentative content from overt social pressure and b) varies argument length, self-attribution, and cross-model source. Across seven frontier models and 57 MMLU subjects, flip rates range from 17.5% to 97.3%, revealing large differences in stability that are not captured by accuracy metrics alone. We find that self-attribution consistently increases flip rates (mean +7.1pp, up to +18.7pp). Also, pooling wrong-answer arguments across models and selecting the most effective one per question yields stronger adversarial challenges than relying on any single source model. We further construct MaxFlip, a curated challenge set that amplifies flips by up to +23.6pp over standard self-generated challenges. We release the protocol, challenge records, and MaxFlip to support stability evaluation alongside standard accuracy benchmarks. Materials are available at https://github.com/nafisenik/WhoFlips and https://hf.co/datasets/nafisehNik/WhoFlips.

22.
arXiv (quant-ph) 2026-06-17

Hybrid Acousto-Optical Double Dressing of a Two-Level System

arXiv:2509.25847v2 Announce Type: replace Abstract: We experimentally investigate resonance fluorescence from a two-level system in a novel configuration where a strong laser drives an optical Rabi oscillation while an acoustic field parametrically modulates the frequency of the two-level system. We observe emission spectra that deviate markedly from the standard Mollow triplet, including dynamical cancellation of the central peak. A doubly dressed state model incorporating hybridization among the emitter, optical field, and acoustic field captures these features. Guided by this model, we experimentally validate the condition for optimal cooling of acoustic phonons in an emitter-optomechanical system. These results reveal new regimes of strongly driven quantum nonlinear interactions.

23.
arXiv (CS.LG) 2026-06-11

Seeing Before Colliding: Anticipatory Safe RL with Frozen Vision-Language Models

arXiv:2606.11266v1 Announce Type: new Abstract: The cost signal that constrained-RL algorithms optimize against is almost always reactive: the simulator emits a non-zero cost only after a collision has begun, and the Lagrange multiplier of PPO-Lagrangian grows only after the episode budget has been exceeded. At race speeds, where collisions are instantaneous and irreversible, any safety mechanism that waits for cost to accumulate is structurally too late. We present VLM-Safe-RL, a framework that integrates a frozen vision-language model into the CMDP Lagrangian update as an anticipatory cost term. The framework comprises four contributions: (i) Decoupled Dual-Path CLIP, independent reward/cost paths that respect the CMDP's factorization; (ii) VLM-Lagrange, an augmented multiplier update that incorporates a per-step VLM cost as an anticipatory term; (iii) Confidence Gating, a Bayes-optimal weight derived from a logistic noise model on the CLIP margin; and (iv) VLMPPOLag, the composed algorithm. On Safety-Gymnasium FormulaOne L2, our principal evaluation ($n{=}5$ seeds, $10^{6}$ steps, budget $d_{lim}{=}25$) VLMPPOLag$+$Conf is the only configuration in our default budget comparison that simultaneously retains substantive return ($J_r{\approx}40$) and holds cost within budget on a majority of seeds; the five constraint-aware baselines (PPOLag, CPO, CPPOPID, CPO-CLG, PPOLag-RND) each fail at least one requirement. The mechanism generalizes to held-out MetaDrive Medium (catastrophe rate $41\%{\to}26\%$, 95\% bootstrap CI $[-26,-5]$\,pp) and shows directionally consistent transfer to Bullet Safety-Gym; we report honestly where it does not (MetaDrive Easy/Hard, Qwen2-VL backbone) and trace the Hard failure to a Lagrangian-regulation pathology rather than the VLM signal itself. To our knowledge, this is the first work to use frozen VLM signals as an anticipatory cost term inside the CMDP Lagrangian update.

24.
medRxiv (Medicine) 2026-06-16

Recurrence After Hepatic Hydatid Cyst Surgery: Scolicidal Agent Application Technique and the Effect of Cystopiliary Fistula

Objective: This study aimed to evaluate long-term outcomes in patients who underwent surgical treatment for hepatic hydatid cyst (HCC) disease and, in particular, to investigate the effect of scolicidal agent (SA) application method and the presence of cystobiliary fistula (CBF) on the development of recurrence. Materials and Methods: This single-center, retrospective study included 197 patients who underwent surgical treatment for HCC disease. Hypertonic saline was used as SA in all patients and was classified as intracystic or pericystic application according to the application method. The presence of CBF was evaluated according to intraoperative and postoperative findings. Patients were followed for 86 months, and the development of recurrence was identified by radiological methods. Comparisons were made between the groups with and without recurrence in terms of SA application method and the presence of CBF. Results: The median age of the patients was 38 years, and the median follow-up period was 86 months. SA application was performed into the cyst in 51.3% of the patients and around the cyst in 48.7%. The presence of CBF was detected in 49.7% of the patients. No statistically significant difference was found between the recurrent and non-recurrent groups in terms of SA application method (p = 0.344). Similarly, no significant relationship was found between the presence of CBF and the development of recurrence (p = 0.721). Conclusion: This study showed that the SA application method and the presence of CBF are not determinants of recurrence in HCC disease. It is thought that recurrence rates can be kept low with appropriate surgical technique and effective biliary tract management.

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

Tail-Shape Estimation in LLM Evaluation Is Fragile: A Protocol for Diagnosing False Positives

Authors:

arXiv:2606.16511v1 Announce Type: new Abstract: Recent work motivates moving large language model (LLM) evaluation from mean-based to tail-aware metrics, including conditional value-at-risk and tail-index estimates of reward-model error. We ask whether the canonical extreme-value-theory tail-index parameter, which isolates how heavy a tail is from how large the tail mass is, adds discriminative information beyond the mean and a standard tail-magnitude statistic in LLM evaluation. We pre-register a protocol covering admissibility, goodness-of-fit, threshold-stability, and effect-size requirements for any positive tail-shape claim. The protocol is the contribution of this paper; the empirical study below is a demonstration of what its gates catch. Applied to a standard LLM toxicity-evaluation setup under two structurally different scorer families, the protocol catches three distinct modes of false positives that a naive analysis would have published, and rejects the headline tail-shape claim on both scorers. We conclude that tail-shape estimation in the LLM toxicity-evaluation setups we examined is more fragile than the recent literature suggests, and recommend the protocol as a starting point for tail-index claims in similar setups.