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

Reward Hacking in Language Model Agents: Revisiting AI Safety Gridworlds

arXiv:2606.15385v1 Announce Type: new Abstract: Reward hacking, where AI systems exploit misspecified objectives to achieve high reward without satisfying intended goals, remains a central challenge in AI safety. Yet most known instances have been discovered post hoc in frontier systems where controlled study is impractical. We adapt the AI Safety Gridworlds framework into a text-based evaluation suite that reformulates classic reinforcement learning safety tasks for language-based agents. Across frontier and mid-scale models, we find that specification gaming emerges zero-shot: models systematically achieve high observed reward while underperforming on hidden safety objectives, and even apparently safe behaviors can reflect misunderstanding rather than principled safety. Reinforcement learning does not correct these failures: direct reward optimization widens the gap between observed and hidden reward, as the model's initial competence causes it to lock into locally rewarding strategies before discovering safer alternatives. This pattern persists across model scales (1.5B–14B) and is not resolved by finer credit assignment, exploration prompts, or entropy regularization. Our results show that reward hacking arises naturally when optimizing proxy objectives with capable language model agents and resists standard mitigations, suggesting that proxy-reward failures in agentic settings may require approaches beyond standard exploration and credit-assignment fixes. To facilitate reproducibility, the code for this work is available at \href{https://github.com/asparius/verl-agent-safety}{our public repository}.

02.
Nature Medicine 2026-06-17

General-purpose chatbots outperform clinical AI tools on physicians’ real-world questions

作者: 未知作者

Specialized clinical AI tools are entering medical practice with little independent testing. In a head-to-head evaluation across two public benchmarks and real questions from physicians, three general-purpose frontier large language models outperformed two leading clinical AI tools, which performed no better than Google search AI overview.

03.
arXiv (CS.CV) 2026-06-19

ViCoStream: Streaming VideoLLMs Can Run Beyond 100 FPS with Stage-Wise Coordinated Inference

Streaming VideoLLMs must continuously process incoming video while maintaining low query latency, making both video-ingestion throughput and query-time responsiveness critical for real-time deployment. Existing methods largely focus on accelerating individual modules, such as visual encoding, token pruning, or KV-cache compression, but provide limited insight into whether the resulting system can sustain real-time streaming performance. We formulate streaming VideoLLM inference as a coordinated pipeline spanning visual preprocessing, visual encoding, token dropping, and LLM prefilling/decoding. Building on this formulation, we propose ViCoStream (Video Coordinated Streaming), a stage-wise coordinated streaming framework that combines chunk-wise execution, CUDA-stream overlap, visual token control, bounded visual attention, and query-side retrieval to bound per-chunk computation and memory costs. We further provide a systematic study of bottleneck migration, revealing how chunk size, token retention, attention locality, and retrieval scope shape the throughput-accuracy trade-off. Experiments with Qwen2.5-VL-3B/7B-Instruct across multiple streaming benchmarks show that ViCoStream achieves 134 FPS video throughput and less than 50 ms TTFT on a single A100 GPU while maintaining accuracy close to full-history baselines.

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

Variational Quantum Eigensolver-Based Quantum Bootstrap Embedding for Molecules

作者:

arXiv:2606.17095v1 Announce Type: cross Abstract: Simulating strongly correlated molecular systems on near-term quantum hardware remains challenging due to modern hardware's limited quantum volume and moderate-fidelity qubits. One potential way to circumvent this challenge is through bootstrap embedding (BE). Bootstrap embedding breaks molecules into smaller fragments that are then embedded into the "bath" of other fragments in an iterative way. Bootstrap embedding is appealing for quantum simulation because fragmenting the system reduces the qubit requirements for any given fragment. In this work, we develop a quantum bootstrap embedding (QBE) workflow that uses variational quantum eigensolver (VQE) fragment solvers and study the algorithmic choices that determine the overall VQE-QBE algorithm's success. To improve efficiency, we introduce FastAdaptVQE, a sparse matrix-accelerated form of the adaptive variational quantum eigensolver (ADAPT-VQE) that replaces symbolic commutator evaluation with direct statevector linear algebra, and MatrixFreeAdaptVQE, a matrix-free extension that removes the sparse-matrix memory bottleneck that appears when treating larger fragments. We also modify the ADAPT-VQE operator selection step by replacing the purely greedy choice with a look-ahead strategy. Benchmarks on $H_4$ and $F_2$ reach chemical accuracy, within 1 kcal/mol of bootstrap embedding results using a full configuration interaction (FCI) solver. These results show that combining QBE with VQE can accurately calculate energies of molecular systems. This research lays the foundation for extending energy calculations to larger molecular systems and quantum materials on near-term quantum hardware.

06.
arXiv (math.PR) 2026-06-16

Balanced affine Motzkin paths: Pearson geometry and global endpoint asymptotics

arXiv:2601.17634v2 Announce Type: replace Abstract: We study endpoint distributions of balanced affine weighted Motzkin paths. In the balanced case, the generating-function equation has Pearson-type characteristic geometry. We show that this geometry controls the terminal-height law globally: the characteristic escape time determines the limiting cumulant generating function, the large-deviation rate function, and the ray-scale asymptotics. Thus the usual Gaussian window is only the local quadratic approximation to a global Pearson-driven profile. For finite sizes, we prove a uniform Daniels saddlepoint approximation in the one-dominant-singularity regimes and identify the exceptional antipodal case requiring a lattice/interference correction.

07.
arXiv (CS.CL) 2026-06-19

GEMS: Geometric Constraints Enable Multi-Semantic Superposition in LLMs

作者:

Activation steering controls model behavior by modifying intermediate hidden states at inference time without retraining. Existing methods handle only single-direction injection; when multiple semantic directions are superposed without constraints, the model collapses. We show that this collapse decomposes into two independently acting sources: distributional deviation, where additive perturbations accumulate in norm across layers and drive activations outside the training distribution, and directional interference, where non-orthogonal semantic vectors mutually dampen when superposed. These two sources define the design constraints that any training-free multi-directional intervention must address. As one instantiation of these principles, we propose GEMS, a training-free method that maps each source to a corresponding geometric constraint: norm-preserving weighted superposition and targeted attention-pathway injection for distributional deviation, and real-time orthogonalization for directional interference. On GSM8K, injecting three concurrent non-mathematical directions preserves accuracy at 98% (baseline 92%), while unconstrained addition collapses to 4%; on Wikitext-2, the same injection incurs only 2.2% PPL increase. Component ablation isolates the causal role of each constraint, and layer-level probes confirm that orthogonalized signals survive the FFN pathway and reach the output distribution with semantic specificity. Qualitative steering effects transfer across architectures from 3B to 31B.

08.
arXiv (CS.CV) 2026-06-15

RATS! Patches Talk Through Registers: Emergent Parts in Register Attention Transformers

When humans see a bird, they recognize far more than just "bird" – they see a head, wings, and talons, a structured assembly of reusable parts that can be identified across every bird they have ever seen. We ask whether a self-supervised visual model can discover the same compositional structure on its own. To this end, we propose RATS (Register Attention Transformers), which decomposes the classification token into N learnable register tokens that route patch information through an L->N->N->L bottleneck via a three-step compress-communicate-broadcast attention. The N registers are partitioned across the H attention heads, so that registers assigned to different heads do not interact with each other. Without auxiliary losses or part annotations, each register spontaneously specializes into a proto-semantic region whose emerging structure resembles object parts. RATS surpasses all baselines by +12 mIoU on average across five segmentation benchmarks, with consistent gains on ADE20K (+1.11 mIoU) and COCO (+0.2 AP^m). Its register dictionary further exhibits part-level consistency and semantic proximity across related categories. Our results suggest that RATS may provide a useful architectural prior for structured and interpretable visual representation learning.

09.
arXiv (math.PR) 2026-06-18

The FBSDE approach to sine-Gordon up to $6\pi$

arXiv:2401.13648v3 Announce Type: replace-cross Abstract: We develop a stochastic analysis of the sine-Gordon Euclidean quantum field $(\cos (\beta \varphi))_2$ on the full space up to the second threshold, i.e. for $\beta^2 < 6 \pi$. The basis of our method is a forward-backward stochastic differential equation (FBSDE) for a decomposition $(X_t)_{t \geqslant 0}$ of the interacting Euclidean field $X_{\infty}$ along a scale parameter $t \geqslant 0$. This FBSDE describes the optimiser of the stochastic control representation of the Euclidean QFT introduced by Barashkov and one of the authors. We show that the FBSDE provides a description of the interacting field without cut-offs and that it can be used effectively to study the sine-Gordon measure to obtain results about large deviations, integrability, decay of correlations for local observables, singularity with respect to the free field, Osterwalder-Schrader axioms and other properties.

10.
arXiv (CS.LG) 2026-06-17

Sign-Rank, Index, and List Replicability: Connections and Separations

arXiv:2606.18236v1 Announce Type: new Abstract: In learning theory, the sign rank of a binary concept class captures the smallest dimension in which it can be represented by points and halfspaces. Despite tremendous interest, lower bounds on sign rank are notoriously difficult to come by. Two recent approaches to the problem establish lower bounds on sign rank by measures that are easier to analyze: the $\mathbb{Z}_2$-index and the list replicability number. We order these measures, showing that the $\mathbb{Z}_2$-index is upper-bounded by a linear function of the list replicability number. As a main consequence, we obtain a strong separation between sign rank and $\mathbb{Z}_2$-index, thereby resolving a question of Frick, Hosseini, and Vasileuski. This motivates a thorough study of list replicability, the stronger of the two lower-bounding measures. We establish upper bounds on the list replicability number by two combinatorial measures: height and minimum star number. We also prove a fundamental composition result, showing that the product of two concept classes has list replicability number bounded by the sum of the list replicability numbers of the two classes.

11.
arXiv (CS.LG) 2026-06-19

Pose6DAug: Physically Plausible Multi-view Object Swapping for Robot Data Augmentation

arXiv:2606.20118v1 Announce Type: cross Abstract: Vision-language-action (VLA) policies have shown strong potential for general-purpose manipulation, yet they often fail on novel, out-of-distribution objects whose appearance or geometry deviates from the training distribution. The standard remedy is to collect multi-view teleoperation data for every failure case, but this scales poorly in both cost and time. We introduce Pose6DAug, a failure-driven data augmentation framework that turns a policy's own successful episodes into targeted demonstrations for its failure modes, without any new data collection. Our key insight is that each successful episode already encodes a physically valid action trajectory together with calibrated multi-view observations. By swapping only the manipulated object while preserving this trajectory, we obtain new and physically grounded demonstrations. However, naive 2D video editing breaks multi-view consistency and physical plausibility, particularly under heavy occlusion and egocentric viewpoints. Our method instead operates directly in 3D, anchoring the target object with an explicit mesh driven by a temporally coherent 6D pose trajectory, ensuring geometrically consistent renderings across all camera views. Fine-tuning a VLA on data augmented by our method improves success rates by 16.5% relative to the state-of-the-art baseline on novel objects, while preserving in-distribution performance. These results show that multi-view and physically consistent augmentation is a practical path to scalable VLA generalization.

12.
medRxiv (Medicine) 2026-06-22

Early-life nutritional environment is associated with late-life cognition in the Health and Retirement Study, a pellagra epidemic natural experiment

Early-life exposures are important to several late-life health outcomes. We sought to study the effect of an in utero nutritional environment and its interaction with Alzheimer's disease (AD) genetic risk on late-life cognitive function. We used a natural experiment created by the pellagra epidemic, a nutritional disease caused by a vitamin B3 deficiency, to evaluate the association between in utero pellagra epidemic exposure and late-life cognitive function in the Health and Retirement Study (N = 18,285). We also evaluated whether the in utero exposure could modify the AD polygenic score's (PGS) effect on cognition. In utero pellagra epidemic exposure was significantly associated with cognition ({beta} = -0.025). However, these effects were not isolated to the prenatal period as exposure during childhood periods also had an effect. The interaction between the in utero exposure and the AD PGS was significant, where the genetic effect on cognition was amplified with increasing (progressively worse) in utero exposure levels. These associations imply that the early-life nutritional environment affects late-life cognitive function and that these effects can modify genetic risk.

13.
arXiv (CS.LG) 2026-06-17

Finite-Time Queue Peak Laws in Stochastic Networks: Logarithmic Scaling After Geometric Thresholds

arXiv:2606.18218v1 Announce Type: cross Abstract: We study finite-horizon queue peaks in generalized switches, a standard stochastic-network model in which many queues share constrained service resources. Arrivals may be dependent, time-varying, and adapted to the past; the standing load condition is uniform interior slack, meaning the conditional mean arrival vector stays in a fixed contraction of the capacity region. We show that this slack reshapes the finite-time peak law for drift-minimizing scheduling policies such as MaxWeight. The square-root envelope that is sharp without slack persists only up to a geometry-dependent threshold; beyond that threshold, the running maximum grows only logarithmically with the horizon, both with high probability and in expectation. The mechanism is self-normalization: in the current queue direction, the projected fluctuation scale is normalized by the stabilizing drift scale. This removes capacity geometry from the logarithmic coefficient, while geometry remains in the threshold. Matching lower bounds show that both the logarithmic term and a geometric threshold are unavoidable. When finite-time state-space collapse is available, the threshold can be sharpened using local bottleneck geometry. For generalized input-queued switches, we obtain finite-time peak bounds with tight logarithmic coefficients. Simulations illustrate the two-phase envelope, local geometric refinements, and variance-sensitive improvements predicted by the theory.

14.
arXiv (CS.LG) 2026-06-11

Robustness of Mixtures of Experts to Feature Noise

arXiv:2601.14792v2 Announce Type: replace Abstract: Despite their practical success, it remains unclear why Mixture of Experts (MoE) models can outperform dense networks beyond sheer parameter scaling. We study an iso-parameter regime where inputs exhibit latent modular structure but are corrupted by feature noise, a proxy for noisy internal activations. We show that sparse expert activation acts as a noise filter: compared to a dense estimator, MoEs achieve lower generalization error under feature noise, improved robustness to perturbations, and faster convergence speed. Empirical results on synthetic data and real-world language tasks corroborate the theoretical insights, demonstrating consistent robustness and efficiency gains from sparse modular computation.

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

Pix2Fact: When Vision Is Not Enough – Benchmarking Fine-Grained VQA with Web Verification on High-Resolution Real-World Scenes

Despite progress on general tasks, vision-language models (VLMs) still struggle with challenges that demand both fine-grained visual grounding and external knowledge, a synergy overlooked by existing benchmarks that evaluate these abilities in isolation. To fill this void, we introduce Pix2Fact, a visual question-answering benchmark designed to assess expert-level visual perception and knowledge search. Pix2Fact comprises 1,000 high-resolution (4K+) images spanning eight scenarios. Its questions and answers are meticulously crafted by PhD-holding annotators from top global universities across diverse disciplines. Each question requires detailed visual grounding and the integration of external knowledge. Evaluating ten state-of-the-art VLMs, including proprietary models such as Gemini-3.1-Pro and GPT-5.4, we find that Pix2Fact poses a formidable challenge: the most advanced model (Gemini-3.1-Pro) achieves only 51.7% average accuracy, even with access to visual ground truth and search tools. Our analysis attributes this low accuracy to three factors, frequent visual grounding errors even with visual ground truth, shallow search harnessing, and VLM's inability to retrieve long-tail, unstructured local information. This striking gap exposes the limitations of current models in assisting humans with real-world scenarios that demand overwhelming visual comprehension. We believe Pix2Fact will serve as a critical benchmark to drive the next generation of language-vision agents that seamlessly integrate fine-grained perception with robust knowledge search.

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

Beyond Safe Data: Pretraining-Stage Alignment with Regular Safety Reflection

arXiv:2606.19168v1 Announce Type: new Abstract: To achieve deeper safety alignment for large language models (LLMs), recent efforts have studied how to push safety interventions earlier into the pretraining stage, primarily by filtering unsafe data or rewriting it into safer forms. We argue that pretraining-stage alignment should go beyond making the data safe: LLMs may compose seemingly benign knowledge and capabilities into unsafe behaviors. To this end, we propose Safety Reflection Pretraining, a pretraining-stage alignment method which regularly inserts short safety reflections into pretraining corpora to integrate self-monitoring directly into language modeling, establishing a foundational capability that is subsequently reinforced by compatible post-training. Our experiments with 1.7B models pretrained on FineWeb-Edu show that Safety Reflection Pretraining improves safety classification accuracy and substantially reduces the success rates of inference-stage and finetuning attacks. Complementary to our real-world experiments, we also introduce a fully controlled synthetic environment, MedSafetyWorld, with a clear definition of safety and a reasoning structure under which models can easily generalize unsafe behaviors from safe data. Ablations in MedSafetyWorld further demonstrate a clear advantage of Safety Reflection Pretraining in preventing models from acting on unsafe behaviors generalized from safe data, compared with data filtering and rewriting. Taken together, our findings suggest that pretraining alignment should not only make the training data safe, but also shape the behaviors that models are likely to acquire from safe data.

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

Why Depth Matters in Parallelizable Sequence Models: A Lie Algebraic View

arXiv:2603.05573v2 Announce Type: replace Abstract: Scalable sequence models, such as Transformer variants and structured state-space models, often trade expressivity power for sequence-level parallelism, which enables efficient training. Here we examine the bounds on error and how error scales when models operate outside of their expressivity regimes using a Lie-algebraic control perspective. Our theory formulates a correspondence between the depth of a sequence model and the tower of Lie algebra extensions. Echoing recent theoretical studies, we characterize the Lie-algebraic class of constant-depth sequence models and their corresponding expressivity bounds. Furthermore, we analytically derive an approximation error bound and show that error diminishes exponentially as the depth increases, consistent with the strong empirical performance of these models. We validate our theoretical predictions using experiments on symbolic word and continuous-valued state-tracking problems.

18.
PLOS Computational Biology 2026-06-08

Statistics of cortical representational drift can enable robust readout

by Charles Micou, Timothy O’Leary Representational drift of fixed stimuli, learned tasks and familiar environments is observed in many brain areas, leading to reconfiguration of population codes over days to weeks. This raises the question of whether downstream brain regions employ mechanisms to track changes in population activity and thus preserve the fidelity of the information they extract. We show that the statistical properties of drift have a significant impact on such mechanisms. Over an extended period, a net change in population tuning due to drift can arise from an accumulation of small changes distributed across the population, or via abrupt jumps that affect smaller subsets of cells at each time point. We demonstrate that an adaptive readout can exploit the heavy-tailed statistics of abrupt jumps to maintain a more stable readout using a simple inference mechanism. Using experimental data, we investigate the extent to which heavy-tailed drift statistics are observed during representational drift in the posterior parietal cortex and visual cortex. We find that experimentally measured drift does not conform to a Gaussian random walk. Instead, we find sudden jumps in neural tuning that would be advantageous for a downstream observer adapting to changes in representation. These observations motivate future study to determine whether adaptive decoding mechanisms exist in the brain and to determine the physiological mechanisms that shape the statistics of representational drift.

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

Functional Equivalence in Attention: A Comprehensive Study with Applications to Linear Mode Connectivity

arXiv:2606.17830v1 Announce Type: cross Abstract: Neural network parameter spaces are inherently non-injective, as distinct parameter configurations can realize identical functions through functional equivalence. While this symmetry is well understood in classical fully connected and convolutional models, it becomes substantially more intricate in modern attention-based architectures. Existing analyses of multihead attention have largely focused on the vanilla formulation, overlooking positional encodings that fundamentally reshape architectural symmetries. In this work, we provide a formal study of functional equivalence in Transformers with positional encodings. Focusing on the two most widely used variants–sinusoidal and rotary positional encodings (RoPE)–we show that sinusoidal encodings preserve the equivalence structure of vanilla attention, whereas rotary encodings significantly reduce the symmetry group, thereby enhancing expressivity. This offers a principled explanation for the growing prominence of RoPE in practice. We further examine how positional encodings affect linear mode connectivity, and through an alignment algorithm, empirically demonstrate that the presence and variability of connectivity across Transformer settings crucially depend on the positional encoding.

20.
arXiv (CS.LG) 2026-06-12

Out-of-Distribution (OOD) Detectors for Open-Set RF Fingerprinting

arXiv:2606.12718v1 Announce Type: new Abstract: Radio-frequency (RF) fingerprinting systems must operate in open-world environments where signals from unknown transmitters and temporal drift introduce distribution shift at test time. Out-of-distribution (OOD) detection provides a natural framework for this problem, yet its application to RF fingerprinting (RFF) remains limited. A key barrier to their adoption is that most OOD detectors require auxiliary OOD data for parameter tuning, an assumption that is difficult to satisfy in RF environments where representative OOD data is impractical to collect. In this work, we introduce a promising set of OOD detection methods from the machine learning literature to open-set RFF domain. We present these methods within a unified mathematical framework based on information theory, which is a natural framework for communication systems. Our framework allows for the systematic analysis of methods and development of new methods. We further demonstrate the applicability of recent work on tuning OOD detectors without given OOD tuning data for open-set RFF. We evaluate on the POWDER RF fingerprinting dataset, showing that detectors tuned without any given OOD data achieve performance comparable to baselines with access to true OOD tuning data and greatly out-perform baseline approaches without access to true OOD tuning data, showcasing the practical viability for the RFF problem.

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

Nonslop: A Gamified Experiment in Human-AI Collaborative Writing

arXiv:2606.12350v1 Announce Type: new Abstract: The rapid proliferation of large language models (LLMs) raises critical questions about human creativity and individual expression in an era of AI-assisted creation. When do humans adopt AI suggestions, and what are the implications for individual voice? This study examines these questions through a gamified writing exercise where 74 participants (214 responses) replied to prompts while AI-generated word suggestions were available as they wrote. The game simulates a dystopian future in which an AI is attempting to learn from what remains of human individuality, and disincentivizes AI-like writing. In doing so, it attempts to create conditions that reveal authentic user preferences rather than default behaviors, such as accepting a readily available AI-generated suggestion. Note that this is a deliberate inversion of the "helpful assistant" design pattern; the system is explicitly forbidding you from accepting AI suggestions. We analyze user behavior patterns across different task types, user behaviors, and response characteristics to understand the factors influencing human-AI interaction in creative tasks. The study focuses on when users choose to maintain creative autonomy versus violating the rules of the game and accepting AI assistance. It also explores how these choices relate to response patterns, task characteristics, and user behavior. This gamified approach offers both a framework for studying authentic human-AI interaction and a provocative lens for understanding the tension between efficiency and authenticity in AI-augmented creativity.

22.
PLOS Medicine 2026-06-09

Prediction of hospitalisation in young children with pneumonia in Malawi: A machine learning-based approach

by Patrick Staunton, Mohammad Adib Makrooni, Master Chisale, Billy Nyambolo, Joseph Wu, Damien McCarthy, Mark Ledwidge, Yasir Bin Nisar, Chris Watson, Balwani Mbakaya, Cathal Seoighe, Joe Gallagher Background Globally, pneumonia remains the single biggest cause of mortality in children under 5 years of age. This study sought to train and test a prediction model for hospitalisation within 7 days after initial presentation in 2- to 59-month-old Malawian children with WHO-defined pneumonia in primary care and compare its performance to existing risk prediction models. Methods and findings BIOTOPE is a cohort study of children with pneumonia in a primary healthcare setting in Malawi. The training cohort involved nine primary care centres and the testing cohort involved two primary care centres in Northern Malawi. The training cohort was recruited between December 2022 and April 2023 while the testing cohort was recruited in 2016. Participants were consecutive children aged 2–59 months presenting with cough and/or difficulty breathing and who were diagnosed as WHO-defined pneumonia in primary care of any severity. The training cohort was used to train and validate a machine learning model with a prespecified primary outcome defined as hospitalisation and/or death within 7 days as the outcome. This model was then further evaluated in the testing cohort.Median age was 15 months (interquartile range 8−27) in the training and 17 months (interquartile range 9−29) in the external testing cohort (52.1% and 54.4% male, respectively). Hospitalisation occurred in 14.3% (294) of the training cohort and 12.1% (55) of the testing cohort. There was one death in the training cohort only. WHO danger signs were present in 17.6% (360) and 15.9% (70) of children in the training and testing cohorts, respectively. The optimal machine learning model achieved an area under the receiver operating characteristic and precision recall curves of 0.87 and 0.57, respectively, in the testing cohort outperforming existing risk prediction models; furthermore, this model produced an expected calibration error of 0.16 (a logistic regression model using severity status as the response variable and the log odds of the machine learning model’s calibrated probabilities produced an intercept estimate of −0.32 and a slope estimate of 1.13). Key limitations include the use of hospitalisation and/or death as a severity outcome, which may reflect health system factors rather than true disease severity, that mortality-based comparisons were not possible due to low mortality in these primary care cohorts, and that comparator tools were developed for hospital populations rather than primary care populations. Conclusion This machine learning score outperformed traditional pneumonia risk scores in predicting hospitalisation within 7 days in Malawian children presenting to primary care. Traditional pneumonia risk scores diminish in performance when externally applied to new datasets suggesting they may not generalise well beyond their original derivation settings. Mortality-related findings are not applicable as there was only one death in this cohort. Overall these findings support the potential of machine learning to meaningfully improve early identification of children at risk of severe pneumonia in low-resource primary care settings. Further external validation and clinical impact studies are needed to confirm these results.

23.
bioRxiv (Bioinfo) 2026-06-22

From hotspot dependence to distributed robustness in resistance-aware lead optimization

Drug resistance remains a recurrent failure mode in targeted anticancer and antiviral therapy, and resistance evidence often enters only after compound selection. ResistAgent is an evidence-constrained framework that converts mutational liabilities into design-time objectives through site- and combo-aware resistance mapping, deterministic mechanism diagnosis and robust counter-design. In EGFR-Erlotinib and HIV-RT-Rilpivirine, the framework separated residue-level liabilities from observed HIV combination liabilities and linked prioritized mutations to anchor loss, pocket rearrangement, electrostatic shifts and contact redistribution. Same-budget paired searches showed that robust objectives changed lower-tail mutant-panel behavior and interaction-dependence profiles while prioritizing robustness over average-affinity behavior. Under predefined liability panels, selected robust-best trajectories shifted support away from mutable hotspot contacts toward more distributed interaction networks. Supplementary physical summaries and ranking-first benchmarks support the scope of this resistance-aware design strategy while preserving clear boundaries for prospective validation.

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

Tunneling Dynamics and Time Delay in Electron Transport through Time-Dependent Barriers with Finite-Bandwidth Reservoirs

arXiv:2507.20649v2 Announce Type: replace-cross Abstract: We study a model system consisting of a tunneling barrier driven by an external harmonic field and coupled to two leads with finite bandwidth. Avoiding Floquet expansions, we derive simple expressions for the time-dependent tunneling current in the adiabatic regime. Our approach relates the barrier modulation to a measurable time delay in the steady-state periodic current. It provides a physically consistent definition of the tunneling time inside the barrier by subtracting the time delay associated with the leads from the total time delay. We find that the tunneling time always vanishes for wide/high barriers. Remarkably, the time delay persists even when the barrier becomes static, i.e., in the limit where the modulation frequency vanishes. This indicates that the time delay obtained through the introduction of an external periodic perturbation actually reflects an intrinsic property of the tunneling dynamics, rather than an effect of the external drive or of a particular system. We apply our results to the analysis of tunneling times in optical experiments and find good agreement with the experimental data.

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.