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01.
medRxiv (Medicine) 2026-06-17

Wearable-Grade Lead Reduction Disproportionately Degrades ECG AI Performance in Elderly Patients: Evidence from PTB-XL and MIT-BIH

Consumer wearable devices increasingly use single-lead electrocardiograms (ECGs) for cardiac monitoring, but these signals contain substantially less spatial information than the clinical 12-lead standard. Whether this reduction dispro- portionately affects older adults, who often present with more complex cardiac conditions, remains poorly understood. In this study, we evaluated the impact of lead reduction on AI-ECG diagnostic performance across age groups. A 1D resid- ual neural network was trained on 21,091 PTB-XL ECG recordings spanning five diagnostic superclasses and assessed using 12-, 6-, 2-, and 1-lead configurations. Under the full 12-lead setting, model accuracy declined from 84.5% in patients younger than 40 years to 66.2% in patients aged 75 years or older. Progressive lead reduction further widened this gap. Under the 1-lead configuration, accuracy decreased by 14.1 percentage points in the 75+ group but by only 0.4 percent- age points in the

02.
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}.

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

Learner-based Concept Drift Detection: Analysis and Evaluation

arXiv:2606.20216v1 Announce Type: cross Abstract: Machine learning algorithms deployed for evolving streaming environments must handle the non-stationary data distributions, commonly referred to as concept drift. The presence of concept drift poses a major challenge for many real-world applications because it can severely degrade their predictive performance, hindering their ability to support robust decision-making. Consequently, the timely and efficient detection of drift events is critical for sustaining high accuracy over time. This study examines theoretically the concept drift characteristics and numerous drift detection algorithms across several categories. Furthermore, we evaluate their performance on both synthetic and real-world datasets exhibiting diverse streaming scenarios and drift characteristics, such as abrupt and gradual changes. This study aims to enhance understanding of the complex notion of concept drift characteristics and behavior of drift detectors, along with their applicability to diverse contexts.

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

GIST-CMTF: Goal-State Inference for Causal Minimal Tool Filtering in LLM Agents

arXiv:2606.16813v1 Announce Type: new Abstract: Tool-augmented LLM agents rely on runtime filtering to decide which tools should be visible at each step. Causal Minimal Tool Filtering (CMTF) reduces tool-choice confusion by exposing only the next causally necessary tool frontier, but it assumes that the user request has already been mapped to a symbolic goal state. In practice, requests such as "handle my appointment" or "take care of this email" may correspond to multiple possible goals. This creates wrong-goal execution, where an agent follows a valid causal tool path for an unintended objective. We introduce GIST-CMTF, a goal-state inference layer that predicts candidate symbolic goals over the same state-transition vocabulary used by CMTF, estimates ambiguity, and either applies CMTF or exposes clarification as a causal action that produces missing goal or state variables. We evaluate GIST-CMTF across seven model backends, six filtering methods, and 120 controlled tool-use tasks. GIST-CMTF achieves 97.0% task success, compared with 80.1% for top-goal CMTF and 82.9% for semantic-goal CMTF. It reduces wrong-goal execution from 19.4% under top-goal CMTF to 2.5%, while preserving the one-tool exposure of causal filtering and using substantially fewer tokens than all-tools exposure. These results suggest that reliable tool-augmented agents should validate goal state, not only tool relevance, before exposing external actions.

05.
arXiv (CS.LG) 2026-06-12

One Step Closer to Ground Truth: A Multi-Scale Residual-Aware Representation Learning Pipeline for Predicting Time Series Data

arXiv:2606.10678v2 Announce Type: replace Abstract: Transformer-based models have emerged as leading paradigms in time-series forecasting in recent years, employing self-attention mechanisms to capture long-range dependencies. Despite their success, these single-stage forecasting architectures exhibit persistent systematic residual biases arising from structural discrepancies, unmodeled stochastic components, or inadequate multi-scale temporal representations. This limitation persists when residuals are treated as irreducible noise, precluding adaptive correction of structured error patterns. To address this limitation, we introduce a two-stage, model-agnostic framework that explicitly decouples forecasting and residual learning into distinct stages of representation learning. A base transformer first generates the initial predictions. Subsequently, a dedicated meta-corrector dynamically models structured error patterns across multivariate channels, preserves cross-variable dependencies, and iteratively refines the residual bias of the base transformer. By formalizing this pipeline as a hypothesis space expansion, our framework addresses approximation limitations inherent in single-stage architectures, removes reliance on restrictive assumptions, and enables end-to-end learning of complex error dynamics. Evaluated on eight popular benchmark datasets using established protocols, our approach achieves state-of-the-art performance, with significant improvements in standard metrics (MSE, MAE). The results demonstrate the framework's ability to mitigate systematic biases and enhance robustness to complex temporal dynamics, advancing the practical applicability of transformer-based forecasting models.

06.
bioRxiv (Bioinfo) 2026-06-11

Robust semi-supervised scRNA-seq integration from virtual adversarial learning

Single-cell RNA sequencing integration methods that rely solely on transcriptomic data often struggle to preserve fine-grained distinctions between closely related cell subtypes. As a result, cell populations that are separable in the raw data may become over-mixed after integration, reducing biological resolution and interpretability. Incorporating marker gene information can potentially address these issues; however, the variability and complexity of available marker sets limit their effective application. To address this, we introduce scCRAFT+, a semi-supervised integration model that innovatively incorporates marker gene information through Virtual Adversarial Training (VAT). By jointly optimizing marker-derived supervision and transcriptome-wide representations, VAT enforces local prediction smoothness among transcriptionally similar cells, improving robustness to noisy marker annotations while enhancing both integration quality and cell type auto-annotation. This targeted approach significantly enhances annotation accuracy and robustness, particularly when faced with incomplete or incorrect marker gene sets. Benchmarking shows that scCRAFT+ achieves consistently stronger performance than current unsupervised and supervised integration approaches, resulting in improved integration quality and biologically meaningful sub-cell type auto-annotations.

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

Lius: Translation Model Based Instructional Lingustic Using Continual Instruction Tuning In Kupang Malay

Large Language Models (LLMs) offer new potential for translation tasks but often experience performance degradation when handling low-resource languages. To address this limitation, we propose an approach for fine-tuning LLMs on a low-resource language, Kupang Malay. Our approach involves designing a set of instructions by leveraging explicit lexical and semantic features from a bilingual dictionary, and introducing Continual Instruction Tuning (CIT), a training paradigm that enables iterative instruction-based training. Experimental results demonstrate that our model, named Lius, yields notable improvements over standard instruction-tuned models by outperforming 4-6 points, and surpassing both Neural Machine Translation (NMT) and Multilingual LLM models by 10-13 points on several evaluation metrics. These findings highlight the potential of our approach to mitigate the reliance on large-scale parallel data in low-resource language translation.

08.
bioRxiv (Bioinfo) 2026-06-21

DeepCDS: Ab initio coding sequence prediction in prokaryotic short reads

Accurate coding sequence prediction in short prokaryotic metagenomic reads remains challenging due to sequence fragmentation, unknown sequence origins, and sequencing errors. Here we introduce DeepCDS, a deep learning-based ab initio coding sequence predictor trained on short prokaryotic sequences with and without simulated Illumina-like sequencing errors. DeepCDS integrates ESM-2 protein language model embeddings with nucleotide-level information to predict complete and fragmented coding sequence regions. Benchmarking on 215 phylogenetically diverse prokaryotic organisms demonstrates that DeepCDS consistently outperforms current state-of-the-art methods in coding sequence detection, start and stop codon localization, and robustness to different sequencing error profiles, while remaining operational at shorter sequence lengths than existing tools support. These findings demonstrate that protein language models capture distinct signals relevant for nucleotide-level coding sequence detection, especially at very short lengths. Ultimately, DeepCDS may help uncover the functional potential of the vast microbial diversity that remains genomically uncharacterized.

09.
arXiv (CS.CV) 2026-06-16

Understanding Cross-Modal Contributions in Continual Vision-Language Models: A Theoretical Perspective

Continual vision-language models are commonly addressed through sequential fine-tuning; however, although this paradigm enables adaptation to new environments (tasks), it inherently emphasizes the contribution of previously learned environments (tasks) at the expense of the stability required to preserve previously acquired knowledge. While existing approaches have adequately studied continual learning and catastrophic forgetting in vision-language models (VLMs), the theoretical understanding of modality-specific contributions across a sequence of environments remains largely unexplored. In this paper, we present a new theoretical perspective to understand the cross-modal (vision-language) contributions to consecutive environments. We empirically evaluate our theoretical findings on large VLMs and demonstrate their effectiveness in capturing environment-level cross-modal contributions. Our analysis provides deeper insights into continual VLMs, highlighting their contribution robustness to varying task orders and inter-task similarities, and their improved generalization performance.

10.
arXiv (math.PR) 2026-06-17

Non-asymptotic Tail Bounds for the Kostlan–Shub–Smale Field: Tensor PCA and Spherical $k$-Spin Complexity

arXiv:2606.17665v1 Announce Type: cross Abstract: This paper builds a hierarchy of explicit, non-asymptotic tail bounds for the supremum of the Kostlan–Shub–Smale (KSS) random field on the sphere, and applies it to two problems: Spiked Tensor PCA and the landscape of the spherical $k$-spin model. For Tensor PCA, we study the non-asymptotic statistical limits of estimating a rank-$R$ symmetric signal tensor of order~$k\ge 3$ and dimension~$d\ge 3$ from a single Gaussian observation at signal-to-noise ratio~$\lambda$, through the profile maximum likelihood estimator, the MLE restricted to normalized rank-$R$ tensors of coherence at least~$\kappa$. Our analysis uses a single reduction: a deterministic geometric inequality (the Tube Method) and a rank-reduction step bound the estimation error by the supremum of the canonical KSS field, which the Kac–Rice formula turns into a Gaussian integral against the expected absolute characteristic polynomial of a shifted Gaussian Orthogonal Ensemble, controlled in turn by the four explicit tail bounds of our hierarchy (three from a Mehta–Fyodorov representation, one from a Ben Arous–Dembo–Guionnet large deviation). The same reduction yields two results, each with explicit constants. For estimation, a finite-$(k,d)$ error bound recovers the asymptotically optimal rate~$\sqrt{d\log k}$ of Perry, Wein and Bandeira, with explicit dependence on the rank~$R$ and the coherence~$\kappa$. For the landscape, a two-sided non-asymptotic bracketing of the annealed complexity of the spherical $k$-spin Hamiltonian recovers the Auffinger–Ben Arous–\v{C}ern\'y complexity function in the high-dimensional limit.

11.
arXiv (math.PR) 2026-06-18

Law of the Iterated Logarithm for $p$-Walks on $\mathbb{Z}$

作者:

arXiv:2606.19131v1 Announce Type: new Abstract: The $p$-rotor walk on $\mathbb{Z}$ is a self-interacting walk that interpolates between the simple random walk and the deterministic rotor walk. While the weak convergence of this model to a perturbed Brownian motion is known, its almost sure asymptotic boundaries have not been characterized. In this paper, we establish the exact Law of the Iterated Logarithm (LIL) for the $p$-rotor walk. Utilizing the decomposition of the walk into a martingale perturbed by its running extrema, we obtain first a functional Law of the Iterated Logarithm for the linearly interpolated paths of the $p$-walk. We then obtain the classical LIL constants by solving a calculus of variations problem over the perturbed Strassen set.

12.
arXiv (CS.CV) 2026-06-11

Performance Analysis of YOLOv11 and YOLOv8 for Mixed Traffic Object Detection under Adverse Weather Conditions in Developing Countries

In modern vehicular systems, robust performance under harsh conditions has become a critical problem of autonomous driving. Our study delivers a comprehensive evaluation of the newest iteration of the YOLO series, which is YOLOv11 Nano architecture benchmarked against the widely adopted YOLOv8 Nano as a baseline on a custom fused dataset that combines the Indian Driving Dataset (IDD) [1] and Berkeley Deep Drive Dataset (BDD100K) [2]. We have analyzed the trade-offs among detection accuracy, inference speed, and computational efficiency in high-entropy scenarios involving dense mixed traffic, rain, and low-light conditions. Specifically, YOLOv11n achieves a mean Average Precision (mAP@50) of 46.6%, with a notable 3.2% improvement in Precision over the baseline, effectively reducing false positives in cluttered scenes. Furthermore, the proposed model exhibits enhanced energy efficiency, requiring 22% fewer FLOPs (6.3G vs. 8.1G) while maintaining real-time inference speed of 70.9 FPS on a Tesla T4 GPU, offering an optimal trade-off for safety-critical edge deployment.

13.
arXiv (CS.AI) 2026-06-18

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

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

14.
arXiv (quant-ph) 2026-06-12

Scalar Quantum Fields: Theory Space and its Geometry

arXiv:2606.12580v1 Announce Type: cross Abstract: Scalar fields provide perhaps the simplest playground in which to develop our understanding of quantum field theory. In this lecture, we consider what it means to write down a scalar quantum field theory and how we can give geometrical interpretations to the space of such theories: the theory space.

15.
arXiv (CS.CV) 2026-06-12

OpenMedQ: Broad Open Pretraining for Medical Vision-Language Models

We present OpenMedQ, a medical vision-language model pretrained on the broadest fully-open medical mix to date: 14 datasets totaling ~3.35M pretraining samples spanning pathology, radiology, microscopy, and text-only clinical QA. OpenMedQ reaches state-of-the-art BLEU-1 on PathVQA (75.9), beating Med-PaLM M variants up to 562B parameters (~80x larger), and matches the best reported VQA-MED BLEU-1 (64.5). Its vision encoder, transferred to 8 unseen medical classification benchmarks under an identical downstream recipe, obtains the highest average macro-F1 (0.757) among BiomedCLIP (0.745), PMC-CLIP (0.745), PubMedCLIP (0.746), and a from-scratch baseline (0.616). We release our code and an interactive demo is publicly available as a reproducible baseline for the community.

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

Benchmarking Large Vision-Language Models on Fine-Grained Image Tasks: From Evaluation to Diagnosis

Recent advancements in Large Vision-Language Models (LVLMs) have demonstrated remarkable multimodal perception and reasoning capabilities. While numerous benchmarks have evaluated LVLMs from holistic or task-specific perspectives, their capabilities on fine-grained image tasks-fundamental to computer vision-remain insufficiently understood. To address this gap, we introduce FG-BMK, a comprehensive fine-grained evaluation benchmark containing 1.01 million questions and 0.28 million images, covering diverse scenarios from common object-centric domains to specialized domains. FG-BMK jointly evaluates dialogue-level fine-grained semantic recognition and feature-level visual discriminability through human-oriented and machine-oriented paradigms, enabling diagnostic analysis of whether LVLM failures arise from insufficient visual representations, weak visual-to-semantic grounding, or limited fine-grained knowledge. Through extensive experiments on a diverse set of representative LVLMs/VLMs, we find that current LVLMs remain inadequate fine-grained recognizers, with failures arising from intertwined bottlenecks in visual representations, semantic grounding, modality alignment, and category-level knowledge. We further analyze training design factors for improving fine-grained capabilities and examine how visual and linguistic perturbations affect LVLM predictions. These findings provide diagnostic insights into the limitations of current LVLMs and offer guidance for future data construction and model design in developing more reliable LVLMs for fine-grained visual tasks. Our code is open-source and available at https://fg-bmk.github.io/.

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

Mordal: Automated Pretrained Model Selection for Vision Language Models

Incorporating multiple modalities into large language models (LLMs) is a powerful way to enhance their understanding of non-textual data, enabling them to perform multimodal tasks. Vision language models (VLMs) form the fastest growing category of multimodal models because of their many practical use cases, including in healthcare, robotics, and accessibility. Unfortunately, even though different VLMs in the literature demonstrate impressive visual capabilities in different benchmarks, they are handcrafted by human experts; there is no automated framework to create task-specific multimodal models. We introduce Mordal, an automated multimodal model search framework that efficiently finds the best VLM for a user-defined task without manual intervention. Mordal achieves this both by reducing the number of candidates to consider during the search process and by minimizing the time required to evaluate each remaining candidate. Our evaluation shows that Mordal can find the best VLM for a given problem using $8.9\times$–$11.6\times$ lower GPU hours than grid search. We have also discovered that Mordal achieves about 69\% higher weighted Kendall's $\tau$ on average than the state-of-the-art model selection method across diverse tasks.

18.
arXiv (quant-ph) 2026-06-12

Matrix phase-space representations for quantum symmetries

arXiv:2606.12769v1 Announce Type: new Abstract: We introduce a general phase-space representation that includes global quantum symmetries in the basis expansion. This method, called matrix phase-space, projects the basis onto a reduced Hilbert space, which can greatly reduce sampling errors of many-body quantum simulations and unifies several previous phase-space methods. The purpose of this paper is to provide detailed proofs of basic theorems and operator identities. We also treat several different types of symmetries. To illustrate the benefits of matrix phase-space methods, we give a detailed derivation of a recent application to the topical problem of verifying the outputs of Gaussian boson sampling (GBS) quantum computers with photon number resolving detectors. This has exponential complexity, and using parity symmetry reduces sampling errors by very large factors relative to earlier methods.

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

Interpretable Alzheimer's Diagnosis via Multimodal Fusion of Regional Brain Experts

Accurate and early diagnosis of Alzheimer's disease (AD) is critical for effective intervention and requires integrating complementary information from multimodal neuroimaging data. However, conventional fusion approaches often rely on simple concatenation of features, which cannot adaptively balance the contributions of biomarkers such as amyloid PET and MRI across brain regions. In this work, we propose MREF-AD, a Multimodal Regional Expert Fusion model for AD diagnosis. It is a Mixture-of-Experts (MoE) framework that models mesoscopic brain regions within each modality as independent experts and employs a gating network to learn subject-specific fusion weights. Utilizing tabular neuroimaging and demographic information from the Alzheimer's Disease Neuroimaging Initiative (ADNI), MREF-AD achieves competitive performance over strong classic and deep baselines while providing interpretable, modality- and region-level insight into how structural and molecular imaging jointly contribute to AD diagnosis. The source code is available at https://github.com/PennShenLab/mref-ad.

20.
arXiv (CS.AI) 2026-06-17

SEAGym: An Evaluation Environment for Self-Evolving LLM Agents

arXiv:2606.17546v1 Announce Type: new Abstract: Self-evolving LLM-based agents improve mainly by changing their agent harness: the structured execution layer around a base model, including prompts, memory, tools, middleware, runtime state, and the model-tool interaction loop. Existing evaluations often reduce this process to isolated task scores or a single sequential curve, obscuring whether an update produces reusable improvement, overfits recent tasks, increases cost, or harms older behavior. We introduce SEAGym, an evaluation environment for measuring agent harness updates across training, validation, test, replay, and cost records. SEAGym turns Harbor-compatible benchmarks into dynamic self-evolution task sources with train batches, frozen update-validation, held-out ID and OOD transfer views, replay diagnostics, and saved snapshot and metric records. Instantiating SEAGym on Terminal-Bench 2.0 and HLE, we compare ACE, TF-GRPO, and AHE under a shared epoch/batch protocol. The results show that these evaluation views provide complementary signals about the evolution process: frequent updates may fail to improve held-out performance, useful intermediate snapshots may collapse later, and source diversity and model backend can affect harness reliability.

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

Signed Compression Progress on a Sealed Audit is Goodhart-Resistant

arXiv:2606.11417v1 Announce Type: cross Abstract: Compression progress is a long-standing proposal for intrinsic motivation: reward an agent when its world model becomes better at predicting or compressing experience. The folk claim is that this reward is "credible" because it is paid only for learning. We make this precise and prove it. If intrinsic reward is the signed decrease of a fixed sealed-audit loss, r_t = E(theta_{t-1}) - E(theta_t), then cumulative reward telescopes exactly to endpoint audit improvement, so no policy can push reward up indefinitely while true audit performance stagnates or degrades. For finite audit panels the same result holds with a sharp false-positive budget: cumulative empirical reward is at most true audit improvement plus 2 Delta_n(F, delta), the uniform audit deviation of the model class. This is horizon-free: adaptivity over time costs nothing once the sealed panel uniformly controls the class. The theorem also identifies the failure modes: the guarantee disappears if progress is clipped, scored on the agent's own stream, exposed to a high-capacity model on a reusable panel, or applied to a neural class that makes Delta_n vacuous. We give a Lean 4 mechanization of the structural core (telescoping, the finite-audit bound, finite Gibbs, and the entropy floor) and an experiment suite on ARC-TGI grid-transformation generators with adaptive holdout attacks. Experiments confirm the theory: finite-audit deviation scales as n^{-0.527}; signed progress resists clip-farming, stream leakage, and noisy-TV curiosity; naive reusable audits are exploitable by black-box scalar feedback, while standard release defenses keep the attack below the 2 Delta_n threshold. Signed compression progress on a sealed audit is an accounting signal of genuine improvement.

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

Flow Matching with In-Context Priors for Out-of-Distribution Brain Dynamics

arXiv:2606.11833v1 Announce Type: new Abstract: Flow matching and diffusion models enable conditional generation across domains ranging from images to proteins, with recent extensions to out-of-distribution contexts. Yet generative models of neural time series have largely remained restricted to categorical conditioning, precluding compositional and zero-shot generalization. In this work, we propose a per-timestep conditioned diffusion transformer for generating realistic fMRI brain dynamics during unseen cognitive tasks by injecting both compositional language and optional spatial priors in-context. Such zero-shot generation could enable counterfactual neuroscience by supporting in-silico design and evaluation of novel cognitive experiments before empirical validation. Leveraging this model, we evaluate across hundreds of held-out task conditions and characterize predictive performance in relation to the training manifold. From language alone, the model recovers region-specific recruitment across tasks and held-out spatial activation patterns. Spatial priors, when available, complement the text pathway by anchoring generation in regions of task space where language alone degrades, while retaining the compositional structure needed for counterfactual task specification. To our knowledge this is the first generative model of whole-cortex fMRI dynamics for unseen cognitive tasks, advancing counterfactual neuroscience and data-driven experimental design.

23.
bioRxiv (Bioinfo) 2026-06-18

Structure Bioinformatics of Eight Human ATP Synthase Fo Subunits and Their AlphaFold3-Predicted Water-Soluble QTY Analogs

Human mitochondrial ATP synthase is an essential rotary motor enzyme that produces most of the cellular ATP through oxidative phosphorylation. Its membrane-embedded Fo sector contains highly hydrophobic transmembrane subunits that are challenging to study in aqueous environments without detergents. This study explores whether applying the QTY code can reduce the hydrophobicity of selected ATP synthase Fo subunits while preserving their overall molecular structures. We applied the QTY code to eight human ATP synthase Fo subunits: ATP6, ATP8, ATPK, ATP68, ATPMK, AT5G1, AT5G2, and AT5G3. Hydrophobic amino acids leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in transmembrane regions were systematically replaced with hydrophilic glutamine (Q), threonine (T), and tyrosine (Y). Four native subunits with available CryoEM structures from human ATP synthase (PDB: 8H9S) were superposed with their AlphaFold3-predicted QTY analogs. The native ATP synthase Fo subunits superposed well with their respective QTY analogs. For the CryoEM-native comparisons, RMSD values ranged from 0.565[A] to 2.546[A]. For the AlphaFold3-native comparisons of subunits without CryoEM structures, RMSD values ranged from 0.204[A] to 0.297[A]. Despite substantial QTY substitutions in the transmembrane regions, ranging from 38.89% to 50.79%, the QTY analogs retained similar overall folds, molecular weights, and isoelectric points. Hydrophobic surface analysis showed that the QTY analogs had reduced hydrophobic patches compared with their native counterparts, with average hydrophobicity decreasing from 0.2959 in native proteins to -1.1023 in QTY analogs. These structural bioinformatics studies suggest that the QTY code can be applied to ATP synthase Fo subunits to generate more hydrophilic, potentially water-soluble analogs while preserving overall structural similarity. These results extend the application of the QTY code to the membrane-embedded Fo sector of ATP synthase and provide a foundation for future experimental studies testing whether these QTY analogs can be expressed, purified, and evaluated for assembly or proton-transfer-related functions.

25.
arXiv (CS.LG) 2026-06-17

Memory-Efficient Meta-Reinforcement Learning for Adaptive Safety-Critical Control in Adversarial Spacecraft Proximity Operations

arXiv:2606.17414v1 Announce Type: new Abstract: Autonomous spacecraft rendezvous and proximity operations (RPO) require controllers that guarantee safety under thrust constraints while minimizing fuel expenditure. Input-constrained control barrier functions (ICCBFs) provide a control method for nonlinear systems with actuation constraints that construct a forward-invariant safe set. Previous work has shown that learning class-$\mathcal{K}$ functions defining the ICCBF recursion via meta reinforcement learning (meta-RL) yields a robust, non-greedy approach to safety-critical control in RPO. This paper extends that framework further by investigating the performance of three recurrent network architectures (Long Short Term Memory (LSTM), Gated Recurrent Unit (GRU), Selective State Space Model (Mamba)) and two training algorithms (Proximal Policy Optimization (PPO) and Soft Actor Critic (SAC)) to identify the best setup for tuning ICCBF class-K functions via meta-RL. In addition to cooperative test cases, performance is evaluated in the presence of adversarial behavior where the target spacecraft behaves in a way that worsens the safety of the chaser spacecraft. Results indicate that state space models such as Mamba when used with PPO achieve superior task completion, safety, and fuel-savings compared to other architectures, across all cooperative and uncooperative scenarios tested.