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01.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

Authors:
Abdel-Rahman↗Gabr↗

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

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02.
Nature Biotechnology 2026-06-23

Mapping and engineering the human cell–cell interactome

Authors:
Dino Di Carlo↗

Efforts to systematically understand how cell interactions tune tissue-level function have motivated transformative advances in single-cell transcriptomics and spatial profiling. Although these technologies can measure molecular states in individual cells and their spatial mapping within tissues, they also reveal that there exists a fundamental knowledge gap of how cells influence each other in context. In this Perspective, we propose an initiative to map and engineer the human cell–cell interactome: a functional atlas of how all major human cell types communicate. We highlight how recent innovations can make this vision achievable. As a first moonshot, we propose the ‘Billion Cell×Cell Project’, which systematically characterizes the outcomes of defined cell–cell dyads across diverse cell types and conditions. We envision this multistage initiative will produce progressively deeper insights and unlock additional avenues for therapeutic discovery. We call on the scientific community to join us in building the tools, datasets and models that will decode and rewrite the language of life between cells. Di Carlo and colleagues discuss technologies required to map and engineer the human cell–cell interactome and the therapeutic avenues such an atlas could unlock.

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03.
arXiv (quant-ph) 2026-06-17

Canonical regularization of the stationary Coulomb problem and an Aufbau-like spectral ordering

Authors:
Anand Aruna Kumar↗

arXiv:2606.17359v1 Announce Type: new Abstract: The stationary hydrogen atom has Coulomb degeneracy across orbital levels, whereas the Aufbau/Madelung ordering is an empirical, many-electron rule established in atomic physics. We examine the hydrogen atom through a regularized de Broglie–Bohm representation, in which stationary amplitude current constraints generate separable Sturm–Liouville branches. In this formulation, the radial, orbital, and magnetic sectors acquire canonical Langer-like inverse square corrections. The modified boundary value problems allow analytical solutions and produce a hydrogen-like spectrum with regularized radial and angular indices. Consequently, radial Coulomb quantization acquires an orbital dependent shift, lifting the Coulomb degeneracy and producing a spectral ordering that follows the Aufbau/Madelung sequence. On this basis, we construct the ordering of the regularized de Broglie–Bohm states and show that the spectral structure retains the standard degenerate Rydberg sequence in the l=0 sector. The separated amplitudes are represented by generalized special function branches, including the associated Laguerre, Legendre, and Bessel functions with non-integral parameters arising from regularized separation. Therefore, the treatment is intended as an analytical examination of spectral ordering in a regularized one center Coulomb problem rather than as a replacement for the many electron atomic structure theory. Keywords: de Broglie–Bohm representation; Coulomb spectrum; canonical regularization; Langer correction; Sturm–Liouville equations; Aufbau principle; Madelung ordering; associated Legendre functions; associated Laguerre functions; Bessel functions.

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

Where Did It Go Wrong? Process-Level Evaluation of Web Agents with Semantic State Tracking

Authors:
Jiwan Chung↗JiHyuk Byun↗Vibhav Vineet↗Seon Joo Kim↗

arXiv:2606.15673v1 Announce Type: new Abstract: Web agents act through long interaction sequences, yet existing benchmarks evaluate only terminal success, discarding all process information and offering little guidance on improvement. In this work, we conduct a process-level analysis of web agents. We introduce WebStep, a benchmark of 1,800 task instances with controlled difficulty and automatic semantic state tracking. Each website exposes a deterministic semantic MDP alongside the GUI: the agent operates on the interface, while the environment records high-level states and transitions in the background, enabling fine-grained analysis without manual annotation. Based on the semantic trajectory, we first show that process metrics reveal differences invisible to outcome evaluation: three agents whose success rates cluster within 31-33% diverge in exploration reach versus execution accuracy. Then, decomposing by skill characterizes the nature of these differences, exposing opposite per-skill rankings hidden within the same website: e.g., on Housing, OpenAI CUA outperforms Qwen3.5 by 23.7% on commit actions yet underperforms it by 15.6% on filtering, pinpointing a concrete skill to improve even within a domain. Bifurcation analysis further localizes the decisive error that loses the task and shows that this error is agent-specific rather than shared. Finally, these differences widen as tasks grow harder: success rate is similar on easy tasks but separates sharply as exploration becomes more demanding. Our process-level analysis opens a new avenue in web agent evaluation, providing fine-grained and actionable insight into where and how each agent should be improved.

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05.
bioRxiv (Bioinfo) 2026-06-11

A quantitative coordinate system for developmental dynamics

Authors:
Wang↗Ren↗Moore↗Kelsh↗R. N↗McDole↗Dumitrascu↗Marioni↗J. C↗

Quantitative comparison of morphogenesis across individuals remains a fundamental challenge, as developing embryos vary in shape, orientation and developmental tempo. Moreover, real-time three-dimensional imaging generates large, heterogeneous four-dimensional datasets that are difficult to directly align. As a result, developmental variability is typically described qualitatively rather than measured. Here we introduce STERN, a quantitative framework that learns continuous spatiotemporal representations of morphogenesis directly from in vivo 4D imaging data. By embedding embryos into a shared spatiotemporal space, STERN defines a quantitative developmental coordinate system that enables direct comparison of developmental trajectories across individuals without requiring explicit registration or staging. Applied to mouse embryogenesis, STERN reveals that embryos follow conserved developmental trajectories while progressing at distinct temporal rates, providing a quantitative measure of developmental heterochrony. Extending this framework to zebrafish neural crest light-sheet timelapse imaging, we further show that developmental order is preserved across distinct imaging views even with altered anatomical coverage, supporting the generality of the learned representation across vertebrate imaging contexts. Finally, in developing mouse hearts, where morphogenesis proceeds through subtle and continuously evolving structural changes, STERN resolves fine-scale developmental dynamics at minute-scale temporal resolution that are difficult to localize reproducibly using human experts or general-purpose multimodal AI. Together, these results establish a shared quantitative coordinate system for morphogenesis, in which developmental trajectories become directly comparable across individuals and developmental variability becomes a measurable property.

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

Reinforcement Twinning for Hybrid Control of Flapping-Wing Drones

Authors:
Romain Poletti↗Lorenzo Schena↗Lilla Koloszar↗Joris Degroote↗Miguel Alfonso Mendez↗

arXiv:2505.18201v2 Announce Type: replace-cross Abstract: Controlling flapping-wing drones requires controllers that handle time-varying, nonlinear, underactuated dynamics from incomplete, noisy sensor data. Recent advances in artificial intelligence (AI), particularly reinforcement learning (RL), have opened new perspectives for addressing such complex control problems through data-driven policy optimization from interaction with the environment. Yet purely data-driven methods are sample-inefficient, demanding extensive, sometimes unsafe exploration, especially without guiding physical models. This motivates hybrid AI-physics frameworks. This article proposes a hybrid model-free/model-based flight-control approach using the reinforcement twinning algorithm. The model-based (MB) component uses an adjoint formulation and an adaptive digital twin continuously identified from live trajectories; the model-free (MF) component uses RL. The two agents share knowledge via transfer learning, imitation learning, and shared experience between the real environment and the digital twin, coordinated by a policy referee that selects which agent acts in reality based on digital-twin performance and a real-to-virtual consistency ratio. The framework is evaluated for the longitudinal control of a flapping-wing drone, modelled as a nonlinear time-varying system driven by quasi-steady aerodynamic forces. The hybrid strategy is tested under three adaptive-model initializations: (1) offline identification from existing data, (2) random initialization with fully online identification, and (3) offline pre-training with biased parameters followed by online adaptation. In all cases, the hybrid framework improves performance, robustness, and sample efficiency over purely model-free and purely model-based approaches.

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07.
arXiv (CS.CL) 2026-06-24

Progressive Alignment Objectives for Aligner-Encoder based ASR

Authors:
Jaeyong Lee↗Masato Mimura↗Takafumi Moriya↗

Aligner-Encoders are recently proposed seq2seq end-to-end ASR models that replace decoder attention by predicting the uth token directly from the u-th encoder position, so the encoder must learn the alignment internally without cross-attention or a transducer lattice. In practice, this alignment often forms abruptly in the upper layers, making training sensitive and brittle on long utterances. We propose InterAligner, which adds an intermediate Aligner objective so alignment can form progressively across depth, together with an intermediate CTC loss (InterCTC) to stabilize optimization. On LibriSpeech with a 17-layer Conformer, a final-only Aligner reaches 5.0/7.8 WER (test-clean/other). InterCTC improves to 3.4/6.0, and InterAligner further reduces WER to 3.1/5.6 with the largest gains on long utterances.

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08.
arXiv (quant-ph) 2026-06-24

Linear optical Bell state measurement for rotation-symmetric cat codes

Authors:
Issa Oe↗Suguru Endo↗Rui Asaoka↗

arXiv:2606.22832v2 Announce Type: replace Abstract: Rotation-symmetric cat (RS-cat) codes are a bosonic-code platform for quantum information processing, combining finite-energy realizability with robustness against photon loss through their discrete rotational symmetry. For applications in long-distance quantum communication and fusion-based quantum computation (FBQC), efficient Bell state measurement (BSM) is a key primitive. In this work, we consider a BSM protocol for RS-cat codes using only a half beam splitter (HBS) and photon-number-resolving detectors (PNRDs). By exploiting the characteristic photon-number structure induced by the discrete rotational symmetry of RS-cat codes, our protocol extracts both photon-number modulo and phase information for Bell-state discrimination. We show that, under ideal loss-free conditions, the proposed BSM protocol becomes deterministic for arbitrary symmetry order $N$ for sufficiently large amplitudes $\alpha$. We further numerically evaluate the success probability under photon loss and identify the loss regime in which higher-order RS-cat codes provide an advantage. Finally, we show that post-selection can enhance the success probability.

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

Allure of Craquelure: A Variational-Generative Approach to Crack Detection in Paintings

Authors:
Laura Paul↗Holger Rauhut↗Martin Burger↗Samira Kabri↗Tim Roith↗

Recent advances in imaging technologies, deep learning and numerical performance have enabled non-invasive detailed analysis of artworks, supporting their documentation and conservation. In particular, automated detection of craquelure in digitized paintings is crucial for assessing degradation and guiding restoration, yet remains challenging due to the possibly complex scenery and the visual similarity between cracks and crack-like artistic features such as brush strokes or hair. We propose a hybrid approach that models crack detection as an inverse problem, decomposing an observed image into a crack-free painting and a crack component. A deep generative model is employed as powerful prior for the underlying artwork, while crack structures are captured using a Mumford–Shah-type variational functional together with a crack prior. Joint optimization yields a pixel-level map of crack localizations in the painting.

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

AUTOGATE: Automated Clock Gating via Toggling-Aware LLM-based RTL Rewriting

Authors:
Yiting Wang↗Chenhui Deng↗Chia-Tung Ho↗Yanqing Zhang↗Zhuo Feng↗Cunxi Yu↗Ang Li↗Gang Qu↗Brucek Khailany↗

arXiv:2606.17461v1 Announce Type: cross Abstract: Fine-grain clock gating (FGCG) is among the most effective techniques for reducing dynamic power, yet current FGCG optimization flows remain largely manual. Recent LLM-based RTL optimization approaches remain limited by two key drawbacks: (1) the inability to process long waveform traces spanning millions of cycles, and (2) the difficulty of scaling optimization to large hierarchical codebases while preserving correctness. In this work, we present AUTOGATE, the first agentic framework for industry-grade RTL power optimization, enabling workload-aware clock-gating optimization across large hierarchical codebases. AUTOGATE introduces a Machine Learning (ML)-LLM co-design that bridges waveform-level analysis and RTL rewriting. Specifically, we design an ML-based clustering algorithm that distills raw toggling traces into compact, structured representations that guide LLM-based RTL rewriting. This enables accurate identification and application of clock-gating opportunities without requiring LLMs to directly process raw waveform data. To enhance scalability, AUTOGATE employs a hierarchical multi-agent architecture that decomposes large designs into independently optimizable modules, enabling coordinated optimization across deep design hierarchies. We evaluate AUTOGATE on a diverse set of designs ranging from small RTL designs to large industrial-grade codebases. Experimental results show that AUTOGATE consistently reduces dynamic power relative to baselines. Across the small-design suite, AUTOGATE reduces dynamic power by 49.31% on average. On industry-scale designs, it achieves 19.34% and 7.96% dynamic power reductions on NVDLA and BlackParrot, respectively, and up to 6.86% on highly optimized proprietary production designs.

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

EventRadar: Long-Range Visual UAV Discovery through Spatiotemporal Event Sensing

Authors:
Zhiting Zhou↗Xingchen Liu↗Xinglin Yu↗Jiashen Chen↗Haoyang Wang↗Jingao Xu↗Yunhao Liu↗Xinlei Chen↗

Unauthorized unmanned aerial vehicle (UAV) activity around airports, public venues, and other sensitive sites has made protected-airspace monitoring increasingly important. A practical sensing system must search a wide angular region, find small long-range targets, and return both bearing support and UAV-specific evidence before a restricted perimeter is breached. Existing UAV detection paths often rely on spatially organized evidence, such as body extent, silhouette, or track continuity. At long range, however, these cues become difficult to preserve and verify as the target footprint weakens and its image-plane support shrinks. EventRadar follows a complementary cue: propeller-induced temporal periodicity, which recent event-camera sensing studies have shown can reveal UAV-specific motion after appearance becomes weak. We extend this cue to kilometer-scale active sensing with an event-camera prototype. Scene-Anchored Geometry Evidence (SAGE) fuses scanning events with IMU pose to maintain a bearing-indexed scene memory, separating transient candidate support from persistent background clutter. Comb-guided Harmonic-Group Learned Iterative Shrinkage and Thresholding Algorithm (CHG) then treats each candidate as a weak high-rate timing signal and recovers phase-insensitive harmonic evidence with fixed compute. Compared with related event-camera baselines on 700-1500 m UAV event recordings, EventRadar achieves 0.990 mAP$_{.3}$ and 0.949 F1$_{.3}$, reduces FN$_{.3}$ to 0.009, and shows real-time feasibility in prototype profiling.

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

Net-Ev$^2$: A Generative Simulator for Network Event Evolution

Authors:
Guangyu Wang↗Zhaonan Wang↗

arXiv:2606.12494v1 Announce Type: new Abstract: Reducing real-world trial and error has long been a central goal of decision making, and generative simulators advance this goal by modeling the evolution of future states. An even more challenging yet meaningful task is simulating how disturbance events (e.g., accidents) propagate their impacts across real-world networks. The existing approaches fall short of modeling both structured attributes and unstructured semantics of events, and capturing topological structures in simulating network event evolution. Therefore, we are motivated to propose Net-Ev$^2$ ($\underline{Net}$work $\underline{Ev}$ent $\underline{Ev}$olution), a novel generative simulator that jointly leverages event cues while preserving network topology in simulations. Specifically, the framework consists of two stages, namely structure-guided masked pre-training and topology-aware diffusion process, which is achieved by U-Net-like graph downsampling and upsampling during denoising. At inference time, Net-Ev$^2$ can generate simulations using natural-language event input only, with greater flexibility for practical usage. Furthermore, we introduce Net-Ev$^2$-6.5M, a multimodal benchmark of aligned event and network traffic data across four large-scale road networks, as well as a new topology-aware metric, namely JL-MMD, to evaluate topological fidelity in generated network dynamics. Extensive experiments demonstrate the state-of-the-art performance and strong generalization ability of Net-Ev$^2$. Code is made available at https://github.com/Guangyu4/Net-Ev-2.

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

Generalised Eigenvalue Geometry of Semantic Adversarial Attacks

Authors:
Martin Anthony↗Kaveh Salehzadeh Nobari↗

arXiv:2606.19212v1 Announce Type: cross Abstract: Recent empirical work shows that semantically equivalent paraphrases can fool financial sentiment classifiers: although a paraphrase remains close to the original under a strong reference embedding, it may shift the target model's representation enough to change the predicted class. Existing robustness theory either assumes a single-model threat model or focuses mainly on empirical attack algorithms. We develop a continuous local model of semantic paraphrase perturbations that captures this two-model structure. We show that the worst-case local displacement of the target representation, subject to a proxy-model budget, is governed by the largest generalised eigenvalue of a matrix pencil $(A,B)$ constructed from the Jacobians of the two embedding maps. The resulting attackability index $\lambda^*(x)$ is intrinsic to the local paraphrase geometry and the chosen embedders, yields a closed-form prediction-flip condition for affine readouts, and supports conservative population and finite-sample attackability certificates. For uniform control over classes of affine readouts, we derive a distribution-free VC bound for binary attackability indicators and a scale-sensitive margin bound based on an attackability-adjusted margin that subtracts a local geometric penalty from the standard classifier margin. We also connect the continuous theory to discrete paraphrase search, identify an asymmetry between successful and unsuccessful finite searches, and give a covering condition under which the discrete and continuous settings agree. Finally, we propose an empirical verification framework using soft-token relaxations and generated paraphrase sets to assess the local eigenvalue geometry, prediction-flip condition, and finite-search approximation on a deployed financial-text classifier.

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

Mitigating Object Hallucinations in LVLMs via Attention Imbalance Rectification

Authors:
Han Sun↗Qin Li↗Peixin Wang↗Min Zhang↗

Object hallucination in Large Vision-Language Models (LVLMs) severely compromises their reliability in real-world applications, posing a critical barrier to their deployment in high-stakes scenarios such as autonomous driving and medical image analysis. Through systematic empirical investigation, we identify that the imbalanced attention allocation, both across modalities (i.e., vision and language) and within modalities (among individual tokens), exhibits a strong causal correlation with the occurrence of object hallucination. Leveraging this insight, we introduce a novel concept termed attention imbalance, which not only quantifies the degree of attention disparity but also visually delineates the underlying patterns (e.g., over-attentiveness to irrelevant language tokens or under-attentiveness to discriminative visual features) that drive object hallucination. To mitigate object hallucination, we further propose Attention Imbalance Rectification (AIR), a lightweight decoding-time intervention method that reallocates attention weights and adjusts attention distributions to rectify modality-wise and token-wise imbalances. Extensive evaluations on four mainstream LVLMs and three benchmarks (CHAIR, POPE, and MM-Vet) with seven baselines demonstrate that AIR consistently reduces object hallucination rates, achieving up to a 35.1% reduction compared to the baselines, while improving up to 15.9% of LVLMs' general capability across diverse vision-language tasks.

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15.
arXiv (CS.LG) 2026-06-16

A Conservation Law for Equilibrium Propagation and Coupled Learning

Authors:
Joshua A. McGinnis↗Adam G. Kline↗Yoichiro Mori↗

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

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16.
arXiv (CS.LG) 2026-06-24

Stabilizing Physics-Informed Consistency Models via Structure-Preserving Training

Authors:
Che-Chia Chang↗Chen-Yang Dai↗Te-Sheng Lin↗Ming-Chih Lai↗Chieh-Hsin Lai↗

arXiv:2602.09303v2 Announce Type: replace Abstract: We propose a physics-informed consistency modeling framework for solving partial differential equations (PDEs) via fast, few-step generative inference. We identify a key stability challenge in physics-constrained consistency training, where PDE residuals can drive the model toward trivial or degenerate solutions, degrading the learned data distribution. To address this, we introduce a structure-preserving two-stage training strategy that decouples distribution learning from physics enforcement by freezing the coefficient decoder during physics-informed fine-tuning. We further propose a two-step residual objective that enforces physical consistency on refined, structurally valid generative trajectories rather than noisy single-step predictions. The resulting framework enables stable, high-fidelity inference for both unconditional generation and forward problems. We demonstrate that forward solutions can be obtained via a projection-based zero-shot inpainting procedure, achieving consistent accuracy of diffusion baselines with orders of magnitude reduction in computational cost.

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17.
Nature (Science) 2026-06-10

Hybrid refinery process turns plant material into industrially important chemical

Authors:
Micaela Chacón↗

An ingredient of nylon has been made in high yields from lignin — revealing a fresh strategy for turning this complex plant biopolymer into industrial chemicals. An ingredient of nylon has been made in high yields from lignin — revealing a fresh strategy for turning this complex plant biopolymer into industrial chemicals.

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

On the Smallness of the Large Language Models Scaling Exponents

Authors:
Sauro Succi↗Peter V. Coveney↗Alex Hansen↗

arXiv:2606.24504v1 Announce Type: new Abstract: We discuss reasons why the scaling exponents of current Large Language Models (LLMs) applications are indicating an unsustainable regime in terms of energy resources. We further show that attributing the smallness of such exponents to a numerical bias due to the neglect of a non-zero value of the loss function in the limit of infinite data (``pedestal effect") does not remove the unsustainability issue. Finally, the effects of the smoothness (roughness) of the data on the scaling exponents is commented upon based on an analogy with phenomenological models of fluid turbulence.

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

Ellipse Meets Bit-Planes: A Novel Approach to RNFL based Glaucoma Detection Using Advanced Image Processing and Deep Learning

Authors:
Snigdha Paul↗Sambit Mallick↗Anindya Sen↗

This work proposes an integrated pipeline for automatic glaucoma detection method from easily available colour fundas images based on an adaptive algorithm for ellipse-based polar transformation, to enhance the analysis of the Retinal Nerve Fiber Layer (RNFL) as the primary biomarker for observing glaucomatous changes, regardless of optic disc and macula position. Utilizing this transformation, we introduce two distinct frameworks tailored to different operational needs. The first framework, a deep learning-inspired feature fusion approach, achieves a 99.3% detection rate, ideal for settings where high precision is essential, despite higher computational demands. The second framework employs a novel image-processing algorithm based on bit-plane slicing, offering 92.31% accuracy and optimized for environments requiring rapid inference with minimal resource consumption. Both frameworks provide scalable and cost-effective solutions for early glaucoma detection. This study highlights the potential of RNFL-based diagnostic tools in addressing the global challenge of glaucoma, particularly in underserved regions.

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20.
medRxiv (Medicine) 2026-06-22

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort

Authors:
Lange↗L. M↗Cerquera-Cleves↗Tan↗A.-H↗Lim↗S.-Y↗Okubadejo↗N. U↗Lin↗C.-H↗Chen↗…

Expanded short tandem repeats contribute to a broad spectrum of neurodegenerative diseases, yet their roles in Parkinson's disease (PD) and parkinsonism remain incompletely characterized, especially across diverse ancestries. We analyzed short-read whole-genome (WGS) and clinical exome sequencing (CES) data from 38,365 individuals (28,861 WGS; 9,504 CES), encompassing 23,242 patients with PD, 4,729 patients with atypical parkinsonism and 10,394 healthy controls from 11 genetic ancestries. To determine carrier frequencies and characterize repeat structures across diverse ancestries, we genotyped 12 established pathogenic loci where normal, intermediate, and pathogenic alleles can be reliably differentiated using short-read sequencing data. Additionally, we conducted threshold-based associations to determine the minimum threshold associated with increased PD risk in 15,995 individuals (8,591 PD, 7,404 controls) of European ancestry. Pathogenic repeat expansions were detected in 62 patients (56 PD and 6 atypical parkinsonism) and 5 controls across seven loci (AR, ATXN1, ATXN2, ATXN3, CACNA1A, HTT and THAP11), spanning seven ancestries. Among these, ATXN2 expansions were the most frequently observed in PD and were present in African, East Asian, European and Middle Eastern ancestries. Additionally, intermediate ATXN2 repeat expansions exhibited a strong, length-dependent association with PD risk in the European population, with individuals with [≥]32 repeats having a more than four-fold increased risk (odds ratio 4.25, 95% confidence interval 1.80-12.05). Overall, >92% of expanded alleles harbor CAA interruptions within the CAG tract. Pathogenic expansions at other loci, such as ATXN3 and THAP11, showed more ancestry-specific distributions. Clinically, individuals with pathogenic ATXN2 and ATXN3 expansions most often presented with typical PD features but frequently showed earlier disease onset and a strong family history of PD. This large-scale, multi-ancestry study comprehensively maps the genetic landscape of pathogenic and intermediate repeat expansions in PD. Our findings confirm a length- and structure-dependent risk association for ATXN2 with PD in the European population, and highlight the pleiotropic effects of repeat expansions across the parkinsonian spectrum.

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21.
arXiv (CS.LG) 2026-06-18

From Mechanistic to Compositional Interpretability

Authors:
Ward Gauderis↗Thomas Dooms↗Steven T. Homer↗Kola Ayonrinde↗Geraint A. Wiggins↗

arXiv:2605.08934v2 Announce Type: replace Abstract: Mechanistic interpretability aims to explain neural model behaviour by reverse-engineering learned computational structure into human-understandable components. Without a formal framework, however, mechanistic explanations cannot be objectively verified, compared, or composed. We introduce compositional interpretability, a category-theoretic framework grounded in the principles of compositionality and minimum description length. Compositional interpretations are pairs of syntactic and semantic mappings that must commute to enforce consistency between a model's decomposition and its observed behaviour. We deconstruct explanation quality into measures of faithfulness and complexity to cast interpretability as a constrained optimisation problem, and introduce compressive refinement to systematically restructure models into simpler parts without altering their function. Finally, we derive a parsimony criterion under which syntactic compression theoretically guarantees more concise, human-aligned explanations. Our framework situates prominent mechanistic methods as subclasses of refinement, and clarifies why their compressibility heuristics tend to align with human interpretability. Our work provides a measurable, optimisable blueprint for automating the discovery and evaluation of mechanistic explanations.

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

Bergson: An Open Source Library for Data Attribution

Authors:
Lucia Quirke↗Louis Jaburi↗David Johnston↗William Z. Li↗Gon\c{c}alo Paulo↗Guillaume Martres↗Girish Gupta↗Stella Biderman↗Nora Belrose↗

arXiv:2606.11660v1 Announce Type: new Abstract: Data attribution is a promising field in interpretability that aims to explain model behavior through the influence of its training data, with applications including debugging undesirable model behavior and training dataset curation. However, significant engineering effort is required to perform it at scale, and many cutting edge techniques lack open-source tooling and support. Bergson is an open source library that aims to enable faster progress in the field by providing a host of techniques that scale to very large language models and pre-training datasets. The library natively supports on-disk gradient stores and multi-node distributed training, and provides quality of life tools for researchers. Finally, we introduce the first open-source implementations of three leading data attribution methods: MAGIC, SOURCE, and TrackStar. The library is available at https://github.com/EleutherAI/bergson .

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23.
arXiv (CS.AI) 2026-06-18

Guava: An Effective and Universal Harness for Embodied Manipulation

Authors:
Haowen Liu↗Xirui Li↗Shaoxiong Yao↗Peng Shi↗Tianyi Zhou↗Jia-Bin Huang↗Furong Huang↗Jiayuan Mao↗

arXiv:2606.18363v1 Announce Type: cross Abstract: Language models trained on large-scale vision-language data have demonstrated strong potential for embodied agents. Harnessing models through embodied tools use offers a promising alternative to end-to-end vision-language-action systems by combining high-level reasoning with external modules for perception, planning, and control. However, it remains unclear what makes an effective harness for embodied manipulation, and to what extent such a harness can unlock embodied capabilities in a wide range of reasoning models. In this work, we present Guava, a harness framework for embodied tool use developed through systematic exploration of the design space of agent workflows, action spaces, and observation spaces. Our study identifies three key ingredients for effective embodied agents: iterative perception-reasoning-action loops, semantic action abstractions, and multimodal observations. To understand whether these design principles are universal even to small models, we develop an end-to-end training pipeline that distills embodied manipulation capabilities into a 4B open-source model using fewer than 2K trajectories collected entirely in simulation. Experimental results in both simulation and real-world environments show performance comparable to frontier proprietary models while exhibiting strong generalization to unseen objects, novel instructions, and long-horizon tasks. Results suggest that a well-designed harness can serve as a scalable, model-agnostic interface for embodied manipulation, enabling strong emergent embodied capabilities in compact open-source models with minimal training data.

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24.
arXiv (quant-ph) 2026-06-25

High-Rate and Resource-Efficient All-Photonic Quantum Repeater Architectures with 9 km Repeater Spacing

Authors:
Ryosuke Shiina↗Kenneth Goodenough↗Nathan Arnold↗Filip Rozp\k{e}dek↗

arXiv:2606.25314v1 Announce Type: new Abstract: Quantum communication between two distant parties will serve as a cornerstone of the future quantum internet. However, generating enough entangled Bell pairs over long distances is a critical bottleneck. Although photons are ideal carriers of quantum information, overcoming photon loss and the exponential attenuation of signals remains a major challenge. We propose an all-photonic quantum repeater architecture that enables quantum communication over 1,000 km with an equidistant repeater spacing of 9 km. This repeater spacing is enabled by elementary entangled Bell pairs protected through the concatenation of continuous-variable and discrete-variable quantum error correction codes, namely, the bosonic Gottesman-Kitaev-Preskill (GKP) code and the [[7,1,3]] Steane code, whose combination yields a synergistic improvement in robustness against photon loss. This architecture incorporates a new ranking criterion and a multi-reflection mirror-based optical cavity as a free-space photonic memory module, which we model in terms of its length and mirror-reflection efficiency. Additionally, we propose two heuristic construction methods for the elementary entangled Bell pairs. One method introduces up to two-qubit correlated errors within each logical qubit but requires a large number of GKP qubits, while the other allows up to three-qubit correlated errors within each logical qubit but requires fewer GKP qubits. To more accurately capture realistic physical conditions during photonic resource preparation, we include switching-induced imperfections in our simulations, in addition to other standard optical imperfections. In the presence of these imperfections, our realization requires only a few thousand GKP qubits per repeater station per protocol run, a resource requirement significantly smaller than the corresponding resource requirements of prior third-generation all-photonic repeater proposals.

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25.
arXiv (CS.CV) 2026-06-11

Tac-DINO: Learning Vision-Tactile Features with Patch Alignment

Authors:
Hong Li↗Yankang Dong↗Yue Xu↗Yihan Tang↗Mingzhu Li↗Jiamin Qiu↗Qihang Yao↗Xing Zhu↗Yujun Shen↗Nan Xue↗Yong-Lu Li↗

Touch is the primary medium through which humans interact with the environment. Currently, tactile learning mainly focuses on image-level pretraining or alignment. However, tactile signals correspond to local object contact, while research into scale alignment and holographic matching remains limited and proper datasets and benchmarks also lack. To bridge this gap, we first construct a data collection system to acquire a large-scale tactile dataset, with over 20 K tactile contacts from 505 real-world objects. Building on this dataset, we design a Vis-Tac Holographic Matching Benchmark to evaluate vision-tactile local-to-global alignment ability. Then we propose Vision-Tactile Patch Alignment (VTPA) methods for vision-tactile representation learning. Experiments demonstrate that these exceed the performance of methods without alignment and align with whole-object images.

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