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01.
medRxiv (Medicine) 2026-06-19

Extraction of Glaucoma Diagnosis, Type, and Severity from Clinical Notes using Secure Cloud-based Large Language Models

Purpose: To evaluate the performance of secure cloud-based large language models (LLMs) in extracting glaucoma diagnosis, type, and severity from free-text clinical notes in the electronic health record (EHR). Design: Retrospective chart review analysis. Participants: 1,250 subjects from the Bascom Palmer Ophthalmic Repository. Methods: Clinical notes of glaucoma-related encounters between 2014 and 2024 were extracted from the Bascom Palmer Ophthalmic Repository. Two fellowship-trained glaucoma specialists annotated clinical notes for glaucoma presence, type, and severity at the eye level. The dataset was split into development (10%), validation (10%), and test (80%) sets. Development and validation sets were used for prompt engineering and refinement, and the held-out test set was used for evaluation. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT-5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Azure AI Foundry within HIPAA-compliant containers. Model performance was assessed using standard metrics. Clinician-entered ICD-10 codes were also compared with adjudicated labels. Main Outcome Measures: Gwet AC1, accuracy, sensitivity, specificity, and F1-score. Results: Inter-grader agreement was high for glaucoma detection (Gwet AC1= 0.930 (95% CI: 0.917-0.945), type classification (Gwet AC1= 0.917 (95% CI: 0.904-0.930), and severity staging (Gwet AC1= 0.901 (95% CI: 0.884-0.916). For glaucoma diagnosis, LLMs demonstrated high overall accuracy, with Claude achieving 97.5%, DeepSeek 96.0%, GPT 96.2%, Grok 94.4%, and Qwen 95.5%. F1 scores for glaucoma detection ranged from 95.4% to 98.9% across models. For glaucoma type classification, accuracies were 97.1%, 94.2%, 94.2%, 94.0%, and 94.4% for Claude, DeepSeek, GPT, Grok, and Qwen, respectively. F1 scores for the most prevalent type (POAG) ranged from 96.3% to 98.9%. For severity staging, accuracies were 95.0%, 94.8%, 94.5%, 94.0%, and 95.2%, respectively, with F1 scores ranging from 89.7% to 96.3% across severity categories and models. ICD-10 codes demonstrated substantially lower performance for type and severity staging, with overall accuracies of 89.2% and 58.5%, respectively. Conclusions: Secure cloud-based LLMs accurately extracted glaucoma diagnosis, type, and severity information from free-text ophthalmology notes, achieving performance approaching expert clinician adjudication while substantially outperforming ICD-based phenotyping approaches, particularly for disease severity classification. These findings demonstrate the potential of LLMs to transform unstructured clinical documentation into scalable, research-ready phenotypic data for large-scale glaucoma cohort development and EHR-based ophthalmic research.

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

Rotational Symmetry based Object Pose Estimation from Point Clouds in the Absence of Known 3D Models

Object pose estimation is crucial to many industrial applications, with one example being automated spray painting using a robot. However, confidentiality concerns often limit access to high-quality 3D models, posing a significant challenge for point-cloud-based pose estimation. In such scenarios, rotational symmetry, a readily accessible characteristic of many industrial objects, can provide valuable prior information to facilitate pose estimation.In this paper, we propose a method that leverages the rotational symmetry commonly found in industrial objects to address the challenge caused by the absence of 3D models. The object pose is jointly estimated with point cloud refinement through an iterative optimization process. This optimization relies on a rotational symmetry constraint loss. To construct this loss, each 3D point is rotated according to the currently estimated pose, and multiple correspondences are identified using nearest-neighbor search by exploiting the rotational symmetry property. These correspondences are then used to compute the rotational symmetry constraint loss, which iteratively refines both the pose and the point cloud.By explicitly incorporating rotational symmetry into the optimization process, the proposed method achieves robust pose estimation and generalizes well across diverse object types. The proposed method is evaluated on a dataset specifically created for point clouds without known 3D models, consisting of four categories of synthetic objects and one real wheel hub collected from a production line. Experimental results demonstrate that the proposed method achieves performance comparable to methods that rely on known 3D models.

03.
arXiv (CS.LG) 2026-06-17

Discovering Functionally Selective Brain Regions with a Deep Topographic Multimodal Model

arXiv:2606.09770v2 Announce Type: replace-cross Abstract: Nearby neurons in cortex share similar response profiles, producing systematic spatial organization across sensory and cognitive systems. Recent topographic models reproduce aspects of this structure but remain unimodal and spatially constrain each layer separately, yielding fragmented maps that capture neither the contiguity of cortical processing streams nor their integration across modalities. We introduce Topo-Omni, a topographic multimodal model in which visual, auditory, and language/cognitive processing share a single contiguous in-silico sheet. Built by fine-tuning a pretrained foundation model with a spatial smoothness objective, this architecture develops clusters across modalities that are consistent with human neuroimaging, from sensory to cognitive systems. Driving or suppressing a cluster selectively biases or impairs perception, paralleling human intervention studies. Finally, we use our model to screen for novel clusters in-silico and discover new natural landscape and animal networks which we validate in human data. A single spatial principle thus organizes representations across modalities and processing stages, yielding testable hypotheses about cortical organization.

04.
bioRxiv (Bioinfo) 2026-06-17

DNA-binding specificity recognition from predicted homologous protein-DNA structures

Predicting protein DNA-binding specificity is essential for understanding gene regulation and disease mechanisms. Existing deep learning methods typically infer specificity from a single protein-DNA complex structure, which limits their ability to capture the diverse geometric patterns underlying protein-DNA recognition. Homologous protein-DNA interfaces provide complementary structural evidence and richer geometric features related to interatomic interactions. To address the limited diversity and coverage of experimentally determined complexes, we constructed a large-scale library of predicted homologous protein-DNA complex structures. Building on this resource, we propose HomoDSP, a template-retrieval-based framework for accurate DNA-binding specificity prediction. Benchmark evaluations and validation on newly released JASPAR 2026 samples indicate that HomoDSP outperforms existing methods in both accuracy and generalization, with particularly substantial gains on high-error samples. Moreover, this performance is largely retained when AlphaFold3-predicted complex structures are used as input. Template- and residue-level interpretability analyses suggest that HomoDSP improves prediction by focusing on DNA-affinity residues across multiple homologous templates. Finally, universal Protein Binding Microarrays evaluations on AI-designed DNA-binding proteins show that HomoDSP rescues a baseline failure mode in which the baseline method produces incorrect predictions because of training-set bias. Together, these results support the use of homologous template interfaces as informative structural priors for decoding protein DNA-binding specificity.

05.
arXiv (CS.LG) 2026-06-16

Adaptive Kernel Density Estimation with Pre-training

arXiv:2605.13092v2 Announce Type: replace-cross Abstract: Density estimation in high-dimensional settings is an important and challenging statistical problem.Traditional methods based on kernel smoothing are inefficient in high dimensions due to the difficulties in specifying appropriate location-adaptive kernels. In this work, we introduce pre-training, a key idea behind many cutting-edge AI technologies, to the context of non-parametric density estimation. By establishing a pre-trained neural network that can recommend an appropriate location-adaptive kernel for each sample point, efficient density estimation with adaptive kernels is achieved in high dimensions. A wide range of numerical experiments show that this strategy is highly effective for improving density-estimation accuracy, when the target distribution is close to the distribution family for pre-training. When the target distribution is substantially different from the pre-training distribution family, the benefit from the proposed pre-training strategy may be diluted, but can be reactivated by an additional fine-tuning procedure.

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

When Cognitive Graphs Meet LLMs: BDEI Cognitive Pathways for Panic Emotional Arousal Prediction

Predicting individual panic emotional arousal timing before manifestation is essential for proactive emergency intervention. Existing methods incorporate cognitive elements but none explicitly model the emotional arousal process, making them ill-suited for emotional arousal timing prediction. We argue that grounding prediction in appraisal emotion theory is necessary because it explicitly models this process, but three problems must be solved. (1) Appraisal theory posits that emotion arises from simultaneous evaluation across multiple threat dimensions, yet no prior work fuses these inputs into risk perception. (2) Existing cognitive models lack an Emotion node, decoupling threat appraisal from emotional arousal and forcing emotions to be inferred indirectly from behaviors. (3) Given their generalizable cognitive reasoning, current approaches adopt LLMs as the primary decision-maker, yet overlook the fragility and hallucination-proneness of their outputs. To address these issues, we introduce PanicCognitivePath (PCP), a framework that addresses all three. A Psychological Safety Distance (PSD) model, grounded in psychological distance theory, maps four-domain signals into a unified risk metric as the entry condition for subsequent cognitive reasoning. An explicit Emotion node grounded in appraisal emotion theory is introduced into BDI, forming a Belief-Desire-Emotion-Intention (BDEI) pathway. Agents whose risk metric exceeds the PSD threshold enter this pathway, coupling threat appraisal directly to emotional arousal. The BDEI pathway governs all state transitions while the LLM is confined to parameter estimation for the Belief-to-Desire transition, confining hallucinations to a single step and preventing error propagation. Experiments on Hurricane Sandy show PCP improves arousal timing accuracy by 10.68% over baselines, reduces peak count error to 7.07%.

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

EmoFSM: A Finite State Machine for Emotional Support Conversation

Emotional support conversation (ESC) aims to alleviate people's emotional distress through effective conversations. Although large language models (LLMs) have made remarkable progress in ESC, most of these studies may not define the diagram from a state-model perspective, thereby providing a suboptimal solution for long-term satisfaction. To address such an issue, we leverage the Finite State Machine (FSM) on LLMs, and propose a framework called EmoFSM. Our framework allows a single LLM to bootstrap the planning during ESC, and self-reason the seeker's emotion, support strategy, and the final response upon each conversation turn. Substantial experiments in ESC datasets suggest that EmoFSM outperforms many baselines, including direct inference, self-fine, chain of thought, finetuning, and externally supported methods, even those with many more parameters.

08.
arXiv (CS.CV) 2026-06-12

BrainDINO: A Brain MRI Foundation Model for Generalizable Clinical Representation Learning

Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis. Code is available at https://github.com/mclwu22/BrainDINO

09.
arXiv (CS.AI) 2026-06-19

Temporal Self-Imitation Learning

arXiv:2606.19752v1 Announce Type: cross Abstract: Long-horizon robot manipulation policies trained with reward shaping can still exploit dense rewards through inefficient interaction, while rare efficient behaviors may be forgotten during training. We argue that temporal efficiency itself provides a powerful and underutilized source of self-supervision for reinforcement learning. We introduce Temporal Self-Imitation Learning (TSIL), a reinforcement learning framework that mines temporally efficient successful trajectories generated during learning and converts them into reusable supervision for future policy improvement. TSIL progressively refines learning using configuration-conditioned adaptive temporal targets derived from fast successful trajectories, while preserving and replaying efficient behaviors through efficiency-weighted self-imitation learning. Across 15 distinct long-horizon manipulation tasks, TSIL consistently improves learning efficiency, task-completion efficiency, revisitation of fast successful behaviors, and robustness to unstable training conditions. More broadly, our results suggest that the temporal structure of successful behavior itself provides a scalable self-supervisory signal for reinforcement learning beyond manually engineered reward shaping alone.

10.
arXiv (CS.CV) 2026-06-16

MNet++: Extended 2D/3D Networks for Anisotropic Medical Image Segmentation

This work demonstrates a full reproduction and extension of MNet, a hybrid 2D/3D convolutional network designed for anisotropic medical image segmentation. The original architecture was re-implemented within the nnU-Net framework to verify its reported performance and robustness to variable voxel spacing, known as anisotropy. Experiments were conducted on PROMISE prostate MRI and a controlled subset of LiTS liver CT under matched preprocessing and compute constraints. The reproduced MNet achieved a Dice similarity coefficient (DSC) of 89.0 +/- 0.9% on PROMISE, within 0.8% of the published result, and 94.3 +/- 1.9% / 54.6 +/- 3.1% for liver and tumor segmentation on LiTS, respectively. Two lightweight extensions were further introduced: (1) a learned Fusion Gating mechanism enabling adaptive 2D-3D feature blending, and (2) a VMamba state-space module for efficient long-range depth modelling. The Spatial Gating variant improved DSC by +0.8% with less than 3% inference overhead, while VMamba improved performance consistency, reducing PROMISE Dice variation to +/- 0.7% and achieving the strongest LiTS liver performance at 95.8% Dice. Both extensions preserved MNet robustness to anisotropy, with delta Dice = 1.5% across 1-4 mm voxel spacing. Overall, the study confirms MNet reproducibility and demonstrates that adaptive fusion and state-space modelling have the potential to further strengthen segmentation reliability under anisotropic conditions. However, further tests are required to provide definitive conclusions.

11.
arXiv (CS.AI) 2026-06-16

Surprise-Guided MergeSort: Budget-Efficient Human-in-the-Loop Ranking via Adaptive Comparison Scheduling

arXiv:2606.15623v1 Announce Type: cross Abstract: Pairwise comparison is the gold standard for subjective ranking tasks; however, exhaustive annotation requires a massive number of human comparisons ($O(n^2)$). While sorting-based methods have reduced this burden to $O(n\log n)$, they still require expensive human judgment for every single comparison. To further improve annotation efficiency, we propose leveraging a Vision-Language Model (VLM) not as an annotator replacement, but as a question prioritizer to identify which comparisons genuinely require human judgment. The proposed Surprise-Guided MergeSort (SGS) framework achieves this through three integrated components: (1) a bottom-up MergeSort scheduler that structures comparisons and exploits transitivity, (2) a composite Surprise Scorer – combining position-bias-cancelled VLM confidence, Elo gap, and vote entropy – to quantify comparison ambiguity, and (3) an adaptive budget allocator that routes high-surprise pairs to humans while automating low-surprise pairs via transitivity inference. Validation was conducted on six diverse benchmarks spanning text similarity (STS-B, BIOSSES, SICKR-STS) and image quality assessment (KonIQ-10k, TID2013, LIVE Challenge). SGS effectively identified and skipped up to 535 non-informative comparisons per session. Consequently, it achieved Kendall's $\tau{\times}100$ improvements of $+6$ to $+12$ over Active Elo under the same total budget. These results demonstrate that combining VLM-guided surprise metrics with algorithmic sorting provides a generally consistent accuracy-efficiency trade-off across diverse domains.

12.
arXiv (quant-ph) 2026-06-11

The quantum harmonic oscillator and the real Hilbert space

arXiv:2606.12060v1 Announce Type: new Abstract: The harmonic oscillator is considered within generalized frameworks using complex and quaternionic numbers. The classical oscillator is considered in terms of a complex position function, and quantum oscillators are examined in terms of complex wave functions, and in terms of quaternionic wave functions as well. Both of the quantum solutions are obtained within the real Hilbert space formalism. The results reveal the complex and quaternionic descriptions as suitable frameworks for non-stationary processes, including damped oscillations, forced oscillations, and additionally self-interacting processes that cannot be appropriately described otherwise.

13.
arXiv (quant-ph) 2026-06-12

Hamiltonian-Aware ADAPT Variational Quantum Eigensolver for Molecular Ground-State Simulation

arXiv:2606.13118v1 Announce Type: new Abstract: Designing compact ansätze in Variational Quantum Eigensolver (VQE) is crucial for solving energetic problems of practical molecules on near-term quantum devices. However, existing Adaptive Derivative-Assembled Pseudo-Trotter (ADAPT) ansätze face two challenges: improper operator selection and accumulation of degraded operators. In this paper, we propose the Hamiltonian-Aware (HA) ADAPT-VQE algorithm to address these issues. First, we establish a novel excitation operator selection criterion. It breaks the local constraint of existing criteria by incorporating Hamiltonian information, prioritizes physically meaningful excitation operators, and incurs no extra classical or quantum computational overhead. Furthermore, we develop a problem-adaptive method for discriminating and pruning redundant excitation operators stemming from improper selection and inevitable degradation. This method balances redundant operator pruning and convergence guarantee, and is applicable to ansätze with arbitrary scales. Systematic numerical experiments on typical strongly correlated molecular systems demonstrate that our HA-ADAPT-VQE avoids energy plateaus and outperforms baseline algorithms in terms of energy error, ansatz size, and measurement cost. This work offers an efficient, robust ansatz construction paradigm, facilitating the development and practical deployment of large-scale VQE in quantum chemistry.

14.
bioRxiv (Bioinfo) 2026-06-15

Multi-platform reassessment of human mitochondrial DNA methylation reveals signals consistent with technical artifacts

The existence and functional relevance of mitochondrial DNA methylation remain controversial. Here, we systematically profiled cytosine methylation and hydroxymethylation across human brain and blood tissues spanning healthy and malignant states using orthogonal sequencing approaches that avoid chemical conversion during library preparation. While nuclear DNA exhibited canonical methylation patterns, mitochondrial DNA consistently showed negligible signal, indistinguishable from background technical noise. By mapping cytosine-guanine sites between mitochondrial DNA and nuclear-embedded mitochondrial sequences, we demonstrate the potential of these nuclear counterparts to confound not only cytosine methylation but also hydroxymethylation measurements, corroborating and extending prior findings implicating nuclear contamination as a potential source of apparent mitochondrial epigenetic signals. Additional technical factors that inflate apparent mtDNA methylation signals were identified, including sequence context biases, flow cell chemistries, and coverage-dependent discrepancies between the heavy and light strands. Collectively, these results provide convergent evidence against the presence of biologically meaningful cytosine methylation or hydroxymethylation in mitochondrial DNA. These findings caution against interpreting apparent mtDNA methylation signals in human adult tissues as meaningful without rigorous orthogonal validation and comprehensive consideration of technical and analytical confounding factors.

15.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

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

LLM-Assisted Stance Detection in Scientific Discourse: A Test Case in Bayesian Cognitive Science

Qualitative coding is central to social science, but expert annotation is difficult to scale. LLMs offer a possible extension, yet require careful validation when the target construct is interpretive, theoretically loaded, and only indirectly expressed. We study this problem in a difficult case: detecting whether authors treat Bayesian models as descriptions of mental and neural mechanisms (realism) or as useful mathematical tools (instrumentalism). Our method combines a theory-driven codebook, expert-coded reference annotations, a diagnostic-gated prompt-optimization search yielding a shared zero-shot prompt for three frontier LLMs (GPT-5.1, Claude Sonnet 4.6, Gemini 3 Pro Preview), and multi-rater reliability analysis. The final prompt achieved a held-out combined reliability score of 0.76 (harmonic mean of ICC = 0.79 and $\alpha$ = 0.74), with all diagnostics satisfied. Deployed on 6,858 quotes from 210 articles, the three LLMs reached substantial quote-level agreement (ICC = 0.80; $\alpha$ = 0.76; combined = 0.78) and near-perfect article-level rank stability ($r$ = 0.96-0.97 across rater pairs). The corpus was predominantly weakly realist, but article-level stances were rarely uniform: only 1.4% of articles used a single band, while 59.5% spanned four or more. Low-level perception/motor articles scored 8.8 Realism points higher than high-level cognition articles ($p < .001$, $d = 0.60$), quantifying a long-held qualitative intuition. We present this as an expert-led case study; the framework is intended to generalize to similar theoretically demanding tasks, not to all qualitative analysis.

17.
arXiv (CS.CV) 2026-06-12

GeoWorld-VLM: Geometry from World Models for Vision-Language Models

Modern Vision-Language Models (VLMs) achieve strong semantic recognition, yet remain brittle on elementary spatial relations such as left of, on, behind, and between. One cause of this failure arises before language reasoning begins: the visual pathway may compress or discard critical 3D structural cues during feature extraction, so the language model receives image representations that are already insufficient for reliable spatial judgment. We introduce GeoWorld-VLM, a VLM-side distillation framework that transfers geometric structure from frozen camera-conditioned video world models into VLMs. GeoWorld-VLM fine-tunes only the image encoder and multimodal projector, aligning post-projector image features with intermediate world-model representations while leaving the main backbone frozen. Given images, a prompt, and a sampled camera trajectory, the world-model teacher converts static visual input into a synthetic multi-view spatial signal. Training combines spatial answer supervision, teacher-student feature alignment, and a preservation anchor to the original VLM. Since the language model remains frozen, GeoWorld-VLM preserves the original model's linguistic capabilities while attributing spatial improvements to the enhanced visual pathway. To evaluate the effectiveness and generality of the proposed method, we apply GeoWorld-VLM to two distinct VLM architectures and observe consistent improvements across both backbones. GeoWorld-VLM improves performance by approximately 4 percent on both the What'sUp and VSR benchmarks, suggesting that world-model-guided visual alignment generalizes across model structures and spatial reasoning datasets.

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

Sonar-TS: Search-Then-Verify Natural Language Querying for Time Series Databases

Natural Language Querying for Time Series Databases (NLQ4TSDB) aims to assist non-expert users retrieve meaningful events, intervals, and summaries from massive temporal records. However, existing Text-to-SQL methods are not designed for continuous morphological intents such as shapes or anomalies, while time series models struggle to handle ultra-long histories. To address these challenges, we propose Sonar-TS, a neuro-symbolic framework that tackles NLQ4TSDB via a Search-Then-Verify pipeline. Analogous to active sonar, it utilizes a feature index to ping candidate windows via SQL, followed by generated Python programs to lock on and verify candidates against raw signals. To enable effective evaluation, we introduce NLQTSBench, the first large-scale benchmark designed for NLQ over TSDB-scale histories. Our experiments highlight the unique challenges within this domain and demonstrate that Sonar-TS effectively navigates complex temporal queries where traditional methods fail. This work presents the first systematic study of NLQ4TSDB, offering a general framework and evaluation standard to facilitate future research.

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

Toward Generalist Autonomous Research via Hypothesis-Tree Refinement

Scientific progress depends on a repeated loop of exploration, experimentation, and abstraction. Researchers test candidate directions, interpret the evidence, and carry the resulting lessons into later attempts. We study how an AI agent can run this loop autonomously over long horizons. We introduce Arbor, a general framework for autonomous research that combines a long-lived coordinator, short-lived executors, and Hypothesis Tree Refinement (HTR), a persistent tree that links hypotheses, artifacts, evidence, and distilled insights across time. The coordinator manages global research strategy over the tree, while executors implement and test individual hypotheses in isolated worktrees. As results return, Arbor updates the tree, propagates reusable lessons, refines the search frontier, and admits verified improvements. This design turns autonomous research from a sequence of local attempts into a cumulative process in which strategy, execution, and evidence are carried across time. We evaluate Arbor under Autonomous Optimization (AO), an operational setting where an agent improves an initial research artifact through iterative experimentation without step-level human supervision. Across six real research tasks in model training, harness engineering, and data synthesis, Arbor achieves the best held-out result on all six tasks, attaining more than 2.5x the average relative held-out gain of Codex and Claude Code under the same task interface and resource budget. On MLE-Bench Lite, Arbor reaches 86.36% Any Medal with GPT-5.5, the strongest result in our comparison.

20.
Nature (Science) 2026-06-10

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1–3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC). The purified AMC enables RNA loading and AGO folding, faithfully recapitulating de novo RISC assembly. Using cryogenic&nbsp;electron microscopy, we determined the structure of AMC bound to a microRNA duplex. In contrast to its conformation&nbsp;in the RISC, AGO adopts a highly open conformation in the AMC: the N domain and the RNA-binding module (PAZ–MID–PIWI) are fully detached and anchored to opposite sides of the HSP90 dimer, connected solely by the unfolded L1 linker. This arrangement exposes a positively charged cleft that accommodates an RNA duplex. AGO folding is facilitated by a small RNA duplex containing a 5′-terminal phosphate—but not by single-stranded RNAs—revealing a role for the RNA duplex as a chaperone-like cofactor that directs AGO domain assembly. These findings elucidate the RISC assembly mechanism and establish the AMC as a molecular tool for probing optimal RNA features and chemical modifications for the&nbsp;rational design of small interfering RNA therapeutics. Our study also sheds light on how chaperones, together with ligands, can guide the folding of client proteins. Structures of the AGO maturation complex reveal how chaperones and an RNA duplex drive assembly of the RNA-induced silencing complex.

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

TreeGRNG: Binary Tree Gaussian Random Number Generator for Efficient Probabilistic AI Hardware

arXiv:2606.16599v1 Announce Type: cross Abstract: Bayesian Neural Networks (BNNs) offer opportunities for greatly enhancing the trustworthiness of conventional neural networks by monitoring the uncertainties in decision-making. A significant drawback for BNN inference at the extreme edge, however, is the imperative need to incorporate Gaussian Random Number Generators (GRNG) within each neuron. State-of-the-art GRNG algorithms heavily depend on multiple arithmetic operations and the use of extensive look-up tables, posing significant implementation challenges for ultra-low power hardware implementations. To overcome this, this paper presents an innovative binary tree random number generator (TreeGRNG) allowing the use of ultra-low-cost constant comparators instead of arithmetic units. We further enhance the TreeGRNG proposal with a set of hardware-aware optimizations exploiting the Gaussian properties. The optimized TreeGRNG surpasses the State-of-the-Art (SoTA) in terms of distribution accuracy while achieving a 3.7$\times$ reduction in energy per sample and boosting the throughput per unit area by 5.8$\times$. Moreover, our TreeGRNG proposal possesses a distinct advantage over the current SoTA in terms of flexibility, as it easily enables designers to adjust the shape of the sampled probability distribution, extending beyond the capabilities of traditional GRNGs, opening the horizon towards future probabilistic AI designs. The TreeGRNG design is available open-source in the link

22.
arXiv (CS.LG) 2026-06-17

Informative Missingness to Generate Irregular Clinical Time Series

arXiv:2606.17106v1 Announce Type: new Abstract: Laboratory tests in electronic health records are collected irregularly, and the absence of a test order can be as informative as the measurement itself. Such missingness reflects clinicians' decisions and patient physiology, making it important to model it directly rather than treat it as a preprocessing artifact. Here we present a diffusion-based approach for generating clinical time series that jointly models laboratory values and their observation patterns using the public Data Analytics Challenge on Missing Data Imputation (DACMI) benchmark derived from MIMIC-III. To preserve realistic sampling, we align chart times into 4-hour intervals and segment admissions into 7-day windows, producing trajectories that pair each lab value with a corresponding observation indicator. Standard transformations and normalization are applied to stabilize training. Our method extends the TimeDiff framework to learn continuous lab values and discrete missingness patterns through complementary diffusion objectives. Experiments show that the generated data closely match real patient trajectories across individual lab distributions and joint value-missingness embeddings, demonstrating that diffusion models can capture clinically meaningful dependencies between patient physiology and clinicians' testing behavior under MNAR-like (missing-not-at-random) missingness. These preliminary results indicate that our model can serve as an initial component toward developing clinical foundation models. By producing synthetic priors that preserve key physiology-missingness relationships, this work motivates the subsequent training of Prior-Data Fitted Networks capable of leveraging informative missingness, which we will investigate in the extended work.

23.
arXiv (CS.AI) 2026-06-19

SleepMaMi: A Universal Sleep Foundation Model for Integrating Macro- and Micro-structures

arXiv:2602.07628v2 Announce Type: replace Abstract: While the shift toward unified foundation models has revolutionized many deep learning domains, sleep medicine remains largely restricted to task-specific models that focus on localized micro-structure features. These approaches often neglect the rich, multi-modal context of Polysomnography (PSG) and fail to capture the global macro-structure of a full night's sleep. To address this, we introduce SleepMaMi , a Sleep Foundation Model engineered to master both hour-long sleep architectures and fine-grained signal morphologies. Our framework utilizes a hierarchical dual-encoder design: a Macro-Encoder to model full-night temporal dependencies and a Micro-Encoder to capture short-term characteristics from biosignals. Macro-Encoder is trained via Demographic-Guided Contrastive Learning, which aligns overnight sleep patterns with objective subject metadata, such as age, sex and BMI to refine global representations. Micro-Encoder is optimized via a hybrid Masked Autoencoder (MAE) and multi-modal contrastive objective. Pre-trained on a massive corpus of $>$20,000 PSG recordings (158K hours),SleepMaMi outperforms or matches state-of-the-art existing foundation models across a diverse suite of downstream tasks, demonstrating superior generalizability and label-efficient adaptation for clinical sleep analysis.

24.
arXiv (CS.CL) 2026-06-19

S2D2: Fast Decoding for Diffusion LLMs via Training-Free Self-Speculation

Block-diffusion language models offer a promising path toward faster-than-autoregressive generation by combining block-wise autoregressive decoding with within-block parallel denoising. However, in the few-step regime needed for practical acceleration, standard confidence-thresholded decoding is often brittle: aggressive thresholds hurt quality, while conservative thresholds require unnecessary denoising steps. Existing approaches that address this issue either require additional training or incur extra test-time compute. We present S2D2, a training-free self-speculative decoding framework for block-diffusion language models. Our key observation is that a block-diffusion model becomes autoregressive when the block size is reduced to one, allowing the same pretrained model to act as both drafter and verifier. S2D2 inserts a speculative verification step into standard block-diffusion decoding and uses lightweight routing policies to decide when verification is worth its cost. This yields a hybrid decoding trajectory in which diffusion proposes tokens in parallel, while the autoregressive mode acts as a local sequence-level critic. Across three mainstream block-diffusion families, S2D2 consistently improves the accuracy-speed tradeoff over strong confidence-thresholding baselines. On SDAR, we observe up to $4.7\times$ speedup over autoregressive decoding, and up to $1.57\times$ over a tuned dynamic decoding baseline while improving accuracy by up to $4.5$ points. On LLaDA2.1-Mini, S2D2 remains complementary to built-in self-correction, including a conservative setting where it is $4.4\times$ faster than the static baseline with slightly higher accuracy.

25.
arXiv (quant-ph) 2026-06-11

A post-selected quantum model of cosmic acceleration

arXiv:2606.12297v1 Announce Type: cross Abstract: The origin of cosmic acceleration remains a central problem in cosmology, commonly attributed to a cosmological constant within the $\Lambda$CDM model or to dynamical dark energy. Here, we develop an alternative approach in which acceleration emerges from quantum post-selection, a standard feature of quantum theory that is not usually incorporated into cosmological modelling. While quantum theory admits both pre-selected and post-selected ensembles, quantum cosmological models are almost exclusively formulated in terms of initial conditions. Building on previous work on post-selected quasiclassical dynamics, we construct a minimal predictive cosmological model in which post-selection and coarse-graining generate effective late-time acceleration without introducing a cosmological constant, dark energy, or modifications of general relativity. The resulting expansion history is highly constrained theoretically and depends on at most two parameters beyond standard Friedmann evolution. Confrontation with type Ia supernova and cosmic chronometer data yields statistically competitive fits while naturally avoiding the coincidence problem. The model also reproduces the standard radiation- and matter-dominated behaviour at early times and predicts a present-day jerk parameter significantly different from the $\Lambda$CDM value. These results suggest that cosmic acceleration may arise as a macroscopic quantum cosmological effect rather than from additional cosmological fluids or modified gravitational dynamics.