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01.
arXiv (CS.LG) 2026-06-18

Wasserstein Policy Learning for Distributional Outcomes

arXiv:2606.19117v1 Announce Type: cross Abstract: Offline policy learning has received growing attention in causal inference. The primary objective is to learn a policy (individualized treatment rule) as a mapping from covariates to treatment that maximizes the empirical welfare defined as the mean of scalar-valued potential outcomes. In this paper, we study offline policy learning with distribution-valued outcomes, where each potential outcome is a probability measure on $\mathbb{R}$ and the reward is defined through a utility functional applied to the Wasserstein barycenter of induced outcome distributions. We establish statistical guarantees for the policy learning framework based on both Inverse Probability Weighting (IPW) and Doubly Robust (DR) estimators. By handling the challenging uniform deviation over the product of the combinatorial policy class and the infinite-dimensional quantile domain, we prove that the finite-sample regret has leading dependence $\widetilde{\mathcal{O}}(\sqrt{\mathrm{N-dim}(\Pi)/N})$. In the one-dimensional Wasserstein setting and under the stated regularity conditions, the leading regret rate is still governed by the policy-class complexity. Moreover, we provide a minimax lower bound establishing the sharpness of the leading dependence on $N$ and $\mathrm{N-dim}(\Pi)$.

02.
arXiv (CS.CL) 2026-06-15

Chronological Thinking in Full-Duplex Spoken Dialogue Language Models

Recent advances in spoken dialogue language models (SDLMs) reflect growing interest in shifting from turn-based to full-duplex systems, where the models continuously perceive user speech streams while generating responses. This simultaneous listening and speaking design enables real-time interaction and the agent can handle dynamic conversational behaviors like user barge-in. However, during the listening phase, existing systems keep the agent idle by repeatedly predicting the silence token, which departs from human behavior: we usually engage in lightweight thinking during conversation rather than remaining absent-minded. Inspired by this, we propose Chronological Thinking, an on-the-fly conversational thinking mechanism that aims to improve response quality in full-duplex SDLMs. Specifically, chronological thinking presents a paradigm shift from conventional LLM thinking approaches, such as Chain-of-Thought, purpose-built for streaming acoustic input. (1) Strictly causal: the agent reasons incrementally while listening, updating internal hypotheses only from past audio with no lookahead. (2) No additional latency: reasoning is amortized during the listening window; once the user stops speaking, the agent halts thinking and begins speaking without further delay. Experiments demonstrate the effectiveness of chronological thinking through both objective metrics and human evaluations show consistent improvements in response quality. Furthermore, chronological thinking robustly handles conversational dynamics and attains competitive performance on full-duplex interaction metrics.

03.
arXiv (CS.AI) 2026-06-12

A Quantitative Experimental Repeated Measures Study of Training Dynamics in a Small Llama Style Language Model Under a Compute-Aware Token Budget

Authors:

arXiv:2606.13370v1 Announce Type: new Abstract: This study examines training dynamics in a small Llama-style language model trained under a fixed, compute-constrained token budget. Rather than evaluating efficiency solely through endpoint performance, the study uses a quantitative experimental repeated measures design to analyze how validation loss, validation perplexity, rolling volatility, backslide behavior, spike behavior, and between-seed variability change across token-based training intervals. Six independent training runs were conducted on a 4.26-million-parameter model using the TinyStories corpus, CPU-based full-precision training, and a target budget of approximately 20 million cumulative training tokens. Metrics were collected across 21 intervals, producing 126 seed-by-interval observations. Repeated measures ANOVA showed statistically significant interval effects for validation loss, validation perplexity, and rolling volatility. Descriptive trajectories revealed rapid early improvement followed by non-monotonic degradation during later training intervals. Mean validation loss decreased from 8.3552 at initialization to 2.7996 near 4 million tokens, but increased to 3.9010 by the final checkpoint. Validation perplexity followed the same pattern, falling sharply early in training before rising later. Derived telemetry further showed recurrent validation-loss backslides and no interval-summary evidence of a stable phase under the predefined criteria. These findings suggest that compute-aware language model evaluation should examine training trajectories rather than endpoint metrics alone. In constrained compute settings, additional token exposure may increase computational cost without producing proportional generalization gains, and interval-level telemetry can reveal instability, regression, and diminishing returns that final metrics may obscure.

04.
arXiv (CS.CL) 2026-06-19

Pruning via Causal Attribution Preserves Reasoning Performance in Large Language Models

Large language models (LLMs) excel at multi-step reasoning but incur substantial inference cost. We introduce Causal Attribution Pruning (CAP), a training-free method that identifies critical attention heads by measuring their causal impact on reasoning tasks and uses these head-level scores to guide fine-grained weight pruning. For each attention head, CAP estimates the expected performance degradation when the head is masked during forward passes on a small calibration set of reasoning problems. These causal scores are then converted into weight-level importance values for the corresponding projection matrices. Unlike magnitude-only or activation-based criteria, CAP's interventional measurement directly captures each head's functional contribution, yielding relative accuracy gains of up to 61% over Wanda on ARC-Challenge at 20% sparsity. We evaluate CAP on GSM8K, StrategyQA, and ARC-Challenge using Llama-3-8B-Instruct and Mistral-7B-Instruct at 10%, 20%, and 50% sparsity. At moderate sparsity (10-20%), CAP improves over Wanda in most model-benchmark configurations. with especially large gains on ARC-Challenge for Llama-3. Our results suggest that attention-head-level causal attribution can better preserve reasoning performance on downstream benchmarks than correlational pruning criteria at equivalent sparsity, while remaining limited by coarse MLP attribution at 50% sparsity.

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

Not All Retrievals are Useful: Cross-Attention for Input-Aware RAG in Time Series Forecasting

arXiv:2603.14709v2 Announce Type: replace Abstract: Retrieval-augmented generation (RAG) enhances zero-shot time series (TS) forecasting by leveraging external knowledge bases, yet existing approaches overlook input-level relevance when fusing retrieved samples with the query. We argue that not all retrievals are equally useful, and irrelevant ones can degrade performance. To this end, we propose Cross-RAG, a zero-shot RAG-based forecasting framework that selectively attends to query-relevant retrieved samples via query–retrieval cross-attention. By modeling input-level relevance between the query and retrieved samples, Cross-RAG jointly incorporates three sources of information: 1) the query itself, 2) the retrieved samples, and 3) their relational interactions. In particular, this input-aware design enables Cross-RAG to remain stable as the number of retrieved samples $k$ grows, whereas prior methods without cross-attention require careful $k$ tuning to avoid degradation from irrelevant retrievals. Extensive experiments demonstrate that Cross-RAG consistently improves zero-shot forecasting performance across multiple TSFM backbones and various RAG methods, with additional analyses confirming its effectiveness across various retrieval scenarios. Code is available at https://github.com/seunghan96/cross-rag/.

06.
bioRxiv (Bioinfo) 2026-06-16

Physics-Driven Zero-Shot Reconstruction of Isotropic 3D Fluorescence Microscopy under Undersampled Acquisition

Three-dimensional (3D) imaging represents the development of next generation of fluorescence microscopy. However, routine axial down-sampling makes isotropic resolution unrealistic. Here, we propose DeepUI, a physical zero-shot framework designed to achieve isotropic 3D fluorescence images from a low axial sampling rate. DeepUI fully leverages the intrinsic characteristics of 3D images through physics-guided degradation, which incorporates spatial-frequency joint learning to generate a scaled optical transfer function, combined with noise degradation and an up-sampling branch. Typically requiring just 5 minutes for training and 0.5 minutes for high-throughput and fast prediction, we demonstrate the superior performance of DeepUI to get isotropic results, and the exclusivity to axial down-sampling conditions, even in more challenging conditions, including defocused background, noise, and resolution blur.

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

Direct Advantage Estimation for Scalable and Sample-efficient Deep Reinforcement Learning

arXiv:2606.20411v1 Announce Type: new Abstract: Direct Advantage Estimation (DAE) has been shown to improve the sample efficiency of deep reinforcement learning algorithms. However, its reliance on full environment observability limits its applicability in realistic settings, and its requirement to model transition probabilities incurs substantial computational overhead for high-dimensional observations. In the present work, we address both limitations. First, we extend the theoretical framework of DAE to partially observable domains with minimal modifications. Second, we reduce its computational complexity by introducing discrete latent dynamics models that efficiently approximate transition probabilities. We evaluate our approach on the Arcade Learning Environment and find that DAE scales effectively with function approximator capacity while retaining high sample efficiency.

08.
arXiv (CS.AI) 2026-06-11

Using Explainability as a Training-Time Reliability Signal for Efficient ECG Classification

arXiv:2606.12252v1 Announce Type: cross Abstract: Training deep neural networks for clinical time-series analysis is computationally demanding, yet many healthcare settings lack the resources required for repeated model development and deployment. This challenge is particularly evident in electrocardiogram classification, where large datasets and long training schedules make efficiency practically important. Progressive Data Dropout reduces training cost by excluding samples from gradient updates once they are learned, but it relies on model confidence and may retain samples that are difficult due to noise or ambiguity rather than useful signal. In this work, we introduce ERTS, an explainability-based reliability training signal for efficient ECG classification. ERTS uses explanation quality during training to distinguish between informative and unreliable uncertainty. Building on progressive data selection, we compute Grad-CAM attention maps for candidate samples and derive a focus score that measures whether model predictions are supported by coherent and localised patterns. Samples with low focus are filtered out, while those with meaningful attention are prioritised for gradient updates. We evaluate ERTS across three ECG datasets and multiple backbone architectures, showing consistent improvements in macro-F1 alongside reduced effective training cost. These results suggest that explanation quality can serve as a practical signal for improving both efficiency and reliability in clinical time-series learning. Code will be released.

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

Bridging the Usability Gap: Lessons from Interpreting Studies for Machine Interpreting Design

Machine interpreting (MI), the live, real-time branch of speech translation, has achieved remarkable progress on standard benchmarks, with some systems approaching human parity on textual fidelity. Yet the user experience remains far inferior to interpreter-mediated communication, revealing what we term the accuracy illusion: systems that appear accurate on paper but fail in practice to support smooth, goal-oriented interaction. This paper defines MI as a distinct subfield of speech translation, with its own characteristics and the need for evaluation methods grounded in communicative effectiveness rather than isolated fidelity metrics. Drawing on insights from interpreting studies, we identify critical dimensions of professional interpreting practice that are overlooked by current systems, and consolidate them into three interdependent design priorities for future MI: agency (context-sensitive initiative and repair), grounding (multimodal and discourse-level situational awareness), and experience (adaptive improvement through real interaction). Together, these priorities chart a path toward closing the usability gap and enabling systems that can sustain authentic multilingual communication in real time.

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

Evaluative Judgement in Teaching AI-based Translation: A Class-room Case Study of AI-Mediated Translation and Post-Editing

Authors:

Drawing on 23 anonymized student pro-jects from a fourth-year Machine Transla-tion and Post-editing course in a BA-level translation programme, this paper exam-ines how structured comparison of gen-eral-purpose LLMs and online MT sys-tems can elicit evaluative judgement in AI-mediated translation. Students translat-ed short specialised English Wikipedia texts into Catalan or Spanish, generated four system outputs, evaluated them using automatic metrics and human adequa-cy/fluency assessment, selected one output for post-editing, and justified their deci-sion in written reports. Descriptive counts are reported for all 23 projects, while qualitative interpretation is based on the 22 cases accompanied by written reports. Results show that students did not treat automatic metrics as final authority: final post-editing selections often diverged from metric rankings and were justified through adequacy, fluency, terminology, naturalness, and expected post-editing ef-fort. The study therefore does not bench-mark systems under controlled conditions; it analyses how students justified system choice within an authentic classroom as-signment.

11.
PLOS Computational Biology 2026-06-17

Combining machine learning and iterative experiments to keep pace with emerging viral variants of concern

by Thomas Sheffield, Ryan C. Bruneau, Stephen Won, Kenneth L. Sale, Brooke Harmon, Le Thanh Mai Pham Modeling and predicting viral mutations before they emerge plays a crucial role in pandemic preparedness, enabling the early identification of emerging variants of concern (VOCs) and guiding timely updates to vaccines, diagnostic tests, and therapeutic strategies. However, existing machine learning models and large-scale experiments lose their predictive power as viral variants evolve further from the original strains in sequence space. Here, we present a scalable framework that integrates random forest and neural network machine learning models with targeted high-throughput experimentation to anticipate and evaluate emerging SARS-CoV-2 receptor-binding domain (RBD) variants. Using public datasets, we trained predictive models for binding to human Angiotensin-converting enzyme 2 (ACE2), RBD expression, and antibody escape, and refined these models through iterative integration of experimental data focused on over 200 variants derived from wild-type (WT) and Omicron strains. Through an indirect transfer learning approach, our machine learning models achieved high accuracy having correlation coefficients of up to 0.79 for antibody binding. The models were also generalizable across diverse antibody types including heavy-chain-only antibodies (HCAbs) by encoding complementarity-determining regions (CDRs) as input features. This dynamic approach enables rapid assessment of emerging variants, facilities prioritization of the therapeutic strategies, and supports a proactive, data-driven response to evolving viral threats.

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

Compositional Skill Routing for LLM Agents: Decompose, Retrieve, and Compose

Authors:

LLM agents increasingly rely on external skills – reusable tool specifications – but real-world tasks often require composing multiple skills, not just selecting one. We formalize this as the Compositional Skill Routing problem: given a complex user query and a large skill library, decompose the query into atomic sub-tasks, retrieve the appropriate skill for each sub-task, and compose an executable plan. We present SkillWeaver, a decompose-retrieve-compose framework combining an LLM task decomposer, a bi-encoder skill retriever with FAISS indexing, and a dependency-aware DAG planner. To support evaluation, we introduce CompSkillBench, a benchmark of 300 compositional queries over 2,209 real MCP server skills spanning 24 functional categories, sourced from the public MCP ecosystem. Our experiments reveal that task decomposition quality is the primary bottleneck: standard LLM decomposition reaches only 34.2% category recall at the step level. To address this, we propose Iterative Skill-Aware Decomposition (SAD), a retrieval-augmented feedback loop that iteratively aligns decomposition with available skills. SAD improves decomposition accuracy from 51.0% to 67.7% (+32.7%, Wilcoxon p < 10^-6) in a single iteration; DA-conditioned analysis confirms that correct granularity is the prerequisite for effective retrieval (CatR@1 rises from 34% to 41% when DA=1). SkillWeaver reduces context window consumption by over 99%, and transfer experiments confirm generalization (+35.6% relative DA gain even when target categories are absent from the retrieval pool).

13.
arXiv (CS.CL) 2026-06-16

Neuron Level Analysis of Large Language Model in Legal Domain Reasoning

We presented a neuron-level analysis of legal-domain reasoning in LLMs, comparing it with other applied domain tasks across seven open-weight models. Using neuron attribution scores to rank and suppress influential neurons, we confirmed that suppressing the identified neurons collapses accuracy on the target task, whereas suppressing the same number of random neurons does not. We further found a small subset of neurons influential across all seven tasks; once these are removed, suppressing the remaining neurons degrades only the task they were identified from, revealing genuinely task-specific neurons in every model studied. Within the legal domain, the three benchmarks exhibit relatively high neuron overlap and tend to be affected jointly, suggesting of legal components neurons that span jurisdictions. The distribution of identified neurons in our experiments suggests that the hypothesis that influential neurons are concentrated in middle MLP layers may depend on the input format and content, rather than being a universal phenomenon.

14.
arXiv (CS.AI) 2026-06-18

SHIFT: Semantic Harmonization via Index-side Feature Transformation for Multilingual Information Retrieval

arXiv:2606.18801v1 Announce Type: cross Abstract: With the rapid expansion of massive multilingual corpora, Multilingual Information Retrieval (MLIR) has emerged as a critical technology for global information access. MLIR enables users to retrieve semantically relevant documents from multilingual text collections using a single-language query. However, recent multilingual dense retrieval models often exhibit a strong preference for documents in the same language as the query. This leads to severe language bias, where top-ranked results are dominated by documents of specific languages, even when documents in other languages contain more semantically relevant information. To address this issue, we propose SHIFT, a training-free method applicable in the indexing stage. Specifically, SHIFT utilizes parallel translation pairs to estimate a relative language vector for each target language with respect to a source language. Subsequently, SHIFT corrects the language-specific offset by subtracting this relative language vector from document embeddings during indexing. Our comprehensive evaluation across four MLIR benchmarks and diverse dense retrieval models confirms that SHIFT can effectively mitigate language bias and enhance MLIR performance.

15.
arXiv (CS.CL) 2026-06-18

SFT Overtraining Predicts Rank Inversion via Entropy Collapse Under RLVR

The standard heuristic of selecting the SFT checkpoint with the highest pass@1 for GRPO can fail when SFT compresses the rollout distribution. For binary rewards, the expected within group advantage variance is $p(1{-}p)(g{-}1)/g$; when early GRPO drives $p$ below $p^*(g)$, most groups have identical rewards and provide no group relative signal. We study SFT depth ladders for Qwen2.5-Coder-3B and DeepSeek-Coder-6.7B. We test Qwen2.5-Coder-3B across five depths and three seeds, and DeepSeek-Coder-6.7B across four matched depths and three seeds. On Qwen, pre RL pass@1 rises with SFT depth, but peak GRPO pass@10 falls from $0.806$ to $0.481$ (3 seed mean, $n{=}20$); pre RL entropy is positively associated with the GRPO outcome ($\rho{=}{+}0.69$). On DeepSeek, pass@1 remains far above $p^*(8){=}0.083$, and GRPO outcomes compress rather than invert. A two stage diagnostic, combining pre RL entropy triage with an early GRPO entropy monitor, flags high risk checkpoints and can stop failing runs early. Simple KL to reference regularisation and label smoothing variants do not rescue the collapsed Qwen checkpoint in our setting, suggesting the failure is not a trivial GRPO hyperparameter artefact.

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

STRIDE: Strategic Trajectory Reasoning via Discriminative Estimation for Verifiable Reinforcement Learning

arXiv:2606.15866v1 Announce Type: new Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) has become an effective post-training paradigm for improving the reasoning abilities of large language models. However, existing RLVR methods typically rely on final-answer correctness to assign trajectory-level rewards, providing sparse supervision and treating all tokens uniformly regardless of their actual contribution to reasoning. Although recent studies introduce intermediate signals such as process rewards, high-entropy tokens, and semantic uncertainty, these signals are often not inherently verifiable and may fail to distinguish beneficial strategic patterns from harmful ones. To address this limitation, we propose STRIDE (Strategic Trajectory Reasoning with Discriminative Estimation), a fine-grained RLVR framework that derives strategic reasoning supervision from verifiable outcomes. STRIDE contrasts successful and failed trajectories within each response group to estimate the outcome-discriminative preference of each $n$-gram strategic pattern, and further combines this signal with reasoning saliency entropy to identify decision-relevant strategic patterns. These patterns are assigned differentiated advantage values during RL optimization, enabling more precise credit assignment while preserving the verifiability of RLVR. Extensive experiments demonstrate that STRIDE consistently improves reasoning performance across diverse models, tasks, and extended settings, including VLMs and agent-based systems.

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

How Inference Compute Shapes Frontier LLM Evaluation

arXiv:2606.17930v1 Announce Type: new Abstract: AI evaluations are shifting toward harder tasks that benefit from longer trajectories involving tool use and iterative problem solving. As a result, performance is increasingly sensitive to the amount and allocation of compute available at test time ("inference compute"). Yet many evaluations still report performance at a single restrictive budget, meaning that low scores may reflect the evaluation setup rather than the model's underlying capability. To test this, we evaluate up to 12 frontier language models on seven challenging benchmarks spanning software engineering, mathematics, medicine, and cybersecurity. We use a controlled setup combining three simple inference-scaling interventions: larger token budgets, context compaction, and repeated submission attempts, guided either by the model itself or by minimal correctness feedback. We find three main results. First, larger token budgets substantially improve performance on benchmarks across multiple domains, including cybersecurity, FrontierMath, Humanity's Last Exam, and TerminalBench. Second, fixed-budget evaluations can increasingly understate frontier capability as models advance. Newer models reach higher performance at large budgets, where they unlock harder tasks and solve them more reliably. Third, benchmarks differ in which inference-scaling methods help most: repeated submission broadly improves performance, but the value of larger token budgets, external feedback, and parallel attempts varies by benchmark. Overall, our results show that benchmark scores are protocol-dependent. We therefore argue that evaluations should report capability as a function of inference-time compute, specify protocol choices explicitly, and compare model generations over a large shared compute range at matched budgets, especially in safety- or policy-relevant settings.

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

TimeProVe: Propose, then Verify for Efficient Long Video Temporal Reasoning in Activities of Daily Living

Long Video Question Answering (LVQA) requires identifying sparse, query-relevant evidence within hours-long untrimmed videos. Existing approaches either process videos densely with large vision-language models (VLMs), incurring prohibitive computational cost, or rely on sparse caption-based reasoning, which often misses temporally localized and motion-centric evidence. We introduce TimeProVe, a cost-efficient hybrid framework for temporally grounded reasoning in long videos. TimeProVe first employs lightweight modules to generate action-grounded answer–evidence hypotheses and subsequently invokes an expensive VLM only for targeted verification. The core of our framework lies in the Action-based Candidate Evidence (ACE) module, which converts temporally localized actions into query-conditioned candidate answers and supporting evidence windows through lightweight LLM reasoning. We further introduce OpenTSUBench (OTB), an open-ended benchmark designed to evaluate temporally grounded reasoning in real-world Activities of Daily Living (ADL) scenarios. Experiments show that TimeProVe outperforms the strongest baseline on OTB by 7.3%, while reducing VLM calls by 75% and inference cost by 93%. Furthermore, without explicit temporal grounding training, TimeProVe achieves competitive performance on Charades-STA, and reaches state-of-the-art results when enhanced with grounding VLMs.

19.
bioRxiv (Bioinfo) 2026-06-22

EventHorizon: A Foundation Model for Clinical Flow Cytometry

Flow cytometry is an essential tool for diagnosis of hematologic malignancies, but existing clinical workflows are highly dependent on expert manual interpretation. Existing machine learning approaches typically require extensive labeled data and are sensitive to variability in panel design, instrumentation, and laboratory workflows, limiting their generalizability. We present EventHorizon, a self-supervised foundation model for clinical flow cytometry that produces unified specimen-level representations from heterogeneous multi-panel data. EventHorizon employs a two-stage hierarchical transformer architecture with marker-aware tokenization, enabling seamless integration of cells measured across different antibody panels into a single shared latent space. We pre-train the model using a DINO-inspired self-distillation strategy with a variety of flow cytometry-specific augmentations on a dataset of more than 100,000 clinical specimens across 17 distinct panels. We evaluate the resulting embeddings on three clinically relevant classification tasks spanning common and rare panels, demonstrating that simple k-nearest neighbor probing of frozen EventHorizon embeddings achieves performance comparable to a fully supervised baseline model and a prior panel-specific self-supervised model. To ensure EventHorizon is not simply shortcut learning on features such as the markers/panels run for a given specimen, we perform a graph-theoretic analysis of EventHorizon's latent space which argues that specimen embeddings are organized primarily by biological diagnosis. Taken together, these results demonstrate that EventHorizon produces biologically meaningful, panel-agnostic specimen representations from clinical flow cytometry data which, with further development and validation, could provide a potential basis for scalable, reproducible diagnostic support across diverse clinical laboratory settings.

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

From Digital to Physical: Digital Agents as Autonomous Coaches for Physical Intelligence

arXiv:2601.21570v2 Announce Type: replace Abstract: The field of Embodied AI is witnessing a rapid evolution toward general-purpose robotic systems, fueled by high-fidelity simulation and large-scale data collection. However, this scaling capability remains severely bottlenecked by a reliance on labor-intensive manual oversight from intricate reward shaping to hyperparameter tuning across heterogeneous backends. Inspired by LLMs' success in software automation and science discovery, we introduce \textsc{EmboCoach-Bench}, a benchmark evaluating the capacity of LLM agents to autonomously engineer embodied policies. Spanning 32 expert-curated RL and IL tasks, our framework posits executable code as the universal interface. We move beyond static generation to assess a dynamic closed-loop workflow, where agents leverage environment feedback to iteratively draft, debug, and optimize solutions, spanning improvements from physics-informed reward design to policy architectures such as diffusion policies. Extensive evaluations yield three critical insights: (1) autonomous agents can qualitatively surpass human-engineered baselines by 26.5\% in average success rate; (2) agentic workflow with environment feedback effectively strengthens policy development and substantially narrows the performance gap between open-source and proprietary models; and (3) agents exhibit self-correction capabilities for pathological engineering cases, successfully resurrecting task performance from near-total failures through iterative simulation-in-the-loop debugging. Ultimately, this work establishes a foundation for self-evolving embodied intelligence, accelerating the paradigm shift from labor-intensive manual tuning to scalable, autonomous engineering in embodied AI field.

21.
bioRxiv (Bioinfo) 2026-06-11

Calibrated Uncertainty Quantification for Patient-Level AML Drug Sensitivity Prediction Using Split Conformal Prediction

Accurate prediction of ex vivo drug sensitivity in acute myeloid leukemia (AML) patients from transcriptomic data is a critical challenge for precision oncology. Existing computational approaches have explored uncertainty quantification in cancer drug response prediction primarily using cell line data, while patient-level AML models typically rely on heuristic confidence measures rather than statistically calibrated uncertainty estimates. Here, we present a framework applying split conformal prediction to patient-level AML drug response modeling using the BeatAML 2.0 cohort. We trained Elastic Net and XGBoost regressors on bulk RNA-seq gene expression profiles from 318 AML patients, analyzing 34,764 patient-drug observations across 122 compounds. Baseline models achieved median Pearson R values of 0.291 (Elastic Net) and 0.281 (XGBoost) across 122 drugs. Wrapping these models with split conformal prediction yielded well-calibrated prediction intervals across three confidence levels: empirical coverages of 81.4%, 90.7%, and 95.5% against nominal targets of 80%, 90%, and 95%, respectively. Analysis of prediction interval widths revealed substantial drug-class-specific uncertainty patterns, with HDAC and BCL-2 inhibitors exhibiting markedly higher uncertainty than MDM2 inhibitors, suggesting a potential association between transcriptomic predictability and drug mechanism of action, although several drug classes were represented by only a small number of compounds. Predictive uncertainty was not significantly associated with ELN2017 molecular risk classification (Kruskal-Wallis p=0.395) or NPM1 mutation status (p=0.788). These results demonstrate that statistically valid uncertainty quantification can be achieved for patient-level AML drug response prediction despite substantial biological heterogeneity. to the best of our knowledge, no published study has applied split conformal prediction to patient-level ex vivo drug sensitivity prediction in the BeatAML cohort, providing a principled alternative to heuristic confidence scoring approaches. Keywords: Acute myeloid leukemia (AML); Ex vivo drug sensitivity; Conformal prediction; Uncertainty quantification; Precision oncology; BeatAML; Transcriptomic biomarkers; Machine learning.

22.
bioRxiv (Bioinfo) 2026-06-12

ProMiSE: Protein Multi-State Evaluation Benchmark in Biological Contexts

Proteins are inherently dynamic, with biological functions often emerging from transitions between multiple conformational states. While recent breakthroughs have largely addressed the static structure prediction problem, no systematic benchmark exists to demonstrate how well current models capture functionally relevant dynamics. We introduce ProMiSE, the first benchmark that provides both a dataset and an evaluation scheme, based on native biological assemblies and integrating major conformational change mechanisms - intrinsic, ligand-induced, and protein-induced - within a single curated dataset. We conducted a comprehensive evaluation of state-of-the-art structure prediction models, including AlphaFold3 and recent generative approaches. Our findings reveal that current models exhibit a limited ability to sample intrinsic multi-states and are often insensitive to biological context in induced scenarios. Internal representation analysis suggests that training-data exposure can shift predictions toward dominant conformational states over alternative biologically relevant states, primarily at the structure module. In contrast, results from BioEmu indicate that reducing decoding-stage bias can substantially improve multi-state sampling without major changes to upstream pair representations.

23.
arXiv (CS.LG) 2026-06-16

PHINN: Persistent Homology Inspired Neural Network for Rare-Event Time Series Generation

arXiv:2606.15452v1 Announce Type: new Abstract: Rare events in time series are critical to model but hard to learn due to data scarcity. Current generative models struggle with extreme values. We observe that rare events leave distinct topological fingerprints - transitions in Betti numbers from point-cloud embeddings - that are more stable and discriminative than statistical moments. We introduce PHINN, a flow-matching framework using dynamic Betti curves as conditioning signals and a persistence landscape loss for homology consistency. It scales to multivariate data, includes a natural-language interface to set Betti targets, supports cross-domain meta-learning and few-shot generation, and provides certified adversarial robustness. On financial, epidemiological, and multi-modal benchmarks, PHINN outperforms statistical and diffusion baselines in topological fidelity (beta-RMSE down 41-63%, transition accuracy up 84%) and matches jump-diffusion models in tail coverage while exceeding them in shape fidelity. All results have 95% confidence intervals.

24.
medRxiv (Medicine) 2026-06-15

Instrumental Activities of Daily Living in Older Adults with Epilepsy: A Cross-Sectional and Longitudinal Multicenter Study

Objective: Instrumental activities of daily living (IADLs) represent a critical but understudied measure of day-to-day function in persons with epilepsy(PWE). In the multicenter Brain Aging and Cognition in Epilepsy (BrACE) study of PWE aged greater than or equal to 55 years, we examined the proportion, clinical correlates, epilepsy-related predictors, and longitudinal trajectory of IADL impairment. Methods: IADLs were assessed using the Functional Activities Questionnaire (FAQ; range=0 to 30; higher=more impaired); a FAQ greater than or equal to 2 defines MCI-level impairment, and a FAQ greater than or equal to 5 defines dementia-level functional impairment. Multivariable logistic regression identified predictors of baseline function. Global cognition (Montreal Cognitive Assessment [MoCA]), individual cognitive measures, and quality of life (QOL) were compared between the impaired and unimpaired groups. Linear regression evaluated predictors of longitudinal functional decline. Results: Of 57 participants (mean age=66.6 years; female=52.6%), 38.6% (n=22) had MCI-level functional impairment and 17.5% (n=10) had dementia-level functional impairment. In univariate analyses, worse FAQ scores were associated with lower education, higher area deprivation index, early-onset epilepsy (EOE less than 60 years), antiseizure medication polytherapy, and epilepsy localization. In multivariable analysis, temporal lobe epilepsy (OR=4.46, 95% CI=1.09, 21.83,p=0.047), EOE(OR=7.14, 95% CI=1.16, 59.97, p=0.046), and lower education(OR=0.70,95% CI=0.49, 0.93, p=0.025) remained independently associated with baseline MCI-level functional-impairment. Lower education (OR=0.55,95% CI=0.29, 0.84, p=0.021) was the only factor associated with dementia-level IADL-impairment. IADL-impaired participants demonstrated lower verbal memory scores (adjusted p=0.041) and MoCA scores (adjusted p

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

Range-Aware Bayesian Optimization for Discovering Diverse Designs within Target Property Windows

arXiv:2606.11574v1 Announce Type: new Abstract: In many materials and product design problems, desirable candidates exhibit properties that fall within an acceptable range rather than achieve a single optimum. Recovering multiple, distinct solutions that satisfy such specifications is also practically valuable, as some candidates may be preferred for reasons of cost, processability, or robustness that are difficult to encode directly in an objective function. Here, we develop a range-aware Bayesian optimization (BO) framework in which the acquisition function directly scores the posterior probability that a candidate satisfies a target range. The framework naturally extends to parallel pursuit of multiple distinct specifications over a shared candidate space. Across benchmark tasks, range-aware acquisition consistently recovers larger and more diverse sets of valid designs than standard BO baselines and recent goal-seeking methods. Its utility is further demonstrated in two practically motivated design case studies involving optimizing reaction conditions for polymer synthesis and sequence-defined oligomer discovery for prescribed optical absorption bands, supported by quantum chemical calculations. These results suggest that range-aware BO can provide a practical and sample-efficient foundation for specification-driven design, particularly when design flexibility and solution diversity are important considerations.