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01.
arXiv (CS.AI) 2026-06-24

Efficient Test-time Inference for Generative Planning Models with OCL Search

arXiv:2606.00618v2 Announce Type: replace Abstract: Generative models have emerged as a powerful paradigm for AI planning, yet their performance remains constrained by the training data distribution. One approach is to improve generated solutions during inference by scaling test-time compute. A more efficient alternative is to optimize the inference process itself. In this paper, we show that a modified version of a classical Open-Closed List (OCL) search provides just such an efficient inference procedure. Our algorithm synergizes two learned components: a generative model that performs fast rollouts from intermediate states and a heuristic model that prioritizes among candidate reasoning paths. Key contributions include novel exploration control mechanisms and integration of learned models within the OCL framework. Across multiple combinatorial planning domains, our approach outperforms both neurosymbolic search baselines and classical solvers in computational efficiency and solution quality.

02.
arXiv (CS.LG) 2026-06-17

Data augmented bootstrap: Unifying confidence interval construction by approximate invariance

arXiv:2606.09049v2 Announce Type: replace-cross Abstract: We propose the data augmented bootstrap (DAB), a framework for constructing confidence intervals from approximately invariant transformations of the data. As special cases, DAB recovers popular methods that rely on exact group symmetries, such as conformal prediction, wild bootstrap for Maximum Mean Discrepancy U-statistics and the recently proposed SymmPI. Meanwhile, DAB also recovers the classical bootstrap method, which exploits the dataset's approximate invariance under uniform sampling of data indices as the dataset size grows. For all DAB methods, we establish theoretical coverage results that interpolate between finite-sample and asymptotic guarantees according to the strength of the invariance, and without assuming a group structure. The approximate invariance is measured in the Kolmogorov distance and, for statistics that satisfy Gaussian universality, reduces to conditional mean and variance matching. This allows us to incorporate data augmentation (DA), a widely used machine learning heuristic based on approximate invariances, into known statistical methods. We empirically test the performance of incorporating DA into bootstrap, wild bootstrap and conformal prediction for simulated settings as well as for image, language and scientific data.

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

Optimizing Appliance Scheduling for Solar Energy Management Using Metaheuristic Algorithms

arXiv:2606.13407v1 Announce Type: new Abstract: Renewable energy is essential for meeting future energy demands; however, solar energy generation, which occurs only during daylight hours often does not align with household consumption patterns. Appliances such as cookers, washing machines, and dryers are typically operated according to user preferred schedules rather than solar energy availability, creating a scheduling optimization problem. The objective is to determine optimal appliance start times to maximize renewable energy utilization while minimizing user inconvenience and adhering to system constraints. This paper presents a metaheuristic approach using Iterated Local Search (ILS) and Simulated Annealing (SA) to optimize appliance start times, while considering appliance operating durations, power consumption, inverter limit, battery state of charge constraints, and solar generation forecasts. Unlike most existing work, the scheduling is extended beyond a single day to accommodate unfinished tasks from previous days (spillover), ensuring operational continuity and enabling sequential operation across multiple days. Experimental results show that the sequential multi-day scheduling framework effectively manages system constraints while ensuring user convenience under exclusive solar generation. These findings also open opportunities for future research on multi-objective trade-offs between investment in equipment of various sizes, return on that investment, and user satisfaction.

04.
arXiv (CS.LG) 2026-06-15

Adaptive Identification and Modeling of Clinical Pathways with Process Mining

arXiv:2512.03787v2 Announce Type: replace Abstract: Clinical pathways are specialized healthcare plans that model patient treatment procedures. They are developed to provide criteria-based progression and standardize patient treatment, thereby improving care, reducing resource use, and accelerating patient recovery. However, manual modeling of these pathways based on clinical guidelines and domain expertise is difficult and may not reflect the actual best practices for different variations or combinations of diseases. We propose a two-phase modeling method using process mining, which extends the knowledge base of clinical pathways by leveraging conformance checking diagnostics. In the first phase, historical data of a given disease is collected to capture treatment in the form of a process model. In the second phase, new data is compared against the reference model to verify conformance. Based on the conformance checking results, the knowledge base can be expanded with more specific models tailored to new variants or disease combinations. We demonstrate our approach using Synthea, a benchmark dataset simulating patient treatments for SARS-CoV-2 infections with varying COVID-19 complications. The results show that our method enables expanding the knowledge base of clinical pathways with sufficient precision, peaking to 95.62% AUC while maintaining an arc-degree simplicity of 67.11%.

05.
arXiv (CS.CL) 2026-06-24

Ensemble Learning for Large Language Models in Text and Code Generation: A Survey

Generative Pretrained Transformers (GPTs) are foundational Large Language Models (LLMs) for text generation. However, individual LLMs often produce inconsistent outputs and exhibit biases, limiting their representation of diverse language patterns. The closed-source nature of many powerful LLMs further restricts industry applications due to data privacy concerns. Inspired by successes in text generation, LLM ensemble techniques are now increasingly explored for code generation. This article reviews these emerging ensemble approaches to enhance understanding, encourage further research, and promote practical implementation in both text and code generation. We categorize LLM ensembles into seven main methods - weight merging, knowledge fusion, mixture-of-experts, reward ensemble, output ensemble, routing, and cascading - analyzing capabilities of those approaches. Our findings highlight key benefits such as improved diversity representation, enhanced output quality, and greater application flexibility. These insights aid model selection for real-world tasks and crucially, lay groundwork for extending ensemble strategies to multimodal LLMs.

07.
medRxiv (Medicine) 2026-06-15

Wellbeing After Stroke-2 (WAterS-2): a feasibility study with process evaluation exploring inclusive, accessible, online psychological support after stroke

Objectives: Explore feasibility and acceptability of upskilling a workforce to deliver a co-developed intervention, based on Acceptance and Commitment Therapy (ACT), to support psychological adjustment post-stroke targeting underserved groups. Design: Multi-site, single-arm feasibility study with embedded mixed-methods process evaluation (ISRCTN17628580). Setting: Four NHS community stroke services across England. Participants: 1. Stroke survivors [≥]18 years of age, [≥]4 months post-stroke, reporting psychological difficulties adjusting to stroke, able to consent and access remote group sessions in English; 2. Group facilitators from NHS stroke services, not ACT specialists. Intervention: WAterS-2: an eight-session, remotely-delivered ACT-informed group intervention. Outcome measures: Recruitment, fidelity, safety, acceptability and perceived value were assessed using fidelity checklists, post-intervention surveys and semi-structured interviews with stroke survivors and facilitators. Clinical outcomes including mood (HADS), wellbeing (ONS4), psychological flexibility (AAQ-ABI), measured post-group and three-months later. Results: Nineteen stroke survivors recruited (mean 9.6 months post-stroke; n=5 (26%) minoritised ethnicities; n=10 (52%) with aphasia). Thirteen facilitators - including two peer support workers - delivered the intervention with fidelity following structured training across four services. Drop-out was low (2/19; 11%); with 15 (79%) attending [≥]5/8 sessions. Remote data collection was feasible (79% follow-up completion), with no adverse events recorded. Acceptability was high: survivors valued peer connection, grounding and mindfulness practices. ACT metaphors were helpful for some but challenging for others, including some with aphasia. Online delivery was suitable but limited informal connection. Facilitators reported increased capability, incorporating ACT skills into routine care. NHS workforce pressures and geographically-constrained referral pathways limited recruitment reach. Conclusions: WAterS-2 is feasible, safe, acceptable and inclusive. A mixed workforce, including NHS peer support workers, can be upskilled to deliver with fidelity. Inclusion of underserved groups is achievable but requires active strategies beyond standard NHS referral routes. Findings inform a provisional logic model and a future pragmatic trial.

08.
arXiv (CS.CV) 2026-06-16

Sinkhorn-CPD: Robust point cloud registration via unbalanced entropic optimal transport

Coherent Point Drift (CPD) is widely used for rigid point cloud registration because of its soft correspondences and closed-form parameter updates. However, CPD's target-side marginal constraint forces every observation, including outliers, to receive exactly unit probability mass. This assumption degrades registration accuracy under heavy outliers and partial overlap. Optimal transport (OT) methods can handle missing mass through unbalanced formulations, but require hand-tuned annealing schedules. In this paper, we propose Sinkhorn-CPD, which replaces CPD's target-side marginal constraint with dual Kullback-Leibler penalties, allowing the algorithm to discard outliers on both sides. The resulting formulation is a fully unbalanced entropic optimal transport problem, which can be efficiently solved by generalized Sinkhorn iterations. Moreover, Sinkhorn-CPD preserves the closed-form Procrustes and variance updates of CPD. In our method, the variance sigma^2 plays the role of the entropic regularization parameter, which induces an automatic annealing schedule from diffuse to sharp correspondences without manual temperature tuning. Experiments on synthetic, cross-category, and scan-to-CAD benchmarks show that Sinkhorn-CPD achieves state-of-the-art accuracy, with strong robustness to outliers and partial overlap.

09.
arXiv (quant-ph) 2026-06-24

Testing quantum-like markers in neural dynamics

arXiv:2508.21490v3 Announce Type: replace-cross Abstract: We propose two experiments for identifying quantum markers in neural data based on quantum variants of well-known equations for neural activity that describe electrical signal propagation on axonal arbors and dendrites. These include (i) testing if power spectra from subthreshold oscillations in neuronal cultures follow the classical Fitzgugh-Nagumo equations or a recently introduced quantum variant of them and (ii) testing if propagation statistics of electrical activity in axons follow the classical diffusive cable equation or a quantum variant of it.

10.
arXiv (CS.CL) 2026-06-12

NOVA: NOise-aware Verbal Confidence CAlibration for Robust Large Language Models in RAG Systems

Accurately assessing model confidence is essential for deploying large language models (LLMs) in mission-critical factual domains. While retrieval-augmented generation (RAG) is widely adopted to improve grounding, confidence calibration in RAG settings remains poorly understood. We conduct a systematic study across four benchmarks, revealing that LLMs exhibit poor calibration performance especially when noisy contexts are retrieved. Specifically, contradictory or irrelevant evidence tends to exacerbate the model's overconfidence issue. To address this, we propose NOVA Rules (NOise-Aware Verbal Confidence CAlibration Rules) to provide a principled foundation for resolving overconfidence under noise. We further design NOVA, a noise-aware calibration framework that synthesizes supervision from ~2K HotpotQA examples guided by these rules. By performing supervised fine-tuning (SFT) with this data, NOVA equips models with intrinsic noise awareness without relying on stronger teacher models. Empirical results show that NOVA yields substantial gains, improving ECE scores by 10.9% in-domain and 8.0% out-of-domain. By bridging the gap between retrieval noise and verbal calibration, NOVA paves the way for both accurate and epistemically reliable LLMs.

11.
arXiv (CS.CL) 2026-06-24

CANDLE: Character-level Arabic Noise Deduplication using Lightweight Encoder

Handling repeated characters in text can be tricky, since they can represent either the correct spelling of a word or informal character elongation often seen in social media posts. We present CANDLE, a lightweight system for character-level Arabic noise deduplication that addresses this challenge without relying on handcrafted rules, dictionaries, or morphological analyzers. At the heart of CANDLE is a novel application of Connectionist Temporal Classification (CTC) to this task, a formulation not previously explored for character deduplication, which frames normalization as a sequence alignment problem over a character-based encoder. Evaluated on three benchmarks spanning clean newspaper, manually curated ambiguous cases, and real-world social media text, the CTC model achieves a Sentence Error Rate (SER) as low as $5.37\%$ and consistently outperforms a classification-based baseline by a large margin. To reduce inference overhead, we distill the 6-layer CTC model into a 2-layer student, achieving a $3\times$ depth reduction with minimal performance degradation. Beyond deduplication accuracy, normalization yields a practical downstream benefit: a relative reduction in tokenizer fertility of up to $12.8\%$ across a diverse set of Arabic LLM tokenizers, directly lowering inference costs and improving context window utilization. We release all code and models publicly to support reproducibility and advance future research\footnote{https://github.com/abjadai/candle}.

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

A2D2: Fine-Tuning Any-Length Discrete Diffusion for Adaptive Decoding

arXiv:2606.13565v1 Announce Type: new Abstract: Discrete diffusion models offer a simple and stable likelihood-based framework for sequence generation, recently extended to any-length settings via token insertion. Principled reward-guided fine-tuning for any-length discrete diffusion, however, remains largely unexplored. We introduce Fine-Tuning Any-Length Discrete Diffusion for Adaptive Decoding (A2D2), a unified framework for reward-guided fine-tuning of any-length discrete diffusion models via joint optimization of the insertion and unmasking policies together with a quality-based inference schedule. We derive the Radon-Nikodym derivative for the joint insertion-unmasking path measures, enabling theoretically guaranteed convergence to the intractable reward-tilted sequence distribution without requiring target samples. Building on this, we establish unmasking and insertion quality as tractable approaches for minimizing decoding error and introduce the Adaptive Joint Decoding (AJD) loss, which provably yields the optimal path measure that generates the reward-tilted distribution. Empirically, A2D2 improves reward optimization while enhancing generation flexibility and accuracy over prior fixed-length fine-tuning and inference-time guidance methods.

13.
arXiv (CS.CV) 2026-06-12

On Pitfalls of $RemOve-And-Retrain$: Data Processing Inequality Perspective

The RemOve-And-Retrain (ROAR) benchmark is widely used to evaluate feature attribution methods, yet its validity remains underexplored from an information-theoretic perspective. We show that model- and data-agnostic post-processing of attribution maps (transformations that, by the data processing inequality, cannot add information about the decision function) can often improve ROAR scores. This means that an improved ROAR ranking is not, by itself, evidence that an attribution map carries more information about the model. We trace this failure mode to a bias toward spatially blurry masks. Experiments on CIFAR-10, SVHN, and CUB-200 show a consistent association between blurriness and ROAR performance, a pattern that also appears in the ROAD variant. We provide guidelines for more cautious removal-based benchmarking, with implications for validating mechanistic understanding of neural network internals.

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

Toward the Whole Picture: Accumulative Fingerprint Mapping and Reconstruction for Small-Area Mobile Sensors

Small-area fingerprint sensing on mobile devices creates a fundamental mismatch between acquisition and recognition: each touch captures only a tiny, pose-varying local patch, while reliable biometric matching ultimately requires a stable and sufficiently complete fingerprint representation. Existing pipelines largely cope with this mismatch by treating repeated touches as independent partial templates, which leads to repeated registration, repeated matching, and no guarantee of adequate global coverage. In this paper, we advocate a different formulation, namely accumulative fingerprint mapping and reconstruction for small-area mobile sensing. Rather than matching every partial patch separately, the proposed perspective converts a sequence of local observations into a unified fingerprint state that is progressively refined as new touches arrive and can be matched only once after consolidation. As a concrete baseline, we present a classical pipeline that performs patch-wise structural feature extraction, feature-level registration and fusion, fingerprint map construction, and phase-based ridge reconstruction. More importantly, we position this baseline within a broader mobile fingerprint framework that integrates structured token learning, two-stage pose reasoning, and diffusion-based generative reconstruction. This viewpoint reframes mobile fingerprint recognition from multi-capture multi-match processing to accumulative map building, state refinement, and one-shot matching, offering a principled route toward efficient, pose-robust, and deployment-friendly biometrics for small-area mobile platforms. The baseline implementation has been publicly released at https://github.com/XiongjunGuan/FpReconstruction.

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

A Large-Scale Multi-Dimensional Empirical Study of LLMs for Conversation Summarization

Despite the significant advancement of LLMs in conversation summarization, their evaluation remains limited by insufficient scenarios, input lengths, and sample sizes. Furthermore, existing benchmarks often omit frontier reasoning systems and efficient small models, or lack fine-grained, multi-dimensional assessments. To bridge these gaps, we propose OmniCSEval, a unified benchmark comprising 1,800 diverse conversations across six real-world scenarios, featuring context lengths ranging from 128 to 32k tokens. For fine-grained evaluation, we employ a bidirectional fact-checking framework that integrates key fact matching to assess completeness and conciseness, alongside summary fact verification to evaluate faithfulness. To ensure reliable assessment, we establish a human-LLM collaborative pipeline for key fact extraction and a multi-LLM consensus verifier for summary fact decomposition. Leveraging this framework, we evaluate 28 LLMs across four distinct categories grouped by reasoning capability and model scale. Our extensive empirical study reveals critical insights regarding the cross-scenario challenges current LLMs continue to face, the impacts of reasoning and scale, and the efficiency and adaptability of reasoning models. We also provide guidance for system selection in real-world deployments.

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

Unassigned Agents in Compilation-based Multi-agent Path Finding

arXiv:2606.15797v1 Announce Type: new Abstract: Compilation-based techniques represent an important stream of solvers for multi-agent path finding (MAPF) due to their modularity and adaptability for non-standard variants of the problem. While in the standard MAPF the task is to navigate all agents from their initial positions to given individual goal positions without any collision, variants where a different requirement for agents is used are also relevant. Such a variant is MAPF with unassigned agents (UA-MAPF) where some agents have the same setting as in the standard MAPF with initial positions and goals while the remaining agents have the initial position but have no goal - unassigned agents. Despite unassigned agent do not need to reach any goal position they have to be moved out of the way of the standard agents if needed which represent a specific challenge. We show in this paper that UA-MAPF can be expressed in recent compilation-based techniques for MAPF based on formulating the problem as Boolean satisfiability, namely we adapt SMT-CBS and NRF-SAT, the recent solvers based on counterexample guided abstraction refinement and non-refined abstractions.

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

Advancing DialNav through Automatic Embodied Dialog Augmentation

arXiv:2606.19948v1 Announce Type: new Abstract: For embodied agents capable of physical interaction, the capability to create and understand dialog is crucial to ensure both safety and effectiveness. While DialNav[han2025dialnav] provides a framework for holistic evaluation of the dialog–execution loop in photorealistic indoor navigation, its performance remains limited by a critical scarcity of training data (2K episodes). To address this, we propose an automatic generation pipeline, and construct the RAINbow dataset, a large-scale training dataset with 238K episodes for DialNav. Our pipeline converts existing VLN datasets into multi-turn dialog and creates cost-efficient and high-quality dataset. Then, we introduce two additional complementary advances to unlock the data's full potential: (1) Dual-Strategy Training, a navigation training scheme to align the navigation training with the dynamic dialog-navigation loop, and (2) a localization model that leverages VLN knowledge. By combining these complementary solutions, our model substantially outperforms the baseline in success rate on both Val Seen (58.24, +89\%) and Val Unseen (29.05, +100\%) splits, establishing a new state of the art.

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

SkillWiki: A Living Knowledge Infrastructure for Agent Skills

While knowledge is managed through Wikipedia and software through GitHub, agent skills still lack an infrastructure for large-scale production, governance, and evolution. SkillWiki is a living knowledge infrastructure that supports the organization, grounding, and continuous evolution of agent skills by transforming heterogeneous knowledge into reusable skill assets linked to their originating evidence. Our demonstration presents the complete skill lifecycle, from knowledge ingestion and skill production to provenance-aware exploration, governance, and execution-driven evolution. SkillWiki highlights a future in which knowledge, skills, and execution experience co-evolve within a shared infrastructure. The live demonstration and source code are publicly available at https://github.com/Huangdingcheng/SkillWiki.

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

LoSoNA: A Benchmark for Local Social Norm Adaptation in Group Conversations

Online group chats are social spaces with local conversational norms that are rarely stated explicitly. The ability and willingness of LLM-based agents to recognize and adapt to these norms remains mostly unexplored. We introduce LoSoNA, a benchmark for local social norm adaptation in multi-party chat. Each scenario gives a subject model a curated group-chat transcript in which non-subject participants demonstrate a hidden local norm, followed by a final elicitor turn that forces a response revealing whether the subject has inferred that norm. We evaluate eight frontier and open-weight models under four prompting conditions that vary how explicitly the model is told to treat the prior conversation as evidence for how it should answer. Naive prompting remains limited for most models; explicit norm-aware prompting helps unevenly, with Gemini 3.1 Pro reaching $84.2\%$ and Claude Fable 5 reaching $81.6\%$, while several other models show small gains or regressions. LoSoNA contributes to recent calls for evaluating LLM social capabilities by testing whether models can infer local conversational norms from precedent and use them in a one-turn group-chat response.

20.
arXiv (CS.LG) 2026-06-19

Recurrent neural networks approximate continuous functions

arXiv:2606.20325v1 Announce Type: new Abstract: Classical approximation theorems ask for a new neural network whenever the target accuracy is improved. This paper studies the opposite possibility: can the network be chosen once and for all, and can accuracy be bought only by letting it run longer? We prove that this is possible for every continuous function on [-1,1]. More precisely, each such function is uniformly approximated by the time evolution of a single ReLU recurrent neural network with fixed weights and fixed hidden dimension. The mechanism behind the construction is a new intermediate model, the Turing machine with neural units (TMNU). This model retains the algorithmic freedom needed to implement polynomial approximation schemes, while remaining rigid enough to be simulated by RNNs with explicit bounds on hidden dimension and weight magnitude. The resulting convergence rates reflect the underlying polynomial approximation rates. We complement the construction with minimax lower bounds showing that runtime is not merely a proof artifact, but an unavoidable resource in this fixed-network approximation paradigm.

21.
arXiv (CS.CL) 2026-06-19

Target-Side Paraphrase Augmentation for Sign Language Translation with Large Language Models

Sign language translation (SLT) remains constrained by the limited availability of paired sign-video/text corpora and by the heavy-tailed vocabularies typical of real-world datasets. We study a target-side augmentation strategy in which a large language model (LLM) generates controlled paraphrase variants of the reference spoken-language sentence while the sign input remains unchanged. Concretely, we use GPT-4o to produce semantically faithful variants of the training targets and train a Signformer-style pose-based Transformer under a two-stage schedule: pre-training on the augmented corpus followed by fine-tuning on the original references. We evaluate this strategy on three datasets that span complementary challenges: PHOENIX14T (German Sign Language), a real-world corpus with moderate lexical diversity; the Greek Sign Language Dataset with highly controlled, repetitive recordings; and LSA-T (Argentinian Sign Language), a naturalistic corpus with a large vocabulary and severe long-tail sparsity. This range allows us to characterize precisely when and why target-side augmentation is beneficial. On PHOENIX14T, augmentation improves BLEU-4 from 9.56 to 10.33, demonstrating that paraphrastic exposure helps the decoder generalize beyond memorized reference phrasing. The near-saturated GSL baseline and the extremely sparse LSA-T setting reveal the limits of the approach: in both cases, single-reference lexical overlap metrics are insufficient to capture the full picture, motivating a complementary semantic evaluation. To our knowledge, this is the first study to examine LLM-generated target-side paraphrases as an augmentation mechanism for SLT, and the first to apply an LLM-as-a-Judge evaluation protocol to SLT. This complementary evaluation reveals gains in semantic fidelity that lexical overlap metrics understate.

22.
arXiv (CS.CV) 2026-06-16

Structural Energy Guidance for View-Consistent Text-to-3D Generation

Text-to-3D generation based on diffusion models often suffers from the Janus problem, leading to inconsistent geometry across viewpoints. This work identifies viewpoint bias in 2D diffusion priors as the main cause and proposes Structural Energy-Guided Sampling (SEGS), a training-free and plug-and-play framework to improve multi-view consistency. SEGS constructs a structural energy in the PCA subspace of U-Net features and injects its gradient into the denoising process. It can be easily integrated into SDS/VSD pipelines without retraining. Experiments show that SEGS reduces the Janus Rate by about 10% on average and improves View-CS scores across multiple baselines, including DreamFusion, Magic3D, and LucidDreamer. This method effectively alleviates viewpoint artifacts while preserving appearance fidelity, providing a flexible solution for high-quality text-to-3D content generation.

23.
arXiv (CS.LG) 2026-06-11

Program Evaluation with Remotely Sensed Outcomes

arXiv:2411.10959v5 Announce Type: replace-cross Abstract: We study causal inference in experiments and quasi-experiments, where the economic outcome is imperfectly measured by a remotely sensed variable. The remotely sensed variable is low-cost, scalable, and predictive of the economic outcome in observational data; examples include satellite imagery and mobile phone activity. We model the remotely sensed variable as post-outcome: variation in the economic outcome causes variation in the remotely sensed variable. For example, changes in environmental quality cause changes in satellite imagery, not vice versa. Under this assumption, we propose a formula to nonparametrically identify the causal parameter by combining experimental and observational data. We develop a method for n^{-1/2} inference that is robust to misspecification and that does not restrict the algorithms used to process remotely sensed variables.

24.
bioRxiv (Bioinfo) 2026-06-19

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

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.

25.
arXiv (CS.CL) 2026-06-24

Escaping the Self-Confirmation Trap: An Execute-Distill-Verify Paradigm for Agentic Experience Learning

Experience-driven self-evolution is critical for large language model (LLM) agents to improve through open-world interaction. However, existing experience learning methods mostly rely on single-agent loops, where the same agent executes tasks, summarizes outcomes, and determines memory content. This setup makes agents vulnerable to the Self-Confirmation Trap: wrong-but-self-consistent trajectories are misidentified as successful experience, leading to cumulative errors during retrieval and reuse. To address this issue, we propose EDV, an Execute-Distill-Verify framework for reliable experience learning. In the Execute stage, multiple heterogeneous agents explore the same task space in parallel to generate diverse candidate trajectories. In the Distill stage, a dedicated third-party agent comparatively analyzes these trajectories to produce candidate experiences, reducing executor-centric summarization bias. In the Verify stage, the execution group validates candidates via a consensus mechanism, and only approved experiences are written into shared or private memory. By decoupling the three stages, EDV transforms experience learning from isolated self-reflection into collaborative construction, filtering erroneous and noisy content before memory insertion. We evaluate EDV on three challenging long-horizon benchmarks: tau2-bench, Mind2Web and MMTB. Results show EDV consistently outperforms strong baselines, validating that reliable experience construction is essential for robust agent self-evolution. Our code is available at https://github.com/shidingz/EDV.