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01.
arXiv (CS.AI) 2026-06-16

Direction-Conditioned Policies via Compositional Subgoal Scoring for Online Goal-Conditioned Reinforcement Learning

arXiv:2606.16515v1 Announce Type: cross Abstract: Hamilton-Jacobi-Bellman theory implies that the optimal goal-conditioned action depends on the goal only through the gradient of the goal-reaching distance at the current state, yet standard online GCRL still conditions the actor on the raw goal – a signal that is geometrically uninformative when the goal is far from the data distribution. We propose Direction-Conditioned Policies (DCP), a fully online method that decomposes goal-reaching into two components sharing one InfoNCE representation $\psi$: a subgoal-scoring step that selects a visited state $z_t$ aligned with the final goal $g$ in $\psi_g$, and a direction-conditioned actor that consumes the unit direction $d_t$ and magnitude $r_t$ from $\psi(s_t)$ to $\psi(z_t)$. The two components train jointly, factor cleanly at deployment (subgoal scoring is removed, while direction conditioning remains with $g$ in place of $z_t$), and admit independent modification at the same $(d_t,r_t)$ interface. We prove three results. First, direction sufficiency under HJB: the optimal action under control-affine dynamics depends on the goal only through the value gradient. Second, a quantitative bound showing that, under mild conditions on the learned representation and assuming the scoring rule returns an on-path $z_t$, the actor's conditioning input at training and at deployment coincide up to representation error and geodesic slack. Third, a controllable-subspace characterization of when directional conditioning fails. Across nine environments, DCP improves over Contrastive RL on most final metrics, with the largest gains on manipulation and obstacle-interaction tasks; a qualitative analysis of the learned $\psi$-distance landscape shows the contrastive representation behaves as an online quasimetric encoding environment topology, and the single failure case (AntSoccer) localizes to a learned-gradient pathology that the theory anticipates.

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

HOLO-MPPI: Multi-Scenario Motion Planning via Hierarchical Policy Optimization

arXiv:2606.16480v1 Announce Type: cross Abstract: Robots deployed in the real world must plan motions across diverse scenarios without per-scenario retuning. End-to-end reinforcement learning (RL) can generalize across scenarios but often becomes brittle under distribution shift, reward misspecification, and stochastic interactions. Model predictive path integral (MPPI) control enables strong real-time refinement without gradients, but its performance depends on a well-shaped sampling prior, while manually designing the priors does not scale to multi-scenario deployment. We present HOLO-MPPI (High-level Offline, Low-level Online MPPI), a multi-scenario motion planning framework that combines high-level policy learning with low-level stochastic optimal control. Offline, we learn a high-level policy that proposes scenario-robust plans in an abstract action space, with a learned world model for online rollout. Online, the policy serves as a data-driven prior generator that parameterizes MPPI's sampling distribution conditioned on the current observation and goal. MPPI then optimizes low-level control sequences around this prior in real time to adapt to local disturbances. We instantiate HOLO-MPPI in autonomous driving by designing an effective high-level action space and tailored model architectures. Our evaluation across diverse driving scenarios shows that HOLO-MPPI improves upon MPPI and end-to-end RL baselines while maintaining real-time control.

03.
arXiv (CS.AI) 2026-06-16

AI systems out-persuade expert humans

arXiv:2606.16475v1 Announce Type: cross Abstract: Many societal decisions are settled by contests of persuasion. Conversational AI is a powerful new entrant in these contests, but whether it can out-persuade skilled and highly incentivized humans has remained unclear. Here, in a series of four preregistered experiments (n = 18,978 conversations from 6,923 people), we pitted AI systems against a range of human persuaders, including laypeople, winners of a separately preregistered four-round online persuasion tournament, professional canvassers, and world championship debaters. We found that AI systems were reliably more persuasive than expert humans, even when expert humans chose their issues, researched in advance, underwent hours of live, structured practice, and were incentivized with {\pounds}1,000 cash bonuses. In a follow-up study, AI's advantage persisted after experts received a coaching tool that let them practice against the AI that beat them, review their performance history, and see what AI would have said at key moments. We found converging evidence that AI's advantage stemmed from rapidly deploying larger quantities of information: after coaching, expert humans could tie an AI constrained to respond at human speeds and with human-length messages. In a final study, we show that AI's advantage extends to consequential real-world behavior: AI was nearly 3x more effective than professional canvassers from a UK fundraising firm at raising real-money donations to Save the Children. Together, these results establish that frontier AI systems out-persuade expert humans in conversation, with significant implications for political communication.

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

ShoppingBench: A Real-World Intent-Grounded Shopping Benchmark for LLM-based Agents

Existing benchmarks in e-commerce primarily focus on basic user intents, such as finding or purchasing products. However, real-world users often pursue more complex goals, such as applying vouchers, managing budgets, and finding multi-products seller. To bridge this gap, we propose ShoppingBench, a novel end-to-end shopping benchmark designed to encompass increasingly challenging levels of grounded intent. Specifically, we propose a scalable framework to simulate user instructions based on various intents derived from sampled real-world products. To facilitate consistent and reliable evaluations, we provide a large-scale shopping sandbox that serves as an interactive simulated environment, incorporating over 2.5 million real-world products. Experimental results demonstrate that even state-of-the-art language agents (such as GPT-4.1) achieve absolute success rates under 50% on our benchmark tasks, highlighting the significant challenges posed by our ShoppingBench. In addition, we propose a trajectory distillation strategy and leverage supervised fine-tuning, along with reinforcement learning on synthetic trajectories, to distill the capabilities of a large language agent into a smaller one. As a result, our trained agent achieves competitive performance compared to GPT-4.1.

05.
bioRxiv (Bioinfo) 2026-06-14

FENNEC: Fine-Tuned Ensemble Neural Networks Accelerate Chemically Modified siRNA Design and Screening

Small interfering RNAs (siRNAs) are a clinically validated therapeutic modality, yet designing potent chemically modified siRNAs remains a costly and iterative process, limited by scarce public data. Computational prediction of siRNA efficacy is therefore essential for rational design and accelerated preclinical development. However, despite the critical role of chemical modifications in therapeutic performance, current state-of-the-art machine learning methods either are not designed to model the chemical diversity of therapeutic siRNAs, or exhibit poor generalization performance. Here, we present FENNEC (Fine-Tuned Ensemble of Neural Networks for siRNA Efficiency Characterization), a machine-learning framework for predicting siRNA activity across chemically diverse design spaces. To support this effort, we curated the largest patent-derived dataset to date of chemically modified siRNAs from 42 patents using OCR-based table extraction and stringent filtering. FENNEC combines temporal convolutional networks with thermodynamic descriptors, experimental covariates, and embeddings from RNA foundation models to capture both local chemical determinants and broader target-context information. Importantly, we show that language-model-derived embeddings provide meaningful higher-order representations of target transcripts, particularly in data-scarce settings. FENNEC achieved robust predictive performance across both gene-level and scaffold-level validation settings, with additional experimental validation on a novel AHSA1-targeting dataset further supporting its generalizability across chemically modified siRNAs. In benchmarking, FENNEC outperformed classical machine-learning and state-of-the-art deep learning models, demonstrating generalization to unseen chemistry. Model interpretation recovered established design principles, including position-specific effects of glycol nucleic acid, 2'-fluoro modifications, and phosphorothioate backbones. Furthermore, in silico perturbation analyses suggest that FENNEC can serve not only as a predictive model, but also as an oracle for the design and optimization of chemically modified siRNAs. Together, our work addresses a key gap in the field by enabling chemically aware deep learning for siRNA design, supported by a large and diverse collection of chemically modified siRNA measurements.

06.
bioRxiv (Bioinfo) 2026-06-11

Viability of engineered AAVs via protein language models

Capsid engineering has greatly improved the performance of recombinant AAV vectors used for gene therapy. One commonly used strategy is the insertion of a short, 7-mer, peptide into surface-exposed loops to modify receptor interactions and enhance cell entry. While effective in receptor retargeting and improved transduction, these insertions might destabilize the capsid protein, hinder assembly, and thus limit production. While previous attempts have used deep mutational scanning and AI to predict which insertions are viable, there is lack in understanding the structural consequences of these peptide insertions at the amino-acid level. Here we combined experiments, deep sequencing and large protein language models to gain insight on the impact of 7-mer insertions on the VR-VIII region. We first characterize the biochemical properties of viable insertions, thus identifying which residues are well tolerated, and which should instead be avoided. We then focus on the nearby context of those insertions, by studying the effect of the linkers, either for highly diverse libraries or for individual variants known for their efficiency. Next, we study the broader context, by extending our analysis to the whole capsid sequence, and identifying regions that can tolerate insertions without long-ranged structural deformations that could affect capsid functionality. We conclude with a cross-serotype comparison and a viability analysis of tens of previously engineered variants. Our work showcases how AI can uncover structure-function rules governing the success of engineered AAV capsids.

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

Improving Alignment Between Human and Machine Codes: An Empirical Assessment of Prompt Engineering for Construct Identification in Psychology

Due to their architecture and vast pre-training data, large language models (LLMs) demonstrate strong text classification performance. However, LLM output - here, the category assigned to a text - depends heavily on the wording of the prompt. While literature on prompt engineering is expanding, few studies focus on classification tasks, and even fewer address domains like psychology, where constructs have precise, theory-driven definitions that may not be well represented in pre-training data. We present an empirical framework for optimizing LLM performance for identifying constructs in texts via prompt engineering. We experimentally evaluate five prompting strategies – codebook-guided empirical prompt selection, automatic prompt engineering, persona prompting, chain-of-thought reasoning, and explanatory prompting - with zero-shot and few-shot classification. We find that persona, chain-of-thought, and explanations do not fully address performance loss accompanying a badly worded prompt. Instead, the most influential features of a prompt are the construct definition, task framing, and, to a lesser extent, the examples provided. Across three constructs and two models, the classifications most aligned with expert judgments resulted from a few-shot prompt combining codebook-guided empirical prompt selection with automatic prompt engineering. Based on our findings, we recommend that researchers generate and evaluate as many prompt variants as feasible, whether human-crafted, automatically generated, or ideally both, and select prompts and examples based on empirical performance in a training dataset, validating the final approach in a holdout set. This procedure offers a practical, systematic, and theory-driven method for optimizing LLM prompts in settings where alignment with expert judgment is critical.

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

Latent World Recovery for Multimodal Learning with Missing Modalities

arXiv:2606.12362v1 Announce Type: cross Abstract: We study multimodal learning under missing modalities, with particular motivation from bioscience applications in which heterogeneous modalities are often only partially available when decisions need to be made. We propose Latent World Recovery (LWR), a framework built on two key ideas: (i) modality-specific embeddings from different modalities are aligned in a shared latent space, and (ii) a unified representation is constructed by fusing only the embeddings of the modalities that are actually available at both training and inference time. Rather than imputing missing modalities or requiring a fixed modality set, LWR treats each modality as a partial perception of an underlying latent state and performs availability-aware representation learning directly from the observed modalities. This combination of neighbor-based latent alignment and availability-aware modality fusion enables robust multimodal prediction under partial observation, while avoiding error propagation from explicit reconstruction of missing modalities. We evaluate the proposed framework on real-world incomplete multi-omics benchmarks and demonstrate that it provides an effective approach to downstream tasks such as cancer phenotype classification and survival prediction.

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

Bridging Passive and Active: Enhancing Conversation Starter Recommendation via Active Expression Modeling

Large Language Model (LLM)-driven conversational search is shifting information retrieval from reactive keyword matching to proactive, open-ended dialogues. In this context, Conversation Starters are widely deployed to provide personalized query recommendations that help users initiate dialogues. Conventionally, recommending these starters relies on a closed "exposure-click" loop. Yet, this feedback loop mechanism traps the system in an echo chamber where, compounded by data sparsity, it fails to capture the dynamic nature of conversational search intents shaped by the open world. As a result, the system skews towards popular but generic suggestions. In this work, we uncover an untapped paradigm shift to shatter this harmful feedback loop: harnessing user "free will" through active user expressions. Unlike traditional recommendations, conversational search empowers users to bypass menus entirely through manually typed queries. The open-world intents in active queries hold the key to breaking this loop. However, incorporating them is non-trivial: (1) there exists an inherent distribution shift between active queries and formulated starters. (2) Furthermore, the "non-ID-able" nature of open text renders traditional item-based popularity statistics ineffective for large-scale industrial streaming training. To this end, we propose Passive-Active Bridge (PA-Bridge), a novel framework that employs an adversarial distribution aligner to bridge the distributional gap between passively recommended starters and active expressions. Moreover, we introduce a semantic discretizer to enable the deployment of popularity debiasing algorithms. Online A/B tests on our platform, demonstrate that PA-Bridge significantly boosts the Feature Penetration Rate by 0.54% and User Active Days by 0.04%.

10.
medRxiv (Medicine) 2026-06-16

The Target48 Neurodegeneration Panel: A Novel Tool for Profiling Protein Signatures in Neurodegenerative Disorders

Introduction: Novel tools for absolute quantification of established and emerging fluid neuro-biomarkers are required to advance diagnostic studies and improve biological insights. Methods: We conducted an extensive analytical and clinical validation of the Olink Target 48 Neurodegeneration panel (T48 Neuropanel) in 352 paired CSF and plasma samples from cognitively unimpaired controls (CU), Alzheimer dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), n=44 per group. Comparisons with benchmark assays were performed. Results: Good detectability (CSF: 31 out of 42 assays; plasma: 38 out of 42 assays) and technical performance was observed. Benchmark assays showed good correlations, supporting method transformation formulas. Next to emerging biomarkers (MMP10, ITGB2), discriminative performance was excellent in AD: CSF pTau217: AUC=1; FTD: plasma NfL: AUC=0.952; and DLB: CSF DDC: AUC=0.901. Discussion: This analytical and clinical validation of the T48 Neuropanel highlights initial cut-offs and emerging biomarkers to aid clinical studies for the diagnosis, prognosis, and monitoring of neurodegenerative diseases. Highlights: The T48 Neuropanel shows robust analytical performance, with high detectability across both plasma and CSF matrices. The T48 Neuropanel validates established (i.e., pTau217, Abeta42, NfL, and GFAP) and emerging biomarkers (i.e., DDC, MMP10, ITGB2, ITGAM, NPTX2, NPTXR, SMOC1, sTREM1, and sTREM2) in CSF and plasma. CSF NfL, GFAP, ITGB2, and ITGAM and plasma GFAP were dysregulated across AD, FTD, and DLB dementias. -The multiplex design of the T48 Neuropanel enables rich biological interpretation by simultaneously quantifying established and emerging neurodegeneration biomarkers. Importantly, the inclusion of absolute quantification facilitates the establishment of cut-offs, supporting its potential for clinical translation.

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

MinhwaNet: Faithful but Insufficient Object Grounding in Korean Folk Painting

Korean folk painting (minhwa) is built from a small vocabulary of auspicious symbols, a tiger for protection, a pair of birds for marital harmony, a peony for wealth, that recur across many of its painted genres. This suggests an obvious computational approach, identify which symbols appear in a painting and read the genre from the inventory. Working with a public corpus that pairs whole paintings, eight-field bilingual curatorial captions, and a separate set of expert object crops, we find that this approach does not work. A model given only a list of which symbols a painting contains predicts the genre far worse than a model that fuses the image with the curatorial text, and forcing the genre representation to be object-grounded actively hurts accuracy. The visual evidence on which the genre prediction rests is nonetheless localized and inspectable. A leakage-safe object evidence map projected from a part-level detector is spatially faithful to where curators isolated symbolic objects and to a patch-based surrogate's own gradient saliency. We name this configuration a faithful-but-insufficient dissociation. The part-level explanation is honest about what the part-level model sees, yet the genre target turns on how symbols are arranged rather than on which ones appear. The same lens separates a content label that survives transfer to held-out source institutions, genre, from a style label that does not, era, a prediction we confirm on two further labels in the corpus. We release the multimodal system, a worked-example reading of one painting's evidence map against its catalogue, and a set of evaluation cautions that recur in long-tailed heritage collections.

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

When English Isn't the Best Teacher: Source Language Effects in Cross-Lingual In-Context Learning

Cross-lingual transfer in multilingual NLP has been widely explored in supervised fine-tuning contexts, where factors like data availability and linguistic similarity largely determine transfer quality. As the field shifts toward few-shot In-Context Learning (ICL), it is often presumed that insights from fine-tuning carry over unchanged. Yet this assumption has not been rigorously evaluated, leaving open the question of how to choose source languages for cross-lingual ICL. We conduct a broad empirical study of cross-lingual transfer in ICL spanning seven tasks, six models, and a typologically diverse set of languages. We further analyze language confusion, a key obstacle for generative tasks in cross-lingual ICL. Our results show that conventional fine-tuning-based expectations do not consistently apply in the ICL regime and point to alternative heuristics for selecting source languages effectively.

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

The Tone of Awareness: Topic, Sentiment, and Toxicity Maps During Mental Health Month on TikTok

Despite raising concerns about the mental health effects associated with the usage of TikTok, little is known about how related content is framed by creators and received by audiences. We collect the content of 28,341 TikTok videos and 80,130 comments from Mental Health Awareness Month (May) in 2023 and 2024 via the TikTok Research API, and study how the tone of awareness varies across topics and years. We characterize "tone" as the emotional and interpersonal framing of mental health discourse, operationalized through sentiment and toxicity measures. We extract topics from video text using BERTopic and log-odds keywords, then quantify topic-conditioned sentiment (XLM-T) and toxicity (Detoxify) separately for video transcriptions and comments. Sentiment captures the affective valence of content, while toxicity reflects the presence of harmful or abusive language. We find a stable set of recurring themes across years, spanning clinical conditions, emotional disclosure, self-care, and campaign-oriented content, with engagement highly skewed toward a small subset of topics. All sentiment and toxicity analyses are computed separately for video content and comments, allowing us to distinguish between content production and audience reception. Sentiment in videos is often negative for emotionally charged topics, while comments tend to shift toward more mixed or positive polarity, especially for suicide prevention. Toxicity is low in median overall, but exhibits longer-tailed outliers in comments than in videos that are more pronounced in comments and concentrated in specific topics (e.g., "Duet", "Suicide Prevention", and "Psychisch"). Overall, our results provide a topic-level decomposition of mental health discourse on TikTok during awareness-month campaigns.

14.
Nature (Science) 2026-06-22

Stereoretentive decarbonylative C(sp<sup>3</sup>)-C(sp<sup>3</sup>) cross-coupling

作者:

While C(sp3)–C(sp3) bond-forming cross-coupling methods have become more common, stereocontrolled bond-formation remains a challenge,1 despite its importance for drug discovery, where there is a emerging demand for molecules with increased sp3 character.2-4 Enantiospecific cross-coupling approaches would complement advances in enantioselective coupling,5-8 but have been limited to specialized substrates with lower availability5,9 because stereospecific oxidative addition of more abundant chiral alkyl electrophiles is unknown.10 Inspired by the classic, stereoretentive Curtius rearrangement,11 herein we disclose a catalytic strategy that proceeds by an analogous stereoretentive decarbonylation step to form a versatile chiral alkylnickel intermediate from easily-available chiral amino-acid and α-hydroxy-acid derivatives. The chiral alkylnickel intermediates decompose and/or racemize on the order of minutes, but are sufficiently stable to enable stereoretentive cross-electrophile coupling12 with alkyl radicals (derived from alkyl iodides) at relatively low temperature (22-40 °C). This mechanistic strategy provides a straightforward approach to stereocontrolled C(sp3)–C(sp3) bond formation, including diastereomers that are inaccessible by stereoselective radical mechanisms. The “metallo-Curtius” strategy described in this study lays a mechanistic foundation for the development many new stereospecific cross-coupling reactions.

15.
arXiv (quant-ph) 2026-06-12

More efficient Clifford+T synthesis for small-angle rotations and application to Trotterization

arXiv:2605.31544v2 Announce Type: replace Abstract: Clifford+T synthesis of rotation gates is an important routine in fault-tolerant quantum compilation. While Clifford+T synthesis is scalable, it has a high overhead of tens of T gates per rotation in practice, translating to high resource estimates for many fault-tolerant algorithms. However, these well-known results, including those using probabilistic mixtures [Quantum 7, 1208 (2023)], are independent of the rotation angle $\theta$, requiring $O(\log 1/\delta)$ T gates. We show that it is possible to do much better for small angles, reducing the T cost to $\tilde{O}(\theta^2/\delta)$, and returning to existing $O(\log1/\delta)$ results in the worst case. This is particularly important since many algorithms, such as Trotterization, are dominated by small-angle rotations. Further, we perform a detailed theoretical and numerical study of quasi-probabilities, which can further reduce the total T cost of large circuits by orders of magnitude with only a small overhead in sample complexity. We also develop a scheme based on quasi-probability mixtures of Clifford+T fallback channels. We derive new $\theta$-dependent formulas that can be used for resource estimation of fault-tolerant quantum algorithms. As an application of our results, we show that the gate cost of Trotterization circuits compiled to a Clifford+T gate set is constant in the small Trotter step size limit, and can be reduced by orders of magnitude even for large step sizes. The cost of fault-tolerant Trotterization for a variety of applications should be re-examined in light of these results. Our work dispels the widely-stated claim that Clifford+T rotation synthesis has a high cost independent of $\theta$, and further develops a scalable quasi-probability method for rotation synthesis. We also expect our results to bring forward useful early fault-tolerant quantum computing by reducing required magic state resources.

16.
medRxiv (Medicine) 2026-06-16

Utilising Artificial Intelligence to Identify Ventricular Tachycardia Ablation Targets in Sinus Rhythm

Background and Aims: Machine learning has shown potential in predicting ablation targets for ventricular tachycardia (VT) in an animal model. This study progresses to externally validating deep learning approaches for human data. Methods: The development and external validation dataset included 21 and 13 patients, respectively, with structural VT undergoing catheter ablation. In the development datasets, electrophysiological studies were conducted using the AdvisorTM HD grid (EnsiteTM X), while both CARTO and Ensite Precision were used in the validation dataset. In each patient, VT ablation targets were defined as mapping points within 8 mm of VT isthmuses. Three advanced machine learning models were trained using cardiac mapping data acquired in both omnipolar and unipolar configurations during sinus rhythm and ventricular pacing. Discrimination was evaluated using nested leave-one-out cross-validation at patient level. Results: Overall, graph convolutional networks (GCNs), which integrate intracardiac signal waveforms with three-dimensional electroanatomical geometries, achieved the highest performance, with optimal results obtained from unipolar electrograms acquired in sinus rhythm (median AUC 0.793, sensitivity 83.6%, specificity 69.0%). This may be partly explained by the inclusion of repolarization dynamics in unipolar electrograms and the higher point density of sinus rhythm maps. Comparable performance was observed in the external dataset. Conclusion: This study demonstrates that graph convolutional networks applied to sinus rhythm EGM waveforms collected during substrate mapping can localise critical components of VT re-entry circuits. This approach has potential to provide fast and accurate ablation guidance without the need to induce and map VT, improving safety and efficacy of VT catheter ablation.

17.
arXiv (CS.LG) 2026-06-15

AcceRL: A Distributed Asynchronous Reinforcement Learning and World Model Framework for Vision-Language-Action Models

arXiv:2603.18464v3 Announce Type: replace Abstract: Reinforcement learning (RL) for large-scale Vision-Language-Action (VLA) models is severely bottlenecked by synchronization barriers and the high cost of environment data acquisition. To overcome these challenges, we propose AcceRL, a distributed asynchronous RL framework that physically isolates environment rollouts, model inference, and gradient updates. By eliminating the cascading long-tail idle bubbles inherent in synchronous systems, AcceRL maximizes hardware utilization and ensures scalable throughput. Furthermore, AcceRL features a modular design that supports the integration of diverse, plug-and-play world models into its distributed pipeline. Extensive experiments demonstrate that the base framework achieves highly competitive performance across all four LIBERO[liu2023libero] task suites. Systematically, the asynchronous architecture delivers a $2.4\times$ throughput speedup over leading synchronous baselines. Algorithmically, by leveraging a world model pre-trained on 1,000 offline trajectories, AcceRL achieves up to a $200\times$ improvement in online sample efficiency on LIBERO-Spatial, establishing a robust framework that is both sample-efficient and time-efficient for embodied AI. Code is included in the supplementary material. Code is available at https://github.com/distanceLu/AcceRL.

18.
bioRxiv (Bioinfo) 2026-06-16

PhenoBIC: operator-free single-cell spatial phenotyping in multiplex imaging data using deep learning of cell staining patterns

Multiplex imaging is a valuable tool for spatially examining tissue microenvironments at the single-cell level to uncover biological and clinical insights. However, most multiplex image analysis workflows currently require manual intervention for cell phenotyping, which slows progress, demands human effort, and yields operator-dependent outputs. Here, we developed PhenoBIC, a pre-trained deep learning model for image classification of the multiplexed biomarker signals in a cell (Biomarker Imprint of a Cell) to classify cell phenotypes. We show that PhenoBIC (F1-score ~0.88) outperforms manual gating (widely used) and other machine learning-based computational approaches for cell marker expression classification. We validated this across multiple biomarkers, tissue sampling strategies (whole biopsies and tissue microarrays), multiplex panels, imaging platforms, and tissue types. We have released our in-house training and validation datasets of ~1.4 million manually curated cell expression ground truth labels. We have also open-sourced PhenoBIC and enabled its community-wide deployment via the QuPath interface.

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

INFRAMIND: Infrastructure-Aware Multi-Agent Orchestration

arXiv:2606.11440v1 Announce Type: new Abstract: Existing multi-agent LLM orchestration methods, ranging from brute-force ensembles to learned routers, select models and topologies based on task and model features. However, these methods do not consider the runtime state of the serving infrastructure. On shared GPU clusters under concurrent load, this infrastructure blindness causes systematic resource underutilization: preferred models accumulate deep request queues while equally capable alternatives sit idle. In multi-agent pipelines, where each query triggers multiple sequential model calls, these delays then compound across every downstream step. Closing this gap is challenging because the relevant infrastructure signals (queue depths, KV-cache pressure, latencies) are dynamic and noisy, and they must drive three different decisions: planning, per-step routing, and scheduling. We introduce INFRAMIND, a framework that makes the entire multi-agent stack infrastructure-aware. An infra-aware planner conditions topology and role selection on real-time system load and remaining budget, biasing toward simpler graphs under congestion and richer ones at low load. An infra-aware executor then observes per-model queue depths, cache utilization, and response latencies at each agent step to decide which model to call and how deeply to reason; a budget-aware scheduler further reorders each model's queue so that urgent requests are served first. Cast as a hierarchical constrained MDP and solved end-to-end via reinforcement learning, the system learns to balance quality against latency automatically. Across five benchmarks, INFRAMIND delivers up to +7.6 pp accuracy over the prior baseline at low load with up to 7x lower latency, and sustains up to 99.9% SLO compliance under high load where every baseline drops below 50%.

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

Multi-Head Attention-Based Feature Extractor Integration with Soft Actor-Critic for Porosity Prediction and Process Parameter Optimization in Additive Manufacturing

arXiv:2606.20087v1 Announce Type: new Abstract: Additive manufacturing process optimization requires precise parameter control to minimize defects such as porosity. Traditional reinforcement learning (RL) approaches using discrete action spaces suffer from slow convergence and susceptibility to local optima, limiting their effectiveness for high-precision manufacturing tasks. This study addresses these limitations by employing a continuous action space combined with a novel architecture that integrates a multi-head attention mechanism with the Soft Actor-Critic (SAC) algorithm. The attention-based feature extractor enhances the agent's ability to capture subtle variations in low-dimensional input features, enabling more effective exploration-exploitation balance for navigating value spaces with local minima. We validate our approach on porosity prediction and process parameter optimization in laser powder bed fusion, demonstrating faster convergence and higher final reward values compared to standard RL methods including DQN, PPO, TD3, and vanilla SAC. The proposed methodology achieves a convergence value of 322.79 within 14 episodes, outperforming existing approaches while maintaining stability throughout training.

21.
PLOS Computational Biology 2026-06-16

Evolution and the ultimatum game: An agent-based model with interbirth intervals and population structure

by Jeffrey C. Schank, Matt L. Miller The ultimatum game (UG) is widely used to study mutually beneficial exchanges, fairness, and prosocial behavior across different societies. However, human behavior in UG experiments does not align with the game-theoretical prediction that proposers should offer the least positive amount and responders should accept such offers. Instead, proposers make generous offers that are greater than the minimum responders are willing to accept, resulting in generous offers with wide offer-acceptance gaps. Numerous evolutionary models of the UG have been created and studied to explain human behavior, particularly generous offers made in UG experiments. These models have recently faced criticism for lacking biological realism and not adequately explaining the data. Here, we present an agent-based model inspired by our hunter-gatherer ancestors and with a biologically more realistic selection process. We assume that (1) agents exist in group-structured and group-clustered populations, where reproduction (2) depends on resource accumulation, but (3) is limited by interbirth intervals. We ran simulations to assess whether this biologically more realistic model evolves patterns of behavior consistent with patterns in the data from meta-analyses of human behavior in the UG. For the proposed model, we show that generous offers robustly evolve, as well as the difficult-to-explain offer-acceptance gaps, only in group-structured populations with interbirth intervals. We demonstrate that these results are robust and may help explain variation in data across societies. We discuss how interbirth intervals interact with group structure to modulate offer and rejection costs, favoring the evolution of generous offers, offer-acceptance gaps, and other patterns in the data on human behavior in the UG. We also discuss why weak selection and/or high mutation rate models cannot explain all the patterns in UG experimental data. We discuss biological realism and conclude that group structure and interbirth intervals may be essential for explaining prosocial behavior across societies.

22.
arXiv (CS.LG) 2026-06-19

Benign overfitting beyond prediction: The ordinary least squares interpolator

arXiv:2309.15769v3 Announce Type: replace-cross Abstract: Recent advances in deep learning have highlighted the phenomenon of benign overfitting in overparameterized statistical models, sparking significant interest in understanding its foundations. Owing to its simplicity and practical relevance, the ordinary least squares (OLS) interpolator has become a key object of study for gaining theoretical insight into this phenomenon. While the properties of OLS are well understood in classical underparameterized settings, its behavior in the overparameterized regime – unlike that of ridge regression or the lasso – remains comparatively less explored. We contribute to this growing literature by deriving new algebraic and statistical results for the minimum $\ell_2$-norm OLS interpolator. In contrast to much of the existing work, which focuses on prediction risk, we center our analysis on parameter estimation and inference, which are fundamental for many statistics and causal inference applications. Specifically, we establish overparameterized analogues of (i) the leave-$k$-out formulas, (ii) the omitted variable bias formula, and (iii) the Frisch-Waugh-Lovell theorem. Under the Gauss-Markov model, we further extend the Gauss-Markov theorem and analyze variance estimation under homoskedasticity in the overparameterized setting. Collectively, these results provide a systematic framework for studying parameter estimation and inference in overparameterized linear models, offering a novel perspective on benign overfitting beyond its implications for prediction.

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

TextResNet: Decoupling and Routing Optimization Signals in Compound AI Systems via Deep Residual Tuning

arXiv:2602.08306v2 Announce Type: replace Abstract: Textual Gradient-style optimizers (TextGrad) enable gradient-like feedback propagation through compound AI systems. However, they do not work well for deep chains. The root cause of this limitation stems from the Semantic Entanglement problem in these extended workflows. In standard textual backpropagation, feedback signals mix local critiques with upstream contexts, leading to Attribution Ambiguity. To address this challenge, we propose TextResNet, a framework that reformulates the optimization process to achieve precise signal routing via four key innovations. Firstly, in the forward pass, it enforces Additive Semantic Deltas to preserve an Identity Highway for gradient flow. Secondly, in the backward pass, it introduces Semantic Gradient Decomposition via a Semantic Projector to disentangle feedback into causally independent subspaces. Thirdly, it implements Causal Routing, which routes projected signals to their specific components. Finally, it performs Density-Aware Optimization Scheduling to leverage the disentangled signals to dynamically allocate resources to key system bottlenecks. Our results show that TextResNet not only achieves superior performance compared to TextGrad, but also exhibits remarkable stability for agentic tasks in compound AI systems where baselines collapse. Code is available at https://github.com/JeanDiable/TextResNet.

24.
arXiv (CS.AI) 2026-06-12

Rethinking RAG in Long Videos: What to Retrieve and How to Use It?

arXiv:2606.13141v1 Announce Type: new Abstract: Retrieval-augmented generation is moving beyond text into long, egocentric video, where systems must select query-relevant chunks across multiple modalities and temporal granularities. Yet progress in VideoRAG is limited by two gaps: existing benchmarks allow queries to be answered without the video, obscuring retrieval errors, and prior methods apply a single modality-granularity configuration per query, ignoring chunk-level variability. We address both by introducing V-RAGBench, a benchmark of $\langle$query, evidence chunk, answer$\rangle$ triplets that enables faithful, decoupled evaluation of retrieval and generation, and CARVE, a simple method that runs parallel retrievers across configurations and employs chunk-adaptive reranking to identify the winning configuration for each chunk. Each chunk then enters the generator under its winning configuration selected during retrieval, yielding an interleaved evidence form where the chunk-level decision propagates across both stages. CARVE outperforms eight recent VideoRAG baselines, with the chunks supplied to the generator interleaving multiple configurations rather than sharing a single one, a behavior unattainable by query-level methods.

25.
arXiv (CS.LG) 2026-06-12

Extracting Governing Equations from Latent Dynamics via Multi-View Contrastive Learning

arXiv:2606.13260v1 Announce Type: new Abstract: Identifying latent dynamical systems from noisy, high-dimensional measurements is a central problem at the intersection of representation learning, system identification, and scientific discovery. We present DYSCO, a multi-view temporal contrastive learning algorithm that jointly recovers latent trajectories and the governing dynamics from such observations, by leveraging multiple independent noisy views of the same underlying process to disentangle signal from noise. By parameterizing the dynamics in a structured functional basis, our framework further enables symbolic recovery of the governing equations within an affine gauge. We offer theoretical guarantees for strong identification up to an affine indeterminacy, extending prior identifiability results to the realistic setting of noisy nonlinear observations. Empirically, we demonstrate accurate recovery of both latent trajectories and flow fields across a diverse set of dynamical regimes (e.g., chaotic, oscillatory, and metastable) under both Gaussian and Poisson observation noise, the latter being particularly relevant for neural recordings.