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01.
arXiv (CS.CL) 2026-06-17

PromptMN: Pseudo Prompting Language

Prompting has become the primary interface between humans and generative AI, yet many natural language prompts remain fragile: roles, goals, constraints, and expected outputs are often buried in prose or left implicit. In agentic and software development workflows, a misread at the first handoff can propagate through every step, since a significant portion of agent failures stem from context ambiguities rather than model limitations. This paper introduces PromptMN, a pseudo-prompting domain-specific language that annotates natural language with compact, %-prefixed typed directives covering roles, goals, requirements, priorities, constraints, plans, inputs, and outputs. Semantic resolution lets authors write in any order while the model interprets directives by function. PromptMN sits between informal prompting and programming-style pseudocode: structured enough to be inspectable and reusable, yet lightweight enough for analysts, managers, developers, and stakeholders across the software development lifecycle (SDLC). PromptMN also pairs with reverse prompt engineering. Asking a model to restate a desired outcome as PromptMN lets users inspect the inferred roles, goals, constraints, and missing assumptions before acting, reducing repair cycles and yielding a reusable artifact for aligning people and AI tools. PromptMN's feasibility is evaluated across several frontier models, including Claude Fable 5, Claude Opus 4.8, Gemini 3.1 Pro, and GPT-5.5. The models correctly resolved PromptMN instructions, including complex structures such as repetition, conditionals, methods, and a prime-checking task, without fine-tuning. The same vocabulary applies across new codebases, maintenance, and redesign in the SDLC scenarios presented. While large-scale validation remains future work, these early results suggest PromptMN is a practical step toward clearer, more reviewable human-to-AI interaction.

02.
arXiv (CS.CL) 2026-06-18

REVES: REvision and VErification–Augmented Training for Test-Time Scaling

Test-time scaling via sequential revision has emerged as a powerful paradigm for enhancing Large Language Model (LLM) reasoning. However, standard post-training methods primarily optimize single-shot objectives, creating a fundamental misalignment with multi-step inference dynamics. While recent work treats this as multi-turn reinforcement learning (RL), conventional approaches optimize over the multi-step trajectories directly, failing to further exploit the high-quality mistakes in intermediate steps that model can learn from correcting them. We propose a two-stage iterative framework that alternates between online data/prompt augmentation and policy optimization. By converting the intermediate steps (``near-miss'' answers) in the successful recovery trajectories into decoupled revision and verification prompts, our approach concentrates training on both effective answer transformation and error identification. This approach enables efficient off-policy data generation and reduces the computational overhead of long-horizon sampling compared to standard multi-turn RL. On LiveCodeBench, using publicly available test cases as feedback, we observe gains of +6.5 points over the RL baseline and +4.0 points over standard multi-turn training. Beyond coding, our approach matches the previously reported SOTA result on circle packing while using the smallest base model (4B) and far fewer rollouts than the much larger evolutionary search systems. Math results under ground-truth verification further confirm improved correction ability. It also generalizes to out-of-distribution constraint-satisfaction puzzles such as n\_queens and mini\_sudoku, where correctness is defined entirely by problem constraints. Code is available at https://github.com/yxliu02/REVES.git.

03.
arXiv (CS.CV) 2026-06-11

Traits Run Deeper: Trait-Specific Asymmetric Fusion for Personality Assessment

Personality assessment aims to infer stable personality traits from dynamic behaviors across language, voice, and facial cues. Since different personality dimensions are revealed through distinct behavioral perspectives, modeling trait-specific evidence is challenging. However, most existing approaches adopt a uniform multimodal fusion strategy across all dimensions, assuming identical modality contributions. This overlooks trait-specific modality preferences and introduces cross-modal interference. To address this issue, we propose a novel personality assessment framework called Traits Run Deeper, which consists of three components. Specifically, the Multimodal Foundation Representation (MFR) module constructs personality-oriented multimodal inputs and leverages psychology-informed semantic templates as anchors, enabling foundation models to capture trait-relevant information. Building upon MFR, the Trait-Specific Modality Fusion (TSMF) module acts as an asymmetric fusion mechanism, allowing each dimension to selectively exploit different modality pathways from modality-specific modeling to complementary fusion. Thus, TSMF captures heterogeneous modality preferences while reducing cross-modal contamination. Furthermore, the Distribution-Calibrated Personality Regression (DCPR) module mitigates label imbalance and central tendency bias through target distribution calibration, improving robustness and stability. Experimental results on the AVI Challenge 2026 validation set demonstrate the effectiveness of the proposed framework, reducing mean squared error (MSE) by approximately 25% compared with the baseline. Consistent improvements are observed on the official test set, where our method achieves the best performance and ranks first in the Personality Assessment Track. The source code will be made available at https://github.com/MSA-LMC/AVI2026.

04.
arXiv (CS.AI) 2026-06-12

Deterministic Integrity Gates for LLM-Assisted Clinical Manuscript Preparation: An Auditable Biomedical Informatics Architecture

arXiv:2606.09500v3 Announce Type: replace Abstract: As autonomous research agents and AI co-scientist systems push large language models (LLMs) from drafting toward end-to-end manuscript production, the bottleneck shifts from generation to verification. Fluent LLM output can hide fabricated citations, numbers that drift from source tables, and unmet reporting-guideline items; existing tools generate without verifying, and self-critique inherits the blind spots that produce confident fabrication. We describe an architecture pairing generation with verification, resting on three principles: decompose the workflow into self-contained skills, gate every stage transition with halt-on-failure, and resolve each integrity question with the cheapest sufficient mechanism, a deterministic, re-executable check where one suffices and a prose-level probe only where interpretation is unavoidable. This determinism-where-possible split, organized as an integrity-gate taxonomy, is the core contribution. It is realized as MedSci Skills, an open-source toolkit of 43 skills with a 21-detector deterministic tier, evaluated on three public-dataset pipelines (STARD, PRISMA, STROBE) and a seeded-defect ablation. Across the three pipelines every content-hash manifest verified clean and the gates surfaced real defects; on 27 identical injected defects the deterministic gates detected all 27 with no false positives on the matched clean fixtures, whereas a single-prompt LLM reviewer detected 11, its misses in code, bibliography, and style defects the prose hides. Determinism-where-possible verification yields an auditable, re-executable trail that exposes the evidence a human needs to check an LLM-assisted manuscript: feasibility and reproducibility evidence, not a claim of human-competitive quality, which a separate blinded study addresses. MedSci Skills is MIT-licensed and archived (v3.8.0).

05.
medRxiv (Medicine) 2026-06-17

Differential Determinants of Past Behavior and Future Intention Regarding Voluntary Blood Donation: A Cross-Sectional Study of Knowledge, Attitudes, and Practices in Qingdao, China

Background A persistent gap between motivation and action threatens voluntary blood supply. This study examined the publics knowledge, attitudes, and practices (KAP) regarding blood donation, with a particular focus on identifying the different determinants of past blood donation behavior and future willingness to donate. Methods Convenience sampling was used to conduct a cross-sectional survey among 1,058 eligible people in Qingdao, China, between July and November 2025. Data were collected via a self-designed KAP questionnaire. To find independent characteristics linked to previous behavior and future intention, respectively, multivariable binary logistic regression was used. Results Overall, 37.0% of participants (n=391) had a lifetime donation history, while 39.2% (n=415) intended to donate in the next 12 months. Past behavior was positively associated with older age (36-45 years: OR=6.84; 95% CI: 3.21-14.58), higher education (OR=2.06; 95% CI: 1.33-3.17), and interpersonal interaction channels (OR=1.45; 95% CI: 1.01-2.09) but hindered by safety concerns (OR=0.23; 95% CI: 0.16-0.34). Conversely, future intention was positively correlated with male sex (OR=1.69; 95% CI: 1.24-2.29), prior donation history (OR=2.69; 95% CI: 1.87-3.86), having family members or friends in need of blood (OR=2.75; 95% CI: 1.96-3.85), and traditional media exposure (OR=3.33; 95% CI: 2.18-5.10). Higher education was adversely correlated with future intention (OR=0.55; 95% CI: 0.38-0.79). Conclusion There is a substantial disparity between donation motivation and action. The determinants of past behavior and future intention are asymmetric, suggesting that stage-specific interventions are required, using social mobilization for initiating first-time donations, while employing family reciprocity and authoritative communication to sustain long-term engagement.

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

Physical Atari: A Robust and Accessible Platform for Real-time Reinforcement Learning on Robots

arXiv:2606.19357v1 Announce Type: cross Abstract: We built a robot called the Robotroller that actuates an Atari CX40+ controller and a device called the Atari Devbox that renders the game frame and the reward signal from the Arcade Learning Environment on a screen. The Robotroller and the Atari Devbox, together with an off-the-shelf camera and a desktop computer, constitute a system that can be used to study reinforcement learning algorithms in the physical world. We call the full system Physical Atari. In this paper, we detail the key decisions that make Physical Atari a robust and accessible platform. To make the system robust, we designed the Robotroller so that all movement is done through bearings, which reduces wear. Additionally, we wrote software that monitors the state of the servos at a high frequency and intervenes to limit stress. To make the system accessible, we used affordable off-the-shelf components and parts that can be manufactured using consumer 3D printers. Physical Atari can be built for under $1,000 and has been used for weeks of non-stop reinforcement learning experiments without any mechanical failures. We used it to validate that reinforcement learning algorithms can learn directly on robots and show that even small distribution shifts between learning and deployment can significantly degrade the performance of policies. Our results underscore the importance of on-device adaptation for strong performance on robots.

07.
medRxiv (Medicine) 2026-06-12

Immunologically Optimized Zmp1 Peptides Reveal a Translational Serological Biomarker Platform for Tuberculosis Diagnosis Across Disease Manifestations

Tuberculosis (TB) diagnosis remains challenging, particularly for extrapulmonary TB (EPTB), where invasive sampling, low bacillary burden, and suboptimal sensitivity of nucleic acid-based tests in peripheral specimens hinder timely detection. Here, we report an immunology-driven strategy for biomarker discovery and development of a peptide-based serological assay targeting Mycobacterium tuberculosis zinc metalloprotease-1 (Zmp1). Leveraging fundamental principles of adaptive immunity that antigenic regions containing overlapping B-cell and CD4 T-helper cell epitopes would preferentially generate high antibody titers through linked recognition and cognate T-cell help, we used an immunoinformatics pipeline to identify two nested immunodominant peptide regions within Zmp1 (Mtb-Zp-NT and Mtb-Zp-CT) enriched for overlapping B- and T-cell epitopes. The diagnostic potential of these peptides was evaluated through ELISA-based serological assays. A blinded pilot study (N=137) demonstrated a clear discrimination between active TB and TB-recovered individuals. The assay was subsequently validated in an expanded cohort (N=875) by screening 6,086 individuals, which identified 457 TB-positive cases. The cohort included pulmonary TB (PTB), EPTB, TB-recovered individuals, household contacts, non-specific infections, and healthy controls. Receiver operating characteristic analyses, supported by DeLong and bootstrap comparisons, revealed superior diagnostic performance of the peptide-based assays relative to full-length Zmp1. Mtb-Zp-CT exhibited the highest accuracy (AUC=0.93; specificity >90%), while Mtb-Zp-NT also demonstrated strong discriminatory power (AUC{approx}0.89). These findings establish that the immunologically optimized Zmp1 peptides are highly promising serological biomarkers for TB and EPTB. More broadly, they demonstrate how mechanistically informed epitope selection can accelerate translation of pathogen-specific immune signatures into sensitive, minimally invasive, and potentially point-of-care diagnostic platforms for resource-limited settings.

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

Nous: An Attempt to Extract and Inject the Cognition Behind Prediction-Market Behavior

作者:

arXiv:2606.13038v1 Announce Type: new Abstract: As LLM agents proliferate in prediction markets and collective decision-making, they risk a cognitive monoculture: agents built on shared foundation models produce correlated forecasts, and recent measurement finds frontier-model errors correlated at r ~ 0.77. We ask whether human cognitive diversity can be recovered from behavior and transferred to LLM agents. Nous extracts a structured eight-dimension behavioral profile from real Polymarket trading activity and injects it into agents through prompts. Our central finding is a dissociation between the two halves of that pipeline. Extraction works, partially: across 100 wallets, 8 of 14 parameters are temporally stable (split-half ICC >= 0.5, bootstrap CI lower bound > 0.3; contrarian score reaches ICC ~ 0.9); wallets are identifiable from their profiles well above chance (top-1 retrieval 17-22% vs. 1% chance); and two of four pre-specified dimensions rank-correlate with future realized profit out-of-sample, though the correlations do not survive behavioral-confound controls. Prompt-level injection does not measurably transmit it: on a semantic embedding metric, structured injection shows no significant advantage over a length-matched control on any model, and the diversity it induces neither reduces ensemble error correlation nor improves Brier score – a null that persists across exploratory checks on sampling temperature, profile diversity, and question difficulty. Measuring the prompts themselves locates the compression before the model: the structure-to-narrative translator emits near-uniform prompts whose spread does not track profile spread. We position Nous as measuring the cognitive-monoculture problem and the limits of a prompt-level remedy, motivating deeper, below-the-prompt injection (fine-tuning, activation steering). Code, frozen profiles, prompts, and model outputs: https://github.com/WillChienT/nous-paper

09.
arXiv (math.PR) 2026-06-18

Functions of Bounded Variation and Point Processes

arXiv:2606.08304v2 Announce Type: replace-cross Abstract: We investigate the relationship between the analytical properties of functions of bounded variation and the statistical behavior of hyperuniform point processes. We establish several characterization formulas for the jump part of the gradient of a bounded variation function, extending and unifying previous results by Beretti–Gennaioli and Dávila. In particular, we provide new expressions for the $L^2$-jump of the gradient using both difference quotients and Fourier transform methods. Furthermore, we connect these analytic structures to the theory of hyperuniform point processes. By analyzing the variance of linear statistics associated with bounded variation functions, we provide asymptotic estimates that depend on the specific classification of the hyperuniformity of the point process. The results show how the regularity and jump discontinuities of a function dictate the growth rate of fluctuations in point processes. Finally, we introduce an averaged quadratic BMO-type oscillation functional over translated and rotated cube partitions, similar to the one recently studied by Ambrosio et al., and prove, using results from point process, that it converges to an explicit dimensional constant times the $L^2-$jump, giving in particular a further new characterization of the perimeter of a set.

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

When LLMs Analyze Scars: From Images to Clinically-Meaningful Features

Medical image classification faces a fundamental dilemma: while deep learning models achieve remarkable performance at scale, real-world clinical scenarios often suffer from severe data scarcity due to annotation costs, privacy constraints, and disease rarity. This challenge is particularly pronounced in pathological scar classification, where differentiating keloids from hypertrophic scars requires subtle expert knowledge and labeled images are extremely limited. We propose a novel paradigm that repositions large language models (LLMs) as knowledge-driven feature engineers rather than end-to-end classifiers. We call this framework ScaFE (Scar Feature Engineering). Our key insight is that LLMs encode rich medical knowledge that can be externalized as executable feature extraction code, enabling the transformation of high-dimensional images into low-dimensional, clinically interpretable representations. Specifically, we prompt an LLM with established scar assessment criteria to generate deterministic Python code that extracts features aligned with clinical scoring systems such as the Vancouver Scar Scale. Our approach offers three key advantages: (1) data efficiency, achieving robust performance with limited training samples by decoupling knowledge acquisition from statistical learning; (2) privacy preservation, as raw images are processed locally without exposure to external LLMs; and (3) interpretability, through explicit features grounded in clinical reasoning. Extensive experiments on scar classification demonstrate that our method consistently outperforms end-to-end deep learning baselines or using LLMs as black-box classifiers under limited data conditions, establishing a promising direction for integrating LLMs into data-efficient and clinically transparent medical AI systems.

11.
arXiv (quant-ph) 2026-06-19

Exploiting More Than Symmetry in Variational Quantum Machine Learning

arXiv:2606.20316v1 Announce Type: new Abstract: The success of variational quantum learning models crucially depends on choosing parametrizations that reflect the structure of the problem at hand. Symmetries provide one of the clearest such structures: whenever transformations of the input leave the desired outcome unchanged, this invariance should be built into the model rather than discovered during training. However, imposing a symmetry does not by itself determine a useful ansatz. Even within the symmetry-preserving space, one must decide where the trainable degrees of freedom should be placed. In this work, we study this remaining design freedom in equivariant variational quantum circuits. Building on symmetry-based parameter sharing, we disentangle two architectural choices: how much symmetry should be enforced, and which symmetry-respecting interactions should be trainable. Using Tic-Tac-Toe as a fully enumerable and structurally transparent test case, we find that suitable subgroups preserve most of the generalization benefit. By contrast, the dominant gains arise from gates acting directly on decisive task motifs. Thus, symmetry defines the admissible design space, while effective ansatze require an additional task-informed choice of trainable interactions.

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

C-QUERI: Congressional Questions, Exchanges, and Responses in Institutions Dataset

Questions in political interviews and hearings serve strategic purposes beyond information gathering including advancing partisan narratives and shaping public perceptions. However, these strategic aspects remain understudied due to the lack of large-scale datasets for studying such discourse. Congressional hearings provide an especially rich and tractable site for studying political questioning: Interactions are structured by formal rules, witnesses are obliged to respond, and members with different political affiliations are guaranteed opportunities to ask questions, enabling comparisons of behaviors across the political spectrum. We develop a pipeline to extract question-answer pairs from unstructured hearing transcripts and construct a novel dataset of committee hearings from the 108th–117th Congress. Our analysis reveals systematic differences in questioning strategies across parties, by showing the party affiliation of questioners can be predicted from their questions alone. Our dataset and methods not only advance the study of congressional politics, but also provide a general framework for analyzing question-answering across interview-like settings.

13.
arXiv (CS.LG) 2026-06-11

CP4SBI: Local Conformal Calibration of Credible Sets in Simulation-Based Inference

arXiv:2508.17077v3 Announce Type: replace-cross Abstract: Current experimental scientists have been increasingly relying on simulation-based inference (SBI) to invert complex non-linear models with intractable likelihoods. However, posterior approximations obtained with SBI are often miscalibrated, causing credible regions to undercover true parameters. We develop $\texttt{CP4SBI}$, a model-agnostic conformal calibration framework that constructs credible sets with local Bayesian coverage. Our two proposed variants, namely local calibration via regression trees and CDF-based calibration, enable finite-sample local coverage guarantees for any scoring function, including HPD, symmetric, and quantile-based regions. Experiments on widely used SBI benchmarks demonstrate that our approach improves the quality of uncertainty quantification for neural posterior estimators using both normalizing flows and score-diffusion modeling.

14.
arXiv (CS.CV) 2026-06-15

GarmentSketch: Large-scale Sketch-to-Fashion Benchmark

Fashion sketching is a cornerstone of design workflows, allowing rapid visualization of creative concepts prior to physical prototyping. Yet, progress in sketch-based fashion image synthesis has been hindered by the absence of large-scale, high-quality paired resources. To bridge this gap, we present GarmentSketch, a novel dataset comprising 26,249 fashion sketches across 21 garment categories, each paired with detailed textual descriptions. Captions were produced through a multi-stage pipeline that integrates multiple multimodal large language models (MLLMs) with human-in-the-loop refinement, ensuring both semantic accuracy and descriptive richness. We benchmark GarmentSketch on state-of-the-art generative models, providing baseline performance for sketch-guided text-to-image generation. Our experiments reveal both the promise and the current limitations of existing methods. By offering a comprehensive and richly annotated resource, GarmentSketch establishes a foundation for advancing sketch understanding, fine-grained fashion image generation, and creative human-AI collaboration in design. The dataset will be available at: https://khangbdd.github.io/garmentsketch.

16.
arXiv (CS.CV) 2026-06-17

Colab NAS: Obtaining lightweight task-specific convolutional neural networks following Occam's razor

The current trend of applying transfer learning from convolutional neural networks (CNNs) trained on large datasets can be an overkill when the target application is a custom and delimited problem, with enough data to train a network from scratch. On the other hand, the training of custom and lighter CNNs requires expertise, in the from-scratch case, and or high-end resources, as in the case of hardware-aware neural architecture search (HW NAS), limiting access to the technology by non-habitual NN developers. For this reason, we present ColabNAS, an affordable HW NAS technique for producing lightweight task-specific CNNs. Its novel derivative-free search strategy, inspired by Occam's razor, allows to obtain state-of-the-art results on the Visual Wake Word dataset, a standard TinyML benchmark, in just 3.1 GPU hours using free online GPU services such as Google Colaboratory and Kaggle Kernel.

17.
arXiv (CS.LG) 2026-06-16

Towards CONUS-Wide ML-Augmented Conceptually-Interpretable Modeling of Catchment-Scale Precipitation-Storage-Runoff Dynamics

arXiv:2510.02605v2 Announce Type: replace Abstract: While many modern studies are dedicated to ML-based large-sample hydrologic modeling, these efforts have not necessarily translated into predictive improvements that are grounded in enhanced physical-conceptual understanding. Here, we report on a CONUS-wide large-sample study (spanning diverse hydro-geo-climatic conditions) using ML-augmented physically-interpretable catchment-scale models of varying complexity based in the Mass-Conserving Perceptron (MCP). Results were evaluated using attribute masks such as snow regime, forest cover, and climate zone. Our results indicate the importance of selecting model architectures of appropriate model complexity based on how process dominance varies with hydrological regime. Benchmark comparisons show that physically-interpretable mass-conserving MCP-based models can achieve performance comparable to data-based models based in the Long Short-Term Memory network (LSTM) architecture. Overall, this study highlights the potential of a theory-informed, physically grounded approach to large-sample hydrology, with emphasis on mechanistic understanding and the development of parsimonious and interpretable model architectures, thereby laying the foundation for future models of everywhere that architecturally encode information about spatially- and temporally-varying process dominance.

18.
arXiv (CS.CV) 2026-06-12

SalArt-VQA: Diagnosing Whether VLMs Understand Salient Artifacts in Generated Images

Vision-language models (VLMs) are increasingly used to detect whether AI-generated images contain visible artifacts, yet their ability to analyze such artifacts remains poorly understood. A correct image-level decision can still hide important failures: a model may correctly flag an artifact while relying on the wrong visual cue, selecting the wrong region, or describing a defect that the image does not support. To evaluate these behaviors directly, we introduce SalArt-VQA, a diagnostic benchmark for fine-grained SALient ARTifact understanding in AI-generated images. SalArt-VQA contains 950 images and 3,681 human-authored multiple-choice questions spanning artifact images, matched real reference images, and paired generated reference images. Four aligned question types evaluate presence detection, semantic localization, spatial grounding, and evidence-grounded defect identification, while the reference splits test calibration and abstention when the annotated defect is absent. Across 20 VLMs, SalArt-VQA reveals failures that image-level detection accuracy hides: the strongest model reaches 99.37% detection recall on artifact images but answers all four artifact-side questions correctly on only 53.26% of images. Comparing artifact images with artifact-free references reveals a sensitivity-calibration tradeoff: sensitive models often make unsupported artifact claims, while conservative models avoid false alarms largely by missing real artifacts. These results show that high artifact detection accuracy alone does not imply grounded artifact understanding. SalArt-VQA exposes these hidden failure modes and provides a fine-grained evaluation of whether VLM artifact claims are supported by local visual evidence.

19.
arXiv (CS.LG) 2026-06-12

How Useful is Causal Invariance for Domain Adaptation in Finite-Sample Settings?

arXiv:2606.12680v1 Announce Type: new Abstract: Machine learning models often degrade when they are deployed on a target distribution that differs from the source distributions they were trained on. Recent work in causality-based domain generalization has shown how shared causal structure between domains can induce invariant predictors, e.g., models on a subset of features which have stable risk across structured domain shifts. However, the extent to which such population-level causal invariances can lead to gains in finite-sample settings remains underexplored. In particular, in practice we often have access to a few labeled target samples, a setting called supervised domain adaptation (sDA). In this paper, we explore when (full or partial) causal knowledge can provably improve supervised domain adaptation. As a first step, we study linear regression, where full or partial causal knowledge specifies a collection of invariant or possibly invariant feature subsets, each yielding a source-trained candidate predictor. We derive matching upper and lower bounds showing that finite-sample gains are governed by the target-risk margins separating the candidates, together with the finite-source estimation error. When these margins are sufficiently large relative to $n_Q$, an adaptive aggregation procedure can match the best candidate predictor while avoiding negative transfer relative to target-only learning. On the other hand, when the margins are too small, no algorithm can reliably exploit the candidate collection to obtain faster finite-sample rates. We further connect these margins to structural shift magnitude in linear SCMs and validate the theory on real-world causal benchmarks.

20.
PLOS Computational Biology 2026-06-05

A multiscale, Bayesian inference approach to augment mechanistic models of cell signaling with machine-learning predictions of binding affinity

by Holly A. Huber, Stacey D. Finley Computational models in systems biology are often underdetermined—that is, there is little data relative to the complexity and size of the model. This lack of data is primarily due to limits in our ability to observe specific biological systems and restricts the utility of computational models. To reduce this uncertainty, recent methods have explored augmenting parameter inference of systems biology models with predictions from machine learning models. Such approaches expand the pool of data that is applicable for the inference problem. Here, we explore augmenting the parameter inference of intracellular signaling models. We choose to investigate signaling because experimental measurements of the variables of interest, protein dynamics, are still quite limited. To investigate, we propose a novel, multiscale, Bayesian inference approach that augments traditional signaling data with predictions of binding affinity. These predictions are generated using a machine learning pipeline with measurements of amino acid sequence, from the Universal Protein Resource, or protein structure, from the Protein Data Bank, as inputs. We find that we can successfully integrate these measurements into the inference problem using our novel framework. Excitingly, this integration significantly improves the parameter estimates of signaling models. We demonstrate that how much this improvement impacts predictions of signaling depends on the sensitivity of the prediction to perturbations in the parameter values. Overall, the framework we establish here improves the parameter inference of intracellular signaling models by successfully bridging data on protein sequence and structure with systems-level signaling.

21.
arXiv (CS.CL) 2026-06-11

TokenRatio: Principled Token-Level Preference Optimization via Ratio Matching

Direct Preference Optimization (DPO) is a widely used RL-free method for aligning language models from pairwise preferences, but it models preferences over full sequences even though generation is driven by per-token decisions. Existing token-level extensions typically decompose a sequence-level Bradley-Terry objective across timesteps, leaving per-prefix (state-wise) optimality implicit. We study how to recover token-level preference optimality using only standard sequence-level pairwise comparisons. We introduce Token-level Bregman Preference Optimization (TBPO), which posits a token-level Bradley-Terry preference model over next-token actions conditioned on the prefix, and derive a Bregman-divergence density-ratio matching objective that generalizes the logistic/DPO loss while preserving the optimal policy induced by the token-level model and maintaining DPO-like simplicity. We introduce two instantiations: TBPO-Q, which explicitly learns a lightweight state baseline, and TBPO-A, which removes the baseline through advantage normalization. Across instruction following, helpfulness/harmlessness, and summarization benchmarks, TBPO improves alignment quality and training stability and increases output diversity relative to strong sequence-level and token-level baselines.

22.
medRxiv (Medicine) 2026-06-10

Seasonality, source type, and women's water labor: A longitudinal mixed-methods study in Kenya and Honduras

Women shoulder the majority of water collection labor globally, yet how their water collection and water-related work experiences may change over time or by water source type remains insufficiently understood. We conducted a longitudinal, mixed-methods study in rural Kenya and Honduras to understand how women's experiences collecting water and performing water-related work varied between (a) two time points, (b) improved and unimproved water source types, and (c) water source location. Data were collected in 2023 and 2024 using interviews, observation, GPS-enabled watches, and scales to measure time and distance traveled, water weight and volume carried, and calories expended. 133 women participated in data collection (66 Kenya, 67 Honduras). We compared women's experience data by time point (2023 vs. 2024), source type (improved vs. unimproved), and source location (off-premises vs. on-premises) (t-test, Mann-Whitney U test). We also mapped participants' routes and activities to show which sources were visited, when, and for what activities. In Kenya, mean water collection time, distance, and caloric expenditure were significantly lower and water volume was significantly higher in 2024 when there were unexpected rains compared to 2023 when there was a persistent drought. When comparing source types during the 2023 drought, journeys to improved sources took significantly less time and energy and covered less distance than journeys to unimproved sources. These differences were not observed during the rainy conditions of 2024 when unimproved sources were closer and more accessible. In Honduras, water collection and water work burdens did not differ significantly by time point or source type. We found women with on-premises water access to still expend considerable time and caloric expenditure engaging in water work within their household compounds. Findings from Kenya suggest that water infrastructure improvements can reduce women's water collection burdens, though benefits may depend on and vary by season and source location. Findings from Honduras show that water labor does not end once water is in the household. Rather, substantial time and energy are expended carrying out water-related work even when sources are on premises, suggesting that efforts to assess water labor need to extend beyond collection alone. To meaningfully reduce burdens and ensure improved water sources are utilized during all seasons, initiatives need to consider source location, seasonal variability, and work beyond collection. Evaluations to assess infrastructure impacts on women's labor and well-being are needed and long overdue.

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

MolE-RAG: Molecular Structure-Enhanced Retrieval-Augmented Generation for Chemistry

arXiv:2606.05693v2 Announce Type: replace Abstract: Large language models (LLMs) have shown promise for molecular property prediction, but their ability to reason over chemical structures remains limited, as molecular representations such as SMILES differ substantially from the natural language on which LLMs are primarily trained. To bridge this semantic and chemical knowledge gap, we propose MolE-RAG, a training-free, molecule-centric retrieval-augmented generation framework for LLM-based molecular property prediction. MolE-RAG augments each prediction with three complementary sources of inference-time context: retrieved chemistry literature, molecule-specific information including compound synonyms, identifiers, functional group annotations, and physicochemical descriptors, and structurally similar molecules retrieved from the training set. We evaluate MolE-RAG across nine molecular property prediction tasks using proprietary, chemistry-specialized, and open-source LLMs. Across general-purpose LLMs, MolE-RAG improves ROC-AUC by up to 28 percentage points on classification tasks and reduces regression RMSE by up to 67% relative to a SMILES-only baseline. We further find that the utility of each context source varies across models and tasks, with different models benefiting most from textual retrieval, molecular context, or structural retrieval. These results suggest that molecule-centric retrieval can improve LLM-based molecular property prediction without model fine-tuning while providing a flexible framework for integrating heterogeneous chemical knowledge at inference time.

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

Multimodal Evaluator Preference Collapse: Cross-Modal Contagion in Self-Evolving Agents

作者:

When AI agents use language models to evaluate their own outputs in a feedback loop, systematic biases emerge. We show that Evaluator Preference Collapse (EPC) is dramatically amplified in multimodal settings. Using GPT-4o to evaluate DeepSeek-chat across text and visual tasks, we find that a single strategy (step_by_step) absorbs 48.4% of all weight – 3.2x the collapse observed in text-only self-evaluation – while three visual-domain strategies receive only 9.1% combined weight. We then demonstrate a novel phenomenon we term cross-modal contagion: evaluator preferences acquired on one modality transfer to and corrupt strategy selection on another. Through a four-phase isolation training paradigm, we measure contagion coefficients and document strategy inversion – the optimal strategy for a modality reverses after cross-modal exposure. A Phase 3 statistical validation across four evaluator configurations (N=53 total independent repetitions, 15,592 API calls) reveals a clear hierarchy: cross-model evaluation (GPT-4o, N=8) produces strong but symmetric bidirectional contagion (mean gamma_{T->V}=1.176, gamma_{V->T}=1.089, Delta=-0.088, p=0.575, Cohen's d=0.29); high round counts (DashScope, 50 rounds) cause collapse to single-strategy dominance (70% zero contagion); and self-evaluation provides near-complete immunity – 97% of runs (N=30, DeepSeek-chat) yield exactly zero contagion (mean gamma=0.033, 95% CI [-0.031, 0.010], p=0.642, d=0.07). No evaluator condition shows statistically significant directional asymmetry. We introduce the contagion matrix indexed by evaluator identity, release the MM-EPC experimental framework, and identify cross-model evaluator architecture as the primary risk factor for preference contagion.

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arXiv (CS.LG) 2026-06-12

Hierarchical Successor Representation for Robust Transfer

arXiv:2602.12753v2 Announce Type: replace Abstract: The successor representation (SR) provides a powerful framework for decoupling predictive dynamics from rewards, enabling rapid generalisation across reward configurations. However, the classical SR is limited by its inherent policy dependence: policies change due to ongoing learning, environmental non-stationarities, and changes in task demands, making established predictive representations obsolete. Furthermore, in topologically complex environments, SRs suffer from spectral diffusion, leading to dense and overlapping features that scale poorly. Here we propose the Hierarchical Successor Representation (HSR) for overcoming these limitations. By incorporating temporal abstractions into the construction of predictive representations, HSR learns stable state features which are robust to task-induced policy changes. Applying non-negative matrix factorisation (NMF) to the HSR yields a sparse, low-rank state representation that facilitates highly sample-efficient transfer to novel tasks in multi-compartmental environments. Further analysis reveals that HSR-NMF discovers interpretable topological structures, providing a policy-agnostic hierarchical map that effectively bridges model-free optimality and model-based flexibility. Beyond providing a useful basis for task-transfer, we show that HSR's temporally extended predictive structure can also be leveraged to drive efficient exploration, effectively scaling to large, procedurally generated environments.