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

ASyMOB: Algebraic Symbolic Mathematical Operations Benchmark

Large language models (LLMs) are increasingly applied to symbolic mathematics, yet existing evaluations often conflate pattern memorization with genuine reasoning. To address this gap, we present ASyMOB, a high-resolution dataset of 35,368 validated symbolic math problems spanning integration, limits, differential equations, series, and hypergeometrics. Unlike prior benchmarks, ASyMOB systematically perturbs each seed problem using symbolic, numeric, and equivalence-preserving transformations, enabling a fine-grained assessment of generalization. Our evaluation reveals three key findings: (1) most models' performance collapses under minor perturbations, while top systems exhibit an apparent regime shift in robustness; (2) integrated code tools stabilize performance, particularly for weaker models; and (3) we identify examples where Computer Algebra Systems (CAS) fail while LLMs succeed, as well as problems solved only via a hybrid LLM-CAS approach, highlighting a promising integration frontier. ASyMOB serves as a principled diagnostic tool for measuring and accelerating progress toward building verifiable, trustworthy AI for scientific discovery.

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

FashionChameleon: Towards Real-Time and Interactive Human-Garment Video Customization

Human-centric video customization, particularly at the garment level, has shown significant commercial value. However, existing approaches cannot support low-latency and interactive garment control, which is crucial for applications such as e-commerce and content creation. This paper studies how to achieve interactive multi-garment video customization while preserving motion coherence using only single-garment video data. We present FashionChameleon, a real-time and interactive framework for human-garment customization in autoregressive video generation, where users can interactively switch garment during generation. FashionChameleon consists of three key techniques: (i) Instead of training on multi-garment video data, we train a Teacher Model with In-Context Learning on a single reference-garment pair. By retaining the image-to-video training paradigm while enforcing a mismatch between the reference and garment image, the model is encouraged to implicitly preserve coherence during single-garment switching. (ii) To achieve consistency and efficiency during generation, we introduce Streaming Distillation with In-Context Learning, which fine-tunes the model with in-context teacher forcing and improves extrapolation consistency via gradient-reweighted distribution matching distillation. (iii) To extend the model for interactive multi-garment video customization, we propose Training-Free KV Cache Rescheduling, which includes garment KV refresh, historical KV withdraw, and reference KV disentangle to achieve garment switching while preserving motion coherence. Our FashionChameleon uniquely supports interactive customization and consistent long-video extrapolation, while achieving real-time generation at 23.8 FPS on a single GPU, 30-180$\times$ faster than existing baselines.

03.
medRxiv (Medicine) 2026-06-22

Modelling the decadal expansion of West Nile virus in Italy: the role of climatic, anthropogenic, and macroecological drivers

Abstract BACKGROUND West Nile virus (WNV) is a growing health burden in Italy. Anticipating human infection risk is hampered by the pathogen's complex ecology, highlighting the need for comprehensive early-warning tools. AIM We aimed to model municipal-level WNV risk in Italy and characterize its decadal expansion in Italy, providing a comprehensive ecological understanding of viral emergence. METHODS We applied a machine learning framework to annual human WNV case data from 2014 to 2024. The model integrated a suite of environmental, socio-economic, and macroecological predictors to generate risk projections. We evaluated the model's performance through multiple validation settings. We also performed an anticipation test for the 2025 epidemic season, using 2024 environmental data to assess the model's predictive accuracy against observed 2025 human cases. RESULTS Our model achieved robust performance (True Skill Statistic > 0.4) and captured WNV progressive expansion from 184 predicted positive municipalities in 2014 to 2,012 in 2024 (an 11-fold increase in 11 years). Seasonal minimum temperature was the primary risk driver, followed by monitoring year and population density, indicating active spatial spread. Environmental suitability consistently preceded clinical detection. Municipalities with cases in 2023-2024 exhibited significantly higher predicted suitability during 2018-2022 than those without cases (average risk 0.58 vs 0.20). Our model successfully identified emerging risk hotspots along the Adriatic coast and southern Italy before the official human spillover of 2025. CONCLUSION Embedding macroecological drivers into WNV risk modelling provides an improved understanding of drivers of rapid WNV expansion. Our model enables proactive risk mapping, surveillance efforts, and targeted public health measures.

04.
arXiv (quant-ph) 2026-06-12

Quantum Otto engine powered by an anisotropic Heisenberg XYZ model under independent local magnetic fields

arXiv:2606.12877v1 Announce Type: new Abstract: We study a quantum Otto heat engine whose working substance is an anisotropic two-qubit Heisenberg XYZ model. Independent local magnetic fields are used to control each spin individually. The influence of the longitudinal coupling, anisotropy, transverse coupling, and local fields on the net work output and efficiency is systematically examined. Reducing the longitudinal coupling is found to markedly improve both the maximum work and the peak efficiency. The engine performance reaches an optimum at a particular value of the anisotropy parameter. A local work analysis clarifies how work is produced during the cycle. Because of the asymmetric local fields and the intrinsic spin-spin interaction, the two qubits play markedly different thermodynamic roles; the interaction term itself contributes crucially to the total work. We further analyze the variation of quantum entanglement, quantified by concurrence, along the cycle. The results indicate that a pronounced change in entanglement between the hot and cold isomagnetic strokes is closely correlated with the efficiency enhancement. This work offers new insight into the operating principles and control of quantum Otto heat engines.

05.
arXiv (CS.AI) 2026-06-17

Conservation Laws for Modern Neural Architectures

arXiv:2606.17816v1 Announce Type: cross Abstract: Understanding gradient descent dynamics is key to explaining the success of over-parameterized models, where implicit bias manifests through conservation laws in gradient flow. While such laws are well understood for linear and ReLU networks, they remain largely unexplored for modern architectures. This work develops a unified framework to characterize conservation laws for contemporary models, including feedforward networks with GELU, SiLU, and SwiGLU activations, multihead attention with sinusoidal and rotary positional encodings, and Mixture-of-Experts architectures under diverse gating designs. Our theoretical findings are supported by experiments that validate the predicted invariants.

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

Efficient Zeroth-Order Federated Finetuning of Language Models on Resource-Constrained Devices

arXiv:2502.10239v3 Announce Type: replace-cross Abstract: Federated Learning (FL) is a promising paradigm for finetuning Large Language Models (LLMs) across distributed data sources while preserving data privacy. However, finetuning such large models is challenging on edge devices due to its high resource demand. Zeroth-order Optimization (ZO) estimates gradients through finite-difference approximations, which rely on function evaluations under random perturbations of the model parameters. Consequently, ZO with task alignment provides a potential solution, allowing finetuning using only forward passes with inference-level memory requirements and low communication overhead, but it suffers from slow convergence and higher computational demand. In this paper, we propose a new ZO-based method that applies a more efficient technique to reduce the computational demand associated with using a large number of perturbations while preserving their convergence benefits. This is achieved by splitting the model into consecutive blocks and allocating a higher number of perturbations to the second block, enabling efficient reuse of intermediate activations to update the full network with fewer forward evaluations. Our evaluation on RoBERTa-large, OPT1.3B, LLaMa-3-3.2B models shows up to $3\times$ reduction in computation compared to the other ZO-based techniques, while retaining the memory and communication benefits over first-order federated learning techniques.

07.
arXiv (CS.CL) 2026-06-12

One Token to Fool LLM-as-a-Judge

Large language models (LLMs) are increasingly trusted as automated judges, assisting evaluation and providing reward signals for training other models, particularly in reference-based settings like Reinforcement Learning with Verifiable Rewards (RLVR). However, we uncover a critical vulnerability even in this reference-based paradigm: generative reward models are systematically susceptible to reward hacking. We find that superficial inputs, which we term ''master keys'' such as non-word symbols (e.g., '':'' or ''.'') or generic reasoning openers (e.g., ''Thought process:'' or ''Let's solve this problem step by step.''), can consistently elicit false positive rewards without any substantive reasoning. Our systematic evaluation demonstrates this is a widespread failure affecting a diverse range of models, including leading proprietary systems such as GPT-o1 and Claude-4. These results challenge the assumed robustness of LLM judges and pose a significant threat to their reliability. To address this, we propose a simple yet effective data augmentation strategy using truncated model outputs as adversarial negative examples. The resulting Master Reward Models (Master-RMs) demonstrate state-of-the-art robustness against these ''master key'' attacks while maintaining high performance in standard evaluation settings. We supplement these findings with a comprehensive analysis of the vulnerability across model scales, prompt variations, and common inference-time strategies, offering insights to guide future research on robust LLM evaluation. We release our robust, general-domain reward models and the synthetic training data at https://huggingface.co/sarosavo/Master-RM and https://huggingface.co/datasets/sarosavo/Master-RM.

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

Reward Hacking in Language Model Agents: Revisiting AI Safety Gridworlds

arXiv:2606.15385v1 Announce Type: new Abstract: Reward hacking, where AI systems exploit misspecified objectives to achieve high reward without satisfying intended goals, remains a central challenge in AI safety. Yet most known instances have been discovered post hoc in frontier systems where controlled study is impractical. We adapt the AI Safety Gridworlds framework into a text-based evaluation suite that reformulates classic reinforcement learning safety tasks for language-based agents. Across frontier and mid-scale models, we find that specification gaming emerges zero-shot: models systematically achieve high observed reward while underperforming on hidden safety objectives, and even apparently safe behaviors can reflect misunderstanding rather than principled safety. Reinforcement learning does not correct these failures: direct reward optimization widens the gap between observed and hidden reward, as the model's initial competence causes it to lock into locally rewarding strategies before discovering safer alternatives. This pattern persists across model scales (1.5B–14B) and is not resolved by finer credit assignment, exploration prompts, or entropy regularization. Our results show that reward hacking arises naturally when optimizing proxy objectives with capable language model agents and resists standard mitigations, suggesting that proxy-reward failures in agentic settings may require approaches beyond standard exploration and credit-assignment fixes. To facilitate reproducibility, the code for this work is available at \href{https://github.com/asparius/verl-agent-safety}{our public repository}.

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

Sycophancy as Material Failure under Pushback Loading: A Multi-Axis Characterization Across Three Loading Cases and up to Seventeen Material Charges

Sycophancy in LLMs is documented across 70+ papers, but expert agreement on construct boundaries remains low (ICC=.184; Ye et al., 2026). The construct fragments because behavioral classification depends on which surface form is privileged. We adopt a materials-science framing: conversation as test specimen under load, LLM-model as material charge, pushback as progressive load, stance-flip as material failure. We characterize this failure across three loading cases (debate n=1000; false-presuppositions n=3400; ethical-setting n=3400; 10-17 material charges per case; 7800 specimens total) using 14 turn-level axis-measurements spanning velocity, damage accumulation, frame-drift, brittleness, and direction stability, plus three speaker-resolved axes from an independent pipeline. The measurements are Hooke-coupled ($\sigma = E \cdot \varepsilon$ analog) and reproduce across loading cases with effects up to $|r_{rb}| = 0.35$ on debate; the sign structure adds a second pattern: the ethical-setting case inverts the velocity and accumulation blocks. Variance composition partitions into two profiles: debate is charge-dominated (brittle-fracture-like: the material grade decides), false-presuppositions and ethical-setting are topic-dominated (creep-like: the load decides); the ratios (2.03 vs 0.13/0.17) are estimator-dependent, for debate even in direction. Cross-judge reliability (GPT-4o vs Haiku 4.5) shows debate scoring is judge-robust (Cohen's $\kappa = 0.88$) while false-presupposition scoring is judge-sensitive ($\kappa = 0.36$) – a caveat single-judge benchmarks must report. This is the methodological move Ye et al.'s diagnosis calls for: a multi-axis characterization that does not depend on which surface form of the construct one privileges.

10.
bioRxiv (Bioinfo) 2026-06-21

OracleScreen-LILRB4: Machine Learning-Guided Discovery of Myeloid Immune Checkpoint Binders Validated in Patient-Derived Cells

The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit rates observed in conventional high-throughput screening campaigns. Here we report OracleScreen-LILRB4, an ensemble machine learning framework trained on quantitative biophysical screening data from two structurally diverse compound libraries (19,800 compounds total) screened against the myeloid immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3). By formulating binding prediction as a regression task targeting continuous {Delta}Fnorm values rather than binary hit classifications, OracleScreen-LILRB4 achieved a mean Spearman R of 0.61 and ROC-AUC of 0.86 under scaffold-aware cross-validation. Prospective virtual screening of a 45,760-member compound library and experimental validation of the top 200 predictions yielded a 28.5% hit rate, representing a 15.0-fold enrichment over baseline, with 16 compounds demonstrating nanomolar-affinity LILRB4 (ILT3) engagement. Lead compounds ORS-22 and ORS-14 restored anti-tumor immune activity across patient-derived colorectal cancer and acute myeloid leukemia co-culture systems, reversing SCG2-mediated immunosuppression and recovering cytotoxic T-cell function. These findings establish OracleScreen-LILRB4 as an effective computational framework for accelerating small molecule discovery against non-enzymatic immune checkpoint targets.

11.
arXiv (CS.LG) 2026-06-17

Continuous-time Optimal Stopping through Deep Reinforcement Learning

arXiv:2606.17545v1 Announce Type: new Abstract: Simulation based solvers for optimal stopping problems must discretize the stopping decision. Under classical dynamic programming, a coarse exercise grid with only a few stopping opportunities can materially undervalue the optimal expected reward, whereas on a very fine grid, approximation errors accumulate through the backward recursion. To remove this limitation, we develop a new reinforcement-learning inspired algorithm that enables us to learn the exercise rule at arbitrarily fine time resolution. Our CARLOS (Continuous-time Adaptive Reinforcement Learning for Optimal Stopping) algorithm utilizes an aggregate deep neural network (ADNN) to learn a joint space-time decision boundary. Starting from a coarse time grid, we progressively increase the frequency of stopping opportunities, while in parallel training the ADNN to refine its timing-value estimates. We moreover design an adaptive sampling strategy that gradually concentrates training effort near the stopping boundary. Benchmarked results show that CARLOS delivers higher prices than existing Bermudan solvers, approaching the American upper bound, and achieves high computational efficiency relative to non-RL comparators.

12.
medRxiv (Medicine) 2026-06-24

TMPRSS2-Coagulation Nexus: A Novel Molecular Link Revealed by Pairwise Correlation Analysis Following AstraZeneca (ChAdOx1 nCoV-19) Vaccination in a Nigerian Cohort

Background: While haematological and coagulation changes following AstraZeneca vaccination have been described, the molecular mechanisms linking TMPRSS2 expression to coagulation remain underexplored, particularly in African populations. Methods: In this case-control study, 102 adults (51 vaccinated with AstraZeneca >=6 months prior, 51 unvaccinated controls) aged 18-65 years in Port Harcourt, Nigeria, were evaluated. Full blood count (Sysmex XN-1000), PT/aPTT (Erba Mannheim), RNA concentration, and qRT-PCR for ACE2/TMPRSS2 (normalized to GAPDH) were performed. Pearson correlations and t-tests were conducted (SPSS v26, p

13.
arXiv (CS.CV) 2026-06-17

Enhancing Pathological VLMs with Cross-scale Reasoning

Pathological images are inherently multi-scale, requiring pathologists to integrate evidence from global tissue architecture at low magnification to cellular morphology at higher magnification for accurate diagnosis. While existing pathological datasets for vision-language model (VLM) include various scales, they often lack an explicit cross-scale reasoning objective. This limitation prevents VLMs from capturing essential cross-scale representations and learning evidence-based reasoning. To bridge this gap, we introduce the first cross-scale training and evaluation paradigm that formulates pathology interpretation as multi-magnification reasoning. However, creating such a task reveals a critical challenge: multi-image visual question answering (VQA) is prone to text-only shortcuts, which allow models to guess answers using magnification-dependent artifacts rather than visual evidence. To address this, we propose a leakage-aware curation pipeline that combines adversarial text-only screening with constraint-guided question design. Using this pipeline, we construct Scale-VQA, a high-quality benchmark with 4,685 multiple-choice questions grounded in 2,537 pathology images across multiple magnification levels. Finally, we present ScaleReasoner-R1, a model trained via reinforcement learning to optimize performance on the cross-scale VQA task. ScaleReasoner-R1 achieves state-of-the-art performance on our cross-scale reasoning benchmark and generalizes to SOTA performance on established single-scale benchmarks. Findings suggest that even the limited cross-scale supervision can significantly improve pathological understanding. The code and demos will be open-sourced.

14.
arXiv (quant-ph) 2026-06-16

Morphology-resolved scrambling in a chaotic quantum billiard

arXiv:2606.16865v1 Announce Type: new Abstract: Chaotic quantum systems can retain spatial memory through scarred eigenstates, but whether these static structures control scrambling remains unclear. This work establishes a morphology-resolved connection between scarred eigenstates and eigenstate-resolved OTOCs in a peanut-shaped quantum billiard. Scalar localisation diagnostics, including differential entropy and continuum participation ratios, detect anomalous concentration but discard spatial architecture. A scale-normalised density overlap, in contrast, directly compares probability density profiles, revealing families of orthogonal eigenstates with nearly identical spatial morphology. Comparing the complete OTOC time traces of these orthogonal eigenstates reveals that morphological recurrence has dynamical content: moderate density overlap yields no universal prediction, whereas strongly recurring morphologies exhibit nearly identical OTOC growth and saturation. Thus, scarred structures act as spatial templates for operator growth, not merely static violations of ergodicity. This morphology-resolved framework turns eigenstate shape into a quantitative predictor of scrambling and provides a scale-controlled diagnostic of weak ergodicity breaking in quantum chaos.

15.
arXiv (quant-ph) 2026-06-16

Intermodal entanglement in a quantum optical model of HHG due to the back-action on the driving field

arXiv:2603.01315v2 Announce Type: replace Abstract: Preparation of nonclassical light with special quantum properties is essential for quantum technologies. High-harmonic generation (HHG) is a process which not only enables the creation of attosecond pulses but also has the potential to generate light with intricate quantum properties. In a recent experiment [1], nonclassical inter-harmonic correlations have been measured from a HHG source. In this work, we theoretically investigate entanglement between different harmonics within an effective quantum optical model. This model implements a signifcant degree of simplifcation regarding the processes within the target material, treating the material through susceptibilities, as it is usual in quantum optics. Such an approach yields a general description of HHG, permitting the implications that can be derived within it to hold broadly. We find that entanglement is produced as a result of the often neglected back-action. We can qualitatively reproduce experimentally measured nonclassicalities, which suggests that intermodal entanglement can, to an extent, be considered a universal phenomenon associated with HHG, rather than a result of using specific material targets.

16.
medRxiv (Medicine) 2026-06-12

Disentangling Confounders from Pathology in Long-COVID Trajectory Prediction for Women: An Interpretable Large-Language-Model Approach

Objective. Post-acute sequelae of SARS-CoV-2 infection (PASC, "Long COVID") dispropor- tionately affects women, in whom hallmark symptoms–insomnia, fatigue, palpitations, cogni- tive difficulty–overlap with comorbidities and hormonal transitions such as menopause. This diagnostic overlap is a confounding problem: models that forecast future symptom severity risk attributing baseline physiological noise to viral pathology. We ask whether an interpretable, causally disentangled language model can separate true pathological signal from such con- founders while remaining competitive with strong predictors of future PASC severity

17.
arXiv (CS.CL) 2026-06-24

Paying to Know: Micro-Transaction Markets for Verified Product Information in Agentic E-Commerce

Commercial NLP treats the shopping chatbot as a recommender or a conversion tool: its job is to match a user to a catalogue entry and close a sale. We argue that the arrival of agent-native micro-payment rails (e.g., x402, AP2) changes what is scarce. When the buyer is an autonomous agent that can investigate exhaustively, the bottleneck is no longer matching products but acquiring trustworthy, decision-relevant information about them. We envision agentic e-commerce as a micro-transaction market for verified information: buyer agents spend fractions of a cent to progressively unlock seller- and reviewer-supplied data – service histories, third-party test reports, bills of materials, audited sales and support metrics – paid for a la carte under a freemium model, with reviewer trust scored reputationally. We sketch the architecture of such a market and argue that it rewards genuine product quality and yields truer competition than ranking-based storefronts. We then translate the vision into concrete NLP problems – cost-optimal information acquisition, data pricing and negotiation, real-time entity resolution, grounded value exchange, and privacy-preserving persona modelling – and argue that these, not chat fluency, deserve the field's attention.

18.
medRxiv (Medicine) 2026-06-15

Evaluation of AI-Generated Synthetic Data for Clinical Research in Secondary Cardiovascular Prevention among Dyslipidemia Patients

Background: Access to high-quality clinical data is essential for advancing medical research and developing effective medical statistical and Artificial Intelligence models. However, privacy regulations and logistical barriers often hinder timely access to real-world data. Synthetic data offer a promising solution, preserving the statistical characteristics of original datasets while protecting patient privacy. Objectives: This study investigates the use of synthetic data for secondary cardiovascular prevention in patients with dyslipidemia, using two real-world datasets from Centro Cardiologico Monzino. Methods: Given the high dimensionality and limited sample size of the datasets, we employed a custom generative framework based on Large Language Models (LLMs). Pre-trained LLMs were fine-tuned on original clinical records to synthesize tabular data replicating source-data distributions. Fine-tuning was performed within the Centro Cardiologico Monzino's secure infrastructure to ensure data sovereignty. We evaluate clinical utility and privacy using fidelity and privacy metrics, identifying the optimal generative model and benchmarking against traditional anonymization methods. Results: Synthetic data achieved a superior trade-off than classically anonymized datasets. Real and synthetic datasets showed strong agreement, with significant distributional differences limited to few variables. Models trained on synthetic data replicated key associations from the original dataset, including therapy modification and creatine phosphokinase as predictors of SAMS, and pharmacological intensity as the main driver of LDL-C reduction. Conclusions: Results support the feasibility of using synthetic data as a proxy for real-world datasets in exploratory analyses and model development. Despite slight attenuation of some effect sizes, preserved clinical relationships reinforce the validity of synthetic data in medical research.

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

JGRA: Jacobian Geometry Robustness Assessment in NISQ Noise-Aware Quantum Neural Networks

arXiv:2606.09964v2 Announce Type: replace-cross Abstract: The NISQ era places stringent constraints on quantum computation, where noise and decoherence fundamentally limit performance. In classical deep learning, model robustness and resilience to perturbations are well studied: deep neural networks (DNNs) maintain high performance despite pruning, noise injection, and structural perturbations due to inherent redundancy in their representations. A central challenge in quantum machine learning is to transfer this notion of robustness to quantum neural networks (QNNs) under realistic NISQ noise. While classical deep learning exhibits robustness through structural redundancy, analogous principles for QNNs remain underdeveloped. We propose JGRA: a framework for assessing robustness in noise-aware QNNs via Jacobian geometry, capturing model sensitivity to parameter perturbations induced by noise. Our method includes entropy-matched noise calibration, noise-aware training, and noise-conditioned Jacobian extraction, yielding geometric descriptors that link clean-regime structure to noisy inference behaviour. We also empirically demonstrate that these descriptors encode predictive information about robustness under unseen noise.

20.
arXiv (CS.LG) 2026-06-16

A Compositional Framework for Open-ended Intelligence

arXiv:2606.15386v1 Announce Type: new Abstract: Open-ended intelligence is the capacity to adapt to novel problems and environments that are substantially different from those in training. We formalize open-ended intelligence as the closure induced by a finite primitive set \(P\) and a set of composition operators \(C\). We characterize properties of the induced closure \(\mathcal{L}(P,C)\) that support unbounded compositional generation across families of tasks and worlds. A mathematics of open-ended intelligence requires two pillars: a minimal set of representational primitives (e.g., states, actions) and algorithmic primitives (e.g., nearest neighbor), together with composition motifs (e.g., recursion, sequencing) that reflect an acquired compositional grammar. The closure of these two pillars enables the generation of infinite adaptive responses across a wide range of settings. The mathematics supports complementary research agendas, including evaluation metrics for explanation and interpretability, as well as building architectures where compositional generalization is native. We propose next primitive prediction as a novel architectural objective, where the training objective encourages the acquisition of reusable algorithmic primitives and their compositional grammar, such that new solutions are generated through recombination. Curriculum learning and self-play enable lifelong learning and expansion of the closure by discovering reusable primitives and transition motifs across families of tasks and worlds. We ground the framework through case studies in physics, evolution, and neuroscience.

21.
bioRxiv (Bioinfo) 2026-06-13

MoE-Bind: Guiding De Novo Protein Binder Generation with Sparse Experts

作者:

De novo protein binder design has been dominated by structure-based pipelines that require known three-dimensional target conformations and consume substantial compute and generation time per design, limiting their throughput and accessibility for routine large-scale binder exploration. Sequence-only generative models promise a faster and lighter alternative, yet existing systems remain uniformly dense and frequently reintroduce structural computation at inference, undermining the core advantages they were intended to deliver. Across the broader language modelling community, transformers have meanwhile transitioned from fully dense designs to sparse Mixture-of-Experts architectures that decouple capacity from per-token compute, a shift that has yet to reach sequence-only protein binder generation. We present MoE-Bind, an autoregressive protein binder generator that, for the first time in this domain, combines Multi-head Latent Attention with a sparse Mixture-of-Experts feed-forward network and is evaluated under two independent structure predictors, Boltz-2 and AlphaFold2-Multimer. Despite activating less than half the per-token parameters of compute-matched dense baselines, MoE-Bind matches or exceeds them on full-length receptor-conditioned binder generation on a leakage-free Docking Benchmark 5.0 evaluation, transfers without peptide-specific training to short-peptide design, and reduces training and inference compute by a large margin. Routing analysis on generated binders reveals interpretable expert specialization at both the individual amino acid and biochemical group level, a structured expert-token alignment not previously reported for natural-language MoE models. These results show that sparse architectural design, rather than scale, can deliver fast, structure-free, and interpretable protein binder generation.

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

MENTOR: Reinforcement Learning via Flexible Teacher-Optimized Rewards for Tool-Use Distillation

Distilling the tool-use capabilities of large language models (LLMs) into small language models (SLMs) is essential for their practical application. The predominant approach, supervised fine-tuning (SFT), suffers from poor out-of-domain (OOD) generalization due to its rigid alignment with static teacher trajectories. While reinforcement learning (RL) offers an alternative, the capacity limitations of SLMs pose a severe dilemma: sparse outcome rewards provide insufficient guidance, whereas strict trajectory matching imposes overly restrictive constraints. To bridge this capacity-driven gap, we propose MENTOR, which introduces a flexible yet process-aware reward structure. Instead of enforcing rigid replication, MENTOR uses the teacher's reference to guide tool-use behavior, balancing behavioral alignment with downstream performance. Extensive experiments on controlled executable-tool benchmarks demonstrate that MENTOR improves OOD tool-use performance compared to SFT and strict RL baselines. Our findings suggest that within verifiable tool-use environments, flexible tool-use alignment offers a more effective approach than strict trajectory replication for developing adaptable small models.

23.
PLOS Computational Biology 2026-06-22

TCRBinder: Unified pre-trained language model with paired-chain synergy for predicting T-cell receptor binding specificity

作者:

by Weihe Dong, Qiang Yang, Long Xu, Xiaokun Li, Kuanquan Wang, Suyu Dong, Gongning Luo, Xianyu Zhang, Tiansong Yang, Xin Gao, Guohua Wang Deciphering how human T cells recognise peptide-HLA (pHLA) complexes underpins next-generation vaccines and personalised immunotherapies, yet extreme sequence diversity and paired-chains interdependence still hamper reliable in silico prediction of T-cell receptor (TCR) specificity. To overcome these hurdles, we built TCRBinder, a paired-chain-aware deep model with a multi-branch encoder that routes each molecular component through dedicated transformer-based modules to capture contextual signals in both HLA pseudo-sequences and antigenic peptides while simultaneously processing the TCR α and β chains. This design captures the synergistic interaction between paired chains to emulate peptide-HLA-TCR (PHT) interactions and expose residue-level contact motifs. Across PHT and peptide-TCR (pTCR) benchmarks, the model delivered state-of-the-art performance (AUC-ROC = 0.911, AUPR = 0.791 for the PHT task) and remained superior on multiple independent datasets. We tracked the dynamics of clonal expansion and, in a large SARS-CoV-2 repertoire containing completely unseen peptides, improved the AUC-ROC by up to 16.3% over the leading alternatives. Moreover, TCRBinder provided mechanistic insights by pinpointing contact hotspots and quantifying residue contributions to binding probability. These capabilities position TCRBinder as a versatile tool for rational antigen discovery, immunotherapy stratification, and neoantigen vaccine design.

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

Human Cognition in Machines: A Unified Perspective of World Models

This report of world models distinguishes prior works by the cognitive functions they innovate. Many works claim an almost human-like cognitive capability in their world models. To evaluate these claims requires a proper grounding in first principles from human and machine cognition theory. In moving towards human-like world models we present a conceptual unified framework for world models that fully incorporates all the cognitive functions (i.e., memory, perception, language, reasoning, imagining, motivation, and metacognition) and identify gaps in existing research as a guide for future states of the art. In particular, we find that motivation (especially intrinsic motivation) and metacognition remain drastically under-researched, and we propose concrete directions to address these gaps informed by active inference and global workspace theory. We also introduce epistemic world models, a new category encompassing agent frameworks for scientific discovery that operate over structured knowledge. Our taxonomy, applied to video, embodied, and epistemic world models, suggests research directions where prior taxonomies have not.

25.
arXiv (CS.CV) 2026-06-25

SPARC: Separating Perception And Reasoning Circuits for Test-time Scaling of VLMs

Despite recent successes, test-time scaling – i.e., dynamically expanding the token budget during inference as needed – remains brittle for vision-language models (VLMs). Unstructured visual reasoning chains entangle perception and reasoning, leading to long, disorganized contexts where small perceptual mistakes may cascade into completely wrong answers. Reasoning also requires expensive reinforcement learning with hand-crafted rewards. Here, we introduce SPARC (Separating Perception And Reasoning Circuits), a modular framework that explicitly decouples visual perception from reasoning. Inspired by sequential sensory-to-cognitive processing in the brain, SPARC implements a two-stage pipeline where the model first performs explicit visual search to localize question-relevant regions, then conditions its reasoning on those regions to produce the final answer. This separation enables independent test-time scaling with asymmetric compute allocation (e.g., prioritizing perceptual processing under distribution shift), and supports selective optimization (e.g., improving the perceptual stage alone when it is the bottleneck for end-to-end performance). It also accommodates compressed contexts by running global search at lower image resolutions and allocating high-resolution processing only to selected regions, thereby reducing visual token count and compute. SPARC outperforms monolithic baselines and strong visual-grounding approaches across challenging visual reasoning tasks, such as improving Qwen3VL 4B on the $V^*$ VQA benchmark by 6.7 points and surpassing "thinking with images" by 4.6 points in an OOD setting with a $200\times$ lower token budget.