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

Qwen-RobotManip Technical Report: Alignment Unlocks Scale for Robotic Manipulation Foundation Models

Foundation models in language and multimodality achieve strong generalization by aligning heterogeneous data under a unified formulation and training at scale. In this report, we investigate whether this scaling recipe can be applied to robotic manipulation to achieve genuine generalization. This is challenging because, unlike text, manipulation data is heterogeneous by nature, expensive to collect, and narrow in diversity, making alignment and scale simultaneously difficult. We present Qwen-RobotManip, a generalizable Vision-Language-Action foundation model built on Qwen-VL. Qwen-RobotManip introduces a unified alignment framework across the representation, motion, and behavioral dimensions of manipulation, making large-scale multi-source training coherent rather than conflicting. This alignment capability in turn enables Qwen-RobotManip to absorb manipulation data at a scale that prior training regimes could not sustain. A human-to-robot synthesis pipeline converts egocentric hand demonstrations into robot trajectories across 15 platforms, and a rigorous curation pipeline harmonizes heterogeneous datasets. Using only open-source datasets and human videos without proprietary data collection, Qwen-RobotManip constructs a ~38,100-hour pretraining corpus and exhibits emergent generalization capabilities, including zero-shot instruction following, robustness to perturbations, reactive error recovery, and cross-embodiment transfer. We find that standard benchmarks fail to capture pretraining quality and instead adopt OOD settings including RoboCasa365, LIBERO-Plus, EBench, RoboTwin-Clean2Rand, RoboTwin-IF, and RoboTwin-XE. Qwen-RobotManip substantially outperforms prior state-of-the-art models, including $\pi$0.5, across all OOD settings, ranks 1st in RoboChallenge with a 20% relative improvement, and is validated on real-robot platforms including AgileX ALOHA, Franka, UR, and ARX.

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

JetParticle-JEPA: An Efficient Self-Supervised Representation Learning method for Jet Tagging in High-Energy Physics

arXiv:2606.14813v1 Announce Type: cross Abstract: Jet tagging at the Large Hadron Collider increasingly relies on deep learning models trained on massive simulated datasets, leading to high computational costs and limited robustness to detector mismodeling. We introduce JetParticle-JEPA (JP-JEPA), a self-supervised Joint-Embedding Predictive Architecture that learns physically meaningful jet representations directly from continuous particle clouds without tokenization or reconstruction of raw inputs. Built on a Particle Transformer backbone, JP-JEPA predicts latent representations of masked particles while preserving fine-grained kinematic correlations. On the JetClass benchmark, JP-JEPA achieves performance comparable to fully supervised state-of-the-art methods on the full dataset, surpasses supervised baselines in low-label regimes, and significantly outperforms existing SSL approaches. On Top Quark and Quark-Gluon Tagging benchmarks, it remains on par with supervised methods. The learned representations also exhibit strong robustness to missing detector information and improved uncertainty behavior, highlighting JP-JEPA as a promising foundation-model framework for robust and data-efficient jet physics at the LHC.

03.
arXiv (CS.AI) 2026-06-19

Configurable Clinical Information Extraction with Agentic RAG: What Works, What Breaks, and Why

arXiv:2606.19602v1 Announce Type: new Abstract: Patient contexts span hundreds of heterogeneous documents and thousands of structured data points, yet the document-level metadata that AI systems need for retrieval and triage is absent or incomplete. Standard retrieval-augmented generation fails on this data, mishandling temporal reasoning, cross-document dependencies, and missing metadata. We deploy ACIE (Agentic Clinical Information Extraction) at University Medicine Essen: an on-premise agentic RAG pipeline that reasons over complete patient contexts and grounds every answer in source passages for clinician verification. We quantify the metadata gap, trace the architectural decisions it shaped, and evaluate extraction alongside an independent retrospective lymphoma registry study, in which nuclear-medicine physicians verify every extracted value against its cited sources. Across 7,326 judgments, clinicians accepted 96.5\% of extractions, with per-type acceptance ranging from 80\% to 99\%.

04.
arXiv (CS.LG) 2026-06-17

Recursive Scaling in Masked Diffusion Models

arXiv:2606.18022v1 Announce Type: new Abstract: Masked diffusion models (MDMs) have recently emerged as a promising paradigm for sequence generation. Scaling MDMs is conventionally achieved by increasing the parameter count or the number of denoising steps. We introduce Recursive Masked Diffusion Models (R-MDMs), which add recursive depth as a third scaling axis by repeatedly applying the same denoising transformer within each diffusion step. Recursion enables iterative refinement of the output through parameter reuse, increasing effective model depth without increasing parameter count. Across structured generation tasks, including Sudoku and Countdown, we show that R-MDMs achieve substantially improved parameter efficiency: a model with $L$ recursive iterations often matches the performance of non-recursive baselines with roughly $L\times$ more parameters. Moreover, recursive refinement can partially substitute for additional denoising steps, allowing recursive models to reach the same generation quality with fewer forward passes at inference time. These results suggest that recursive depth is a practically useful scaling mechanism for MDMs, improving both parameter efficiency and the allocation of test-time compute.

05.
arXiv (CS.LG) 2026-06-11

Higher-Order Token Interactions via Quantum Attention

arXiv:2606.11673v1 Announce Type: cross Abstract: Standard dot-product self-attention computes, in a single layer, only pairwise (order-2) interactions between tokens; representing a generic order-$k$ interaction is known to require either super-quadratic resources in one layer or composition across depth. We introduce Quantum Higher-Order Attention (QHA), a shallow, hardware-realizable quantum attention head that, via data re-uploading and an all-to-all non-Clifford entangler, synthesizes order-$k$ token interactions inside the circuit and exposes them through a local single-qubit read-out. We prove (i) an expressivity separation: any single standard self-attention layer with embedding dimension $m$, $H$ heads and $p$-bit precision satisfying $mHp=o(N/\log\log N)$ cannot represent the order-$k$ correlation family that one QHA head represents with circuit depth $O(\log k)$ ($O(k)$ two-qubit gates); and (ii) a trainability guarantee for its local-design instantiation: with a local read-out and $O(\log n)$ depth the gradient variance is $\Omega(1/\mathrm{poly}(n))$ (no barren plateau), which we confirm empirically – while being explicit that the more expressive all-to-all instantiation we benchmark is trained empirically and shows exponentially decaying gradients. Empirically, at a $6.5\times$ smaller parameter budget, QHA generalizes hidden-subset parity of every order $k\le6$ from disjoint inputs, whereas the larger classical attention head collapses past order~2; consistent with theory, the size of the advantage tracks the target's Fourier degree - largest for parity and shrinking when low-order structure is present. As an application, QHA serves as a compact high-order interaction detector across three domains - genetic epistasis, learning-parity-with-noise, and graph triangle detection - reaching the noise ceiling at the smallest parameter budget where field-standard linear methods fail.

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

Design and Scheduling of an AI-based Queueing System

arXiv:2406.06855v3 Announce Type: replace-cross Abstract: To leverage prediction models to make optimal scheduling decisions in service systems, we must understand how predictive errors impact congestion due to externalities on the delay of other jobs. Motivated by applications where prediction models interact with human servers (e.g., content moderation), we consider a large queueing system comprising of many single server queues where the class of a job is estimated using a prediction model. By characterizing the impact of mispredictions on congestion cost in heavy traffic, we design an index-based policy that incorporates the predicted class information in a near-optimal manner. Our theoretical results guide the design of predictive models by providing a simple model selection procedure with downstream queueing performance as a central concern, and offer novel insights on how to design queueing systems with AI-based triage. We illustrate our framework on a content moderation task based on real online comments, where we construct toxicity classifiers by finetuning large language models.

07.
arXiv (CS.CL) 2026-06-16

Evaluating LLM Personalization via Semantic Constraint Verification

Current evaluation paradigms for Large Language Model (LLM) personalization rely heavily on brittle surface-matching metrics or computationally expensive LLM-as-a-judge protocols, both of which lack interpretability. To address these limitations, we introduce Natural Language Inference Constraint Verification (NLICV), a scalable, semantically invariant framework that maps sentence meanings to truth-condition sets to verify personalization constraints via a Natural Language Inference (NLI) model. Moving beyond binary scoring, NLICV categorizes LLM behaviors into four distinct modes: personalization, generalization, sycophancy, and failure. Extensive experiments demonstrate that NLICV aligns closely with human annotations while drastically reducing the latency and token costs associated with LLM judges (up to 2100 inference speedup). Finally, through an ablation-based procedure, NLICV pinpoints the exact sentences driving the constraint verification, yielding faithful, understandable evidence for its evaluations.

08.
arXiv (CS.AI) 2026-06-18

Large-Scale OD Matrix Estimation with A Deep Learning Method

arXiv:2310.05753v2 Announce Type: replace Abstract: The estimation of origin-destination (OD) matrices is a crucial aspect of Intelligent Transport Systems (ITS). It involves adjusting an initial OD matrix by regressing the current observations like traffic counts of road sections (e.g., using least squares). However, the OD estimation problem lacks sufficient constraints and is mathematically underdetermined. To alleviate this problem, some researchers incorporate a prior OD matrix as a target in the regression to provide more structural constraints. However, this approach is highly dependent on the existing prior matrix, which may be outdated. Others add structural constraints through sensor data, such as vehicle trajectory and speed, which can reflect more current structural constraints in real-time. Our proposed method integrates deep learning and numerical optimization algorithms to infer matrix structure and guide numerical optimization. This approach combines the advantages of both deep learning and numerical optimization algorithms. The neural network(NN) learns to infer structural constraints from probe traffic flows, eliminating dependence on prior information and providing real-time performance. Additionally, due to the generalization capability of NN, this method is economical in engineering. We conducted tests to demonstrate the good generalization performance of our method on a large-scale synthetic dataset. Subsequently, we verified the stability of our method on real traffic data. Our experiments provided confirmation of the benefits of combining NN and numerical optimization.

09.
arXiv (CS.LG) 2026-06-12

Fed-FBD: Federated Functional Block Diversification for Isolation, Privacy, and Surgical Unlearning

arXiv:2606.12679v1 Announce Type: new Abstract: Federated learning (FL) enables collaborative model training without sharing raw patient data, but standard approaches such as FedAvg treat each client as a black box and provide no mechanism for isolating an adversarial contributor, auditing per-client influence, or honoring a departed participant's right to be forgotten. We present Fed-FBD (Federated Functional Block Diversification), a modular federated architecture that decomposes a ResNet backbone into six functional blocks (the stem, four residual groups, and the classification head) and maintains a warehouse of N color variants, each assembled from independently tracked and contributor-stamped blocks. Fed-FBD provides three capabilities absent in FedAvg: (i) architecturally guaranteed block-level isolation, so that an adversarial or mislabelled client cannot contaminate the clean colous; (ii) privacy-by-design, where membership inference advantage is already indistinguishable from chance before any privacy mechanism is applied; and (iii) surgical machine unlearning of a departed participant's contribution at sub-second cost and without retraining. Experiments on six MedMNIST-2D datasets, PathMNIST at 224x224, and CIFAR-10 show that Fed-FBD trades a modest 0.3%-3.1% IID accuracy gap on the adequately sized datasets for these guarantees, remains within 0.8%-4.0% of FedAvg at Dirichlet alpha=1.0 on three of four datasets, and confines all six adversarial attacks we study to the poisoned client's own blocks with at most +/-0.01 AUC drift on the clean colors.

10.
arXiv (CS.CL) 2026-06-11

FlowBank: Query-Adaptive Agentic Workflows Optimization through Precompute-and-Reuse

Large Language Model (LLM)-based multi-agent systems are increasingly powerful, but current agentic workflow optimization paradigms make an unsatisfying trade-off. Task-level methods spend substantial offline compute yet deploy only a single workflow, leaving complementary candidates unused, while query-level methods synthesize a new workflow per query at substantial inference cost. Our motivating analysis shows these paradigms are more complementary than competing: workflows discovered during offline search often solve different subsets of queries, and many queries handled by expensive query-level generation can already be solved by cheaper precomputed workflows. This suggests a different objective: rather than searching for one universally best workflow or regenerating one per instance, we should build a compact bank of reusable, complementary workflows and select among them adaptively at inference time. Doing so requires solving three coupled problems: generating complementary rather than redundant candidates, compressing them into a small deployable portfolio, and assigning each query to the right workflow under a performance-cost trade-off. To this end, we present FlowBank, a three-stage framework for portfolio-based agentic workflow optimization. Diversifying proposes DiverseFlow to steer search toward under-covered queries and produce a high-coverage candidate pool. Curating proposes CuraFlow to compress this pool into a compact portfolio with minimal redundancy. Matching casts deployment as edge-value prediction on a query-workflow bipartite graph and routes each incoming query to the portfolio member with the best predicted utility. Across five benchmarks, FlowBank achieves the highest average score among the evaluated methods while remaining cost-competitive, improving over the strongest automated and handcrafted baselines by 4.26% and 14.92% relative, respectively.

11.
arXiv (quant-ph) 2026-06-16

Watching a Superconducting Coplanar Waveguide Heat Up with a Single Color Center

arXiv:2606.15398v1 Announce Type: new Abstract: Single color centers in diamond offer a local probe of their cryogenic environment, providing a direct way to quantify heating in spin-control hardware. Here, we establish a single spectrally stable tin-vacancy (SnV) center as an on-chip thermometer for a diamond membrane and use it to characterize microwave- and radio-frequency-induced heating in a superconducting coplanar waveguide patterned on the same chip. We first calibrate the temperature dependence of the optical C-transition frequency and linewidth from $20\,\mathrm{K}$ down to the few-kelvin regime. At lower temperatures, where the optical response becomes weakly temperature dependent, we use the spin-lattice relaxation time $T_1$ as a complementary thermometer and tune its sensitivity with the transverse magnetic-field component. Applying this local thermometer to a niobium coplanar waveguide, we observe magnetic-field-dependent superconducting breakdown under GHz drive, accompanied by abrupt heating of the diamond. In contrast, at $20\,\mathrm{MHz}$ and $400\,\mathrm{mT}$, relevant for nuclear-spin control, we detect no measurable heating up to the breakdown threshold of $9.4\,\mathrm{dBm}$, corresponding to $B_\mathrm{ac}\sim1.2\,\mathrm{mT}$. These results define a safe operating window for superconducting microwave and RF control structures in diamond-based quantum nodes.

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

Attention by Synchronization in Coupled Oscillator Networks

arXiv:2606.12059v1 Announce Type: new Abstract: We address transformer attention on energy-constrained physical substrates. Softmax attention requires exponentiation and global reduction, operations with high energy cost on von Neumann hardware and no natural physical analog. We show that Kuramoto synchronization dynamics (which arise in electrical, mechanical, superconducting, and charge-density-wave oscillator arrays, among other physical systems) implement a well-defined attention operation without either. The resulting mechanism, fixed-query oscillator attention, replaces softmax's arithmetic with the equilibration of a gradient flow on the sphere: queries are learned anchors fixed on the sphere, and free oscillators evolve under Kuramoto-Lohe dynamics until they settle at positions encoding attention weights via cosine similarity. Because the computation is equilibration, it requires no exponentiation; the only global operation is an affine normalization at readout. The fixed point is provably unique and globally attractive from almost every initial condition, a guarantee that holds across every physical realization. Empirically, at the minimal hardware configuration (oscillator dimension $d_{\mathrm{osc}}$ = 2), oscillator attention outperforms softmax on keyword spotting (+1.00 pp) and on subject-verb agreement (+5.27 pp on hard sentences, with zero training failures versus one in five for softmax). On causal language modeling, where softmax retains an advantage, oscillator attention closes the gap as $d_{\mathrm{osc}}$ grows: from +11.09 PPL at $d_{\mathrm{osc}}$ = 2 to +2.98 PPL at $d_{\mathrm{osc}}$ = 32 on WikiText-2, and from +2.39 PPL at $d_{\mathrm{osc}}$ = 2 to +0.57 PPL at $d_{\mathrm{osc}}$ = 32 on TinyStories. The main objective of this work is not to replace softmax in software but to provide a mathematically grounded blueprint for accurate attention on physical substrates.

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

DAM-VLA: Decoupled Asynchronous Multimodal Vision Language Action model

Vision-language-action (VLA) models inherit a shared synchronous clock from vision-language pretraining, processing every input at one rate. This is misaligned with physical interaction, where a high-frequency modality changes at hundreds of hertz, vision evolves more slowly, and language stays constant across an episode. A synchronous VLA oversamples slow modalities, undersamples fast ones, and caps action generation at the lowest effective frequency. We hypothesize that decoupling temporal processing per modality, letting each update and retain information at its own sensor rate, yields stronger representations and more robust control. We present DAM-VLA, which maintains per-modality latent buffers refreshed at sensor rates and read continuously by the action head, integrating new high-frequency modalities through gated cross-attention that leaves the pretrained backbone intact. Across seven contact-rich real-world manipulation tasks, DAM-VLA more than doubles the average success rate of the strongest synchronous baseline (95.2\% vs.\ 40.95\%) while sustaining smooth, reactive 100\,Hz control. Project website: \href{https://intuitive-robots.github.io/DAM-VLA/}{intuitive-robots.github.io/DAM-VLA/}

14.
arXiv (CS.LG) 2026-06-12

Adjusted Cup-Product Neural Layer

arXiv:2606.13568v1 Announce Type: new Abstract: Many important observables in physics and geometry are cup products of cochains. The adjusted cup product neural layer has been introduced in this paper. It is a neural primitive that hard wires the cup product with an adjustment term from higher gauge theory. This creates a readout that is gauge invariant by design. Their main theoretical result shows that on a closed cycle the output relies entirely on the adjustment coefficient. Setting this coefficient to zero removes the output completely regardless of other parameters. Thus the adjustment is the only source of gauge invariant signal. They prove this observable is a nonzero quadratic form and is exactly invariant under one and two gauge transformations.

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

FireRed-Image-Edit-1.0 Technical Report

We present FireRed-Image-Edit, a diffusion transformer for instruction-based image editing that achieves state-of-the-art performance through systematic optimization of data curation, training methodology, and evaluation design. We construct a 1.6B-sample training corpus, comprising 900M text-to-image and 700M image editing pairs from diverse sources. After rigorous cleaning, stratification, auto-labeling, and two-stage filtering, we retain over 100M high-quality samples balanced between generation and editing, ensuring strong semantic coverage and instruction alignment. Our multi-stage training pipeline progressively builds editing capability via pre-training, supervised fine-tuning, and reinforcement learning. To improve data efficiency, we introduce a Multi-Condition Aware Bucket Sampler for variable-resolution batching and Stochastic Instruction Alignment with dynamic prompt re-indexing. To stabilize optimization and enhance controllability, we propose Asymmetric Gradient Optimization for DPO, DiffusionNFT with layout-aware OCR rewards for text editing, and a differentiable Consistency Loss for identity preservation. We further establish REDEdit-Bench, a comprehensive benchmark spanning 15 editing categories, including newly introduced beautification and low-level enhancement tasks. Extensive experiments on REDEdit-Bench and public benchmarks (ImgEdit and GEdit) demonstrate competitive or superior performance against both open-source and proprietary systems. To support future research, our code, models, and benchmark suite are publicly available at https://github.com/FireRedTeam/FireRed-Image-Edit/ .

16.
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.

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

Machine-learning-based multipoint optimization of fluidic injection parameters for improving nozzle performance

arXiv:2409.12707v2 Announce Type: replace-cross Abstract: Fluidic injection offers a promising solution to improve the performance of the overexpanded single expansion ramp nozzles (SERNs) during vehicle acceleration. However, determining the injection parameters that yield the best overall performance across multiple nozzle operating conditions remains a challenge. The gradient-based optimization method requires gradients of injection parameters at each design point, which can lead to high computational costs when using computational fluid dynamics (CFD) simulations. This paper uses a pretrained neural network to replace CFD during optimization, enabling quick calculation of the nozzle flow field at multiple design points. Considering the physical characteristics of the nozzle flow field, a prior-based prediction strategy is adopted to enhance the model's accuracy. In addition, the neural network's back-propagation algorithm computes gradients quickly by running the computation only once, thereby greatly reducing gradient computation time compared to the finite difference method. As a test case, the average nozzle thrust coefficient of an SERN at seven design points is optimized, resulting in a 1.14\% improvement. The time cost is greatly reduced compared with traditional optimization methods, even when the time required to establish the training database is included.

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

LoComposition: Terrain-Adaptive Energy-Efficient Quadruped Locomotion without Gait Priors

arXiv:2606.15896v1 Announce Type: cross Abstract: Learning-based quadrupedal locomotion typically relies on complex reward formulations that entangle task specification, operational limits, gait preference, and terrain adaptation within a single optimization objective. We instead treat these functions through distinct mechanisms: rewards for task specification, constraints for operational limits, energy minimization for gait preference, and exteroceptive perception for adapting energy use to terrain difficulty. We show that these components jointly enable efficient, terrain-adaptive locomotion, and that removing each component exposes a distinct failure mode. Our formulation removes explicit gait priors (including air-time, contact-count, and foot-clearance targets) in favor of emergent behavior. Compared to a conventional complex-reward baseline, our formulation achieves comparable terrain traversal while reducing cost of transport by 56% and operational-limit violations by 96%. The resulting policies transfer zero-shot to a physical Unitree Go2 using LiDAR-based elevation mapping. Project website with videos: https://tinyurl.com/locomposition.

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

S$^2$COPE: Self-Supervised Concept Discovery via Preference Learning

Current representation learning paradigms force a fundamental compromise: self-supervised methods scale to massive datasets but yield opaque features, whereas interpretable models remain bottlenecked by the need for dense human annotation. We introduce Self-Supervised Concept discOvery via Preference lEarning (\model), a label-free framework that resolves this dilemma. Instead of treating Vision-Large-Language Models (VLLMs) as static feature extractors, \model leverages them as active participants in a self-supervised preference optimization loop. By autonomously hypothesizing, validating, and reinforcing candidate visual attributes directly from raw imagery, our framework discovers novel, structured concepts without a single label. Extensive experiments across natural, medical, and physics domains demonstrate that \model successfully extracts domain-specific concepts where standard VLLMs often fail to generate. By amortizing concept discovery directly into the VLLM backbone through our self-supervised preference objective – rather than relying on static generation and disjoint filtering – we achieve up to a 24-point absolute improvement in downstream top-1 classification accuracy on unseen data. Our work suggest that interpretability can emerge through a model's autonomous interaction with incidental visual structures, without any human supervision.

20.
medRxiv (Medicine) 2026-06-12

Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk

Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 significant cell-type-specific CpG sites in 106 loci and 68 risk genes in 40 loci, including 26 previously unreported loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-{beta} signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.

21.
bioRxiv (Bioinfo) 2026-06-12

Generalisable tissue-wide molecular reconstruction from histology

Spatial transcriptomics technologies measure gene expression within intact tissues but remain difficult to scale across large tissue sections and patient cohorts. Consequently, many studies rely on tissue microarrays (TMAs) or sparse spatial profiling designs, where molecular measurements are available for only limited tissue regions and are often generated using heterogeneous gene panels. Existing H&E to spatial gene expression prediction methods remain challenged by sparse molecular measurements, partially overlapping gene panels and tissue-wide reconstruction across heterogeneous spatial datasets. Here, we present GHIST+, a framework for tissue-wide reconstruction of single-cell molecular states from H&E histology. GHIST+ integrates cellular morphology, local tissue context and shared tissue representations to extend sparse molecular measurements into tissue-wide molecular maps across heterogeneous spatial datasets. Across multiple cancer types and GTEx breast tissues, GHIST+ reconstructs biologically meaningful tissue-wide molecular organisation from sparse TMA-derived measurements while preserving spatial tissue structure, cell-type organisation and age-associated tissue states across cancer and non-cancer settings. GHIST+ establishes a scalable framework for transforming sparse spatial profiling experiments into tissue-wide molecular maps, enabling cohort-scale molecular reconstruction from routine histology under heterogeneous spatial transcriptomic settings.

22.
arXiv (CS.CV) 2026-06-17

BrainWorld: A Structural-Prior-Conditioned Generative Model for Whole-Brain 4D fMRI Dynamics

Whole-brain 4D fMRI generation is valuable for modeling functional brain dynamics, yet existing fMRI foundation models mainly target representation learning and downstream prediction rather than conditional predictive generation. We introduce BrainWorld, a structural-prior-conditioned generative model for whole-brain 4D fMRI dynamics. BrainWorld uses sMRI as subject-level anatomical context to guide future fMRI generation, integrating structural information into the denoising process rather than treating it as a parallel modality. Evaluated on 22 datasets spanning diverse cohorts and brain states, BrainWorld generates stable 4D fMRI trajectories up to 400 frames, improves downstream performance through generated-example augmentation, and learns transferable multimodal representations that outperform baselines. Together, these results establish BrainWorld as a condition-aware generative framework for long-horizon brain dynamics modeling and multimodal representation learning.

23.
arXiv (CS.LG) 2026-06-19

Structure-Oriented Randomized Neural Networks for Poisson-Nernst-Planck and Poisson-Nernst-Planck-Navier-Stokes Systems

arXiv:2606.19912v1 Announce Type: cross Abstract: We develop a structure-oriented randomized neural network framework, termed SO-RaNN, for the Poisson-Nernst-Planck (PNP) system and the Poisson-Nernst-Planck-Navier-Stokes (PNP-NS) system. The decoupled linearized subproblems are solved iteratively by randomized neural networks in a space-time framework. For the concentration variables, a pointwise cut-off is used to enforce positivity at the value level, and discrete mass-scaling factors are computed at selected correction instants and interpolated in time, so as to ensure exact mass matching at those instants and to promote approximate mass preservation between them. To introduce an auxiliary discrete dissipation mechanism, we further employ an SAV-type post-processing correction, which yields monotonicity of the SAV auxiliary variable under the ideal SAV update. For the PNP-NS system, a structure-preserving randomized neural network (SP-RaNN) is used for the velocity field, so that the velocity approximation satisfies the incompressibility constraint pointwise by construction. On the theoretical side, we derive residual-based estimates for the raw, uncorrected RaNN solvers of the linearized subproblems, formulate a conditional local-in-time convergence result for the raw outer Picard iteration of the PNP system, and analyze the value-level positivity correction together with the mass-correction and SAV post-processing steps. For the PNP-NS system, we establish an approximation result for the SP-RaNN space and provide a conditional error statement for the corresponding linearized Oseen-type problem. Numerical experiments demonstrate approximation accuracy in the source-driven manufactured tests and illustrate the intended value-level positivity correction, selected-time mass matching, computed free-energy curves based on the final gauge-fixed potential, and divergence-free approximation in benchmark tests.

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

Cross-Model Disagreement as a Label-Free Correctness Signal

arXiv:2603.25450v2 Announce Type: replace Abstract: Detecting when a language model is wrong without ground truth labels is a fundamental challenge for safe deployment. Existing approaches rely on a model's own uncertainty – such as token entropy or confidence scores – but these signals fail critically on the most dangerous failure mode: confident errors, where a model is wrong but certain. In this work we introduce cross-model disagreement as a correctness indicator – a simple, training-free signal that can be dropped into existing production systems, routing pipelines, and deployment monitoring infrastructure without modification. Given a model's generated answer, cross-model disagreement computes how surprised or uncertain a second verifier model is when reading that answer via a single forward pass. No generation from the verifying model is required, and no correctness labels are needed. We instantiate this principle as Cross-Model Perplexity (CMP), which measures the verifying model's surprise at the generating model's answer tokens, and Cross-Model Entropy (CME), which measures the verifying model's uncertainty at those positions. Both CMP and CME outperform within-model uncertainty baselines across benchmarks spanning reasoning, retrieval, and mathematical problem solving (MMLU, TriviaQA, and GSM8K). On MMLU, CMP achieves a mean AUROC of 0.75 against a within-model entropy baseline of 0.59. These results establish cross-model disagreement as a practical, training-free approach to label-free correctness estimation, with direct applications in deployment monitoring, model routing, selective prediction, data filtering, and scalable oversight of production language model systems.

25.
bioRxiv (Bioinfo) 2026-06-20

Evaluation of Trypanosoma brucei Phosphofructokinase Allosteric Inhibition: An In-Silico Study

Human African trypanosomiasis, caused by a protozoan parasite Trypanosoma brucei, is a neglected tropical disease for which well-tolerated, conveniently administered, and highly efficacious medicines are still missing. Previously, T. brucei Phosphofructokinase was targeted by small-molecule inhibitor development efforts. This approach has shown promise both in vitro and in vivo. In this study, we have used these wet-lab results, evaluated the compounds already characterised by Molecular Dynamics simulations, found relationships between in silico and wet-lab data and used these observations to evaluate compounds that we selected through several different approaches of virtual screens. We observed that inhibitor-ATP interactions are highly predictive of the inhibitory activity. Several compounds selected through virtual screens have outperformed previously characterised compounds.