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

SPRI: SVD-Partitioned Residual Initialization for Data-Constrained MoE Upcycling

arXiv:2606.16456v1 Announce Type: cross Abstract: Mixture-of-Experts (MoE) models enable efficient scaling, but training them from scratch remains prohibitively expensive. MoE upcycling mitigates this cost by converting pretrained dense models into sparse MoE models. However, existing upcycling methods typically rely on large-scale continued training and often perform poorly under data-constrained supervised adaptation, due to either homogeneous experts or overly disruptive perturbations to pretrained parameters. In this setting, effective upcycling must leverage pretrained weight structure while introducing sufficient diversity among routed experts. To this end, we propose SVD-Partitioned Residual Initialization (SPRI), which distributes SVD-partitioned residuals derived from pretrained feed-forward network (FFN) weights across routed experts, introducing controlled expert diversity grounded in pretrained spectral structure. We further introduce a two-stage training strategy to improve adaptation stability. We evaluate SPRI on multilingual speech-to-text translation, where limited supervised data challenges MoE upcycling and multiple target languages provide natural routing heterogeneity. On CoVoST2 across 15 En-to-XX directions, SPRI improves average BLEU and COMET over fully fine-tuned dense models by 2.58 and 3.32 points, respectively, and outperforms the prior best MoE upcycling baseline by 3.39 BLEU and 4.34 COMET points.

02.
arXiv (CS.CV) 2026-06-19

CrossFlow: One-Step Generation Across Latent and Pixel Spaces

Most diffusion and flow-matching generators define the prior, probability path, and prediction target in the same representation space. Latent diffusion improves efficiency by moving this path into an autoencoder latent space, but the final sample is still produced by a separately trained decoder. This separation creates a mismatch: the generator is optimized for latent-space prediction, while final quality depends on how the decoder handles generated latents that may differ from clean encoder outputs. We introduce CrossFlow, a cross-space flow formulation that maps noisy latent inputs directly to pixel-space images. The key technical step is a velocity-free one-step objective: the latent trajectory defines the training path, but the supervised prediction is an image rather than a latent displacement. This lets one model act both as a one-step latent-to-pixel generator and as a decoder replacement for latent diffusion pipelines. On class-conditional ImageNet-1k at $256\times256$, CrossFlow-XL achieves 1.62 FID with one function evaluation. Ablations show that the latent encoder and pixel-space perceptual and adversarial losses are important for fidelity. These results indicate that cross-space flow objectives can combine the efficiency of latent representations with direct pixel-space supervision, without requiring a separate decoder at inference.

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

Token Complexity Theory for AI-Augmented Computing

作者:

arXiv:2606.12647v1 Announce Type: cross Abstract: AI-augmented computing delegates natural language queries, code generation requests, and other open-ended tasks to a cluster of AI models that processes queries and generates responses. This paradigm introduces a resource dimension that neither classical time nor space complexity captures: the cost of sending queries to and receiving responses from such a cluster. We introduce token complexity, a formal resource measure defined as the minimum expected token cost to achieve a specified level of output quality on a task, and develop a taxonomy classifying AI systems by the strength of their probabilistic properties. We develop token complexity within the framework of AI-Oracle Turing machines, in which a probabilistic Turing machine interacts with a stochastic oracle via dedicated query and response tapes. We prove basic theorems establishing that token complexity behaves as expected: monotonicity (higher quality costs more tokens), convexity (quality improvements become progressively more expensive), price sensitivity (small price changes produce bounded cost changes), and price-relativity of task ordering (the token complexity ordering of tasks can reverse depending on the query-to-response cost ratio). We prove that the complexity frontier, defined as the set of all feasible resource bounds in tokens, time, and space, is non-empty, upward-closed, and convex.

04.
arXiv (CS.LG) 2026-06-16

Biarchetype analysis for univariate functional data. An application to macroeconomic financial time series

arXiv:2606.15881v1 Announce Type: cross Abstract: We introduce biarchetype analysis for the first time in the context of univariate functional data. This unsupervised methodology extends archetype analysis by simultaneously identifying archetypal structures across both the cases (countries, in our application) and the temporal argument. Both cases and time points are expressed as mixtures of biarchetypes, yielding a concise and highly interpretable representation of complex functional observations. Although biarchetype analysis is not intended as a clustering technique, it offers superior interpretability compared with biclustering approaches, as it is based on extreme, representative patterns rather than average centroids, thereby enhancing human comprehension. We apply the proposed method to 10-year government bond yields of European countries over the period 2001-2025. The results identify three distinct time regimes (the pre-crisis period, the euro-area sovereign debt crisis, and the post-crisis period), and reveal Germany, Greece, and Hungary as country archetypes.

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

Capacity-Constrained Online Convex Optimization with Delayed Feedback

arXiv:2606.11711v1 Announce Type: new Abstract: Online learning with delayed feedback typically assumes that the learner can track all pending rounds until their feedback arrives. In practice, tracking resources are finite, and feedback from untracked rounds is permanently lost. In this paper, we study delayed online convex optimization (OCO) under a hard capacity constraint, where at most $C$ pending rounds can be tracked at any time. To model delay information, we introduce a semi-clairvoyant model that refines the clairvoyant assumption from prior work: rather than requiring delays to be known at prediction time, the learner observes delay expirations online, consistent with the classical unconstrained delayed setting. Our approach proceeds via a reduction to a novel ``delayed and weighted'' OCO problem, using a scheduler that randomizes tracking decisions and importance-weights the resulting observations. For this base problem, we propose and analyze Delayed-Weighted FTRL and its bandit analogue, establishing regret bounds that explicitly characterize the interaction between time-varying weights and delayed feedback. Combining these base learners with our schedulers yields the first regret guarantees for capacity-constrained OCO under convex and strongly convex losses, for both first-order and bandit feedback. For first-order feedback, capacity $C = \Omega(\log T)$ suffices to recover standard delayed OCO rates up to logarithmic factors. For bandit feedback, the regret rates are modulated by powers of $(1 + \sigma_{max}/C)$, where $\sigma_{max}$ is the maximum number of pending observations at any time. This allows the regret bound to degrade gracefully when $C < \sigma_{max}$, while remaining sublinear.

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

What Does the Weight Norm Control in Grokking? Logit-Scale Mediation under Cross-Entropy

arXiv:2606.18465v1 Announce Type: cross Abstract: Grokking, the delayed jump from memorization to generalization, is usually tied to the weight norm: a smaller norm generalizes sooner. We ask what the norm actually controls. Holding the weight norm fixed by clamping and varying only an output temperature, we slide the grokking delay across its entire norm-induced range under cross-entropy; matching the effective logit scale back to baseline recovers about 85% of the delay at two moduli. Across a grid of norms and temperatures the delay collapses onto the logit scale alone (R2 = 0.97), with the norm adding 1-2% beyond it. The effect is loss-dependent: under mean-squared error the logit scale is pinned and the norm acts through a different route. A memorization control, a float64 softmax-collapse audit, and a no-LayerNorm transformer point to the same channel. Forking arms from one identical state, the delay follows the held norm value and not the clamp operation, which closes a rescaling-artifact concern. The proximal variable is the logit scale and the softmax saturation it drives; the weight norm is only an upstream handle. All numbers, tables, and figures reproduce from released code and data.

07.
arXiv (CS.AI) 2026-06-11

SkillJuror: Measuring How Agent Skill Organization Changes Runtime Behavior

arXiv:2606.11543v1 Announce Type: new Abstract: Agent Skills augment large language model (LLM) agents with procedural knowledge at inference time, but current benchmarks rarely distinguish what a Skill says from how it is organized. We study this distinction through Progressive Disclosure, where a concise root file points agents to supporting resources on demand, and compare it with a normalized flat baseline. We present SkillJuror, a framework for evaluating Skill writing paradigms through semantically controlled variants, matched multi-trial evaluations, and trajectory evidence while holding task knowledge fixed. In an 82-task SkillsBench study, Progressive Disclosure changes runtime behavior before aggregate outcomes: distinct Skill resources touched per trajectory rise from 1.18 to 3.85, and effective uptake events rise from 1.33 to 3.92. It also yields 17 additional verifier-passing trials out of 410 matched trials (+4.1%) over the normalized flat baseline. The benefit is task-dependent. Progressive Disclosure helps when supporting resources guide implementation, checking, or repair, but is weaker when success hinges on exact output conventions, numerical thresholds, or long artifact-generation pipelines. These results show that Skill organization is not mere presentation: it can change how agents search and apply procedural knowledge, while outcome gains depend on whether the exposed resources are actionable for the task. Code is available at https://github.com/zhiyuchen-ai/skill-juror.

08.
bioRxiv (Bioinfo) 2026-06-17

DesignMaster: A Multi-Conditional Diffusion Framework for Rational PROTAC Design

Motivation: Proteolysis-targeting chimeras (PROTACs) enable targeted protein degradation through ternary complex formation with E3 ubiquitin ligase. However, the rational design of PROTACs remains highly challenging due to limited structure-activity relationship data and the vast conformational diversity of linkers. Existing computational approaches can be broadly divided into structure-based ternary modelling methods and fragment-based linker generation models. Although these approaches have advanced PROTAC design, they typically neglect key physicochemical constraints and linker-length control during the generation process, causing the generated PROTACs to lack balanced structural properties required for effective ternary complex formation with drug-like characteristics. Results: To address these limitations, we propose DesignMaster, a diffusion-based generative framework that explicitly incorporates linker length and physicochemical properties as controllable conditioning signals. DesignMaster employs an E(3)-equivariant graph Transformer with a gated multi-condition fusion module to inject linker length and physicochemical constraints throughout the diffusion process, enabling fine-grained and constraint-aware molecular generation. Experiments on PROTAC-DB 2.0 and 3.0 demonstrate that DesignMaster outperforms state-of-the-art baselines, with a 3.2% improvement in validity and a 34.4% improvement in recovery. The Case study shows DesignMaster achieves a 51.78% reduction in RMSD when predicting the linker of PROTAC BCPyr targeting 6W7O, highlighting its potential for practical structure-guided PROTAC design. Availability: The source code and datasets are available at https://github.com/ABILiLab/DesignMaster.

09.
Nature (Science) 2026-06-17

Cortical development dynamics across autism spectrum disorder mouse models

Despite the functional diversity of over 100 causal genes1–3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD. Using single-nucleus multi-omic sequencing, diverse autism spectrum disorder-linked gene mutations converge on transient, stage-specific disruptions in early brain development, and highlight sex-specific gene expression alterations.

10.
Nature Medicine 2026-06-15

Activity-dependent adaptive deep brain stimulation improves gait in Parkinson’s disease

Parkinson’s disease leads to a spectrum of locomotor deficits that vary in severity with the nature of daily activities and the fluctuating physiology of patients. Many of these deficits remain inadequately addressed by existing deep brain stimulation therapies that rely on activity-agnostic parameters optimized for cardinal motor symptoms. By contrast, therapies embedding activity-specific parameters have the potential to better address the entire range of symptoms. Here we expose physiological principles that enable real-time decoding of ongoing locomotor activities across motor fluctuations from the neural dynamics of the subthalamic nucleus. This decoding steered activity-dependent adaptations of deep brain stimulation therapies that improved locomotor deficits while preserving efficacy for cardinal motor symptoms across activities of daily living. Our activity-dependent framework provides a blueprint for next-generation neuromodulation therapies that continuously select parameters optimized to the behavioral context and fluctuating physiology of each patient. ClinicalTrials.gov registration NCT06791902 . Neural decoding algorithms that leverage physiological principles of locomotor encoding support activity-dependent deep brain stimulation therapies that improve locomotor deficits in people with Parkinson’s disease.

11.
arXiv (CS.CV) 2026-06-15

HPSv3++: Scaling Reward Models Across the Full Spectrum of Diffusion Model Capabilities

Reward models guide text-to-image (T2I) systems toward outputs aligned with human preferences. However, typical reward models such as HPSv3 are trained on pre-annotated data from earlier T2I models, without accounting for quality discriminative shifts arising from evolving model capabilities and reinforcement learning (RL) iterations, limiting their broader applicability. In this work, we propose HPSv3++, a reward model framework that elevates the HPSv3 model for varying T2I model capabilities and their RL iteration changes across the full capability-iteration spectrum. Specifically, we first introduce HPDv3++, a 212K dual-dimension preference dataset annotated for text fidelity and aesthetic quality using a recent high-capability (Qwen-Image) model with human supervision. We then propose a two-stage training framework. Stage 1 employs data-aware orthogonal gradient projection to incorporate diverse aesthetic perception from HPDv3++ while preserving the original effective human preference knowledge in HPSv3. Stage 2 further leverages unlabeled data from T2I models spanning different capability levels and RL iterations, and introduces a joint capability-iterations conditioned signal for the reward model together with a standard deviation-driven unsupervised guidance mechanism, strengthening reward model across the capability-iteration spectrum. HPSv3++ achieves state-of-the-art preference prediction, outperforming HPSv3 9.8% on HPDv3, 5.5% on GenAI-Bench, while achieving 79.1%/88.1% on our proposed HPDv3++. When used for T2I RL training, it consistently improves GenEval scores across diverse T2I models, demonstrating its wide-range capabilities. The code is available at https://github.com/PlantPotatoOnMoon/HPSv3-PlusPlus.

12.
medRxiv (Medicine) 2026-06-22

Cumulative Metabolic Exposure to Hyperglycemia and Risk of Cardiovascular and Limb Events in Peripheral Artery Disease

Background: Although diabetes is a potent risk factor for the development of peripheral artery disease (PAD), the effect of cumulative metabolic exposure to hyperglycemia on risk of cardiovascular or limb events in patients with PAD remains unclear. Methods: The Peripheral Artery Disease: Long-term Survival (PEARLS) is a longitudinal registry of Veterans with newly diagnosed PAD identified using a natural language processing approach. Included patients had ankle brachial index [&le;]0.9 or toe brachial index [&le;]0.7, and no history of lower extremity revascularization or major amputation. Among patients with diabetes in this cohort, we assessed cumulative exposure to hyperglycema based on a 24-month rolling average of hemoglobin (Hgb) A1c values, categorized as [&le;]7%, >7% to [&le;]8%, and >8%. Multivariable Cox regression models evaluated the association between categories of HgbA1c, modeled as a time-varying exposure, and risk of cardiovascular (CV: myocardial infarction or stroke) and limb (chronic limb threatening ischemia [CLTI] or major amputation) events. Results: Among 45,109 patients with new diagnosis of PAD and pre-existing diabetes, the mean HgbA1c at baseline was 7.5%, with nearly one-third (30.4%) having HgbA1c >8%. The mean age was 70.4 years, 19.8% were Black and 4% were Hispanic. Patients with baseline HgbA1c >8% were younger and compared to those with HgbA1c [&le;]7%, more likely to have coronary disease, kidney disease, and obesity. Over a median follow up of 4.2 years, 8,306 (18.4%) patients experienced a CV event, and 8,199 (18.2%) experienced a limb event. The adjusted association between HgbA1c and hazard of CV events was 12% higher in patients exposed to HgbA1c >7% to [&le;]8% (HR 1.12; 95%CI: 1.05-1.18) and 38% higher in those exposed to HgbA1c >8% (HR 1.38; 95%CI: 1.30-1.46), compared to HgbA1c 7% to [&le;]8% (HR 1.20; 95%CI: 1.13-1.28) and HgbA1c >8% (HR 1.60; 95%CI: 1.51-1.70), respectively when compared to HgbA1c [&le;]7%. These findings were consistent in subgroups based on age and severity of PAD. Conclusions: Among diabetic patients with PAD, cumulatiave metabolic exposure to hyperglycemia is associated with a markedly increased risk of clinical events, especially limb events.

13.
arXiv (CS.LG) 2026-06-15

Decoupled Latent Optimization of Diffusion Models for Full Waveform Inversion

arXiv:2606.14139v1 Announce Type: new Abstract: Full waveform inversion (FWI) recovers subsurface velocity from seismic recordings by solving a severely ill-posed, nonconvex PDE-constrained optimization. Classical regularizers stabilize the inversion but fail to reproduce realistic geological structures; recent diffusion-prior methods improve realism at the cost of a fragile trade-off between data fidelity and prior consistency. We propose Decoupled Latent Optimization (DLO), which relaxes the standard latent-optimization formulation into a quadratic-penalty objective over an auxiliary physical variable and a latent variable. The data-fidelity gradient acts in physical space, the diffusion sampler contributes only through a decoded prior sample, and the standard smoothed-velocity initialization of classical FWI is preserved. On the OpenFWI benchmark, DLO outperforms classical regularizers and existing diffusion-based methods under clean, noisy, and missing-trace acquisitions. The prior, trained on 70*70 OpenFWI models, transfers directly to the Marmousi and Overthrust benchmarks, where DLO recovers intricate fault structures and remains robust to initialization smoothing and measurement noise.

14.
arXiv (quant-ph) 2026-06-11

Implementing Hamiltonian Renormalization Group Flow on Quantum Computers with VAPOR

arXiv:2606.11306v1 Announce Type: cross Abstract: While Hamiltonian Lattice Gauge Theory is gaining traction, today's limited numerical capacity leaves simulations affected by discretization errors. This motivates the implementation of renormalization group (RG) techniques to find discretization-error-free operators. To this end, we introduce VAPOR, a variational quantum algorithm that decomposes operators into Pauli strings, identifies RG flow orbits, and determines fixed points of a naively discretized operator. We illustrate this using a toy model of a kinematic operator in a symmetry-restricted SU(2) Yang-Mills theory.

15.
arXiv (CS.AI) 2026-06-12

From AGI to ASI

arXiv:2606.12683v1 Announce Type: new Abstract: Over the last decade, building human-level artificial general intelligence has moved from far-fetched speculation to being a concrete next-decade target for many of the largest AI organisations. Achieving this goal would have profound and far-reaching impacts on human society, which raises many complex questions for the decade ahead. This report investigates how AI itself might continue to develop in a post-AGI world along the continuum of machine intelligence. The endpoint of this continuum, Universal AI, is theoretically well understood, which provides some formal grounding for the main focus of this report: the transition from human-level AGI to artificial general superintelligence, which, intuitively, can be understood as a system that is more intelligent and cognitively capable than large organisations of humans. After characterizing ASI, the report discusses four potential pathways from AGI to ASI: scaling AGI, AI paradigm shifts, recursive improvement, and ASI emerging from large-scale multi-agent collectives. The report then discusses possible frictions and bottlenecks along these pathways. Determining whether the impact of these frictions will be negligible or substantial raises a number of concrete open research questions. Due to large uncertainties for predicting ASI progress, it cannot be ruled out that AI progress might continue to accelerate over the next years. This could imply that the image of a single transformative step change, caused by the introduction of human-level AGI into our society, could be inaccurate. More apt might be the prospect of a series of transformative societal changes caused by AI-enabled progress and breakthroughs across many areas of science and technology. Preparing for this prospect requires a massively interdisciplinary endeavour of global scope and interest.

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

Moebius: 0.2B Lightweight Image Inpainting Framework with 10B-Level Performance

While 10B-level industrial foundation models have pushed the boundaries of image inpainting, their prohibitive computational costs severely hinder practical deployment. Constructing a highly optimized task-specific specialist offers a promising solution; however, extreme structural compression inevitably triggers a severe representation bottleneck. To conquer this, we propose Moebius, a highly efficient lightweight inpainting framework. We systematically reconstruct the diffusion backbone by introducing the Local-$\lambda$ Mix Interaction ($L\lambda MI$) block. Comprising Local-$\lambda$ and Interactive-$\lambda$ modules, it elegantly summarizes spatial contexts and global semantic priors into fixed-size linear matrices, preserving complex latent interactions while drastically shedding parameters. Furthermore, to unlock the full representational capacity of this highly compact architecture, we synergistically pair it with an adaptive multi-granularity distillation strategy. Operating strictly within the latent space to avoid expensive pixel-space decoding, this strategy dynamically balances multiple gradient-based losses to achieve high-fidelity alignment. Extensive experiments across natural and portrait benchmarks demonstrate that this optimal synergy enables Moebius to rival or even surpass the generation quality of the 10B-level industrial generalist FLUX.1-Fill-Dev. Remarkably, Moebius achieves this using less than 2\% of the parameters (0.22B vs. 11.9B) while delivering a $>15\times$ acceleration in total inference time, setting a new efficiency standard for high-fidelity inpainting. Project page at https://hustvl.github.io/Moebius.

17.
arXiv (math.PR) 2026-06-16

A Low-Regularity Semigroup Sewing Lemma via Quotient Structures

arXiv:2606.16164v1 Announce Type: new Abstract: We develop a low-regularity Sewing theory for the semigroup coboundary $\hat\delta=\delta-a$ associated with a strongly continuous semigroup $S$. Unlike the ordinary low-regularity Sewing problem, the semigroup setting has an intrinsic algebraic non-uniqueness below the threshold $1$, in the sense that solutions are canonical only modulo semigroup cocycles. Accordingly, the natural target is a quotient space rather than an increment space. We identify this quotient structure and construct the corresponding semigroup Sewing map. The construction uses a frozen terminal-time transform, which rewrites semigroup defects, for each terminal time, as ordinary low-regularity Sewing problems on a frozen simplex. This reduction, however, does not by itself produce a genuine semigroup increment; the main additional step is to prove that the frozen solution classes are compatible as the terminal time varies and hence assemble into a canonical quotient class for $\hat\delta$. This yields canonical classes for $0

18.
bioRxiv (Bioinfo) 2026-06-14

Somatic variant detection in normal tissues from single-cell sequencing data

A crucial advantage of single-cell sequencing (SCS) is its ability to identify somatic variants in individual cells, enabling phylogenetic analysis of cellular populations within bulk tissues. While identifying somatic variants in tumor tissues via SCS has become a common practice, doing so in normal tissues remains challenging due to the rarity of somatic variants in normal cells. To evaluate the feasibility of somatic variant calling from widely available single-nucleus RNA-seq (snRNA-seq) and single-nucleus ATAC-seq (snATAC-seq) data, we profiled a Cell-line mix of six HapMap samples prepared by the SMaHT consortium using 10x Genomics 5' snRNA-seq (12k cells with 36k mean reads per cell) and snATAC-seq (11k cells with 14k median high-quality fragments per cell) for variant calling. PacBio long-read whole genome sequencing (WGS) data (109x) generated from individual cell lines were used as ground truth. Two computational tools, Monopogen and SComatic, were used for somatic variant calling from the SCS data. Monopogen achieved single nucleotide variant (SNV) detection accuracies of 93.30% in the snRNA-seq and 99.64% in the snATAC-seq data, both of which outperformed SComatic (74.35% and 94.29%, respectively). Monopogen also consistently detected somatic SNVs at cellular fractions as low as 0.5% (2.54% in snRNA and 0.81% in snATAC) in individual samples. Notably, snATAC-seq exhibited higher genomic coverage breadth and larger number of variants detected than snRNA-seq. While the SCS data have lower overall genome coverage than that of the bulk WGS, the single-cell level variant resolution allows Monopogen to assign variants to their cells of origin with over 80% accuracy in both RNA and ATAC modalities, thereby facilitating studies of clonal evolution and cell-type-specific mutagenesis. Other benchmarking methods were also evaluated (DeepVariant, Cellsnp-lite and Mutect2) for comparison. In conclusion, our study demonstrated the feasibility of performing reliable single-cell somatic mutation calling in a cell-line mixture and discussed the strengths and limitations of current computational methods when applied to normal tissues.

20.
medRxiv (Medicine) 2026-06-10

Global and local genetic overlap among ME/CFS, irritable bowel syndrome and psychiatric traits: a hypothesis-generating analysis

作者:

Background. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and irritable bowel syndrome (IBS) frequently co-occur following infection, yet shared genetic architecture at the locus level has not been systematically characterised. Aims. To estimate global and local genetic correlations between ME/CFS (including infection-onset subgroup), IBS, major depressive disorder (MDD) and loneliness/isolation, and characterise ME/CFS cell-type heritability enrichment. Method. GWAS summary statistics: DecodeME (15,579 ME/CFS; 9,738 infection-onset), FinnGen R9 (9,296 IBS), PGC MDD Wave 2 (45,396) and UK Biobank loneliness (N=455,364). LDSC for global correlations; LAVA for local correlations across 2,495 loci; MAGMA for cell-type enrichment (Descartes Human atlas); coloc.abf for colocalisation. Results. All pairwise global correlations were significant after Bonferroni correction, including ME/CFS-all-MDD (rg=0.598, 95% CI 0.46-0.74) and ME/CFS-all-IBS (rg=0.573, 0.39-0.75). Of 4,232 local tests, 16 reached FDR

21.
arXiv (CS.LG) 2026-06-18

Enhanced Graph Neural Networks using K-Hop Gaussian Diffusion

arXiv:2606.18317v1 Announce Type: new Abstract: Most graph neural network (GNN) cores rely on graph convolutions, typically implemented as message passing between direct (single-hop) neighbors. In many real-world graphs, edges can be noisy or poorly defined, limiting information propagation to local neighborhoods. Existing diffusion kernels, such as Personalized PageRank (PPR) and Heat Kernel, alleviate this issue through global propagation, but still struggle with complex local structures and distant node noise. To address these limitations, we propose a K-Hop Gaussian (KHG) diffusion kernel as a preprocessing module for graph data. KHG introduces multi-hop diffusion with Gaussian weighting for remote nodes, balancing local and global information propagation before applying standard GNNs. Experiments on multiple benchmark datasets demonstrate that KHG significantly outperforms traditional message-passing GNNs, as well as PPR and Heat Kernel diffusion, particularly in noisy or structurally complex graphs.

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

Through the PRISM: Preference Representation in Intermediate States of Video Diffusion Models

Evaluating video generation with clean, pixel-based reward models disconnects evaluation from the noisy diffusion process and incurs massive VAE decoding costs. In this paper, we challenge this paradigm by asking a fundamental question: Can a powerful video generator inherently discriminate preferences directly from noisy latents? To answer this, we introduce PRISM (Preference Representation in Intermediate States of Diffusion Models). PRISM employs a lightweight Query-based Aggregation head with a frozen video diffusion backbone to decode preference signals from noisy latents. Surprisingly, PRISM not only achieves SOTA preference accuracy but also unlocks strong noise-robustness, which enables early-stage Best-of-$N$ sampling. This allows for filtering suboptimal candidates at the very beginning of denoising, drastically reducing computation while boosting video quality. We also reveal a strong positive correlation between a backbone's generative performance and its inherent evaluative power, enabling self-improving video backbones.

23.
Science (Express) 2026-06-04

Long-range extended chains arising from polymerization-driven spontaneous assembly | Science

作者: 未知作者

A central challenge for conjugated polymers is to achieve long-range order while remaining solution-processable, which is essential for matching the electrical performance of their counterparts of crystalline inorganic semiconductors. Here we show that n-doped poly(benzodifurandione) (n-PBDF) can undergo polymerization-driven spontaneous assembly (PSA), in which chain growth, chemical doping, and structural ordering are intrinsically coupled, yielding long-range chain extension over hundreds of nanometers. We reveal that the spontaneously formed n-PBDF nanoribbons arise from a self-initiated, convergent growth mechanism driven by cooperative monomer–polymer interactions and stabilized by proton-coupled duplex chains and the polymer’s intrinsic polyelectrolyte character. With long-range extended chains in the nanoribbons, the aligned n-PBDF thin films demonstrate metallic-level conductivity (>10 4 Siemens per centimeter).

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

Toward Preference-aligned Large Language Models via Residual-based Model Steering

Preference alignment is a critical step in making Large Language Models (LLMs) useful and aligned with (human) preferences. Existing approaches such as Reinforcement Learning from Human Feedback or Direct Preference Optimization typically require curated data and expensive optimization over billions of parameters, and eventually lead to persistent task-specific models. In this work, we introduce Preference alignment of Large Language Models via Residual Steering (PaLRS), a training-free method that exploits preference signals encoded in the residual streams of LLMs. From as few as one hundred preference pairs, PaLRS extracts lightweight, plug-and-play steering vectors that can be applied at inference time to push models toward preferred behaviors. We evaluate PaLRS on various small-to-medium-scale open-source LLMs, showing that PaLRS-aligned models achieve consistent gains on mathematical reasoning and code generation benchmarks while preserving baseline general-purpose performance. Moreover, when compared to models aligned with DPO and SimPO, they perform better with great time-savings. Our findings highlight that PaLRS offers an effective, much more efficient and flexible alternative to standard preference optimization pipelines, offering a training-free, plug-and-play mechanism for alignment with minimal data.

25.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.