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

Sumi: Open Uniform Diffusion Language Model from Scratch

Diffusion models have become a promising alternative to autoregressive models. Among these, uniform diffusion language models (UDLMs) permit any token to be updated at any step, in principle enabling more flexible generation. However, no UDLM has yet been pretrained from scratch at both large parameter scale and large token budget. Both autoregressive modeling and masked diffusion modeling already have capable models at scale that the community can study and build on; uniform diffusion has none. A scratch-pretrained UDLM at scale would provide a clean reference point for studying scaling behavior, generation dynamics, controllability, and trade-offs against established autoregressive and masked diffusion models. To this end, we introduce Sumi ("ink" in Japanese), a fully open 7B uniform diffusion language model pretrained from scratch on 1.5T tokens. Sumi performs competitively with autoregressive models trained at comparable token budgets on knowledge, reasoning, and coding benchmarks, while under-performing on commonsense benchmarks, where our education-heavy data mixture is a likely contributor. We release our model weights, checkpoints, and full training recipe, including a complete specification of the data mixture over publicly available corpora. We hope this release enables the community to study native uniform diffusion at scale and catalyzes work on its as-yet poorly understood aspects.

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

ParaScale: Scale-Calibrated Camera-Motion Transfer via a Gauge-Invariant Parallax Number

作者:

arXiv:2606.19805v1 Announce Type: cross Abstract: Transferring the camera motion of a reference video to a freshly generated one lets creators reuse cinematic moves. Yet reference and target often live at incompatible scales – a sweep across a galaxy versus a nudge across a desk – and naively reusing the recovered trajectory yields either imperceptible or violently exaggerated motion. We trace this to a geometric fact: translation-induced image motion scales as ||T||/Z, so a monocular trajectory is meaningful only up to a depth-scale gauge. We distill this into the Parallax Number Pi = ||Delta T|| / Zbar, a dimensionless, gauge-invariant descriptor of how strongly a camera move is felt, and prove that it – not the raw trajectory – is the quantity that scale-faithful transfer must preserve. ParaScale is a plug-and-play module that reads Pi off any reference video and re-realizes it against the target scene's own depth, per frame, leaving rotation untouched. Sitting between pose extraction and pose injection, it requires no retraining and drops into any pose-conditioned generator. We further introduce the Parallax Consistency Error (PCE), a scale-symmetric metric that – unlike the similarity-aligned TransErr – exposes scene-scale mismatch. Across scale regimes spanning four orders of magnitude and multiple backbones, ParaScale keeps the realized parallax on the identity line and cuts PCE by more than 3x over uncalibrated transfer with no loss of visual fidelity.

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

Context-Aware RL for Agentic and Multimodal LLMs

Large language models (LLMs) often fail when answering requires identifying a small but decisive piece of evidence within a long or complex context, such as a single line in a tool trace or a subtle detail in an image. We propose ContextRL, a context-aware reinforcement learning (RL) method that improves long-horizon reasoning and multimodal performance through an indirect auxiliary objective. Instead of supervising only the final answer, ContextRL presents the model with a query, an answer, and two highly similar contexts, and rewards it for selecting the context that supports the query–answer pair, thereby encouraging fine-grained grounding. We construct contrastive context data in two domains: for coding agents, trajectories serve as contexts, yielding 1k pairs built via condition filtering; for multimodal reasoning, images serve as contexts, yielding 7K pairs built via generative editing and similarity search. ContextRL achieves average gains of +2.2% over standard GRPO on 5 long-horizon benchmarks, and +1.8% across 12 diverse visual question answering benchmarks. To disentangle the effect of the proposed objective from that of additional data, we compare against data-augmentation baselines that repurpose the same contrastive contexts as standard query–context–answer examples. These baselines provide little to no improvement, showing that the gains arise from the proposed context-selection objective rather than from the contrastive data alone.

04.
arXiv (CS.CL) 2026-06-18

Rethinking Reward Supervision: Rubric-Conditioned Self-Distillation

Post-training of reasoning language models is commonly driven by supervised distillation and reinforcement learning with verifiable rewards. Distillation often relies on chain-of-thought annotations that are expensive to obtain and may themselves be noisy, incomplete, or partially incorrect; even when the final solution is correct, an imperfect rationale can interfere with learning. Reinforcement learning with verified rewards, on the other hand, typically compresses evaluative feedback into a scalar signal, obscuring which aspects of a response should be improved. We propose Rubric-Conditioned Self-Distillation, a framework that incorporates rubrics as structured, fine-grained feedback for on-policy self-distillation. Our method conditions the teacher model on criterion-level rubrics and uses it to provide token-level guidance on the student's own sampled trajectories. This design avoids treating a single reference rationale as the sole supervision target. Instead, rubrics specify what a strong response should satisfy, enabling more fine-grained credit assignment over the reasoning process than scalar reward optimization. We instantiate this framework with a two-stage pipeline that first learns to generate task-specific rubrics and then trains a rubric-guided reasoner. We evaluate on a diverse suite of science reasoning benchmarks and results show that rubric-conditioned self-distillation effectively converts rubric-level criteria into token-level guidance over the reasoning process, surpassing GRPO by 1.0 points and OPSD by 0.9 points on average.

05.
arXiv (CS.AI) 2026-06-16

Hybrid NARX-LLM for Greenland Iceberg Discharge: Prompt-Driven Residual Correction

arXiv:2606.15288v1 Announce Type: cross Abstract: Greenland iceberg discharge exhibits complex nonlinear dynamics with limited observability, challenging traditional predictive models. We present a Hybrid NARX-LLM framework that combines a nonlinear autoregressive model with exogenous inputs (NARX) and a large language model (LLM) for residual correction. We further propose a Physics-Informed Prompt (PIP) method that transforms unstructured physical knowledge into structured prompts for zero-shot in-context reasoning. The primary objective is to explore the corrective potential of this framework for modeling Greenland iceberg discharge, rather than merely optimizing predictive accuracy. The NARX component captures intrinsic temporal dependencies, while the LLM, guided by PIP, encodes glacier dynamics and environmental drivers and perceives key trend patterns to correct systematic prediction errors. This integration allows the model to reason about unmodeled factors and produce interpretable residuals, enhancing overall predictive accuracy. Applied to Greenland iceberg discharge time series, our approach addresses extreme events that are difficult to predict due to rare variations and nonstationary trends, a limitation often overlooked by traditional methods. By fusing structured time-series modeling with knowledge-driven foundation AI, the framework offers a scalable and interpretable pathway to bridge data-limited climate forecasting with physics-informed LLM reasoning. The code is available.

06.
medRxiv (Medicine) 2026-06-18

Plasma proteomics reveals clinical and mechanistic heterogeneity among individuals who develop coronary artery disease

BACKGROUND: Individuals who develop coronary artery disease (CAD) are clinically and mechanistically heterogeneous, and understanding this variation is crucial for precise risk stratification and tailored interventions. However, the molecular mechanisms that connect these two kinds of heterogeneity remain unclear, limiting progress toward biologically grounded risk stratification and targeted interventions. Here, we investigated the heterogeneity of individuals who develop CAD by leveraging plasma proteomic signatures, placed individuals along continuous metabolic gradients and revealed the molecular programs underlying these patterns, thereby linking mechanistic variation to clinical heterogeneity. METHODS AND RESULTS: From 42,803 UK Biobank participants, including 3,713 individuals who developed CAD within 10 years (incident CAD), we first identified a 320-protein panel from 2,923 baseline proteins that improved prediction of incident CAD beyond clinical risk scores. Using reverse graph embedding, we reduced the proteomic data to two dimensions and mapped each incident case onto the resulting two-dimensional latent proteomic space. These proteomic dimensions show significant associations with cardiometabolic and kidney-related clinical markers. The patterns were replicated in the EPIC-Norfolk study. Phenome-wide Cox regression analyses further linked these proteomic dimensions to 10-year incidence rates for various diseases, including type 2 diabetes, obesity, and chronic kidney disease (CKD). Furthermore, adding the proteomic dimensions to clinical variable-based Cox regression model improved prediction of 10-year incidence of CKD and other diseases, demonstrating the value of proteomic dimensions beyond conventional clinical risk factors. Moreover, individuals with prevalent CAD (diagnosed before proteomic sampling) exhibited high, metabolically adverse dimension values, indicating that these axes capture cumulative metabolic burden. Pathway enrichment analyses implicated altered extracellular matrix organization and immune programs among the proteins contributing to the proteomic dimensions. CONCLUSIONS: Our findings demonstrate that plasma proteomic signatures can dissect the heterogeneity of individuals who develop CAD in continuous phenotypic gradients, improve prediction of CAD and comorbidities, and map underlying biological mechanisms.

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

Re-feeding Is Not Replaying: Measuring Replay Noise in Counterfactual Token-Credit Estimation

Per-token counterfactual credit estimation asks which token in a language-model rollout caused the final answer to be right or wrong: cut the transcript at a pivot, substitute an alternative token, replay continuations, and compare outcomes. Published methods re-feed the transcript prefix as a fresh prompt, assuming this reproduces the state the model passed through during generation. We measure what that assumption costs on a stock inference engine, with a three-pass design: continuations resumed from the verified decode-time KV state, an identical second exact pass (a replica noise floor), and a re-feed pass. Across six configurations and three models (including a GRPO-trained checkpoint), at low-margin decision tokens, re-feeding changes the credit estimate at rates 14-28 percentage points above the replica floor (7-21pp under a treatment-independent conditioning; problem-clustered t = 2.9-6.4). Most changes are zero-boundary crossings of the quantized estimator rather than polarity reversals, and the perturbation is consistent with mean-zero, so averaged quantities are largely safe; but selection is not: a critical-token set chosen by thresholding $|\hat{A}_t|$ under re-feed overlaps the exact-resume selection at Jaccard 0.34-0.90, versus a 0.63-0.96 replica ceiling. A causal confirmation closes the loop: under vLLM's batch-invariant kernels all three passes are identical on every measured channel, with both disagreement rates exactly zero. Replica passes themselves disagree on 9-23% of eligible estimates: single-sample credit measurements at decision tokens are unreliable under any replay. Settings were fixed in advance; exact-pass cache hits in the second campaign are instrumented (100% hit rate, 3,434 pivots); total compute was under 10 USD. We recommend that counterfactual credit studies resume decoder state or use batch-invariant kernels, and report a replica floor.

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

Airport Terminal Passenger Queue Forecasting for Departure Gates and Security Checkpoints

arXiv:2606.07622v2 Announce Type: replace Abstract: Accurate passenger queue forecasting in airport terminals is essential for efficient departure operations, as it enables proactive congestion management. However, time-varying passenger demand and heterogeneous facility usage across multiple departure facilities make forecasting challenging. In this work, we propose a passenger queue forecasting framework that learns historical passenger flow patterns from operational data. The proposed model employs a Transformer-based architecture to capture temporal dependencies and inter-facility correlations using past queue length and waiting time at departure gates and security checkpoints, together with passenger throughput at check-in islands. The learned representations are mapped to two facility-specific prediction heads to predict queue length and waiting time at departure gates and security checkpoints. Experimental results demonstrate accurate forecasts up to two hours ahead. The proposed approach offers practical real-time decision support for proactive queue management and staff reallocation in airport terminal operations.

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

Lightweight and Interpretable Transformer via Mixed Graph Algorithm Unrolling for Traffic Forecast

arXiv:2505.13102v4 Announce Type: replace-cross Abstract: Unlike conventional "black-box" transformers with classical self-attention mechanism, we build a lightweight and interpretable transformer-like neural net by unrolling a mixed-graph-based optimization algorithm to forecast traffic with spatial and temporal dimensions. We construct two graphs: an undirected graph $\mathcal{G}^u$ capturing spatial correlations across geography, and a directed graph $\mathcal{G}^d$ capturing sequential relationships over time. We predict future samples of signal $\mathbf{x}$, assuming it is "smooth" with respect to both $\mathcal{G}^u$ and $\mathcal{G}^d$, where we design new $\ell_2$ and $\ell_1$-norm variational terms to quantify and promote signal smoothness (low-frequency reconstruction) on a directed graph. We design an iterative algorithm based on alternating direction method of multipliers (ADMM), and unroll it into a feed-forward network for data-driven parameter learning. We periodically insert graph learning modules for $\mathcal{G}^u$ and $\mathcal{G}^d$ that play the role of self-attention. Experiments show that our unrolled networks achieve competitive traffic forecast performance as state-of-the-art prediction schemes, while reducing parameter counts drastically.

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

NTIRE 2024 Challenge on Image Super-Resolution (x4): Methods and Results

This paper reviews the NTIRE 2024 challenge on image super-resolution ($\times$4), highlighting the solutions proposed and the outcomes obtained. The challenge involves generating corresponding high-resolution (HR) images, magnified by a factor of four, from low-resolution (LR) inputs using prior information. The LR images originate from bicubic downsampling degradation. The aim of the challenge is to obtain designs/solutions with the most advanced SR performance, with no constraints on computational resources (e.g., model size and FLOPs) or training data. The track of this challenge assesses performance with the PSNR metric on the DIV2K testing dataset. The competition attracted 199 registrants, with 20 teams submitting valid entries. This collective endeavour not only pushes the boundaries of performance in single-image SR but also offers a comprehensive overview of current trends in this field.

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

Interpretable Neural Marked Statistics for Cosmological Inference

arXiv:2606.11295v1 Announce Type: cross Abstract: Recovering cosmological information beyond the power spectrum is a central goal for upcoming cosmological surveys, since late-time non-Gaussian signal in the matter density cannot be accessed through two-point statistics alone. Marked statistics fold part of this information back into the two-point level by reweighting the field with non-linear functions. We propose a neural marking scheme to generalize this process through a set of interpretable, physically motivated transformations that directly allow to interpret the gain in cosmological information at the morphological level. We employ a contrastive learning objective to align learnable marked summaries with the underlying cosmological parameters. At $k_{\max}=0.2\,h\mathrm{Mpc}^{-1}$, our neural mark tightens the marginalized constraint on $\sigma_8$ by $2.9\times$ and on $\Omega_m$ by $1.8\times$ compared to classical marks, breaking the $\Omega_m-\sigma_8$ degeneracy at the Fisher information level. It further reduces the parameter MSE across our cosmological parameter prior by $1.45\times$ over the best classical mark. The learned latent geometry aligns with the $\Omega_m$ and $\sigma_8$ directions in parameter space, indicating that the contrastive objective recovers the dominant axes of cosmological information. Our approach opens the door to more powerful, interpretable summary statistics for cosmological inference.

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

N(CO)$^2$: Neural Combinatorial Optimization with Chance Constraints to Solve Stochastic Orienteering

arXiv:2606.18514v1 Announce Type: cross Abstract: Neural combinatorial optimization (NCO) offers a promising alternative to traditional heuristic-based methods for solving complex graph optimization problems by proposing to learn heuristics through data. This class of problems frequently arises in automation, as it can be used to model a variety of applications. While NCO has been extensively studied for deterministic combinatorial optimization problems, there are only a few works that aim to solve stochastic combinatorial optimization problems. In this work, we present N(CO)$^2$: Neural Combinatorial Optimization with Chance cOnstraints to solve the Stochastic Orienteering Problem (SOP) without the use of hand-crafted heuristics. By integrating a reinforcement learning (RL) framework, the model optimizes path selection under uncertainty, effectively balancing exploration and exploitation. Empirical results demonstrate that our method generalizes well across diverse SOP instances, achieving competitive performance compared to the state-of-the-art mixed-integer linear program (MILP) for the task. The proposed approach reduces human effort in heuristic design while enabling adaptive and efficient decision-making in uncertain environments.

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

Range-Aware Bayesian Optimization for Discovering Diverse Designs within Target Property Windows

arXiv:2606.11574v1 Announce Type: new Abstract: In many materials and product design problems, desirable candidates exhibit properties that fall within an acceptable range rather than achieve a single optimum. Recovering multiple, distinct solutions that satisfy such specifications is also practically valuable, as some candidates may be preferred for reasons of cost, processability, or robustness that are difficult to encode directly in an objective function. Here, we develop a range-aware Bayesian optimization (BO) framework in which the acquisition function directly scores the posterior probability that a candidate satisfies a target range. The framework naturally extends to parallel pursuit of multiple distinct specifications over a shared candidate space. Across benchmark tasks, range-aware acquisition consistently recovers larger and more diverse sets of valid designs than standard BO baselines and recent goal-seeking methods. Its utility is further demonstrated in two practically motivated design case studies involving optimizing reaction conditions for polymer synthesis and sequence-defined oligomer discovery for prescribed optical absorption bands, supported by quantum chemical calculations. These results suggest that range-aware BO can provide a practical and sample-efficient foundation for specification-driven design, particularly when design flexibility and solution diversity are important considerations.

14.
arXiv (quant-ph) 2026-06-17

Cavity-enhanced superconducting response in an underdoped cuprate

arXiv:2606.18084v1 Announce Type: cross Abstract: Superconductors carry electrical current without resistance when paired electrons condense into a coherent macroscopic quantum state. In underdoped cuprates, evidence suggests that pairing-related correlations and superconducting fluctuations can survive above the temperature at which global coherence is lost, pointing to phase fluctuations as a key limitation on superconductivity in this regime. Motivated by recent demonstrations of cavity-modified collective states in quantum materials, we investigate whether superconducting coherence can be stabilized by engineering the electromagnetic environment of the superconductor. We study an underdoped YBa$_2$Cu$_3$O$_{7-\delta}$ thin film in a tunable terahertz cavity formed with a semi-transparent gold mirror. From temperature-dependent terahertz transmission measurements, we find that the cavity enhances the superconducting response below the critical temperature, with an increase of the inferred superfluid weight. The effect becomes more pronounced at smaller cavity lengths and is accompanied by an upward shift of the superconducting onset temperature. Calculations based on a cavity-coupled model for phase-fluctuating superconductors capture these trends and support an interpretation in terms of cavity-enhanced phase stiffness. These results showcase the potential of cavity engineering for designing emergent functionalities in correlated systems.

15.
arXiv (CS.LG) 2026-06-18

Giskard : Byzantine Robust and Confidential Aggregation for Large-Scale Decentralized Learning

arXiv:2606.19129v1 Announce Type: cross Abstract: Dealing simultaneously with confidentiality and Byzantine behaviors in decentralized learning is a challenging problem. Indeed, in decentralized learning, clients train a machine learning model while keeping their data locally and share their model parameters or gradients with a set of neighbors. While enforcing confidentiality calls for hiding the exchanged model parameters/gradients (e.g., by using cryptographic techniques), dealing with Byzantine contributions often requires inspecting the latter. Hence, most research works address these objectives separately. A recent line of work proposes to employ secure multi-party computation (MPC) to implement robust aggregators against model poisoning, thereby enforcing both confidentiality and Byzantine resilience. However, these solutions scale badly: they either require all-to-all communication between participants or delegate the entire computation to a small subset, whose computational and communication load grows proportionally with the size of the network. In this paper, we present Giskard, a protocol for confidential and Byzantine-robust decentralized aggregation. Giskard organizes $n$ parties into a tree of committees of size $O(\log n)$ and evaluates a coordinate-wise approximate median via a committee-adapted distributed binary search over the value domain, using BGW-style MPC within each committee. We assess Giskard both theoretically by proving its security and confidentiality properties and experimentally through extensive experiments involving up to one million participants. Compared to its closest competitors, Giskard reduces per-party communication complexity asymptotically while exhibiting comparable model utility under up to $n/4$ Byzantine parties.

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

The Culture Funnel: You Can't Align What isn't in the Data

Current cultural alignment approaches focus on inference-time interventions, assuming models already contain sufficient cultural knowledge. We argue modern LLM pipelines suffer from a cultural data funnel. Using a multidimensional tagging framework across pretraining, fine-tuning, alignment, and reasoning datasets, we show explicit cultural signals decline sharply during post-training, while geographically concentrated, task-specialized data dominates. Multilinguality enhances geographic diversity of cultural knowledge but does not ensure balanced representation. Our tags improve downstream cultural benchmark performance, demonstrating that advances require shifting focus in training data pipelines. To facilitate future research, we release our culturally tagged dataset with 5.6M samples at https://huggingface.co/datasets/CohereLabs/CultureMarkers.

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

VHDLSuite: Unified Pipeline for LLM VHDL Generation with Data Synthesis and Evaluation

arXiv:2606.13735v1 Announce Type: cross Abstract: Large Language Models (LLM) have shown impressive capabilities in Register Transfer Level (RTL) code generation, particularly for Verilog. However, evaluating their performance with other Hardware Description Languages (HDL), especially VHDL, remains limited although its distinct language characteristics, such as stricter semantic rules, introduce evaluation considerations that differ from Verilog. This lack of coverage restricts fully understanding of how well current models generalize across hardware design languages with differing structures and semantics. To address this gap, we introduce VHDLSuite, a benchmark-centered infrastructure for scalable VHDL generation evaluation, integrating automated benchmark synthesis, executable validation, and multi-model diagnostic analysis. First, we propose a data pipeline that automatically converts Verilog designs and their accompanying testbenches into executable VHDL benchmark instances, followed by VUnit/GHDL-based validation to ensure each released task is compilable, runnable, and consistently checkable in the VHDL environment. Second, we introduce VHDLBench, a benchmark with over 200 VHDL problems with complete and validated testbenches across a wide range of complexity levels. Third, we extensively evaluate cutting-edge LLMs and uncover key challenges specific on LLM-aided VHDL generation. Our findings provide important insights and support future work in multi-language hardware design automation.Our data pipeline, benchmark, and evaluation framework will be open-sourced.

18.
arXiv (quant-ph) 2026-06-17

Quantum conditional entropies from convex trace functionals

arXiv:2410.21976v4 Announce Type: replace Abstract: We study geometric properties of trace functionals that generalize those in [Zhang, Adv. Math. 365:107053 (2020)], arising from a novel family of conditional entropies with applications in quantum information. Building on new convexity results for these functionals, we establish data-processing inequalities and additivity properties for our entropies, demonstrating their operational significance. We further prove completeness under duality, chain rules, and various monotonicity properties for this family. Our proofs draw on tools from complex interpolation theory, multivariate Araki–Lieb and Lieb–Thirring inequalities, variational characterizations of trace functionals, and spectral pinching techniques.

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

Context-Aware Multimodal Claim Verification in Spoken Dialogues

Every day, millions absorb claims from podcasts and streams that no fact-checker ever sees. Spoken misinformation is built through conversation, where credibility comes not from facts alone but from how claims are framed, reinforced, or left unchallenged across turns. Yet fact-checking has focused on isolated text, leaving dialogue audio under-studied. We introduce MAD2, a new Multi-turn Audio Dialogues benchmark for spoken claim verification, containing 1,000 two-speaker dialogues with 3,368 check-worthy claims and approximately 10 hours of audio, and propose calibrated multimodal fusion of a context-aware audio encoder and a dialogue-aware text model. Across settings, adding dialogue context improves verification, but the gains depend on scenario type. Using only preceding context often matches offline performance, supporting live-moderation settings, and audio contributes most when transcript-based models are destabilized by additional context. Overall, conversational structure matters more for verification than misinformation framing.

20.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

21.
arXiv (quant-ph) 2026-06-12

Intermediate State Formation of Topologically Associated Chromatin Domains using Quantum Annealing

arXiv:2505.23289v2 Announce Type: replace Abstract: Topologically Associating Chromatin Domains are spatially distinct chromatin regions that regulate transcription by segregating active and inactive genomic elements. Empirical studies show that their formation correlates with local patterns of epigenetic markers, yet the precise mechanisms linking 1D epigenetic landscapes to 3D chromatin folding remain unclear. Recent models represent chromatin as a spin system, where nucleosomes are treated as discrete-state variables coupled by interaction strengths derived from genomic and epigenetic data. Classical samplers struggle with these models due to high frustration and dense couplings. Here, we present a quantum annealing (QA) approach to efficiently sample chromatin states, embedding an epigenetic Ising model into the topology of D-Wave quantum processors. Rather than reconstructing exact TAD size distributions or insulation scores, our method reproduces statistical features, such as mean marker incidences and intra-/inter-nucleosome correlations, while generating configurations that exhibit TAD-like structural motifs. These results demonstrate QA as an alternative to explore the chromatin architecture and provide a foundation in epigenetic modeling.

22.
PLOS Medicine 2026-05-21

Novel symptoms associated with eclampsia could improve detection and save lives

by Alice Beardmore-Gray, Andrew Shennan Eclampsia is a life-threatening complication of pre-eclampsia, yet remains difficult to predict. In this Perspective, Alice Beardmore-Gray and Andrew Shennan highlight a recent study that identifies 10 novel prodromal symptoms of eclampsia, with potential to better predict which women are at risk and therefore reduce delays in intervention.

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

Boundary Embedding Shaping with Adaptive Contrastive Learning for Graph Structural Disentanglement

arXiv:2606.20283v1 Announce Type: cross Abstract: Graph neural networks (GNNs) excel at aggregating neighbor information for classification, yet their performance is hindered by graph structural entanglement, where spurious correlations from semantically irrelevant neighbors contaminate node embeddings. This challenge is most acute for nodes near class boundaries in the embedding space, where amplified structural noise blurs decision boundaries and destabilizes predictions. Existing robust GNN methods largely treat all nodes uniformly, ignoring boundary vulnerabilities. In this paper, to improve classification performance, we tackle graph structural disentanglement by identifying boundary-region entanglement as the primary bottleneck and propose Boundary Embedding Shaping (BES), an adaptive contrastive learning GNN plug-in module that selectively suppresses spurious structural noise at decision boundaries with minimal model parameter perturbation. Extensive experiments demonstrate that BES consistently improves boundary discrimination and outperforms existing leading methods. Notably, BES boosts GCN performance by an average of 3.3% in node classification (up to 5.0% on WikiCS) and achieves superior accuracy in link prediction.

24.
medRxiv (Medicine) 2026-06-11

Population-scale detection of methylation outliers from long-read genome sequencing

Background: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. Methods: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. Results: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. Conclusions: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

25.
Nature Medicine 2026-06-22

<b>PROTEUS trial heralds perioperative therapy for prostate cancer</b>

Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer. Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer.