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01.
arXiv (quant-ph) 2026-06-12

Measuring Control-Plane Openness in Near-Term Quantum Computing: A Rubric, Its Validation, and an Application to Thirteen Vendor Stacks

arXiv:2605.15233v2 Announce Type: replace Abstract: Public access to pulse-level and control-electronics interfaces in commercial quantum computing has bifurcated. This paper proposes a six-axis rubric for measuring control-plane openness, the layer between gate-level circuit specification and physical control electronics, defined operationally so that the same evidence produces the same grade across vendors. The rubric is validated three ways: a blinded re-grading pass, thirty-nine days after the evidence cutoff, that tests whether the cited evidence and the level definitions alone reproduce the recorded grades; a boundary-case methodology that fixes where each level begins and ends; and a published grading protocol that lets others reproduce and contest any cell. We establish that the rubric measures change rather than describing a snapshot by comparing the catalog against the documented control plane before the February 2025 removal of pulse-level access from IBM hardware, and reporting the cells that moved. The rubric is applied to thirteen commercial vendors across superconducting, trapped-ion, neutral-atom, and photonic modalities as of May 1, 2026, as its first application, and one of the three harms the rubric is designed to detect is demonstrated through a reproduction-access audit of five pre-2025 IBM Qiskit Pulse experiments against the access available on current hardware, carried through to a client-side structural port of the audit's selected target to Rigetti Quil-T. The catalog ships as a separate machine-readable artifact under CC-BY-4.0 with per-cell source URLs (https://doi.org/10.5281/zenodo.20163276). The catalog readings will change as vendor policies shift; the rubric is the contribution that survives them.

02.
arXiv (CS.LG) 2026-06-17

Generalization Guarantees for Multi-Input Neural Operator Learning in Sobolev Spaces

arXiv:2606.17419v1 Announce Type: new Abstract: We develop approximation and generalization error estimates for multi-input neural operators, with the output error measured in Sobolev norms. In contrast to standard operator-learning settings with a single input function, our framework allows multiple input functions defined on possibly different domains, with different dimensions and Sobolev regularities. The derived rates explicitly quantify the contribution of each input space to the final error bound. In particular, in the balanced regime, the approximation and generalization rates are governed by the interaction between the input dimensions, regularities, and Sobolev orders, while the dependence on the model complexity retains a \(\log\log/\log\)-type structure. Our analysis provides a general theoretical framework for multi-input operator learning, including Sobolev training, and is applicable to operator learning problems arising from partial differential equations and scientific computing.

03.
arXiv (quant-ph) 2026-06-11

Mixed-State Topological Order under Coherent Noise

arXiv:2411.03441v2 Announce Type: replace Abstract: Mixed-state phases of matter under local decoherence have recently garnered significant attention due to the ubiquitous presence of noise in current quantum processors. One of the key issues is understanding how topological quantum memory is affected by realistic coherent noise, such as random rotation noise and amplitude-damping noise. In this work, we investigate the intrinsic error threshold of the two-dimensional toric code (TC), a paradigmatic topological quantum memory, under these types of coherent noise by employing both analytical and numerical methods based on the doubled-Hilbert-space formalism. A connection between the mixed-state phase of the decohered TC and a non-Hermitian Ashkin-Teller-type statistical-mechanics model is established, and the mixed-state phase diagrams under the coherent noise are obtained. We find remarkable stability of mixed-state topological order under random rotation noise with axes near the $Y$-axis of qubits. We also identify intriguing extended critical regions at the phase boundaries, highlighting a connection with non-Hermitian physics. We argue that these phase boundaries provide upper bounds for the intrinsic error threshold, beyond which quantum error correction becomes impossible. We complement these findings by estimating the error thresholds for random rotation noise under standard quantum error correction, thereby providing lower bounds on the intrinsic error threshold.

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

From Benchmarks to Skills: Low-Rank Factors for LLM Evaluation

Current evaluations of large language models (LLMs) rely heavily on a growing collection of benchmarks and on aggregate benchmark scores, yet it remains unclear what this comparison actually captures, and what these scores reveal about models' underlying capabilities. Here, we propose a new paradigm for LLM evaluation, by asking whether benchmark performance reflects many independent abilities, or rather relies on a small number of shared dimensions. To answer this, we apply Factor Analysis (FA) to a massive performance matrix of LLMs versus benchmarks \((60\times44)\) revealing an intrinsically low-rank structure of that matrix. That is, a small number of latent factors captures most of the structure in the full task space. This low-rank geometry reveals substantial redundancy across existing tasks and explains why many benchmarks appear to be measuring overlapping abilities. We further show that these latent factors correspond to coherent, skill-like, dimensions of LLM behavior. Leveraging this latent skill-space, we deliver three practical tools for LLM evaluation and downstream users: (i)~identifying redundant tasks, (ii)~profiling new models using a small subset of tasks, and (iii)~selecting models aligned with desired skill profiles. Our method provides a solid alternative to the de-facto standard of a single aggregate score, and establishes an interpretable and practical framework for understanding and benchmarking LLM core capabilities.

05.
arXiv (CS.CL) 2026-06-12

Emergence of Hierarchical Emotion Organization in Large Language Models

As large language models (LLMs) increasingly power conversational agents, understanding how they model users' emotional states is critical for ethical deployment. Inspired by emotion wheels, i.e., a psychological framework that argues emotions organize hierarchically, we analyze probabilistic dependencies between emotional states in model outputs. We find that LLMs naturally form hierarchical emotion trees that align with human psychological models, and larger models develop more complex hierarchies. We also uncover systematic biases in emotion recognition across socioeconomic personas, with compounding misclassifications for intersectional, underrepresented groups. Human studies reveal striking parallels, suggesting that LLMs internalize aspects of social perception. Beyond highlighting emergent emotional reasoning in LLMs, our results hint at the potential of using cognitively-grounded theories for developing better model evaluations.

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

Revisiting Active Speaker Detection: An In-the-Wild Benchmark for Generalization and Robustness

We present UniTalk, a novel dataset emphasizing challenging scenarios to enhance model generalization for the task of active speaker detection (ASD). Previously established benchmarks such as AVA predominantly comprise old movies and thus exhibit significant domain gaps with real-world video. In contrast, UniTalk covers diverse video types reflecting challenging real-world conditions, including underrepresented languages, noisy backgrounds, and crowded scenes, while being on par with AVA in scale. Extensive evaluations reveal that ASD remains unsolved under realistic conditions: state-of-the-art models near-perfect on AVA fail to reach saturation on UniTalk. Conversely, models trained on UniTalk generalize better to modern in-the-wild datasets including Talkies and ASW. UniTalk thus establishes a new benchmark for ASD, providing researchers with a valuable resource for developing and evaluating versatile and resilient models.

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

SAGE: Answer-Conditioned Uncertainty Targets for Verbal Uncertainty Alignment

Large language models increasingly express uncertainty through natural-language statements, yet these expressions often fail to reflect the model's sampled behavior. We study verbal uncertainty alignment as a distributional calibration problem: the appropriate uncertainty target for a prompt should be estimated from repeated model outputs rather than from an isolated response. However, group rollouts alone are insufficient, since the resulting target must provide a useful training signal. Existing targets only partially satisfy this requirement. We propose SAGE, Semantic-Answer Guided Entropy, a group-level uncertainty target that constructs an answer-conditioned uncertainty geometry over sampled responses. SAGE preserves categorical, numeric, and symbolic answer distinctions while maintaining a smooth and scale-preserving calibration signal. We further apply this target through Group-Uncertainty Preference Optimization, or GUPO, an uncertainty-channel training framework that supervises verbal uncertainty expressions rather than the full response. Experiments across factual, mathematical, and multiple-choice reasoning tasks show improved uncertainty ranking, lower calibration error, and reduced overconfidence.

08.
arXiv (CS.CV) 2026-06-17

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

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

09.
arXiv (quant-ph) 2026-06-17

Universal Design and Physical Applications of Non-Uniform Cellular Automata on Translationally Invariant Lattices

arXiv:2605.13379v2 Announce Type: replace Abstract: Motivated by recent theoretical and experimental advances, hyperbolic lattices have emerged as a paradigmatic setting in which geometry becomes an active organizing principle of quantum systems. Their negative curvature, exponential volume growth, and non-Abelian translation symmetry make them fundamentally distinct from Euclidean lattices and give rise to rich geometry-dependent physics, but also hinder the direct application of well-established analytical and computational approaches originally developed for physical systems defined on Euclidean lattices. To establish a unified framework for geometry-dependent physics on Euclidean and hyperbolic lattices, we develop higher-order non-uniform cellular automata (NUCA) as a local-to-global construction for translationally invariant regular lattices. This construction derives geometry-dependent update rules through a lattice-deforming procedure that embeds hyperbolic lattices into a Euclidean square lattice, thereby encoding hyperbolic geometry while preserving physical locality. It thus provides a systematic route toward quantum and classical physics on hyperbolic lattices. We demonstrate the framework in three applications ranging from quantum many-body physics to non-equilibrium statistical physics. First, on the hyperbolic $\{5,4\}$ lattice, a linear NUCA generates exactly solvable subsystem symmetry-protected topological (SSPT) models and spontaneous subsystem symmetry-breaking models. Second, as a quantum generalization, we construct non-uniform Clifford quantum cellular automata (CQCA) for the hyperbolic cluster state. Third, we formulate a probabilistic NUCA for directed percolation (DP) on the hyperbolic lattice.

10.
arXiv (CS.CL) 2026-06-15

BayLing-Duplex: Native Full-Duplex Speech Dialogue with a Single Autoregressive LLM

Real-time, full-duplex speech interaction is a key feature of next-generation spoken chatbots, allowing the model to listen and speak at the same time and to handle natural phenomena such as overlap, hesitation, and barge-in. Existing speech language models (SpeechLMs) such as LLaMA-Omni and GLM-4-Voice are still turn-based and rely on an external Voice Activity Detection (VAD) module to mark the end of the user's turn, which fundamentally limits their interactive ability. In this paper, we introduce BayLing-Duplex, a native full-duplex SpeechLM where a single autoregressive LLM decides when to listen, when to speak, and when to stop, with no auxiliary turn-taking module. The design adds only a few special tokens to the standard vocabulary, so it transfers across LLMs and reuses existing training and serving stacks with no architectural adaptation. Starting from the public GLM-4-Voice checkpoint and using only 400K full-duplex samples for fine-tuning followed by a lightweight DPO stage, BayLing-Duplex reaches 92% turn-taking success and 100% interruption success on InstructS2S-Eval, while improving the speech-response score from 2.17 to 3.39 over Moshi. BayLing-Duplex also matches or surpasses its turn-based counterpart on Llama Questions, Web Questions, and Alpaca-Eval, showing that simultaneous listen-and-speak modeling does not sacrifice response quality.

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

RAGPPI: RAG Benchmark for Protein-Protein Interactions in Drug Discovery

Retrieving the biological impacts of protein-protein interactions (PPIs) is essential for target identification (Target ID) in drug development. Given the vast number of proteins involved, this process remains time-consuming and challenging. Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have supported Target ID; however, no benchmark currently exists for identifying the biological impacts of PPIs. To bridge this gap, we introduce the RAG Benchmark for PPIs (RAGPPI), a factual question-answer benchmark of 4,420 question-answer pairs that focus on the potential biological impacts of PPIs. Through interviews with experts, we identified criteria for a benchmark dataset, such as a type of QA and source. We built a gold-standard dataset (500 QA pairs) through expert-driven data annotation. We developed an ensemble auto-evaluation LLM that incorporates expert labeling characteristics, average fact-abstract similarity (F1), and low-similarity fact counts (F2), enabling the construction of a silver-standard dataset (3,720 QA pairs). We are committed to maintaining RAGPPI as a resource to support the research community in advancing RAG systems for drug discovery QA solutions.

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

Authorship Attribution in Multilingual Machine-Generated Texts

As Large Language Models (LLMs) have reached human-like fluency and coherence, distinguishing machine-generated text (MGT) from human-written content becomes increasingly difficult. While early efforts in MGT detection have focused on binary classification, the growing landscape and diversity of LLMs require a more fine-grained yet challenging authorship attribution (AA), i.e., being able to identify the precise generator (LLM or human) behind a text. However, AA remains nowadays confined to a monolingual setting, with English being the most investigated one, overlooking the multilingual nature and usage of modern LLMs. In this work, we introduce the problem of Multilingual Authorship Attribution, which involves attributing texts to human or multiple LLM generators across diverse languages. Focusing on 18 languages – covering multiple families and writing scripts – and 8 generators (7 LLMs and the human-authored class), we investigate the multilingual suitability of monolingual AA methods in terms of their cross-lingual transferability, and the impact of generators on attribution performance. Our results reveal that while certain monolingual AA methods can be adapted to multilingual settings, significant limitations and challenges remain, particularly in transferring across diverse language families, underscoring the complexity of multilingual AA and the need for more robust approaches to better match real-world scenarios.

13.
arXiv (CS.CL) 2026-06-12

WildIFEval: Instruction Following in the Wild

Recent LLMs have shown remarkable success in following user instructions, yet handling instructions with multiple constraints remains a significant challenge. In this work, we introduce WildIFEval - a large-scale dataset of 7K real user instructions with diverse, multi-constraint conditions. Unlike prior datasets, our collection spans a broad lexical and topical spectrum of constraints, extracted from natural user instructions. We categorize these constraints into eight high-level classes to capture their distribution and dynamics in real-world scenarios. Leveraging WildIFEval, we conduct extensive experiments to benchmark the instruction-following capabilities of leading LLMs. WildIFEval clearly differentiates between small and large models, and demonstrates that all models have a large room for improvement on such tasks. We analyze the effects of the number and type of constraints on performance, revealing interesting patterns of model constraint-following behavior. We release our dataset to promote further research on instruction-following under complex, realistic conditions.

14.
arXiv (CS.LG) 2026-06-16

Representation Costs in Data Science: Foundations and the Quasi-Banach Spaces of Deep Neural Networks

arXiv:2606.14954v1 Announce Type: cross Abstract: We develop a general framework for analyzing representation costs of parametric data-fitting methods through their parameter-space regularizers. From this abstract perspective, we define representation costs for arbitrary parametric models and reveal their induced (native) function spaces. This unifies recent function-space views of data-fitting methods. We also prove that many natural results hold in this abstract setting, including representer theorems for parametric methods on their native spaces. The framework also rigorously connects parametric methods with their equivalent nonparametric descriptions under sufficient overparameterization. Classical methods and their native spaces, such as kernel methods / reproducing kernel Hilbert spaces, wavelets / Besov spaces, and shallow neural networks / variation spaces emerge as special cases of our abstract framework. A byproduct of "axiomatizing" the study of representation costs is that we also immediately obtain new results for deep neural networks: For depth-$L$ feedforward ReLU networks, their induced native spaces are $p$-normable quasi-Banach spaces with $p = 2/L$. This reveals that the inductive bias of deep neural networks (as given by the representation cost) cannot be captured by norms for depths $L > 2$.

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

Beyond Independent Genes: Learning Module-Inductive Representations for Single-Cell Gene Perturbation Prediction

arXiv:2602.04901v2 Announce Type: replace-cross Abstract: Predicting transcriptional responses to genetic perturbations is a central problem in functional genomics. In practice, perturbation responses are rarely gene-independent but instead manifest as coordinated, program-level transcriptional changes among functionally related genes. However, most existing methods do not explicitly model such coordination, due to gene-wise modeling paradigms and reliance on static biological priors that cannot capture dynamic program reorganization. To address these limitations, we propose scBIG, a module-inductive perturbation prediction framework that explicitly models coordinated gene programs. scBIG induces coherent gene programs from data via Gene-Relation Clustering, captures inter-program interactions through a Gene-Cluster-Aware Encoder, and preserves modular coordination using structure-aware alignment objectives. These structured representations are then modeled using conditional flow matching to enable flexible and generalizable perturbation prediction. Extensive experiments on multiple single-cell perturbation benchmarks show that scBIG consistently outperforms state-of-the-art methods, particularly on unseen and combinatorial perturbation settings, achieving an average improvement of 6.7% over the strongest baselines. The code is available at https://github.com/ttruan2426-dot/scBIG.

16.
medRxiv (Medicine) 2026-06-22

AFFORDABILITY OF INTOXICATION FROM CHEAP ETHANOL: EVIDENCE FROM RETAIL ALCOHOL MARKETS IN UGANDA

Background: Alcohol affordability is a determinant of consumption and alcohol-related harm. In many low- and middle-income countries (LMICs), informal production, variable alcohol strength, and non-standard packaging complicate conventional affordability measures, limiting evidence on the economic accessibility of alcohol and the cost of intoxication. Objective: To assess the affordability of intoxication in Uganda by estimating the cost of obtaining ethanol to reach intoxication across alcohol products, packaging types, and retail contexts. Methods: Data were collected on 824 alcoholic beverages from urban, rural, and urban-slum retail markets. Ethanol-standardized pricing (price per gram of alcohol) was calculated, and the cost of consuming 60 g of ethanol was estimated. Multivariate regression identified determinants of ethanol affordability. Results: Affordability varied by product type and packaging. Opaque beers and illicit spirits provided the cheapest pathways to intoxication, with median costs of UGX 1,200-1,500 per 60 g of ethanol. Plastic packaging was associated with lower ethanol costs than glass packaging. Ethanol prices differed across formal and informal markets (p < 0.01), while rural areas and urban informal settlements had 20-25% lower costs than urban areas. Regulatory status alone did not predict affordability. Conclusions: In Ugandas diverse alcohol market, affordability is driven by access to ethanol rather than beverage price alone. Low-cost, high-strength alcohol sold through informal channels enables intoxication at minimal expense, among disadvantaged populations. Implications: Alcohol policies should target ethanol content through minimum unit pricing, alcohol-content-based taxation, and regulation of informal markets and packaging practices to reduce harmful consumption and inequities.

17.
bioRxiv (Bioinfo) 2026-06-18

A data-driven rediscovery of the specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that assemble structurally diverse peptides, many of pharmacological importance, including antibiotics and immunosuppressants. Within each NRPS module, the adenylation (A) domain selects the substrate to be incorporated, a choice governed by a small set of residues lining the binding pocket. For two decades, computational prediction of A-domain substrate specificity has relied on residue sets - most prominently the Stachelhaus code and the 34-residue "8 Angstrom code" - that were defined by spatial proximity to the substrate rather than by demonstrated predictive value. Here we revisit which residues govern substrate specificity from a purely data-driven perspective. We assembled a non-redundant dataset of 5,366 A-domain sequences (4,693 bacterial and 673 fungal) and used information-theoretic measures to rank alignment positions by their statistical association with substrate identity, without restricting candidate positions to any predefined structural shell. This procedure yielded two compact, kingdom-specific codes: IG15B (15 positions) for bacterial and IG13F (13 positions) for fungal A-domains. Both match or exceed the predictive accuracy of the 34-residue 8 Angstrom code while using fewer than half its positions, and both independently recover the majority of the classical Stachelhaus positions. Notably, our analysis identifies four positions (242, 280, 281, and 284) that lie outside all conventional codes yet carry non-redundant specificity information and co-localize with classical determinants on two helices flanking the binding pocket. These positions provide new candidate sites for the rational engineering of A-domain specificity.

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

Kernel of Partition Paths: A Unified Representation for Tree Ensembles

arXiv:2606.18853v1 Announce Type: cross Abstract: A recent line of work has reframed individual decision trees as linear models on engineered features associated with their splits, opening routes for oracle inequalities and feature-importance reinterpretation, but leaving open the question of what unified geometric object a forest induces when one indexes its feature map by nodes rather than by splits. The present paper studies that object. KPP indexes the feature map by the nodes of the forest, weighted by a path metric that turns each coordinate into a component of a squared-Euclidean path-isometric embedding. KPP unifies four pillars under a single non-diagonal Gram that carries a metric: prediction, exact additive attribution, deterministic Lipschitz robust radius in the KPP metric, and uniform Rademacher risk bounds for regression and classification under fixed, honest, or cross-fit conditioning. All probabilistic guarantees are conditional on the representation and are stated under three explicit conditioning regimes; the robust-radius guarantee is deterministic in the KPP metric rather than in a norm on the raw input. Conjectured fast-rate refinements for both regression and classification are stated as open problems and are not claimed as theorems.

19.
arXiv (CS.CL) 2026-06-17

Olmo Hybrid: From Theory to Practice and Back

Recent work has demonstrated the potential of non-transformer language models, especially linear recurrent neural networks (RNNs) and hybrid models that mix recurrence and attention. Yet there is no consensus on whether the potential benefits of these new architectures justify the risk and effort of scaling them up. To address this, we provide evidence for the advantages of hybrid models over pure transformers on several fronts. First, theoretically, we show that hybrid models do not merely inherit the expressivity of transformers and linear RNNs, but can express tasks beyond both, such as code execution. Putting this theory to practice, we train Olmo Hybrid, a 7B-parameter model largely comparable to Olmo 3 7B but with the sliding window layers replaced by Gated DeltaNet layers. We show that Olmo Hybrid outperforms Olmo 3 across standard pretraining and mid-training evaluations, demonstrating the benefit of hybrid models in a controlled, large-scale setting. We find that the hybrid model scales significantly more efficiently than the transformer, explaining its higher performance. However, its unclear why greater expressivity on specific formal problems should result in better scaling or superior performance on downstream tasks unrelated to those problems. To explain this apparent gap, we return to theory and argue why increased expressivity should translate to better scaling efficiency, completing the loop. Overall, our results suggest that hybrid models mixing attention and recurrent layers are a powerful extension to the language modeling paradigm: not merely to reduce memory during inference, but as a fundamental way to obtain more expressive models that scale better during pretraining.

20.
medRxiv (Medicine) 2026-06-11

Advancing Clinical Implementation of Cardiovascular Polygenic Risk Scores Through Patient-Level Robustness Assessment

Background and Aims: Polygenic risk scores (PRSs) for atherosclerotic cardiovascular disease (ASCVD) can perform equivalently at the population level yet disagree for individual patients. We examined whether such intra-individual variability reflects genuinely complementary risk information or mainly statistical and methodological uncertainty, and whether it affects clinical classification once PRSs are integrated into SCORE2-OP. Methods: In 4,137 ASCVD-free participants of the CoLaus|PsyCoLaus cohort (478 incident events over a median 14.4 years), we identified 16 ASCVD-PRSs with practically equivalent population-level performance using Bayesian equivalence testing. We quantified intra-individual variability (standard deviation, coefficient of variation, intraclass correlation, Cohen's kappa, extreme discordance), tested whether discordance exceeded chance, decomposed scores into shared and unique genetic components, and assessed variability after integration into SCORE2-OP, benchmarked against perturbation of systolic blood pressure. Results: For a typical individual, risk estimates varied by 18 percentile points across PRSs. Discordance matched chance expectations under a shared-signal model, with no distinct phenotypic profile among discordant individuals, and predictive power resided overwhelmingly in the shared genetic component. Variability tracked PRS size and weighting rather than distinct variants. After integration into SCORE2-OP, 75.6% of participants were placed in different categories by at least one model and 54.6% as both low and high risk; instability was concentrated near guideline thresholds and far exceeded that from blood-pressure measurement error. Conclusions: Equivalent population-level performance is not sufficient to treat PRSs as interchangeable at the individual level, and methodological standardisation and pragmatic clinical trials remain necessary to determine whether PRS integration improves long-term cardiovascular outcomes.

21.
bioRxiv (Bioinfo) 2026-06-20

A network approach to DNA methylation clocks

Biological age predicts health and lifespan better than chronological age, but remains difficult to measure. One leading molecular proxy for biological age is DNA methylation, which underlies age predictors known as "clocks". These clocks use penalized linear regression to predict chronological age from methylation levels using selected cytosine–guanine pairs (CpGs) along DNA. Although they predict chronological age within a few years and track mortality risk, there are several issues. Different clocks share a vanishingly small number of CpG sites, many of which show weak associations with age. Also, the clocks often do not transfer across methylation array platforms. This paper takes a network approach to better understand these issues. By using 12 public datasets from human blood, we build a co-methylation network of the sites that show the strongest age correlation. After pruning weak links, we find that it has a small number of large modules of covarying CpGs surrounded by many small modules and singleton sites. These modules are biologically interpretable, as they are associated with CpG island contexts and enriched for distinct Gene Ontology functions. We also map five established clocks onto this network (Horvath, Hannum, AltumAge, Skin & Blood, and Han) and find that they select some CpGs from the same module. This suggests that they are more similar than they appear. The network structure also suggests new ways to build clocks. A simple clock that retains one CpG per module matches the performance of established clocks. A second one, built from module-level principal components, outperforms all five established clocks in three validation cohorts and is transferable across array platforms (Illumina Infinium Methylation 450K or EPIC arrays). Overall, the network perspective shifts attention from individual CpG sites to modules of covarying sites. This perspective helps explain why DNA methylation clocks perform so well despite their differences and provides a more systematic approach for developing the next generation of aging biomarkers.

22.
bioRxiv (Bioinfo) 2026-06-10

HOMED enables hierarchical and multimodal optimization of DNA methylation deconvolution across tissues

Cellular heterogeneity is a major confounder in bulk DNA methylation data for epigenome-wide association studies. Existing reference-based DNAm deconvolution methods often ignore hierarchies among related cell types and may generalize poorly across datasets due to limited variability in reference profiles. We developed HOMED (Hierarchically Optimized Methylation Deconvolution), a framework that integrates cell-lineage hierarchies, single-cell RNA sequencing-guided deconvolution, and paired bulk RNA-seq/DNAm data for CpG signature optimization. Across simulated and real peripheral blood mononuclear cell, lung, and placental datasets, HOMED consistently yielded the highest PCCs and lowest RMSEs, outperforming existing scRNA-seq-guided DNAm deconvolution methods, improving accuracy, resolution, and cross-tissue generalizability.

23.
arXiv (CS.CL) 2026-06-12

HyperTool: Beyond Step-Wise Tool Calls for Tool-Augmented Agents

Tool-augmented LLM agents commonly rely on step-wise atomic tool calls, where each invocation, observation, and value transfer is exposed in the main reasoning trace. This creates an execution-granularity mismatch: locally deterministic tool workflows are unfolded into repeated model-visible decisions, consuming context and forcing the model to manage low-level dataflow in the trace. We introduce HyperTool, a unified executable MCP-style tool interface that changes the model-visible unit of tool execution. A model invokes HyperTool with a code block that can call existing tools through their original schemas, manipulate returned values, and pass intermediate results locally, folding deterministic tool subroutines into a single outer call. To train models to use this interface, we synthesize HyperTool-format trajectories from cross-tool compositional tasks and verify them in real MCP environments. On MCP-Universe, HyperTool improves average accuracy from 15.69\% to 35.29\% on Qwen3-32B and from 9.93\% to 33.33\% on Qwen3-8B, and surpass GPT-OSS and Kimi-k2.5 on average accuracy, showing that our HyperTool can substantially improve multi-step tool use.

24.
arXiv (quant-ph) 2026-06-19

Optimal Shadow Estimation with Minimal Measurement Settings

arXiv:2606.20003v1 Announce Type: new Abstract: Shadow estimation is a powerful framework for predicting quantum properties from randomized measurements. While $3$-design protocols achieve optimal worst-case performance, the minimal number of measurement bases required for such optimality has remained open. Here we prove that $\Theta(d^2)$ measurement bases are both necessary and sufficient for worst-case optimal shadow estimation and construct an explicit basis family. In stark contrast, any state $2$-design already suffices for average-case optimality: the mean squared shadow norm of normalized observables is bounded by a universal constant, and we prove strong concentration for Haar-random states, yielding constant sample complexity for generic pure-state fidelity estimation. Easily implementable $2$-designs – from mutually unbiased bases, cyclic measurements, or shallow $\mathcal{O}(\log n)$-depth circuits – enable optimal average-case protocols with remarkably simple measurement strategies. Our results establish a fundamental complexity separation: worst-case estimation requires $\Theta(d^2)$ bases, whereas average-case performance requires only $\Theta(d)$ bases, with broad implications for quantum information theory and near-term experiments.

25.
arXiv (CS.CL) 2026-06-16

Control-Plane Placement Shapes Forgetting: An Architectural Study of Agent Memory Across Thirteen System Configurations

作者:

Where an LLM sits in an agent memory pipeline – between the recall plane that retrieves stored facts (extensively benchmarked) and the control plane that mutates them via supersede, release, purge (largely untested) – shapes which forgetting failure modes the system recovers. Comparing thirteen system configurations on a 385-case adversarial surface, we observe three placement regimes with partly complementary coverage: deterministic primitives suffice for lexical/temporal categories but fail canonicalization (5% on identifier-obfuscation, 0% on cross-lingual); inscribe-time LLM recovers canonicalization (100%) but cannot help intent-aware deletion (0% on prefix-collision and compound-fact); a mutation-time hook recovers intent-aware deletion (78-85%) and brightens nearly all categories simultaneously (91.7-93.2% overall, $0.17 per 385-case run, 2.3s/case mutation latency vs. 64-191ms/case deterministic, recall path unchanged). We expose the trade-off via ForgetEval, a 1000-case templated suite plus a 385-case adversarial layer (132 hand-crafted + 253 LLM-drafted oracle-validated) scored by deterministic substring match, paired with a six-method Adapter Protocol with honest N/A scoring that lets heterogeneous memory stores enter in 130 lines. Admission is corroborated by 10-annotator IAA (Fleiss' kappa = 0.958) and a 77-case external-authored subset (four blind contributors) that replicates the canonicalization asymmetry and amplifies the joint-placement lift (+27.8 pt). Production failures are predominantly forgetting failures rather than recall failures, yet existing benchmarks measure only recall. ForgetEval and all adapters are released under MIT.