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

CAP: Towards PPG Universal Representation Learning with Patient-level Supervision

arXiv:2606.15284v1 Announce Type: cross Abstract: Photoplethysmography (PPG) plays a central role in wearable health monitoring and clinical decision support. Yet existing approaches to universal PPG representation learning largely focus on signal-level objectives and often overlook patient-level health context, which limits generalization to complex clinical tasks and heterogeneous cohorts. To address this gap, we construct a large-scale paired PPG-EHR multimodal dataset by distilling fragmented medical histories and clinical records into cohesive, patient-level electronic health records (EHR). Building on this resource, we propose Clinical Anchored Pretraining for PPG (CAP). During pretraining, CAP performs cross-modal contrastive alignment that anchors PPG representations to patient-level clinical semantics, guiding the encoder beyond waveform fitting toward modeling consistency in a patient's overall physiological state. During downstream adaptation, the pretrained PPG encoder provides clinically grounded representations that strengthen inductive bias and improve robustness and transferability. Experiments demonstrate that CAP consistently outperforms strong baselines on four diverse downstream tasks. CAP achieves a particularly large gain on respiratory rate prediction (up to +87.6% relative improvement over the state-of-the-art baseline) and delivers an average relative +26.7% across all tasks. We further enhance the interpretability of our approach through comprehensive analyses, including ablations and multiple complementary visualizations of the learned representations. The code for our experiments is available at: https://github.com/gody123gody/CAP .

02.
arXiv (CS.LG) 2026-06-15

How Task Structure Limits Multi-Agent Success: An Information-Theoretic Analysis

arXiv:2606.13733v1 Announce Type: cross Abstract: Multi-agent systems (MAS) were expected to overcome the limitation of single-agent systems (SAS) through collaboration. However, under typicality conditions on the task's constraint graph and bounded inter-agent communication, we prove that the success probability of a MAS is closely tied to the connectivity of task constraints, where each agent has limited information-processing capacity. Specifically, the success probability decays exponentially with an information bottleneck that emerges from partitioning the task's constraint graph among agents. We define this quantity as the minimum cut cost $C_{\min}$ of the potential constraint graph of each task. This information-theoretic bound applies to both open systems with external feedback and closed systems without. We validate our theory on both synthetic experiments and real-world empirical data from SWE-bench submissions. From our framework, effective MAS design should incorporate task-inherent constraints alongside engineering optimization, and when $\Cmin$ is high, practitioners should restructure tasks rather than simply scaling agents or communication.

03.
arXiv (CS.CL) 2026-06-17

Securing Multi-Agent GIS Systems: Risk Evaluation and Prompt Hardening Optimization

Agentic systems are increasingly integrated with geographic information systems (GIS), where multi-agent coordination enables complex conversational and spatial analysis but introduces security risks. This work presents a security-oriented framework for risk identification, evaluation, and mitigation in a multi-agent GIS system while maintaining adaptability to broader agentic architectures. We test the agentic system of a commercial geospatial partner while developing a modular state-machine-based orchestration framework that abstracts agent behavior into reusable components. We evaluate robustness using a red-teaming framework with an adaptive attacker LLM and a deterministic judge that produces binary outcomes with supporting rationales across multi-turn attacks. We further improve resilience with a prompt optimization framework that treats prompts as structured signatures and injects adversarial demonstrations, enabling systematic security improvements without degrading task performance.

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

Scalar-Stepsize Nonuniform Monte Carlo Optimistic Policy Iteration: A Certified Counterexample

Authors:

arXiv:2606.15978v1 Announce Type: new Abstract: Tsitsiklis proved convergence of Monte Carlo optimistic policy iteration under a uniform update structure and identified nonuniform update frequencies as a delicate obstruction. We give a certified negative answer for the natural scalar-stepsize, unnormalized asynchronous state-value recursion with fixed nonuniform state-selection probabilities. In a three-state, two-action discounted MDP, the nonuniform update frequencies induce a diagonally scaled greedy-policy mean field with a certified nonconstant attracting hybrid periodic orbit. With a bounded unbiased geometric-horizon estimator and Robbins–Monro stepsizes, the original stochastic recursion remains trapped near the cycle with positive probability and therefore fails to converge. The example pinpoints a geometric obstruction: uniform sampling gives radial residual contraction, whereas scalar nonuniform sampling anisotropically distorts the residual dynamics and can generate switched attracting cycles.

05.
medRxiv (Medicine) 2026-06-10

Documented clinical genetic testing among carriers of hereditary breast and ovarian cancer variants: Ancestry and socioeconomic disparities in the All of Us research program

Importance: Hereditary breast and ovarian cancer (HBOC) variant carriers benefit from risk-reducing interventions, but only if identified. The extent to which carriers are clinically recognized, and whether recognition is equitable across diverse populations, is poorly characterized in a single large U.S. cohort. Objective: To estimate P/LP HBOC carrier prevalence across genetic ancestry groups, quantify documented clinical genetic testing among carriers, and evaluate ancestry and socioeconomic disparities in testing. Design, Setting, and Participants: Cross-sectional analysis of the All of Us Research Program Controlled Tier (Curated Data Repository v8/C2024Q3R9), comprising participants with short-read whole genome sequencing and linked electronic health record (EHR) and survey data. Carriers were ascertained from research genomic data independent of clinical testing. Exposures: Genetically inferred ancestry (African [AFR], Admixed American [AMR], East Asian [EAS], European [EUR], Middle Eastern [MID], South Asian [SAS]); self-reported household income and educational attainment. Main Outcomes and Measures: (1) Carrier prevalence with Wilson 95% CIs; (2) documented clinical genetic testing (procedure codes) among carriers; (3) adjusted odds of documented testing among women, by ancestry, before and after socioeconomic adjustment, using multivariable logistic regression. Results: Among 414,830 participants, P/LP HBOC carrier prevalence was 1.42% (95% CI, 1.38-1.45) overall and similar across ancestry groups (AFR 1.24%, AMR 1.32%, EAS 1.19%, EUR 1.52%, MID 1.68%, SAS 1.33%; overlapping CIs). Among 250,071 women in the testing analysis, documented clinical genetic testing was rare: only 74 of 5,878 carriers overall (1.3%) and 59 of 3,572 European-ancestry carriers (1.7%) had a documented test, with counts below reportable thresholds in all other ancestry groups. African-ancestry women had lower adjusted odds of documented testing than European-ancestry women (Model 1 adjusted odds ratio [aOR], 0.32; 95% CI, 0.27-0.39), an association that attenuated but persisted after adjustment for income and education (Model 2 aOR, 0.48; 95% CI, 0.40-0.58; P < 0.001); Admixed American women also had reduced adjusted odds (aOR, 0.71; 95% CI, 0.61-0.84). Lower income and lower education were independently and dose-dependently associated with lower testing odds (income

06.
Nature (Science) 2026-06-23

Europe as science superpower: what it will take to rival the US and China

Amid chaos in US science and geopolitical turmoil, Europe wants to position itself as a research haven — but questions about funding and innovation remain. Amid chaos in US science and geopolitical turmoil, Europe wants to position itself as a research haven — but questions about funding and innovation remain.

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

DYNA-PRUNER: Input-Adaptive Data-Model Co-Pruning for Efficient and Scalable Spatio-Temporal Media Prediction

Spatio-temporal prediction supports radar/satellite nowcasting and city-scale traffic monitoring, but modern models are often too expensive for real-time deployment. This stems from a mismatch between dense computation and strong input-dependent redundancy (e.g., calm seas or clear skies). To enable automated, resource-aware architecture optimization in scalable media analysis, we propose Dyna-Pruner, an end-to-end framework for input-dependent co-pruning of data and model structure. A shared-importance synchronization mechanism generates coupled masks that prune redundant regions and their corresponding computational units (e.g., convolutional filters), yielding per-sample sparse sub-networks at inference time. Experiments on WeatherBench, SEVIR, and TaxiBJ show seamless integration with CNN, RNN, and Transformer backbones, reducing FLOPs by up to $70\%$ and achieving a $2.5\times$ speedup on NVIDIA Jetson AGX Orin with negligible accuracy loss ($

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

DeepMine-Mamba: Mitigating Information Dilution in Mamba-Based State Space Models for Document Image Binarization

Document image binarization aims to separate foreground text from degraded backgrounds while preserving thin, broken, and low-contrast strokes. Although deep learning methods have improved binarization performance, most existing approaches rely on convolutional, transformer-based, or generative architectures, while Mamba-based state space models remain largely unexplored for this task. In this work, we investigate Mamba-based feature propagation and observe that direct state-space propagation may dilute weak foreground cues during long-range modeling, especially faint ink traces, fragmented characters, and boundary-sensitive stroke details. To address this problem, we propose DeepMine-Mamba, a Mamba-based binarization framework equipped with a novel Anti-Dilution Gate that estimates propagation-induced feature changes and selectively restores stroke-sensitive local responses while suppressing unnecessary background enhancement. Experiments on DIBCO/H-DIBCO benchmarks under a strict leave-one-year-out protocol show that DeepMine-Mamba achieves competitive overall performance, with strong average FM and Fps across benchmark years. Ablation results further show that the Anti-Dilution Gate is the key component for mitigating propagation-induced foreground dilution and improving stroke preservation.

10.
bioRxiv (Bioinfo) 2026-06-08

HydraMPP: A lightweight library for distributed massive parallel processing in Python - threading at scale.

We now exist in the era of massive datasets from genomics, large language models, and all the known knowledge of humanity right at our fingertips. Much of this data is becoming more accessible; however, processing such data remains an ongoing issue across systems including high performance computing (HPC) infrastructures. Massively parallel computing (MPP) has solved this using a divide and conquer approach by splitting workloads across independent nodes (i.e., central processing units (CPU) allowing for higher scaling of data). The main engine for this in python is Ray; however, it has many issues including a large code space, security issues, debugging opacity, and memory management issues. Here, we present HydraMPP, a lightweight, ease of use and utilization, with high auditability, and with SLURM ergonomics.

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

One Probe Won't Catch Them All: Towards Targeted Deception Detection

arXiv:2602.01425v2 Announce Type: replace Abstract: Linear probes are a promising approach for monitoring AI systems for deceptive behaviour. Previous work has shown that a linear classifier trained on a contrastive instruction pair and a simple dataset can achieve good performance. However, these probes exhibit notable failures even in straightforward scenarios, including spurious correlations and false positives on non-deceptive responses. In this paper, we demonstrate that deception detection is inherently heterogeneous: while a single universal probe achieves modest improvements (+0.032 AUC), post-hoc oracle analysis reveals substantially higher potential (+0.108 AUC) when probes are matched to specific deception types, and synthetic validation experiments suggest this ceiling is achievable a priori when the deception type is known in advance. Our findings reveal that instruction pairs capture deceptive intent rather than content-specific patterns, explaining why prompt choice dominates probe performance (70.6% of variance). Given this heterogeneity, we conclude that organizations should define their specific threat models and deploy appropriately matched probes rather than seeking a universal deception detector.

12.
arXiv (CS.CL) 2026-06-16

Who Should Lead Decoding Now? Tracking Reliable Trajectories for Ensembling Masked Diffusion Language Models

Masked Diffusion Language Models (MDLMs) have emerged as a distinct paradigm for sequence generation. As MDLMs become diverse in capabilities and knowledge coverage, an important question is how to combine their knowledge. Toward this, we first investigate the unique decoding dynamics of MDLMs. We find that successful generations exhibit stable confidence dynamics over answer-relevant positions, while unreliable trajectories can often be corrected by injecting promising intermediate states from other models. Guided by this observation, we propose $TIE$ ($T$rajectory-based $I$terative $E$nsembling), a knowledge fusion framework in which MDLMs iteratively identify reliable decoding trajectories and relay them across models. TIE tracks confidence dynamics over answer-relevant positions to determine which model currently follows a more reliable trajectory and selectively transfers partially denoised sequences across models. As the model on the more promising trajectory often changes across denoising steps, TIE allows different models to contribute complementary strengths at different stages of generation. Strong performance across diverse reasoning tasks, along with our analyses, suggests that TIE offers a practical approach to the underexplored problem of MDLM ensembling.

13.
arXiv (math.PR) 2026-06-24

Negative index, matchings, and nonnegative eigenvalues of tridiagonal stochastic matrices

arXiv:2606.21122v2 Announce Type: replace Abstract: We study negative eigenvalues of $n\times n$ stochastic matrices whose off-diagonal support is constrained by a sparse graph. The main tool is a matching-based inertia principle: if $G$ is bipartite with matching number $\mu(G)$, $S$ is a real symmetric matrix supported on $G$ with nonnegative diagonal entries and whose negative index (i.e. number of negative eigenvalues counted with their multiplicities) is denoted by $\nu_{-}(S) $, then \[ \nu_{-}(S)\leq \mu(G). \] In particular, every $n\times n$ nonnegative tridiagonal stochastic matrix $P$ satisfies $ \nu_{-}(P)\leq \left\lfloor \frac{n}{2}\right\rfloor. $ Consequently, after ordering the eigenvalues of $P$ in the decreasing order, we have $ \lambda_{\lceil n/2\rceil}(P)\geq0, \ and hence \ \lambda_2(P)\geq0, \mbox{ for } n\geq3. $ This gives an all-dimensional strengthening of the previously known $4\times4$ tridiagonal stochastic result. Next, we show that this tridiagonal bound is sharp in every dimension in both reducible and irreducible cases. Finally, we explore some possible extension and raise some open questions.

14.
arXiv (CS.AI) 2026-06-15

Actionable Interpretability Must Be Defined in Terms of Symmetries

arXiv:2601.12913v4 Announce Type: replace Abstract: This paper argues that interpretability research in Artificial Intelligence (AI) is fundamentally ill-posed as existing definitions of interpretability fail to describe how interpretability can be formally tested or designed for. We posit that actionable definitions of interpretability must be formulated in terms of *symmetries* that inform model design and lead to testable conditions. Under a probabilistic view, we hypothesise that four symmetries (inference equivariance, information invariance, concept-closure invariance, and structural invariance) suffice to (i) formalise interpretable models as a subclass of probabilistic models, (ii) yield a unified formulation of interpretable inference (e.g., alignment, interventions, and counterfactuals) as a form of Bayesian inversion, and (iii) provide a formal framework to verify compliance with safety standards and regulations.

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

Training-Free Metrics for Synthetic Object Detection Data: A Proxy for Detector Performance

With the recent advent of image generative models, synthetic data are increasingly being used to supplement limited real datasets for training computer vision models. However, not all synthetic datasets improve performance equally, and their effectiveness can only be assessed by training a downstream model, which is computationally expensive and time-consuming. This problem is pronounced in the task of object detection, where the required annotations are much more dense due to bounding boxes. In this paper, we propose a pre-computable metric family, dubbed Conditional-Composition Domain Match (CCDM), which serves as a proxy for the relative utility of candidate synthetic training sets for downstream detection. Experiments on the VisDrone-DET dataset show that the CCDM metric families achieve a Spearman correlation of 1.0 with the downstream performance of YOLOv8, clearly outperforming existing metrics for synthetic image evaluation.

16.
arXiv (CS.LG) 2026-06-12

Normative Robustness as a Frontier for Non-Verifiable Reasoning in LLMs

arXiv:2606.12731v1 Announce Type: new Abstract: As LLMs increasingly serve in advisory and deliberative roles, users rely on them for non-verifiable reasoning in domains lacking objective ground truths. However, traditional evaluations of LLM reasoning focus almost exclusively on fact-based domains, such as mathematics and science, leaving uncertainty over whether and to what degree models can handle ambiguous, subjective, or value-laden problems over time. To address this concern, we propose moral reasoning as a paradigmatic subdomain of non-verifiable reasoning. We define moral robustness as a model's capacity to exhibit sound moral reasoning across time and contexts, and we introduce a scalable, adversarial, multi-turn evaluation framework to empirically measure this capability. We simulate 48,000 user-agent moral deliberations across four frontier LLMs, varying premise relevance, premise order, conversation duration, and the user's stated moral view. We find that models successfully ignore morally-irrelevant distractors, but shift their reasoning by up to 6.5%, on average, towards the user's stated preferred moral view, and varying their reasoning depending on factors such as order (altering moral judgments by order in 13-22% of the cases) and duration (altering moral judgments between single-turn and multi-turn in 10-24% of the cases). Our analysis indicates that models tailor not just their final verdicts but their underlying justifications to align with a user's moral viewpoint - a failure mode we characterize as moral deliberative sycophancy.

17.
arXiv (quant-ph) 2026-06-19

Truncated Wigner dynamics of biclique quantum spin glasses

Authors:

arXiv:2606.20187v1 Announce Type: cross Abstract: Quantum spin glasses are often considered testbeds for studying quantum optimization algorithms and as such have been the subject of various quantum advantage claims. Here we investigate the near adiabatic dynamics of biclique quantum spin glasses within the (discrete) truncated Wigner approximation (TWA). Benchmarks on small systems show that TWA recovers sample-to-sample fluctuations of the Edwards-Anderson order parameter, over a wide range of annealing times, with increasing fidelity when the system size increases. We extract critical exponents from the Binder cumulant in line with theoretical expectations, reproducing recent quantum experiments. The computational cost of the method is minimal and it can easily be applied to tens of thousands of qubits.

18.
arXiv (CS.CV) 2026-06-24

Predicting brain tumour enhancement from non-contrast MR imaging with artificial intelligence: a multi-cohort retrospective diagnostic accuracy study

Brain tumour MRI typically requires both pre- and post-contrast imaging, but gadolinium is not always desirable (frequent follow-up, renal impairment, allergy, paediatric patients). We developed and validated a deep learning model to predict tumour contrast enhancement from non-contrast MRI alone. We assembled 11,089 brain MRI studies (2006-2024) from 10 datasets across four countries and three continents, spanning adult and paediatric populations with glioma, meningioma, metastases, and post-resection appearances. Three architectures were trained to detect and segment enhancing tumour from T1w, T2w and FLAIR alone. Performance was assessed in a 1,109-study held-out test set (primary endpoint: patient-level enhancement detection; secondary: voxel-level Dice). Eleven expert radiologists attempted the same task on a 564-case subset (100 cases each), blinded to history, prior imaging, and referral. The best model, nnU-Net, achieved 83.0% balanced accuracy (95% CI 79.1-87.2; sensitivity 91.5%, specificity 74.4%) for detection, with R2 = 0.859 for enhancement volume. Of enhancing cases, 76.8% reached Dice >= 0.3, 67.5% >= 0.5, and 50.2% >= 0.7. Under blinded conditions, radiologists' majority vote was lower (71.7% balanced accuracy; sensitivity 77.6%, specificity 65.8%). The proportion reaching Dice >= 0.3 varied by pathology (meningioma 93%, presurgical glioma 76%, metastases 74%, postoperative glioma 74%) and was lowest for paediatric cases (45%). Deep learning can identify contrast-enhancing brain tumours from non-contrast MRI. These models show promise as a triage or decision-support adjunct, such as in flagging studies likely to enhance so that contrast can be added to a non-contrast protocol, and may reduce gadolinium dependence in neuro-oncology imaging. Future work should optimise these models with radiologists.

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

Geometrical fairness in graph neural networks

arXiv:2606.17684v1 Announce Type: cross Abstract: Graph-based learning methods have become increasingly prominent due to their strong performance across diverse applications. Among these, recent frameworks grounded in diffusion processes provide a unifying perspective that extends traditional graph neural network formulations while addressing limitations of standard message-passing mechanisms. Despite these advances, concerns remain regarding the fairness of such models, as they may propagate or amplify biases present in the data. In this work, we introduce a fairness-aware adaptation of graph-based diffusion by modifying the underlying Laplacian operator. Our approach incorporates multiple complementary transformations, including subspace projections, spectral adjustments, and frequency-based filtering, to mitigate bias-related components. Leveraging the intrinsic smoothing properties of graph diffusion, we provide a principled analysis of the resulting behavior and establish theoretical insights into fairness properties. We evaluate the proposed framework on both synthetic and real-world datasets, demonstrating that it achieves competitive performance while improving fairness metrics with limited additional computational cost.

20.
arXiv (CS.LG) 2026-06-15

Implicit Variational Rejection Sampling

arXiv:2606.14235v1 Announce Type: new Abstract: Variational Inference (VI) is a fundamental inference technique in Bayesian machine learning for approximating complex posterior distributions. Traditional VI often relies on the mean-field factorization, which can inadequately capture true posterior complexity. Recent advancements have leveraged neural networks to model implicit distributions, offering increased flexibility. However, the practical constraints of neural network architectures still produces inaccuracies. In this paper, we propose a method called Implicit Variational Rejection Sampling (IVRS), which integrates implicit distributions with rejection sampling to improve the posterior approximation. Our method uses neural networks to construct implicit proposal distributions, and rejection sampling with a discriminator network that estimates the density ratio between the implicit proposal and the true posterior for refining the approximation. Towards this end, we introduce the Implicit Resampling Evidence Lower Bound (IR-ELBO) as a metric to characterize the resampled distribution's quality and derive a tighter variational lower bound. Experimental results demonstrate that our method outperforms traditional variational inference techniques.

21.
arXiv (quant-ph) 2026-06-11

Scaling-optimal purification of noisy qubit unitary channels

arXiv:2606.12394v1 Announce Type: new Abstract: We consider the problem of purifying noisy qubit unitary channels. Given the ability to apply an unknown qubit unitary channel followed by depolarizing noise, we aim to construct a superchannel that purifies the noisy unitary back to the original unknown unitary. We first provide numerical evidence that sequential strategies can strictly outperform parallel strategies when the number of channel uses is finite, highlighting the fundamental distinction from state purification. We then provide a concrete $\mathrm{U}(2)$-covariant parallel protocol based on a novel entanglement-assisted quantum error-correcting code that suppresses the first-order noise strength as $O(1/n)$ with $n$ channel uses and show this scaling is asymptotically optimal in the low-noise regime, even when sequential strategies are allowed.

22.
arXiv (math.PR) 2026-06-24

Perron–Frobenius theorem for a general tree-valued growth-fragmentation-isolation process

arXiv:2606.24599v1 Announce Type: new Abstract: A general tree-valued dynamics is considered in continuous time: new vertices are added, and the percolation happens on the links, and the connected components can be frozen. The model is an infinite-type branching process. The main result establishes the Perron–Frobenius type theorem on this model, which extends the previous work [Ann. Appl. Probab. 33 (6B) 5233 - 5278]. The proof does not rely on any property of the uniform random recursive tree.

23.
arXiv (CS.CV) 2026-06-17

GeoDisaster: Benchmarking Orchestrated Agents for Operational Disaster Geo-Intelligence

Remote-sensing vision-language models (RS-VLMs) have advanced Earth-observation analysis toward visual interpretation and instruction-following, yet fall short of operational geo-intelligence, which demands tool-grounded spatial reasoning and structured, evidence-backed decisions. We introduce GeoDisaster, an operational geospatial disaster reasoning benchmark with 2,921 verified instances across 43 question types and five task families: deforestation monitoring, multi-hazard analysis, building-damage assessment, flood-safe routing, and Sentinel-1 SAR flood monitoring. Instances integrate heterogeneous EO/GIS evidence-optical and SAR imagery, raster masks, vector geometries, road networks, and exposure layers-spanning hazard detection, damage assessment, exposure estimation, and diagnostic report generation. Ground-truth answers are grounded in executable geospatial workflows and deterministic consistency checks, removing the need for language-model annotation. We further propose an orchestrated multi-agent framework with 18 disaster-oriented tools, where role-specialized agents coordinate through explicit execution contracts, aligned via Role-Contract Expectation Alignment (RCEA): failure-aware supervised fine-tuning combined with contract-grounded reinforcement learning over dense step-level signals. Experiments show that GeoDisaster challenges existing RS-VLMs and agentic systems, while RCEA improves tool use, evidence grounding, state consistency, and decision generation.

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

Sobolev Approximation by Fixed-Size Neural Networks with Arbitrary Accuracy

arXiv:2606.16975v1 Announce Type: cross Abstract: In this work, we investigate new activation functions for achieving arbitrary-accuracy Sobolev approximation by fixed-size neural networks. We first show that any function in $W^{2,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy, measured in the $W^{1,\infty}$-norm, by a fixed-size neural network using the Elementary Universal Activation Function ($\mathrm{EUAF}$). To extend this result to $W^{s,\infty}((a,b)^d)$ for $s\in\mathbb{N}$, we introduce a smooth activation $\mathrm{DUAF}_{\infty}$ from the family of Differentiable Universal Activation Functions ($\mathrm{DUAF}_n$). We prove that any function in $W^{s,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy in the $W^{s-1,\infty}$-norm by a fixed-size $\mathrm{DUAF}_{\infty}$-activated network. We further construct sigmoidal variants $\widetilde{\mathrm{DUAF}}_n$ and show that, for every $1\leq s\leq n$, fixed-size $\widetilde{\mathrm{DUAF}}_n$-activated networks still approximate any $f\in W^{s,\infty}((a,b)^d)$ with arbitrary accuracy in the $W^{s-1,\infty}$-norm. In all these results, the width and depth bounds are computed explicitly, and the proposed activations are elementary.

25.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Authors:

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.