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01.
arXiv (CS.LG) 2026-06-19

Shifting-based Optimizable Linear Relaxations for General Activation Functions

arXiv:2606.20292v1 Announce Type: new Abstract: The use of neural networks (NNs) is rapidly increasing, including in safety- and security-critical domains. To provide formal guarantees about NN behavior, many verification methods rely on optimizable linear relaxations of activation functions. However, existing techniques depend on hand-crafted relaxations for each activation function. Extension to state-of-the-art activation functions therefore requires substantial manual effort. In contrast, our approach SLiR (Shifting-based Linear Relaxations) is broadly applicable, requiring only a Lipschitz constant or a set of critical points. SLiR parameterizes relaxations by their slope and computes the corresponding offset via a shifting procedure that ensures sound upper and lower bounds over the input domain, enabling efficient optimization while maintaining correctness. Our experiments show that SLiR produces tight relaxations across a wide range of practical activation functions and enables verification of up to 7.8x more properties compared to state-of-the-art methods.

02.
arXiv (CS.LG) 2026-06-12

Metriplectic Conditional Flow Matching for Dissipative Dynamics

arXiv:2509.19526v2 Announce Type: replace Abstract: Metriplectic conditional flow matching (MCFM) learns dissipative dynamics without violating first principles. Neural surrogates often inject energy and destabilize long-horizon rollouts; MCFM instead builds the conservative-dissipative split into both the vector field and a structure preserving sampler. MCFM trains via conditional flow matching on short transitions, avoiding long rollout adjoints. In inference, a Strang-prox scheme alternates a symplectic update with a proximal metric step, ensuring discrete energy decay; an optional projection enforces strict decay when a trusted energy is available. We provide continuous and discrete time guarantees linking this parameterization and sampler to conservation, monotonic dissipation, and stable rollouts. On a controlled mechanical benchmark, MCFM yields phase portraits closer to ground truth and markedly fewer energy-increase and positive energy rate events than an equally expressive unconstrained neural flow, while matching terminal distributional fit.

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

Fabricating fiber cavity mirror substrates compatible with high coupling efficiency

arXiv:2606.12168v1 Announce Type: cross Abstract: Fiber optical cavities offer small mode volumes and correspondingly strong light-matter interactions in an open Fabry-Perot geometry. However, existing fabrication techniques do not reliably produce substrates with surface profiles amenable to high mode matching between the cavity mode and fiber core, thereby limiting the achievable collection efficiency. Here we present a technique to fabricate fiber mirror substrates while using $in situ$ reflectometry to constrain the achievable mode matching prior to coating. By measuring the back-reflection from freshly cleaved fiber tips, we pre-select 138 fibers compatible with 96.5-99.5% mode matching, and after a single CO$_2$ laser ablation pulse, these fibers remained compatible with 95.3-99.2\%. This simple technique provides rapid feedback during each stage of substrate fabrication, greatly enhancing the yield of viable fiber mirror substrates prior to (expensive) coating runs.

04.
Science (Express) 2026-06-04

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

Authors: Unknown Author

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

05.
arXiv (CS.CL) 2026-06-15

Knowing When to Quit: A Principled Framework for Dynamic Abstention in LLM Reasoning

LLMs utilizing chain-of-thought reasoning often waste substantial compute by producing long, incorrect responses. Abstention can mitigate this by withholding outputs unlikely to be correct. While most abstention methods decide to withhold outputs before or after generation, dynamic mid-generation abstention considers early termination of unpromising reasoning traces at each token position. Prior work has explored empirical variants of this idea, but principled guidance for the abstention rule remains lacking. We present a formal analysis of dynamic abstention for LLMs, modeling abstention as an explicit action within a regularized reinforcement learning framework. An abstention reward parameter controls the trade-off between compute and information. We show that abstaining when the value function falls below this reward strictly outperforms natural baselines under general conditions. We further derive a principled and efficient method to approximate the value function. Empirical results on mathematical reasoning and toxicity avoidance tasks support our theory and demonstrate improved selective accuracy over existing methods.

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

SwiftCTS: Fast Cross-Design Prediction and Pareto Optimization of Clock Tree Metrics via Few-Shot Calibration

arXiv:2606.11348v1 Announce Type: new Abstract: Clock Tree Synthesis (CTS) is a computationally expensive stage in the physical design flow, requiring iterative EDA tool invocations to navigate a vast configuration space for optimal power, wirelength, and timing skew. Existing machine learning approaches require computationally expensive retraining or fine-tuning cycles to adapt to unseen macro architectures and are architecturally mismatched to the millions of evaluations demanded by exhaustive combinatorial search. We present SwiftCTS, a physics-informed surrogate framework that addresses both limitations simultaneously. By coupling lightweight, physics-grounded statistical features with gradient-boosted ensembles, SwiftCTS trains in under five seconds on a CPU and delivers sub-millisecond inference without GPU support. To handle out-of-distribution (OOD) designs without retraining or fine-tuning, we introduce a K-shot multiplicative calibration mechanism that anchors predictions to just one or two physical reference runs, reducing power prediction error from 24.5\% to 3.3\% and wirelength error from 56.6\% to under 1\% on unseen macros. Integrating this engine with an evolutionary optimizer, SwiftCTS evaluates 100,000 CTS configurations in under ten seconds, yielding Pareto-optimal frontiers that are physically validated within the OpenROAD flow. Closed-loop validation confirms prediction errors below 0.5\% for power and wirelength, and timing skew predictions within five picoseconds on an OOD benchmark, consistently outperforming default tool heuristics across all target metrics. Code publicly available at: \href{https://anonymous.4open.science/r/SwiftCTS-7E6E}{https://github.com/BarsatKhadka/SwiftCTS}

07.
arXiv (CS.CL) 2026-06-12

S-GBT: Smooth Growth Bound Tensor for Certified Robustness Against Word Substitution Attacks in NLP

Despite recent progress in Natural Language Processing (NLP), models remain vulnerable to word substitution attacks. Most existing defenses focus on first order sensitivity and measure how much the output changes when the input is slightly perturbed. However, they ignore how this sensitivity evolves, which is described by curvature. When gradients vary sharply, models can still fail. This paper introduces the Smooth Growth Bound Tensor (S-GBT), a second order method that bounds the Hessian element-wise, for which we provide formal theoretical proofs on the resulting robustness bounds. A regularization term is added during training to minimize these bounds. This yields tighter certified robustness against word substitution attacks. The change in the output under word substitution is bounded by both a linear term and a quadratic term. S-GBT is derived for two architectures: Long Short-Term Memory (LSTM) and Convolutional Neural Networks (CNN). The method is integrated directly into the training objective. Its effectiveness is evaluated on multiple benchmark datasets. The results show that combining first and second order regularization improves certified robust accuracy by up to 23.4% compared to prior methods, while clean accuracy remains competitive. These findings indicate that controlling both the gradient and its variation is a promising direction for building more robust models.

08.
arXiv (math.PR) 2026-06-17

Extreme value theory for geometric Brownian motion and pricing of short maturity options

Authors:

arXiv:2505.08036v2 Announce Type: replace Abstract: We investigate the limiting distribution of geometric Brownian motion conditional on its running maximum taking large values. The Freidlin-Wentzell large deviations theory predicts that the conditional distribution of the sample paths converge weakly to a deterministic exponential curve. We complement this result by showing that the conditional sample paths in fact converge in strong sense, and obtain quantitative bounds on the rate of convergence. As an application of our results to financial mathematics, we obtain new closed form asymptotic formulae for the fair price of barrier options with general path dependent payoff in the short maturity limit, with quantitative error estimates. We provide exact formulae for Asian and lookback style payoffs.

09.
arXiv (math.PR) 2026-06-18

Formation of clusters and coarsening in weakly interacting diffusions

arXiv:2510.17629v3 Announce Type: replace-cross Abstract: This paper studies the clustering behavior of weakly interacting diffusions under the influence of sufficiently localized attractive interaction potentials on the one-dimensional torus. We describe how this clustering behavior is closely related to the presence of discontinuous phase transitions in the mean-field PDE. For local attractive interactions, we employ a new variant of the strict Riesz rearrangement inequality to prove that all global minimizers of the free energy are either uniform or single-cluster states, in the sense that they are symmetrically decreasing. We analyze different timescales for the particle system and the mean-field (McKean-Vlasov) PDE, arguing that while the particle system can exhibit coarsening by both coalescence and diffusive mass exchange between clusters, the clusters in the mean-field PDE are unable to move and coarsening occurs via the mass exchange of clusters. By introducing a new model for this mass exchange, we argue that the PDE exhibits dynamical metastability. We conclude by presenting careful numerical experiments that demonstrate the validity of our model.

10.
arXiv (CS.AI) 2026-06-19

PiDR: Physics-Informed Inertial Dead Reckoning for Autonomous Platforms

arXiv:2601.03040v2 Announce Type: replace-cross Abstract: A fundamental requirement for full autonomy is the ability to sustain accurate navigation in the absence of external data, such as GNSS signals or visual information. In these challenging environments, the platform must rely exclusively on inertial sensors, leading to pure inertial navigation. However, the inherent noise and other error terms of the inertial sensors in such real-world scenarios will cause the navigation solution to drift over time. Although conventional deep-learning models have emerged as a possible approach to inertial navigation, they are inherently black-box in nature. Furthermore, they struggle to learn effectively with limited supervised sensor data and often fail to preserve physical principles. To address these limitations, we propose PiDR, a physics-informed inertial dead-reckoning framework for autonomous platforms in situations of pure inertial navigation. PiDR offers transparency by explicitly integrating inertial navigation principles into the network training process through the physics-informed residual component. PiDR plays a crucial role in mitigating abrupt trajectory deviations even under limited or sparse supervision. We evaluated PiDR on real-world datasets collected by a mobile robot and an autonomous underwater vehicle. We obtained more than 29% positioning improvement in both datasets, demonstrating the ability of PiDR to generalize different platforms operating in various environments and dynamics. Thus, PiDR offers a robust, lightweight, yet effective architecture and can be deployed on resource-constrained platforms, enabling real-time pure inertial navigation in adverse scenarios.

11.
arXiv (CS.CV) 2026-06-16

Beyond Self-Attention: Sub-Quadratic Vision Transformers for Fast Image Captioning

Image captioning is a challenging and significant task that aims to generate coherent and semantically meaningful textual descriptions for given images. To accomplish this task, it requires a deep understanding of visual content along with the ability to express that understanding in natural language. Despite remarkable progress with transformer-based architectures, existing approaches often suffer from limitations, such as a lack of rich local feature representations and the high computational cost of quadratic self-attention. The proposed model focuses on improving computational efficiency by restructuring the vision transformer architecture. In designing this approach, the standard self-attention mechanism in Vision Transformers is replaced with a probabilistic transformer approach based on a Gaussian Mixture Model (GMM), a soft-clustering technique. Instead of computing pairwise attention among all image patches, the model groups similar patches into a fixed number of clusters using an Expectation-Maximization (EM) algorithm. This clustering-based mechanism reduces the computational complexity from quadratic O(n^2) to linear O(nK), where K

12.
bioRxiv (Bioinfo) 2026-06-18

Elucidating the Design Space of Generative Models for Single-Cell Perturbation Prediction

Next-token prediction has produced predictable scaling in language, but the recipe presumes a sequence of tokens with a meaningful order. Single-cell RNA-seq counts have no natural gene ordering, so applying the recipe directly to raw expression fails under an ill-suited left-to-right bias. We instead ask whether a learned latent can supply the structure the recipe needs. We introduce texttt{ExpressionVAE} (eVAE), a discrete-latent perturbation model that compresses each cell into a short sequence of discrete codes through a finite-scalar-quantization (FSQ) bottleneck and trains a perturbation-conditioned discrete prior over those codes. On Replogle and Parse~1M, eVAE sets a new state of the art on every distributional metric and leads on most cell-eval perturbation metrics, with Fr'echet distance and $mathrm{MMD}^2$ roughly $3$ to $20times$ lower than the strongest continuous-latent baseline. Swapping the prior between autoregressive and masked discrete diffusion leaves performance near-identical, isolating the gain to the discrete latent itself rather than the prior family. A decoder-head ablation then exposes a single design axis, the richness of the predictive distribution at inference, that splits the standard metrics into two groups, variance-sensitive and mean-sensitive, which move in opposite directions along the axis. Finally, on a held-out CRISPRi reversion benchmark of $1{,}732$ perturbations under inflammatory cytokine stress, the frozen eVAE encoder outperforms UMAP and differential expression and matches scGPT on perturbation ranking at a fraction of the data.

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

Two Wrongs, No Right: Auditing Social-Desirability Bias in LLM Annotators for Computational Social Science

Authors:

LLM annotators are increasingly used in computational social science (CSS), but it is unclear whether their alignment-shaped errors preserve the empirical conclusions a researcher would report. We audit three open-source 7B instruction-tuned models (Zephyr, Mistral-Instruct, Qwen2.5-Instruct) across six TweetEval tasks under four prompt conditions (72 cells) and find that social-desirability failures do not run in a single direction. Zephyr exhibits leniency bias, systematically under-applying harmful labels (offensive language: false benign rate 0.729, false alarm rate 0.031). Mistral and Qwen exhibit overcorrection, over-applying the same labels (Mistral hate-speech FAR = 0.604). All three models exhibit neutrality bias on abortion stance, underestimating opposition prevalence by 24 to 40 percentage points and inflating the neutral label. None of the four prompting interventions we test (neutral, safety framing, depersonalized, chain-of-thought) corrects these failures across models; safety framing can worsen stance distortion. Strikingly, Zephyr's hate-speech prevalence estimate matches the gold rate exactly while its class-conditional errors are large in both directions, an accidental cancellation that misleads aggregate validation. We translate these patterns into a three-part taxonomy with diagnostic FBR/FAR signatures and a lightweight gold-sample validation protocol. The headline for trustworthy CSS: a model that looks calibrated on aggregate metrics can still flip the substantive empirical conclusion a researcher would report.

14.
arXiv (CS.AI) 2026-06-17

FinAcumen: Financial Multimodal Reasoning via Self-Evolving Experience Memory Harness

arXiv:2606.17642v1 Announce Type: new Abstract: Financial multimodal reasoning requires agents to coordinate numerical computation, retrieval, visual interpretation, and temporal grounding across heterogeneous evidence sources. Existing tool-augmented agents improve execution fidelity, yet remain largely stateless across episodes, repeatedly rediscovering reasoning strategies and failure patterns. In high-stakes financial settings, this leads to unreliable tool routing, noisy retrieval, and hallucination-prone reasoning. We present FinAcumen, a financial reasoning agent framework centered on selective experience memory for tool-augmented multimodal reasoning. FinAcumen accumulates financially grounded reasoning experience from prior trajectories, distilling successful strategies and failure-derived cautionary rules into a persistent memory bank. During inference, retrieved experiences condition reasoning only when semantic relevance exceeds a calibrated threshold, while irrelevant memory is explicitly suppressed through a fallback mechanism. A deterministic financial tool environment further grounds numerical computation, retrieval, visual decoding, and answer verification.Across four financial multimodal reasoning benchmarks, FinAcumen consistently improves a frozen 8B vision-language model over finance-specialized models and approaches leading proprietary general-purpose models. Further analysis shows that selective experience activation improves reasoning reliability under retrieval uncertainty. Our code is anonymously available at https://anonymous.4open.science/r/FinAcumen

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

EyeMVP: OCT-Informed Fundus Representation Learning via Paired CFP–OCT Pretraining

Color fundus photography (CFP) is the mainstay for large-scale retinal screening, yet its diagnostic capacity is constrained by the lack of depth-resolved structural information. Optical coherence tomography (OCT) provides cross-sectional retinal anatomy, but is less accessible in population-level screening. Here, we present EyeMVP, a cross-modal retinal foundation model that uses paired CFP–OCT pretraining to learn OCT-informed CFP representations. EyeMVP is pretrained on 674,893 strict same-eye same-day paired CFP–OCT image triples from 112,642 patients across eight hospitals in China. The model uses cross-modal masked reconstruction to enrich CFP representations with OCT-associated supervision, while requiring only CFP images at inference. To accommodate the non-aligned imaging geometry between en-face CFP and cross-sectional OCT, EyeMVP combines source-constrained cross-attention with CFP-derived structural masks. Across 16 downstream tasks, including classification, segmentation, few-shot adaptation, and cross-modal retrieval, EyeMVP outperforms representative retinal foundation models and shows consistent gains on tasks involving macular and optic nerve structure. For CFP-challenging macular diseases, EyeMVP achieves an AUROC of 0.948 for macular edema (vs.~0.852 for EyeCLIP) and 0.825 for myopic macular schisis. In an exploratory reader study, EyeMVP exceeds junior and intermediate ophthalmologist groups but does not reach senior ophthalmologist performance on macular edema, while showing numerically higher balanced accuracy than all reader groups on myopic macular schisis. These results suggest that pixel-level cross-modal reconstruction can enrich CFP representations with OCT-associated supervision, providing a practical route toward stronger CFP-based retinal analysis in screening settings.

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

Coping in Crisis: Computational Modeling of Coping Styles in Digital Crisis Discourse During the 2023 Turkiye Earthquake

How do people cope when disaster strikes and can we detect it at scale, in real time, from what they write? This study addresses that question using over one million Turkish-language tweets posted in the aftermath of the February 6, 2023 earthquake in Turkiye, which unfolded in a deeply polarized political context just months before a national election. Drawing on Lazarus and Folkman's (1984) coping theory, we develop a multi-label BERTurk classifier to detect three coping styles (problem-focused, emotion-focused, and meaning-making) across four theoretically motivated crisis phases. BERTurk achieves a macro F1 of 0.693, substantially outperforming a zero-shot mDeBERTa baseline (macro F1 = 0.324). Applied to the full corpus, the classifier reveals a clear temporal trajectory: problem-focused coping dominates the urgency phase and declines sharply, emotion-focused coping rises and stabilizes, and meaning-making increases monotonically. Anger correlates most strongly with meaning-making (Spearman r = 0.387), suggesting it functions as a mobilizing force toward blame attribution rather than practical action. These findings demonstrate that coping theory can be reliably operationalized in real-world digital crisis data and that doing so can help humanitarian organizations tailor their responses to where a population actually is.

17.
arXiv (CS.CL) 2026-06-18

G-IdiomAlign: A Gloss-Pivoted Benchmark for Cross-Lingual Idiom Alignment

Idioms are difficult to transfer across languages due to their non-compositionality and weak surface-form grounding, making literal mappings unreliable. We present G-IdiomAlign, a gloss-pivoted benchmark where each idiom is anchored by an English gloss from Wiktionary. We further construct a high-confidence reference alignment set for reproducible evaluation. G-IdiomAlign supports two protocols: (1) a controlled Multiple-Choice Idiom Equivalence with typed distractors for error attribution; and (2) a Gloss-Contrastive Generation contrasting No-gloss and With-gloss inputs to isolate the effect of an explicit semantic pivot. Across diverse LLMs, a bias to literal translation is a dominant failure mode, especially when the target is a low-resource language. Glosses consistently improve Gloss-Contrastive Generation under an embedding-based semantic proxy, but performance remains modest, indicating substantial headroom in the open output space. Subsequent analysis on Qwen3-8B further suggests that cross-condition differences are concentrated more in attention heads than in layers, while better With-gloss generations coincide with stronger gloss anchoring.

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

Urdu Katib Handwritten Dataset: A Historical Document Dataset for Offline Urdu Handwritten Text Recognition with CRNN-Based Baseline Evaluation

Automatic Handwritten Text Recognition (HTR) is inherently a challenging task, and its complexity is further increased when dealing with cursive scripts. Although significant efforts have been made on various cursive scripts, research regarding Urdu Handwritten Text Recognition (UHTR) has been relatively limited. This lag of research is primarily due to the unique challenges posed by its script, and the scarcity and unavailability of benchmark datasets. Therefore, to advance research in UHTR, this study presents a specialized real dataset called the Urdu Katib Handwritten Dataset (UKHD). To the best of our knowledge, this is the first offline Urdu handwritten text lines dataset specifically curated from the materials written by Katibs in historical times. It encompasses a diverse range of flat nib writing variations in the Nastalique calligraphic style. Additionally, the effectiveness of different CRNN-based hybrid models has been evaluated to identify the optimal architecture for Urdu Katib Handwriting Recognition (UKHR). Among the analyzed models, the CNN-BGRU-CTC model showed more robust performance, with low Character Error Rate (CER) and Word Error Rate (WER). This research work aims to support and encourage the research community in developing a robust recognition system for preserving Urdu handwritten literature.

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

Controlled Comparison of Machine Learning Models for Fault Classification and Localization in Power System Protection

arXiv:2510.00831v2 Announce Type: replace Abstract: The increasing complexity of modern power systems, driven by the integration of inverter-based and distributed energy resources, challenges the reliability of conventional protection schemes and motivates the use of machine learning for protection tasks. However, published results are often difficult to compare because datasets, sensing assumptions, and decision horizons vary across studies. This paper presents a controlled comparison of machine learning models for fault classification (FC) and fault localization (FL) under identical sensing, timing, and validation conditions on a common electromagnetic transient dataset, using decision windows of 10-50 ms to reflect protection-relevant time scales. For FC, the best-performing nonlinear models achieve F1 scores above 0.98 already at 10 ms, while lower-capacity models degrade at shorter horizons but improve with longer windows, indicating that relevant fault-type information is already present in the earliest transient. For FL, the top-performing models reach a stable localization error of about 10 % of normalized line length across all evaluated horizons, while weaker models form a clearly separated second performance tier. Line-resolved analysis shows that localization accuracy varies across grid segments, indicating topology-dependent difficulty rather than insufficient temporal context alone. These findings provide a controlled reference for comparing machine learning models across two protection tasks with fundamentally different information requirements.

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

MirrorCheck: Efficient Adversarial Defense for Vision-Language Models

Vision-Language Models (VLMs) are increasingly susceptible to sophisticated adversarial attacks, including adaptive strategies specifically designed to bypass existing defenses. To address this vulnerability, we propose MirrorCheck, a robust and model-agnostic detection framework that operates effectively in both unimodal and multimodal settings. MirrorCheck leverages Text-to-Image (T2I) models to regenerate visual content from captions produced by the target model and assesses semantic consistency by comparing feature-space embeddings between the original and synthesized images. To enhance robustness against adaptive attacks, MirrorCheck introduces a stochastic defense strategy that randomly selects T2I generators and image encoders from a diverse model zoo. Additionally, we incorporate a novel One-Time-Use (OTU) perturbation applied to the selected encoder embeddings, regulated by a scaling factor, which decreases the effectiveness of adaptive attacks. Extensive experiments across multiple threat scenarios demonstrate that MirrorCheck consistently outperforms baseline methods, and maintains its utility even under strong adaptive adversarial conditions.

21.
arXiv (CS.AI) 2026-06-16

Evidence of an Emergent "Self" in Continual Robot Learning

arXiv:2603.24350v3 Announce Type: replace-cross Abstract: A key challenge to understanding self-awareness has been a principled way of quantifying whether an intelligent system has a concept of a "self", and if so how to differentiate the "self" from other cognitive structures. We propose that the "self" can be isolated by seeking the invariant portion of cognitive process that changes relatively little compared to more rapidly acquired cognitive skills - because our self is the most persistent aspect of our experiences. We used this principle to analyze the cognitive structure of robots under two conditions: One robot learns a constant task, while a second undergoes continual learning under variable tasks. We find that robots subjected to continual learning develop an invariant subnetwork that is significantly more stable (p < 0.001) compared to the control, and that this subnetwork is also functionally important: preserving it aids adaptation while damaging it impairs performance. We validate this pattern across three different robots spanning locomotion and manipulation.

22.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Authors:

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

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

X-MADAM-RAG: Diagnosing and Handling Chinese-English Evidence Conflict in Retrieval-Augmented Generation

Retrieval-augmented generation (RAG) systems may receive evidence that is not merely noisy but mutually contradictory. This issue becomes particularly salient in multilingual settings, where retrieved Chinese and English evidence may support incompatible answer candidates. We study this problem through X-RAMDocs-ZHEN, a controlled Chinese-English benchmark derived from RAMDocs for diagnosing evidence conflict in RAG. The benchmark contains 300 examples across six balanced conditions, including monolingual support, bilingual agreement, reversed conflict directions, and conflict with optional noise. We further examine X-MADAM-RAG, an interpretable pipeline that decomposes evidence handling into per-document candidate extraction, visible-evidence repair, deterministic candidate grouping, and conflict-aware aggregation. On the original controlled benchmark with Qwen2.5-7B-Instruct, X-MADAM-RAG achieves 0.9667 strict accuracy and 0.9767 conflict-aware success, outperforming an evidence-normalized single-call baseline. However, a zero-call rule-only extractor reaches 1.0000 on the same benchmark, revealing strong template regularity. To probe this limitation, we construct a deterministic naturalized stress test that removes explicit answer templates while preserving candidate strings. On its 100-sample subset, rule-only extraction falls to 0.0000, but X-MADAM-RAG also drops to 0.3000 strict accuracy, below both naive and evidence-normalized baselines. A privileged oracle remains perfect, indicating that document-level extraction is the main bottleneck. These findings position X-RAMDocs-ZHEN and X-MADAM-RAG as diagnostic tools for controlled evidence conflict rather than as evidence of general hallucination detection or robustness to natural retrieval.

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

SLU-2K: A Question-Based Benchmark for Semantic Evaluation of Sign Language Translation

Sign Language Translation (SLT) is typically evaluated with surface-form metrics such as BLEU and ROUGE, which reward lexical overlap but do not directly measure whether a translation preserves the meaning of the source sign sequence. This is in contrast with the final objective of integrating SLT in assistive technology. In this work, we shift the focus from Sign Language Translation (SLT) to Sign Language Understanding (SLU), with particular emphasis on semantic understanding. Specifically, we evaluate systems based on their ability to correctly recover, from the input video, key semantic aspects of the original sentence, such as actions taking place and facts about people and objects. To enable this evaluation systematically, we propose SLU-2K, a dataset of 2,350 closed-ended video question-answer pairs based on the popular PHOENIX-2014T and CSL-Daily datasets. To obtain SLU-2K, we propose and extensively evaluate an automated data generation pipeline which produces questions across 7 categories, namely actions, locations, numbers, objects, people, time, and weather conditions. We show the potential of SLU-2K by evaluating popular Multimodal Large Language Models (MLLMs) and two representative state-of-the-art systems, MMSTL and SpaMo. Our results show that MLLMs reach near-random performance, highlighting the need for a more systematic integration of SLU in current AI systems. Furthermore, state-of-the-art translation systems carefully fine-tuned on in-domain data still exhibit a substantial semantic gap, with results ranging from 56.7% to 75.2%. These findings suggest that current SLT evaluation protocols overestimate true understanding and that future progress should be measured not only by fluency and n-gram overlap, but also by semantic correctness. Code, prompts, and benchmark files are available at https://github.com/ZenoTsT/SLU-2K

25.
arXiv (CS.LG) 2026-06-15

Denoising Score Matching with Random Features: Insights on Diffusion Models from Precise Learning Curves

arXiv:2502.00336v3 Announce Type: replace Abstract: We theoretically investigate the phenomena of generalization and memorization in diffusion models. Empirical studies suggest that these phenomena are influenced by model complexity and the size of the training dataset. In our experiments, we further observe that the number of noise samples per data sample ($m$) used during Denoising Score Matching (DSM) plays a significant and non-trivial role. We capture these behaviors and shed insights into their mechanisms by deriving asymptotically precise expressions for test and train errors of DSM under a simple theoretical setting. The score function is parameterized by random features neural networks, with the target distribution being $d$-dimensional Gaussian. We operate in a regime where the dimension $d$, number of data samples $n$, and number of features $p$ tend to infinity while keeping the ratios $\psi_n=\frac{n}{d}$ and $\psi_p=\frac{p}{d}$ fixed. By characterizing the test and train errors, we identify regimes of generalization and memorization as a function of $\psi_n,\psi_p$, and $m$. Our theoretical findings are consistent with the empirical observations.