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

Contrastive Regularization for Accent-Robust ASR

arXiv:2605.03297v2 Announce Type: replace-cross Abstract: ASR systems based on self-supervised acoustic pretraining and CTC fine-tuning achieve strong performance on native speech but remain sensitive to accent variability. We investigate supervised contrastive learning (SupCon) as a lightweight, accent-invariant auxiliary objective for CTC fine-tuning. An utterance-level contrastive loss regularizes encoder representations without architectural modification or explicit accent supervision. Experiments on the L2-ARCTIC benchmark show consistent WER reductions across multiple pretrained encoders, with up to 25 – 29\% relative reduction under unseen-accent evaluation. Analysis using within-transcript cosine dispersion indicates that SupCon promotes more compact and stable representation geometry under accent variability. Overall, SupCon provides an effective and model-agnostic regularization strategy for improving accent robustness.

02.
arXiv (quant-ph) 2026-06-12

Scalar Quantum Fields: Theory Space and its Geometry

arXiv:2606.12580v1 Announce Type: cross Abstract: Scalar fields provide perhaps the simplest playground in which to develop our understanding of quantum field theory. In this lecture, we consider what it means to write down a scalar quantum field theory and how we can give geometrical interpretations to the space of such theories: the theory space.

03.
arXiv (quant-ph) 2026-06-16

A complexity theory for non-local quantum computation

arXiv:2505.23893v2 Announce Type: replace Abstract: Non-local quantum computation (NLQC) replaces a local interaction between two systems with a single round of communication and shared entanglement. Despite many partial results, it is known that a characterization of entanglement cost in at least certain NLQC tasks would imply significant breakthroughs in complexity theory. Here, we avoid these obstructions and take an indirect approach to understanding resource requirements in NLQC, which mimics the approach used by complexity theorists: we study the relative hardness of different NLQC tasks by identifying resource efficient reductions between them. Most significantly, we prove that $f$-measure and $f$-route, the two best studied NLQC tasks, are in fact equivalent under $O(1)$ overhead reductions. This result simplifies many existing proofs in the literature and extends several new properties to $f$-measure. For instance, we obtain sub-exponential upper bounds on $f$-measure for all functions, and efficient protocols for functions in the complexity class $\mathsf{Mod}_k\mathsf{L}$. Beyond this, we study a number of other examples of NLQC tasks and their relationships.

04.
arXiv (CS.CV) 2026-06-19

ReA-OVCD: Reliability-Aware Open-Vocabulary Change Detection via Semantic and Spatial Refinement

Unlike traditional remote sensing change detection that relies on predefined categories, Open-Vocabulary Change Detection (OVCD) identifies land cover changes flexibly using arbitrary text prompts. However, existing methods suffer from an inherent trade-off when modeling changes: instance-level comparison overlooks fine-grained semantic variations (e.g., partial building extensions), while direct pixel comparison proves unreliable, yielding unstable responses and boundary artifacts due to semantic ambiguity and spatial inconsistency. To this end, we propose an efficient training-free Reliability-Aware Open-Vocabulary Change Detection (ReA-OVCD) framework. It first derives candidate change regions from pixel-wise semantic discrepancies to ensure flexible and detailed localization. To ensure reliability, it subsequently introduces a collaborative refinement strategy to explicitly model change validity from both semantic and spatial perspectives. Specifically, we develop a Semantic Change Reasoning (SCR) module that reassesses changes by jointly analyzing distributional divergence and response variation, enabling the suppression of incidental inconsistencies while preserving reliable semantic shifts. In addition, a Boundary-aware Change Refinement (BCR) module is designed to mitigate artifacts stemming from boundary misalignment and uncertainty through validating whether candidate regions are supported by reliable interior pixels. Extensive experiments across multiple datasets (LEVIR-CD, WHU-CD, DSIFN, and SECOND) demonstrate that our method consistently outperforms state-of-the-art approaches, achieving $\mathrm{F}_{1}^{C}$ improvements of 2.13\% to 9.75\% with higher computational efficiency. The code is publicly available at \https://github.com/Funny0101/ReA-OVCD

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

Sub-Semantic Image Segmentation

Images can be segmented based on visual cues (i.e., texture segmentation) or into objects (i.e., semantic segmentation). We propose a new category of sub-semantic image segmentation that blurs the line between the two. In sub-semantic image segmentation, language is not used to name whole objects. Instead, it is used to partition an image into stable appearance patterns that can be described by language. To do that, we couple a general-purpose vision-language model to SAM 3, a promptable segmentation backbone whose native text pathway can ground rich descriptions into masks. Simple coupling fails for a number of reasons that we identify in the paper, and we overcome them by introducing DETECTURE that resolves three concrete failure modes – language leakage between texture regions, prompt competition inside the segmentation backbone, and semantic distortion at the language-to-mask interface. Since there is no dataset of sub-semantic image segmentation, we introduce one, termed TextureADE. The new dataset is derived from the ADE20K dataset using a system we designed. We compare DETECTURE to a number of baselines and find that it achieves the strongest performance on several datasets using different metrics. Code is available at https://github.com/Scientific-Computing-Lab/TextureDetecture.

06.
arXiv (quant-ph) 2026-06-16

Decoupling local classicality from classical explainability: A noncontextual model for bilocal classical theory and a locally-classical but contextual theory

arXiv:2511.19266v2 Announce Type: replace Abstract: We construct an ontological model for the theory known as bilocal classical theory doi.org/10.1103/PhysRevA.102.052216. To our knowledge, this is only the second time that an ontological model has been constructed for an entire theory, rather than just for some particular scenarios within a theory. This result refutes a conjecture from doi.org/10.1103/PhysRevA.102.052216 which suggested that there might be no local-realist ontological model for bilocal classical theory. Moreover, it is the first time that an ontological model has been constructed for a theory that fails to be locally tomographic, showing that the assumption of local tomography underpinning the structure theorem in doi.org/10.22331/q-2024-03-14-1283 is a genuine limitation of the theorem. This demonstrates that in general there is no tension between failures of local tomography and classical explainability (i.e., generalised noncontextuality). In fact, bilocal classical theory is in many ways more simply understood via the underlying ontological model than it is within its original formulation (much as how odd-dimensional stabiliser subtheories can be more simply understood via Spekkens' toy theory). Furthermore, this result naturally leads to the question, does every locally-classical theory admit of an ontological model? By constructing a concrete counterexample, we show that this is not the case. Our findings demonstrate that there is no straightforward relationship between theories being locally-classical, and them being classically-explainable. This shows that the fundamental status of compositional properties (such as local tomography) is not a technical side-issue, but a central and unavoidable question for a coherent understanding even of classicality itself.

07.
arXiv (CS.AI) 2026-06-17

Optimism Stabilizes Thompson Sampling for Adaptive Inference

arXiv:2602.06014v2 Announce Type: replace-cross Abstract: Thompson sampling (TS) is widely used for stochastic multi-armed bandits, yet its inferential properties under adaptive data collection are subtle. Classical asymptotic theory for sample means can fail because arm-specific sample sizes are random and coupled with the rewards through the action-selection rule. We study adaptive inference for Thompson sampling with Gaussian randomized indices in $K$-armed stochastic bandits with independent sub-Gaussian reward noises, and identify optimism as a key mechanism for restoring stability, meaning that each arm's pull count concentrates around a deterministic scale. This stability yields asymptotically valid Wald inference despite adaptive sampling. First, we prove that variance-inflated TS is stable for any $K \ge 2$, including the challenging regime where multiple arms are optimal, with asymptotically uniform allocation over optimal arms and sharp logarithmic pull-count asymptotics for suboptimal arms. This resolves the $K$-armed extension question raised by \citet{halder2025stable}, using new winner-map and Lyapunov-drift techniques to control allocation among multiple optimal arms. Second, we analyze an alternative optimistic modification that keeps the Gaussian index variance unchanged but adds an explicit mean bonus to the index center, and establish a similar stability conclusion. In summary, suitably implemented optimism stabilizes Thompson sampling and enables asymptotically valid Wald inference in multi-armed bandits, while incurring only a mild additional regret cost.

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

A Closer Look at Failure Modes in Temporal Understanding of Large Audio-Language Models

arXiv:2606.17417v1 Announce Type: cross Abstract: Large Audio Language Models (LALMs) achieve strong performance on a variety of audio understanding tasks but continue to struggle with temporal reasoning, a fundamental capability central to human auditory perception. Understanding the causes of these failures remains challenging as existing benchmarks report performance gaps without probing underlying mechanisms. To address this, we introduce a benchmark with 1,657 questions across three foundational tasks designed specifically for mechanistic analysis. Examining model outputs across varying input settings (behavioral analysis) reveals that models often under-utilize audio when textual cues are available. We also provide the first causal mechanistic analysis of temporal reasoning failures in LALMs. Comparing attention upweighting against scaling, we find that redistributing attention across audio tokens is more effective than increasing audio attention. Targeting task-relevant tokens yields further gains. These findings suggest that modality imbalance alone cannot explain failures. Attention scaling at bottleneck layers improves accuracy from 55.9% to 59.1% without fine-tuning, demonstrating a promising direction for future work.

09.
arXiv (CS.LG) 2026-06-11

Mechanisms of Introspective Awareness

arXiv:2603.21396v5 Announce Type: replace Abstract: Recent work has shown that LLMs can sometimes detect when steering vectors are injected into their residual stream and identify the injected concept – a phenomenon termed "introspective awareness." We investigate the mechanisms underlying this capability in open-weights models. First, we find that it is behaviorally robust: models detect injected steering vectors at moderate rates with 0% false positives across diverse prompts and dialogue formats. Notably, this capability emerges specifically from post-training; we show that preference optimization algorithms like DPO can elicit it, but standard supervised finetuning does not. We provide evidence that detection cannot be explained by simple linear association between certain steering vectors and directions promoting affirmative responses. We trace the detection mechanism to a two-stage circuit in which "evidence carrier" features in early post-injection layers detect perturbations monotonically along diverse directions, suppressing downstream "gate" features that implement a default negative response. This circuit is absent in base models and robust to refusal ablation. Identification of injected concepts relies on largely distinct later-layer mechanisms that only weakly overlap with those involved in detection. Finally, we show that introspective capability is substantially underelicited: ablating refusal directions improves detection by +53%, and a trained bias vector improves it by +75% on held-out concepts, both without meaningfully increasing false positives. Our results suggest that this introspective awareness of injected concepts is robust and mechanistically nontrivial, and could be substantially amplified in future models. Code: https://github.com/safety-research/introspection-mechanisms.

10.
Nature Biotechnology 2026-06-22

Affordable centimeter-scale 3D microscopy with submicrometer resolution

作者: 未知作者

Submicrometer-resolution three-dimensional (3D) imaging of large samples has been constrained by the short working distance, high cost and inflexible design of immersion objectives. We developed hybrid solid–liquid optics (HySIL) — a refractive framework with index-matched components — for submicrometer-resolution 3D imaging of centimeter-scale samples in various immersion media using inexpensive air objectives.

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

NetBurst: Event-Centric Forecasting of Bursty, Intermittent Time Series

arXiv:2510.22397v2 Announce Type: replace-cross Abstract: Network operators monitor their infrastructure by collecting telemetry data such as packet counts, byte rates, or flow volumes, yet answering the questions that effective operations demand – forecasting future load, diagnosing and characterizing anomalies, and searching for and retrieving historical precedents – requires more than raw measurements. Bridging this gap calls for learned representations: compact per-entity summaries that capture temporal dynamics from each entity's univariate time series. Time-series foundation models are the natural starting point, but they are designed for dense, periodic benchmark datasets – the mild statistical regime. However, network telemetry data inhabits the wild regime: operationally relevant events are rare, separated by variable-length stretches of low or no activity (``ebbs''), with intermittent bursts of heavy-tailed extremes (``tides''). We present NetBurst, an event-centric pipeline that collapses ebbs, separates each time series into a stream of burst timings and a stream of burst magnitudes, and learns a single representation serving all three operational tasks. Compared to the strongest competitors among eight baselines – including Amazon's Chronos-2 and Datadog's Toto – and across nine production telemetry configurations, NetBurst reduces median forecasting error by $1.3$–$116\times$ on wild-regime data with a $1.0$–$7.5\times$ better match to the true burst distribution, and matches baselines on mild-regime benchmarks. For characterizing anomalies, NetBurst produces balanced, well-spread clusters that are $16\times$ more describable in operator-familiar terms under a novel interpretability score, and cluster-filtered search delivers $7.5\times$ faster end-to-end retrieval.

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

On Pitfalls of $RemOve-And-Retrain$: Data Processing Inequality Perspective

The RemOve-And-Retrain (ROAR) benchmark is widely used to evaluate feature attribution methods, yet its validity remains underexplored from an information-theoretic perspective. We show that model- and data-agnostic post-processing of attribution maps (transformations that, by the data processing inequality, cannot add information about the decision function) can often improve ROAR scores. This means that an improved ROAR ranking is not, by itself, evidence that an attribution map carries more information about the model. We trace this failure mode to a bias toward spatially blurry masks. Experiments on CIFAR-10, SVHN, and CUB-200 show a consistent association between blurriness and ROAR performance, a pattern that also appears in the ROAD variant. We provide guidelines for more cautious removal-based benchmarking, with implications for validating mechanistic understanding of neural network internals.

13.
arXiv (CS.CV) 2026-06-16

Latent Action Pretraining Through World Modeling

Vision-Language-Action (VLA) models have gained popularity for learning robotic manipulation tasks that follow language instructions. State-of-the-art VLAs, such as OpenVLA and $\pi_{0}$, were trained on large-scale, manually labeled action datasets collected through teleoperation. More recent approaches, including LAPA and villa-X, introduce latent action representations that enable unsupervised pretraining on unlabeled datasets by modeling abstract visual changes between frames. Although these methods have shown strong results, their large model sizes make deployment in real-world settings challenging. In this work, we propose LAWM, a model-agnostic framework to pretrain imitation learning models in a self-supervised way, by learning latent action representations from unlabeled video data through world modeling. These videos can be sourced from robot recordings or videos of humans performing actions with everyday objects. Our framework is able to transfer learned knowledge across tasks, environments, and embodiments. It outperforms models pretrained with ground-truth robot actions and other similar pretraining methods on the LIBERO benchmark and real-world setup, while being efficient and practical for real-world settings.

14.
arXiv (CS.CV) 2026-06-19

Spectral Query-Key Product Weight Steering for Training-Free VLM Hallucination Mitigation

Vision-language models (VLMs) often generate fluent but visually unsupported descriptions, especially by mentioning objects absent from the image. We propose QK Product Steering, a data-free, training-free, and zero-inference-cost weight edit for reducing object hallucination. The method directly edits the per-head query-key product, the operator that produces pre-softmax attention logits, by suppressing a small number of dominant singular modes in selected middle layers. The edited product is then mapped back to the query weights through a closed-form query-only update while keeping shared key weights fixed, making the edit compatible with grouped-query attention. We further decompose the QK product into symmetric and antisymmetric components to distinguish mutual content-similarity patterns from directional attention patterns. Across three GQA-based VLMs, QK Product Steering achieves an average relative CHAIR$_s$ reduction of $4.0\%$, while matched random-mode controls show negligible change. Interpretability ablations show that the hallucination signal is specific to dominant QK modes and is primarily localized to the symmetric mutual-attention channel. Overall, QK Product Steering offers a simple alternative to decoding-time mitigation, requiring no additional data, fine-tuning, or inference-time overhead while largely preserving general multimodal capability.

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

FlowFake: Liquid Networks for Audio Deepfake Detection

arXiv:2606.19579v1 Announce Type: cross Abstract: Audio deepfakes generated by neural text-to-speech and voice-cloning systems threaten speaker verification and public discourse at scale. The core challenge is cross-dataset generalization: detectors trained on one synthesis pipeline collapse on unseen forgeries. We argue that this failure is primarily because of structural synthetic speech artifacts which are multi-timescale trajectory anomalies. Though every existing detector aggregates a fixed-window frame statistics, this misaligns the architecture with the signal. We propose FlowFake, a Liquid Time-Constant (LTC) architecture whose hidden state evolves via a learned ODE, with per-neuron adaptive time constants simultaneously resolving spectral (10ms) and prosodic (2s) cues. At only 34K parameters FlowFake achieves formal BIBO stability and O(dt^4) integration error. On a four-dataset cross domain benchmark (ASVspoof2019-LA, FakeOrReal, InTheWild, MLAAD), FlowFake reaches 75.29% on ASVspoof2019 trained only on FakeOrReal and 79.97% trained only on MLAAD. It outperforms RawGAT-ST and Whisper-DF on every evaluated pair and matching SSL Wav2vec2 (300x larger) at 0.01% of its parameter count. The source code is available on : https://github.com/GhostRider2023/FlowFake

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

SafeLLM: Extraction as a Hallucination-Resistant Alternative to Rewriting in Safety-Critical Settings

Large language models (LLMs) are increasingly used to access organisational documentation, including standard operating procedures (SOPs), HR policies and institutional guidelines. However, retrieval-augmented generation (RAG) systems that rely on free-form rewriting can introduce hallucinations and unstable trade-offs between completeness and conciseness, particularly in safety- and compliance-critical settings. Objectives: To evaluate extraction as a hallucination-resistant alternative to rewriting-based RAG and compare strategies that balance precision, recall and safety across document types and model scales. Methods: We compare multiple prompting strategies, including line-number-based source selection, extraction of relevant guideline sentences with explicit safety annotations, and a multi-stage pipeline that refines draft answers using supporting evidence from source guidelines. Experiments are conducted on documents of varying length and structure, including local NHS acute care and oncology guidelines and UK-wide NICE guidelines, using both frontier-scale and locally deployable models. Performance is assessed using automatic metrics and human expert evaluation of relevance and completeness. Results: Line-number selection achieves the strongest results, outperforming direct copying and safety-focused strategies across both large and small models while maintaining high term recall (up to 95%) and close alignment with source text. Safety-oriented approaches improve precision but introduce systematic omissions, while multi-stage filtering further amplifies this trade-off. Performance varies with document structure: line-based extraction excels in protocol-like content, whereas alternative strategies perform better on more verbose documents (up to 97% term recall).

17.
arXiv (CS.AI) 2026-06-12

Under What Conditions Can a Machine Become Genuinely Creative?

作者:

arXiv:2606.13196v1 Announce Type: new Abstract: Recent AI systems can generate texts, software architectures, hypotheses, designs, and scientific workflows that appear creative. This paper asks under what conditions a machine can become genuinely creative, and how human agency can be preserved within shared cognitive and creative environments. It develops a requirement framework derived from Designics, the science of meaning-bearing intentional change. The paper argues that genuine machine creativity should not be defined by output novelty, current performance, or transient architecture alone. Instead, creativity is understood as the structural transformation of incomplete situations through recursive intervention dynamics. On this view, it depends on ten requirements: environment representation, scoped perception, conflict identification, intervention capability, consequence observation, knowledge and environment update, rescoping, local-to-global unfolding, value-based scoping, and human-AI co-living. These are organized through the three laws of Designics: perception, conflict, and capability. The paper illustrates the computational tractability of these requirements through selected cyber-physical and cyber-biological studies, including recursive element extraction, autonomous mesh generation, and neurophysiological and workload analysis. It then treats open-ended systems, automated discovery frameworks, self-modifying agents, foundation models, and agentic workflows as pressure cases: they demonstrate powerful generative means but do not by themselves establish genuine machine creativity. Finally, the paper argues that proactive AI ethics is internal to genuine machine creativity rather than an after-the-fact filter. Value-based scoping and human-AI co-living must shape how creative machines perceive environments, identify conflicts, select interventions, observe consequences, update knowledge, and rescope future action.

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

Learning in the Recurrent State: Gradient Descent with Linear Recurrent Networks

arXiv:2410.11687v3 Announce Type: replace-cross Abstract: Linear recurrent networks (LRNNs) offer linear-time sequence modeling, but standard recurrent updates do not directly expose the supervised products needed for in-context gradient descent. We propose a sufficient constructive inductive bias for LRNNs: equip a diagonal recurrent state with multiplicative readout and a short sliding-window cross-product self-attention update. The resulting architecture, Gradient-based Recurrent In-context Learner (GRIL), can implement minibatch gradient descent on a task-specific linear predictor during a single forward pass. The same design extends to multi-step updates and cross-entropy classification, with a limited MLP-based extension to non-linear regression. Empirically, trained GRILs recover the behavior and parameters predicted by the construction on synthetic ICL tasks, and the same architectural bias yields useful performance on Long Range Arena and language modelling. These results present windowed cross-product self-attention as a practical, testable inductive bias for LRNNs that learn in context through gradient-descent-like updates.

19.
bioRxiv (Bioinfo) 2026-06-22

CellTosg2Sequence: A Unified Text-Omics-Signaling-Graph Large Language Model for Single-Cell Analysis

bioRxivLaTeXUnicodeabstract — In single-cell (sc)-based scientific discovery, text-formatted biomedical prior knowledge and signaling graphs are essential for annotating and interpreting numeric sc-omics data and for generating novel testable hypotheses. A major limitation of existing single-cell large language models (scLLMs) is that they rely on numeric expression data with gene names as the only textual signal, while comprehensive biomedical priors – cellular localization, gene function, disease associations, and signaling interaction patterns – remain absent from the model input. We introduce CellTosg2Sequence, a textual-prior- and signaling-graph-augmented cell-omics-sentence language model. A lightweight heterogeneous graph encoder maps a curated 62,507-node biomedical knowledge graph (KG) into compact virtual tokens that are prepended to each cell sentence, allowing the language model to condition on biological structure with minimal sequence-length overhead. We train CellTosg2Sequence with a three-stage objective: Stage I anchors the KG channel under autoregressive language-model pretraining, leveraging Qwen2.5-32B's own language reasoning for rapid KG alignment; Stage II aligns labels via supervised fine-tuning with KG-anchored InfoNCE; Stage III applies Group Relative Policy Optimization (GRPO) with an ontology-hierarchy reward, enabling free-generation cell-type prediction that generalizes beyond the closed training vocabulary. Across multiple benchmarks and ablation experiments, CellTosg2Sequence outperforms strong baselines. All results are achieved with lightweight LoRA training and a single unified checkpoint.

20.
medRxiv (Medicine) 2026-06-22

Starting, stopping and restarting. Patterns of Methylphenidate Use over 14 years in a large public health system

Background Persistence with stimulant medication is poor in children and adolescents with ADHD, and the evidence base is derived predominantly from high-income countries. We describe methylphenidate utilisation patterns and predictors of 12-month retention across 14 years in a large South African public health service. Methods Retrospective cohort study using routine pharmacy data from the Western Cape provincial health service (2011-2024). Children aged 5-18 at first prescription were included. Treatment episodes were defined as continuous prescription sequences with no gap exceeding 90 days and classified as initiations or restarts. Logistic regression modelled 12-month retention against early visit frequency and formulation type as pre-specified exposures. Findings 421,925 prescription events for 23,243 children across 115 facilities generated 65,885 treatment episodes. Median age at first prescription was 10 years (IQR 8-12); 77.6% were male. Kaplan-Meier 12-month survival was 28.2% for initiations and 15.4% for restarts, substantially below high-income country comparators. A quarter of all initiating prescriptions were not followed by a subsequent dispensing event; nearly 40% of patients had three or more treatment episodes. Early visit frequency was the strongest predictor of 12-month retention (high vs low: OR 2.85, 95% CI 2.65-3.06). The sustained-release formulation effect was present but attenuated on multivariable adjustment. Treatment re-initiations showed a marked seasonal pattern consistent with the South African school calendar. Interpretation Twelve-month retention was markedly lower than high-income country rates. Against a backdrop of high attrition, both early visit frequency and sustained-release formulation access predicted persistence; clinical engagement and reducing structural barriers to access are modifiable factors in this setting. Funding None.

21.
arXiv (CS.CL) 2026-06-11

Pretrained self-supervised speech models can recognize unseen consonants

Modern pretrained self-supervised automatic speech recognition models are trained on large-scale audio data to encode speech into contextualized representations. However, their training data are heavily skewed toward high-resource languages with little data from low-resource languages, raising concerns about the potential underrepresentation of typologically uncommon speech sounds such as click consonants primarily found in Khoisan languages. This leads to our central research question: Can these models recognize click consonants as accurately as other speech sounds? To address this question, we fine-tune and compare pretrained self-supervised speech models (Wav2Vec2 and HuBERT) on data from two click-rich Khoisan languages (G|ui and West !Xoon). Our results reveal that the fine-tuned models consistently recognize clicks more accurately than non-clicks, suggesting that self-supervision enables generalization across human speech sounds including rare phonemes.

22.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

23.
Nature (Science) 2026-06-10

Gene ancestries reveal diverse microbial associations during eukaryogenesis

The origin of eukaryotes remains a central enigma in biology1. Continuing debates agree on the pivotal role of a symbiosis between an alphaproteobacterium and an Asgard archaeon2,3. However, the nature, timing and contributions of other potential bacterial partners4–6 and the role of interactions with viruses7–9 remain contentious. To address these questions, we used advanced phylogenomic approaches and comprehensive datasets spanning the known diversity of cellular life and viruses. Our analysis provided a revised reconstruction of the last eukaryotic common ancestor (LECA) proteome, in which we traced the phylogenetic origin of each protein family. We found compelling evidence for multiple waves of horizontal gene transfer from diverse bacterial donors, with some likely to have preceded mitochondrial endosymbiosis. We inferred plausible traits of the major donors and their functional contributions to the LECA. Our findings support a contribution of horizontal gene transfers to shaping the proteomes of pre-LECA ancestors and suggest a facilitating role of Nucleocytoviricota viruses. Taken together, our results suggest that ancient eukaryotes may have originated within complex microbial ecosystems through a succession of diverse associations that left a footprint of horizontally transferred genes. Phylogenomic reconstruction of the proteome of the last eukaryotic common ancestor sheds light on the origin of eukaryotes, indicating an important role of horizontal transfer of genes from diverse bacterial and viral donors.

24.
arXiv (quant-ph) 2026-06-15

Link-Free Multi-Node Timing Synchronization for Scalable Quantum Networking

arXiv:2606.14077v1 Announce Type: new Abstract: Precise timing synchronization is essential for distributed quantum networking, enabling entanglement distribution, quantum teleportation, and entanglement swapping across remote nodes. Existing synchronization architectures rely on dedicated timing-distribution infrastructure, most notably White Rabbit networks, which constrain topology, scalability, and deployment in free-space and satellite environments. Here we demonstrate link-free synchronization of quantum network nodes using independently operating miniature rubidium atomic clocks and computational post-processing. We validate the approach on a deployed metropolitan-scale telecom fiber network spanning three geographically separated nodes. Following drift correction, atomic-clock-based synchronization achieves timing performance approaching that of a White Rabbit benchmark and remains stable over continuous 8-hour operation. As a stringent test of quantum-network functionality, we observe Hong-Ou-Mandel interference across spatially separated nodes with visibility exceeding 70%, statistically equivalent to that obtained using dedicated White Rabbit timing links. To the best of our knowledge, this represents the first observation of quantum interference across a deployed metropolitan-scale telecom fiber network synchronized entirely without dedicated timing-transfer infrastructure. These results establish atomic-clock-based synchronization as a scalable, topology-independent alternative to conventional timing-distribution architectures and a practical pathway toward terrestrial, airborne, and space-based quantum networks where dedicated timing links are unavailable.

25.
arXiv (CS.CL) 2026-06-12

HyPE: Category-Aware Hypergraph Encoding with Persistent Edge Embeddings for Persona-Grounded Dialogue

Persona-grounded dialogue systems aim to produce responses consistent with a speaker's persona, yet existing methods treat personas as a flat set of sentences and fail to model the high-order relations among persona attributes-e.g., that several persona sentences share a topical category. We propose HyPE (Hypergraph Persona Encoder), a framework that (i) analyzes each persona-bearing text as a (Core, Expression, Sentiment, Category) quadruple, and (ii) organizes persona elements into a hypergraph whose hyperedges are induced by shared category labels. An HyperGCN hypergraph neural network propagates this structure into a persona summary vector and a soft-memory bank that condition the response generator. We further propose Persistent Edge Embeddings (PEE), lightweight per-category learnable priors fused into the HyperGCN message-passing step. On PersonaChat under greedy decoding, HyPE consistently outperforms sentence-level pooling baselines across GPT-2, LLaMA-3.2-3B, and Qwen2.5-3B backbones by demonstrating that structured hyperedge-level persona encoding provides a transferable advantage across model scales.