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01.
Nature (Science) 2026-06-10

Mitochondria tethered to the nucleus secure its energy supply

Direct interactions between the cell’s powerhouses and nuclear pores might channel energy straight into the nucleus, fuelling cell division and differentiation. Direct interactions between the cell’s powerhouses and nuclear pores might channel energy straight into the nucleus, fuelling cell division and differentiation.

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

Analyzing and Improving Fine-grained Preference Optimization in Medical LVLMs

Large Vision-Language Models (LVLMs) have achieved strong performance across medical imaging tasks, yet they remain prone to factual inconsistencies, poor visual grounding, and misalignment with clinically meaningful feedback. Existing post-training alignment approaches, including Direct Preference Optimization (DPO) and its variants, face three critical limitations in the medical domain: (1) sequence-level reward signals treat clinically critical tokens identically to generic filler text; (2) reliance on static supervised fine-tuning references as preferred responses introduces an off-policy distribution shift, steering optimization toward stylistic artifacts over clinical correctness; and (3) alignment objectives lack explicit visual grounding constraints, leaving models insensitive to subtle yet diagnostically decisive pathological features. Our method leverages a bidirectional token-wise KL regularizer alongside a visual-contrastive grounding objective that pairs clean and lesion-corrupted images to penalize responses generated without adequate visual evidence. Together, these components form a fine-grained, on-policy alignment framework that constructs preference pairs by minimally editing model-generated outputs, correcting only clinically erroneous spans while preserving the original linguistic style. Extensive experiments across medical imaging tasks and clinical text generation benchmarks validate the effectiveness of our approach.

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

Conditional Attribution for Root Cause Analysis in Time-Series Anomaly Detection

arXiv:2604.17616v3 Announce Type: replace Abstract: Root cause analysis (RCA) for time-series anomaly detection is critical for the reliable operation of complex real-world systems. Existing explanation methods often rely on unrealistic feature perturbations and ignore temporal and cross-feature dependencies, leading to unreliable attributions. We propose a conditional attribution framework that explains anomalies relative to contextually similar normal system states. Instead of using marginal or randomly sampled baselines, our method retrieves representative normal instances conditioned on the anomalous observation, enabling dependency-preserving and operationally meaningful explanations. To support high-dimensional time-series data, contextual retrieval is performed in learned low-dimensional representations using both variational autoencoder latent spaces and UMAP manifold embeddings. By grounding the retrieval process in the system's learned manifold, this strategy avoids out-of-distribution artifacts and ensures attribution fidelity while maintaining computational efficiency. We further introduce confidence-aware and temporal evaluation metrics for assessing explanation reliability and responsiveness. Experiments on the SWaT and MSDS benchmarks demonstrate that the proposed approach consistently improves root-cause identification accuracy, temporal localization, and robustness across multiple anomaly detection models. These results highlight the practical utility of conditional attribution for explainable anomaly diagnosis in complex time-series systems. Code and models are available at: https://github.com/dfki-av/Conditional-Attribution-for-Root-Cause-Analysis-in-Time-Series-Anomaly-Detection.

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

SMGFM: Spectral Multimodal Graph Pretraining for Multimodal-Attributed Graphs

arXiv:2606.12867v1 Announce Type: new Abstract: Multimodal-attributed graphs (MAGs) couple graph topology with node semantics from text, images, and other modalities. Traditional graph learning contextualizes node semantics by coupling topology with node features. However, this coupling design becomes troublesome in MAGs, where structure-induced and modality-intrinsic semantics may contribute differently to downstream tasks. Structure-induced semantics promote relational consistency through smooth topological variation, whereas modality-intrinsic semantics often encode local, fine-grained distinctions that should not be uniformly smoothed or aligned. Therefore, the key challenge is to identify semantic roles before cross-modal fusion. To this end, we leverage graph-frequency variation as a prior, where low-frequency components capture topology-consistent semantics and high-frequency components preserve modality-specific semantics. Based on this intuition, we propose SMGFM, a spectral multimodal graph pretraining framework that decomposes each modality-specific node signal into graph-frequency bands and assigns band-level semantic roles before cross-modal interaction. Concretely, SMGFM constructs frequency-resolved modality tokens with scalable Chebyshev filters, estimates their coupling reliability through topology-conditioned routing, and performs band-modality interaction before fusion. Its frequency-routed objectives align smooth consensus routes while preserving modality-specific routes, mitigating spatial-domain entanglement and uniform cross-modal alignment. Extensive experiments conducted on the MAG datasets demonstrate that SMGFM achieves state-of-the-art performance across graph-level and modality-level tasks.

05.
arXiv (CS.CV) 2026-06-11

Periodic-MAE: Periodic Video Masked Autoencoder for rPPG Estimation

In this paper, we propose Periodic-MAE, a self-supervised framework for learning generalizable spatio-temporal representations of periodic physiological signals from unlabeled facial videos. The proposed method leverages a masked autoencoder (MAE), which learns high-dimensional facial representations by reconstructing masked video tokens without relying on remote photoplethysmography (rPPG) specific supervision. To explicitly align representation learning with the characteristics of rPPG, we introduce a periodicity-aware frame masking strategy based on video resampling, enabling the encoder to learn representations that capture quasi-periodic temporal patterns relevant to pulse signal estimation. In addition, physiological bandlimit constraints are integrated into the MAE pre-training framework, exploiting the sparsity of pulse signals in the frequency domain to guide the learned representations toward physiologically meaningful patterns. After pre-training, the learned representations are transferred to downstream rPPG estimation, where the encoder serves as a generic feature extractor for recovering pulse-related signals from facial videos. We conduct extensive experiments on four benchmark datasets, including PURE, UBFC-rPPG, MMPD, and V4V. Moreover, we evaluate the proposed approach on a real-world rPPG dataset collected under unconstrained lighting conditions and subject motion. Experimental results demonstrate that Periodic-MAE consistently improves rPPG estimation performance, particularly in challenging cross-dataset and real-world evaluation settings. Our code is available at https://github.com/ziiho08/Periodic-MAE.

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

ALAS: An Automatic Latent Alignment Score for Audio Language Models

Large Language Models (LLMs) are extended into Speech-LLMs, and the quality of the audio–text alignment they learn affects most downstream Spoken Language Understanding (SLU) behavior. Yet despite a growth of fusion strategies, there is no standard way to measure how well a Speech-LLM internally binds audio frames to text tokens. We introduce ALAS (Automatic Latent Alignment Score), a model and task-agnostic metric that probes the LLM's per-layer hidden states, scoring the cross-modal cosine similarity between audio and text representations against a Whisper-derived reference. ALAS needs only a frozen forward pass and an off-the-shelf ASR reference, with no training or fitted classifier, and is calibrated to an interpretable uniform baseline comparable across tasks. Applying ALAS to four open-source Speech-LLMs (AF3, Qwen2-Audio, Qwen-Omni, SALMONN) across emotion recognition (IEMOCAP), open-ended SQA (LibriSQA), and multi-choice audio understanding (MMAU-speech), we find that the depth and strength of alignment reflect each model's audio-encoder design and the acoustic-versus-semantic demands of the task, and that ALAS tracks but does not duplicate task accuracy, exposing models that score well without genuinely grounding in the audio. We release ALAS as an open-source library so that practitioners can probe their own Speech-LLMs or try it on new tasks.

07.
arXiv (CS.AI) 2026-06-18

Deep Learning-Driven Inverse Design of Doherty Power Amplifiers Using Pixelated Combiners and Dual-State Impedance Synthesis

arXiv:2606.18395v1 Announce Type: cross Abstract: The output combiner of a Doherty power amplifier (PA) integrates load modulation, impedance matching, and phase compensation within a single network, making its design and synthesis highly challenging. In this paper, we propose a three-port Doherty combiner design methodology that combines deep convolutional neural networks (CNNs), pixelated layout representations, and genetic algorithms (GA) with dual-state impedance synthesis to address both peak and back-off power conditions. As a proof of concept, two GaN HEMT Doherty PA prototypes incorporating three-port pixelated combiners are designed and fabricated. Both prototypes achieve a measured saturated output power exceeding 44.2 dBm with peak drain efficiency above 71.2% within 2.6-2.8 GHz. Furthermore, a drain efficiency as high as 64% is measured at the 6-dB back-off level. After applying digital predistortion, each prototype achieves an adjacent channel leakage ratio (ACLR) better than -51.3 dBc.

08.
arXiv (CS.LG) 2026-06-18

A Guide to Estimating Conditional Average Treatment Effects in Competing Risks Settings

arXiv:2606.18281v1 Announce Type: cross Abstract: Conditional average treatment effects (CATEs) are central to treatment decision-making in personalized medicine. In competing risks settings, estimating CATEs from survival data allows for patient-specific assessments of treatment effectiveness for a specific event of interest while properly accounting for alternative event types. This distinction is essential in the presence of comorbidities, where competing causes of death may otherwise confound the therapeutic benefit. Focusing on right-censored survival times with binary treatment, we examine CATEs defined as covariate-conditional differences in the absolute risk for the event of interest at a fixed time. To this end, we study meta-learners which adapt machine learning algorithms for CATE estimation in competing risks scenarios. We systematically compare six meta-learners, combining Cox regression or random survival forests for risk modeling with elastic net regression or random forests for direct CATE modeling. To provide practical guidance on model selection, we evaluate their performance in multiple simulation settings, that differ in hazard complexity, treatment heterogeneity, treatment assignment, event type distribution and censoring. To facilitate applied use, we provide the R package, crsurvlearners, which implements all considered approaches.

09.
Nature (Science) 2026-06-17

Navigating a crowded developing brain leaves neurons with broken DNA

As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails. As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails.

10.
arXiv (CS.CV) 2026-06-16

A biological vision inspired framework for machine perception of abutting grating illusory contours

Higher levels of machine intelligence demand alignment with human perception and cognition. Deep neural networks (DNN) dominated machine intelligence have demonstrated exceptional performance across various real-world tasks. Nevertheless, recent evidence suggests that DNNs fail to perceive illusory contours like the abutting grating, a discrepancy that misaligns with human perception patterns. Departing from previous works, we propose a novel deep network called illusory contour perception network (ICPNet) inspired by the circuits of the visual cortex. In ICPNet, a multi-scale feature projection (MFP) module is designed to extract multi-scale representations. To boost the interaction between feedforward and feedback features, a feature interaction attention module (FIAM) is introduced. Moreover, drawing inspiration from the shape bias observed in human perception, an edge detection task conducted via the edge fusion module (EFM) injects shape constraints that guide the network to concentrate on the foreground. We assess our method on the existing AG-MNIST test set and the AG-Fashion-MNIST test sets constructed by this work. Comprehensive experimental results reveal that ICPNet is significantly more sensitive to abutting grating illusory contours than state-of-the-art models, with notable improvements in top-1 accuracy across various subsets. This work is expected to make a step towards human-level intelligence for DNN-based models.

11.
arXiv (CS.CL) 2026-06-18

LLMZero: Discovering Adaptive Training Strategies for RL Post-Training via LLM Agents

RL post-training strategies are dataset-dependent and reveal a recurring empirical pattern: capacity parameters accumulate monotonically across stages, while regularization parameters predominantly oscillate in response to shifting training dynamics. This distinction matters because fixed schedules commit all parameters to fixed trajectories and therefore cannot express the non-stationary exploration-exploitation tradeoffs that regularization must track; the principle provides actionable design rules for multi-stage training. We discover this through LLMZero, a system where LLM agents search over training trajectories via tree search, diagnosing pathologies at each checkpoint and proposing coordinated multi-parameter transitions. Across 4 diverse GRPO tasks, LLMZero discovers strategies that improve over the base model by 9% to 140% relative and over grid search by 6% to 15% relative, consistently outperforming random search and the skill-based agent. The structural principle transfers across tasks, providing an explanation for why discovered strategies take qualitatively different forms yet share similar parameter dynamics.

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

Trajectory Geometry of Transformer Representations Across Layers

arXiv:2606.09287v2 Announce Type: replace Abstract: Understanding how transformer representations evolve across layers, not merely what they encode, remains an open problem in mechanistic interpretability. We recast the transformer forward pass as a discrete population trajectory through a high-dimensional representation manifold, drawing on geometric tools from computational neuroscience. Rather than probing for pre-specified features, we characterize trajectory geometry using five metrics computed directly in the ambient space: trajectory length, curvature, a semantic convergence index, layerwise cosine similarity, and representational stability. Across three model families (GPT-2, TinyLlama, Qwen2.5) and five controlled prompt families, we report four findings. First, semantically related prompts converge significantly in middle-to-late layers (peak CI 0.41–0.58, p

13.
arXiv (CS.CV) 2026-06-19

Learning When to Denoise: Optimizing Asynchronous Schedules for Latent Diffusion

Multi-representation diffusion models can improve visual synthesis by denoising complementary views of an image, but their performance depends critically on the asynchronous schedule that determines when each representation is denoised. We propose to learn this schedule. Our method formulates asynchronous flow matching over multiple representation spaces and uses a schedule-corrected objective that keeps each representation's local noising-time weights fixed as the schedule changes. We instantiate the schedule with a flexible parametric class that is convex and monotone by construction, and learn it using a fast joint probe with less than 1% additional training compute. On ImageNet 256x256, the learned schedule substantially improves both convergence speed and final quality under a matched 675M-parameter XL backbone. With AutoGuidance, our 200-epoch model reaches FID 1.05, matching the 800-epoch SFD-XL baseline with 4x less training. Training to 600 epochs further improves to FID 1.02, outperforming the 1B-parameter SFD-XXL result of FID 1.04 while using a smaller model. In the unguided setting, our 200-epoch model reaches FID 2.37, already below the best 800-epoch SFD-XL result (2.54) at 4x less training, and improves to FID 2.14 at 600 epochs. Code is available at https://github.com/bsq532087/LWD

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

TerraMind: Large-Scale Generative Multimodality for Earth Observation

arXiv:2504.11171v5 Announce Type: replace-cross Abstract: We present TerraMind, the first any-to-any generative, multimodal foundation model for Earth observation (EO). Unlike other multimodal models, TerraMind is pretrained on dual-scale representations combining both token-level and pixel-level data across modalities. On a token level, TerraMind encodes high-level contextual information to learn cross-modal relationships, while on a pixel level, TerraMind leverages fine-grained representations to capture critical spatial nuances. We pretrained TerraMind on nine geospatial modalities of a global, large-scale dataset. In this paper, we demonstrate that (i) TerraMind's dual-scale early fusion approach unlocks a range of zero-shot and few-shot applications for Earth observation, (ii) TerraMind introduces "Thinking-in-Modalities" (TiM) – the capability of generating additional artificial data during finetuning and inference to improve the model output – and (iii) TerraMind achieves beyond state-of-the-art performance in community-standard benchmarks for EO like PANGAEA. The pretraining dataset, the model weights, and our code are open-sourced under a permissive license.

15.
arXiv (CS.LG) 2026-06-12

Multi-Token Residual Prediction

arXiv:2605.18817v2 Announce Type: replace Abstract: Diffusion Language Models (DLMs) generate text by iteratively denoising masked token sequences, offering a tradeoff between parallelism and quality compared to autoregressive models. In current practice, the number of tokens decoded per step is controlled by a confidence threshold, and quality degrades monotonically as more tokens are denoised per step. We introduce Multi-token Residual Prediction (MRP), a lightweight module that enables dependency-aware multi-token denoising within a single backbone forward pass. MRP exploits a key property of the denoising process: the logit distributions at adjacent denoising steps are remarkably similar. Rather than running the backbone a second time to obtain the next-step logits, MRP predicts the residual between steps from the backbone's hidden states, effectively denoising more tokens per backbone forward at a fraction of the cost. We apply MRP across the two operating regimes of DLM decoding. In the high-quality-low-throughput static denoising regime, MRP serves as a drafter for speculative decoding: its proposals are verified against the backbone, yielding lossless acceleration of up to 1.4x in SGLang. In the low-quality-high-throughput dynamic denoising regime, MRP instead drives a remasking scheme that revokes over-eager reveals, recovering most of the accuracy lost to aggressive low-threshold decoding and improving accuracy by up to 22.6 points on code generation task HumanEval and 17.7 points on reasoning task GSM8K.

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

RaLMPH: Reliability-aware Learning for Multi-Pathologist Harmonization in Whole-Slide Image Classification

Multiple Instance Learning (MIL) is a standard paradigm for Whole-Slide Image (WSI) analysis and has achieved strong results in computational pathology. However, most MIL pipelines assume a single "gold" label per slide, which conflicts with clinical practice where substantial inter-pathologist variability is common. Existing multi-annotator learning and label-refinement methods typically estimate global annotator reliability or rely on single-instance assumptions, making them poorly suited to MIL and to localized diagnostic contexts where experts disagree. We propose RaLMPH (Reliability-aware Learning for Multi-Pathologist Harmonization), a MIL-based label reconciliation framework for WSIs annotated by multiple pathologists. RaLMPH introduces a reliability field that jointly models (i) local neighborhood structure in WSI feature space and (ii) expert uncertainty (entropy), enabling per-sample identification of trustworthy reference neighborhoods. Leveraging this field, RaLMPH performs sample-wise local annotator ranking to select reliable opinions per slide and applies an adaptive gating mechanism to fuse labels conditioned on local reliability. Experiments on a clinical WSI dataset with labels from six pathologists, as well as controlled simulated benchmarks, show that RaLMPH consistently outperforms existing approaches. Further analyses clarify how our reliability-aware mechanism improves label reconciliation and downstream MIL performance.

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

Shift-Invariant Attribute Scoring for Kolmogorov-Arnold Networks via Shapley Value

arXiv:2510.01663v2 Announce Type: replace-cross Abstract: For many real-world applications, understanding feature-outcome relationships is as crucial as achieving high predictive accuracy. While traditional neural networks excel at prediction, their black-box nature obscures underlying functional relationships. Kolmogorov–Arnold Networks (KANs) address this by employing learnable spline-based activation functions on edges, enabling recovery of symbolic representations while maintaining competitive performance. However, KAN's architecture presents unique challenges for network pruning. Conventional magnitude-based methods become unreliable due to sensitivity to input coordinate shifts. We propose ShapKAN, a pruning framework using Shapley value attribution to assess node importance in a shift-invariant manner. Unlike magnitude-based approaches, ShapKAN quantifies each node's actual contribution, ensuring consistent importance rankings regardless of input parameterization. Extensive experiments on synthetic and real-world datasets demonstrate that ShapKAN preserves true node importance while enabling effective network compression. Our approach improves KAN's interpretability advantages, facilitating deployment in resource-constrained environments.

18.
arXiv (CS.LG) 2026-06-11

Neuro-Relational Programs: Unifying Queries and Neural Computation over Structured Data

arXiv:2606.11946v1 Announce Type: cross Abstract: The conventional approach to deep learning over relational databases applies neural models, such as Graph Neural Networks (GNNs), to a graph representation of the database. Recent approaches instead operate on databases directly, associating tuples with embeddings and extending query mechanisms to jointly process embeddings and relational content. Inspired by these developments, we introduce Neuro-Relational Programs (NRPs), a declarative query language for relational databases whose facts carry numeric vector embeddings. NRPs extend Datalog-style rules with operations that combine, aggregate, and transform embeddings, thereby interleaving relational reasoning and learnable neural components within a single formalism. This yields a general approach to neural computation over relational data: an NRP can be read both as a query plan with trainable components and as a neural architecture with relational structure built in. Natural syntactic fragments of NRPs recover existing architectures and query formalisms. Zero-ary NRPs correspond to non-adaptive query algorithms; monadic NRPs generalize GNN-style message passing and precisely capture Deep Homomorphism Networks, a connection that we extend to frontier-guarded NRPs over databases with row-ids. We characterize the expressive power of unrestricted NRPs with ReLU-FFN transformations by FOCQ, an extension of first-order logic with counting interpreted over real-weighted structures, yielding a precise connection with uniform TC$^0$ over ordered databases. Together, these results establish NRPs as a broad declarative framework for querying and neural computation over relational data.

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

FUSER: Feed-Forward MUltiview 3D Registration Transformer and SE(3)$^N$ Diffusion Refinement

Registration of multiview point clouds conventionally relies on extensive pairwise matching to build a pose graph for global synchronization, which is computationally expensive and inherently ill-posed without holistic geometric constraints. This paper proposes FUSER, the first feed-forward multiview registration transformer that jointly processes all scans in a unified, compact latent space to directly predict global poses without any pairwise estimation. To maintain tractability, FUSER encodes each scan into low-resolution superpoint features via a sparse 3D CNN that preserves absolute translation cues, and performs efficient intra- and inter-scan reasoning through a Geometric Alternating Attention module. Particularly, we transfer 2D attention priors from off-the-shelf foundation models to enhance 3D feature interaction and geometric consistency. Building upon FUSER, we further introduce FUSER-DF, an SE(3)$^N$ diffusion refinement framework to correct FUSER's estimates via denoising in the joint SE(3)$^N$ space. FUSER acts as a surrogate multiview registration model to construct the denoiser, and a prior-conditioned SE(3)$^N$ variational lower bound is derived for denoising supervision. Extensive experiments on 3DMatch, ScanNet and ArkitScenes demonstrate that our approach achieves the superior registration accuracy and outstanding computational efficiency.

20.
arXiv (CS.CL) 2026-06-16

Beyond Monolingual Deep Research: Evaluating Agents and Retrievers with Cross-Lingual BrowseComp-Plus

Deep research agents are increasingly evaluated on their ability to search for evidence, reason over retrieved sources, and produce grounded answers. Existing browsing benchmarks, however, largely assume that the user's query and the supporting evidence are written in the same language, leaving open whether agentic search systems can operate when relevant evidence appears in another language. We introduce XBCP (Cross-lingual BrowseComp-Plus), a controlled benchmark that preserves the English question-and-answer space of BrowseComp-Plus but varies the languages of the supporting documents. XBCP instantiates two complementary settings: in the cross-lingual setting, each query is paired with evidence in a single assigned language. In the multilingual setting, the full evidence corpus is distributed equally and randomly across 12 languages spanning high-resource and low-resource regimes. We evaluate four deep research agents using sparse and dense multilingual retrievers, measuring answer accuracy, evidence recall, search behavior, calibration, citation fidelity, and oracle retrieval. Results reveal substantial degradation when evidence is translated. Even strong, dense retrievers lose evidence recall, and agents become less calibrated and cite evidence less reliably. Notably, accuracy remains lower even when all gold evidence is supplied directly. These findings suggest that cross-lingual deep research exposes both retrieval failures and an independent, agent-side difficulty in integrating language-mismatched evidence.

21.
arXiv (CS.CV) 2026-06-17

AnnotateAnything: Automatic Annotation of 3D Assets for Robot Manipulation

Simulation enables scalable robot data collection, but raw 3D assets provide only geometry, lacking the semantic, interactive, and physical knowledge needed to specify where and how robots should act. In this work, we present AnnotateAnything, a general automatic annotation framework that converts passive 3D assets into manipulation-ready assets with structured, diverse, and executable manipulation labels. AnnotateAnything is built around two complementary pipelines. First, a unified visual-language annotation pipeline using vision-language reasoning to infer object semantics, interaction constraints, and 3D-grounded cues, providing human-prior guidance for identifying meaningful interaction regions. Second, a fully automatic and massively parallel physics annotation pipeline grounds these priors in each asset's geometry and physical constraints through candidate generation, geometry optimization and trajectory generation. This pipeline produces diverse and executable action annotations, including grasp poses, dexterous contacts, articulation waypoints, insertion directions, hanging affordances, and navigation targets. Using the generated annotations, we further build an asynchronous parallel simulation data-collection system across diverse objects, tasks, and robot embodiments. Experiments demonstrate that AnnotateAnything achieves superior annotation efficiency, data-collection efficiency, and task success rates over existing annotation and data-generation pipelines, while also supporting downstream tasks such as affordance detection, robotic VQA, and visual instruction finetuning. We provide project materials on the project page and plan to release the full code, annotations, and benchmark to facilitate future research. Videos, code, demo assets, and annotations are provided in supplementary materials Project page: https://tourmaline-caramel-169490.netlify.app.

22.
Nature Medicine 2026-06-10

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

Authors:

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

Efficient Online 3D Multi-Camera Multi-Object Tracking and Pose Estimation

This paper proposes a fast and online method for jointly performing 3D multi-object tracking and pose estimation using multiple monocular cameras. Our algorithm requires only 2D bounding box and pose detections, eliminating the need for costly 3D training data or computationally expensive deep learning models. Our solution is an efficient implementation of a Bayes-optimal multi-object tracking filter, enhancing computational efficiency while maintaining accuracy. We demonstrate that our algorithm is significantly faster than state-of-the-art methods without compromising accuracy, using only publicly available pre-trained 2D detection models. We also illustrate the robust performance of our algorithm in scenarios where multiple cameras are intermittently disconnected or reconnected during operation.

24.
arXiv (CS.AI) 2026-06-11

Planning under Distribution Shifts with Causal POMDPs

arXiv:2602.23545v2 Announce Type: replace Abstract: In the real world, planning is often challenged by distribution shifts. As such, a model of the environment obtained under one set of conditions may no longer remain valid as the distribution of states or the environment dynamics change, which in turn causes previously learned strategies to fail. In this work, we propose a theoretical framework for planning under partial observability using Partially Observable Markov Decision Processes (POMDPs) formulated using causal knowledge. By representing shifts in the environment as interventions on this causal POMDP, the framework enables evaluating plans under hypothesized changes and actively identifying which components of the environment have been altered. We show how to maintain and update a belief over both the latent state and the underlying domain, and we prove that the value function remains piecewise linear and convex (PWLC) in this augmented belief space. Preservation of PWLC under distribution shifts has the advantage of maintaining the tractability of planning via $\alpha$-vector-based POMDP methods.

25.
Nature (Science) 2026-06-10

Confirmation that bryozoan animals were present during the Cambrian explosion

Authors: Unknown Author

Bryozoans are marine invertebrates that live in colonies and have long been considered absent from the Cambrian explosion — a rapid evolutionary event that began around 538 million years ago. Newly discovered fossils from the Cambrian period reveal that the bryozoan phylum had already diversified by this time. Fossils of two forms of bryozoans show evidence of soft tissue still preserved inside their mineralized skeletons.