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Looking beyond stereotyped neuron structures reveals links between beading and morphological rearrangements in aging phenotypes.

Understanding how neuronal morphology changes during aging and acute stress is essential for elucidating mechanisms of neurodegeneration. The highly branched PVD neuron of Caenorhabditis elegans provides a powerful model for studying dendritic remodeling and degeneration-associated phenotypes such as dendritic beading. However, the complexity of this arbor presents substantial challenges for automated segmentation and quantitative analysis. In this study, we adapted a convolutional neural network (CNN)-guided region growing framework for automated dendrite tracing, coupled with two topology-based algorithms for categorizing dendritic segments by branching degree. The segmentation algorithm achieved high accuracy relative to manual tracing, with a median Dice coefficient of 0.82, while reducing analysis time by approximately tenfold. Automated dendrite categorization demonstrated strong agreement with manual annotations across branching orders, though position-based mapping performance declined with age due to progressive morphological distortion. Leveraging this platform, we investigated mechanistic differences in dendritic beading patterns observed during aging and cold shock. Consistent with prior work, aging was associated with decreased inter-bead spacing, whereas cold shock produced increased bead dispersion with stress severity. Structural analysis revealed that these trends were not driven by dendritic pruning or reduced arbor complexity. Instead, while a traditional anatomically unflexible paradigm falsely implicated lower-degree dendrites as highly vulnerable, our branching-informed framework revealed that age-dependent beading is fundamentally dictated by a segments history of successive branching events. Conversely, acute cold shock triggered systemic beading that expanded across all dendritic orders in a severity-dependent manner. Together, these findings demonstrate that chronic aging and acute stress engage distinct degenerative pathways (compartment-specific lineage vulnerability versus global architectural collapse) rather than gross morphological loss, as well as highlighting the need for paradigms that enable reliable analysis of changing morphologies.

Deployment-Centered Evaluation: Predicting Query-Level Rejection Risk in a Clinical LLM System

arXiv:2606.12702v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly integrated into clinical systems, making it essential to evaluate the real-world utility of these systems. However, static benchmarks tend to measure correctness rather than user acceptance, aggregate performance across queries, and require densely annotated datasets – leading to major blind spots for evaluating clinical systems. In this work, we perform a deployment-centered evaluation of an LLM system embedded within electronic health records at an academic medical center, where user feedback is sparse but closely reflects the deployment conditions. Specifically, we train a pre-response classifier that estimates the risk that a future interaction will result in the user rejecting the LLM response, based on query content and deployment-specific context available before generation. We conduct a prospective analysis of our model over 4.5 months of user feedback, finding that our prediction model achieves an AUROC of 0.719. Further, we estimate the benefit of such predictions in two downstream use cases (guardrail triggering and abstention). Our key conceptual insight is that making use of deployment-specific context (i.e., the provider type, department name, language model used for response), as opposed to only query content, improves the ability to predict whether the user will reject the system output. Altogether, our empirical case study demonstrates the feasibility of predicting user rejection using deployment-specific context, opening the door to targeted guardrails.

Nemotron 3 Ultra: Open, Efficient Mixture-of-Experts Hybrid Mamba-Transformer Model for Agentic Reasoning

We introduce Nemotron 3 Ultra, a 550 billion total and 55 billion active parameter Mixture-of-Experts Hybrid Mamba-Attention language model. We pre-trained Nemotron 3 Ultra on 20 trillion text tokens, then extended the context length to 1M tokens, and post-trained using Supervised Fine Tuning (SFT), Reinforcement Learning (RL), and Multi-teacher On-Policy Distillation (MOPD). Nemotron 3 Ultra is our most capable model yet, employing multiple key technologies - LatentMoE, Multi Token Prediction (MTP), NVFP4 pre-training, multi-environment RLVR, MOPD, and reasoning budget control. Nemotron 3 Ultra achieves up to ~6x higher inference throughput as compared to state-of-the-art publicly available LLMs while attaining on-par accuracy. The state-of-the-art accuracy, high inference throughput, and 1M token context length make Nemotron 3 Ultra ideal for long-running autonomous agentic tasks. We open-source the base, post-trained, and quantized checkpoints, along with the training data and recipe on HuggingFace.

Cosmos 3: Omnimodal World Models for Physical AI

We introduce Cosmos 3, a family of omnimodal world models designed to jointly process and generate language, image, video, audio, and action sequences within a unified mixture-of-transformers architecture. By supporting highly flexible input-output configurations, Cosmos 3 seamlessly unifies critical modalities for Physical AI – effectively subsuming vision-language models, video generators, world simulators, and world-action models into a single framework. Our evaluation demonstrates that Cosmos 3 establishes a new state-of-the-art across a diverse suite of understanding and generation tasks, demonstrating omnimodal world models as scalable, general-purpose backbones for embodied agents. Our post-trained Cosmos 3 models were ranked as the best open-source Text-to-Image and Image-to-Video models by Artificial Analysis, and the best policy model by RoboArena at the time the technical report was written. To accelerate open research and deployment in Physical AI, we make our code, model checkpoints, curated synthetic datasets, and evaluation benchmark available under the Linux Foundation's OpenMDW-1.1 License at https://github.com/nvidia/cosmos and https://huggingface.co/collections/nvidia/cosmos3. The project website is available at https://research.nvidia.com/labs/cosmos-lab/cosmos3.