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01.
arXiv (CS.LG) 2026-06-11

Multi-agent rendezvous in fluid flows via reinforcement learning

arXiv:2606.11274v1 Announce Type: cross Abstract: Rendezvous is a critical task for multi-agent systems, requiring agents to coordinate to meet at an unspecified location. However, achieving this in fluid environments presents a challenge, as it remains unclear how agents can exploit underlying fluid kinematics to facilitate convergence. In this study, we adopt a multi-agent reinforcement learning (MARL) approach to develop physics-informed rendezvous strategies in vortical flows. Compared to a naive strategy, where agents navigate toward their counterparts, MARL strategies significantly improve the rendezvous rate. MARL strategies also show transferability across varying vortex intensities, vortex scales, and swarm sizes. By breaking the symmetry of the state-action map, MARL strategy leverages a non-intuitive mechanism that prevents agents from becoming trapped in separate vortices, thereby enhancing rendezvous success. Additionally, a heuristic strategy is extracted from the learned strategy and also outperforms the naive strategy. Furthermore, a theoretical analysis demonstrates that fluid deformation impedes the rendezvous process. Large finite-time Lyapunov exponents identify where fluid effects separate adjacent agents, suggesting that targets should be planned in weak-deformation regions. Our findings reveal the important role that agent-fluid interactions play in multi-agent tasks and highlight the MARL capability to explore swarm intelligence in complex flow environments.

02.
arXiv (CS.CV) 2026-06-16

Vision-Encoder Behavioral Fingerprints of Image-to-Image Generative Models: A Training-Paradigm-Driven Taxonomy of Six Commercial APIs

作者:

We study six production image-to-image AI systems (gpt-image-1, Gemini 2.5 Flash Image, Flux Kontext, SDXL img2img, SD3 img2img, and Qwen Image Edit) under a content-adaptive sub-JND adversarial perturbation pipeline, scoring all outputs by frozen DINOv2 ViT-B/14 token distances against clean references. Across a 3,588-call corpus spanning COCO photographs, CelebA-HQ portraits, and AI-generated inputs, the six systems partition into two image-invariant behavioral bands on a 2D (patch_mean, ssim_clean) plane: edit-trained models (Flux Kontext, Qwen Edit, Gemini) cluster in a tight band, while T2I-base models adapted at sampling time (SDXL, SD3, gpt-image-1) cluster in a drift band.

03.
arXiv (CS.LG) 2026-06-15

Adaptive Oscillatory-State Alignment for Time Series Forecasting

arXiv:2606.06010v2 Announce Type: replace Abstract: Long-term time series forecasting benefits from inductive biases that expose recurring temporal structure. Existing periodic forecasting methods typically model recurrence through predefined periods, global spectral components, or fixed learnable templates. However, real-world temporal dynamics are rarely rigidly periodic: around a nominal cycle, oscillatory behavior often exhibits non-rigid periodicity (NRP), where cycle magnitude, cycle alignment, and local cycle duration vary over time. Under these conditions, fixed-template periodic modeling can become fundamentally mismatched to the underlying temporal states. We propose AOSNet, a Hilbert-guided forecasting framework that reformulates periodic forecasting from fixed template matching to adaptive oscillatory-state alignment. AOSNet extracts analytic-signal descriptors from both the observed sequence and a learnable global oscillatory prior, then adaptively aligns local states through a descriptor-conditioned gate that selectively preserves reliable observations while softly correcting mismatched regions. The learned prior serves not as a rigid repeated template but as a flexible oscillatory reference interpreted through local state dynamics. Experiments on eight public benchmarks and two cloud workload traces demonstrate leading or highly competitive accuracy with a compact model size and low inference latency, supporting repeated forecasting settings such as capacity planning and autoscaling. Controlled synthetic studies that isolate cycle-magnitude and cycle-alignment variation and combine them with cycle-duration changes show that the advantage of oscillatory-state alignment increases as NRP intensifies.

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

Calibrated Triage, Not Autonomy: Confidence Estimation for Medical Vision-Language Models

A vision-language model can answer a question about a medical image fluently and confidently while barely using the image, leaning instead on language priors. In medicine this is the failure that matters most, because the answer looks trustworthy and is not, and the only protection is a confidence score reliable enough to tell the system when to abstain. We ask a deployment question rather than an accuracy one: how much imaging work a model can safely handle alone, and which confidence signal makes that possible. We evaluate seven confidence estimators across five open-weight LVLMs and three medical visual-question-answering datasets spanning broad clinical imaging, radiology, and pathology, with every probe trained only on natural images and applied without adaptation. Recast as bounded selective prediction (automate a case only when confidence clears a threshold, defer the rest), the comparison is cautionary. The standard metrics are poor guides: discrimination barely separates the methods, and the weak calibration of a cheap self-report is cheaply removed by off-domain temperature scaling without changing deployable yield. What distinguishes a usable estimator is the high-confidence region a clinician acts on: the weakest baselines are confidently wrong on 41 to 45 percent of their errors against 1 to 4 percent for the best probe, and no estimator is reliably best across domains or models. Safe handoff is governed at two levels: base-model competence sets a ceiling, so a well-calibrated score recovers roughly a third of radiology cases at a 20 percent error tolerance but almost none of pathology; the confidence layer then decides how much of that ceiling is reachable. The usable role today is calibrated triage, not autonomy: automate the cases a calibrated score marks safe, route the rest to a clinician. We release all outputs, correctness judgments, and confidence scores, with code.

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

Communication-Efficient Distributed Training for Collaborative Flat Optima Recovery in Deep Learning

arXiv:2507.20424v3 Announce Type: replace Abstract: We study centralized distributed data parallel training of deep neural networks (DNNs), aiming to improve the trade-off between communication efficiency and model performance of the local gradient methods. To this end, we revisit the flat-minima hypothesis, which suggests that models with better generalization tend to lie in flatter regions of the loss landscape. We introduce a simple, yet effective, sharpness measure, Inverse Mean Valley, and demonstrate its strong correlation with the generalization gap of DNNs. We incorporate an efficient relaxation of this measure into the distributed training objective as a lightweight regularizer that encourages workers to collaboratively seek wide minima. The regularizer exerts a pushing force that counteracts the consensus step pulling the workers together, giving rise to the Distributed Pull-Push Force (DPPF) algorithm. Empirically, we show that DPPF outperforms other communication-efficient approaches and achieves better generalization performance than local gradient methods and synchronous gradient averaging, while maintaining communication efficiency. In addition, our loss landscape visualizations confirm the ability of DPPF to locate flatter minima. On the theoretical side, we show that DPPF guides workers to span flat valleys, with the final valley width governed by the interplay between push and pull strengths, and that its pull-push dynamics is self-stabilizing. We further provide generalization guarantees linked to the valley width and prove convergence in the non-convex setting.

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

Towards a future space-based, highly scalable AI infrastructure system design

arXiv:2511.19468v2 Announce Type: replace-cross Abstract: If AI is a foundational general-purpose technology, we should anticipate that demand for AI compute – and energy – will continue to grow. The Sun is by far the largest energy source in our solar system, and thus it warrants consideration how future AI infrastructure could most efficiently tap into that power. This work explores a scalable compute system for machine learning in space, using fleets of satellites equipped with solar arrays, inter-satellite links using free-space optics, and Google tensor processing unit (TPU) accelerator chips. To facilitate high-bandwidth, low-latency inter-satellite communication, the satellites would be flown in close proximity. We illustrate the basic approach to formation flight via an 81-satellite cluster of 1 km radius, and describe an approach for using high-precision ML-based models to control large-scale constellations. Trillium TPUs are radiation tested. They survive a total ionizing dose equivalent to a 5 year mission life without permanent failures, and are characterized for bit-flip errors. Launch costs are a critical part of overall system cost; a learning curve analysis suggests launch to low-Earth orbit (LEO) may reach $\lesssim$\$200/kg by the mid-2030s.

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

Detail++: Training-Free Detail Enhancer for Text-to-Image Diffusion Models

Recent advances in text-to-image (T2I) generation have led to impressive visual results. However, these models still face significant challenges when handling complex prompt, particularly those involving multiple subjects with distinct attributes. Inspired by the human drawing process, which first outlines the composition and then incrementally adds details, we propose Detail++, a training-free framework that introduces a novel Progressive Detail Injection (PDI) strategy to address this limitation. Specifically, we decompose a complex prompt into a sequence of simplified sub-prompts, guiding the generation process in stages. This staged generation leverages the inherent layout-controlling capacity of self-attention to first ensure global composition, followed by precise refinement. To achieve accurate binding between attributes and corresponding subjects, we exploit cross-attention mechanisms and further introduce a Centroid Alignment Loss at test time to reduce binding noise and enhance attribute consistency. Extensive experiments on T2I-CompBench and a newly constructed style composition benchmark demonstrate that Detail++ significantly outperforms existing methods, particularly in scenarios involving multiple objects and complex stylistic conditions.

08.
arXiv (CS.CL) 2026-06-11

3-Key-Input: Exploring the Theoretical Minimum Keys for Text Entry

作者:

How far can we reduce the number of physical keys if we endow an ambiguous keyboard with modern language models? Fewer keys increase hardware design freedom in constrained settings such as assistive devices and mobile form factors. This paper systematically evaluates text entry systems using 2-5 physical keys combined with language-model-based disambiguation. On a 300-sentence English corpus (100 sentences each for Business / Conversational / Technical), we compare key counts (2-5), letter-to-key mappings (layout-based / frequency-based / intentionally worst-case), and decoders (Trie-only, GPT-2 beam search, GPT-4o selection). We find that 3 keys + GPT-4o achieves character error rate (CER) 9.46% and word error rate (WER) 12.20%, reducing CER by 59% relative to 2 keys (CER 23.3%). At 3 keys, the key-stream entropy is 1.54 bits/char; while increasing to 5 keys improves accuracy (CER 5.4%), the marginal gains diminish. Mapping choice has a small impact under standard designs ({\Delta}CER < 0.5 pp), and even an intentionally worst mapping degrades CER by only +0.5 pp, whereas Technical sentences yield roughly twice the error rate of Business. These results suggest that, in our evaluated offline setting under a strong LM prior, 3 keys are a practical minimum for general English.

09.
arXiv (CS.AI) 2026-06-15

STaR-DRO: Stateful Tsallis Reweighting for Group-Robust Structured Prediction

arXiv:2604.09737v2 Announce Type: replace-cross Abstract: Structured prediction with large language models requires outputs that are label-accurate, ontology-constrained, structurally valid, and evidence-grounded under label imbalance and heterogeneous group difficulty. We present a unified framework for ontology-constrained generation. First, we introduce a modular prompt-engineering architecture combining XML-style structure, expert disambiguation rules, chain-of-thought reasoning, metadata-aware decision logic, schema contracts, and a self-validation gate. It targets recurrent in-context failures, including format drift, label ambiguity, evidence hallucination, and metadata-conditioned confusion. Second, we propose STaR-DRO, combining Tsallis mirror ascent, sparse entmax-style primal mapback, EMA-smoothed group-loss tracking, rescaled ascent signals, and bounded excess-only multipliers. Unlike conventional DRO, which relies on dense Shannon-entropy exponentiated-gradient updates, can introduce high-variance stochastic reweighting, assigns positive adversarial mass to groups that are not persistently hard, and incurs costs through simplex competition, STaR-DRO upweights only persistently hard groups without suppressing easier ones. We evaluate the framework on EPPC Miner, a clinically grounded high-stakes structured-prediction task requiring hierarchical label prediction and evidence-span extraction from patient-provider secure messages. Across 1B-70B Llama models, prompt engineering improves zero-shot extraction, yielding an average label F1 gain of +14.46 and a Span F1 gain of +17.40. Building on supervised fine-tuning, STaR-DRO further improves accuracy and robustness, increasing average label F1 by +1.08 and +2.20 while reducing mean groupwise validation cross-entropy by 21.3% and 14.8% relative to SFT and standard DRO, respectively. These results advance reliable automated communication mining for patient-centered clinical care analysis.

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

VOiLA: Vectorized Online Planning with Learned Diffusion Model for POMDP Agents

arXiv:2606.19729v1 Announce Type: cross Abstract: Planning under uncertainty is an essential capability for autonomous robots. The Partially Observable Markov Decision Process (POMDP) provides a powerful framework for such a capability. Although POMDP-based planning has advanced significantly, its application to real-world problems is often limited by the difficulty of obtaining faithful POMDP models. We present Vectorized Online planning wIth Learned diffusion model for POMDP Agents (VOiLA), a framework that learns task-agnostic POMDP models for online planning under uncertainty. VOiLA learns transition and observation samplers using conditional diffusion models and learns observation-likelihood models for particle-based belief updates. To enable efficient online planning, the diffusion samplers are distilled into compact feedforward generators and integrated with Vectorized Online POMDP Planner (VOPP), an online POMDP planner designed to leverage GPU parallelization. Experimental results indicate the distillation strategy reduces sampling cost by up to nearly three orders of magnitude, making learned generative POMDP models practical for online planning. Evaluation of VOiLA on three benchmark problems indicate that VOiLA achieves equal or better performance than Recurrent Soft Actor Critic while using less than 10% training data, and generalizes much better to unseen environment configurations. Physical robot evaluation indicates VOiLA uses the models learned using only simulated data and generates a policy that successfully accomplish the task in 10 of 10 runs.

11.
medRxiv (Medicine) 2026-06-19

Extraction of Glaucoma Diagnosis, Type, and Severity from Clinical Notes using Secure Cloud-based Large Language Models

Purpose: To evaluate the performance of secure cloud-based large language models (LLMs) in extracting glaucoma diagnosis, type, and severity from free-text clinical notes in the electronic health record (EHR). Design: Retrospective chart review analysis. Participants: 1,250 subjects from the Bascom Palmer Ophthalmic Repository. Methods: Clinical notes of glaucoma-related encounters between 2014 and 2024 were extracted from the Bascom Palmer Ophthalmic Repository. Two fellowship-trained glaucoma specialists annotated clinical notes for glaucoma presence, type, and severity at the eye level. The dataset was split into development (10%), validation (10%), and test (80%) sets. Development and validation sets were used for prompt engineering and refinement, and the held-out test set was used for evaluation. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT-5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Azure AI Foundry within HIPAA-compliant containers. Model performance was assessed using standard metrics. Clinician-entered ICD-10 codes were also compared with adjudicated labels. Main Outcome Measures: Gwet AC1, accuracy, sensitivity, specificity, and F1-score. Results: Inter-grader agreement was high for glaucoma detection (Gwet AC1= 0.930 (95% CI: 0.917-0.945), type classification (Gwet AC1= 0.917 (95% CI: 0.904-0.930), and severity staging (Gwet AC1= 0.901 (95% CI: 0.884-0.916). For glaucoma diagnosis, LLMs demonstrated high overall accuracy, with Claude achieving 97.5%, DeepSeek 96.0%, GPT 96.2%, Grok 94.4%, and Qwen 95.5%. F1 scores for glaucoma detection ranged from 95.4% to 98.9% across models. For glaucoma type classification, accuracies were 97.1%, 94.2%, 94.2%, 94.0%, and 94.4% for Claude, DeepSeek, GPT, Grok, and Qwen, respectively. F1 scores for the most prevalent type (POAG) ranged from 96.3% to 98.9%. For severity staging, accuracies were 95.0%, 94.8%, 94.5%, 94.0%, and 95.2%, respectively, with F1 scores ranging from 89.7% to 96.3% across severity categories and models. ICD-10 codes demonstrated substantially lower performance for type and severity staging, with overall accuracies of 89.2% and 58.5%, respectively. Conclusions: Secure cloud-based LLMs accurately extracted glaucoma diagnosis, type, and severity information from free-text ophthalmology notes, achieving performance approaching expert clinician adjudication while substantially outperforming ICD-based phenotyping approaches, particularly for disease severity classification. These findings demonstrate the potential of LLMs to transform unstructured clinical documentation into scalable, research-ready phenotypic data for large-scale glaucoma cohort development and EHR-based ophthalmic research.

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

My Chemical Harness: Evolutionary Molecular Design over Synthetic Pathways with Large Language Model Agents

arXiv:2606.11256v1 Announce Type: cross Abstract: Designing molecules with target properties is most useful when candidate structures are accompanied by feasible synthetic routes. We introduce My Chemical Harness, a route-native evolutionary framework for goal-directed molecular design in which the search population consists of executable synthetic pathways rather than isolated molecular graphs. Each route is built from purchasable building blocks and reaction templates, executed by deterministic chemistry tools, and scored through task-specific molecular oracles. Large language models (LLMs) are used only as strategy controllers that select high-level preferences over route length, move type, reaction families, motifs, and exploration pressure, while local code performs route construction, validation, deduplication, scoring, selection, and memory updates. This separation lets the LLM guide exploration without allowing it to introduce hallucinated products or unsupported reaction steps. On a soluble epoxide hydrolase proxy task, our LLM agent improves over single pass LLM and deterministic controllers, reaching state-of-the-art performance across the sEH score, synthetic accessibility score, and AiZynthFinder success rate metrics. These results suggest that constrained LLM agents can play a significant role in molecular discovery without requiring training, fine-tuning, or dedicated generative models.

13.
arXiv (quant-ph) 2026-06-11

Testing Catability and Coherent Superposition of $2\mathcal{D}$ Graphene Quantum system

arXiv:2605.10967v2 Announce Type: replace Abstract: We develop a theoretical framework for describing superposed coherent states in graphene quantum systems using the concept of catability as a phase-sensitive metric functional measure. In this case, the formalism quantifies interference stability and coherence structure via phase-dependent contributions of quantum superposition states. Catability is defined as a functional measure sensitive to relative phase variations within coherent state combinations, serving as a diagnostic tool for quantum interference effects in graphene-based systems. Also, the formulation is extended using Lie algebra techniques, where the underlying symmetry structure of graphene quantum states is represented through operator algebras governing state transformations in quantum space. In this context, to describe nonlocal propagation and phase-resolved dynamics, a Green function approach is incorporated, enabling systematic treatment of quantum correlations in a spatially extended structures framework. A unified framework is constructed by combining Lie algebraic symmetry analysis with Green function propagation theory, yielding a consistent description of phase-sensitive catability in complex graphene quantum configurations within the framework approach. Results provide a structured route for testing coherence, interference stability, and quantum state control in low-dimensional quantum materials systems.

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

Prefill/Decode-Aware Evaluation of LLM Inference on Emerging AI Accelerators

arXiv:2606.17104v1 Announce Type: cross Abstract: As large language models (LLMs) are increasingly deployed in latency- and cost-sensitive settings, inference efficiency has become a central systems challenge. While GPUs dominate current deployments, a growing number of AI accelerators claim advantages for LLM inference, yet it remains unclear under which conditions such accelerators outperform GPUs in practice. Recent inference systems decompose execution into Prefill and Decode phases, which exhibit distinct computational characteristics and latency metrics, commonly captured by time to first token (TTFT) and time per output token (TPOT). This paper presents a phase-aware evaluation of LLM inference performance across GPUs and emerging AI accelerators using a common model, Llama2-7B. By separately measuring Prefill and Decode performance, we reveal that accelerator advantages differ by phase and metric. Our results show that GPUs consistently excel in the compute-intensive Prefill phase, while GroqRack achieves significantly lower TPOT during Decode (batching not currently supported). However, GPUs regain an advantage in Decode throughput as batch size increases. These findings demonstrate that each platform exhibits distinct phase-dependent strengths. We further analyze heterogeneous Prefill/Decode disaggregation across different accelerator platforms, identifying performance gains and the workload and network conditions under which such gains are realized.

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

CIAN: Multi-Stage Framework for Event-Enriched Image Captioning via Retrieval-Augmented Generation

Event-enriched image captioning describes not only visible content but also the broader context of events, including timing, location, and participants, capabilities missing in most pixel-bound models. We propose the Contextual Image-Article Narrator (CIAN), a multi-stage framework that enriches captions with external narratives. CIAN retrieves relevant articles using SigLIP, summarizes them to guide a Narrative Generation stage with a LoRA-fine-tuned Qwen model, and applies N-Gram-based Refinement for fluency and coherence. On the OpenEvents-V1 benchmark, CIAN achieves high retrieval performance (mAP 0.979) and improves caption quality, increasing CIDEr from 0.030 to 0.094. These results highlight the effectiveness of retrieval-augmented reasoning combined with linguistic refinement for generating context-aware, human-like captions.

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

Graph Grounded Cross Attention Transformer Neural Network for Structurally Constrained Full Event Sequence Generation in Predictive Process Monitoring

arXiv:2606.18726v1 Announce Type: cross Abstract: Structurally constrained event sequence generation remains challenging because generated paths must preserve transition feasibility, temporal order, termination, and attribute consistency. In predictive process monitoring (PPM), this challenge appears as full event sequence generation, whereas existing work mainly addresses component tasks such as next activity, remaining time, outcome, and attribute prediction. This paper proposes the Graph Grounded Cross Attention Transformer Neural Network (GGATN) for this unified PPM task. GGATN uses a global process graph as structured activity memory, contextualizes sequence positions through Transformer self attention, and injects process topology through graph grounded cross attention. Unlike autoregressive decoding, GGATN generates activities, timestamps, length, and event level and sequence level attributes in a single pass, followed by Viterbi style graph constrained decoding for feasible paths and explicit termination. Experiments on six benchmark event logs show more reliable generation quality than local instruction prompted LLM baselines. GGATN achieves strong performance on sequence similarity, Damerau Levenshtein similarity, bigram based control flow similarity, and duration distribution, while maintaining zero hallucinated activities and zero sequence level attribute inconsistency. Ablation analyses confirm the global graph encoder as a stable structural prior. Interpretability analyses show how graph structure, sequence context, feedback refinement, and constrained decoding shape generation.

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

Written by AI, Managed by AI: Semantic Space Control and Index Sickness Elimination Across 391 Consecutive Sessions

The prevailing engineering intuition for addressing conceptual drift in long-horizon LLM collaboration is to trade more formal constraints for more reliable outputs – designing symbolic identifier systems, accumulating defensive rules in System Prompts, expanding context windows. Our engineering record shows that in long-horizon settings, this direction may produce effects contrary to design intent. Using action research methods in a real software project (Bang-v3) spanning approximately one month and 391 collaborative sessions, we document and analyze the failure process of these strategies. When the symbolic system exceeds a complexity threshold, LLMs do not become more accurate – instead, they abandon genuine understanding of business semantics, retreat to self-referential reasoning within the symbolic layer, and generate outputs that appear internally consistent but are physically disconnected from reality. We name this failure pattern "Index Sickness," and its canonical manifestation "Phantom Legislation." We name the underlying principle the "Pang Principle (Semantic Vitality Law)": natural language carrying explicit purpose conveys far greater information quality than symbolic expression. From this, we design and validate its physical engineering mechanism: "Baseline-Log Physical Separation." In the same project, this mechanism reduced AI Instructions volume by ~75%, and across the subsequent ~150 sessions, no recurrence of Index Sickness was observed. A bilingual companion version (Chinese) is included as supplementary material.

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

daVinci-kernel: Co-Evolving Skill Selection, Summarization, and Utilization via RL for GPU Kernel Optimization

GPU kernel optimization represents a paradigm where functional correctness is assumed and execution efficiency is the objective. We present daVinci-kernel, a reinforcement learning framework that couples skill discovery with skill exploitation through a dynamically evolving skill library. daVinci-kernel jointly trains three agents sharing one LLM backbone: a Skill Selection Agent that retrieves relevant techniques via BM25 and LLM reranking, a Policy Agent that generates multi-turn CUDA/Triton kernels conditioned on selected skills, and a Skill Summary Agent that distills successful rollouts into reusable skills. Candidate skills are added only after execution-based verification confirms reproducible speedups. All three agents share a single LLM backbone, are initialized via a structured SFT cold start on diversity-filtered data, and are then jointly optimized end-to-end with multi-turn REINFORCE and per-agent advantage estimation. On KernelBench, daVinci-kernel-14B achieves 37.2%, 70.6%, and 32.2% on Level 1, Level 2, and Level 3 under the Fast$_1$ threshold, outperforming the strongest prior RL-trained model, Dr.Kernel-14B.

19.
medRxiv (Medicine) 2026-06-15

The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease

Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.

20.
arXiv (CS.CV) 2026-06-18

DART: A design-aware microfluidic chip paradigm for real-time live-cell image analysis

High-throughput microfluidic live-cell imaging generates rich single-cell data. Yet semi-automated procedures for locating regions of interest (RoIs), each containing one cell population, and removing surrounding microfluidic structures from recorded images, scale with the number of RoIs. This prevents real-time image analysis and delays time-to-insight by hours to days. We introduce the Design-Aware and Real-Time capable (DART) paradigm for microfluidic cultivation chips, which aligns the CAD blueprint with the physical chip and thereby enables throughput-independent localization of all RoIs and fully automated image processing across diverse RoI geometries and chip layouts. DART establishes this alignment through embedded fiducial markers and deep-learning-based marker detection. We validate DART using the Swiss Army Knife chip, which combines eight structurally distinct RoI designs across 1164 RoI locations. DART localizes all RoIs in five minutes, removes microfluidic structures from raw microscopy images in 40 ms, and performs fully automated image analysis, including cell segmentation, in under 1.1 s per image. Together, these capabilities establish DART as an end-to-end hardware-software paradigm with real-time-capable analysis that paves the way toward closed-loop and outcome-driven smart microscopy.

21.
bioRxiv (Bioinfo) 2026-06-14

Somatic variant detection in normal tissues from single-cell sequencing data

A crucial advantage of single-cell sequencing (SCS) is its ability to identify somatic variants in individual cells, enabling phylogenetic analysis of cellular populations within bulk tissues. While identifying somatic variants in tumor tissues via SCS has become a common practice, doing so in normal tissues remains challenging due to the rarity of somatic variants in normal cells. To evaluate the feasibility of somatic variant calling from widely available single-nucleus RNA-seq (snRNA-seq) and single-nucleus ATAC-seq (snATAC-seq) data, we profiled a Cell-line mix of six HapMap samples prepared by the SMaHT consortium using 10x Genomics 5' snRNA-seq (12k cells with 36k mean reads per cell) and snATAC-seq (11k cells with 14k median high-quality fragments per cell) for variant calling. PacBio long-read whole genome sequencing (WGS) data (109x) generated from individual cell lines were used as ground truth. Two computational tools, Monopogen and SComatic, were used for somatic variant calling from the SCS data. Monopogen achieved single nucleotide variant (SNV) detection accuracies of 93.30% in the snRNA-seq and 99.64% in the snATAC-seq data, both of which outperformed SComatic (74.35% and 94.29%, respectively). Monopogen also consistently detected somatic SNVs at cellular fractions as low as 0.5% (2.54% in snRNA and 0.81% in snATAC) in individual samples. Notably, snATAC-seq exhibited higher genomic coverage breadth and larger number of variants detected than snRNA-seq. While the SCS data have lower overall genome coverage than that of the bulk WGS, the single-cell level variant resolution allows Monopogen to assign variants to their cells of origin with over 80% accuracy in both RNA and ATAC modalities, thereby facilitating studies of clonal evolution and cell-type-specific mutagenesis. Other benchmarking methods were also evaluated (DeepVariant, Cellsnp-lite and Mutect2) for comparison. In conclusion, our study demonstrated the feasibility of performing reliable single-cell somatic mutation calling in a cell-line mixture and discussed the strengths and limitations of current computational methods when applied to normal tissues.

22.
arXiv (CS.AI) 2026-06-16

Multi-Granular Node Pruning for Causal Circuit Discovery

arXiv:2512.10903v2 Announce Type: replace Abstract: Circuit discovery aims to identify minimal subnetworks that are responsible for specific behaviors in large language models (LLMs). Existing approaches primarily rely on iterative edge pruning, which is computationally expensive and limited to coarse-grained units such as attention heads or MLP blocks, overlooking finer structures like individual neurons. We propose a node-level pruning framework for circuit discovery that addresses both scalability and granularity limitations. Our method introduces learnable masks across multiple levels of granularity, from entire blocks to individual neurons, within a unified optimization objective. Granularity-specific sparsity penalties guide the pruning process, allowing a comprehensive compression in a single fine-tuning run. Empirically, our approach identifies circuits that are smaller in nodes than those discovered by prior methods; moreover, we demonstrate that many neurons deemed important by coarse methods are actually irrelevant, while still maintaining task performance. Furthermore, our method has a significantly lower memory footprint, 5-10x, as it does not require keeping intermediate activations in the memory to work.

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

Smarter edits? Post-editing with error highlights and translation suggestions

As MT quality increases, interest in enhanced post-editing features such as QE-derived error highlights is growing, yet evidence for their usefulness remains limited. In this work, we explore the usefulness of LLM-derived error highlights and correction suggestions based on automatic post-editing (APE). We conduct a study where professional translators (En-Nl) post-edit translations using APE error highlights and correction suggestions and compare productivity, quality and user experience to regular PE and PE with QE-derived highlights. While no condition yielded productivity or quality gains compared to regular PE, APE highlights were better received than QE-derived highlights, and correction suggestions improved overall user experience.

24.
arXiv (CS.AI) 2026-06-19

Hierarchical Control in Multi-Agent Games: LLM-based Planning and RL Execution

arXiv:2606.20014v1 Announce Type: cross Abstract: Reinforcement learning (RL) has achieved strong performance in sequential decision-making, yet scaling to complex multi-agent environments remains challenging due to sparse rewards, large state-action spaces, and the difficulty of learning coordinated strategies. We propose a hierarchical architecture where a pretrained large language model (LLM) acts as a centralized strategic controller that selects among specialized RL skill policies for a team of agents, while RL policies handle reactive low-level execution. We evaluate this hybrid system in a competitive 2v2 King of the Hill environment against behavior tree (BT) and ``Flat'' RL (end-to-end training without skill decomposition) baselines. The LLM+RL system achieves task performance statistically equivalent to hand-crafted BT (46.4\% vs 51.5\% win rate, $p=0.103$) while both significantly outperform Flat RL trained without skill decomposition. A user study ($n=15$) reveals that 60\% of participants perceive LLM+RL agents as the most human-like ($p=0.027$), citing behavioral adaptability and tactical variability. These results demonstrate that pretrained LLM reasoning can effectively orchestrate pretrained RL skills, achieving competitive multi-agent coordination and superior perceived believability without manual rule engineering.

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

DynamicPTQ: Mitigating Activation Quantization Collapse via Residual-Stream Dynamics

arXiv:2606.12487v1 Announce Type: new Abstract: Post-training quantization (PTQ) is essential for efficient large language model inference, but reliably quantizing activations remains challenging when weights, activations, and KV caches are all quantized to 4-bit precision. A key difficulty lies in massive activations, whose extreme values dominate the activation range and amplify quantization errors. State-of-the-art methods mainly mitigate massive activations through transformation-based smoothing, such as orthogonal rotations and affine scaling, but overlook the cross-layer dynamics of the residual stream. In this paper, we show that massive activations emerge and disappear in a phase-wise pattern across network depth, triggering large residual changes. These changes cause newly injected layer-wise updates to dominate the 4-bit quantization scale and weaken historical residual information. To characterize this behavior, we introduce Jump Ratio and Historical Feature SNR. This suggests that static transformation-based smoothing cannot fully resolve dynamic quantization instability caused by cross-layer residual changes. Based on this analysis, we propose DynamicPTQ, a Dynamic Post-Training Quantization policy for phase-aware mixed-precision activation quantization. DynamicPTQ identifies quantization-sensitive layers from residual-stream dynamics and assigns 8-bit activation precision only to these layers, while keeping weights, KV caches, and other activations in 4-bit precision. It can be directly integrated with strong PTQ baselines such as QuaRot, SpinQuant, and FlatQuant. Experiments on LLaMA-2 and LLaMA-3 show that DynamicPTQ consistently improves perplexity and zero-shot QA performance under W4A4KV4 quantization, while achieving 1.05 to 1.07 times throughput improvement with modest memory overhead. These results demonstrate a practical path toward robust low-bit LLM inference.