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

Not All Skills Help: Measuring and Repairing Agent Knowledge

LLM agents can improve without weight updates by accumulating natural-language skills from experience, but current systems entrust every decision about which skills to keep and how to apply them to LLM judgment alone. We argue that this conflates two distinct roles: generating a skill from experience is a creative act that judgment handles well, while deciding whether that skill actually helps requires empirical evidence across many tasks. Measuring per-skill causal contributions via randomized masking, we find that skill libraries exhibit pervasive causal heterogeneity: individual skills routinely help on some task types while hurting on others, yet their opposing effects cancel in aggregate, making them invisible to global curation methods. We propose ASSAY, a framework that separates generation from curation: it computes a per-skill causal attribution on a small development set, restructures the library offline, and suppresses skills with negative predicted effect for each test task. Across seven base models spanning four providers and two benchmarks (AppWorld and tau-bench), ASSAY consistently improves over prior skill-curation approaches. On AppWorld's hardest split, DeepSeek-V3 achieves 69.3% task-goal completion (47.4% relative improvement), a new state of the art among all published methods including weight-tuned approaches. On tau-bench retail, GPT-4.1 improves by 8.7% relative, advancing past o4-mini, o1, and GPT-4.5 on the public leaderboard without any weight modification. Ablation traces the dominant gain to per-task masking, confirming that the bottleneck is matching skills to tasks at inference time, not removing bad skills globally. Code is available at https://github.com/aiming-lab/assay.

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

AdaSTORM: Scaling LLM Reasoning on Dynamic Graphs via Adaptive Spatio-Temporal Multi-Agent Collaboration

arXiv:2606.16328v1 Announce Type: new Abstract: Large Language Models (LLMs) demonstrate remarkable potential in dynamic graph reasoning, but suffer from a scaling bottleneck: current models can only handle graphs with tens of nodes, constrained by exponential reasoning overhead and finite context windows. While multi-agent systems (MAS) offer collective reasoning and topology-aware orchestration, capabilities naturally suited for graph-structured tasks, their application to dynamic graphs remains unexplored. This paper presents Scaling LLM Reasoning on Dynamic Graphs via Adaptive Spatio-Temporal Multi-Agent Collaboration (AdaSTORM), a framework that reformulates large-scale dynamic graph reasoning into two stages: (i) Adaptive Partitioning, partitioning large-scale dynamic graphs into subregions that match the model's reasoning capacity while minimizing inference cost; and (ii) Collaborative Reasoning, aligning graph partition topologies with a spatio-temporal decoupled multi-agent architecture. AdaSTORM is the first multi-agent framework tailored for dynamic graph reasoning. Extensive experiments show that AdaSTORM successfully breaks through the scaling bottleneck, scaling reasoning to thousand-node graphs with over 90% accuracy across several large-scale dynamic graph settings without external tools, significantly outperforms seven competitive baselines. Furthermore, it achieves state-of-the-art accuracy on existing benchmarks and generalizes robustly to real-world datasets. The source code is available at: https://github.com/irisorchid107/AdaSTORM/.

03.
arXiv (CS.AI) 2026-06-12

Structured Testbench Generation for LLM-Driven HDL Design and Verification-Oriented Data Curation

arXiv:2606.12983v1 Announce Type: new Abstract: Automated testbench generation has become a critical bottleneck in large language model (LLM)-driven Register Transfer Level (RTL) workflows, where large numbers of candidate designs must be verified rapidly and reliably. Existing prompt-based approaches treat testbench generation as unconstrained code synthesis, yielding stochastic outputs with high token cost, low reproducibility, and insufficient coverage. To address this gap, we present STG, a Structured Testbench Generation framework that exploits the inherent structure of hardware designs to generate deterministic testbenches. As a direct verification tool, STG runs 720x faster than an iterative LLM-based testbench generation flow and higher rate of successful compilation, achieves higher coverage, and reduces false-pass verdicts on incorrect DUTs. STG also helps identify errors in RTL generation benchmarks by exposing faulty benchmark testbenches. As a data curation engine, it is 11x faster than LLM-based filtering on a single CPU core with 127x less energy, and the resulting distilled models provide state-of-the-art performance in our multi-benchmark evaluation. As a test-time scaling oracle, it reduces node count by 14-47\%. Our models are available at https://huggingface.co/collections/AS-SiliconMind/siliconmind-v12.

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

TurboGS: Accelerating 3D Gaussian Splatting via Error-Guided Sparse Pixel Sampling and Optimization

Consumer-level applications require fast optimization of 3D Gaussian Splatting (3DGS) with high-fidelity novel view rendering. However, existing 3DGS acceleration approaches still incur substantial computation on redundant pixels while sacrificing fine details. In this paper, we present TurboGS, an error-guided training framework that accelerates 3DGS by concentrating optimization on perceptually informative pixels. TurboGS is built upon four core components: (1) a tile-wise sparse pixel sampling, which, driven by multi-view reconstruction errors during training, prioritizes challenging regions and skips well-reconstructed ones to avoid redundant gradient computation; (2) a tile-wise structure-aware loss with sparse Normalized Cross-Correlation, which provides sparse yet effective supervision to preserve fine details and stabilize training; (3) an error-driven Gaussian density control strategy, which dynamically allocates model capacity and removes redundant primitives; and (4) a tailored hybrid optimizer that couples Hessian-informed updates with Adam moment damping to stabilize and improve convergence under sparse supervision. Experiments on standard benchmarks demonstrate that TurboGS can deliver on par or superior rendering quality within 100 seconds on a single RTX 5090 GPU card (up to 10x training speedup over vanilla 3DGS).

05.
bioRxiv (Bioinfo) 2026-06-10

A Unified Spatial AI Framework for Cross-Domain Tissue-State Analysis in Trauma, Oral, and Cardiovascular Pathology

作者:

Objective: To develop a cross-domain spatial AI framework for identifying conserved tissue-state organisation across trauma, oral disease, and cardiovascular tissue using spatial transcriptomic data. Methods: Four public spatial transcriptomic datasets spanning wound healing, periodontitis, oral squamous cell carcinoma, and cardiac tissue were integrated using recurrence modelling, graph-based spatial learning, fuzzy tissue-state analysis, and tensor decomposition. Cross-domain coupling, spatial fragmentation, recurrence structure, and permutation-based topological validation were evaluated. Results: Six conserved fuzzy tissue states were identified, dominated by extracellular matrix remodelling, fibroblast/stromal activation, endothelial signalling, and inflammatory pathways. Latent embedding analysis demonstrated strong overlap between trauma and oral domains, while cardiovascular tissue exhibited more compact spatial organisation. Oral inflammatory tissue showed the highest fragmentation, whereas cardiovascular tissue demonstrated greater recurrence coherence. Tensor decomposition identified conserved stromal-remodelling programmes across domains. Permutation testing confirmed significantly elevated graph modularity and reduced spatial entropy relative to null distributions. Conclusion: The proposed framework identified conserved spatial tissue-state architecture linking wound healing, oral pathology, and cardiovascular tissue despite differences in tissue origin, pathology, and acquisition technology. Significance: These findings demonstrate the potential of spatial AI for investigating conserved stromal and inflammatory microenvironmental organisation across clinically related disease systems and may support spatial biology research in trauma–oral–systemic health.

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

Enhancing Spectral Embedding through Robust and Flexible Knowledge Transfer in Electronic Health Records

arXiv:2606.11570v1 Announce Type: cross Abstract: We propose a spectral-based, unsupervised representation learning framework to derive low-dimensional embeddings for clinical concepts and patients in rare disease cohorts from electronic health records, where data are high-dimensional but sample sizes are limited. To overcome this challenge, we incorporate a knowledge matrix extracted from a broader population that shares a partially overlapping subspace with the rare-disease cohort. Our method departs from existing approaches by relaxing restrictive one-to-one signal-alignment assumptions between the latent data matrix and knowledge matrix, allowing more flexible and realistic forms of structured sharing. We introduce a novel two-step spectral embedding procedure: first, we identify and remove irrelevant components from the knowledge matrix; then, we apply a projection-based method to separately recover shared and heterogeneous components. Simulations and an analysis of a real-world multiple sclerosis cohort show that the proposed method outperforms competing approaches, particularly in challenging scenarios where shared signals are weak and only partially aligned, as is common in rare-disease data.

07.
arXiv (CS.CV) 2026-06-19

InfantFace: Detecting infant faces in neonatal clinical environments

Reliable localisation of the neonatal face is the first step for several video-camera based non-contact assessments such as pain and distress related facial expression analysis, pain scoring, cardiorespiratory signal extraction and cessation of breathing alerts. However, major challenges persist in neonatal clinical environments. Cluttered backgrounds, illumination changes and poor lighting conditions can reduce the accuracy of face detection models. Clinical interventions, monitoring equipment and, in some cases, medical devices can obstruct the face, making visual assessment difficult. We propose a one-stage YOLOv11m-based model tailored for face detection of infants in neonatal clinical environments. We combined multiple publicly available datasets (VGGFace2, CelebA, FDDB, WIDER FACE) to train and evaluate our proposed model. We then fine-tuned our model on a neonatal research dataset involving 228 videos from 114 recording sessions of 113 independent infants. Before fine-tuning, our model achieved an AP50 of 0.87, surpassing the performance of three state-of-the-art general face detectors. Performance improved further to an AP50 of 0.96 after clinical-domain adaptation. Evaluating face detection performance across different datasets remains a challenge due to the lack of publicly available neonatal datasets. Prioritising the creation of such datasets, while upholding appropriate privacy safeguards and ethical standards in their creation and use, would greatly support further progress in this field.

08.
arXiv (CS.CL) 2026-06-19

Towards Truly Multilingual ASR: Generalizing Code-Switching ASR to Unseen Language Pairs

Automatic Speech Recognition (ASR) has become a key technology for human–AI interaction. However, code-switching ASR (CS-ASR) remains particularly challenging due to the severe scarcity of multilingual CS speech resources across diverse language pairs. Existing approaches primarily improve CS-ASR performance through synthetic CS speech generation or pair-specific fine-tuning on limited bilingual datasets. Nevertheless, these approaches face an inherent scalability limitation, as support for CS must be developed separately for language pairs whose number grows combinatorially with the number of supported languages. In this work, we investigate whether CS capabilities learned from a limited set of seen language pairs can generalize to unseen language pairs through model merging and domain generalization methods. Our experiments show that merged bilingual CS-ASR models modestly generalize to unseen language pairs, suggesting limited transfer of bilingual CS capabilities across language pairs.

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

Interpretable Alzheimer's Diagnosis via Multimodal Fusion of Regional Brain Experts

Accurate and early diagnosis of Alzheimer's disease (AD) is critical for effective intervention and requires integrating complementary information from multimodal neuroimaging data. However, conventional fusion approaches often rely on simple concatenation of features, which cannot adaptively balance the contributions of biomarkers such as amyloid PET and MRI across brain regions. In this work, we propose MREF-AD, a Multimodal Regional Expert Fusion model for AD diagnosis. It is a Mixture-of-Experts (MoE) framework that models mesoscopic brain regions within each modality as independent experts and employs a gating network to learn subject-specific fusion weights. Utilizing tabular neuroimaging and demographic information from the Alzheimer's Disease Neuroimaging Initiative (ADNI), MREF-AD achieves competitive performance over strong classic and deep baselines while providing interpretable, modality- and region-level insight into how structural and molecular imaging jointly contribute to AD diagnosis. The source code is available at https://github.com/PennShenLab/mref-ad.

10.
arXiv (CS.CV) 2026-06-17

A Benchmark for Omni-Modal Reasoning in Long Videos

Long-form omni-modal video understanding requires integrating vision, speech, and ambient audio with coherent long-context reasoning. Existing video benchmarks often trade off temporal scale, modality coverage, open-ended interaction, and interpretable scoring. To address this gap, we introduce LongShOTBench, a long video understanding benchmark designed around three coupled goals: holistic omni-modal integration, intent-driven open-ended interaction, and rubric-level diagnosis. It builds single- and multi-turn questions from real viewing scenarios, with systematic tasks probing visual, speech, ambient-audio, temporal, and cross-modal reasoning. Each item includes a reference answer and a weighted criterion-level rubric, letting evaluation identify which perceptual facts, temporal links, modality-grounding requirements, and reasoning steps are satisfied or missed. All samples are manually verified to improve grounding, clarity, and rubric reliability. We also introduce LongShOTAgent, a training-free omni-modal evidence-seeking agent coupling full-video preprocessing with targeted retrieval, query-adaptive segment refinement, and explicit claim verification over visual, speech, and non-speech audio evidence. Its iterative search-refine-verify loop exposes intermediate evidence and lets modality-specific specialists re-analyze relevant moments before answering. We evaluate 105 video-capable models spanning open-source omni-modal models, vision-language systems, audio LLMs, agentic pipelines and closed-source APIs. Current MLLMs remain far from saturating LongShOTBench, while our LongShOTAgent is the strongest training-free system, reaching 66.64% overall. By releasing the benchmark, leaderboard, and method, we provide a shared, interpretable testbed for advancing long-form omni-modal video reasoning. Code, data, and the leaderboard are available at https://longshot.cvmbzuai.com/.

11.
medRxiv (Medicine) 2026-06-19

Rumination as a cognitive vulnerability factor in perinatal bereavement: evidence from the CARING study

Purpose. Perinatal loss is associated with a high risk of persistent psychological distress, including prolonged grief, depression, anxiety, and post-traumatic stress symptoms. Cognitive processes such as rumination may play a crucial role in maintaining and amplifying distress following loss, yet their specific contribution in perinatal bereavement remains underexplored. Methods. The CARING (Cognitive Analysis and Rumination INvestigation in perinatal Grief) study employed a cross-sectional design involving 298 parents who experienced perinatal loss within the previous five years. Participants completed an anonymous online survey including measures of depressive rumination (Ruminative Response Scale, RRS), angry rumination (Anger Rumination Scale, ARS), perinatal grief (Perinatal Grief Scale, PGS), general psychopathology (SCL-90), and post-traumatic stress symptoms (NSESSS). Non-parametric analyses were conducted to examine associations between rumination patterns and psychological outcomes. Results. Higher levels of rumination were significantly associated with greater perinatal grief, depressive and anxiety symptoms, and post-traumatic stress. Depressive rumination showed consistently stronger associations with all outcomes compared to angry rumination. Participants presenting both depressive and angry rumination exhibited the highest levels of grief intensity, psychological distress, and PTSD symptoms, suggesting a graded relationship between rumination patterns and severity of distress. Rumination levels were not significantly associated with gestational age at loss or with having received psychological support. Conclusions. Rumination, particularly in its depressive form, appears to function as a transdiagnostic cognitive vulnerability factor in perinatal bereavement. These findings highlight rumination as a potential target for early screening and tailored psychological interventions aimed at reducing long-term distress following perinatal loss.

12.
arXiv (quant-ph) 2026-06-16

Linear algebra at exponential scale via tensor network dimension reduction

arXiv:2606.15350v1 Announce Type: cross Abstract: Many problems in modern scientific computing are challenging because of a curse of dimension, where their mathematical formulation involves objects whose dimension is exponential in the nominal "size" of the problem. Tensor networks can provide a compact representation for exponentially large vectors and matrices that arise in applications, but these representations do not always lead to reliable algorithms. This paper develops and analyzes techniques for randomized dimension reduction of tensor network data. These techniques support a suite of efficient algorithms for provably solving exponential-scale linear algebra problems, including trace estimation and eigenvalue approximation. The paper includes several stylized illustrations from quantum many-body physics with ambient dimension up to $2^{200}$.

13.
arXiv (CS.AI) 2026-06-18

IPSL-AID: Generative Diffusion Models for Climate Downscaling from Global to Regional Scales

arXiv:2604.03275v2 Announce Type: replace-cross Abstract: Effective adaptation and mitigation strategies for climate change require high-resolution projections to inform strategic decision-making. Conventional global climate models, which typically operate at resolutions of 150 to 200 kilometers, lack the capacity to represent essential regional processes. IPSL-AID is a global to regional downscaling tool based on a denoising diffusion probabilistic model designed to address this limitation. Trained on ERA5 reanalysis data, it generates 0.25 degree resolution fields for temperature, wind, and precipitation using coarse inputs and their spatiotemporal context. It also models probability distributions of fine-scale features to produce plausible scenarios for uncertainty quantification. The model accurately reconstructs statistical distributions, including extreme events, power spectra, and spatial structures. This work highlights the potential of generative diffusion models for efficient climate downscaling with uncertainty

14.
arXiv (CS.AI) 2026-06-12

Modern analog computing for solving differential and matrix equations

arXiv:2606.13179v1 Announce Type: cross Abstract: In recent years, driven by the computational demands of data-intensive applications such as artificial intelligence and scientific computing, analog computing has gained renewed interest. Given the diversity of computational tasks and recent advancements in analog CMOS circuits and resistive memory technologies, we refer to the evolving landscape as modern analog computing. In this context, we identify three core computational primitives: solving differential equations, solving matrix equations, and performing matrix-vector multiplications, and we explore the connections among them. We also examine various hardware implementations of these analog computing operators, including those built with discrete components, integrated circuits, and resistive memory devices. Among these, resistive memory arrays emerge as particularly promising due to their implementation efficiency. The paper then surveys recent progress in leveraging modern analog computing to solve differential and matrix equations using both advanced analog CMOS circuits and resistive memory arrays. Finally, we discuss the applications of these circuits, the precision and scalability issues and their potential solutions, the relationship with in-memory computing, and the unique computational complexity of analog computing. This paper provides a unified perspective on analog computing, highlighting its strengths, current developments, and challenges, and positioning it as a pivotal enabler of next-generation computational frontiers.

15.
arXiv (CS.AI) 2026-06-11

Compiler-First State Space Duality and Portable $O(1)$ Autoregressive Caching for Inference

arXiv:2603.09555v2 Announce Type: replace-cross Abstract: High-throughput Mamba-2 inference is usually tied to fused CUDA and Triton kernels, limiting portability across accelerator backends. We show that the state space duality (SSD) recurrence has a compiler-friendly structure: diagonal per-head dynamics, fixed-size chunking, einsum-dominated compute, and static control flow. Expressing this structure in standard JAX primitives gives a single-source inference path with no custom kernels, a registered JAX PyTree cache, and a compiled on-device autoregressive loop. On a single Google Cloud TPU v6e, batch-1 prefill reaches approximately 140 TFLOPS, or 15% model FLOP utilisation (MFU), the roofline ceiling for this regime, and cached decode reaches up to 64% hardware bandwidth utilisation (HBU). At a 4096-token context, cached decode is 27x–36x faster than full-prefix recomputation across five Mamba-2 checkpoints from 130M to 2.7B parameters. The same source runs unmodified on NVIDIA L40S, where cached decode remains sequence-length independent across all model scales. WikiText-103 validation perplexity matches the Triton reference mamba_ssm v2.2.2 within +/-0.0005 points, and hidden states agree to float32 rounding tolerance. Code is available at https://github.com/CosmoNaught/mamba2-jax.

16.
arXiv (CS.CV) 2026-06-17

SegDINO: Introducing Multi-Scale Structure into DINO for Efficient Medical Image Segmentation

Self-supervised DINO models provide strong transferable visual representations, yet applying them directly to image segmentation remains challenging. Existing approaches commonly rely on heavy decoders with complex upsampling, introducing substantial parameter and computational overhead. We observe that introducing scale into DINO features is far more critical than increasing decoder capacity. In this work, we present SegDINO, an efficient segmentation framework that integrates a DINOv3 backbone with lightweight scale modeling. SegDINO introduces Token Pyramid Adaptation (TPA) to reorganize intermediate DINO features into a pseudo multi-scale hierarchy, and Scale-Aware Decoding (SAD) for efficient intra-scale refinement and top-down multi-scale propagation. We further curate PanCT, a new CT dataset containing 284 patients with expert-annotated pancreatic tumors, to assess SegDINO's ability to handle difficult small-lesion cases. Extensive experiments on PanCT and three public benchmarks demonstrate that SegDINO achieves state-of-the-art results with high efficiency. The code is available at https://github.com/script-Yang/segdino_v2.

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

Intelligence as Managed Autonomy: Failure, Escalation, and Governance for Agentic AI Systems

arXiv:2605.27628v2 Announce Type: replace Abstract: As autonomous and agentic AI systems scale in robotic and human-machine environments, managing hallucination and persistent but unjustified action remains an open challenge. Rather than attributing these failures solely to model or alignment limitations, this paper explores the architectural vulnerability of unbounded autonomy - the presumption that an agent should continue operating regardless of rising uncertainty. It introduces a theory of managed autonomy that defines intelligent behavior through the formal capacity to detect epistemic drift, suspend reasoning, attempt recovery, and ultimately surrender control when reliability diminishes. We instantiate this theory via the SMARt (Self-Managing Multi-tier Autonomous Reasoning with Regulated/Revoked transitions) model, a four-layer framework featuring Stable, Meta-cognitive, Assisted, and Regulated states. By developing a timed, guarded Petri net formulation, we establish theoretically bounded properties for the system, demonstrating how architecture can formally mandate escalation, constrain invalid outputs, and ensure governance reachability under specified conditions. We further analyze how incorporating domain-specific trigger sets across varied operational settings (e.g., healthcare, robotics, etc.) can systematically preserve safety, assuming completeness and soundness criteria are met. Because these triggers are designed to be adaptive, the SMARt model accommodates the safe, controlled expansion of an agent's operational scope over time. We conclude that formalizing failure management within the autonomy lifecycle is a crucial step toward realizing reliable and governed artificial intelligence.

18.
arXiv (quant-ph) 2026-06-12

Simple analytical flux-tuned iSWAP pulses for leakage suppression

arXiv:2606.13052v1 Announce Type: new Abstract: Fast, high-fidelity two-qubit gates are a key requirement for fault-tolerant quantum computation. Tunable coupler architectures provide a flexible approach for implementing entangling gates through flux control with large on-off ratios, but fast flux modulation can induce diabatic transitions and population leakage to non-computational states, limiting gate performance. Here we present an analytical flux control method enabling derivative removal by adiabatic gate ($\Phi$-DRAG) for suppressing leakage in flux tunable two-qubit gates. We show that $\Phi$-DRAG differs fundamentally from conventional microwave implementations and derive modified flux modulation protocols that suppress leakage below $10^{-4}$ for fast entangling gates. The method remains effective across a range of asymmetry between qubit anharmonicities and different circuit parameters, enabling high-fidelity two-qubit gates within the fifteen nanosecond range.

19.
arXiv (math.PR) 2026-06-11

Patterned matrices with random walk entries

arXiv:2512.04612v3 Announce Type: replace Abstract: It is well known that the weak limit of a suitably scaled continuous-time random walk (CTRW) is the Brownian motion. We investigate the convergence of certain patterned random matrices whose entries are independent CTRWs and their time-changed versions, in a non-commutative probability framework. For the Wigner link function, the limits are free Brownian motion and its time-changed version driven by an inverse stable subordinator. For the symmetric circulant and the circulant with CTRW entries, we use their explicit eigenvalue expressions to define some empirical processes that converge weakly to a Brownian motion and a complex Brownian motion, respectively. For matrices with iid entries, and for elliptic matrices, the algebraic limits are equal in $*$-distribution to processes whose marginals are circular and elliptic variables, respectively. A random time-changed variant of these results is also established.

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

Repeated Bilateral Trade: The Quest for Fairness

arXiv:2606.15369v1 Announce Type: new Abstract: We study repeated bilateral trade from a fairness perspective. At each round, a fresh seller-buyer pair arrives, and the platform posts a price before observing the traders' valuations. Trade occurs only if both agents accept the price. Rather than maximizing only the gain from trade, we consider platforms that seek balanced divisions of the generated surplus. We show that natural fairness desiderata lead to a one-parameter Rawls-to-Nash family of fair-gain objectives, obtained by aggregating the seller's and buyer's net gains through nonpositive Hölder means. Unlike the standard gain-from-trade objective and the Rawlsian fair-gain objective studied in prior work, our proposed objectives induce a new statistical structure in which expected rewards are recovered from threshold feedback through a two-dimensional singular-kernel integral identity. This leads to a nonstandard pure-exploration problem whose natural estimators are rectangular double sums with row-column dependence and singular weights. Assuming independent i.i.d. seller and buyer valuation sequences with arbitrary unknown marginals, we characterize the optimal learning rates for the whole Rawls-to-Nash family of fair-gain objectives, giving matching fixed-confidence sample-complexity and regret bounds up to polylogarithmic factors.

21.
arXiv (CS.CV) 2026-06-18

Conditional Latent Diffusion Model with Fourier-based Motion Modelling for Virtual Population Synthesis

In-silico trials of medical devices require the generation of virtual populations of anatomies. In cardiovascular applications, virtual anatomy is typically represented as a 3D+t mesh sampled from a generative model. However, most existing mesh generators focus on static anatomy, while sequence models often lack explicit periodicity. To this end, we propose 4D F-MeshLDM, a conditional generative framework comprising a convolutional mesh VAE to encode meshes, a structural latent space that parameterises motion using a truncated Fourier series, and a diffusion prior that learns the latent distribution over Fourier coefficient tokens. By conditioning the diffusion process on clinical covariates via affine modulation, we enable controllable synthesis. Sampling tokens and performing inverse Fourier synthesis yield cycle-consistent latent trajectories, which can be decoded into 3D+t cardiac mesh sequences. Experiments on 5,000 UK Biobank subjects demonstrate that 4D F-MeshLDM outperforms state-of-the-art baselines in anatomical fidelity and achieves near-zero cycle closure error. Furthermore, the generated cohorts accurately preserve clinical functional indices, highlighting the potential of our framework for reliable in-silico cardiac trials.

22.
medRxiv (Medicine) 2026-06-23

Innate immunity associates with protection from pneumococcal colonisation, but colonisation does not confer capsule-independent protection

Nasopharyngeal colonisation with Streptococcus pneumoniae is a prerequisite for transmission and disease and represents an important immunising event. While colonisation induces serotype-specific immunity, the mechanisms underlying heterologous protection remain unclear. We developed a controlled human infection model using pneumococcal serotype 15B and investigated colonisation dynamics, immunogenicity, and cross-protection against subsequent heterologous challenge with serotype 6B. Fifty-four healthy adults were intranasally inoculated with 15B at escalating doses. Colonisation rates peaked at 31.4% with 8 x 10 CFU per naris, lower than those historically observed with 6B and 3 strains. Density was also lower than previously observed with other strains. In vitro assays demonstrated that 15B adhered more readily to epithelial cells than 6B, but was less efficiently internalised, potentially reducing attack rates and colonisation density. Colonisation with 15B induced capsular polysaccharide-specific serum IgG, but baseline humoral immune measures did not predict protection from acquisition. Prior colonisation with 15B did not reduce acquisition of 6B upon re-challenge. Analysis of nasal microbiopsy samples revealed distinct innate activation signatures. Resistance to colonisation was associated with elevated baseline MIP-1 and MIP-1{beta} responses upon in vitro stimulation, whereas carriage was associated with enhanced chemokine and IL-6 responses. Local innate immune activation, rather than circulating antibody responses alone, may therefore contribute to colonisation control. We demonstrate that experimental colonisation with 15B does not confer heterologous protection against 6B and highlight the importance of mucosal innate immune conditioning in serotype-independent defence. Strategies enhancing nasal innate immune recruitment and activation may be required for broader protection against pneumococcal colonisation.

23.
arXiv (CS.AI) 2026-06-19

Cost-Optimal LLM Routing with Limited User Feedback under User Satisfaction Guarantees

arXiv:2606.19376v1 Announce Type: cross Abstract: Inference costs for large language model (LLM) applications are rapidly growing, driven by surging demand and rising infrastructure cost. Users expect high-quality responses, and in commercial settings this is formally codified in Service Level Agreements (SLAs), creating a fundamental tension between cost and quality. Recent progress on cost-aware LLM request routing has shown potential to resolve this tension, but existing approaches rely on complete feedback signals, offline training, extensive per-workload tuning, and most lack SLA guarantees or inference-time adaptivity. We introduce SLARouter, an online routing algorithm that learns a cost-optimal policy from the sparse, one-sided user feedback available in production systems. SLARouter provides theoretical guarantees for both cost optimality and strict SLA compliance. Experiments across a wide range of LLM benchmarks show that SLARouter satisfies SLA constraints without the need for per-benchmark tuning, reducing operating cost by up to 2.2x over existing baselines.

24.
arXiv (CS.LG) 2026-06-15

Implicit Variational Rejection Sampling

arXiv:2606.14235v1 Announce Type: new Abstract: Variational Inference (VI) is a fundamental inference technique in Bayesian machine learning for approximating complex posterior distributions. Traditional VI often relies on the mean-field factorization, which can inadequately capture true posterior complexity. Recent advancements have leveraged neural networks to model implicit distributions, offering increased flexibility. However, the practical constraints of neural network architectures still produces inaccuracies. In this paper, we propose a method called Implicit Variational Rejection Sampling (IVRS), which integrates implicit distributions with rejection sampling to improve the posterior approximation. Our method uses neural networks to construct implicit proposal distributions, and rejection sampling with a discriminator network that estimates the density ratio between the implicit proposal and the true posterior for refining the approximation. Towards this end, we introduce the Implicit Resampling Evidence Lower Bound (IR-ELBO) as a metric to characterize the resampled distribution's quality and derive a tighter variational lower bound. Experimental results demonstrate that our method outperforms traditional variational inference techniques.

25.
arXiv (math.PR) 2026-06-18

On a class of unbalanced step-reinforced random walks

arXiv:2504.14767v4 Announce Type: replace Abstract: A step-reinforced random walk is a discrete-time stochastic process with long-range dependence. At each step, with a fixed probability $\alpha$, the so-called positively step-reinforced random walk repeats one of its previous steps, chosen randomly and uniformly from its entire history. Alternatively, with probability $1-\alpha$, it makes an independent move. For the so-called negatively step-reinforced random walk, the process is similar, but any repeated step is taken with its direction reversed. These random walks have been introduced respectively by Simon (1955) and Bertoin (2024) and are sometimes refered to the self-confident step-reinforced random walk and the counterbalanced step-reinforced random walk respectively. In this work, we introduce a new class of unbalanced step-reinforced random walks for which we prove the strong law of large numbers and the central limit theorem. In particular, our work provides a unified treatment of the elephant random walk introduced by Schutz and Trimper (2004) and the positively and negatively step-reinforced random walks.