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01.
arXiv (CS.LG) 2026-06-12

Metriplectic Conditional Flow Matching for Dissipative Dynamics

arXiv:2509.19526v2 Announce Type: replace Abstract: Metriplectic conditional flow matching (MCFM) learns dissipative dynamics without violating first principles. Neural surrogates often inject energy and destabilize long-horizon rollouts; MCFM instead builds the conservative-dissipative split into both the vector field and a structure preserving sampler. MCFM trains via conditional flow matching on short transitions, avoiding long rollout adjoints. In inference, a Strang-prox scheme alternates a symplectic update with a proximal metric step, ensuring discrete energy decay; an optional projection enforces strict decay when a trusted energy is available. We provide continuous and discrete time guarantees linking this parameterization and sampler to conservation, monotonic dissipation, and stable rollouts. On a controlled mechanical benchmark, MCFM yields phase portraits closer to ground truth and markedly fewer energy-increase and positive energy rate events than an equally expressive unconstrained neural flow, while matching terminal distributional fit.

02.
medRxiv (Medicine) 2026-06-18

Consistency of sleep timing and duration are associated with more physical activity and favorable heart rate metrics in a naturalistic cohort

Background: Regularity of sleep patterns over time has increasingly gained traction as an important axis of sleep health. Since sleep habits are under some degree of behavioral control, understanding such patterns in naturalistic settings is particularly important. We quantified sleep variability and tested the hypothesis that regularity correlates with physical activity, resting heart rate (rHR), and heart rate variability (HRV). Methods: We analyzed real-world digital health data from over 81,000 participants (over 18 million nights) who provided informed consent to participate in the Apple Heart and Movement Study and elected to contribute sleep, activity, and heart rate data to the study. Variability was quantified using the standard deviation (SD) computed from total sleep time (TST), sleep start time (S-start), end time (S-end), and midpoint time (MP), as well as the Sleep Regularity Index (SRI). Results: The SD-based variability metrics correlated with one another (R values 0.74-0.92), and with the SRI metric (R values 0.62-0.64). More consistent sleep, by any metric, was associated with more activity and better rHR and HRV. The most consistent tertile for TST variability had higher median TST (6.9 vs 5.9 hours), more daily exercise (32.8 vs 20.4 minutes), lower rHR (62.4 vs 65.6 beats per minute), and higher HRV (40.6 vs 37.3), all p

03.
arXiv (CS.CL) 2026-06-18

Freeing the Law with LOCUS: A Local Ordinance Corpus for the United States

Progress in legal AI increasingly depends on access to authoritative legal text at scale. Yet one of the most consequential layers of American law remains largely absent from existing machine-readable corpora: local ordinances. Local codes govern zoning, housing, business licensing, public health, noise, animal control, and many other domains of everyday regulation, but they are fragmented across vendor platforms designed for human browsing rather than bulk research access. We introduce LOCUS - the Local Ordinance Corpus for the United States - a comprehensive corpus and county-harmonized access layer for U.S. municipal and county ordinance codes. The raw corpus, available for release to researchers, represents nearly all publicly available municipal and county ordinance codes. The resulting raw corpus contains codes from 9,239 cities and counties. A smaller county-harmonized LOCUS access layer provides coverage for the largest 2,309 of 3,144 U.S. counties, accounting for a majority of the population. We use OCR to handle the myriad of document formats that have kept the law from being a public resource. We release the corpus with coverage metadata to support reproducibility, downstream legal AI research, and the incremental expansion of machine-readable access to local law. We train a collection of ModernBERT-based classifiers and scorers to facilitate analyzing U.S. local law among several dimensions, such as opacity and paternalism, that have not previously been studied at this scale. LOCUS-v1 and its derivative models are available at: https://huggingface.co/datasets/LocalLaws/LOCUS-v1

04.
Nature (Science) 2026-06-24

Daily briefing: Sperm whales have different dialects

Authors:

Whales in different areas of the Mediterranean use varying patterns of clicks and pauses. Plus, a technique to make protein samples one billion times bigger and the science of grief. Whales in different areas of the Mediterranean use varying patterns of clicks and pauses. Plus, a technique to make protein samples one billion times bigger and the science of grief.

05.
arXiv (CS.CV) 2026-06-12

SemanticXR: Low Power and Real-time Queryable Semantic Mapping with an Object-Level Device-Cloud Architecture

Semantic mapping is a core service that enables grounded interactions in emerging Extended Reality (XR) applications such as AI assistants and spatial object search. Deploying this capability on mobile XR devices requires a system that is open-vocabulary, real-time, and low-power. Existing approaches are compute-intensive and assume server-class resources. Cloud offloading offers a practical path, but no existing system splits semantic mapping across the device-cloud boundary or manages its communication, execution, and memory footprint. We present SemanticXR, the first device-cloud system for real-time, open-vocabulary semantic mapping and querying under XR power, bandwidth, and memory constraints. Our key insight is to elevate semantically identifiable objects to first-class units of communication, execution, and memory across the device and server. On the server, object-level parallelism and geometry downsampling improve mapping latency, while object-level depth-mapping co-design reduces upstream bandwidth. On the device, an object-level sparse local map with incremental updates and update prioritization enables network-robust querying with bounded memory and downstream bandwidth. Object-level configurable resource usage vs. quality trade-offs let applications and the system adapt mapping to application requirements and operating conditions, respectively. Against a device-cloud baseline with the same perception models, object-level organization improves server-side mapping latency by 2.2X at equal semantic quality. Depth-mapping co-design maintains upstream bandwidth under 2.5 Mbps. On the device, SemanticXR sustains sub-100 ms query latency for up to 10,000 objects even under network drops, supports tens of thousands of objects within 500 MB, and scales downstream bandwidth with map changes, not total scene size. The system adds only 2% device power during normal operation.

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

CacheWeaver: Cache-Aware Evidence Ordering for Efficient Grounded RAG Inference

Retrieval-Augmented Generation (RAG) improves factual grounding, but it also lengthens prompts and raises prefill cost. Prefix caching in serving engines such as vLLM reduces this cost only when requests share the same token prefix. In grounded generation, however, adjacent queries may retrieve overlapping evidence in different orders, so set overlap does not become reusable prefix overlap. We present CacheWeaver, a lightweight prompt-layer method for cache-aware evidence ordering. The method keeps a prefix tree over recently served evidence sequences and uses a greedy walk to place the most reusable prefix first, while leaving the serving engine and retrieved evidence set unchanged. Across three vLLM configurations, the method lowers median time-to-first-token (TTFT) by about 20-33 percent relative to retrieval-order prefix caching, without hurting answer quality in our QA tests. The greedy policy reaches 97.5 percent of the median TTFT gain from oracle ordering, indicating that most reusable prefix locality can be recovered by a simple scheduling layer between retrieval and inference.

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

The Almost Intelligent Revolution: Options for Scaling Up Deliberation and Empowering People with AI

Authors:

The increasing prominence of Large Language Models (LLMs) in public discourse presents both opportunities and challenges for democratic deliberation. While red teaming strategies help mitigate specific risks, broader concerns persist regarding linguistic constraints, biases, and the sycophantic tendencies of LLMs. This chapter explores how LLMs can be used to significantly scale up and democratise deliberation, particularly in fostering inclusivity and empowering traditionally marginalised groups. Drawing on concepts from Systemic-Functional Linguistics, the chapter examines how variations across language users (for example, with respect to socio-demographic groups) and across language use (for example, with respect to communicative functions) shape participation in AI-supported deliberation. The chapter presents AI-driven deliberation studies and assesses their potential to scaffold argumentation, enhance access, and reduce the influence of exclusionary linguistic norms and biases which are embedded in prestigious registers. At the same time, the chapter cautions against both overclaiming, which leads to unrealistic expectations, and underclaiming, which risks missed opportunities for AI-assisted engagement. The chapter concludes by identifying future research directions to maximise the democratic potential of AI-assisted participation while embedding ethical safeguards to counteract the reproduction of linguistic inequalities.

08.
arXiv (CS.LG) 2026-06-24

Hessian-augmented Supervised Learning for Hamilton-Jacobi-Bellman PDEs

arXiv:2606.23827v1 Announce Type: cross Abstract: A data-driven method is developed for approximating value functions in deterministic optimal control problems with nonlinear control-affine dynamics. The Pontryagin Maximum Principle optimality system is solved from multiple initial conditions to generate training data consisting of values, gradients, and Hessians of the value function, where Hessian information is obtained from a matrix Riccati equation along optimal trajectories. These quantities augment a weighted least-squares regression over sparse polynomial bases on hyperbolic cross index sets, with gradients and Hessians contributing additional linear equations per sample and substantially reducing sample complexity compared to value-only regression. Feedback laws are recovered analytically from the learned value function. In high dimensions, a partial Hessian strategy controls the cost of data generation. The approach is validated on problems of increasing state dimension, where second-order data augmentation is shown to improve approximation accuracy and closed-loop performance, with up to an order-of-magnitude reduction in the number of training samples required relative to lower-order methods.

09.
arXiv (CS.CL) 2026-06-16

Data-Driven Decoding of Russell's Circumplex Model of Affect

Affective computing increasingly relies on deep learning to represent emotions, yet latent spaces often remain opaque, high-dimensional black boxes. This paper investigates whether Transformers' embeddings recover the geometric regularities of Russell's circumplex model. We unify two complementary experiments testing the hypothesis that, after training models on text and speech, their resulting latent spaces encode a topology consistent with valence-arousal and reproduce human-like neighborhood relations. Specifically, we evaluate deep representations extracted from Transformer-based text (RoBERTa) and speech (wav2vec 2.0) encoders, along with a multimodal Transformer fusion architecture, across naturalistic datasets like MSP-Podcast and controlled LLM-generated stimuli. Our analysis reveals that multimodal fusion of text and audio yields perfect topological alignment with Russell's primary emotion ordering. Furthermore, in a zero-shot setting using generic text embeddings, projected fine-grained emotion terms fall close to their established human-mapped coordinates. Our contribution is a novel, data-driven framework for validating emotion models, demonstrating that Russell's circumplex structure is intrinsically encoded in the embeddings of these modalities rather than being solely an artifact of human labeling, thereby bridging the gap between psychological theory and representation learning.

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

Mutual Distillation of Dual-Foundation Models for Semi-Supervised PET/CT Segmentation

Organ segmentation from PET/CT is critical for quantitative analysis and radiotherapy planning in oncology. To ease the high annotation cost of PET/CT segmentation, semi-supervised learning (SSL) provides a practical and effective solution for developing deep models with limited labeled data. Recent developments in visual foundation models have demonstrated remarkable adaptability with improved efficiency. In this work, we propose a mutual distillation framework that seamlessly exploits both structural and functional foundation models, which act as modality-specific generalists for distilling knowledge from structural CT and metabolic PET imaging. By bridging the gap between the task-specific precision of student models and the segmentation priors of generalist foundation models, we propose MuDuo, a mutual distillation framework that synergistically leverages SAM-Med3D for CT and SegAnyPET for PET to distill their knowledge into a lightweight student network. Our approach eliminates the need for manual prompts while maximizing the utility of unlabeled data for automatic segmentation, achieving state-of-the-art performance on the AutoPET dataset with only 5 labeled cases. Our source code is available at https://github.com/Wu-beining/MuDuo.

11.
arXiv (CS.AI) 2026-06-16

AQ4SViT: An Automated Quantization Framework with Search Gating Policy for Compressing Spiking Vision Transformers

arXiv:2606.15523v1 Announce Type: cross Abstract: Spiking Vision Transformers (SViTs) have emerged as alternative low-power ViT models, but their large sizes hinder their deployments on resource-constrained embedded AI systems. To address this, state-of-the-art works proposed quantization techniques to compress SViT models, but their manual, human-guided approach needs a huge design time and power/energy consumption to find the appropriate quantization setting for each given network, making this approach not scalable for quantizing multiple networks. Toward this, we propose AQ4SViT, a novel automated quantization framework for SViTs that can provide quick quantization settings with good trade-offs between accuracy and memory. To achieve this, AQ4SViT employs the following key ideas: quantization search strategy that evaluates the quantization setting candidates while considering the accuracy constraint; and search gating policy that quickly evaluates and selects promising quantization candidates by leveraging membrane potential drift as a performance proxy. In the search gating policy, AQSViT employs two search algorithm variants to provide trade-off options: Greedy search, which performs fast but may lead to local optima; and Beam search, which performs slower but has better performance in finding global optima selection due to a wider search space. Experimental results show that AQ4SViT-Greedy quickly finds the appropriate quantization settings, achieving up to 6.6x faster search time and up to 82.5% memory saving compared to the state-of-the-art; while AQ4SViT-Beam further reduces the memory footprint by up to 90% compared to the state-of-the-art, but with 4.5x longer search time; all these results are obtained while maintaining high accuracy within 1.5% from the original/non-quantized models on the ImageNet dataset. These results highlight that AQ4SViT framework offers advancements toward SViT deployments on embedded AI systems.

13.
medRxiv (Medicine) 2026-06-20

EpiLink: a simulation-based compatibility model for genomic transmission clustering in infectious disease surveillance

Identifying recently linked infections from pathogen genome sequences is central to infectious disease surveillance, yet many clustering approaches rely on fixed genetic distance thresholds whose relationship to transmission is often unclear. This limitation is especially important in rapidly growing outbreaks and superspreading events, where many cases may be sampled close together in time and share little genetic variation, making true transmission links difficult to distinguish from other closely related infections. Supervised models can improve discrimination, but they require labelled transmission data that are rarely available during outbreak response. We developed EpiLink, a threshold-free method that estimates whether two cases are compatible with recent transmission. Here, compatibility means how well the observed genetic distance and sampling-time difference between two cases fit what would be expected if they were linked by defined recent transmission scenarios. EpiLink simulates plausible recent transmission histories while accounting for uncertainty in infection timing, testing delay, and mutation accumulation, then assigns higher scores to pairs whose observed differences are typical of those simulations. EpiLink was evaluated using both synthetic and empirical SARS-CoV-2 outbreak data from the 2020 Boston epidemic. Two EpiLink variants were compared to a logistic regression model trained on labelled transmission data. One EpiLink variant assumed deterministic mutation accumulation, with genetic differences proportional to elapsed evolutionary time; the other accounted for stochasticity by sampling mutation counts from a Poisson distribution. The logistic regression model performed better at distinguishing linked from unlinked pairs, but EpiLink achieved comparable clustering accuracy. In the Boston data, EpiLink recovered clusters enriched for documented conference and skilled nursing facility outbreaks. EpiLink thus provides an interpretable, simulation-based approach for identifying recent transmission clusters when fixed thresholds are difficult to justify and labelled transmission data are unavailable.

14.
arXiv (quant-ph) 2026-06-24

Thermodynamics of quantum processes: An operational framework for free energy and reversible athermality

arXiv:2510.12790v4 Announce Type: replace Abstract: We explore the thermodynamics of quantum processes (quantum channels) by axiomatically introducing the free energy for channels, defined via the quantum relative entropy with an absolutely thermal channel whose fixed output is in equilibrium with a thermal reservoir. This definition finds strong support through its operational interpretations in designated quantum information and thermodynamic tasks. We construct a resource theory of athermality for quantum processes, where free operations are Gibbs preserving superchannels and golden units are unitary channels with respect to absolutely thermal channel having fully degenerate output Hamiltonian. We exactly characterize the one-shot distillation and formation of quantum channels using hypothesis-testing and max-relative entropy with respect to the absolutely thermal channel. These rates converge asymptotically to the channel free energy (up to a multiplicative factor of half the inverse temperature), establishing its operational meaning and proving the asymptotic reversibility of the athermality. We show the direct relation between the resource theory of athermality and quantum information tasks such as private randomness and purity distillation, and thermodynamic tasks of erasure and work extraction. Our work connects the core thermodynamic concepts of free energy, energy, entropy, and maximal extractable work of quantum processes to their information processing capabilities.

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

Functional Equivalence in Attention: A Comprehensive Study with Applications to Linear Mode Connectivity

arXiv:2606.17830v1 Announce Type: cross Abstract: Neural network parameter spaces are inherently non-injective, as distinct parameter configurations can realize identical functions through functional equivalence. While this symmetry is well understood in classical fully connected and convolutional models, it becomes substantially more intricate in modern attention-based architectures. Existing analyses of multihead attention have largely focused on the vanilla formulation, overlooking positional encodings that fundamentally reshape architectural symmetries. In this work, we provide a formal study of functional equivalence in Transformers with positional encodings. Focusing on the two most widely used variants–sinusoidal and rotary positional encodings (RoPE)–we show that sinusoidal encodings preserve the equivalence structure of vanilla attention, whereas rotary encodings significantly reduce the symmetry group, thereby enhancing expressivity. This offers a principled explanation for the growing prominence of RoPE in practice. We further examine how positional encodings affect linear mode connectivity, and through an alignment algorithm, empirically demonstrate that the presence and variability of connectivity across Transformer settings crucially depend on the positional encoding.

16.
arXiv (CS.CV) 2026-06-25

MJEPA: A Simple and Scalable Joint-Embedding Predictive Architecture for Audio-Visual Learning

Self-supervised learning from large-scale video data has emerged as a dominant paradigm for visual representation learning. Since audio and visual streams naturally co-occur in video data, extending this success to jointly learn from both modalities is a natural next step, yet it remains challenging. Existing audio-visual self-supervised methods rely on modality-specific encoders and complex combinations of contrastive or reconstruction objectives, limiting cross-modal synergy and scalability. Joint Embedding Predictive Architectures (JEPAs) offer a simple, modality-agnostic alternative, but have to date been applied primarily to individual modalities. We introduce MJEPA, a joint-embedding predictive architecture for audio-visual learning that uses a single, unified encoder for both modalities. Our approach uses only a single predictive objective, applied both within and across modalities. We show that cross-modal prediction is critical: without it, a shared encoder degrades below unimodal baselines; with it, each modality's representation benefits from the other. Our frozen ViT-g model outperforms the best prior frozen baseline by over 6.8 mAP on AudioSet-20K, surpasses fully finetuned models on ESC-50 and FSD50K, and is competitive on video benchmarks despite using 10x less video data.

17.
arXiv (CS.AI) 2026-06-24

Breaking Shortcut Learning for Cross-Trial EEG-Guided Target Speech Extraction via Two-Stage Training

arXiv:2606.24164v1 Announce Type: cross Abstract: Recent end-to-end models for EEG-guided target speech extraction report impressive results, underscoring potential for neuro-steered hearing technologies. However, our analysis reveals that high within-trial performance can be driven by trial-specific EEG structure that acts as shortcuts for target selection, leading to poor generalization on unseen trials. To overcome this gap, we propose TRUST-TSE, a two-stage framework to mitigate shortcut learning. By introducing contrastive pretraining with attended-speaker negative sampling, we encourage the EEG encoder to capture fine-grained EEG–speech alignment while suppressing trial-identity cues. We also employ a confidence-weighted extraction objective based on EEG–source similarity to guide extraction using the learned representations. Experiments on KUL and DTU datasets show that TRUST-TSE outperforms end-to-end baselines under strict cross-trial protocols, addressing a key reliability bottleneck of existing approaches.

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

P3D-Bench: Benchmarking MLLMs for Parametric 3D Generation and Structural Reasoning

Multimodal large language models can write code to produce complex programs as well as use programs to do 3D modeling, which opens up a new avenue for 3D generation powered by their priors, world knowledge and reasoning. Yet existing benchmarks rarely evaluate 3D modeling through code. Such modeling demands more than runnable code: from a text or visual specification, a model must generate a parametric 3D program that is geometrically precise, semantically aligned and assembly-consistent. We introduce P3D-Bench, a benchmark for parametric 3D generation. Unlike a 3D mesh, a parametric 3D program exposes explicit dimensions, construction operations and part relations, revealing whether a model recovers a design's structure, not just its appearance. Under a unified protocol, P3D-Bench covers three task families (Text-to-3D, Image-to-3D and Assembly-3D) and scores each output for executability, geometric fidelity, topology, text-grounded constraints, multiview semantic alignment and part-level structure. We evaluate frontier MLLMs and text-only LLMs on 400 text cases, 400 image cases and 203 annotated assemblies, with domain-specific models as reference points. Our extensive evaluation yields three findings. First, assemblies are the hardest setting, where models still fail to compose multiple parts into a coherent structure. Second, models can often recover the global shape and semantic identity of the target object, yet fail to reproduce the precise parametric geometry specified by the input. Third, part-level modeling remains weak on assemblies, where models recover neither the geometry of each part nor the right number of parts. These results position P3D-Bench as a benchmark for evaluating precise parametric geometry and part-level structure in parametric 3D generation.

19.
arXiv (CS.LG) 2026-06-16

How to Score Experts for One-Shot MoE Expert Pruning: A Unified Formulation and Selection Principle

arXiv:2606.15716v1 Announce Type: new Abstract: Mixture-of-Experts (MoE) language models reduce per-token computation through sparse expert activation, yet deployment still requires storing the full expert pool, making one-shot expert pruning a practical approach for reducing memory usage. Although effective, existing criteria are largely heuristic, and no single criterion is universally optimal. Thus, establishing a principle for selecting pruning criteria suited to different deployment objectives remains an important yet largely underexplored problem in one-shot expert pruning. To this end, we introduce a unified formulation for one-shot MoE expert pruning organized around three factors: routing frequency, gate weighting, and activation strength. The formulation yields a criteria selection principle: task-agnostic pruning should favor routed-token-averaged, gate-free activation-based criteria, whereas task-specific pruning can benefit from retaining routing-frequency and gate-weight information. Beyond this principle, the formulation also provides a systematic view of existing heuristic criteria and gives rise to two new task-agnostic criteria, Mean Activation Norm (MAN) and Mean Squared Activation Norm (MSAN). Across four representative MoE models and 16 diverse benchmarks, MAN and MSAN are consistently strong in the task-agnostic setting, obtain the top-two average ranks, and improve average performance by up to 8.8 points over the strongest baseline.

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

An Exploratory Study of Blood Glucose Estimation from Photoplethysmography Signals using Machine Learning

arXiv:2606.15927v1 Announce Type: new Abstract: Diabetes and extreme blood sugar levels are some of the major health problems faced by humans today across the world. While Continuous Glucose Monitoring (CGM) has emerged as an effective technology for management of diabetes as well as for monitoring blood sugar levels, this technology has traditionally been invasive (that is, requiring the piercing of the skin) and carries the risk of irritation, induration, etc. This highlights the need for accurate and non-invasive CGM methods that can be deployed at scale. With the emergence of various sensing technologies and their integration in wearables like the smart-watch, we now have the capability to continuously monitor body signals like the Photoplethysmogram (PPG) in a non-invasive manner. Having the ability to continuously monitor blood glucose through CGMs and continuously monitor PPG signals through a smart-watch offers an opportunity to get dense data on these two, opening the possibility of building machine learning and deep learning based models to estimate blood glucose level from PPG signals. In this work, we first present a paired dataset comprising continuous PPG signals from a smartwatch along with glucose values recorded using a CGM device. We also present the results of some preliminary experimental explorations performed on our dataset. These preliminary results suggest that some predictive signals may exist, though more exploration is needed with more data from a larger number of individuals. The dataset can be accessed at https://zenodo.org/records/20577959

21.
medRxiv (Medicine) 2026-06-12

Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk

Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 significant cell-type-specific CpG sites in 106 loci and 68 risk genes in 40 loci, including 26 previously unreported loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-{beta} signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.

22.
arXiv (CS.LG) 2026-06-11

Impact of Connectivity on Laplacian Representations in Reinforcement Learning

arXiv:2603.08558v3 Announce Type: replace Abstract: Learning compact state representations in Markov Decision Processes (MDPs) has proven crucial for addressing the curse of dimensionality in large-scale reinforcement learning (RL) problems. Existing principled approaches leverage structural priors on the MDP by constructing state representations as linear combinations of the state-graph Laplacian eigenvectors. When the transition graph is unknown or the state space is prohibitively large, the graph spectral features can be estimated directly via sample trajectories. In this work, we prove an upper bound on the approximation error of linear value function approximation under the learned spectral features. We show how this error scales with the algebraic connectivity of the state-graph, grounding the approximation quality in the topological structure of the MDP. We further bound the error introduced by the eigenvector estimation itself, leading to an end-to-end error decomposition across the representation learning pipeline. Additionally, our expression of the Laplacian operator for the RL setting, although equivalent to existing ones, prevents some common misunderstandings, of which we show some examples from the literature. Our results hold for general (non-uniform) policies without any assumptions on the symmetry of the induced transition kernel. We validate our theoretical findings with numerical simulations on gridworld environments.

23.
arXiv (CS.CL) 2026-06-11

When More Documents Hurt RAG: Mitigating Vector Search Dilution with Domain-Scoped, Model-Agnostic Retrieval

Retrieval-augmented generation degrades when scaled to large, heterogeneous document collections, where dense similarity loses discriminative power, and top-k retrieval increasingly returns semantically similar but contextually incorrect chunks. We refer to this failure mode as vector search dilution. Even when using hybrid dense+sparse retrieval, we observed this firsthand in a deployed Wyoming Department of Transportation corpus, where scaling from 54 to 1,128 documents (88,907 chunks) reduced accuracy from 75% to below 40%. To address this dilution, we propose MASDR-RAG ( Multi-Agent Scoped Domain Retrieval for RAG) and evaluate it on 200 expert-validated queries across five LLM backbones, six corpora, and two index stacks. Our results indicate that domain scoping using organizational metadata is the key fix, significantly improving P@10 from 0.77 to 0.86 ($p < 0.05$). Furthermore, our investigation of multi-agent orchestration revealed that a high degree of configuration dependence results –creating what we call the precision-faithfulness paradox. Based on these varied outcomes, our practical recommendation is simple: scope first, then perform a single synthesis call, reserving full multi-agent orchestration for genuinely multi-domain corpora paired with native-tool-call backbones. Code and Data will be made public upon acceptance.

24.
bioRxiv (Bioinfo) 2026-06-10

SPARQ-MI leverages end-to-end spatial single-cell analysis of the tumor microenvironment

Detailed spatial analysis of the tumor micro-environment (TME) through multiplexed fluorescence imaging requires quantitative image-processing and data-analysis methods. While data-preprocessing down to segmentation of individual cells is captured by available methods, statistical analysis of single-cell features is compromised by the uneven noise distribution especially in complex tissues such as the TME, as well as by labor-intensive manual cell-type annotation and region segmentation. Here, we present SPARQ-MI (Spatial Phenotyping, Architecture Reconstruction and Quantification from Multiplexed Imaging) for streamlined spatial single-cell analysis, along with a tissue microarray PhenoCycler data-set with 37 fluorescent channels from melanoma patients under immunotherapy. We demonstrate that SPARQ-MI enables robust reconstruction of the cellular and spatial composition in this and other tissue types. Our analysis reveals associations of the cell-state and spatial location of CD8 T cells with response to immunotherapy. Overall, SPARQ-MI allows for quantitative analysis of complex fluorescence histology samples under minimal user input, and accounting for spatially uneven coverage of antibody signals, setting the stage for quantitative analysis of clinical samples.

25.
Nature (Science) 2026-06-24

The mutational landscape of STING-induced immunity

Authors:

Stimulator of interferon genes (STING) is an evolutionary conserved immune signalling protein with key roles in host defence, cancer, senescence and inflammation1–3. Downstream of STING, type I interferon, inflammatory cytokine signalling and non-canonical autophagy are governed by a multilayered mechanism integrating ligand-induced structural transitions, protein–protein interactions and coordinated intracellular trafficking4–13. Despite its central role in immunity and relevance as therapeutic target14, the sequence elements that govern STING (in)activation in cells remain incompletely&nbsp;understood. Here we developed a massively parallel assay to systematically chart the sequence-function landscape of STING. Profiling thousands of single amino-acid variants, we identified structural and functional determinants that shape the&nbsp;immunostimulatory capacity of STING and its ability to translate ligand recognition into distinct signalling outputs. Cryogenic-electron microscopy structures of select STING hyperactive variants revealed new regulatory principles dictating conformational transition from inactive to signalling-competent states of STING. Mutational effects are widespread across the functional landscape and can sensitize STING towards the natural ligand 2′3′-cGAMP15–18 or decouple interferon induction from non-canonical autophagy, demonstrating a diversity of possible responses that can be accessed through single point substitutions. Finally, our data showed the clinical and evolutionary relevance of naturally occurring STING protein variants. Collectively, these findings define molecular principles that tune STING activity and chart the landscape of its functional potential across immune contexts. A massively parallel assay systematically charts the sequence-function landscape of the STING signalling protein, and the findings define molecular principles that tune STING activity and show its functional potential across immune contexts.