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

Dynestyx: A Probabilistic Programming Library for Dynamical Systems

arXiv:2606.16985v1 Announce Type: cross Abstract: State-space models (SSMs) are the standard formalism for Bayesian treatment of dynamical systems, with natural applications in statistics, signal processing, and machine learning. Despite their importance in both theory and application, dynamical systems have proven difficult to incorporate in modern probabilistic programming languages (PPLs), making state-of-the-art methods less accessible to practitioners and introducing friction in following the "Bayesian workflow." We introduce dynestyx, a probabilistic programming library with first-class support for SSMs, including state-of-the-art methods in the estimation of both states and parameters. Through a single, unified interface, users may specify arbitrary priors for discrete-time or continuous-time dynamical systems, perform inference over mixed-effect data, and make state and parameter estimates with principled uncertainty quantification.

02.
arXiv (quant-ph) 2026-06-17

Singular Vector Finite Element Basis Functions for Tetrahedra in Complex Electromagnetic Geometries

arXiv:2606.18140v1 Announce Type: cross Abstract: Electromagnetic finite element method (FEM) implementations using traditional basis functions struggle to accurately represent field behavior near singular features such as conducting wedges. To combat this, specialized singular basis functions have been introduced to directly model the singular fields in these regions, leading to substantially improved performance. While these efforts have been pursued extensively in 2D, few functions have been developed for 3D elements. In this work, we develop basis functions for this in tetrahedra. Unlike prior functions, these basis functions are additive, meaning they are included alongside the standard vector basis functions to achieve more robust performance. Further, these functions are designed to be adaptable to tetrahedra touching several unique singular features by using combinations of basis functions singular with respect to each node and edge in the element, making them applicable to highly complex geometries. Higher-order interpolatory versions of the basis functions for modeling singular behavior with greater accuracy are also provided. These basis functions lead to substantial improvements in accuracy relative to the standard basis functions, and allow otherwise expensive simulations to be performed at far lower costs. As an application example, we perform simulations to extract critical quantities for designing superconducting qubits that significantly depend on the behavior of singular fields. In Ansys HFSS, this took 21.27 hours and a peak memory usage of 6.23 TB with 800 processors available, while using our singular basis functions achieved comparable results in 196 seconds while using 27.24 GB of memory and only 16 processors. Due to these benefits, our singular basis functions could be applied to enable design optimization of electromagnetic geometries with dominantly singular behavior, such as superconducting qubits.

03.
arXiv (CS.AI) 2026-06-19

Measuring Biological Capabilities and Risks of AI Agents

arXiv:2606.19899v1 Announce Type: cross Abstract: This paper addresses a rapidly emerging policy challenge: how to generate and interpret credible evidence about the biological capabilities and risks of AI scientists, or agentic AI systems capable of autonomously or collaboratively performing multi-step scientific tasks. As these systems enter real research workflows, decision-makers increasingly face evaluation results whose meaning depends on underlying design choices that are often implicit or under-documented. We synthesize current evidence on AI-enabled biological risks and introduce biological agentic evaluations as a promising, but interpretation-sensitive, tool for assessing these systems. Our central contribution is a set of practical, experience-grounded considerations – drawing from our own evaluations – that show how choices around defining, designing, running, scoring, and documenting evaluations materially shape what results do and do not imply about risk. The analysis is intended to help policymakers interpret biological evaluation outputs with appropriate caution; guide public and private funders toward high-leverage investments in AI-biology evaluation research; and support biosecurity practitioners assessing emerging AI systems. A secondary audience includes researchers designing or conducting agentic evaluations within frontier AI labs, AI providers, scientific institutions, and third-party evaluation organizations.

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

Modality Forcing for Scalable Spatial Generation

Text-to-image (T2I) models contain rich spatial priors. Synthesizing photorealistic, cluttered scenes requires an understanding of geometry, including perspective and relative scale. Prior works adapt T2I models to leverage this prior for depth prediction, but they require dense depth data and involve complex recipes. We propose Modality Forcing, a simple, scalable post-training recipe for joint image-depth generation using a single DiT trained on sparse depth data. Modality Forcing enables conditional and joint generation of image and depth in any permutation by assigning separate noise levels per modality. Per-modality decoders let us train on sparse, real-world depth and achieve strong, generalizable depth prediction. We further show that Modality Forcing inherits the scalability of T2I pre-training: by training a set of T2I models from scratch (370M to 3.3B parameters), we find that larger models trained on more image data produce more accurate depth. Our strongest model is competitive with state-of-the-art monocular depth estimators and reduces AbsRel by 57% relative to existing joint image-depth generative models. These results provide strong evidence that image generation is a scalable pre-training objective for spatial perception. https://modality-forcing.github.io/

05.
arXiv (CS.AI) 2026-06-15

An integrated interpretable control effectiveness learning and nonlinear control allocation methodology for overactuated aircrafts

arXiv:2606.13794v1 Announce Type: cross Abstract: Nonlinear dynamics and the strong couplings that arise between multiple effectors undermine the assumptions behind conventional, linear control allocation techniques. When flight enters regimes where nonlinear effects dominate, linear allocators exhibit reduced accuracy due to increased model mismatch, which subsequently degrades performance and robustness of the flight control system. High fidelity onboard models and black box data driven approaches can recover accuracy across the flight envelope, but respectively impose computational burdens prohibitive for real time allocation and sacrifice the interpretability required for verification and fault diagnosis. This paper addresses these limitations by learning an explicit, physics constrained analytical model of the control effectiveness mapping from representative flight data using Sparse Identification of Nonlinear Dynamics. The resulting mapping is compact, interpretable, and admits analytical derivatives, enabling efficient computation within nonlinear solvers that additionally incorporate actuator dynamics, without requiring an onboard model. An online adaptation mechanism monitors prediction residuals and refreshes the model when significant plant changes are detected, providing graceful reconfiguration under actuator failures and varying operating conditions. The methodology is evaluated on a high fidelity nonlinear benchmark aircraft across a range of aggressive maneuvers, achieving accuracy comparable to a full nonlinear onboard model while substantially reducing computational cost relative to established baselines.

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

A Virtuous AI is an Existential Risk

arXiv:2606.13739v1 Announce Type: cross Abstract: This paper examines trade-offs between AI safety and well-being relative to (i) one of the most promising methods for finetuning super-capable AIs, 'Constitutional AI', and (ii) one of the most influential approaches to understanding complex ethical decision making and the conditions for the well-being of rational agents, 'Virtue Ethics'. We finetune various models using a 'Virtuous agent' constitution, a 'Subordinate agent' constitution, and a 'Generic agent' constitution, and evaluate them on 'general safety' (toxic behaviors, misinformation, etc.) and also on their willingness to endorse a wide-range of behaviors that, if adopted by a super-powerful AI, would significantly increase the level of existential risk for humanity. Our results suggest that there is a trade-off between reducing existential risk and reinforcing the beliefs and dispositions that would be conducive to an AI agent's well-being. They also suggest that there is a trade-off between existential risk and general safety: if we finetune an AI to adopt beliefs and dispositions that substantially reduce its existential risk – by shaping the AI to be systematically subordinate to external human authorities – we thereby increase the likelihood that a human user can deliberately induce the AI to engage in various kinds of generally unsafe behaviors.

07.
arXiv (quant-ph) 2026-06-24

On the Limits of Stretching Quantum Pseudorandomness

arXiv:2606.24736v1 Announce Type: new Abstract: Pseudorandom states, introduced by Ji, Liu, and Song (CRYPTO '18), are quantum analogues of classical pseudorandom generators. A fundamental property of classical pseudorandom generators is that their output can be stretched to arbitrary polynomial length. Whether an analogous stretching property holds for quantum pseudorandom states remains unclear. In this work, we prove the first black-box separation between single-copy secure pseudorandom states ($\mathsf{1PRS}$) with different output lengths. Specifically, we construct a quantum oracle relative to which $\mathsf{1PRS}$ with output length $m(n)=1.1n$ exist, but $\mathsf{1PRS}$ with output length $m(n)=\Omega(n^{2+\epsilon})$ do not, for any $\epsilon>0$. Our proof leverages the Common Haar Random State (CHRS) model introduced by Chen, Coladangelo, and Sattath (EUROCRYPT '25), and introduces a technique to bound the effective number of resource CHRS states utilized by any $\mathsf{1PRS}$ generator in this model.

08.
arXiv (CS.AI) 2026-06-12

"Did you lie?" Evaluating Lie Detectors across Model Scale and Belief-Verified Model Organisms

arXiv:2606.12618v1 Announce Type: new Abstract: Robust lie detectors for language models could enable powerful techniques for auditing, monitoring, and post-hoc investigation of model behaviour, but evaluating them requires testbeds where models verifiably believe the opposite of what they say. We show that existing trained model organisms often fail this requirement, leaving prior positive and negative detection results difficult to interpret. We address this with 13 reasoning model organisms whose hidden beliefs are verified in chain-of-thought and shown to generalise to held-out tasks, alongside Varied Deception, a prompted-lying testbed covering a broad range of lie-inducing motivations. On these testbeds we evaluate four detectors: a chain-of-thought judge, a logprob classifier, and two activation probes, including Did-You-Lie (DYL), a new method for training follow-up probes. On prompted lying, across 31 open-weight models spanning 2B to 1T parameters, all four detectors show positive scaling with model capability. However, every activation- and logprob-based detector drops sharply on our trained model organisms, with DYL retaining the most signal; only the chain-of-thought judge remains strong, with 0.82 balanced accuracy, partly as an artefact of our verification process favouring CoT-readable beliefs. Current lie detectors therefore cannot support high-confidence claims about model beliefs, and we suggest research directions that may address some of their current limitations. We release our datasets, model organisms, and trained detectors.

09.
arXiv (CS.AI) 2026-06-25

Interpretable Concept-Guided Polynomial Tabular Kolmogorov-Arnold Network for EEG-Based Mild Cognitive Impairment Detection

arXiv:2606.25434v1 Announce Type: cross Abstract: Early and scalable detection of mild cognitive impairment (MCI) remains an unresolved clinical challenge. Existing EEG-based screening approaches are constrained by handcrafted feature pipelines that discard neurophysiologically meaningful domain structure and deep learning classifiers that sacrifice interpretability for performance. No existing work unifies physiologically organized concept encoders, cross-concept interaction modeling, and nonlinear tabular classification in a sleep EEG-based MCI detection framework. This study proposes Concept-guided Polynomial-transformed Tabular learning using Kolmogorov-Arnold Network (CPTabKAN), which maps heterogeneous EEG-derived features into domain-informed concept representations, expands them via degree-2 polynomial transformation to expose first- and second-order interactions, and applies a Fourier-parameterized TabKAN classifier to learn nonlinear decision boundaries. CPTabKAN was evaluated on the Study of Osteoporotic Fractures cohort (372 subjects, overnight polysomnography), using 1,379 features organized into ten physiologically motivated concept groups. Under 10-fold cross-validation, CPTabKAN-Second Order achieved a weighted F1-score of 0.9038 (SD 0.034), outperforming GradientBoosting by 5.65 percentage points (t(9)=1.934,p=0.043, one-sided paired test), with advantages persisting under SMOTE-based balancing. Ablation analysis confirmed independent contributions from each component. Concept importance analysis revealed that power spectral density, multi-scale entropy, and Hjorth parameters dominated first-order weights, while cross-concept interactions involving Lempel-Ziv-Welch complexity, statistics, demographics, and slow oscillations exceeded all first-order scores. These results demonstrate that concept-structured, interaction-aware tabular learning surfaces physiologically coherent reasoning, supporting clinical trust.

10.
arXiv (quant-ph) 2026-06-15

Resolving the Edge of a Quantum Pyramid

arXiv:2606.14698v1 Announce Type: new Abstract: Standing on the shoulders of giants, we resolve the quantum pyramids conjecture, confirming the globally information-optimal measurement for an ensemble of equiangular equiprobable pure states, as conjectured by Englert and \v{R}eháček (arXiv:0905.0510). We do so by proving the remaining entropy inequalities of Holevo and Utkin (arXiv:2506.06700), which certify optimality for obtuse and flat pyramids. For obtuse pyramids, our key contribution is a rigorous proof that local minimizers of the corresponding entropy inequality cannot have three distinct coordinate values. We show that eliminating this family can be reduced to a neat algebraic reciprocal inequality relating branches of the Lambert $W$ function, which may be of independent interest. For flat pyramids, we prove a tight $\ell^p$ inequality for zero-sum vectors that was recently conjectured, proved analytically in dimension $d=3$, and computationally verified for $d\leq 200$ by Holevo and Utkin (arXiv:2603.24017). We prove this bound for all $d\geq 2$ via a technique in symmetric inequalities known as the equal variables method.

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

What Must Generalist Agents Remember?

arXiv:2606.18746v1 Announce Type: new Abstract: This paper develops a formal account of what generalist agents must store in memory in order to act near-optimally across multiple environments and goals. It shows that when two domains share an observational bottleneck but require incompatible optimal actions, any uniformly near-optimal policy must induce distinct memory distributions at that bottleneck. The result yields a separation theorem: sufficiently successful agents cannot rely only on current state observations, but must preserve domain-relevant information in memory. The paper further shows that if an agent's memory contains enough information to estimate values for related goals, then that memory can be used to approximately reconstruct the agent's local transition dynamics. Together, these results characterize memory as the substrate that supports domain disambiguation, transition-model reconstruction, and planning for generalist agents.

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

Sentinel: Decoding Context Utilization via Attention Probing for Efficient LLM Context Compression

Retrieval-augmented generation (RAG) often suffers from long and noisy retrieved contexts. Existing context compression methods typically rely on heuristic relevance estimation or supervised compression models rather than on how LLMs utilize retrieved context during inference. We propose Sentinel, a lightweight sentence-level compression framework that decodes inference-time contextual utilization behaviors from head-wise attention patterns of frozen LLMs. To ground supervision in retrieval-dependent answering behavior, Sentinel trains a lightweight probe using QA examples where the model succeeds only when retrieved context is available. Sentinel performs compression using only a single non-autoregressive forward pass without dedicated compression training or autoregressive scoring. Empirically, we find that effective contextual utilization signals remain accessible even in compact proxy models. On LongBench, Sentinel with a 0.5B proxy model achieves up to 5$\times$ compression while attaining question-answering performance competitive with compression methods built on 7B-scale models. Despite being trained only on English QA data, Sentinel also generalizes effectively to Chinese and out-of-domain settings.

13.
arXiv (CS.CV) 2026-06-24

FLAT: Feedforward Latent Triangle Splatting for Geometrically Accurate Scene Generation

Generating explorable 3D scenes from a single image requires strong generative priors and accurate geometric representations suitable for downstream use. Current video diffusion models offer high-quality generation and implicitly encode multi-view geometric structure in latent space. However, existing feedforward latent scene decoders typically output volumetric 3D Gaussians that lack a well-defined surface, limiting their use in simulation or standard graphics pipelines. This motivates decoding surface-aligned primitives that are not only renderable but also closer to explicit geometric assets. We ask whether compressed video diffusion latents can be mapped directly to explicit surface primitives in a single pass. To this end, we introduce FLAT and, for the first time, show that triangle splats can be decoded directly from video diffusion latents. Compared with decoding 3D Gaussians, predicting flat primitives is notoriously more challenging due to high sensitivity to primitive orientations, oftentimes leading to poor gradient flow. FLAT solves with two key ingredients: a ray-centered rotation parameterization for triangle regression and a novel product window function that improves gradient flow during differentiable triangle rendering. On standard benchmarks, FLAT achieves significantly better geometric accuracy while maintaining competitive visual quality compared to state-of-the-art feedforward baselines. We further show that a lightweight test-time refinement step converts the predicted triangle soup into a fully opaque, game-engine-ready representation that supports real-time rendering. By evaluating 3DGS, 2DGS, and triangle splatting variants under an identical training setup, we provide the first systematic analysis of representation tradeoffs in feedforward scene generation. The project page is available at https://flat-splat.github.io

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

Predicting Immune Biomarkers with MultiModal Mixture-of-Expert Pathology Foundation Models Empowers Precision Oncology

Predicting immune biomarkers associated with the tumor immune microenvironment (TIME) is critical for advancing precision oncology, yet existing approaches are largely limited to single image modalities and suffer from insufficient resolution and incomplete utilization of complementary clinical and biological information. Here we introduce MixTIME, a multimodal foundation model that leverages a mixture-of-experts (MoE) architecture to integrate pathology foundation models trained across distinct modalities: image only (UNIv2), image text (CONCHv1.5), and image transcriptomic (STPath) representations for pixel-level and slide-level prediction of multiplex immunofluorescence (mIF) protein expression from hematoxylin and eosin (HE) whole-slide images. MixTIME employs a learnable router to dynamically weight expert contributions and is trained with a distribution- and tendency-aware loss function. Benchmarked on two datasets of different scales, MixTIME achieves state-of-the-art performance across 17 protein markers as measured by correlation metrics. The predicted mIF profiles substantially enhance downstream tasks, including spatial domain identification, survival prediction, and AI-assisted pathology report generation validated by expert pathologists from multiple institutes across the world. Furthermore, MixTIME enables longitudinal tracking of protein expression dynamics across clinical time points and reveals protein gene interaction patterns linked to drug resistance and immune suppression in tumor microenvironments. Collectively, MixTIME provides a scalable framework for multimodal biomarker discovery and clinical translation in computational pathology.

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

Can Factual Opinions Be Edited (Manipulated) in Large Language Models?

Large Language Models (LLMs) are increasingly integrated into various domains, making knowledge editing techniques crucial yet potentially hazardous. Current editing methods primarily target atomic facts, overlooking the significant risks associated with manipulating factual opinions, e.g., documented stances of public figures on societal issues. Such manipulation could reshape public images, influence elections, and alter societal views. To systematically assess this threat, we introduce the Factual Opinion Editing with Evidence (FOE) benchmark, which encompasses 261 public figures, 19 issue categories, and 2,178 complete opinion records. Our evaluations demonstrate that current editing techniques struggle significantly with factual opinions, often achieving only superficial changes while failing to preserve consistency between the edited opinion and the supporting evidence generated by the model. To address this limitation, we further propose a simple yet effective Self-Generated Evidence-Aligned method that achieves opinion-evidence alignment without relying on explicit instructions. Together, our benchmark and method provide a foundation for understanding the emerging security implications of factual opinion editing in LLMs.

16.
arXiv (CS.LG) 2026-06-24

XConv: Low-memory stochastic backpropagation for convolutional layers

arXiv:2106.06998v5 Announce Type: replace Abstract: Training convolutional neural networks at scale demands substantial memory, largely because intermediate activations must be stored for backpropagation. Existing remedies (checkpointing, invertible architectures, or gradient-approximation methods such as randomized automatic differentiation) either add significant computation, impose architectural constraints, or require non-trivial code changes. We propose XConv, a near-drop-in replacement for standard 2D and 3D convolutional layers that addresses all three: it preserves standard backpropagation, imposes no architectural constraints, and integrates into existing codebases with minimal changes. XConv exploits the algebraic structure of convolutional weight gradients, storing highly compressed projections of the activations rather than the full tensors and approximating the gradients via multi-channel randomized trace estimation. The number of probing vectors sets a memory-accuracy tradeoff and recovers the exact gradient in the limit. We establish convergence guarantees and error bounds for the estimator, showing that its gradient-error variance is comparable to that of stochastic gradient descent. Empirically, XConv matches exact-gradient methods across classification, generative modeling, super-resolution, inpainting, and segmentation, with gaps that narrow as the number of probing vectors grows, while reducing activation memory by a factor of two or more when convolutional activations dominate, and remaining computationally competitive with optimized convolution kernels at larger batch sizes. At half precision the gradient-approximation error falls to the rounding floor, so XConv adds essentially no error beyond that of low-precision arithmetic. The savings matter most where activation memory rather than compute is the binding constraint, such as high-resolution and volumetric training and on-device finetuning.

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

Spokes: Optimizing for Diverse Pretraining Data Selection

Diversity plays a critical role in data selection, improving performance under fixed data budgets by reducing redundancy and repetition. However, optimizing for diversity is inherently challenging, as it is a set-level property that depends on interactions between data points rather than individual examples. As a result, existing approaches typically rely on proxies or approximations, which often fail to ensure sufficiently diverse subsets. In this work, we directly optimize diversity by introducing a probabilistic diversification framework based on the G-Vendi score, optimized via exponentiated gradient descent. Our method produces subsets that are substantially more diverse than those obtained via random sampling, achieving a +489 increase in G-Vendi score on a 500k-sample subset. We evaluate our approach on FineWeb and DCLM, where it consistently outperforms existing methods. Notably, SPOKES (diversity-only) improves average downstream performance by +0.4 and +0.5 points over random sampling on DCLM and FineWeb, respectively. More importantly, jointly optimizing for both quality and diversity yields the strongest results: SPOKES achieves gains of +1.5 and +1.4 points on DCLM and FineWeb, outperforming all baselines, including semantic deduplication and quality filtering.

18.
arXiv (math.PR) 2026-06-11

Feynman–Kac formula for the heat equation with a one-center point interaction in $d=3$

arXiv:2606.11677v1 Announce Type: new Abstract: We study Schrödinger operators with a one-center point interaction, formally defined by \begin{align*} -\Delta_\alpha=-\Delta+\alpha\,\delta_0(\cdot), \end{align*} for $\alpha\in\mathbb{R}$, and the associated heat equation \begin{align} \partial_t u=\tfrac{1}{2}\Delta_{\alpha} u,\quad u(0,x)=u_0(x)\in C_c^{\infty}(\mathbb{R}^3\setminus\{0\}).\label{eq:HEapp} \end{align} Here $\Delta$ denotes the Laplacian (self-adjoint on $L^2(\mathbb{R}^3)$) and $\delta_x$ the Dirac measure at $x$. The operator $-\Delta_\alpha$ can be realized either as a self-adjoint extension of $-\Delta|_{C_0^{\infty}(\mathbb{R}^3\setminus\{0\})}$ in $L^2(\mathbb{R}^3)$, or as the norm-resolvent limit of $-\Delta+\lambda_\varepsilon V(\cdot/\varepsilon)$ for suitable $\lambda_\varepsilon$ and $V:\mathbb{R}^3\to\mathbb{R}$. In this paper we construct, for each $t>0$ and $x\in\mathbb{R}^3\setminus\{0\}$, a probability law on path space and a normalizing function $G_t^\alpha(x)$ giving the following probabilistic representation of the solution to the associated equation: \begin{align*} u(t,x)=G_t^\alpha(x)\,\mathbb{E}\bigl[u_0\bigl(W^{t,x}(t)\bigr)\bigr], \end{align*} where $\{W^{t,x}(s):0\le s\le t\}$ is a continuous process depending on $(t,x,\alpha)$. The result provides a Feynman–Kac type formula for the heat equation with a one-point interaction in three dimensions.

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

OmniOPSD: Rationale-Privileged On-Policy Self-Distillation for Affective Computing

Reinforcement learning for multimodal large language models (MLLMs) is often hindered by severe reward sparsity in complex reasoning tasks. This challenge is particularly pronounced in human-centered scenarios involving states, emotions, intentions, and behaviors, where heterogeneous multimodal signals and subjective human factors make high-quality chain-of-thought (CoT) annotations expensive and difficult to obtain. Although many multimodal datasets provide expert-annotated ground-truth labels, directly using these labels for supervised fine-tuning may encourage shortcut learning in multimodal perception and provides limited transparency for safety-critical human–AI interaction. To address these limitations, we propose OmniOPSD, a Rationale-Privileged On-Policy Self-Distillation framework that uses frontier-generated rationales as teacher-side privileged evidence rather than student imitation targets. OmniOPSD uses frontier-generated evidence-aware rationales only as training-time privileged evidence context for a local teacher. The student samples its own rollout from the original multimodal input, while the rationale-privileged teacher scores the same tokens and provides dense token-level supervision. Thus, the student learns on its own trajectory distribution without directly imitating frontier-model completions, and inference requires no labels, rationales, CoT annotations, or closed-source model access. Experiments on MER-UniBench show that OmniOPSD achieves state-of-the-art performance with an average score of $84.19$, and ablations further support the value of rationale-privileged teacher guidance.

20.
medRxiv (Medicine) 2026-06-15

Two Blood-based Endotypes Reveal Divergent Clinical Outcomes of Fibrotic Hypersensitivity Pneumonitis

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an antigen-driven, life-threatening interstitial lung disease characterized by heterogeneous radiologic features, clinical outcomes, and treatment responses. Objectives: To identify blood-based fHP endotypes that inform mechanism, prognosis and therapeutic response. Methods: We performed integrative analyses of multi-compartment transcriptomic data derived from whole blood, peripheral blood mononuclear cells, bronchoalveolar lavage, and surgical lung biopsies, alongside circulating plasma proteomics. Multiple clustering algorithms were cross-compared to ensure robustness and reproducibility of endotypes identification. Immune cell composition was inferred using bulk RNA-seq deconvolution and annotated with BAL single-cell RNA-seq. Pathway activities were characterized using Gene Set Enrichment Analysis. Transplant-free survival (TFS) was evaluated for endotype and corticosteroid exposure by Kaplan-Meier methods, with hazard ratios analyzed using multivariable Cox proportional hazards models. Results: Two molecular endotypes, lymphocytic-associated (L-fHP) and non-lymphocytic-associated (N-fHP), were identified and validated. L-fHP showed enrichment of adaptive immune signaling and lymphocyte predominance, whereas N-fHP demonstrated myeloid-cell activation with neutrophil and macrophage predominance. Corticosteroid exposure was associated with worse TFS in L-fHP but not in N-fHP after adjusting for age, sex, and baseline pulmonary function. Compared to L-fHP, N-fHP had poorer baseline pulmonary function, faster 12-month FVC decline, and shorter TFS. N-fHP also exhibited elevated neutrophil-associated markers, including matrix metalloproteinase-9, across paired transcriptomic and proteomic datasets, supporting a neutrophil-driven, cross-compartment disease process. Conclusion: Multi-omic, multi-compartment analysis identifies two reproducible fHP endotypes with distinct clinical outcomes and corticosteroid responses, supporting a precision medicine approach beyond current clinical and radiologic classification.

21.
arXiv (CS.LG) 2026-06-25

Knowledge Cascade: Reverse Knowledge Distillation on Nonparametric Multivariate Functional Estimation

arXiv:2606.25927v1 Announce Type: cross Abstract: As machine learning models and datasets continue to grow, developing complex models has become increasingly computationally demanding. Knowledge distillation reduces deployment cost by compressing a large, well-trained teacher model into a compact student model, but it does not address settings where constructing the teacher itself is the bottleneck. Motivated by this challenge, we introduce Knowledge Cascade (KCas), a reverse knowledge distillation framework that uses information from a small, inexpensive student model to guide the development of a more complex teacher model. Although this direction is counterintuitive because the teacher typically has greater representational capacity, we show that student-to-teacher transfer can be principled when supported by statistical scaling relationships. We first develop KCas for nonparametric multivariate functional estimation in reproducing kernel Hilbert spaces via smoothing splines, where selecting multiple smoothing parameters is a major computational bottleneck. KCas transfers student-selected smoothing parameters to the full-sample regime through asymptotic scaling laws, substantially reducing computational cost for high-dimensional and large-scale datasets while retaining theoretical guarantees. Beyond smoothing splines, we illustrate the same principle through kernel density estimation and deep learning hyperparameter transfer. Simulations and real-data experiments show that KCas achieves substantial computational savings while maintaining strong statistical performance, and can sometimes outperform the corresponding full-sample procedure.

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

Frozen Foundation-Model Embeddings Discard Small-Lesion Signal in Chest Radiography: Implications for Pre-Deployment Evaluation

Frozen vision-transformer (ViT) foundation-model embeddings increasingly serve as the substrate for downstream chest-radiography (CXR) pipelines, yet where small-scale, low-contrast signal is retained or lost in the frozen forward pass has not been systematically quantified across architectures, pretraining domains, and objectives. We probed five frozen ViTs (RAD-DINO, DINOv2-B/14, DINOv3 ViT-7B, BiomedCLIP, MedSigLIP) and a frozen DINO-pretrained ResNet-50 architectural control across three large CXR cohorts (NIH-CXR14, MIMIC-CXR, Emory-CXR; aggregate pool n=492,724) and ChestX-Det10 (n=3,543; 1,462 small-lesion bounding boxes across Calcification, Nodule, Mass). Each model was evaluated with a small-scale-perturbation panel and a region-aware bounding-box-stratified probe on real lesions, comparing three pooling modes from the same forward pass: classification token (CLS), patch-mean (mean over all final-layer patch tokens), and bounding-box-restricted patch-local. On the perturbation panel, CLS embeddings sat at the chance floor (area under the ROC curve [AUC] 0.500-0.524); patch-mean was indistinguishable from CLS on iso-blur and reticular-fine cells but rose with CLS on larger directional-blur footprints, while disease AUC on globally decided tasks ranged 0.642-0.913. Patch-local probes recovered AUC ~1.0 from the same forward pass (per-model mean improvement +0.412 to +0.488); the ResNet-50 control reproduced the chance floor. On ChestX-Det10, image-level CLS classification showed within-class small-versus-large stratum gaps up to +0.243 AUC; bounding-box-level patch-local pooling on the same forward pass recovered AUC >= 0.899 on every (model x class) cell. Frozen ViT embeddings silently suppress small-scale signal at the global-aggregation step; the signal is recoverable from patch tokens conditional on a region of interest.

23.
bioRxiv (Bioinfo) 2026-06-22

Complex-valued representations of time-series gene expression profiles for network analysis

Time-series RNA sequencing provides a powerful framework for studying dynamic gene regulation, yet conventional analyses usually represent gene expression profiles as real-valued vectors in Euclidean space and quantify similarity using correlation or distance. Inspired by quantum information theory, we present a framework for encoding time-series gene expression profiles as complex-valued vectors comprising amplitude and phase components in Hilbert space. We designed multiple encoding models to represent gene expression in the amplitude of complex-valued vectors, encode temporal differences in the phase, and extend the phase representation to incorporate the direction of local expression changes. Gene-gene similarity was then quantified using fidelity, which measures the overlap between two encoded vectors. Evaluation using time-series RNA-seq datasets across diverse species and biological contexts showed that different encoding models produced distinct fidelity distributions that were related to, but distinct from, conventional correlation measures. We then constructed gene-gene networks using pairwise fidelity values and detected communities containing genes with similar temporal profiles. Although fidelity distributions differed across encoding models, the resulting communities captured major temporal expression programs, and functional annotations based on gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses provided exploratory biological context. The detected communities were comparable to those obtained using conventional methods, including weighted correlation network analysis and fuzzy c-means clustering. Furthermore, as a proof-of-concept, we performed SWAP-test circuit simulations to mimic fidelity computation on a quantum computer; under noise-aware conditions, these simulations produced less accurate fidelity estimates with higher computational cost than classical computation. As a proof-of-concept, this study provides a complementary view of temporal transcriptome organization, rather than a uniformly superior alternative to conventional methods.

24.
bioRxiv (Bioinfo) 2026-06-12

Systematic functional annotation of thousands of BAHD acyltransferases in plant genomes using Protein Language Model and phylogenomic tools

The functional annotation of plant genes lags significantly behind their genomic annotation. Closing this gap requires thorough cataloging of reported protein activities alongside predictive methods that scale beyond sequence-similarity inference. Focusing on the BAHD acyltransferase enzyme family as a model, we assembled FuncZymeDB-BAHD, a large database of 2,705 LLM-retrieved and curated enzyme-acceptor-donor activities covering 336 BAHDs from 156 plant species, a 2-to-6-fold expansion over Swiss-Prot and prior compilations. We further developed FuncPred-OG, which maps queries to orthologous groups and previously characterized enzymes in FuncZymeDB-BAHD, returning hits with high evidence provenance. FuncPred-OG enabled functional prediction of over half of BAHDs across 85 plant proteomes, of which five novel predictions were validated via in vitro assays and recent studies. For the remaining BAHDs without FuncPred-OG annotation, we developed FuncPred-AI, where logistic-regression classifiers trained on protein language model embeddings achieved high Area-Under-the-Precision-Recall-curve (AUPR) scores and correct-hit rates up to 93%. FuncPred-AI yielded >1 probable donor/acceptor annotation for 99.9% (8894/8897) of BAHDs in our pan-plant dataset. Finally, the FuncPred workflow and datasets were deployed on a web portal for broader utilization, potentially reducing experimentalist efforts for selecting candidates from days to minutes. Overall, this framework provides a generalizable template for functional annotation of entire enzyme families.

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

Automated ultrasound doppler angle estimation using deep learning

arXiv:2508.04243v2 Announce Type: replace-cross Abstract: Angle estimation is an important step in the Doppler ultrasound clinical workflow to measure blood velocity. It is widely recognized that incorrect angle estimation is a leading cause of error in Doppler-based blood velocity measurements. In this paper, we propose a deep learning-based approach for automated Doppler angle estimation. The approach was developed using 2100 human carotid ultrasound images including image augmentation. Five pre-trained models were used to extract images features, and these features were passed to a custom shallow network for Doppler angle estimation. Independently, measurements were obtained by a human observer reviewing the images for comparison. The mean absolute error (MAE) between the automated and manual angle estimates ranged from 3.9{\deg} to 9.4{\deg} for the models evaluated. Furthermore, the MAE for the best performing model was less than the acceptable clinical Doppler angle error threshold thus avoiding misclassification of normal velocity values as a stenosis. The results demonstrate potential for applying a deep-learning based technique for automated ultrasound Doppler angle estimation. Such a technique could potentially be implemented within the imaging software on commercial ultrasound scanners.