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01.
arXiv (CS.CV) 2026-06-18

Clinically Aligned Geometry Constraints for Robust IVUS Vessel Boundary Segmentation

Intravascular ultrasound (IVUS) lumen and external elastic membrane (EEM) segmentation is important for quantitative coronary plaque burden assessment. Errors in lumen or EEM delineation directly propagate to plaque area, plaque burden and geometric measurements. However, standard methods prioritising overlap scores often suffer from boundary drift and topology errors, leading to inaccurate clinical measurements. We present GeoCat, a geometry-consistent network that processes 5-frame IVUS clips using dual Cartesian-polar encoders with cross-domain attention and temporal fusion. A differentiable geometry consistency loss directly supervises clinically relevant descriptors including diameters, orientations, and cross-sectional areas. The model is trained on 12,242 annotated frames from 146 patients acquired with two commercial IVUS systems. We evaluate performance using both segmentation accuracy and plaque-relevant clinical metrics, including Dice/IoU, boundary measures(95HD (mm), ASSD), topology violation rate, and clinical geometry errors (dmax/dmin, angles, and areas). On our dataset, GeoCat achieves a Dice of 0.93, reduces 95HD to 0.14 mm, and lowers topology violations to 1.0%. Importantly, it significantly improves geometric fidelity, yielding diameter errors of 0.13-0.16 mm and angular errors of ~8 degrees, supporting reliable plaque burden quantification.

02.
arXiv (CS.AI) 2026-06-11

Artificial Intelligence in Ship Finance: Applications, Opportunities, and a Case Study in AI-Augmented Loan Origination

arXiv:2606.11238v1 Announce Type: cross Abstract: Ship finance is a data-intensive and document-heavy segment of asset-based lending, requiring the integration of financial, technical, contractual, and regulatory information from heterogeneous and largely unstructured sources. Increasing environmental regulation and ESG reporting requirements are adding further complexity to underwriting and loan-origination processes. Recent advances in artificial intelligence (AI), particularly large language models (LLMs), create new opportunities for processing and analysing such information. This paper reviews potential applications of AI in ship finance, with a particular focus on LLM-based systems for document comprehension, information extraction, and workflow automation. We present ShipFinance.ai, a modular agentic architecture to support loan application workflows in ship finance. The proposed system combines an LLM-based extraction module, financial analysis components, external maritime data services, and a controlled document-generation module with a chatbot interface to support the preparation of standardized financing applications. The paper discusses the key challenges for using such models in production. We argue that AI-assisted systems can support maritime finance professionals in managing increasingly complex information and reporting requirements.

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

LoHoSearch: Benchmarking Long-Horizon Search Agents Beyond the Human Difficulty Ceiling

Search agent benchmarks exemplified by BrowseComp have rapidly saturated over the past year, with the strongest models surpassing 90% accuracy. Since these benchmarks are predominantly human-authored, annotators lack a global perspective on entity statistics and cannot systematically maximize search space size and structural complexity. This creates a difficulty ceiling that is hard to break. To address this, we introduce LoHoSearch (Long-Horizon Search Agents), a challenging benchmark comprising 544 human-verified questions across 11 domains. LoHoSearch is constructed via an automated pipeline built upon a knowledge graph covering over 7 million Wikipedia entities, which selects relations with large search spaces and assembles them into structurally complex questions with KG-verified unique answers. Our evaluation demonstrates that even the strongest model achieves only 34.74% accuracy, and existing context management strategies (best +6.8%) yield far smaller gains than on prior benchmarks. LoHoSearch provides a more demanding standard for evaluating long-horizon reasoning and context management in search agents.

04.
arXiv (CS.AI) 2026-06-11

Human-Guided Agentic AI for Multimodal Clinical Prediction: Lessons from the AgentDS Healthcare Benchmark

arXiv:2602.19502v2 Announce Type: replace Abstract: Agentic AI systems are increasingly capable of autonomous data science workflows, yet clinical prediction tasks demand domain expertise that purely automated approaches struggle to provide. We investigate how human guidance of agentic AI can improve multimodal clinical prediction, presenting our approach to all three AgentDS Healthcare benchmark challenges: 30-day hospital readmission prediction (Macro-F1 = 0.8986), emergency department cost forecasting (MAE = $465.13), and discharge readiness assessment (Macro-F1 = 0.7939). Across these tasks, human analysts directed the agentic workflow at key decision points, multimodal feature engineering from clinical notes, scanned PDF billing receipts, and time-series vital signs; task-appropriate model selection; and clinically informed validation strategies. Our approach ranked 5th overall in the healthcare domain, with a 3rd-place finish on the discharge readiness task. Ablation studies reveal that human-guided decisions compounded to a cumulative gain of +0.065 F1 over automated baselines, with multimodal feature extraction contributing the largest single improvement (+0.041 F1). We distill three generalizable lessons: (1) domain-informed feature engineering at each pipeline stage yields compounding gains that outperform extensive automated search; (2) multimodal data integration requires task-specific human judgment that no single extraction strategy generalizes across clinical text, PDFs, and time-series; and (3) deliberate ensemble diversity with clinically motivated model configurations outperforms random hyperparameter search. These findings offer practical guidance for teams deploying agentic AI in healthcare settings where interpretability, reproducibility, and clinical validity are essential.

05.
arXiv (quant-ph) 2026-06-11

On-Chip Quantum Randomness Amplification

arXiv:2606.12173v1 Announce Type: new Abstract: Randomness amplification, the task of extracting uniform private bits from biased seeds that may be partly known by a malicious third party, is of central importance in cryptography. The highest security in this task is provided by a class of quantum protocols known as device-independent, which however are challenging to integrate into scalable devices. Semi-device-independent (SDI) protocols are a promising alternative that guarantees security under few natural assumptions, such as bounds on the amount of energy used by the devices. Here, we provide the first demonstration of SDI randomness amplification on an integrated silicon photonic chip, achieving a throughput rate of 20 Mbps suitable for practical applications. This rate is achieved through a novel technique for SDI entropy certification, which delivers strictly tighter von Neumann entropy bounds compared to existing methods and remains valid even if the preparation and measurement devices share quantum correlations. Overall, the methods developed in this work enable the integration of SDI technology into portable telecom devices, opening up a new generation of quantum cryptographic hardware.

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

Shift-and-Sum Quantization for Visual Autoregressive Models

Post-training quantization (PTQ) enables efficient deployment of deep networks using a small set of data. Its application to visual autoregressive models (VAR), however, remains relatively unexplored. We identify two key challenges for applying PTQ to VAR: (i) large reconstruction errors in attention-value products, especially at coarse scales where high attention scores occur more frequently; and (ii) a discrepancy between the sampling frequencies of codebook entries and their predicted probabilities due to limited calibration data. To address these challenges, we propose a PTQ framework tailored for VAR. First, we introduce a shift-and-sum quantization method that reduces reconstruction errors by aggregating quantized results from symmetrically shifted duplicates of value tokens. Second, we present a resampling strategy for calibration data that aligns sampling frequencies of codebook entries with their predicted probabilities. Experiments on class-conditional image generation, inpainting, outpainting, and class-conditional editing show consistent improvements across VAR architectures, establishing a new state of the art in PTQ for VAR.

07.
arXiv (CS.CV) 2026-06-18

NeuMesh++: Towards Versatile and Efficient Volumetric Editing with Disentangled Neural Mesh-based Implicit Field

Recently neural implicit rendering techniques have evolved rapidly and demonstrated significant advantages in novel view synthesis and 3D scene reconstruction. However, existing neural rendering methods for editing purposes offer limited functionalities, e.g., rigid transformation and category-specific editing. In this paper, we present a novel mesh-based representation by encoding the neural radiance field with disentangled geometry, texture, and semantic codes on mesh vertices, which empowers a set of efficient and comprehensive editing functionalities, including mesh-guided geometry editing, designated texture editing with texture swapping, filling and painting operations, and semantic-guided editing. To this end, we develop several techniques including a novel local space parameterization to enhance rendering quality and training stability, a learnable modification color on vertex to improve the fidelity of texture editing, a spatial-aware optimization strategy to realize precise texture editing, and a semantic-aided region selection to ease the laborious annotation of implicit field editing. Extensive experiments and editing examples on both real and synthetic datasets demonstrate the superiority of our method on representation quality and editing ability. Project page: https://zju3dv.github.io/neumeshplusplus/

08.
arXiv (CS.AI) 2026-06-17

ANEForge: Python for direct computation on the Apple Neural Engine

arXiv:2606.17090v1 Announce Type: cross Abstract: ANEForge is a Python package that programs the Apple Neural Engine (ANE), the fixed-function neural accelerator on every recent Apple device, directly and without CoreML. In production the engine is reachable only through CoreML, which treats it as a scheduling option: no configuration requires the ANE, and a model can silently run on the CPU or GPU instead. ANEForge compiles a lazy tensor graph, built from 58 fused operators and 19 native bridge operators, into a single ANE program. The program is dispatched through the same ANE daemon and kernel-driver stack as Apple's internal framework. Beyond inference, the package reaches the engine's native fused attention, streams int8, int4, and sparse weights, keeps decoder and optimizer state resident across steps, and runs the forward pass, backward pass, and optimizer update of training on the engine. A small fused program completes a call in about 90us, near the engine's 70us per-program dispatch floor, and a pretrained ResNet-18 forward runs end-to-end in 0.33ms. ResNet-18, a sentence encoder, and a Vision Transformer run end-to-end against framework references, and a Stable Diffusion U-Net validates its forward pass. ANEForge targets Apple Silicon under macOS 14 and later. Each release is verified against a recorded macOS and ANE-compiler version.

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

The Curse and Blessing of Mean Bias in FP4-Quantized LLM Training

arXiv:2603.10444v2 Announce Type: replace-cross Abstract: FP4 training promises substantial memory and compute savings for large language models, but remains fragile because blockwise quantization is dictated by extreme activation magnitudes, which inflate dynamic range and compress long-tail signals. We identify a counterintuitive source of this failure: dominant activation outliers are not merely arbitrary sparse events, but are largely induced by a coherent rank-one mean bias, whose direction aligns with the leading anisotropic spectral component. This mean component strengthens during training, is amplified and reshaped by attention and FFN operators, and increasingly dominates top activation magnitudes. Crucially, this discovery reveals that a seemingly complex outlier-suppression problem admits a truly simple solution: isolate the coherent mean before quantization. We therefore propose Averis, a mean-residual splitting quantization method that separates the mean component using only reductions and elementwise subtractions before FP4 quantization. Across Qwen3 0.6B Dense trained on 100B tokens and Qwen3 7B A1.5B MoE trained on 50B tokens, Averis enables robust W4A4G4 FP4 training, reducing BF16 loss gaps to 1.19%/0.81% versus 2.05%/1.10% for NVIDIA's recently released Hadamard-based outlier-smoothing method, while limiting downstream gaps to 0.89/0.71 points. With only 2.20% end-to-end overhead over vanilla NVFP4, about 30% of NVIDIA's Hadamard-based design, Averis provides a hardware-efficient path to stable low-bit LLM training. Complementary to Hadamard, Averis further reduces the Qwen3-0.6B loss and downstream gaps to 0.94% and 0.73 points when combined. Code is available at: https://anonymous.4open.science/r/averis-504D.

10.
medRxiv (Medicine) 2026-06-19

Grey- and white-matter resilience to tau, cognition and sex in Alzheimer's disease

INTRODUCTION: Brain resilience to tau has been mainly studied in relation to grey matter, while its role in white matter remains unclear in Alzheimer's disease (AD). Sex may moderate associations between brain resilience and cognition. METHODS: We analyzed medial temporal lobe tau PET SUVR, entorhinal cortical thickness, cingulum-hippocampal mean diffusivity, and cognition in 205 amyloid-positive individuals from ADNI. Associations between grey- and white-matter resilience to tau and cognitive performance or decline were examined using linear and mixed-effects models, including sex interactions and stratified analyses. RESULTS: Higher grey-matter resilience to tau related to better cross-sectional memory and language performance (p

11.
arXiv (CS.LG) 2026-06-17

Evaluating Intersectional Fairness across Clinical Machine Learning Use Cases using Fairlogue and the All of Us Research Program

arXiv:2604.16450v2 Announce Type: replace-cross Abstract: Intersectional biases in healthcare data can produce compound disparities in clinical machine learning models, yet most fairness evaluations assess demographic attributes independently. FairLogue, a toolkit for intersectional fairness auditing, was applied across multiple clinical prediction tasks to evaluate disparities across combined demographic groups. Using the All of Us dataset, two published models were selected for replication and evaluation: (A) prediction of selective serotonin reuptake inhibitor associated bleeding events and (B) two-year stroke risk in patients with atrial fibrillation. Observational fairness metrics were computed across race, gender, and intersectional subgroups, followed by counterfactual analysis to evaluate whether disparities were attributable to group membership. Intersectional evaluation revealed larger disparities than single-axis analyses; however, counterfactual diagnostics indicated that most observed disparities were comparable to those expected under randomized group membership. These results highlight the importance of intersectional fairness auditing and demonstrate how FairLogue provides deeper insight into bias in clinical machine learning systems.

12.
arXiv (CS.CL) 2026-06-16

A Survey on Agentic Security: Applications, Threats and Defenses

LLM-based agents are now used throughout cybersecurity. While these agents facilitate powerful and autonomous security applications, their autonomy opens up new attack surfaces, and the security community is actively building defenses to secure them. Yet the literature on this subject has grown quickly and unevenly. Existing surveys treat applications, threats, and defenses in isolation, leaving no unified account of how an agent's capabilities, vulnerabilities, and countermeasures interconnect. In this work we present the first holistic survey of the agentic security landscape, structuring the field around the fundamental pillars of Applications, Threats and Defenses. We provide a comprehensive taxonomy of over 260 papers, explaining how agents are used in downstream cybersecurity applications, inherent threats to agentic systems, and countermeasures designed to protect them. In addition, we provide detailed pillar-specific and cross-cutting analyses that show the security-lifecycle coverage of agentic applications, comparison between red-teaming and blue-teaming agents, and the adversarial use of red-teaming applications. On the threat side, we analyze the entry points and agent-loop stages that attacks target, their specificity to the agentic setting, and the threat models they assume. On the defense side, we analyze the prevailing defense strategies, their cost and security trade-offs, and where in the agent lifecycle they are deployed. We further map which defenses cover which attack classes and chart trends in agent architecture, backbone model usage, data modality coverage, and the growth of attack and defense research over time. Taken together, these findings indicate that agentic systems are structurally fragile by default and that securing them will require defenses that span the full agent lifecycle rather than single-layer fixes.

13.
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.

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

Beyond Native Success: Auditing Deployment-Interface Exposure of CLIP Backdoors

Contrastive Language-Image Pre-training models are widely reused across downstream interfaces, including feature extraction, retrieval, reranking, and selection. Existing CLIP backdoor, however, usually validate attacks on a small attack-native task, leaving unclear whether the same poisoned checkpoint remains exposed, weakens, or becomes not applicable when reused through other interfaces. We introduce DIFE, a Deployment-Interface Footprint Evaluation framework that audits backdoored CLIP checkpoints across deployment interfaces. DIFE makes various evaluations comparable by specifying each interface's component readout, trigger channel, target event, reference condition, and metric. DIFE also introduces effective-footprint diagnosis to identify the reusable CLIP component or component combination that carries exposure and explains where risk transfers. Auditing reproduced CLIP backdoors with DIFE reveals a structured landscape: native success is not a checkpoint-level risk certificate, exposure follows component footprints, text-side poisoning does not yield textual-encoder control, and some coupled attacks remain mechanism-bound. This audit reveals a import gapin existing CLIP backdoors: a textual encoder that itself becomes a reusable carrier of adversarial behavior. We therefore introduce BadTextTower to fill this gap. BadTextTower produces strong text-conditioned retrieval, reranking, and selection exposure while leaving visual-only reuse nearly clean.

15.
arXiv (quant-ph) 2026-06-11

Residual-Squeezing Mechanism of Mismatch in Inverse-Squeezing Kennedy Receivers

arXiv:2601.19093v4 Announce Type: replace Abstract: The discrimination of quantum states is fundamental to quantum information processing. Inverse-squeezing Kennedy (IS-Kennedy) receivers can outperform the coherent-state BPSK Helstrom benchmark at the same energy by converting transmitter-side squeezing into an effective coherent-state separation gain, without violating the Helstrom bound for the squeezed-state alphabet. This work investigates how squeezing mismatch degrades this mechanism. We show that imperfect inverse squeezing transforms the ideally nulled output into a residually squeezed state, thereby altering the photon-number statistics before detection. This residual-squeezing picture reveals a strong physical asymmetry between squeezing-magnitude and squeezing-phase mismatches. Magnitude mismatch produces an energy-independent error floor in the high-signal-energy regime, whereas phase mismatch generates a residual squeezing term that grows with signal energy. In the small-residual-squeezing regime, this leads to a polynomial growth of the leading error contribution and a rapid collapse of the SQL advantage. We also identify a parity-step effect in photon-number-resolving detection: because the nulled residual squeezed vacuum contains only even photon numbers, increasing detector resolution improves the high-energy robustness only when the effective saturation threshold crosses the next even photon number. These results identify phase locking as the dominant bottleneck for IS-Kennedy-type non-Gaussian receivers under unitary squeezing mismatch and provide design guidelines for robust squeezed-state quantum receivers.

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

FitVTON: Fit-aware Virtual Try-On via Body-Garment Size Control

While diffusion-based virtual try-on has achieved impressive visual realism, most methods treat the task as 2D inpainting, prioritizing texture preservation over physical plausibility. Consequently, they often produce plausible-looking images that fail to reflect authentic garment fit across diverse body shapes. We present FitVTON, a Fit-aware virtual try-on model on different bodies in the wild. FitVTON encodes garment-body size through structured text prompts, and learn from simulated try-on triplets from parameterized garment model. To improve the fitting effects over garment silhouettes, we introduce two auxiliary head to predict the masks for both the garment and the exposed body. We further introduce a texture rectification stage to improve realistic appearance from simulated data. To evaluate the fitting fidelity, we curate a real-world dataset, FittingEffect3K, combining VLM-based scoring protocol. Both subjective and quantitive experiments show that FitVTON demonstrate authentic fitting fidelity, with significant sizing accuracy and shape preservation over state-of-the-art methods while maintaining competitive image quality. Project Page: https://zenoning.github.io/FitVTON/.

17.
arXiv (CS.CV) 2026-06-11

RSTR: Reducing SpatioTemporal Redundancy in Diffusion Transformers

Diffusion Transformers (DiTs) have achieved remarkable success in image generation, yet their deployment is hindered by high computational costs. We identify two sources of redundancy. First, temporal redundancy: Classifier-Free Guidance (CFG) applies costly dual forward passes at every timestep, yet guidance matters only at specific steps, and variable scales at critical steps can compensate for skipping others. Second, spatial redundancy: under variable guidance, different transformer blocks exhibit heterogeneous sensitivity, yet uniform calibration across all blocks wastes computation while failing to address their varying requirements. We present RSTR, the first framework to jointly reduce spatiotemporal redundancy in diffusion transformers. Stage-1 addresses temporal redundancy through evolutionary search, discovering sparse guidance schedules with variable scales. Stage-2 addresses spatial redundancy through adaptive rank allocation, assigning calibration capacities to transformer regions based on their sensitivity. Experiments on DiT-XL/2, PixArt-$\alpha$, FLUX, and state-of-the-art Qwen-Image demonstrate 50%-70% compute savings while maintaining or improving quality. On DiT-XL/2, RSTR achieves 57% savings with 15% FID improvement; on Qwen-Image, 3.43$\times$ speedup with preserved quality.

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

FoundCause: Causal Discovery with Latent Confounders from Observational Data

arXiv:2606.17516v1 Announce Type: cross Abstract: Causal discovery from observational data remains challenging due to the need to recover directed structure and latent confounding without interventions. We propose FoundCause, an amortized causal discovery model trained entirely on synthetic data that maps datasets directly to causal graphs in a single forward pass. By learning from large collections of simulated structural causal models, FoundCause captures transferable statistical patterns that generalize beyond individual datasets. The architecture incorporates several key inductive biases for causal discovery. It uses a permutation-invariant transformer encoder with alternating attention over samples and variables to jointly model cross-variable dependence and per-variable distributions. Pairwise statistical features derived from classical asymmetry measures are injected through statistics-conditioned attention, guiding the model toward known causal signals. A factorized decoder separates edge existence from direction, while a triangular refinement module enables reasoning over higher-order causal motifs such as chains and colliders. In addition, a dedicated confounder module based on learnable latent tokens explicitly models hidden common causes, and the model explicitly handles missing data via its masked input representation. To our knowledge, FoundCause is the first amortized causal discovery approach to explicitly model latent confounding. FoundCause outperforms 11 classical non-amortized methods (e.g., PC, GES, NOTEARS-style optimization) and 4 amortized causal discovery methods on 15 real-world datasets, achieving +9.6% improvement in $F_1$, +1.2% in AUROC, and an 18.9% reduction in structural Hamming distance relative to the strongest non-amortized methods, while performing inference in a single forward pass.

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

Circuit Tracing in Autoregressive Protein Language Models

arXiv:2606.16044v1 Announce Type: new Abstract: Protein language models (pLMs) can generate novel protein sequences with properties beyond those observed in nature, yet the mechanisms underlying protein generation remain poorly understood. Existing mechanistic interpretability methods based on sparse autoencoders and transcoders primarily focus on protein representation learning models and do not capture the computation required for autoregressive generation. Here, we introduce ProGenMech, a mechanistic interpretability framework for generative protein language models that extends cross-layer transcoders (CLTs) to ProGen3, a sparse Mixture-of-Experts model trained for both causal generation and span infilling. Unlike per-layer approaches, CLTs reconstruct each layer using sparse latent variables from all preceding layers, enabling faithful recovery of inter-layer generative computation. We further develop a zero-shot circuit discovery framework to identify sparse latent circuits responsible for protein generation and fitness prediction. In causal generation and zero-shot fitness estimation tasks, ProGenMech outperforms local transcoder baselines in recovering ProGen3's probability distribution and functional scoring behavior, while matching the original model's generative distribution in span infilling tasks. Moreover, the recovered circuits reveal biologically meaningful motifs and functional regions associated with conserved sequence patterns and protein fitness landscapes, establishing a foundation for interpretable and steerable protein generation.

20.
arXiv (quant-ph) 2026-06-15

Calibrated Helstrom geometry on the Bloch ball via Connes spectral distance

arXiv:2606.13824v1 Announce Type: new Abstract: We show that the equal-prior Helstrom trace-distance geometry of qubit states is recovered from Connes spectral distance in a finite scalar-qubit-scalar model. The two scalar reference sectors couple isotropically to the qubit block through identity Dirac links, so that the full Bloch ball, including mixed states, inherits its standard chordal trace-distance geometry from the finite spectral metric. The scalar-sector distances serve a distinct calibration role: they determine the individual link lengths, satisfy a Pythagorean consistency relation, and reconstruct the middle-sector scale.

21.
bioRxiv (Bioinfo) 2026-06-11

DeePEn - A Depth sensitive benchmark for Protein Engineering

Recent progress in modeling techniques and high-throughput screening has significantly enhanced the accessibility of protein engineering. Nevertheless, further progress gets hindered by the lack of robust benchmarks that capture the practical challenges for real-world protein engineering. Here, we introduced DeePEn, a Depth-sensitive benchmark for Protein Engineering that quantifies a models generalization capabilities when predicting protein fitness at increasing mutational distance from the wildtype or training data. We defined distance as the number of simultaneous point mutations, i.e., single amino acid variants (SAVs), moving from wild-type to mutant (edit distance in computer science jargon). Specifically selecting four deep mutational scanning (DMS) datasets with sufficient multi-mutation data points from ProteinGym, we assessed recent predictive models, including general and biophysics-informed protein Language Models (pLMs), and a non-transformer neural network. Our results highlight how the performance of all models deteriorates with increasing mutational distance and that no single metric sufficiently captures the diverse requirements of protein engineering. To overcome these shortcomings, DeePEn provides a readily available resource for multi-metric benchmarking that focuses on the prediction of distant variants.

22.
arXiv (CS.LG) 2026-06-17

A Diffusion Approximation for Temporal-Difference Learning with Linear Features under Markovian Noise

arXiv:2606.18183v1 Announce Type: cross Abstract: Temporal difference (TD) learning with linear function approximation is a core method for policy evaluation. Its classical continuous-time description is an ordinary differential equation (ODE), which captures the asymptotic mean dynamics but neglects stochastic fluctuations determining the error floor. We introduce a stochastic differential equation (SDE) approximation for linear TD(0) under Markovian noise. The resulting model distinguishes the contraction dynamics governed by the projected Bellman operator from the influence of Markovian sampling. As a consequence, the model explains the constant-stepsize error floor through the interaction between Markovian long-run covariance and the contraction geometry of the projected Bellman operator.

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

TivTok: Broadcasting Time-Invariant Tokens for Scalable Video Tokenization

Video tokenization is fundamental to scalable video generation, as the number of tokens directly determines the computational cost and the length of videos that can be modeled. Existing tokenizers mainly improve scalability by compressing videos into fewer tokens, but they often continue to represent persistent content, such as static backgrounds and consistent object appearances, repeatedly across frames and chunks. In this paper, we propose TivTok (Time-Invariant Tokenizer), a reuse-aware video tokenizer that makes persistent information reusable across time. TivTok represents a clip with Time-Invariant (TIV) tokens that encode information shared across frames and Time-Variant (TV) tokens that encode frame-specific residuals. To obtain this factorization, we introduce Scope-Induced Factorization (SIF), which assigns different attention scopes to the two token groups: TIV tokens attend to the full clip, whereas each TV token only accesses its corresponding frame together with the TIV tokens. In the decoder, Invariant Broadcasting (IB) reuses the same TIV tokens across frames and chunks for parallel reconstruction and long-video tokenization. Experiments show that TivTok achieves an rFVD of 12.65 on the standard $16{\times}256{\times}256$ benchmark and improves compression efficiency by 2.91$\times$ for 128-frame videos compared with the evaluated baselines, while using only 1.1\% of the tokens required by downsample-based tokenizers in our evaluation.

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

The Dark Regulome: Disentangling Predictability from Regulation in Genomic Foundation Models

High-grade gliomas integrate into neural circuits through functional synapses with neurons, raising the question of which noncoding elements shape synaptogenic gene expression in tumor cells. The regulatory program written across the dark genome, what we call the $dark regulome$, is the natural substrate to probe, and sequence foundation models offer a zero-shot route through in-silico mutagenesis (ISM); yet likelihood-based scoring is tautologically coupled to local sequence predictability, leaving the regulatory interpretation underdetermined. Across three architecturally distinct foundation models (Caduceus-Ph, HyenaDNA, Enformer) and 30,448 dark genome elements at 92 glioma-relevant loci, we introduce a residualization-and-permutation diagnostic that separates predictability-driven from regulation-driven RIS variance. A sharp 10kb proximal-regulatory horizon survives every control we apply, but the LM-derived element-class hierarchy does not: a six-feature linear baseline matches Caduceus top-decile membership at AUC $= 0.985$. Cross-architecture decomposition cleanly separates a sequence-predictability layer (the two language models co-rank long well-predicted transposable elements) from a regulatory-output layer (Enformer alone retains residual cCRE-discriminative signal), with literally zero overlap between the two top-100 lists. Conservation, brain cis-eQTL, and STRING-PPI cross-checks then anchor what biology survives: top-100 elements across all three models are $3.3\times$ enriched per model for matching brain eQTLs ($p_\mathrm{emp} < 5\times 10^{-3}$), while a tempting transposable-element regulatory layer and a striking NRXN1+NLGN1 protein-pair convergence both fail proper permutation tests once those tests are constructed. We deliver the diagnostic as a general methodological tool for any ISM-based regulatory study.

25.
Nature Biotechnology 2026-06-09

Hybrid solid−liquid optics enable scalable, high-resolution light-sheet microscopy across diverse immersion media

作者:

Many data-driven approaches rely on scalable and affordable three-dimensional (3D) imaging across subcellular to organ scales. Although advances in tissue clearing, expansion microscopy and light-sheet microscopy (LSM) have enabled high-resolution imaging of intact specimens, scalability in sample size, throughput and accessibility remains fundamentally limited by detection optics. Here we introduce hybrid solid−liquid optics (HySIL), a flexible refractive design framework in which a solid optical element and a refractive index (RI)-matched liquid function as a continuous optical system for wavefront correction and numerical aperture enhancement. We implement this framework as SCOPE and Super-SCOPE, enabling submicron-resolution, aberration-corrected LSM using long-working-distance air objectives. We demonstrate high-resolution volumetric imaging across diverse biological contexts, including cleared and expanded mouse, salamander and cavefish brains, human induced pluripotent stem cell (iPSC)-derived brain organoids and large intact human tissues for 3D histopathology. By combining enhanced optical performance with low-cost, long-working-distance and multi-immersion compatibility, HySIL provides an accessible and scalable foundation for next-generation volumetric imaging and data-driven biological discovery. Hybrid solid–liquid optics improve light-sheet imaging of intact biological samples.