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

Null-Space Diffusion Distillation Unlocks Speed, Fidelity and Realism in Lensless Imaging

Lensless imaging reconstructs scenes from highly multiplexed measurements, resulting in a severely ill-posed inverse problem. In this work, we identify a fundamental trade-off between measurement consistency, perceptual quality, and inference speed across lensless reconstruction paradigms. Traditional methods favor consistency but produce perceptually degraded results, supervised approaches achieve high-quality reconstructions with fast inference but may violate physical constraints, and diffusion-prior methods achieve high perceptual quality and consistency–particularly when structured constraints such as range-null decomposition are used–but remain slow due to iterative sampling. Motivated by this observation, we propose Null-Space Diffusion Distillation (NSDD), a single-pass reconstruction model that distills structured diffusion-prior inference into an efficient feed-forward network. NSDD learns to produce high-quality reconstructions that preserve measurement consistency while avoiding costly iterative sampling. Experimental results demonstrate that NSDD achieves perceptual quality and consistency competitive with diffusion-prior methods, while providing significantly faster inference and offering a favorable balance across all three objectives. Furthermore, ablation experiments show that distilling the range–null decomposition improves reconstruction quality and robustness over unstructured full-reconstruction distillation, including on unseen real scenes. These results highlight the potential of structure-aware distillation for efficient lensless imaging. Code is available at github.com/JRCSAVSN/NullSpaceDiffusionDistillation.

02.
arXiv (CS.CV) 2026-06-19

Occ-VLM: Occupancy Grounded Vision Language Model for Indoor Scene Understanding

Recently, vision-language models (VLMs) have made significant progress in 3D scene understanding, driving advances in applications such as embodied intelligence and robotic vision. However, existing approaches typically either rely directly on explicit 3D inputs (e.g., point clouds or RGB-D sequences), or introduce an additional 3D geometry encoder to derive 3D-aware visual tokens from 2D images. Such designs structurally decouple 3D geometric perception from the rich 2D semantics learned via vision-language pre-training, hindering the development of a unified 3D vision-language representation. In this work, we propose Occ-VLM, a novel framework for 3D scene understanding that operates purely on posed RGB images and employs a single 2D vision encoder. Specifically, Occ-VLM reconstructs 3D scene occupancy as an auxiliary geometric prior, which is utilized to spatially associate foreground 2D tokens with 3D space. These tokens are then decoded by a Large Language Model (LLM) for unified scene understanding. Extensive experiments demonstrate that Occ-VLM achieves both accurate geometric perception and robust vision-language reasoning: it attains state-of-the-art performance on multi-view occupancy prediction, while performing on par with 3D-input VLMs on 3D Visual Question Answering (VQA) and 3D dense captioning benchmarks.

03.
bioRxiv (Bioinfo) 2026-06-18

Bayesian modeling of longitudinal metatranscriptomes of broiler meat spoilage microbiomes shows shared predictive signature associated with spoilage at refrigerated temperatures

Microbial spoilage of packaged meat is driven by complex microbial succession and related metabolic activity, yet conventional shelf-life assessment is mainly based on shelf-life studies relying on culturing and sensory analysis. In routine quality assurance, results are obtained retrospectively, and they are only indirectly linked to the metabolic activity related to sensory deterioration. Functional, time informative approaches that capture the active metabolic state of the spoilage microbiome and predict the rate of spoilage are lacking. We developed a censoring-aware Gaussian process (CAGP) framework to model longitudinal pathway expression profiles from broiler meat metatranscriptomes collected over consecutive storage days at 4 or 6{degrees}C. Samples were annotated using odor-based sensory scores defining fresh, early-spoilage, and late-spoilage phases. Because observed zeros in pathway-level data may reflect non-detection rather than true absence, the model treats low values as left-censored observations below a detection threshold while estimating smooth temporal trajectories with uncertainty. In leave-one-out prediction within the 4{degrees}C time series, predicted sampling days differed from the true days by an average of 0.43 days, and predicted spoilage phases agreed with the sensory classification. Trajectories learned at 4{degrees}C also transferred to an independent 6{degrees}C time series at the spoilage-phase level, suggesting that shared functional spoilage programs are preserved despite temperature-dependent changes in spoilage rate. Cross-entropy ranking further identified pathway modules carrying time- and phase-informative signals across temperatures. Overall, this framework provides a probabilistic approach for linking metatranscriptomic functional dynamics to sensory spoilage progression, supporting shelf-life assessment beyond retrospective microbial enumeration.

04.
arXiv (quant-ph) 2026-06-11

Sharing quantum indistinguishability with multiple parties

arXiv:2512.15199v3 Announce Type: replace Abstract: Quantum indistinguishability of non-orthogonal quantum states is a valuable resource in quantum information applications such as cryptography and randomness generation. In this article, we present a sequential state-discrimination scheme that enables multiple parties to share quantum uncertainty, in terms of the max relative entropy, generated by a single party. Our scheme is based upon maximum-confidence measurements and takes advantages of weak measurements to allow a number of parties to perform state discrimination on a single quantum system. We review known sequential state discrimination and show how our scheme would work through a number of examples where ensembles may or may not contain symmetries. Our results will have a role to play in understanding the ultimate limits of sequential information extraction and guide the development of quantum resource sharing in sequential settings.

05.
bioRxiv (Bioinfo) 2026-06-18

Structure-Based Immunoinformatics Design of a CTB-Adjuvanted Multi-Epitope Mucosal Vaccine Against Helicobacter pylori

Background: Helicobacter pylori coloniz the gastric mucosa of nearly half of the global population and is classified as a Group I carcinogen by the World Health Organization due to its strong association with gastric cancer. The growing prevalence of antibiotic-resistant H. pylori strains significantly compromises current therapeutic strategies, emphasizing the urgent need for effective prophylactic approaches. Research design and methods; In this study, a novel multi-epitope vaccine was designed targeting H. pylori, incorporating epitopes from four key virulence proteins: BabB, SabB, SabA, and VacA. Using an immunoinformatics-guided structural vaccinology approach, B- and T-cell epitopes were predicted, prioritized based on immunogenicity, conservation, population coverage, and non-homology to human proteins, and assembled into the final vaccine construct. To enhance immunogenicity and specifically stimulate mucosal immune responses, the cholera toxin B subunit (CTB) was fused at the N-terminal via an EAAAK linker, a novel application in H. pylori multi-epitope vaccines. The PADRE universal epitope and additional linkers were incorporated to optimize epitope presentation and helper T-cell activation. Results: Comprehensive evaluations of physicochemical, antigenic, allergenic, and toxic properties were conducted, followed by secondary and tertiary structure modeling, refinement, and validation. Conformational B-cell epitopes were mapped, and molecular docking, binding affinity analysis, energy minimization, and molecular dynamics simulations confirmed structural stability and receptor interactions. Codon optimization and in silico cloning predicted efficient expression in Escherichia coli, while immune simulations suggested robust humoral and cellular responses. Conclusions: This study presents a promising multi-epitope vaccine candidate against H. pylori, offering a rational framework for future experimental validation and potential clinical application.

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

A Convex Quasilinearization Method for Solving Nonlinear PDEs with Physics-Informed Neural Networks

arXiv:2606.18175v1 Announce Type: cross Abstract: We present a numerical method for the forward solution of nonlinear partial differential equations (PDEs) in which Bellman-Kalaba quasilinearization reduces the nonlinear problem to a sequence of linear subproblems, each discretized by collocation onto a trial space that is linear in its parameters and solved by a single direct linear least-squares QR factorization. The trial space, which we term Linear-in-Learnables (LiL), comprises representations whose trainable parameters enter linearly, including random-feature extreme learning machines, spectral polynomial bases, and trigonometric expansions, each implemented as a physics-informed neural network. The method thus replaces the nonconvex gradient-based training that limits standard PINNs with a convex per-step solve. We establish local Newton-Kantorovich convergence of the outer iteration to a residual-limited neighborhood under an explicit smallness condition, with the limiting accuracy governed by the best-approximation residual of the trial space rather than by an optimization tolerance. The method, denoted LiL-Q, is assessed on seven benchmarks spanning scalar nonlinear PDEs (Bratu, viscous Burgers, Buckley-Leverett), coupled systems (plane-strain elasticity and the incompressible Navier-Stokes equations in two and three spatial dimensions), and steady-state Darcy flow with heterogeneous permeability. Across these problems, LiL-Q converges in single-digit outer iterations in most cases, even at the coarsest basis sizes and independent of the parameter count. When the exact solution lies in the span of the trial space, the method recovers it to machine precision in a single solve. On the Navier-Stokes benchmarks, it matches or exceeds published PINN solvers with up to two orders of magnitude fewer trainable parameters, without gradient-based optimization.

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

Quantifying Aleatoric Uncertainty of In-Context Learning for Robust Measure of LLM Prediction Confidence

In-Context Learning (ICL) allows LLMs to adapt to new tasks from a few demonstrations, but its reliability remains a concern: predictions are highly sensitive to both prompt design and the model's ability to understand the context, obscuring whether failures arise from data properties or model limitations. Uncertainty decomposition-separating aleatoric from epistemic sources-is particularly crucial in this setting, yet existing methods, designed for standard generation tasks, fail to capture the unique dynamics of ICL. To address this, we introduce a concept of self-function vectors, built upon Bayesian views and the mechanistic interpretability of ICL. These vectors leverage internal model representations to model the latent concept learned during in-context prompting, thereby enabling a direct estimation of aleatoric uncertainty within a Bayesian framework and circumventing the reliance on brittle input or decoding manipulations. Given the lack of established benchmarks and suitable evaluation protocols, we also propose the first and rigorous evaluation protocol, in which data is manipulated in controlled ways so as to quantify aleatoric uncertainty precisely and separately from epistemic uncertainty. With this new evaluation framework, initially grounded in synthetic tasks for conceptual development and subsequently extended to real-world datasets, we show that our proposed methodology can measure uncertainty of LLM predictions made under ICL more reliably than existing alternative methods. Moreover, we show it can be used as a practical tool for trustworthy-related applications, such as hallucination detection. Our findings pave a new direction for connecting the quantitative view of uncertainty with the mechanistic understanding of model behavior.

08.
arXiv (CS.AI) 2026-06-15

VikingMem: A Memory Base Management System for Stateful LLM-based Applications

arXiv:2605.29640v3 Announce Type: replace Abstract: Large Language Models have revolutionized interactive applications; however, their finite context windows pose a critical data management challenge for maintaining stateful, long-term interactions. Existing memory approaches often rely on simplistic extraction methods that lead to incomplete memories or use rigid, single-purpose memory extraction prompts tailored to a single use case, such as chatbots. Consequently, they lack generalizability and perform poorly across diverse downstream tasks. To bridge this gap, we introduce the Memory Base, a novel data management paradigm for managing the persistent state of long-term interactions. It is characterized by three core principles: selective extraction of high-value memories from raw information streams; inherent statefulness and evolution, where memory content is progressively summarized, corrected, and temporally weighted to prioritize recent interactions; and a generalizable abstraction paradigm designed for robust transferability across diverse applications, including education, recommendation, and agent memory. Building on this foundation, we present VikingMem, an end-to-end Memory Base Management System implemented on the VikingDB vector engine. VikingMem materializes this paradigm through interconnected event and entity abstractions. It features event-centric memory extraction to selectively handle complex information streams, while entities are dynamically updated by events to achieve stateful evolution. Using temporal compression via a topic-wise timeline and time-weighted recall, the system progressively produces high-level summary memories, prioritizes recent items, and compresses and fades older ones. Extensive evaluations on long-term memory benchmarks demonstrate that VikingMem outperformes baselines by up to 30% in memory retrieval effectiveness while maintaining the low latency essential for interactive applications.

09.
medRxiv (Medicine) 2026-06-15

CDH13 is associated with cellular viability after exposure to ionizing radiation using genome-wide screening

Background: It is well known that genetic variants contribute to cellular sensitivity to chemotherapeutic agents and ionizing radiation (IR). The aim of this study was to identify single nucleotide polymorphisms (SNPs) and genes associated with the spectrum of normal cellular sensitivity of lymphoblastoid cell lines (LCLs) towards ionizing radiation and mitomycin C (MMC). Methods: In a first step, we determined the viability of LCLs established from male participants of the Berlin Aging Study II (BASE-II) aged >=62 years following treatments with increasing doses of IR (n=137 cell lines) or MMC (n=140 cell lines) using the alamarBlue assay. Results from intra-experimental triplicates and three independent experiments for each cell line and treatment were used to calculate the area under the curves (AUCs) representing the specific sensitivity to IR and MMC of each LCL. The data from these experiments were subsequently used as outcomes in genome-wide association studies (GWASs). In addition, we calculated polygenic risk scores (PGS) from UK Biobank GWAS results for four cancer-related phenotypes and assessed the extent to which the variance in the IR and MMC sensitivity is explained by these PGS. Results: The GWAS analyses revealed one variant, rs74728080, located in CDH13 on chromosome 16, to show genome-wide significant (p < 5 x 10-8, beta = 2.81) association with cellular viability after treatment with IR. In the GWAS on MMC sensitivity the most interesting signal was elicited by SNP rs113978558 in an intron of the PLD5 gene on chromosome 1 (p = 9.232 x 10-8; beta = 1.44). Several other SNPs with statistically suggestive (i.e., p < 1 x 10-5) evidence of association with IR or MMC sensitivity were identified. PGSs calculations from GWAS of four cancer-related traits in UKB explained ~5% and ~3% of phenotypic variance in IR- and MMC-induced cell viability, respectively. Conclusion: The genome-wide significant association of rs74728080 with IR sensitivity and the location of this variant in CDH13 is interesting and functionally highly plausible given its known involvement in oxidative-stress response and function as tumor suppressor. Taken together, our novel data suggest that CDH13 may be genuinely involved in regulating cellular IR sensitivity.

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

Adaptive and Explicit safe: Triggering Latent Safety Awareness in Large Reasoning Models

arXiv:2606.16808v1 Announce Type: new Abstract: While Large Reasoning Models (LRMs) excel at complex tasks, they remain highly vulnerable to sophisticated jailbreaks and direct harmful queries. To address this vulnerability, prior works depend heavily on external manual data annotation for safety alignment. However, we observe that LRMs can inherently identify safety risks when being re-presented with original queries alongside their own reasoning trajectories – a capability we term Latent Safety Awareness. To leverage this safety awareness, we first employ Supervised Fine-Tuning (SFT) to explicitly induce safe tags to trigger safety analysis and guidance following the initial reasoning content for unsafe queries, while preserving standard responses for general queries to ensure adaptive triggering. Subsequently, we apply Direct Preference Optimization (DPO) to further enhance the correctness and stability of the safety analysis and guidance. Notably, responses required for both training stages are entirely generated by models being optimized. With (Safe Trigger) SFT and DPO, experimental results demonstrate significant safety enhancement. For example, the Attack Success Rate (ASR) of DeepSeek-R1-Distill-Llama-8B, on average, drops 24.65% and 36.72% on harmful and jailbreak benchmarks, respectively. Finally, our Safe Trigger method exerts almost no negative impact on general performance or user experience.

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

EKF-Based Depth Camera and Deep Learning Fusion for UAV-Person Distance Estimation and Following in SAR Operations

arXiv:2602.20958v2 Announce Type: replace-cross Abstract: Vision-based Unmanned Aerial Vehicles (UAVs) frameworks aid human search tasks by detecting and recognizing specific individuals, then tracking and following them while maintaining a safe distance. A key safety requirement for UAV following is the accurate estimation of the distance between camera and target object under real-world conditions, achieved by fusing multiple image modalities. As part of the system for automatic people detection and face recognition using deep learning, in this paper we present the fusion of depth camera measurements and monocular camera-to-body distance estimation for robust tracking and following. Deep learning based filtering of depth camera data and estimation of camera-to-body distance from a monocular camera are achieved with YOLO-pose, enabling real-time fusion of depth information using the Extended Kalman Filter (EKF) algorithm. The proposed subsystem, designed for use in drones, estimates and measures the distance between the depth camera and the human body keypoints, to maintain the safe distance between the drone and the human target. Our system provides an accurate estimated distance, which has been validated against motion capture ground truth data. The system has been tested in real time indoors, where it reduces the average errors, RMSE and standard deviations of distance estimation up to 15,3% in three tested scenarios. Based on the test results, the EKF fusion-based approach increases the depth detection range by reducing the errors outside the optimal depth camera working range. It also shows improved robustness and precision in challenging conditions, such as reflections and poor visibility, making it suitable for SAR.

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

S-GBT: Smooth Growth Bound Tensor for Certified Robustness Against Word Substitution Attacks in NLP

Despite recent progress in Natural Language Processing (NLP), models remain vulnerable to word substitution attacks. Most existing defenses focus on first order sensitivity and measure how much the output changes when the input is slightly perturbed. However, they ignore how this sensitivity evolves, which is described by curvature. When gradients vary sharply, models can still fail. This paper introduces the Smooth Growth Bound Tensor (S-GBT), a second order method that bounds the Hessian element-wise, for which we provide formal theoretical proofs on the resulting robustness bounds. A regularization term is added during training to minimize these bounds. This yields tighter certified robustness against word substitution attacks. The change in the output under word substitution is bounded by both a linear term and a quadratic term. S-GBT is derived for two architectures: Long Short-Term Memory (LSTM) and Convolutional Neural Networks (CNN). The method is integrated directly into the training objective. Its effectiveness is evaluated on multiple benchmark datasets. The results show that combining first and second order regularization improves certified robust accuracy by up to 23.4% compared to prior methods, while clean accuracy remains competitive. These findings indicate that controlling both the gradient and its variation is a promising direction for building more robust models.

13.
arXiv (CS.AI) 2026-06-11

Sample-Efficient Hypergradient Estimation for Decentralized Bi-Level Reinforcement Learning

arXiv:2603.14867v4 Announce Type: replace-cross Abstract: Many strategic decision-making problems, such as environment design for warehouse robots, can be naturally formulated as bi-level reinforcement learning (RL), where a leader agent optimizes its objective while a follower solves a Markov decision process (MDP) conditioned on the leader's decisions. In many situations, a fundamental challenge arises when the leader cannot intervene in the follower's optimization process; it can only observe the optimization outcome. We address this decentralized setting by deriving the hypergradient of the leader's objective, i.e., the gradient of the leader's strategy that accounts for changes in the follower's optimal policy. Unlike prior hypergradient-based methods that require extensive data for repeated state visits or rely on gradient estimators whose complexity can increase substantially with the high-dimensional leader's decision space, we leverage the Boltzmann covariance trick to derive an alternative hypergradient formulation. This enables efficient hypergradient estimation solely from interaction samples, even when the leader's decision space is high-dimensional. Additionally, to our knowledge, this is the first method that enables hypergradient-based optimization for 2-player Markov games in decentralized settings. Experiments highlight the impact of hypergradient updates and demonstrate our method's effectiveness in both discrete and continuous state tasks.

14.
arXiv (CS.CV) 2026-06-24

3DCarGen: Scalable 3D Car Generation via 3D-consistent Multi-view Synthesis

High-quality 3D vehicle assets are essential for autonomous driving simulation. Although multi-view diffusion-based paradigms enable controllable single-image reconstruction, they typically produce limited viewpoints and exhibit cross-view geometric inconsistencies, thereby reducing reconstruction fidelity in real-world scenarios. In this work, we introduce 3DCarGen, a scalable single-view 3D car generation framework designed for real-world images by synthesizing an arbitrary number of 3D-consistent multi-view images. Specifically, given a single image as input, we first synthesize a set of images from fixed viewpoints. These images are then fed into a feed-forward reconstruction model, resulting in a coarse 3D representation based on 3D Gaussian Splatting. Conditioned on this explicit 3D prior, our multi-view diffusion model generates 3D-consistent images from arbitrary camera viewpoints. We further extend a fast mesh reconstruction algorithm by incorporating color-normal joint optimization to recover detailed and coherent 3D vehicle models from the synthesized dense views. Extensive experiments on synthetic and real-world datasets demonstrate that our approach achieves robust geometric consistency and reconstruction fidelity compared to existing methods. Code and models will be released.

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

Grammar-Constrained Decoding Can Jailbreak LLMs into Generating Malicious Code

Large Language Models (LLMs) are increasingly used for code generation, raising concerns that they may be misused to produce malicious code. Meanwhile, Grammar-Constrained Decoding (GCD) has been widely adopted to improve the reliability of LLM-generated code by enforcing syntactic validity. In this paper, we reveal a counterintuitive risk: this reliability-oriented technique can itself become an attack surface. We uncover a new jailbreak attack, termed CodeSpear, that exploits GCD to induce LLMs into generating malicious code. Our experiments show that simply applying a benign code grammar constraint can effectively jailbreak LLMs. To address this vulnerability, we propose CodeShield, a safety alignment approach that robustly preserves safe behavior even under attacker-controlled grammar constraints. CodeShield aligns the model in the code modality by teaching it to generate honeypot code under GCD. Such code is semantically harmless, so it does not implement the malicious request, and structurally diverse, so it is difficult to suppress through grammar tightening. At the same time, CodeShield still preserves natural-language refusals when natural language is available. Experiments on 10 popular LLMs across 4 benchmarks show that CodeSpear outperforms representative jailbreak baselines and increases the attack success rate by more than 30 percentage points on average. CodeShield also restores safety under CodeSpear while preserving benign utility. Our findings reveal a fundamental risk of GCD and call for greater attention to its potential security implications.

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

SSD: Spatially Speculative Decoding Accelerates Autoregressive Image Generation

Autoregressive models excel in visual generation by treating images as 1D sequences of discrete tokens, mirroring language modeling. However, this flattening discards the intrinsic 2D spatial locality of visual signals, creating severe computational bottlenecks during inference. We introduce Spatially Speculative Decoding (SSD), a framework that aligns the predictive objective with the natural geometry of images. Rather than predicting only the immediate next token in a 1D sequence, our model simultaneously predicts the adjacent horizontal token and the token directly below it. By capitalizing on this 2D spatial correlation, spatially speculative decoding overcomes the memory wall in visual inference. Our approach accelerates autoregressive image generation by up to 13.3x while maintaining high fidelity on DPG-Bench and GenEval. Our results suggest that respecting the underlying geometry of vision unlocks massive computational efficiencies, paving the way for real-time, high-resolution autoregressive generative models.

17.
medRxiv (Medicine) 2026-06-24

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing

Rare diseases collectively affect 1 in 10 individuals, yet current genetic testing fails to identify a causal variant for most cases. At present, cytogenetic methods and/or sequencing approaches such as exome (ES) or short-read genome sequencing (srGS) represent the state-of-the-art for comprehensive clinical discovery of sequence and structural variants (SVs), including copy number variants, balanced SVs, complex SVs, and tandem repeats (TRs). Recently, long-read genome sequencing (lrGS), coupled with multiomics data, has presented great promise to resolve variation in genomic regions recalcitrant to characterization by srGS such as highly repetitive simple repeat sequences and segmental duplications. However, there are few guidelines to enable clinical interpretation of genetic variation in these highly repetitive genomic regions, and the enthusiasm of the field in adopting lrGS has made it difficult to assess the true added diagnostic yield of this technology due to widely variable and inconsistently applied analytic pipelines and variable degrees of pre-screening by ES or srGS. Here, we investigated the contribution of SVs to rare diseases using srGS as a front-line strategy when paired with highly sensitive SV discovery and evaluate the added diagnostic yield of incorporating lrGS for a subset of cases. Our srGS analysis encompassed 1,462 families (3,450 individuals) recruited through the Broad Institute Center for Mendelian Genetics and the Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) programs. Diagnostic SVs were identified in 5.4% of cases (79/1,462), of which 80% were uniquely detectable by srGS compared to standard cytogenetic techniques. For 96 families (including 10 families with a heterozygous variant observed in a known recessive gene of clinical relevance), we performed lrGS with methylation profiling, as well as long-read transcriptomic analyses in a subset of 20 trios. Analyses with lrGS yielded over 25,000 SVs per genome, 63% of which were not captured by srGS, along with an additional ~200 rare SNV/indels per genome not previously captured and 12 differentially methylated regions per genome. Among these, we identified only one diagnostic variant not interpreted by srGS, an apparently mosaic de novo SNV in CASK that was absent in the srGS callset due to allelic imbalance. No new diagnoses were supported by long-read transcriptomics or episignatures. In this well characterized rare disease cohort, the added diagnostic yield was thus 1.04% (1/96 families). Following a systematic literature review of prior lrGS studies, we find that most reported diagnoses were detectable by srGS and that our added diagnostic yield is consistent with those prior studies. These studies emphasize the significant impact of comprehensive SV discovery in rare disease cases and further demonstrate the power for increased discovery of novel genomic variation and episignatures from lrGS. Nonetheless, they also serve to temper expectations of dramatic diagnostic advances in rare disease patients until there is more extensive annotation of the functional and clinical impact of all coding and noncoding variation uniquely accessible to lrGS with extensive reference databases spanning highly repetitive genomic sequencing that could be enabled by this transformative technology.

18.
bioRxiv (Bioinfo) 2026-06-14

TopoMIL: Topology Improves Multiple Instance Learning in Diagnostic Microscopic Images

Microscopic images of cells and tissues are central to disease diagnosis. In computational pathology, multiple instance learning (MIL) has emerged as a key paradigm for analyzing numerous images within a single patient sample. While the representative distribution of cells in a sample is important for diagnosis, existing MIL frameworks largely overlook it. We introduce TopoMIL, a framework that extracts the representative topological structure of the sample and integrates it into the MIL classifier. Three topological representations are assessed, each with distinct advantages and computational costs. We evaluate TopoMIL on four histopathology and cytomorphology datasets, each presenting unique challenges. Integrating the sample's topological information into MIL enhances classification across average, max, attention-based, and transformer pooling, yielding AUCROC gains of 3.3%, 4.2%, 5.9%, and 0.5%, respectively, with moderate computational cost. Our work underscores the potential of TopoMIL as a scalable extension to existing morphology-based models in computational pathology.

19.
arXiv (CS.CL) 2026-06-12

Recursive Agent Harnesses

Recursive language models (RLMs) showed that recursion over model calls is an effective strategy for long-context reasoning, and production coding agents have begun to write code that spawns subagents at scale, most recently in Anthropic's dynamic workflows. We name and study the pattern between these two lines of work, where the recursive unit is a full agent harness with filesystem tools, code execution, and planning rather than a model call with no tools. We call this the Recursive Agent Harness (RAH) and frame it as harness recursion, the code-first extension to the model recursion of RLMs. A parent agent generates and runs an executable script that spawns subagent harnesses in parallel for fine-grained workloads and uses structured function calls for small subtasks. We provide a controlled evaluation on long-context reasoning. With the backbone held fixed at GPT-5 to match the published Codex and RLM baselines, RAH improves the Codex coding-agent baseline from 71.75% to 81.36% on Oolong-Synthetic (199 samples, 13 context-length buckets up to 4M tokens), a gain attributable to the harness rather than the model. With a stronger backbone, Claude Sonnet 4.5, the same design reaches 89.77%.

20.
bioRxiv (Bioinfo) 2026-06-12

PeptiDIA: A Machine Learning Framework for Enhanced Peptide Identification in Fast-Gradient Data-Independent Acquisition Proteomics

Data-independent acquisition (DIA) mass spectrometry has become increasingly prevalent in proteomics as advances in instrumentation, chromatography, and computational analysis have enabled robust proteome identification across complex biological samples. However, analytical depth achieved with fast chromatographic gradients remains lower than that obtained using long-gradients, reflecting a throughput-depth trade-off. Here, we present PeptiDIA, a machine learning framework that enhances peptide identification in fast-gradient DIA data by leveraging paired fast and long-gradient acquisitions from identical samples. PeptiDIA processes DIA-NN outputs generated at relaxed false discovery rate thresholds to obtain expanded candidate peptide pools and trains gradient-boosted decision tree models using long-gradient identifications as reference labels. The model integrates DIA-NN features with engineered peptide descriptors and applies isotonic regression to calibrate probabilities, enabling controlled peptide recovery relative to the long-gradient reference. Applied to human and murine datasets spanning six tissues acquired on an Orbitrap Exploris 480, PeptiDIA increased peptide identifications by 25-34% at 1% target reference-discordance rate (RDR) and increased the number of protein groups containing at least one rescued peptide by 15-17%. Overall, PeptiDIA improves the identification depth of fast-gradient DIA-NN workflows without altering acquisition strategies. The framework is available as a web application and command-line tool at https://github.com/Jordano700/PeptiDIA.

21.
arXiv (CS.LG) 2026-06-24

Natural Identifiers for Privacy and Data Audits in Large Language Models

arXiv:2606.24408v1 Announce Type: new Abstract: Assessing the privacy of large language models (LLMs) presents significant challenges. In particular, most existing methods for auditing differential privacy require the insertion of specially crafted canary data during training, making them impractical for auditing already-trained models without costly retraining. Additionally, dataset inference, which audits whether a suspect dataset was used to train a model, is infeasible without access to a private non-member held-out dataset. Yet, such held-out datasets are often unavailable or difficult to construct for real-world cases since they have to be from the same distribution (IID) as the suspect data. These limitations severely hinder the ability to conduct scalable, post-hoc audits. To enable such audits, this work introduces natural identifiers (NIDs) as a novel solution to the above-mentioned challenges. NIDs are structured random strings, such as cryptographic hashes and shortened URLs, naturally occurring in common LLM training datasets. Their format enables the generation of unlimited additional random strings from the same distribution, which can act as alternative canaries for audits and as same-distribution held-out data for dataset inference. Our evaluation highlights that indeed, using NIDs, we can facilitate post-hoc differential privacy auditing without any retraining and enable dataset inference for any suspect dataset containing NIDs without the need for a private non-member held-out dataset.

22.
arXiv (CS.CV) 2026-06-15

Pix2Pix-Hybrid: Structure-Guided Conditional Synthesis of Hajj Crowd Images with Multi-Channel Conditioning and Weak Attribute Supervision

Developing accurate crowd-counting models for Hajj pilgrimage scenes remains challenging because domain-specific annotated images are scarce and data collection during large gatherings raises privacy concerns. To address these limitations, this paper proposes Pix2Pix-Hybrid (P2P-H), a hybrid conditional GAN for structure-guided Hajj crowd-image synthesis and data augmentation. P2P-H builds on Pix2Pix and employs a U-Net generator conditioned on eight input channels that jointly encode structural cues (edges and grayscale) and contextual attributes (crowd density and time of day). To capture detailed textures in dense scenes, the framework integrates two multi-scale PatchGAN discriminators operating at different resolutions. The training procedure combines adversarial, perceptual, and feature-matching objectives with adaptive data augmentation and stabilization strategies. The model was trained on 993 real Hajj frames collected from 60 publicly available video sources, with conditioning attributes derived automatically to reduce manual labeling effort. Using this framework, we constructed CrowdH, a synthetic dataset of 10,000 high-resolution Hajj crowd images. Experimental results show that P2P-H improves structure-preserving conditional synthesis quality compared with Pix2Pix and StyleGAN2-ADA baselines and shows favorable transfer to other crowd datasets. To assess downstream utility, we further constructed CrowdH-Mix-469, an annotated mixed real-synthetic dataset comprising 384 real Hajj images and 85 selected synthetic images,and evaluated five crowd-counting models under real-only and real-plus-synthetic training. The selected synthetic data reduced MAE across all five models, with the strongest gain observed for CSRNet.

23.
arXiv (CS.AI) 2026-06-18

UBP2: Uncertainty-Balanced Preference Planning for Efficient Preference-based Reinforcement Learning

arXiv:2606.19328v1 Announce Type: cross Abstract: Preference-based RL provides an approach to learning reward models from pairwise comparisons of behaviors, bypassing the need for explicit reward design. However, existing methods typically rely on passive data collection and suffer from poor sample efficiency, especially during the early stages of learning. We introduce a model-based approach that actively directs exploration by jointly reasoning over uncertainties in the reward, dynamics, and value functions. Our method, Uncertainty-Balanced Preference Planning (UBP2), uses ensembles of reward, dynamics, and value function models to evaluate candidate trajectories according to a unified score that combines expected reward, terminal value, and epistemic uncertainty. Planning under this objective yields an explicit tradeoff between exploitation and information acquisition without requiring ad hoc exploration heuristics. Under standard regularity assumptions, we establish sublinear regret guarantees for both finite-horizon and infinite-horizon settings. Empirically, experiments on the Meta-World benchmark show UBP2 achieves substantially higher sample efficiency than model-free preference-based methods and non-optimistic model-based baselines.

24.
PLOS Computational Biology 2026-06-05

Heuristic multi-site optimization for protein sequence design using Masked Protein Language Models

作者:

by Lijuan Wang, Yuze Wang, Chen Qiu, Liwei Xiao, Xianliang Liu, Junjie Chen Protein sequence design for tailored functional properties is a fundamental task in protein engineering, with critical applications in drug discovery and therapeutic development. Efficient navigation of the combinatorial vastness of protein sequence space to identify functional variants remains a formidable challenge. Conventional approaches, which predominantly rely on template-based local search or single-residue mutagenesis, are constrained by their susceptibility to local optima and their potential risk of destabilizing native structural stability. In this study, we introduce ProtHMSO, a heuristic multi-site optimization framework leveraging masked protein language models (ProtLMs) for context-aware sequence exploration. ProtHMSO mimics natural evolutionary mechanisms by employing ProtLM-derived substitution probabilities to guide heuristic searches for synergistic mutations, thereby constraining combinatorial search spaces through evolutionary and biophysical priors. ProtHMSO is further applied to replace the exploration strategies in genetic algorithms (GAs) and Monte Carlo tree search (MCTS) for improving their convergence efficiency. Benchmark experiments demonstrate that protein sequences generated by ProtHMSO exhibit superior functional performance and closer alignment with natural sequence distribution, compared with state-of-the-art methods. These advancements highlight that ProtHMSO has strong potential and compatibility to accelerate functional protein discovery, offering a robust framework for efficient and context-aware exploration of protein sequence space.

25.
arXiv (CS.AI) 2026-06-18

Towards Understanding What State Space Models Learn About Code

arXiv:2602.06774v2 Announce Type: replace Abstract: State Space Models (SSMs) have emerged as an efficient alternative to the Transformer architecture. Prior work shows that, when trained under comparable conditions, SSMs can match or surpass Transformers on code understanding tasks. However, their internal mechanisms remain a black box. We present the first systematic analysis of what SSM-based code models learn along with the direct comparison between SSM and Transformer models in this domain. Our analysis shows that SSMs capture syntactic and semantic structure more effectively than Transformers during pretraining but forgets certain relations during fine-tuning on some tasks. To investigate this behavior, we introduce SSM-Interpret, a frequency-domain framework that exposes a spectral shift toward short-range dependencies during fine-tuning. Guided by these findings, we propose architectural modifications that significantly improve the performance of SSM-based code model by upto +6 MRR on NLCodeSearch. This demonstrates that our analysis not only explains model behavior but also leads directly to better designs.