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01.
arXiv (CS.LG) 2026-06-19

Influence-Guided Concolic Testing of Transformer Robustness

arXiv:2509.23806v2 Announce Type: replace-cross Abstract: Concolic testing for neural networks alternates concrete execution with constraint solving to search for inputs that flip model decisions. We present a concolic tester for Transformer classifiers that uses SHAP estimates to rank pending path predicates by their impact on the current prediction. To support self-attention with multiple heads in execution backed by SMT solving, we implement attention semantics in pure Python that are compatible with the solver and make the softmax boundary explicit by concretizing exponentiation arguments. We evaluate our method on CIFAR-10 across three compact Transformer classifiers, ResNet18, and VGG16 under a one-pixel budget and a 900s horizon. Across the 500 model–input pairs in this matched comparison, our method achieves 60% success, compared with 15% for a differential evolution baseline that treats the model as a black box. In the primary two-layer Transformer branch-ordering study, SHAP-based predicate prioritization raises success from 56% to 60% and reduces median attack time by 51%. These results show that influence-guided path exploration can make concolic testing a practical way to find adversarial examples in Transformer models.

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

Temporal Difference Learning for Diffusion Models

Diffusion models are typically trained with objectives that focus on local denoising targets at individual time steps (or adjacent pairs), which do not enforce consistency between predictions along the denoising trajectory. This lack of cross-time consistency can degrade performance, especially for few-step samplers. We introduce a temporal difference (TD) objective that penalizes inconsistency of the model's multi-step progress along the denoising path. By reformulating the diffusion process as a Markov reward process and casting denoising as a policy evaluation problem in reinforcement learning, we derive a unified TD approach that applies to both discrete- and continuous-time diffusion formulations. We further propose a principled sample-based reweighting method that stabilizes training. Empirically, we show that using our TD training can significantly improve sample quality measured by FID, with stronger advantages when the number of sampling steps is small, highlighting its practical utility under low-computation-budget scenarios. We provide ablation studies to justify our design choices, including pairwise loss reweighting, regularization weight, and one-step stride. Overall, our TD approach can be a general drop-in that enforces cross-time consistency and improves generation quality across different diffusion generative models.

03.
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.

04.
medRxiv (Medicine) 2026-06-24

Generative AI avatar videos for tobacco prevention on social media: a randomized controlled trial

Short-form video platforms increasingly shape how young audiences encounter health information. Generative artificial intelligence can produce standardized avatar-based messages at scale, but randomized evidence for tobacco prevention is scarce. In this three-arm randomized online intervention study with pre-post assessment, participants aged 16 years or older were assigned to an AI avatar video emphasizing short-term smoking consequences, an AI avatar video presenting long-term cancer-related information matched to an American Cancer Society fact sheet, or the same fact sheet in written form. The primary outcome was post-intervention intention to avoid smoking and secondhand smoke exposure, adjusted for baseline intention. Among 400 randomized participants, 272 had complete data for the primary baseline-adjusted analysis. Intention increased from baseline to post-intervention in all conditions, with no statistically significant between-group differences. These findings support AI avatar videos as a scalable, social-media-compatible format for digital tobacco prevention, while not establishing superiority or equivalence.

05.
arXiv (CS.LG) 2026-06-16

Bayesian Networks with Latent Time Embedding for Stage-Aware Causal Modeling of Alzheimer's Disease Progression

arXiv:2606.15784v1 Announce Type: new Abstract: Alzheimer's disease (AD) progression is often described through the amyloid-tau-neurodegeneration, or AT(N), cascade. However, most longitudinal models represent this cascade either as a fixed sequence of biomarkers or as a black-box forecasting task. This makes it difficult to determine when biologically guided biomarker relationships influence future regional pathology. In this study, we introduce Bayesian Networks with Latent Time Embedding (BN-LTE), a Bayesian structural framework for stage-aware modeling of AD progression. BN-LTE estimates disease pseudotime from baseline biomarker profiles and constrains directed dependencies according to biologically plausible AT(N) ordering. Posterior spline-varying structural equations are then used to link initial multimodal measurements with future annualized regional tau-PET change. Across repeated subject-disjoint evaluations using ADNI data, BN-LTE shows strong spatial reconstruction of tau progression compared with the included forecasting baselines. Beyond spatial reconstruction, BN-LTE recovers posterior stage-varying AT(N)-constrained effects and identifies a mid-pseudotime window of amyloid sensitivity. This window is supported by model-implied g-formula contrasts, root-adjusted AIPW, mechanism-sensitive ablations, and robustness analyses across spline and prior specifications. Overall, these findings position BN-LTE as a Bayesian structural framework for forecasting tau progression while examining stage-dependent AT(N)-cascade mechanisms in observational longitudinal neuroimaging data. Our code is available at https://github.com/danleneurocom/BN-LTE.

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

Improving Crash Frequency Prediction from Simulated Traffic Conflicts Using Machine Learning Based Microsimulation

arXiv:2606.12500v1 Announce Type: cross Abstract: Traffic microsimulation combined with surrogate safety measures has increasingly been used as a proactive alternative to historical crash data for predicting crash frequency for current or planned road infrastructure designs. However, existing microsimulation-based safety studies have adopted simplified rule-based behaviour models, which reproduce traffic flow reasonably well but often fail to generate realistic conflict dynamics, limiting crash prediction accuracy. Recent advances in machine learning (ML)-based behaviour models offer a promising opportunity to potentially improve microsimulation realism and crash frequency predictions by learning human driving behaviour directly from large-scale trajectory datasets. To investigate this possibility, traffic microsimulation was conducted for five real-world signalised intersections in Leeds, UK, using both a standard rule-based model and a state-of-the-art ML model. Simulated vehicle trajectories were analysed using a two-dimensional Time-to-Collision metric to identify simulated conflicts, which were then modelled using Extreme Value Theory to predict crash frequency. Results show that conflicts from the ML model yielded crash predictions in line with the real-world crash data, whereas the rule-based model did not permit meaningful predictions, presumably due to a lack of model calibration to the specific simulated intersections. Directly using ML-generated simulated crashes to predict real-world crash frequency also yielded poor results, suggesting that while current ML models can realistically reproduce conflicts, they are not yet able to generate realistic crashes. Overall, the findings demonstrate that ML-based behaviour models are promising for improving crash prediction from simulated conflicts, without a need for location-specific model calibration, and suggest clear future directions for ML-based traffic microsimulation.

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

Flexible Catalysis

arXiv:2510.01065v2 Announce Type: replace Abstract: In quantum information and computation, a central challenge is to determine which quantum states can be transformed into which others under restricted sets of free operations. While many transformations are impossible directly, catalytic processes can enable otherwise forbidden conversions: an auxiliary quantum state (the catalyst) facilitates the transformation while remaining unchanged. In this work, we introduce flexible catalysis, a generalization in which the catalyst is allowed to transform into a different auxiliary state, provided it remains a valid catalyst. We show that this framework subsumes both standard catalytic and multicopy transformations, and we analyse its advantages across several classes of free operations. In particular, we prove that when the free operations are local unitaries or permutation matrices, flexible catalysis enables state extractions that are unattainable with standard catalysis alone.

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

Communication Policy Evolution for Proactive LLM Agents

arXiv:2606.14314v1 Announce Type: new Abstract: LLM agents have rapidly evolved into autonomous systems, yet a persistent information gap remains between users and agents: communication is costly, while users' identical preferences further limit information exchange. To investigate how agents should communicate across modalities, this paper formalizes Communication Policy, establishes textual and UI-based policies, and then evaluates communication policies across diverse environments, personas, and model combinations. Building information asymmetry for proactive agents, we set up two complementary settings, User-Agent and Planner-Executor. Experimental results reveal complementary strengths between interaction channels: text-based interaction often facilitates task performance, while structured UI improves agents' response quality and persona compliance. Motivated by that, a hybrid method combines these advantages. We further propose Communication Policy Evolution (CPE), a self-evolution framework for refining communication policies through rollout and prompt-level evolving. Without model modification, CPE achieves the best task success across multiple settings using prompt refinement alone. Our findings identify communication behavior as a critical yet underexplored design dimension for LLM agents.

09.
arXiv (math.PR) 2026-06-16

Universality in the target arrival statistics of non-conservative search processes

arXiv:2606.16025v1 Announce Type: cross Abstract: Stochastic search processes in which searchers are continuously introduced to and removed from a target search domain are fundamental to a wide class of physical and artificial systems. The theory of such non-conservative search processes is, however, much less developed than for search processes with a fixed number of particles. Here we exploit a natural mapping between non-conservative stochastic search and queueing theory to derive the full time-dependent distribution of target arrivals under minimal assumptions on the underlying search process. Remarkably, we find that the steady-state inter-arrival time distribution is exactly exponential, regardless of the details of the search process, showing a robust universality that emerges directly from the queueing framework. Thus, counterintuitively, the arrival statistics of a non-conservative search process are much simpler than sequential search-and-capture processes involving a fixed number of searchers. This has major implications for target resource accumulation, where the delivery of resources is counter-balanced by their downstream consumption.

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

BRDFusion: Physics Meets Generation for Urban Scene Inverse Rendering

Inverse rendering of urban scenes from captured videos enables numerous applications, including content creation and autonomous driving simulation. Physically-based rendering methods follow and control lighting physics, but suffer from reconstruction and rendering artifacts. While generative models produce realistic videos, they offer limited consistency and controllability. We present BRDFusion, a unified framework that combines two complementary models for inverse and forward rendering. Specifically, BRDFusion recovers explicit, consistent scene properties with physical modeling and alleviates optimization ambiguity with generative priors. During forward rendering, the physical model provides controllable rendering from the scene configuration, and the generative model denoises and fixes artifacts. Therefore, our method produces high-quality videos while allowing precise control, outperforming baselines in real and synthetic scenes. Moreover, BRDFusion supports novel-view relighting, night simulation, and dynamic object insertion/editing. Project page: https://shigon255.github.io/brdfusion-page/

11.
Nature (Science) 2026-06-12

‘Student Geng’ ignites research-integrity scandal in China after calling out senior academics<b> </b>

作者:

Video blogger’s viral accusations of data manipulation in Nature journals have sparked intense debate and speedy institutional investigations. Video blogger’s viral accusations of data manipulation in Nature journals have sparked intense debate and speedy institutional investigations.

12.
arXiv (CS.CV) 2026-06-25

MVTrack4Gen: Multi-View Point Tracking as Geometric Supervision for 4D Video Generation

Synthesizing a novel-view video from a monocular reference video along a target camera trajectory requires both geometric consistency and motion fidelity with respect to the reference video. Existing methods based on explicit 3D representations are limited by the accuracy of off-the-shelf reconstruction modules, which often produce inaccurate geometry for dynamic objects in monocular videos. In contrast, camera-conditioning-only methods can achieve high visual quality but often struggle to preserve geometric and motion consistency. In this work, we introduce MVTrack4Gen (Multi-View point Tracking for Novel-View Generation), a motion-aware training framework that leverages multi-view point tracking as an additional geometric and motion supervision signal for camera-conditioning-only novel-view video diffusion models. Our key finding is that specific attention layers encode strong correspondence cues, where query features attend to key features at geometrically corresponding locations across views and over time, and the misalignment of these correspondences causes motion inconsistency. Based on this observation, we route these features into an auxiliary multi-view tracking head and jointly train the diffusion model with a point-tracking objective. By explicitly strengthening these motion-aware correspondences, MVTrack4Gen improves existing models to better follow the motion in the reference view and maintain cross-view geometric consistency. Across diverse benchmarks, our method achieves state-of-the-art geometric consistency and competitive camera accuracy.

13.
arXiv (CS.CV) 2026-06-12

Distributional Loss for Robust Classification

This paper proposes a novel loss concept for supervised classification tasks. Rather than enforcing a direct mapping from each input sample to a single assigned label, we define an optimization objective over all classifier outputs as a bimodal Gaussian distribution. This softer target formulation implicitly captures class ambiguity, mitigates overfitting, and encourages the learning of more robust decision boundaries, all without requiring additional label information. Experimental results demonstrate consistent improvements in robustness, with particularly pronounced gains in low-data regimes, while requiring only minimal modifications to standard training pipelines.

14.
arXiv (CS.AI) 2026-06-15

Where's the Plan? Locating Latent Planning in Language Models with Lightweight Mechanistic Interventions

arXiv:2605.07984v2 Announce Type: replace-cross Abstract: We study planning site formation in language models – where internal representations of structurally-constrained future tokens form during the forward pass, and whether they causally drive generation. Using rhyming-couplet completion as a clean test of forward-looking constraint, we apply two lightweight methods (linear probing and activation patching) across Qwen3, Gemma-3, and Llama-3 at more than ten scales. Probing shows that future-rhyme information is linearly decodable at the line boundary, with signal that strengthens with scale in all three families. Activation patching reveals that only Gemma-3-27B causally relies on this encoding, exhibiting a handoff in which the causal driver migrates from the rhyme word to the line boundary around layer 30. Every other model we test conditions on the rhyme word throughout generation, with near-zero causal effect at the line boundary despite strong probe signal. We localize the Gemma-3-27B handoff to five attention heads through two-stage path patching that recover ~90% of the rhyme-routing capacity at the newline.

15.
arXiv (CS.CV) 2026-06-25

CustomX: Unified Character, Action, and Scene Customization in Video World Models

Recent advances in world models have greatly enhanced interactive environment simulation. Existing methods mainly fall into two categories: (1) static world generation models, which construct 3D environments without active agents, and (2) controllable-entity models, which allow a single entity to perform limited actions in an otherwise uncontrollable environment. In this work, we introduce CustomX, leveraging the realism and structural grounding of static world generation while extending controllable-entity models to support user-specified characters capable of performing open-ended actions. Users can provide a 3DGS scene and a character, then use natural language to direct the character to perform diverse behaviors, ranging from basic locomotion to object-centric interactions, while freely exploring the environment. CustomX synthesizes temporally coherent video clips that preserve visual fidelity with the provided scene and character, formulated as a conditional autoregressive video generation problem. Built upon a pre-trained video generator, our training strategy significantly enhances motion dynamics while maintaining generalization across actions and characters. Our evaluation covers a broad range of aspects, including visual quality, character consistency, action controllability, and long-horizon coherence.

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

Few-Shot Resampling for Scalable Statistically-Sound Data Mining

arXiv:2606.11235v1 Announce Type: new Abstract: A key step in knowledge discovery is the evaluation of data mining results. In several applications, including pattern mining, graph analysis, and others, this step includes the evaluation of the statistical significance of the results, to avoid spurious discoveries due only to noise or random fluctuations in the data. While specialized procedures have been developed for some specific applications, resampling-based approaches are widely used, in particular for complex analyses where analytical results cannot be derived. However, current resampling-based approaches require the generation and analysis of thousands of resampled datasets, and are therefore impractical for large datasets or computationally intensive analyses. In this paper, we introduce FewRS, a simple and effective resampling-based approach to assess the statistical significance of data mining results with rigorous guarantees on the probability of false discoveries. Our approach can be used in every situation where resampling-based approaches are applied. FewRS builds on our derivation of a novel bound to the supremum deviation of test statistics representing the quality of data mining results. We prove that FewRS needs to generate and analyze an extremely small number of resampled datasets, leading to a highly scalable approach with wide applicability. We test our approach on common tasks such as pattern mining and network analysis. In all cases, our approach results in a reduction of up to two orders of magnitude in running time compared to the state of the art, while preserving high statistical power, enabling the statistical validation of data mining results on large-scale real-world datasets.

17.
medRxiv (Medicine) 2026-06-24

MedGenesis: Toward a World Model for Autonomous Clinical and Translational Research

Clinical research advances slowly because its core tasks, from evidence synthesis to mechanistic validation, remain fragmented. We present MedGenesis, a clinical artificial intelligence (AI) scientist built on a world-model reasoning loop that jointly updates a Latent Hypothesis Space and a Latent Action Space under expected information gain (EIG), uncertainty reduction (UR), and a safety prior P(safe), and integrates longitudinal electronic health records (EHRs) via the Virtual Clinical Trajectory and Observation Representation (ViCTOR) for cohort retrieval, trajectory stratification, and time-to-event analysis. On two benchmarks - ClinicalResBench (1,697 expert-curated questions) and ClinicalRepBench (40 paper-reproduction tasks) - MedGenesis outperformed frontier language models and biomedical AI systems while reducing hallucination. Across 1 million patient observations spanning five clinical evidence formats, it generated traceable outputs across meta-analysis, randomized controlled trials, real-world trajectories, case-control studies, and case reports, with one wet-lab-coupled run nominating a 3-hydroxybutyrate - neutrophil axis modulating antitumor immunity. These results compress hypothesis-to-evidence cycles from years to hours, creating a continuous clinical discovery process.

18.
arXiv (CS.AI) 2026-06-12

CRAFTIIF: Cross-Resolution Analytic Four-Type Interpretable Isolation Forest for Multivariate Time Series Anomaly Detection

arXiv:2606.13486v1 Announce Type: cross Abstract: Anomaly detection in multivariate time series is challenged by four structurally distinct anomaly types – point (isolated spikes), distributional (level shifts), temporal (rhythm changes), and collective (inter-sensor correlation breakdowns) – each requiring different feature representations. Most unsupervised methods target only one or two types and provide limited interpretability. We present CRAFTIIF (Cross-Resolution Analytic Four-Type Interpretable Isolation Forest), a fully unsupervised framework targeting all four types without dataset-specific tuning. CRAFTIIF generates K=500 random analytic wavelet feature draws across four families (Morlet, DOG, Haar, Coiflet), each targeting a specific anomaly type, feeding five structured Isolation Forests – one per type plus a meta-IF for compound anomalies. An adaptive Otsu/MAD threshold calibrates detection automatically across anomaly rates from 0.1% to 69.2%. Because each IF is trained exclusively on type-specific features, branch firing provides direct anomaly-type attribution by construction, without post-hoc explanation. Evaluated on all 19 datasets of the mTSBench benchmark (Zhou et al., TMLR 2026), CRAFTIIF achieves mean F1=0.228 (all 19 datasets) and F1=0.322 (13 detectable datasets), ranking first among all 25 evaluated methods on VUS-PR (0.463 vs. previous best 0.329, +40.7%). A diagnostic framework – oracle F1, detectability limits, and branch separation ratios – identifies 6 of 19 datasets as fundamentally undetectable by any unsupervised method. Ablation over 11 conditions confirms adaptive thresholding (+38% F1), four-branch structure (+20%), and meta-IF (+23%) are each essential. Code: https://github.com/smitswil/craftiif

19.
arXiv (CS.LG) 2026-06-24

An Agnostic Machine Learning Model of Photosynthetic Habitability

arXiv:2606.24458v1 Announce Type: cross Abstract: The search for exoplanet biosignatures is guided by whether planetary environments can sustain photosynthesis. As such, the Photosynthetic Habitable Zone (PHZ) was recently proposed, as the overlap between the canonical habitable zone and the orbital range where stellar irradiance is sufficient to drive photosynthesis. Existing PHZ estimates rely on empirical light-response curves from Earth phytoplankton, and thus include implicit Earth-centric biases. We introduce an agnostic PHZ derived from a generalized model of photosynthesis grounded in thermodynamics and redox chemistry, without reference to model organisms. The model is built on a generic photochemical reaction in which photon capture couples oxidation of a donor molecule to the reduction of CO2. The optical properties and CO2 reduction rate are optimized against irradiance spectra for exoplanets orbiting main-sequence stars, using a genetic algorithm that mimics evolution by natural selection. Our simulations predict that photosynthetic organisms compensate for reduced flux by evolving larger light-harvesting structures. As a result, photosynthetic viability declines only linearly with orbital distance, despite stellar flux falling off quadratically. As such, the agnostic PHZ expands well beyond previous Earth-based estimates. Earth-like (visible light) oxygenic photosynthesis is flux-limited at the outer habitable zone for cool M-dwarf stars; however, both anoxygenic photosynthesis and a hypothetical, NIR-driven oxygenic photosynthesis are viable across the entire habitable zone for M, K, and G stars. This implies that M-dwarf exoplanets could sustain robust oxygenic photosynthesis, though it would be different to that found on Earth, presenting reflectance biosignatures in the NIR band rather than the visible.

20.
arXiv (CS.CL) 2026-06-24

AVOC: Enhancing Hour-Level Audio-Video Understanding in Omni-Modal LLMs via Retrieval-Inspired Token Compression

Multimodal Large Language Models have achieved remarkable progress in short-form audio-video understanding, yet long-form audio-video comprehension remains challenged by limited context windows and severe information redundancy. To address these bottlenecks, we propose AVOC, a framework for long-form audio-video understanding in Omni-modal Large Language Models. AVOC introduces a learnable token compression module between the modality encoders and the LLM backbone. We reframe multimodal token compression as a top-$K$ retrieval problem: given a fixed context budget, the module must retrieve a compact subset of tokens that best supports answering the user query. We draw inspiration from three classical Information Retrieval criteria for selecting informative units from a large candidate pool: relevance, importance, and diversity. AVOC instantiates each criterion as a tailored mechanism for audio-video understanding, and integrates them into a unified retrieval-style compression pipeline. Experiments show that AVOC achieves state-of-the-art performance on long-form audio-video benchmarks, surpassing the second-best model by 4.9 and 5.5 points in average accuracy on OmniVideoBench and LVOmniBench, respectively. Moreover, AVOC maintains robust performance on Audio-Video Needle-in-a-Haystack task at durations up to one hour.

21.
Science (Express) 2026-05-07

Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design | Science

作者: 未知作者

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

22.
arXiv (CS.CL) 2026-06-16

MAWARITH: A Dataset and Benchmark for Legal Inheritance Reasoning with LLMs

Islamic inheritance law is challenging for large language models because solving inheritance cases requires complex, structured, multi-step reasoning and the correct application of juristic rules to compute heirs' shares. We introduce MAWARITH, a large-scale annotated dataset of 12,500 Arabic inheritance cases for training and evaluating models on the full reasoning chain: (i) identifying eligible heirs, (ii) applying blocking (\d{hajb}) and allocation rules, and (iii) computing exact inheritance shares. To the best of our knowledge, MAWARITH is the first Arabic corpus and benchmark designed for end-to-end Islamic inheritance reasoning. Unlike prior datasets that restrict inheritance case solving to multiple-choice questions, MAWARITH supports the full reasoning chain and provides step-by-step solutions with justifications grounded in classical juristic sources and established inheritance rules, as well as exact share calculations. This enables models to learn how to generate detailed, step-by-step responses to user queries that reflect real-world Islamic inheritance cases. To evaluate models beyond final-answer accuracy, we propose MIR-E (Mawarith Inheritance Reasoning Evaluation), a weighted multi-stage metric that scores key reasoning stages and captures error propagation across the pipeline. We evaluate six large language models in a zero-shot setting. A commercial model achieves about 90\%, whereas all evaluated open-source models remain below 50\%. Our error analysis identifies recurring failure patterns, including scenario misinterpretation, errors in heir identification, errors in share allocation, and missing or incorrect application of key inheritance rules such as \textquotesingle awl and radd. The MAWARITH dataset is publicly available at https://gitlab.com/nlpresearcher/mawarith.

23.
bioRxiv (Bioinfo) 2026-06-18

A unified smoothing framework for protein domain bigram model

Biomolecular sequences can be represented as strings over an alphabet, an analogy that has motivated many applications of computational linguistic techniques to biological problems. However, such methods must be adapted to the characteristic scale and organization of biomolecular data. Here, we consider the problem of bigram smoothing for multidomain protein architectures, where domain bigram frequency data is extremely sparse and differs from textual data in alphabet size, string length distribution, the relationship between bigram and unigram frequencies, tandem repeat lengths, and the distribution of domain adjacencies. Moreover, some domain combinations are unobserved because they are biologically incompatible, others because the data are incomplete. A smoothing method that distinguishes these two cases is required. We propose a unified smoothing framework based on interpolation that can be tuned to accommodate different bigram data characteristics. Within this framework, we design specific model variants suited to protein domain bigram data: these assign low adjusted counts to pairs that are likely incompatible, while making appropriate adjustments for undersampled pairs. We demonstrate empirically that this approach distinguishes the two cases while preserving the characteristic signatures of multidomain data.

24.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

25.
arXiv (CS.LG) 2026-06-24

Sakana Fugu Technical Report

arXiv:2606.21228v2 Announce Type: replace Abstract: The capabilities of frontier Large Language Models (LLMs) continue to advance, with different providers increasingly specializing in distinct domains. This raises a natural next objective: how to combine the individual specializations of various LLMs into a collectively intelligent system. To this end, we report the development of Sakana Fugu, a family of orchestrator models that harness and amplify the capabilities of an LLM agent team. Fugu models are themselves language models trained to understand user queries and dynamically devise agentic scaffolds to solve them. Through these adaptive scaffolds, Fugu accesses performance beyond any individual LLM agent, achieving state-of-the-art results compared to other publicly accessible models across a range of challenging tasks, including SWE-Bench Pro, Terminal Bench, LiveCodeBench, GPQA-Diamond, Humanity's Last Exam, and CharXiv Reasoning. We release two models: Fugu, which balances performance with latency for everyday use, and Fugu-Ultra, which prioritizes answer quality on the hardest problems. We describe our training paradigm, which encompasses large-scale fine-tuning, evolutionary algorithms, and reinforcement learning approaches, along with the infrastructure and core design principles that turn these methods into a production system. We hope this report encourages further research into multi-agent systems and dynamic, query-adaptive agentic scaffolds as a path toward the next frontier of AI capabilities, accessed through collective intelligence.