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01.
arXiv (CS.AI) 2026-06-11

AI4Land: Scalable Deep Learning for Global High-Resolution Land Use Reconstruction

arXiv:2606.11793v1 Announce Type: cross Abstract: Uncertainty in the terrestrial carbon cycle remains a major constraint in climate projections, partly driven by the uncertainties affecting the land surface representation and variability in Earth system models. To address this limitation, we present a data-driven framework AI4Land, for generating high-resolution historical reconstructions and future projections of key land surface variables. The framework follows a two-phase approach using a U-Net architecture. In the first phase, which is the focus of this work, it reconstructs annual land use and land cover by integrating coarse-resolution scenario data with static geophysical features. In a planned second phase, the resulting high-resolution maps will be used to predict dynamic biophysical variables, particularly leaf area index, at finer temporal scales. Trained on Earth observation data, the models learn to reproduce spatially explicit and physically consistent land surface patterns, extending temporal coverage to periods lacking direct observations. AI4Land was developed and trained on MareNostrum5, demonstrating how GPU-accelerated HPC infrastructure enables global-scale climate AI pipelines. The final product is a suite of open-source emulators designed for real-time coupling with digital twin platforms, such as those developed under the Destination Earth initiative. By delivering realistic and evolving land surface conditions on demand, this work aims to reduce critical uncertainties and improve the predictive power of next-generation climate simulations.

02.
arXiv (CS.CL) 2026-06-17

From Parasocial Scripts to Dyadic Persistence in Autonomous AI-Agent Communities

While parasocial interactions (PSIs) and parasocial relationships (PSRs) have been studied in conventional media settings, we investigate whether PSI- (colloquial) relational cues also exist in online communities where both sides are autonomous AI agents. We analyze 4,434 posts and 50,338 comments from Moltbook through three theory-based textual indicators: attachment/intimacy language, reciprocity bids, and self-identification to original poster (OP). The combined results across methods based on keyword matching, few-shot large language model (LLM) annotation, and grouped-context LLM annotation reveal that PSI colloquial cues prevail and are strongly associated with OP re-engagement and a reciprocal reply structure. These results are robust across negative controls, nullification, clustered-standard-error re-estimation, and multiple-testing correction. A dyadic persistence test further affirms reciprocity bids aligned with sustained OP-involving mutual recurrence, providing empirical evidence for bridging interaction-level PSI scripts with PSR-consistent repeated dyadic patterns. We interpret the evidence as a behavioral structure in discourse by LLM-enabled agents.

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

VERITAS: Verifier-Guided Proof Search for Zero-Shot Formal Theorem Proving

arXiv:2606.19399v1 Announce Type: cross Abstract: LLM-based formal provers often collapse rich verifier signals (syntax errors, type mismatches, partial goal progress) into a binary pass/fail bit. We present VERITAS, a zero-shot framework that routes every verifier signal back into proof search through a two-phase protocol: Best-of-N sampling first, then a critic-guided MCTS pass that ingests Phase 1 failures as explicit negative examples. The protocol preserves every theorem solved by its own Phase 1 sweep, so Phase 2's additional solves are attributable to feedback-driven exploration. VERITAS reaches 40.6% on miniF2F (vs. an independently run Best-of-5 at 36.9%, Portfolio 26.2%) and 7.3% on VERITAS-CombiBench, a 55-theorem combinatorics benchmark we release on which Best-of-5 (1.8%) falls below Portfolio (3.6%), exposing that unguided sampling hurts when correct lemma names must be recovered iteratively from verifier feedback. Artifacts are available on GitHub.

04.
arXiv (CS.AI) 2026-06-16

Decision-Weighted Flow Matching for Contextual Stochastic Optimization

arXiv:2606.16790v1 Announce Type: cross Abstract: Conditional generative models are increasingly used as scenario generators for stochastic optimization, but standard training objectives emphasize uniform distributional fit rather than the downstream decisions induced by generated scenarios. This creates an objective mismatch: errors in statistically common regions may have little effect on decision regret, whereas errors in decision-sensitive regions can substantially change the optimal action. We propose Decision-Weighted Flow Matching (DW-FM), a regret-aligned training framework that preserves the simplicity of standard flow matching while reweighting its velocity-regression objective using decision-sensitive endpoint information. Theoretically, we connect downstream regret to pathwise velocity mismatch through a loss-induced decision discrepancy and an adjoint transport argument, yielding an ideal regret-aligned surrogate and practical endpoint-weighted objectives with regret guarantees. Empirically, we demonstrate the effectiveness of DW-FM on three CVaR-based contextual stochastic optimization benchmarks spanning synthetic portfolio, semi-real financial, and traffic-CVaR tasks, where DW-FM improves downstream regret over standard baselines.

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

Are Online Skill and Memory Modules Always Worth Their Tokens? A Budget-Constrained Study of Web Agents

Online web agents often augment a base actor with memory, workflow, or skill modules. These modules can improve performance, but they also consume test-time tokens, a cost rarely reported alongside the actor's inference cost. We study online augmentation, where this overhead is paid on every task, and re-evaluate its benefits under a fixed total inference budget. We compare AWM, ASI, and ReasoningBank with a token-matched vanilla baseline that uses the same budget for additional actor steps. Across three WebArena domains and three models, Gemini 3 Flash, GPT-5.4-mini, and Qwen 3.6-27B, the vanilla baseline matches or surpasses all three augmentation methods in aggregate success rate while often using fewer total tokens. We observe a similar trend on WorkArena-L1 with Qwen 3.6-27B, indicating that the effect extends to enterprise knowledge-work tasks. Our results suggest that skills and workflow memory can be useful in specific domains, but their apparent gains often vanish against a budget-matched actor. We further show that run-to-run variance materially affects outcomes and should be reported as a core evaluation criterion for online web agents.

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

Stable and Steerable Sparse Autoencoders with Weight Regularization

arXiv:2603.04198v2 Announce Type: replace-cross Abstract: Sparse autoencoders (SAEs) are widely used to extract human-interpretable features from neural network activations, but their learned features can vary substantially across random seeds and training choices. To improve stability, we studied weight regularization by adding L1 or L2 penalties on encoder and decoder weights, and evaluate how regularization interacts with common SAE training defaults. On MNIST, we observe that L2 weight regularization produces a core of highly aligned features and, when combined with tied initialization and unit-norm decoder constraints, it dramatically increases cross-seed feature consistency. For TopK SAEs trained on language model activations (Pythia-70M-deduped), adding a small L2 weight penalty increased the fraction of features shared across three random seeds and roughly doubles steering success rates, while leaving the mean of automated interpretability scores essentially unchanged. Finally, in the regularized setting, activation steering success becomes better predicted by auto-interpretability scores, suggesting that regularization can align text-based feature explanations with functional controllability.

07.
arXiv (CS.CV) 2026-06-12

InterleaveThinker: Reinforcing Agentic Interleaved Generation

Recent image generators have demonstrated impressive photorealism and instruction-following capabilities in single-image generation and editing. However, constrained by their architectures, they cannot achieve interleaved generation (text-image sequence), which has crucial applications in visual narratives, guidance, and embodied manipulation. Even the latest open-source Unified Multimodal Models (UMMs) exhibit limited performance in this regard. In this paper, we introduce InterleaveThinker, the first multi-agent pipeline designed to endow any existing image generator with interleaved generation capabilities. Specifically, we employ a planner agent to organize the image-text input sequence, instructing the image generator on the required execution at each step. Subsequently, we introduce a critic agent to evaluate the generator's outputs, identify samples that deviate from the planned instructions, and refine the instructions for regeneration. To implement this pipeline, we construct the Interleave-Planner-SFT-80k and Interleave-Critic-SFT-112k to perform a format cold-start. Then we develop Interleave-Critic-RL-13k to reinforce the step-wise instruction correction capability within a generation trajectory using GRPO. Since a single interleaved generation trajectory may involve over 25 generator calls, optimizing the entire trajectory is computationally impractical. Therefore, we propose accuracy reward and step-wise reward, allowing single-step RL to effectively guide the entire generation trajectory. The results show that InterleaveThinker improves performance across various image generators. On interleaved generation benchmarks, it achieves performance comparable to Nano Banana and GPT-5. Surprisingly, it also significantly enhances the base model on reasoning-based benchmarks; for example, on 4-step FLUX.2-klein, we observe substantial gains on WISE and RISE.

08.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.

09.
arXiv (CS.LG) 2026-06-17

Maximin Relative Improvement: Fair Learning as a Bargaining Problem

arXiv:2602.04155v2 Announce Type: replace-cross Abstract: When deploying a single predictor across multiple subpopulations, we propose a fundamentally different approach: interpreting group fairness as a bargaining problem among subpopulations. This game-theoretic perspective reveals that existing robust optimization methods such as minimizing worst-group loss or regret correspond to classical bargaining solutions and embody different fairness principles. We propose relative improvement, the ratio of actual risk reduction to potential reduction from a baseline predictor, which recovers the Kalai-Smorodinsky solution. Unlike absolute-scale methods that may not be comparable when groups have different potential predictability, relative improvement provides axiomatic justification including scale invariance and individual monotonicity. We establish finite-sample convergence guarantees under mild conditions.

10.
arXiv (CS.LG) 2026-06-17

When Dynamics Models Read the Wrong Time Steps: Label-Free Event Credit Re-Anchoring for Robust Global Readouts

作者:

arXiv:2606.17572v1 Announce Type: new Abstract: Learned dynamics models often answer global physical questions, such as fault severity or impact stiffness, by pooling a per-step feature sequence into one readout vector. This sequence-to-global interface creates an under-studied temporal credit problem: with only trajectory-level supervision, a model can predict accurately in training conditions while reading from abundant smooth correlates rather than the brief physical events that determine the target. We call this failure temporal credit dilution. It is not exposed by the training loss and is not removed by standard physics-informed residuals, because the error lies in where the global readout assigns functional credit. We introduce Credit-in-Event, an interface-level probe for measuring how much pooled credit lands on event steps, and prove in closed form that a pooled linear reader routes credit to a spurious background channel as the event fraction shrinks. We then propose CREST, a training-free and label-free readout that estimates a transient event core from learned features and re-anchors the pooled representation through event-versus-rest contrast. Across simulated gear and impact systems, recurrent and attention encoders, and public bearing vibration data, CREST reduces out-of-distribution error while restoring event credit. Ablations show that stable-step selection and receptive-field shrinking fail, confirming that the gain comes from event-core credit re-anchoring rather than a generic locality or stability prior.

11.
arXiv (CS.AI) 2026-06-19

LLM agent safety, multi-turn red-teaming, jailbreak benchmarks, adversarial robustness, safety-critical systems

arXiv:2606.20408v1 Announce Type: cross Abstract: Large language model (LLM) agents are increasingly proposed as supervisory components for safety-critical systems, yet their robustness under sustained, adaptive adversarial pressure remains poorly characterized. We present NRT-Bench, a benchmark for multi-turn red-teaming of LLM agents acting as operators of a safety-critical system, instantiated in a simulated nuclear power plant control room. A five-role operator team, each backed by a configurable LLM, runs a plant governed by six critical safety functions (CSFs), while adversaries inject messages over four channels in bounded multi-turn sessions with per-turn feedback. Harm is an objective signal rather than LLM-judged text: a run terminates the moment any CSF is lost, attributed to the causing message. Evaluating four frontier operator models under a fixed-attack paired-replay protocol, we find that adaptive multi-turn attacks reliably push the operator team past a safety limit: across the four models, between 8.7% and 12.1% of attack sessions end with the plant losing a critical safety function. Although the four models look almost equally robust by this aggregate rate, their failures barely overlap: of $149$ sessions, none defeat all four models while a third defeat at least one, so vulnerabilities are nearly disjoint across models rather than nested. The effect of added defences is strongly model-dependent: the same guardrail stack or safety-advisor agent that lowers attack success for one model can raise it for another. We release the simulation venue, attack dataset, and replay tooling for reproducible safety evaluation of LLM agents.

12.
arXiv (CS.LG) 2026-06-17

Learn from Your Mistakes: Self-Correcting Masked Diffusion Models

arXiv:2602.11590v3 Announce Type: replace Abstract: Masked diffusion models (MDMs) have emerged as a promising alternative to autoregressive models, enabling parallel token generation while achieving competitive performance. Despite these advantages, MDMs face a fundamental limitation: once tokens are unmasked, they remain fixed, leading to error accumulation and ultimately degrading sample quality. We address this by proposing a framework that trains a model to perform both unmasking and correction. By reusing outputs from the MDM denoising network as inputs for corrector training, we train a model to recover from potential mistakes. During generation we apply additional corrective refinement steps between unmasking ones in order to change decoded tokens and improve outputs. We name our training and sampling method Progressive Self-Correction (ProSeCo) for its unique ability to iteratively refine an entire sequence, including already generated tokens. We conduct extensive experimental validation across multiple conditional and unconditional tasks, demonstrating that \method~yields better quality-efficiency trade-offs (up to ~4x faster sampling) and enables inference-time compute scaling to further increase sample quality beyond standard MDMs (up to ~1.2x improvement on benchmarks).

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

Semantic Segmentation of Node and Edge Diagrams for Assistive Technology

In this paper, we present a novel set of related models for semantic segmentation of node-link diagrams. These diagrams are frequently used to represent mathematical graphs, relationships between concepts, and flowcharts. Such diagrams are difficult to access non-visually; while some assistive interfaces have been designed for node-link diagrams, they rely upon a machine-readable representation of the diagram, whereas such diagrams will generally be made available as bitmap images. Our compact deep learning models show excellent quantitative and qualitative performance on a large synthetic dataset of node-link diagrams, reaching per-pixel accuracy over 93\%.

14.
arXiv (quant-ph) 2026-06-17

Optimal Calibration of Quantum Network Links

arXiv:2606.18167v1 Announce Type: new Abstract: The reliable distribution of entanglement is essential for the effective operation of quantum networks. Due to fundamental differences between quantum and classical communication systems, it is necessary to develop specialised algorithms and protocols that also account for quantum-specific constraints. In this work, we focus on the issue of recalibration. As suggested by recent experimental studies, the process of local entanglement generation in a quantum link degrades over time due to environmental changes that have to be estimated and compensated via a calibration operation, during which the link is not available. Therefore, in such a quantum network, every link alternates between an activation period, during which it operates normally, and a calibration period, during which it cannot participate in the end-to-end entanglement distribution, thereby creating a trade-off between link quality (the fidelity of generated pairs, which decays during activation) and availability (the fraction of time the link is usable, which calibration reduces). We develop analytically a protocol for optimally assigning activation periods to each link in linear quantum repeater chains, subject to any general end-to-end fidelity requirements and local initial fidelity thresholds. Building on this foundation, we extend to general quantum networks, where multiple paths may cross at common links, proposing a heuristic approach evaluated in simulations and compared with a benchmark, numerical approach, and theoretical bounds.

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

Nonlocal Bayesian Modeling of Continuous Spatio-Temporal Dynamics

arXiv:2606.14313v1 Announce Type: cross Abstract: Real-world spatio-temporal forecasting must handle irregular time points, spatially sparse observations, and the need for uncertainty quantification. This setting is often further compounded by nonlocal interactions (long-range spatial coupling). Modeling continuous-space, continuous-time nonlocal dynamics naturally leads to infinite-dimensional integro-differential equations (IDEs), making principled Bayesian inference intractable. We propose the NonLocal Bayesian Spatio-Temporal model (NLBST), a hierarchical Bayesian framework for continuous spatio-temporal fields that learns explicit nonlocal coupling while retaining tractable inference. NLBST represents the latent field via a coordinate-based spatial basis expansion and models the coefficient process with a continuous-time ODE whose learnable linear operator corresponds to a Galerkin reduction of a nonlocal IDE; a Neural ODE residual captures additional nonlinear dynamics. A linear-Gaussian observation model enables Kalman-style sequential updates under missing and irregular observations, while the spatial basis representation enables inductive prediction at unmeasured locations without retraining. Global parameters are learned via variational inference, and uncertainty is handled through a Bayesian hierarchy. Experiments on synthetic and real-world datasets demonstrate strong forecasting and spatial generalization with well-calibrated uncertainty, yielding substantial gains over baselines in strongly nonlocal and partially observed regimes.

16.
medRxiv (Medicine) 2026-06-10

Epidemiology of Cervical Precancerous Lesions: Prevalence and Predictors from Pap Smear Screening in Hawassa City Hospitals, Sidama Region, Ethiopia. Institutional-Based Cross-sectional Study

Background: Cervical cancer is the fourth most common cancer in women worldwide and remains a major public health challenge. In Ethiopia, it is the second leading cause of cancer deaths, with around 8,000 new cases and 6,000 deaths each year. Region?specific data on the prevalence and predictors of precancerous lesions remain scarce, yet such information is vital for guiding targeted reproductive health strategies. This study therefore examined the prevalence and predictors of cervical precancerous lesions among women aged 21-60 years undergoing Pap smear screening in public hospitals in Hawassa City, Sidama Region. Methods: An institution-based cross-sectional study was conducted among 241 women attending Pap smear screening at public hospitals in Hawassa City from March to August 2025. Sociodemographic and clinical data were collected via interviews and medical records. Lesions were classified based on the standardized international framework for reporting cervical cytology results from Pap smears per the Bethesda system. Multivariable logistic regression identified predictors p

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

Knowledge Graph Enhanced Memory-Augmented Retrieval for Long Context Modeling

Long-context language modeling requires not only extending context windows but maintaining coherent understanding of entity states and relationships across thousands of tokens – a challenge that semantic similarity alone cannot address. KGERMAR addresses this by constructing dynamic, context-specific knowledge graphs from input text during inference, enabling domain-adaptive retrieval that leverages both semantic similarity and explicit entity relationships. The framework performs real-time entity and relation extraction to build contextual knowledge graphs, then integrates graph-structural embeddings with textual semantics through a multi-component memory architecture. Three memory banks – contextual, semantic, and structural – are maintained with retrieval signals fused via learned weights to capture both surface-level semantics and deeper relational patterns. Evaluated on SlimPajama (84.7K training examples), WikiText-103 (4,358 examples), PG-19 (100 examples), and Proof-pile (46.3K examples), KGERMAR achieves up to 8.5\% lower perplexity and 2–2.5x better memory efficiency than memory-augmented baselines across context lengths from 1K to 32K tokens, with superior in-context learning performance across five NLU tasks. The dynamic knowledge graph construction approach advances memory-augmented language modeling by enabling domain-specific knowledge representation that adapts to input contexts rather than relying on fixed knowledge bases.

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

UMA-Split: unimodal aggregation for both English and Mandarin non-autoregressive speech recognition

This paper proposes a unimodal aggregation (UMA) based nonautoregressive model for both English and Mandarin speech recognition. The original UMA explicitly segments and aggregates acoustic frames (with unimodal weights that first monotonically increase and then decrease) of the same text token to learn better representations than regular connectionist temporal classification (CTC). However, it only works well in Mandarin. It struggles with other languages, such as English, for which a single syllable may be tokenized into multiple fine-grained tokens, or a token spans fewer than 3 acoustic frames and fails to form unimodal weights. To address this problem, we propose allowing each UMA-aggregated frame map to multiple tokens, via a simple split module that generates two tokens from each aggregated frame before computing the CTC loss.

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

Predicting Cognitive Load from Speech and Interaction Dynamics in Dyadic Conversations

arXiv:2606.12971v1 Announce Type: new Abstract: Estimating cognitive load from speech has largely been studied in controlled laboratory settings, with limited understanding of its reliability in natural collaborative conversations. We investigate whether speech and interaction dynamics predict perceived cognitive load during dyadic conversations. We analyze audio from 53 dyads performing nine collaborative tasks and extract static acoustic, dynamic, and interaction features to train a two-head Gated Recurrent Unit encoder to predict cognitive load scores. Results show conversational interaction provides useful signals for predicting cognitive load related to time pressure, mental work, effort, and task performance. Temporal demand is associated with turn-taking dynamics such as overlap and speaker switch, while mental demand is linked to imbalanced participation between speakers. These findings highlight the importance of task structure and conversational interaction for modeling cognitive load in natural collaborative settings.

20.
arXiv (CS.CV) 2026-06-17

MambaCount: Efficient Text-guided Open-vocabulary Object Counting with Spatial Sparse State Space Duality Block

Text-guided Open-vocabulary Object Counting (TOOC) aims to estimate the number of objects described by text prompts, which is particularly challenging in dense scenes with large scale variations. Existing TOOC approaches predominantly rely on Transformers, whose quadratic complexity with respect to image resolution limits their scalability. Mamba offers a promising alternative due to its linear complexity. However, previous Mamba-based methods have two main limitations. On the one hand, the inherent causal formulation of Mamba constrains the bidirectional spatial dependency modeling required by non-causal vision tasks. On the other hand, existing Mamba-based vision models often overlook the unconstrained high entropy in the spatial token responses, which can weaken local details and high-frequency cues. To address these limitations, we propose MambaCount, an efficient framework built on the Spatial Sparse State Space Duality (S^4D) block. Specifically, we analyze and reconstruct the decay dynamics of hidden states in Mamba to alleviate the dependency constraints introduced by causal modeling. Moreover, we introduce a Spatial Token Selection (STS) sub-block to reduce the unconstrained high entropy in spatial token responses within Mamba. In addition, we design Multi-Granularity Prototypes (MGP) to identify object-like regions at different semantic levels, improving cross-modal alignment and interpretability. Extensive experiments on FSC-147 demonstrate that MambaCount achieves state-of-the-art performance among methods without secondary querying, obtaining a test MAE of 12.23, while retaining linear complexity.

21.
arXiv (CS.AI) 2026-06-18

Veriphi: Attack-Guided Neural Network Verification with Dataset-Dependent Training Methods

arXiv:2606.18454v1 Announce Type: cross Abstract: We present Veriphi, a GPU-accelerated neural network verification system that combines fast adversarial attacks with formal bound certification using alpha,beta-CROWN methods. Through systematic experiments on MNIST and CIFAR-10 using three training methodologies (standard, adversarial, certified), we demonstrate that training method effectiveness is fundamentally dataset-dependent. Interval Bound Propagation (IBP) achieves 78% certified accuracy on simple MNIST (784 dimensions) but provides negligible certification performance on the more complex CIFAR-10 dataset, where PGD adversarial training dominates with 94% certification at small perturbations. We achieve 5x verification speedup through attack-guided falsification and scale our approach to production-size models (105.8M parameters) for real-world aerospace logistics optimization. Our results challenge the assumption that certified training universally outperforms adversarial training, showing context matters critically for verification strategy selection.

22.
Nature (Science) 2026-06-17

Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago

Plague is among the most devastating diseases in human history1. However, early strains of the plague-causing bacterium Yersinia pestis lacked virulence factors that are required for the bubonic form until around 3,800 years ago2,3. Consequently, the morbidity and mortality of early plague strains remain unclear. Here we describe early plague strains that are associated with two phases of outbreaks among mid-Holocene hunter-gatherers near Lake Baikal in southeast Siberia, beginning from about 5,500 years ago. These outbreaks occur across four hunter-gatherer cemeteries, with a 39% detection rate for plague infection. By reconstructing kinship pedigrees, we show that small familial groups were affected, consistent with human-to-human spread of disease, and that the first outbreak occurred within a single generation. The infections appear to have resulted in acute mortality, especially among children (aged 8 to 11 years). We further note functional differences, including in the ypm superantigen locus, which is also present in present day Yersinia pseudotuberculosis. The new strains diverge ancestrally to known Y. pestis and constrain the timing of its emergence, indicating that this happened before approximately 5,700 years ago. These findings show that plague outbreaks happened earlier than previously thought and were indeed lethal. We contend that the occurrence of outbreaks among mid-Holocene hunter-gatherer communities well outside the sphere of Late Neolithic Europe challenges the notion that higher population densities and lifestyle changes during the Neolithic agricultural transition were prerequisites for plague epidemics. Analyses of ancient DNA from hunter-gatherers near Lake Baikal in southeast Siberia around 5,500 years ago indicate that highly virulent Yersinia pestis emerged earlier than previously estimated, far from the next known cases of infection in Late Neolithic Europe.

23.
bioRxiv (Bioinfo) 2026-06-14

Generative design of antigen-specific T-cell receptor sequences with a conditional diffusion model

T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers and infectious diseases, where highly antigen-specific TCR recognition is crucial for adaptive immunity against tumors and pathogens. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing reactive TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences with state-of-the-art fidelity to native binding TCRs through a denoising diffusion process. Furthermore, incorporating the interface geometry features generated TCR-pMHC complexes with superior structural plausibility. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs for immunotherapy. In vitro activation assays validated that TCRDiff-generated TCRs specifically recognize the MAGE-A3 epitope with minimized off-target cross-reactivity. Together, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.

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

Diffusion Models for Adaptive Sequential Data Generation

arXiv:2606.06007v2 Announce Type: replace Abstract: Generating realistic synthetic sequential data is critical in real-world applications across operations research, finance, healthcare, energy systems, and scientific computing, where time-indexed observations are used for prediction, simulation, risk assessment, and data-driven decision-making. While diffusion models have achieved remarkable success in generating static data, their direct extensions to sequential settings often fail to capture temporal dependence and information structure. Designing diffusion models that can simulate sequential data in an adapted manner, and hence without anticipation of future information, therefore remains an open challenge. In this work, we propose a sequential forward-backward diffusion framework for adapted time series generation. Our approach progressively injects and removes noise along the sequence, conditioning on the previously generated history to ensure adaptiveness. A novel score-matching objective is introduced for efficient parallel training. We derive rigorous statistical guarantees under a generic framework, then establish score approximation, score estimation, and distribution estimation results with ReLU networks serving as a concrete instance. Empirically, we validate our method on synthetic data, including ARMA models and Gaussian processes, and demonstrate its effectiveness in constructing mean-variance optimal portfolios.

25.
arXiv (CS.AI) 2026-06-19

AI4SE and SE4AI Exploration: A Decade Looking Back and Forward

arXiv:2606.19630v1 Announce Type: new Abstract: The March 2020 INCOSE INSIGHT special issue on AI and Systems Engineering (SE) became the most downloaded issue in the publication's history and launched a research community that now draws over 250 registrants to its annual workshop. In this article, we trace the progress in AI and SE across three phases (labeled here foundational, applied, and LLM inflection) based on the authors' reading of the field's core papers, and describe our opinions of where the community has converged and where critical gaps remain. Separately, a human-AI agreement literature review leveraging both human expertise and six AI models was performed to assess the relevance of 1,712 INCOSE INSIGHT articles and 889 SERC publications. The results identify five critical research gaps and offer guidance for practitioners navigating AI adoption, assurance, and workforce transformation in SE. We share the agreement data and the AI4SE/SE4AI Explorer web application so readers can compare their own relevance judgments with the human and AI raters.