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01.
arXiv (CS.CV) 2026-06-15

Generation of Maximal Snake Polyominoes Using a Deep Neural Network

Maximal snake polyominoes are difficult to study numerically in large rectangles, as computing them requires the complete enumeration of all snakes for a specific rectangle size, which corresponds to a brute force algorithm. This hinders the study of maximal snakes in larger rectangles. Moreover, most enumerable snakes lie in small rectangles, obscuring large-scale patterns. In this paper, we investigate the contribution of a deep neural network to the generation of maximal snake polyominoes from a data-driven training, where the maximality and adjacency constraints are not encoded explicitly, but learned. To this extent, we experiment with a denoising diffusion model, which we referred as Structured Pixel Space Diffusion (SPS Diffusion). We find that SPS Diffusion generalizes from small rectangles to larger ones, generating valid snakes up to 28x28 squares and producing maximal snake candidates on squares close to the current computational limit. The model is, however, prone to errors such as branching, cycles, or multiple snake components. Overall, the diffusion model is promising and suggests that complex combinatorial objects can be understood by deep neural networks, which is useful in their investigation.

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

The Faithfulness Gap: Certifying Semantic Equivalence Between Natural-Language and Formal Mathematical Statements

arXiv:2606.16541v1 Announce Type: new Abstract: Autoformalization, translating natural-language mathematics into formal proof assistants, is bottlenecked not by translation fluency but by faithfulness: a formal statement can typecheck and be provable, yet still encode a different theorem than the source intended. We introduce Bidirectional Provability Fingerprinting (\bpf{}), a framework that certifies faithfulness by characterizing each candidate through its forward and backward consequence neighborhoods in the ambient theory and matching these against probes derived from the natural-language statement. We further introduce four novel components: (i) Counterfactual Probe Generation (\cpg{}), a contrastive procedure that synthesizes probes targeting specific drift directions; (ii) the Equivalence Spectrum, a continuous faithfulness score that replaces brittle binary verdicts; (iii) Adaptive Probe Budget Allocation (\apba{}), an information-theoretic budget router; and (iv) Faithfulness-Guided Decoding (\fgd{}), which uses \bpf{} signals as a reward during autoformalization. We prove a drift detection theorem and a PAC-faithfulness result establishing that the equivalence class of a natural language statement is learnable from $\mathcal{O}(\log(1/\delta)/\varepsilon)$ probes under mild assumptions. We release \driftbench{}, a benchmark of $2{,}183$ NL/Lean~4 pairs with controlled drift labels across six subfields of mathlib4. \bpf{}\,+\,\cpg{} detects $89.6\%$ of drifted formalizations at a $3.0\%$ false-positive rate-against $41.2\%$ for typecheck and $63.3\%$ for LLM-judge baselines, and \fgd{} reduces the rate at which a state-of-the-art autoformalizer emits drifted statements by $47\%$. https://pmlrbd.github.io/BPF/

03.
arXiv (CS.CV) 2026-06-16

CLAD: Constrained Latent Action Diffusion for Vision-Language Procedure Planning

We propose CLAD, a Constrained Latent Action Diffusion model for vision-language procedure planning in instructional videos. Procedure planning is the challenging task of predicting intermediate actions given a visual observation of a start and a goal state. However, future interactive AI systems must also be able to plan procedures using multi-modal input, e.g., where visual observations are augmented with language descriptions. To tackle this vision-language procedure planning task, our method uses a Variational Autoencoder (VAE) to learn the latent representation of actions and observations as constraints and integrate them into the diffusion process. This approach exploits that the latent space of diffusion models already has semantics that can be used. We use the latent constraints to steer the diffusion model to better generate actions. We report extensive experiments on the popular CrossTask, Coin, and NIV datasets and show that our method outperforms state-of-the-art methods by a large margin. By evaluating ablated versions of our method, we further show that the proposed integration of the action and observation representations learnt in the VAE latent space is key to these performance improvements.

04.
arXiv (math.PR) 2026-06-24

Critical Erd{\H o}s-Rényi digraph: all eigenvectors away from zero are delocalized

arXiv:2606.24887v1 Announce Type: new Abstract: We consider the adjacency matrix of the directed Erd{\H o}s-Rényi graph. As long as the expected degree is larger than the logarithm of the number of vertices, the graph is connected, we show that all eigenvectors are completely delocalized. Below this critical scale, we prove eigenvector delocalization if the corresponding eigenvalue is away from zero. This contrasts the undirected or Hermitian setting, where large eigenvalues have localized eigenvectors [arXiv:2005.14180]. Our results also hold for sparse random matrices with independent entries, which can be viewed as weighted Erd{\H o}s-Rényi digraphs.

05.
medRxiv (Medicine) 2026-06-15

Dysplasia-Stratified Management of Barrett's Esophagus: An Incidence-Based U.S. Cost-Effectiveness Analysis

作者:

Background and Aims Barrett's esophagus (BE) is the principal precursor of esophageal adenocarcinoma (EAC), whose incidence has risen sharply in Western countries since the 1960s. Effective, dysplasia stratified surveillance strategies are needed to prevent progression. This study evaluated the cost effectiveness of dysplasia stratified surveillance intervals and endoscopic eradication therapy (EET) across the BE spectrum. Methods We developed an incidence-based Markov state transition model of BE progression calibrated to U.S. epidemiologic data from a healthcare sector perspective over a lifetime horizon. Four hypothetical cohorts of 50-year-old individuals with short segment BE (SSBE), nondysplastic BE (NDBE), low grade dysplasia (LGD), or high-grade dysplasia (HGD) were evaluated. Strategies included no surveillance; surveillance at 1-, 2-, 3-, 4-, 5-, or 10-year intervals; standard or AI assisted endoscopy; non endoscopic screening (sponge, breath, miRNA tests); and EET for LGD and HGD. Outcomes included costs, quality adjusted life years (QALYs), incremental cost effectiveness ratios (ICERs), net monetary benefits (NMBs), EAC cases, and EAC-related deaths. Sensitivity analyses used a willingness to pay threshold of US$100,000 per QALY. Results No surveillance was the most cost-effective strategy for SSBE and NDBE. For LGD, upfront EET was more cost effective than all surveillance strategies, with results sensitive to EAC incidence and recurrence. For HGD, EET was cost saving and yielded the greatest QALYs, with findings robust in 99.9% of simulations. EET prevented 12,614 and 44,295 EAC related deaths per 100,000 individuals with LGD and HGD, respectively. Conclusion Dysplasia-stratified management is essential for optimizing surveillance and treatment strategies in BE. Any degree of dysplasia should receive EET followed by targeted post-treatment monitoring, establishing EET as the central therapeutic pathway for dysplastic BE.

06.
arXiv (quant-ph) 2026-06-12

Fibonacci Steady-States and Persistent Oscillations in an Ordered Multimode Dicke Model

arXiv:2606.13072v1 Announce Type: new Abstract: Ultracold atoms in multimode optical cavities provide a rich testbed for many-body phenomena enabled by light-mediated interactions. Recent experiments include realizations of spin glasses and associative memories, as described by multimode Dicke models with disordered couplings. However, the properties of multimode Dicke models with ordered coupling geometries remain largely unexplored. In this work, we investigate the stable steady-states of the multimode Dicke model with an ordered nearest-neighbor coupling geometry, where $n_c$ atomic clusters are coupled via $n_c-1$ cavity modes. We show that the number of mean-field stable steady-states in the superradiant phase exhibits Fibonacci scaling with the number of atomic clusters, and that a subset of these steady-states exhibit persistent oscillations. Using both the truncated Wigner approximation and the numerically-exact hierarchy of pure states, we further demonstrate that these features of the stable steady-state solutions persist for finite cluster sizes. Ordered multimode Dicke models, such as the nearest-neighbor coupling geometry considered here, are accessible with current experimental technologies and point toward a broader class of strongly interacting dissipative systems with similarly rich behavior.

07.
arXiv (CS.LG) 2026-06-16

p-PSO: A Penalized Particle Swarm Optimization Technique for Finding D-Optimal Designs with Mixed Factors in Generalized Linear Models

arXiv:2606.15962v1 Announce Type: cross Abstract: Finding D-optimal designs for generalized linear models (GLMs) is challenging due to the dependence of the Fisher information matrix on unknown parameters and the lack of closed-form solutions, particularly when input factors include both discrete and continuous variables. Although classical algorithms and recent metaheuristic approaches have offered partial solutions, there remains a need for robust and computationally efficient methods. In this paper, we propose a penalized Particle Swarm Optimization (PSO) approach, named $p$-PSO. Here we introduce a new, general-purpose penalty formulation for constrained optimization and demonstrate its effectiveness in optimal design problems. The formulation is algorithm-agnostic and applicable to a broad class of black-box optimization methods. Results show that the method is highly efficient, with its primary contribution being a penalty formulation that enables the direct use of an off-the-shelf PSO algorithm and extends naturally to more general constrained optimization tasks.

08.
arXiv (CS.CL) 2026-06-16

Can LLM Coding Agents Reason About Time Series?

Large language models (LLMs) are increasingly being used for automated decision-making systems in finance, healthcare, or environmental monitoring. Time series data are ubiquitous in these fields, yet hard to process automatically. Can time series be analyzed by LLM agents? We examine three approaches: providing the agent with raw numerical data, using the LLM as a coding agent, or a combination of both. In the coding agent setup, the model iteratively queries the data using Python code. Using two time series understanding benchmarks, we show that agents with code access can outperform models processing raw data by up to 10%. However, even the best performing agent still answers about 22-34% of the questions incorrectly. To get insights into models' strategies and reasoning gaps, we analyze the model outputs with a strong LLM judge. Our analysis reveals that coding agents can select appropriate statistical tests, but often miss important nuances. Meanwhile, models with access to raw data can reach the right conclusions using back-of-the-envelope calculations.

09.
arXiv (CS.CL) 2026-06-12

Reward Modeling for Multi-Agent Orchestration

Multi-Agent Systems (MAS) built on Large Language Models (LLMs) require effective orchestration to coordinate specialized agents, yet training such orchestrators is hindered by limited supervision and high computational cost. We propose Orchestration Reward Modeling (OrchRM), a self-supervised framework for evaluating orchestration quality without human annotations. OrchRM leverages intermediate artifacts from multi-agent executions to construct win-lose pairs for Bradley-Terry reward model training. Unlike existing MAS test-time scaling and orchestrator training frameworks that rely on costly sub-agent rollouts, OrchRM operates directly at the orchestration level, enabling efficient and high-performing reward-guided orchestrator training and MAS test-time scaling. OrchRM improves training efficiency by up to 10x in token usage while improving MAS test-time scaling performance by up to 8% in accuracy. These gains consistently transfer across multiple domains, including mathematical reasoning, web-based question answering, and multi-hop reasoning, demonstrating orchestration-level reward modeling as a scalable direction for robust multi-agent orchestration. Code will be available at https://github.com/Wang-ML-Lab/OrchRM.

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

LoopCoder-v2: Only Loop Once for Efficient Test-Time Computation Scaling

arXiv:2606.18023v1 Announce Type: cross Abstract: Looped Transformers scale latent computation by repeatedly applying shared blocks, but sequential looping increases latency and KV-cache memory with the loop count. Parallel loop Transformers (PLT) alleviate this cost through cross-loop position offsets (CLP) and shared-KV gated sliding-window attention, making loop count a practical design choice. We therefore study PLT loop-count selection through a gain–cost view: an extra loop may refine representations, but CLP also introduces a positional mismatch at each loop boundary. We instantiate this study by training LoopCoder-v2, a family of 7B PLT coders with different loop counts, from scratch on 18T tokens, followed by matched instruction tuning and evaluation. Empirically, the two-loop variant delivers broad gains over the non-looped baseline across code generation, code reasoning, agentic software engineering, and tool-use benchmarks, improving SWE-bench Verified from 43.0 to 64.4 points and Multi-SWE from 14.0 to 31.0 points. In contrast, variants with three or more loops regress, revealing a strongly non-monotonic loop-count effect. Our diagnostics show that loop 2 provides the main productive refinement, while later loops yield diminishing, oscillatory updates and reduced representational diversity. Because the CLP-induced mismatch remains roughly fixed as refinement gains shrink, the offset cost increasingly dominates. This gain–cost trade-off explains PLT's saturation at two loops and provides diagnostics for loop-count selection.

11.
medRxiv (Medicine) 2026-06-10

Developmental Associations Linking Childhood Trauma and Early Cannabis Use to Adolescent DNA Methylation and Psychotic-Like Experiences

Background. Psychotic-like experiences (PLEs) index early risk for psychotic disorders and are consistently associated with childhood trauma, yet underlying biological mechanisms remain poorly understood. DNA methylation (DNAm) may capture the biological embedding of early adversity, while adolescent exposures such as cannabis use may modify these processes. We examined epigenome-wide associations of childhood trauma and PLEs, tested the moderating role of early cannabis use, and evaluated DNAm as a potential mediator. Methods. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Childhood trauma was assessed prospectively and retrospectively. Epigenome-wide DNAm was measured in peripheral blood at ~17 years using the Illumina 450K array, and PLEs were assessed at 18 using a structured interview. Epigenome-wide association studies were conducted for trauma-DNAm and DNAm-PLEs associations in the final sample (n = 1,457), adjusting for demographic, biological, and technical covariates. Differentially methylated regions (DMRs) were identified using DMRff, followed by functional enrichment analyses. Cannabis use at 15.5 was modelled as a moderator with multiple imputation for missing data. Mediation was tested using the Divide-Aggregate Composite-null Test (DACT). Results. Childhood trauma was associated with widespread DNAm differences, primarily at the regional level, with enrichment in pathways related to cellular stress responses. In contrast, DNAm associated with PLEs was more limited and implicated loci involved in epigenetic regulatory processes. These signatures were largely distinct, and there was no evidence supporting mediation after multiple testing correction. Incorporating cannabis use altered the pattern and extent of DNAm associations, with stronger and more significant signals observed at both CpG and regional levels, although these did not translate into evidence of mediation. Conclusion. Childhood trauma and PLEs show distinct DNAm signatures in adolescence, with trauma-related DNAm reflecting broad stress-related processes and PLE-associated DNAm implicating regulatory mechanisms. We found little evidence that DNAm mediates the trauma-PLE association. Instead, adolescent exposures, particularly cannabis use, may distinctly influence trauma-related epigenetic variation with limited detectable downstream effects on PLEs. These findings support a context-dependent model of epigenetic risk and highlight the need for larger longitudinal studies to clarify causal pathways linking early adversity to psychosis.

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

SAFformer:Improving Spiking Transformer via Active Predictive Filtering

Spiking Neural Networks (SNNs) offer notable advantages in biological plausibility and energy efficiency, making them promising candidates for building low-power Transformers. However, existing Spiking Transformers largely adhere to a passive reactive paradigm, which struggles to focus on task-relevant information and incurs substantial computational overhead when processing redundant visual data. To overcome this fundamental yet underexplored limitation, we propose SAFformer, a novel Spiking Transformer architecture based on an active predictive filtering paradigm. Inspired by the brain's predictive coding mechanism, SAFformer actively suppresses predictable signals and focuses on salient visual features. Extensive experiments show that SAFformer establishes new state-of-the-art performance on CIFAR-10/100 and CIFAR10-DVS. Remarkably, on ImageNet-1K, it achieves 80.44% Top-1 accuracy with only 26.58M parameters and an energy consumption of 5.88 mJ, demonstrating an exceptional balance between accuracy and efficiency.

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

Emergence of Hierarchical Emotion Organization in Large Language Models

As large language models (LLMs) increasingly power conversational agents, understanding how they model users' emotional states is critical for ethical deployment. Inspired by emotion wheels, i.e., a psychological framework that argues emotions organize hierarchically, we analyze probabilistic dependencies between emotional states in model outputs. We find that LLMs naturally form hierarchical emotion trees that align with human psychological models, and larger models develop more complex hierarchies. We also uncover systematic biases in emotion recognition across socioeconomic personas, with compounding misclassifications for intersectional, underrepresented groups. Human studies reveal striking parallels, suggesting that LLMs internalize aspects of social perception. Beyond highlighting emergent emotional reasoning in LLMs, our results hint at the potential of using cognitively-grounded theories for developing better model evaluations.

14.
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.

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

Adaptive Identification and Modeling of Clinical Pathways with Process Mining

arXiv:2512.03787v2 Announce Type: replace Abstract: Clinical pathways are specialized healthcare plans that model patient treatment procedures. They are developed to provide criteria-based progression and standardize patient treatment, thereby improving care, reducing resource use, and accelerating patient recovery. However, manual modeling of these pathways based on clinical guidelines and domain expertise is difficult and may not reflect the actual best practices for different variations or combinations of diseases. We propose a two-phase modeling method using process mining, which extends the knowledge base of clinical pathways by leveraging conformance checking diagnostics. In the first phase, historical data of a given disease is collected to capture treatment in the form of a process model. In the second phase, new data is compared against the reference model to verify conformance. Based on the conformance checking results, the knowledge base can be expanded with more specific models tailored to new variants or disease combinations. We demonstrate our approach using Synthea, a benchmark dataset simulating patient treatments for SARS-CoV-2 infections with varying COVID-19 complications. The results show that our method enables expanding the knowledge base of clinical pathways with sufficient precision, peaking to 95.62% AUC while maintaining an arc-degree simplicity of 67.11%.

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

Improving Code-Switching ASR with Code-Mixing Guided Synthetic Speech

arXiv:2606.19381v1 Announce Type: cross Abstract: Code-switch (CS) Automatic Speech Recognition (ASR) remains challenging due to limited availability of high quality CS text-speech pairs for training. Although synthetic data augmentation via Text-to-speech (TTS) has been explored, existing CS TTS approaches primarily optimise reconstruction fidelity and do not explicitly enforce language-boundary consistency, thereby limiting their effectiveness for CS ASR augmentation. This paper proposes a code-mixing guided preference-learning framework that steers synthetic speech generation toward improved code-switching fidelity using the Code Mixing Index (CMI). Experiments on the SEAME Mandarin-English conversational corpus demonstrate that the proposed method enhances the utility of synthetic data for ASR fine-tuning. Specifically, when fine-tuning Whisper Large, the proposed approach reduces Mixed Error Rate (MER) from 12.1%/17.8% to 8.9%/14.2% on the DevMAN and DevSGE sets, respectively.

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

Renewable Lasso without Batch-Number Constraints: A Gradient-Enhanced Approach

arXiv:2606.11738v1 Announce Type: cross Abstract: We study online estimation for high-dimensional generalized linear models with streaming data. First, for the non-distributed setting, we propose a gradient-enhanced surrogate loss that approximates the cumulative loss using only historical summaries, which modifies and improves upon the existing renewable estimation approach for the same model in the high-dimensional setting, and removes the batch-number constraint in previous studies. We then extend the method to distributed streaming data under the master-client architecture, where batches are partitioned across sites and only summaries (gradient vectors) are exchanged. Instead of directing applying the popular method of Jordan et al. (2019) to the surrogate quadratic loss, our adjusted approach does not require the clients to compute the full surrogate loss. We derive non-asymptotic error bounds under the high-dimensional scaling, without the stringent constraint on the number of batches in the previous studies. Simulation results under linear and logistic models, together with a real-data application, show improved accuracy over existing renewable estimators.

18.
arXiv (CS.CV) 2026-06-19

Collaborative Multi-Modal Coding for High-Quality 3D Generation

3D content inherently encompasses multi-modal characteristics and can be projected into different modalities (e.g., RGB images, RGBD, and point clouds). Each modality exhibits distinct advantages in 3D asset modeling: RGB images contain vivid 3D textures, whereas point clouds define fine-grained 3D geometries. However, most existing 3D-native generative architectures either operate predominantly within single-modality paradigms-thus overlooking the complementary benefits of multi-modality data-or restrict themselves to 3D structures, thereby limiting the scope of available training datasets. To holistically harness multi-modalities for 3D modeling, we present TriMM, the first feed-forward 3D-native generative model that learns from basic multi-modalities (e.g., RGB, RGBD, and point cloud). Specifically, 1) TriMM first introduces collaborative multi-modal coding, which integrates modality-specific features while preserving their unique representational strengths. 2) Furthermore, auxiliary 2D and 3D supervision are introduced to raise the robustness and performance of multi-modal coding. 3) Based on the embedded multi-modal code, TriMM employs a triplane latent diffusion model to generate 3D assets of superior quality, enhancing both the texture and the geometric detail. Extensive experiments on multiple well-known datasets demonstrate that TriMM, by effectively leveraging multi-modality, achieves competitive performance with models trained on large-scale datasets, despite utilizing a small amount of training data. Furthermore, we conduct additional experiments on recent RGB-D datasets, verifying the feasibility of incorporating other multi-modal datasets into 3D generation.

19.
bioRxiv (Bioinfo) 2026-06-10

HOMED enables hierarchical and multimodal optimization of DNA methylation deconvolution across tissues

Cellular heterogeneity is a major confounder in bulk DNA methylation data for epigenome-wide association studies. Existing reference-based DNAm deconvolution methods often ignore hierarchies among related cell types and may generalize poorly across datasets due to limited variability in reference profiles. We developed HOMED (Hierarchically Optimized Methylation Deconvolution), a framework that integrates cell-lineage hierarchies, single-cell RNA sequencing-guided deconvolution, and paired bulk RNA-seq/DNAm data for CpG signature optimization. Across simulated and real peripheral blood mononuclear cell, lung, and placental datasets, HOMED consistently yielded the highest PCCs and lowest RMSEs, outperforming existing scRNA-seq-guided DNAm deconvolution methods, improving accuracy, resolution, and cross-tissue generalizability.

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

Toward Controllable Catalyst Inverse Design via Large-Scale Autoregressive Pretraining

arXiv:2606.17445v1 Announce Type: new Abstract: Inverse design of heterogeneous catalysts remains challenging because catalyst surfaces exhibit substantial structural complexity with coupled surface-adsorbate interactions across a vast chemical space that is difficult to explore efficiently through conventional screening alone. Although machine learning-based high-throughput screening has accelerated catalyst discovery, its efficiency inevitably declines as the search space grows, motivating the development of generative models that can directly construct catalysts with target properties. Here, we present a conditional catalyst generative model based on the Generative Pretrained Transformer architecture with a numerical embedding layer that enables the generation of catalyst structures conditioned on both categorical and continuous properties within a single autoregressive framework. The model was pretrained on 133 million catalyst structures and subsequently fine-tuned on approximately 460,000 optimized structures with associated categorical properties and binding energies for conditional generation. The resulting model achieved 98% structural validity, 95% optimization validity, and high categorical condition fidelity, with a 93 % joint match rate for adsorbate type and composition. For binding energy conditioning, the match rate of approximately 20% represents a four-fold improvement over the baseline training distribution, and the generated distributions shift systematically toward the target values, enabling a 1.5 to 4-fold improvement in screening efficiency for reaction-targeted catalyst discovery without additional fine-tuning. These results show that large-scale autoregressive pre-training, combined with explicit property conditioning, provides a practical route toward controllable catalyst generation and accelerated catalysts discovery.

21.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

作者:

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach limits cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides a new approach to precision disease treatments for undruggable targets.

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

Autoregressive Direct Preference Optimization

arXiv:2602.09533v2 Announce Type: replace Abstract: Direct preference optimization (DPO) has emerged as a promising approach for aligning large language models (LLMs) with human preferences. However, the widespread reliance on the response-level Bradley-Terry (BT) model may limit its full potential, as the reference and learnable models are assumed to be autoregressive only after deriving the objective function. Motivated by this limitation, we revisit the theoretical foundations of DPO and propose a novel formulation that explicitly introduces the autoregressive assumption prior to applying the BT model. By reformulating and extending DPO, we derive a novel variant, termed Autoregressive DPO (ADPO), that explicitly integrates autoregressive modeling into the preference optimization framework. Without violating the theoretical foundations, the derived loss takes an elegant form: it shifts the summation operation in the DPO objective outside the log-sigmoid function. Furthermore, through theoretical analysis of ADPO, we show that there exist two length measures to be considered when designing DPO-based algorithms: the token length $\mu$ and the feedback length $\mu'$. To the best of our knowledge, we are the first to explicitly distinguish these two measures and analyze their implications for preference optimization in LLMs.

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

The Chandra-Gaia Catalog of Counterparts: Resolving ambiguous Gaia matches to X-ray sources in the Chandra Source Catalog using Machine Learning

arXiv:2606.19329v1 Announce Type: cross Abstract: We present a framework to cross-match sources from the Chandra Source Catalog (CSC v2.1) with optical sources from Gaia Data Release 3. Unlike purely spatial approaches, we use source properties such as magnitudes, colors, and distances to identify true counterparts, detect chance coincidences, and resolve ambiguities when multiple plausible candidates exist. We define a training set of high-confidence matches using NWAY, a Bayesian cross-matching framework that accounts for positional errors and source densities. We train a gradient-boosted classifier (LightGBM) on a variety of features from both catalogs. Of the ~$254$k unique X-ray sources, we find counterparts for ~$113$k sources, of which plausible multiple counterparts are found for ~$7$k. We find no counterparts for ~$20$k sources for which separation-based cross-matching does find a match, and attribute half of these to chance coincidences. We validate the pipeline on the Chandra Orion Ultradeep Project (COUP), where the machine-learning matches reproduce 95% of NWAY cross-matches without using any positional information. We release a catalog of the ~$113$k Chandra-Gaia counterparts, together with ~$7$k alternative matches and ~$20$k ambiguous NWAY associations, supporting future population studies of sources detectable by both Chandra and Gaia. We discuss limitations and provide a generalization of the framework that is applicable in other cross-matching scenarios.

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

Pre-Training for Simulation-Based Science: A Study on Jet Foundation Model Training Objectives

arXiv:2606.14870v1 Announce Type: cross Abstract: Foundation models (FMs) trained on large datasets and fine-tuned on downstream tasks have emerged as a powerful paradigm in AI for science. Industrial FMs are typically trained using self-supervision with masking due to the lack of labels. In many scientific domains, accurate simulations are plentiful and facilitate large, labeled datasets. This opens up new possibilities for pre-training. We present a systematic comparison of pre-training methods using the OmniLearned High Energy Physics FM framework. We test supervised classification, flow-matching generation, and self-supervised masked particle modeling. All models are pre-trained on the JetClass dataset and fine-tuned on two representative downstream tasks, top jet classification and JetNet conditional generation. Among other observations, for classification tasks, we find that pure classifier pre-training is optimal when downstream labels and model capacity are plentiful, but combining it with self-supervised masked particle modeling (MPM) is uniquely powerful in the low-finetuning label regime. Flow matching-based generative pre-training seems to provide little benefit for downstream classification, and interestingly, for downstream generation, we find that flow matching must be in the pre-training objective to see a significant finetuning advantage, hinting at the orthogonality of classification and generation tasks. That is, for a model to transfer to both generative and classification downstream tasks, it must be pre-trained on both. This study provides a template for controlled scaling analysis of pre-training objectives for foundation models in simulation-based sciences.

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

ReA-OVCD: Reliability-Aware Open-Vocabulary Change Detection via Semantic and Spatial Refinement

Unlike traditional remote sensing change detection that relies on predefined categories, Open-Vocabulary Change Detection (OVCD) identifies land cover changes flexibly using arbitrary text prompts. However, existing methods suffer from an inherent trade-off when modeling changes: instance-level comparison overlooks fine-grained semantic variations (e.g., partial building extensions), while direct pixel comparison proves unreliable, yielding unstable responses and boundary artifacts due to semantic ambiguity and spatial inconsistency. To this end, we propose an efficient training-free Reliability-Aware Open-Vocabulary Change Detection (ReA-OVCD) framework. It first derives candidate change regions from pixel-wise semantic discrepancies to ensure flexible and detailed localization. To ensure reliability, it subsequently introduces a collaborative refinement strategy to explicitly model change validity from both semantic and spatial perspectives. Specifically, we develop a Semantic Change Reasoning (SCR) module that reassesses changes by jointly analyzing distributional divergence and response variation, enabling the suppression of incidental inconsistencies while preserving reliable semantic shifts. In addition, a Boundary-aware Change Refinement (BCR) module is designed to mitigate artifacts stemming from boundary misalignment and uncertainty through validating whether candidate regions are supported by reliable interior pixels. Extensive experiments across multiple datasets (LEVIR-CD, WHU-CD, DSIFN, and SECOND) demonstrate that our method consistently outperforms state-of-the-art approaches, achieving $\mathrm{F}_{1}^{C}$ improvements of 2.13\% to 9.75\% with higher computational efficiency. The code is publicly available at \https://github.com/Funny0101/ReA-OVCD