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

Evaluating Factual Density in Multi-Source RAG: A Study in Medical AI Accuracy

Retrieval-Augmented Generation (RAG) is the current industry standard for grounding AI in real-world facts. Traditional retrieval methods rely on keyword matching and topic proximity, ranking content based on how closely it sounds like the user's query. What they do not measure is how many verified facts the content actually contains. This structural gap, termed the Expert Blindness Effect, causes standard RAG pipelines to consistently bury high-density factual evidence in favor of lexically dominant text on the same topic. To address this gap, this paper introduces Factual Density (FD*), a novel retrieval optimization signal that measures the proportion of verified atomic claims relative to total token count. Using the NexusAgentics Ghost Audit preprocessing pipeline, raw text is scored for factual specificity using probabilistic factuality analysis to filter content before corpus ingestion. An initial formulation introduced a severe document-length confound (Pearson R = -0.8636, p = 2.27e-07). Implementing Z-score normalization within length bins resolved this bias, validating FD* as a length-independent density signal (p = 0.0749). Evaluated against the HealthFC benchmark (750 health claims labeled Supported, Refuted, or No Evidence by medical experts), FD*-optimized retrieval was the only condition to achieve 100% systematic review saturation in top-5 results, surfacing Cochrane evidence that standard cosine similarity ranked outside the top ten. Ground truth verification confirmed 25 mappings across seven HealthFC-supported claims. While full statistical validation across n=50 queries remains future work due to constraints on corpus-benchmark alignment, these findings establish factual density reranking as a low-cost, high-impact intervention for improving factual precision in health RAG architectures.

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

ATLAS: Active Theory Learning for Automated Science

arXiv:2606.12386v1 Announce Type: cross Abstract: Advancing scientific understanding through mechanistic modeling requires posing the right experimental questions to yield maximally informative data. To automate this pursuit within cognitive science, we introduce ATLAS (Active Theory Learning for Automated Science), an active learning framework for the data-driven discovery of interpretable behavioral models. ATLAS iterates between generating mechanistic hypotheses–instantiated as a diverse ensemble of sparse neural networks (Disentangled RNNs)–and designing experiments that optimally distinguish between them. We test this approach on the problem of recovering reinforcement learning agents from their behavior in bandit tasks. ATLAS designs varied sequences of qualitatively novel experiments with temporal structure tailored to underlying agent characteristics. The models trained on these experiments are evaluated against a comprehensive set of metrics for mechanistic modeling that capture behavioral, structural, and computational similarity. ATLAS achieves a 5-10x improvement in sample efficiency across all metrics compared to random experimentation, and its performance is further validated against expert-designed experiments derived from literature. These in silico results showcase ATLAS's potential to accelerate human-interpretable insights in cognitive science and other domains where scientific inquiry relies on discovering mechanistic models.

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

Modeling Day-Long ECG Signals to Predict Heart Failure Risk with Explainable AI

arXiv:2601.00014v2 Announce Type: replace-cross Abstract: Heart failure (HF) affects 11.8% of adults aged 65 and older, reducing quality of life and longevity. Preventing HF can reduce morbidity and mortality. We hypothesized that artificial intelligence (AI) applied to 24-hour single-lead electrocardiogram (ECG) data could predict the risk of HF within five years. To research this, the Technion-Leumit Holter ECG (TLHE) dataset, including 69,663 recordings from 47,729 patients, collected over 20 years was used. Our deep learning model, DeepHHF, trained on 24-hour ECG recordings, achieved an area under the receiver operating characteristic curve of 0.80 that outperformed a model using 30-second segments and a clinical score. High-risk individuals identified by DeepHHF had a two-fold chance of hospitalization or death incidents. Explainability analysis showed DeepHHF focused on arrhythmias and heart abnormalities. This study highlights the feasibility of deep learning to model 24-hour continuous ECG data, capturing paroxysmal events essential for reliable risk prediction. Artificial intelligence applied to single-lead Holter ECG is non-invasive, inexpensive, and widely accessible, making it a promising tool for HF risk prediction.

04.
arXiv (CS.AI) 2026-06-15

When the Tool Decides: LLM Agents Defer Blindly to Graph Neural Network Tools, and Stronger Backbones Defer More

arXiv:2606.14476v1 Announce Type: new Abstract: A growing line of work equips large language model (LLM) agents with graph neural networks (GNNs) as callable tools, assuming the agent exercises judgment over when and how much to rely on such a tool. We test this directly. We expose a frozen GNN to a ReAct-style LLM agent as an explicit tool and measure, on node classification over a text-attributed graph (ogbn-arxiv, replicated on WikiCS), whether the agent uses the tool or merely obeys it. We find the agent does not exercise judgment: its predictions agree with the raw GNN's 97.6-99.2% of the time (5 seeds), collapsing into a GNN parrot that adopts the tool's output wholesale and bypasses its own reasoning. Sweeping backbone capability (Qwen2.5 0.5B-7B), the deference is not a weak-model artifact: among models able to invoke the tool, agreement rises with capability (0.60 to 0.98 from 1.5B to 7B). Crucially, the cost of deference does not shrink as capability grows and grows where alternatives emerge: a per-node oracle over the available actions beats the parrot by 0.09-0.18 at 3B and 0.12-0.22 at 7B, roughly doubling at high homophily, because the parrot is pinned to the frozen GNN while the agent's alternatives improve; at 7B a simple neighbour-label tool overtakes the GNN at high homophily (0.81 vs 0.71) yet the agent still defers. A simple selective-invocation gate recovers about half of that high-homophily gap (0.71 to 0.83) but yields no net global gain, and held-out estimates bound the best achievable gate over standard test-time features to at most a third of the oracle headroom: reliable selective invocation looks limited by available information, not merely router design. Our results are a cautionary measurement: evaluations of agent+tool systems cannot assume the agent adds judgment on top of the tool, and selective invocation must be designed in rather than expected to emerge from scale.

05.
arXiv (CS.CL) 2026-06-11

Massive Open-Vocabulary Keyword Spotting

Automatic speech recognition systems have been shown to under-perform when it comes to transcribing words rarely seen in the training data, namely specialized terminology. Open-vocabulary keyword spotting, combined with contextual biasing, has been shown to mitigate this issue. However, existing systems can only handle glossaries of a few hundred terms without becoming an infeasible bottleneck. We propose a system that stores features with a memory footprint up to 128 times smaller than a comparable baseline and allows users to process massive databases while remaining open-vocabulary. Without fine-tuning the speech recognition model, our system achieves a comparable entity recall as uncompressed solutions, even in languages not seen during training.

06.
bioRxiv (Bioinfo) 2026-06-15

SMLMFlow: Improving Structural Resolution in Single Molecule Localization Microscopy with Flow Matching

While Single Molecule Localization Microscopy (SMLM) aims to generate precise coordinates of molecular targets in cells, the resulting point clouds are inherently blurred by additive noise sources across the experimental, imaging, and processing workflow. This blurring often limits SMLM's ability to accurately quantify complex assembled structures required to address biological issues, despite reported localization precision down to a couple of nanometers. Here, we present SMLMFlow, a machine learning framework for improving structural resolution in SMLM datasets that combines a graph neural network and a hierarchical transformer with flow matching. We show that SMLMFlow improves structural resolution and downstream quantification across different structures, including filaments and protein nano-clusters, and generalizes to new unseen photophysics models.

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

Identifiability Without Gaussianity: Symbolic World Models and Near-Infinite Temporal Consistency

Klindt, LeCun, and Balestriero (arXiv:2605.26379) proved that Joint-Embedding Predictive Architectures (JEPAs) achieve linear identifiability, the linear recovery of the world's true latent variables, if and only if the world's latent dynamics follow a Gaussian, stationary process. This Gaussian boundary implies a fundamental limit on temporal consistency: for any non-Gaussian physical system, the representation error of a statistical World Model grows monotonically with time. We prove that this limit is an artifact of the statistical alignment mechanism, not a property of World Models in general. We introduce the Physics-Grounded Symbolic Architecture (PGSA) and prove three results: (1) a PGSA achieves exact linear identifiability for all physical regimes, regardless of the latent distribution; (2) the per-step error of a PGSA is bounded by numerical precision alone; and (3) as a direct consequence, a PGSA maintains temporal consistency for an unbounded number of transitions, a property we term near-infinite temporal consistency. We further prove that statistical World Models cannot achieve this property for any non-Gaussian system, regardless of model capacity or the volume of training data. The algebraic cores of four of the theorems are formalized in Lean 4 with Mathlib4 v4.31.0 (zero sorry placeholders); the Klindt et al. converse is taken as an external premise. The contrast establishes that symbolic grounding in the causal generator of the world's dynamics is the sufficient condition and, in non-Gaussian regimes, the only condition for near-infinite temporal consistency.

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

MoonSplat: Monocular Online Gaussian Splatting with Sim(3) Global Optimization

Online 3D reconstruction from monocular image sequences is a challenging and ongoing research topic. 3D Gaussian Splatting (3DGS), leveraging its high-quality real-time rendering capability, empowers online 3D reconstruction to represent dense scenes with enhanced expressiveness, and thus holds great promise for a wide range of applications such as robotics and AR/VR. However, existing online 3DGS methods still suffer from some key challenges: fragile camera pose estimation due to the lack of global optimization, and low optimization efficiency in large-scale or long-sequence scenarios. To address these issues, we propose a robust and efficient online voxelized 3DGS reconstruction framework integrated with global $Sim(3)$ optimization, which enables reliable camera tracking and efficient global loop closure for both camera poses and voxelized 3DGS. To accelerate the convergence of the voxelized 3DGS, we further introduce a color residual learning strategy, which not only boosts optimization speed but also enhances rendering quality. Extensive experiments on diverse indoor and outdoor datasets demonstrate that our method achieves state-of-the-art performance in both camera pose estimation accuracy and rendering quality, while retaining real-time efficiency. Additionally, we develop and deploy a real-world UAV-based active reconstruction system grounded on our proposed method, validating its robustness and generalizability for practical online 3D reconstruction tasks. Our code and data are available at https://github.com/TrickyGo/MoonSplat.

09.
arXiv (CS.CL) 2026-06-16

PACT: Privileged Trace Co-Training for Multi-Turn Tool-Use Agents

Multi-turn tool-use agents must reason, call tools, and adapt to observations across several interaction turns. Post-training such agents is challenging, as reinforcement learning often suffers from sparse rewards and weak credit assignment despite matching the prompt-only inference setting, while supervised fine-tuning on expert traces provides dense process supervision but can over-constrain the model to fixed trajectories. To tackle this, we propose PACT, a Privileged trAce Co-Training framework for multi-turn tool-use agents. The key idea is to use expert traces only as training-time optimization signals rather than rollout-time hints. PACT keeps rollout generation prompt-only, then uses expert traces to guide optimization through two complementary signals: a trace-conditioned RL surrogate that evaluates prompt-only rollouts under expert-trace context, and a component-aware SFT loss that supervises reasoning prefixes and tool-calls with annealed strength. To reduce over-reliance on the training-only trace context, PACT further introduces a prompt-only anchoring. We also provide a latent-trace view that connects the two trace-based objectives and explains how expert traces can guide optimization without being used during rollout generation. Experiments on FTRL, BFCL, and ToolHop show that PACT consistently improves over strong SFT- and RL-based baselines, highlighting the value of privileged trace co-training for multi-turn tool-use learning.

10.
arXiv (CS.LG) 2026-06-11

Learning Patterns and Abstractions from Perceptual Sequences

作者:

arXiv:2503.10973v2 Announce Type: replace Abstract: Cognition swiftly breaks high-dimensional sensory streams into familiar parts and uncovers their relations. Why do structures emerge, and how do they enable learning, generalization, and prediction? What computational principles underlie this core aspect of perception and intelligence? A sensory stream, simplified, is a one-dimensional sequence. In learning such sequences, we naturally segment them into parts – a process known as chunking. In the first project, I investigated factors influencing chunking in a serial reaction time task and showed that humans adapt to underlying chunks while balancing speed and accuracy. Building on this, I developed models that learn chunks and parse sequences chunk by chunk. Normatively, I proposed chunking as a rational strategy for discovering recurring patterns and nested hierarchies, enabling efficient sequence factorization. Learned chunks serve as reusable primitives for transfer, composition, and mental simulation – letting the model compose the new from the known. I demonstrated this model's ability to learn hierarchies in single and multi-dimensional sequences and highlighted its utility for unsupervised pattern discovery. The second part moves from concrete to abstract sequences. I taxonomized abstract motifs and examined their role in sequence memory. Behavioral evidence suggests that humans exploit pattern redundancies for compression and transfer. I proposed a non-parametric hierarchical variable model that learns both chunks and abstract variables, uncovering invariant symbolic patterns. I showed its similarity to human learning and compared it to large language models. Taken together, this thesis suggests that chunking and abstraction as simple computational principles enable structured knowledge acquisition in hierarchically organized sequences, from simple to complex, concrete to abstract.

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

When Does Language Matter? Multilingual Instructions Reveal Step-wise Language Sensitivity in Vision-Language-Action Models

Vision-Language-Action (VLA) models have shown strong performance in language-conditioned robotic manipulation, yet their robustness to linguistic variation remains poorly understood. In this work, we present the first systematic multilingual evaluation of VLA models by translating the LIBERO benchmark into ten languages, revealing severe performance degradation under non-English instructions, with success rates dropping by 30-50%. Through fine-grained analysis of task executions, we find that language influence is highly non-uniform across steps: certain steps exhibit strong language dependence and dominate overall task failure, while others are largely language-agnostic. Based on this insight, we propose a step-wise inference-time intervention that aligns representations according to step language sensitivity, substantially improving performance under linguistic variation. Our results indicate that language robustness in VLA models is fundamentally a step-wise control problem, highlighting the importance of temporally structured analysis for reliable embodied agents.

12.
arXiv (quant-ph) 2026-06-15

Reaffirming a Challenge to Bohmian Mechanics

arXiv:2509.06584v4 Announce Type: replace Abstract: In our recent work, we reported the first measurement of the speed of tunnelling particles using a coupled waveguide system. The measured speed is operationally defined through a comparison of two orthogonal motions in a coupled waveguide system, is compatible with the standard definition of dwell time and with the Büttiker-Landauer tunnelling time, and does not presuppose a trajectory picture. Here we respond to objections raised in comments, referee reports, preprints, and articles. We distinguish two questions that are often conflated: whether Bohmian mechanics reproduces the measured density, and whether the standard guiding equation assigns the correct state of motion to the particles. The first point follows under the usual quantum equilibrium assumptions. The second is a separate physical assumption, since the standard guiding equation does not follow from the Schrödinger equation alone. We argue that, in the evanescent regime, the state of motion assigned by the standard guiding equation is in disagreement with the measured speed. To make the distinction explicit, we also present a bidirectional Bohmian model that reproduces the same stationary density while assigning finite speeds compatible with the speed inferred in the evanescent regime.

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

Minimal surfaces, Knots, and Neural Networks

arXiv:2605.26234v2 Announce Type: replace-cross Abstract: A recent conjecture by Joel Fine posits a relationship between the coefficients of the HOMFLY polynomial of a knot $K$ in the 3-sphere $S^3$, and the signed count of minimal surfaces in hyperbolic 4-space $\mathrm{H}^4$ meeting the sphere at infinity at $K$, with prescribed genus and self-intersection number. In this paper, we develop a novel machine learning framework based on Physics-Informed Neural Networks (PINNs) to solve the minimal surface equation in hyperbolic space. We utilise this framework to test Fine's Conjecture by constructing near-minimal surfaces bounding various families of knots in $S^3$. Furthermore, we develop an algorithmic method to find self-intersections and compute their sign. For every knot analysed, the computationally discovered minimal surfaces and their self-intersection numbers perfectly align with the predictions of Fine's Conjecture, providing empirical evidence for it.

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

Creating squeezed and non-classical collective motional many-body states through stroboscopic Rydberg dressing

arXiv:2606.17849v1 Announce Type: cross Abstract: Realizing conditional quantum operations, e.g., quantum gates, for quantum computing and simulation requires controlled interactions between particles. Often, these interactions depend on the interparticle distance, and accordingly, an uncertainty of the relative particle position may translate into gate infidelities. We consider here a quantum computing platform based on an array of neutral atoms and present a method that allows to reduce the uncertainty of all interatomic distances. Our approach exploits the coupling between atomic motion and stroboscopically excited atomic Rydberg states. It allows to collectively squeeze the modes corresponding to interatomic displacements, thereby reducing distance fluctuations down to a fraction of the motional vacuum state. Furthermore, the method permits the creation of non-classical states with substantial Wigner negativity. These correlated states may allow reducing motional decoherence, increasing gate fidelity, and potentially yield a resource for quantum-enhanced metrology.

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

TWLA: Achieving Ternary Weights and Low-Bit Activations for LLMs via Post-Training Quantization

arXiv:2606.13054v1 Announce Type: cross Abstract: Large language models (LLMs) exhibit exceptional general language processing capabilities, but their memory and compute costs hinder deployment. Ternarization has emerged as a promising compression technique, offering significant reductions in model size and inference complexity. However, existing methods struggle with heavy-tailed activation distributions and therefore keep activations in high precision, fundamentally limiting end-to-end inference acceleration. To overcome this limitation, we propose TWLA, a post-training quantization (PTQ) framework that achieves 1.58-bit weight compression and 4-bit activation quantization while maintaining high accuracy. TWLA comprises three components: (1) Euclidean-to-Manifold Asymmetric Ternary Quantizer (E2M-ATQ) minimizes layer-output error under weight ternarization via a two-stage optimization from Euclidean initialization to manifold relocation; (2) Kronecker Orthogonal Tri-Modal Shaping (KOTMS) applies a Kronecker-structured orthogonal rotation to reshape weights into ternary-friendly tri-modal distributions, while the shared rotation statistically suppresses activation outliers; and (3) Inter-Layer Aware Activation Mixed Precision (ILA-AMP) explicitly introduces adjacent-layer second-order interaction costs in bit allocation and jointly optimizes for the layer-wise disparity of activation quantization gains induced by the shared orthogonal transform, preventing cascades triggered by a few weak layers. Extensive experiments demonstrate that TWLA maintains high accuracy under W1.58A4, while delivering significant inference acceleration. The code is available at .

16.
arXiv (math.PR) 2026-06-15

Uniform-in-time error estimates for McKean-Vlasov SDEs with common noise and stochastic algorithms

arXiv:2606.14170v1 Announce Type: new Abstract: In this work, by construct an asymptotic coupling by reflection, we first explore the uniform-in-time estimate on probability distance for two measure-valued processes induced by a McKean-Vlasov SDE with common noise and an interacting particle system, where the drift terms are dissipative merely in the long distance. As direct applications of this estimate, we establish the uniform-in-time error estimates for the numerical solutions derived via backward/tamed/adaptive Euler-Maruyama methods. Moreover, as another direct application, the uniform-in-time conditional propagation of chaos is quantified.

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

MemRerank: Preference Memory for Personalized Product Reranking

LLM-based shopping agents increasingly rely on long purchase histories and multi-turn interactions for personalization, yet naively appending raw history to prompts is often ineffective due to noise, length, and relevance mismatch. We propose MemRerank, a preference memory framework that distills user purchase history into concise, query-independent signals for personalized product reranking. To study this problem, we build an end-to-end benchmark and evaluation framework centered on an LLM-based 1-in-5 selection task, which measures both memory quality and downstream reranking utility. We further train the memory extractor with reinforcement learning (RL), using downstream reranking performance as supervision. Experiments with two LLM-based rerankers show that MemRerank consistently outperforms no-memory, raw-history, and off-the-shelf memory baselines, yielding up to +10.61 absolute points in 1-in-5 accuracy. These results suggest that explicit preference memory is a practical and effective building block for personalization in agentic e-commerce systems.

18.
arXiv (CS.LG) 2026-06-15

On the Geometry and Optimization of Polynomial Convolutional Networks

arXiv:2410.00722v3 Announce Type: replace Abstract: We study convolutional neural networks with monomial activation functions. Specifically, we prove that their parameterization map is regular and is an isomorphism almost everywhere, up to rescaling the filters. By leveraging on tools from algebraic geometry, we explore the geometric properties of the image in function space of this map - typically referred to as neuromanifold. In particular, we compute the dimension and the degree of the neuromanifold, which measure the expressivity of the model, and describe its singularities. Moreover, for a generic large dataset, we derive an explicit formula that quantifies the number of critical points arising in the optimization of a regression loss.

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

Source-Grounded Data Generation for Text-to-JSON Learning

From financial filings to clinical records, legacy industries rely heavily on long, unstructured documents to store high-value information. Reliably extracting this information into structured, machine-readable representations is a key prerequisite to making the contents accessible to automated systems. JSON is a natural target for such structured extraction, yet constructing reliable and scalable text-to-JSON training data remains challenging. To address this gap, we propose STAGE (Spreadsheet-grounded Text-to-JSON Artifact GEneration), a source-grounded data generation pipeline that constructs reports and JSON schema by using LLMs for scalable synthesis while validating ground-truth values against the underlying spreadsheet. Evaluations on STAGE-Eval, our source-grounded benchmark with an 851-example test set, show that STAGE produces stronger training data than existing approaches. This improves Qwen3-4B exact match from 31.37% to 74.27% and value accuracy from 45.46% to 90.69%.

20.
arXiv (math.PR) 2026-06-11

Improved Amenability Bounds for Local Coordination Games

arXiv:2606.01963v2 Announce Type: replace-cross Abstract: We study local pure coordination games on finite social networks, continuing the framework of Hutchcroft, Rospuskova, and Tamuz. They showed that low inefficiency in local coordination forces the underlying graph to be amenable, with a square-root loss in the amenability parameter. We improve this loss in the binary unbiased setting. Using Shapley values of a mutual-information game associated with the players' local outputs, we prove that if the average disagreement is at most $\varepsilon$, then the graph is $(O(\varepsilon\log(1/\varepsilon)),r)$-amenable. This gives a sharper quantitative converse between local coordination and graph amenability.

21.
arXiv (CS.CL) 2026-06-16

PathRouter: Aligning Rewards with Retrieval Quality in Agentic Graph Retrieval-Augmented Generation

Agentic GraphRAG trains language-model agents to iteratively retrieve and reason over graph-structured evidence, enabling more accurate and context-aware decision-making by efficiently navigating complex information networks. However, outcome-only reinforcement learning suffers from answer-path reward aliasing, where correct answers may come from shortcuts rather than useful evidence paths. It also exhibits search-update ambiguity, as scalar trajectory-level feedback does not indicate which retrieval actions to adjust. To mitigate these shortcomings, we present PathRouter, a path-aware training framework for agentic GraphRAG. PathRouter jointly evaluates each trajectory along answer correctness and evidence-path overlap, yielding four trajectory categories with differentiated GRPO advantage scaling that suppresses shortcut reinforcement while preserving evidence-seeking behavior. For evidence-poor trajectories, a frozen gold-evidence teacher provides token-level KL guidance on reasoning and search-query tokens, excluding answer tokens to avoid direct response imitation. Experiments on six QA benchmarks across three model sizes show that PathRouter consistently improves answer F1 and evidence-path overlap, achieving average F1 gains of 3.1 on 3B and 4.9 on 7B models compared to a strong baseline.

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

Towards a Unified Generative Model for Scarce Time Series with Domain Experts

arXiv:2606.15172v1 Announce Type: new Abstract: Synthesizing realistic time series with generative models has wide-ranging applications in real-world scenarios. Despite recent progress, most existing methods are trained under the assumption of abundant training data, which substantially limits their effectiveness in data-scarce settings. In this paper, we propose TimeMoDE, a novel framework that integrates Diffusion Transformers with Mixture-of-Experts to exploit both domain adaptability and diffusion-stage awareness for time series generation under data scarcity. It is pre-trained on a large-scale collection of multi-domain datasets to extract domain-agnostic temporal representations and domain-specific information benefiting generalization during fine-tuning. We propose Domain Prompts to condition expert assignment for indistinguishable noised tokens, mitigating the limitations of capturing inter-dataset relationships. Moreover, we incorporate diffusion timestep signals to equip the experts with awareness of time series degradation variations, facilitating adaptive calibrate to stage-dependent denoising requirements. Extensive experiments demonstrate that TimeMoDE outperforms existing methods under diverse low-data settings. It establishes an innovative paradigm for advanced time series few-shot generation.

23.
PLOS Computational Biology 2026-06-05

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

作者:

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

24.
arXiv (CS.LG) 2026-06-11

Spectrally Regularized Latent Flow Matching for Turbulence Generation

arXiv:2606.11691v1 Announce Type: new Abstract: Latent diffusion and flow matching have emerged as leading approaches for synthetic turbulence generation, yet they systematically under-represent dissipation-range amplitudes. We introduce a latent flow matching framework with a spectrally regularized compression stage that directly targets this failure mode. On a 256^2 DNS dataset at Re_f \approx 2250, replacing an MSE-trained VAE with a zone-weighted log-spectral objective raises deep-dissipation retained spectral power from 25% to 94% in reconstruction and from 20% to 79% in unconditional generation. The improved latent representation also yields a substantially better sampling cost-fidelity tradeoff: the MSE-trained latent space imposes a fundamental quality ceiling near DD bias -0.70 that no integrator or step-count can overcome, while the spectrally regularized latent space reaches DD bias -0.117 at just 20 function evaluations. Mechanistically, encoder-decoder swap experiments show that the improvement is driven primarily by encoder-induced latent reorganization rather than decoder capacity, while a support-amplitude decomposition reveals that MSE-trained models behave as conservative suppression models, minimizing pointwise error by attenuating intermittent high-wavenumber structure. Both pipelines recover the second-order structure function and the correct sign of S_3, indicating the correct cascade direction without explicit supervision. A small residual gap in the magnitude of S_3 suggests that phase-coherent triadic organization remains a complementary axis to amplitude fidelity for future generative turbulence models.

25.
arXiv (CS.CL) 2026-06-11

When Probing Accuracy Saturates, Fragility Resolves: A Complementary Metric for LLM Pre-Training Analysis

Standard linear probing declares a property "encoded" when a classifier on hidden states achieves high accuracy. The protocol works well on a snapshot but breaks across pre-training: probe accuracy saturates within the first few thousand steps, leaving most of training invisible to the instrument. We introduce fragility, a complementary per-layer metric defined as the activation-noise level at which probe accuracy collapses. Fragility is sensitive to both the margin of separability and the redundancy of representation, both of which keep evolving long after accuracy plateaus. Applied to open-checkpoint language models, fragility recovers structure that accuracy alone cannot see. Moralized representations emerge along a lexical $\to$ compositional gradient: lexical moral detection first, compositional moral encoding later. Because probe accuracy on its own tracks how lexically separable a dataset is, we establish the compositional encoding directly, by showing it transfers across construction types that share no contrast tokens. A layer-depth robustness gradient develops monotonically across training while accuracy stays flat. And matched fine-tuning corpora that produce identical probing accuracy leave distinct fragility fingerprints, showing that data curation reshapes probe robustness without changing probe accuracy. In every comparison we test, where probing accuracy returns a flat answer, fragility returns a structured one.