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01.
arXiv (CS.CL) 2026-06-17

A Framework for Evaluating Agentic Skills at Scale

Agent skills – structured, reusable knowledge artifacts that augment LLM agent capabilities – have been rapidly adopted in industry, yet their cross-domain impact and use across commercial and open-source models remain under-studied, and no reusable methodology exists for evaluating an individual skill. In this work, we present an evaluation framework that lets a skill author construct realistic tasks to rigorously assess the aspects of a skill that matter most to them, and that estimates skill utility by solving those tasks. Further, we apply our evaluation approach at scale to 500 real-world skills, generating 1,000 tasks derived from the skills' content, along with instruction-following and goal-completion scoring rubrics. Using these metrics, we evaluate how 19 agent-model configurations, both proprietary and open-source, perform on the tasks. Our results show that models vary widely in how closely they adhere to the instructions encoded in skills, leading to substantial differences in their performance gains. Furthermore, we show that access to a skill significantly changes model behavior compared to the no-skill setup, providing an essential mechanism for encoding opinionated workflows into LLM agents. We release our evaluation dataset to support future work on agent skills.

02.
arXiv (CS.CV) 2026-06-18

Structured Spectral Graph Representation Learning for Multi-label Abnormality Analysis from 3D CT Scans

With the growing volume of CT examinations, there is an increasing demand for automated tools such as organ segmentation, abnormality detection, and report generation to support radiologists in managing their clinical workload. Multi-label classification of 3D Chest CT scans remains a critical yet challenging problem due to the complex spatial relationships inherent in volumetric data and the wide variability of abnormalities. Existing methods based on 3D convolutional neural networks struggle to capture long-range dependencies, while Vision Transformers often require extensive pre-training on large-scale, domain-specific datasets to perform competitively. In this work, we propose a 2.5D alternative by introducing a new graph-based framework that represents 3D CT volumes as structured graphs, where axial slice triplets serve as nodes processed through spectral graph convolution, enabling the model to reason over inter-slice dependencies while maintaining complexity compatible with clinical deployment. Our method, trained and evaluated on 3 datasets from independent institutions, achieves strong cross-dataset generalization, and shows competitive performance compared to state-of-the-art visual encoders. We further conduct comprehensive ablation studies to evaluate the impact of various aggregation strategies, edge-weighting schemes, and graph connectivity patterns. Additionally, we demonstrate the broader applicability of our approach through transfer experiments on automated radiology report generation and abdominal CT data.

03.
arXiv (quant-ph) 2026-06-11

Unifying Quantum Smoothing Theories with Extended Retrodiction

arXiv:2510.08447v2 Announce Type: replace Abstract: Estimating the state of an open quantum system monitored over time requires incorporating information from past measurements (filtering) and, for improved accuracy, also from future measurements (smoothing). While classical smoothing is well understood within a Bayesian framework, its quantum generalization has been challenging, leading to distinct and seemingly incompatible approaches. In this work, we demonstrate that quantum state smoothing hinges on a uniquely quantum feature: the fundamental dependence of retrodiction on prior correlations. We introduce auxiliary systems into the prior belief to capture correlations formed during preparation and evolution and develop a comprehensive framework for quantum state smoothing based on extended Bayesian retrodiction. This framework identifies all previous approaches as different choices of the extended prior, and naturally extends it to other choices that have not been considered before. We also give an information-theoretic characterization of the choices of prior, in terms of the average entropy of the smoothed states. Our results establish quantum state smoothing as a fundamentally retrodictive process just like classical smoothing, with proper quantum features clearly identified.

04.
arXiv (CS.LG) 2026-06-17

Overcoming the Incentive Collapse Paradox

arXiv:2603.27049v2 Announce Type: replace-cross Abstract: AI-assisted task delegation is increasingly common, yet human effort in such systems is costly and typically unobserved. Recent work by Bastani and Cachon (2025); Sambasivan et al. (2021) shows that accuracy-based payment schemes suffer from incentive collapse: as AI accuracy improves, sustaining positive human effort requires unbounded payments. We study this phenomenon in a budget-constrained principal-agent framework with strategic human agents whose output accuracy depends on unobserved effort. Our first contribution is a general impossibility result showing that incentive collapse is not merely a limitation of simple linear payments, but arises for any payment rule based only on observed task accuracy.To overcome this barrier, we propose a sentinel-auditing payment mechanism that enforces a strictly positive and controllable level of human effort at finite cost, independent of AI accuracy. Building on this incentive-robust foundation, we develop an incentive-aware active statistical inference framework that jointly optimizes (i) the auditing rate and (ii) active sampling and budget allocation across tasks of varying difficulty to minimize the final statistical loss under a single budget. Experiments demonstrate improved cost-error tradeoffs relative to standard active learning and auditing-only baselines.

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

A biological vision inspired framework for machine perception of abutting grating illusory contours

Higher levels of machine intelligence demand alignment with human perception and cognition. Deep neural networks (DNN) dominated machine intelligence have demonstrated exceptional performance across various real-world tasks. Nevertheless, recent evidence suggests that DNNs fail to perceive illusory contours like the abutting grating, a discrepancy that misaligns with human perception patterns. Departing from previous works, we propose a novel deep network called illusory contour perception network (ICPNet) inspired by the circuits of the visual cortex. In ICPNet, a multi-scale feature projection (MFP) module is designed to extract multi-scale representations. To boost the interaction between feedforward and feedback features, a feature interaction attention module (FIAM) is introduced. Moreover, drawing inspiration from the shape bias observed in human perception, an edge detection task conducted via the edge fusion module (EFM) injects shape constraints that guide the network to concentrate on the foreground. We assess our method on the existing AG-MNIST test set and the AG-Fashion-MNIST test sets constructed by this work. Comprehensive experimental results reveal that ICPNet is significantly more sensitive to abutting grating illusory contours than state-of-the-art models, with notable improvements in top-1 accuracy across various subsets. This work is expected to make a step towards human-level intelligence for DNN-based models.

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

PHINN: Persistent Homology Inspired Neural Network for Rare-Event Time Series Generation

arXiv:2606.15452v1 Announce Type: new Abstract: Rare events in time series are critical to model but hard to learn due to data scarcity. Current generative models struggle with extreme values. We observe that rare events leave distinct topological fingerprints - transitions in Betti numbers from point-cloud embeddings - that are more stable and discriminative than statistical moments. We introduce PHINN, a flow-matching framework using dynamic Betti curves as conditioning signals and a persistence landscape loss for homology consistency. It scales to multivariate data, includes a natural-language interface to set Betti targets, supports cross-domain meta-learning and few-shot generation, and provides certified adversarial robustness. On financial, epidemiological, and multi-modal benchmarks, PHINN outperforms statistical and diffusion baselines in topological fidelity (beta-RMSE down 41-63%, transition accuracy up 84%) and matches jump-diffusion models in tail coverage while exceeding them in shape fidelity. All results have 95% confidence intervals.

07.
bioRxiv (Bioinfo) 2026-06-10

ECMME: an atlas of selection pressures on the mammalian extracellular matrix reveals contrasting evolutionary dynamics

The extracellular matrix (ECM) is a fundamental metazoan innovation that provides structural support and regulatory cues essential for multicellular life. While core matrisome components are subject to strong functional constraints, their evolutionary dynamics at the molecular level remain incompletely characterized. Here, we present a comprehensive per-residue analysis of selection pressures across 272 human core matrisome proteins using high-quality orthologous sequences from up to 228 placental mammal species. We developed an automated pipeline integrating ortholog identification, codon-aware alignments, and site-specific selection analyses with the MEME and FUBAR methods from the HyPhy suite. Results reveal pervasive strong purifying selection across the matrisome, consistent with its structural and functional indispensability. This is accompanied by episodic positive selection and rarer pervasive positive selection, with collagens exhibiting significantly elevated episodic positive selection compared to glycoproteins and proteoglycans. To facilitate community access, we developed ECMME (ECM Molecular Evolution) browser, an intuitive open-access web resource that visualizes selection metrics plotted directly onto protein topologies. ECMME allows researchers to seamlessly browse and investigate the data, providing a powerful framework for interpreting functional sites. It is available online and requires no local installation or set-up (https://izzilab-ecmme.share.connect.posit.cloud/).

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

The Reservoir Attention Network: Cross-Pass State in Pretrained Transformers via Content-Addressable Reservoir Injection

Authors:

arXiv:2606.15678v1 Announce Type: cross Abstract: A feasibility and dynamics study of the Reservoir Attention Network (RAN), an architecture that injects a fixed, randomly-initialized reservoir into the mid-layer attention of a pretrained transformer to carry state across forward passes. Experiments span GPT-2 (124M, 355M) to Qwen2.5 (0.5B, 1.5B) on a single consumer GPU. The tasks are minimal probes chosen to isolate individual mechanisms; the broader always-alive agent vision is treated throughout as compute-limited future work, not a claim of this paper. The reservoir is left untrained (fixed random) by design: this isolates whether untrained recurrent dynamics alone suffice to carry usable cross-pass state, leaving trained recurrence as a complementary, more expensive direction.

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

StereoFactory: A Unified Merging Framework for Robust Stereo Matching

Stereo matching has advanced through foundation models trained on large-scale datasets, yet this paradigm suffers from a scalability bottleneck: incorporating new data requires costly joint retraining. Model merging offers a scalable post-hoc alternative by integrating knowledge from specialized models after source checkpoints are available. However, existing merging methods typically retain all available models or rely on greedy inclusion, which can preserve harmful task-vector interference. We propose StereoFactory, a coarse-to-fine evolutionary framework for adaptive model merging. Stage~1 employs a genetic algorithm to search the combinatorial space of model subsets, determining which models should participate. Stage~2 addresses module-level knowledge specialization (different functional modules exhibit distinct preferences for knowledge sources) through CMA-ES optimization of architecture-adaptive routing over the selected task vectors, with optional module-level scaling. Experiments across two architectures and four benchmarks demonstrate that StereoFactory consistently achieves the best four-benchmark average under the same checkpoint pool, reducing the average error from 3.80 to 3.30 on NMRF and from 2.88 to 2.19 on FoundationStereo relative to the strongest controlled baseline. The post-hoc search requires only 2.7–3.7\% of the corresponding joint-retraining wall-clock time. Analysis reveals that knowledge contributions are inherently module-specific, and selected subsets can transfer across architectures with minimal degradation. Code will be publicly released upon acceptance at: https://github.com/XiandaGuo/StereoFactory.

10.
arXiv (math.PR) 2026-06-15

Stationary measures for higher spin vertex models on a strip

Authors:

arXiv:2309.04897v2 Announce Type: replace-cross Abstract: We introduce a higher spin vertex model on a strip with fused vertex weights. This model can be regarded as a generalization of both the unfused six-vertex model on a strip arXiv:2212.09111 and an 'integrable two-step Floquet dynamics' model introduced in arXiv:1711.08884. We solve for the stationary measure using a fused version of the matrix product ansatz and then characterize it in terms of the Askey-Wilson process. Using this characterization, we obtain the limits of the mean density along an arbitrary down-right path. It turns out that all these models share a common phase diagram, which, after an appropriate mapping, matches the phase diagram of open ASEP. This provides evidence for the universality of this phase diagram.

12.
arXiv (CS.CV) 2026-06-16

Efficient Flow Matching using Latent Variables

Flow matching models have shown great potential in image generation tasks among probabilistic generative models. However, most flow matching models in the literature do not explicitly utilize the underlying clustering structure in the target data when learning the flow from a simple source distribution like the standard Gaussian. This leads to inefficient learning, especially for many high-dimensional real-world datasets, which often reside in a low-dimensional manifold. To this end, we present $\texttt{Latent-CFM}$, which provides efficient training strategies by conditioning on the features extracted from data using pretrained deep latent variable models. Through experiments on synthetic data from multi-modal distributions and widely used image benchmark datasets, we show that $\texttt{Latent-CFM}$ exhibits improved generation quality with significantly less training and computation than state-of-the-art flow matching models by adopting pretrained lightweight latent variable models. Beyond natural images, we consider generative modeling of spatial fields stemming from physical processes. Using a 2d Darcy flow dataset, we demonstrate that our approach generates more physically accurate samples than competing approaches. In addition, through latent space analysis, we demonstrate that our approach can be used for conditional image generation conditioned on latent features, which adds interpretability to the generation process.

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

P3D-Bench: Benchmarking MLLMs for Parametric 3D Generation and Structural Reasoning

Multimodal large language models can write code to produce complex programs as well as use programs to do 3D modeling, which opens up a new avenue for 3D generation powered by their priors, world knowledge and reasoning. Yet existing benchmarks rarely evaluate 3D modeling through code. Such modeling demands more than runnable code: from a text or visual specification, a model must generate a parametric 3D program that is geometrically precise, semantically aligned and assembly-consistent. We introduce P3D-Bench, a benchmark for parametric 3D generation. Unlike a 3D mesh, a parametric 3D program exposes explicit dimensions, construction operations and part relations, revealing whether a model recovers a design's structure, not just its appearance. Under a unified protocol, P3D-Bench covers three task families (Text-to-3D, Image-to-3D and Assembly-3D) and scores each output for executability, geometric fidelity, topology, text-grounded constraints, multiview semantic alignment and part-level structure. We evaluate frontier MLLMs and text-only LLMs on 400 text cases, 400 image cases and 203 annotated assemblies, with domain-specific models as reference points. Our extensive evaluation yields three findings. First, assemblies are the hardest setting, where models still fail to compose multiple parts into a coherent structure. Second, models can often recover the global shape and semantic identity of the target object, yet fail to reproduce the precise parametric geometry specified by the input. Third, part-level modeling remains weak on assemblies, where models recover neither the geometry of each part nor the right number of parts. These results position P3D-Bench as a benchmark for evaluating precise parametric geometry and part-level structure in parametric 3D generation.

14.
arXiv (CS.LG) 2026-06-12

Let's Ask Gauss: Improved One-Run Privacy Auditing

arXiv:2606.12733v1 Announce Type: new Abstract: Privacy auditing provides an important safeguard by estimating the actual information leaked by a model, thus ensuring that theoretical privacy guarantees hold in practice. We study empirical privacy auditing for differentially private (DP) machine learning, focusing on efficient one-run methods for mechanisms such as DP-SGD. Prior one-run approaches threshold training examples or "canaries" into binary membership guesses, which discards useful information. We show that, in the white-box DP-SGD setting, canary-aligned signals naturally form a sequence of random variables whose normalized sum is asymptotically Gaussian. Leveraging this distributional perspective, we develop a DP-auditing framework that leads to tighter privacy lower bounds from a single training run.

15.
arXiv (quant-ph) 2026-06-17

Quantum Resources and Wigner Symmetry in Nucleon-Nucleon Scattering from Effective Field Theory

arXiv:2606.17148v1 Announce Type: cross Abstract: We study quantum resources in the spin degrees of freedom, such as entanglement, stabilizer magic, and non-local magic, in low-energy nucleon-nucleon scattering through next-to-leading order in pionless effective field theory. Treating each nucleon spin as a qubit, we calculate the corresponding resource-generating powers of the scattering operator at generic center-of-mass momentum and scattering angle $\Theta$. The analysis retains $S$- and $P$-wave channels generated by two-derivative contact interactions. When the microscopic physics exhibits Wigner's $SU(4)$ spin-flavor symmetry, the neutron-proton amplitude becomes proportional to the spin-space identity operator and therefore generates no new resources after scattering, extending an observation previously made for leading-order $S$-wave scattering. The same-nucleon channel remains resource-generating because constraints from identical particles project out part of the Hilbert space. These results show how enhanced symmetries, partial-wave structure, and resource generation are intertwined in low-energy two-body scattering.

16.
arXiv (CS.CV) 2026-06-12

Skeleton Sparsification and Densification Scale-Spaces

The Hamilton-Jacobi skeleton, also known as the medial axis, is a powerful shape descriptor that represents binary objects in terms of the centres of maximal inscribed discs. Despite its broad applicability, the medial axis suffers from sensitivity to noise: Minor boundary variations can lead to disproportionately large and undesirable expansions of the skeleton. Classical pruning methods mitigate this shortcoming by systematically removing extraneous skeletal branches. This sequential simplification of skeletons resembles the principle of sparsification scale-spaces that embed images into a family of reconstructions from increasingly sparse pixel representations. We combine both worlds by introducing skeletonisation scale-spaces: They leverage sparsification of the medial axis to achieve hierarchical simplification of shapes. Unlike conventional pruning, our framework inherently satisfies key scale-space properties such as hierarchical architecture, controllable simplification, and equivariance to geometric transformations. We provide a rigorous theoretical foundation in both continuous and discrete formulations and extend the concept further with densification. By growing the skeleton successively instead of shrinking it, we allow inverse progression from coarse to fine scales. Densification scale-spaces can even reach beyond the original skeleton to produce overcomplete shape representations with relevancy for practical applications. Through proof-of-concept experiments, we demonstrate the effectiveness of our framework for practical tasks including robust skeletonisation, shape compression, and stiffness enhancement for additive manufacturing.

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

A theory of learning data statistics in diffusion models, from easy to hard

arXiv:2603.12901v2 Announce Type: replace-cross Abstract: While diffusion models have emerged as a powerful class of generative models, their learning dynamics remain poorly understood. We address this issue first by empirically showing that standard diffusion models trained on natural images exhibit a distributional simplicity bias, learning simple, pair-wise input statistics before specializing to higher-order correlations. We reproduce this behaviour in simple denoisers trained on a minimal data model, the mixed cumulant model, where we precisely control both pair-wise and higher-order correlations of the inputs. We identify a scalar invariant of the model that governs the sample complexity of learning pair-wise and higher-order correlations that we call the diffusion information exponent, in analogy to related invariants in different learning paradigms. Using this invariant, we prove that the denoiser learns simple, pair-wise statistics of the inputs at linear sample complexity, while more complex higher-order statistics, such as the fourth cumulant, require at least cubic sample complexity. We also prove that the sample complexity of learning the fourth cumulant is linear if pair-wise and higher-order statistics share a correlated latent structure. Our work describes a key mechanism for how diffusion models can learn distributions of increasing complexity.

18.
medRxiv (Medicine) 2026-06-23

Default Handling of the Non-Assessable Verbal Glasgow Coma Scale Misclassifies Illness Severity in Mechanically Ventilated Patients: A Retrospective Analysis

Background: The Glasgow Coma Scale (GCS) is a universal neurologic severity score in the intensive care unit and is incorporated into APACHE, SOFA, mortality prediction models, ICU benchmarking, and quality metrics. In mechanically ventilated patients, however, the verbal component cannot be assessed. Common conventions, including assigning a normal total GCS of 15 or excluding patients with missing verbal scores, may misclassify the sickest patients as neurologically normal or remove them from analysis. Objective: To quantify non-assessable verbal GCS examinations after acute brain injury and determine how different handling conventions affect severity scoring and mortality-model performance across two independent critical care databases. Materials and Methods: We conducted a retrospective cohort study of adults with acute brain injury during their first ICU stay in MIMIC-IV, with replication in eICU-CRD. A verbal examination was considered non-assessable when documented as No Response-ETT. We measured the burden and determinants of non-assessability, compared the MIMIC-IV derived GCS convention with a component-aware GCS, and evaluated mortality-model handling strategies. Results: Among 14,230 patients, 45.2% had a non-assessable verbal examination, and 47.5% of ventilated patients had no assessable verbal score in the first 24 hours. Non-assessability was strongly associated with mechanical ventilation and mortality. The MIMIC-IV derived GCS assigned a score of 15 to 42.9% of patients and placed 11.6% in the lowest severity category despite eye and motor findings consistent with GCS [≤]9. Complete-case handling excluded 28.5% of patients, who accounted for 50.2% of deaths. Similar distortions were observed in eICU-CRD/APACHE across 171 hospitals. Discussion: Default-to-normal scoring can make severely ill intubated patients appear neurologically normal, while complete-case analysis removes the highest-risk patients. Conclusion: Non-assessable verbal GCS in mechanically ventilated patients should be explicitly flagged and reported in ICU severity scores, risk-adjusted mortality models, and benchmarking systems.

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

Surrogate-Assisted Framework for SI-Compliant Interconnect Design Optimization Using the Earth Mover's Distance

arXiv:2606.15234v1 Announce Type: cross Abstract: This work presents a deterministic, machine-assisted framework for SI-compliant PCB design based on the Earth Mover's Distance (EMD). In contrast to conventional surrogate-based optimization methods that rely on iterative black-box search procedures, the proposed approach follows an interpretable, sequential evaluation strategy. Neural surrogate models are first used to efficiently predict waveform describing features from topology-dependent design parameters. A decision tree then acts as a physically motivated quality gate that identifies SI-compliant waveforms according to predefined SI criteria. Within the resulting valid solution space, the Earth Mover's Distance is employed as a similarity metric to rank candidate designs according to their proximity to an ideal reference signal. This enables not only the deterministic identification of admissible parameter regions but also a transparent prioritization of physically superior solutions without inverse modeling or stochastic search procedures. The methodology is demonstrated using a large-scale set of simulated DDR3 fly-by waveforms. By combining surrogate prediction, interpretable classification, and EMD-based waveform evaluation, the framework provides an explainable and computationally efficient alternative to conventional optimization strategies for supporting PCB development with AI-based methods.

20.
arXiv (CS.AI) 2026-06-16

Visual-Seeker: Towards Visual-Native Multimodal Agentic Search via Active Visual Reasoning

arXiv:2606.15231v1 Announce Type: new Abstract: Multimodal large language models (MLLMs) have demonstrated impressive capabilities in many visual tasks, but they often struggle with factual grounding when confronted with complex, open-world scenarios. While recent multimodal deep search agents attempt to address this issue by utilizing external tools, the visual-native search paradigm remains underexplored. Existing methods primarily rely on simple images with explicit semantics and text-only evidence trajectories, limiting the agent's ability to perform multi-hop, cross-modal reasoning and search. To address these limitations, we propose Visual-Seeker, a visual-native multimodal deep search agent via active visual reasoning. Rather than treating vision as a static input, our agent actively attends to fine-grained visual details, dynamically harvests visual evidence throughout the search process. To unlock its visual-native potential, we design an active visual reasoning data pipeline and synthesize 5K high-quality multimodal trajectories for model training. Extensive experiments demonstrate the state-of-the-art performance across five challenging multimodal search benchmarks, even surpassing several proprietary models, validating robust visual-native reasoning and search in real-world web environments. The code and data can be accessed at: https://github.com/ZhengboZhang/Visual-Seeker.

21.
arXiv (CS.CV) 2026-06-15

Self-Evolving Visual Questioner

Vision-language models (VLMs) are typically trained as passive answerers, while their ability to actively ask diverse, non-trivial, visual-centric and grounded questions remains underexplored. Existing visual questioners' performance is bottlenecked by the availability of high-quality training data or the cost of curating them. We show that a VLM can continuously improve itself as a visual questioner without any external supervision. We propose a self-evolving framework that uses a VLM itself as both a proposer and a filter to produce harder, more informative, and visual-centric questions, while maintaining their exploration diversity to avoid training collapse. These questions are then used to train the VLM in both questioner and answerer modes. To evaluate the questioner, we introduce an agentic protocol that assesses questions along perception, reasoning, and diversity dimensions. Experiments across various backbone VLMs show that our method substantially enhances the quality and substantially expands the difficulty boundary of autonomous question generation. Under the same budget, our self-supervision is more effective than training on the static source data. Moreover, the self-evolving questioner remains a competitive or even better answerer.

22.
arXiv (CS.LG) 2026-06-12

EPM-JEPA: Operator-Side Experience Modulation in JEPA-Family World Models

Authors:

arXiv:2606.12979v1 Announce Type: new Abstract: JEPA-family world models use a static predictor whose weights do not adapt when test-time dynamics diverge from training. We compare two mechanisms for incorporating accumulated experience into a JEPA predictor under distribution shift: operand-side injection, where a compressed experience representation is added as a residual to the predictor's hidden state (EI-JEPA), and operator-side modulation, where the same representation generates low-rank weight deltas via LoRA applied to the predictor's weights (EPM-JEPA). On a pre-registered comparison (Moving MNIST, gravity shift), EPM-JEPA (D_shift^{n=50} = 0.7848 +/- 0.0078, three seeds) differs from EI-JEPA (0.8238) by delta = 4.74% - Outcome C: a null result - by our stated criterion, a valid outcome. As a secondary, non-pre-registered observation, EPM-JEPA improves 1.90% over a no-memory baseline (0.8000), consistently across seeds, while EI-JEPA underperforms the baseline, indicating the benefit is specific to weight-level modulation. Our primary contribution is a mechanism analysis: the D_shift^{n=50} trajectory reflects three independent dynamical processes - buffer cycling, EMA target drift, and an intrinsic LoRA settling transient of +0.021 - rather than convergence to equilibrium. These findings motivate PEM-JEPA, a physics-grounded successor addressing this dynamical-peak limitation.

23.
bioRxiv (Bioinfo) 2026-06-12

Computational Design of Optimal Sequences for Targeted Hypermutagenesis Using Recombination-Coupled Diversity-Generating Retroelements

Diversity-generating retroelements (DGRs) are natural systems that accelerate evolution via targeted hypermutation at adenines. We previously developed DGRec, a system combining DGRs and recombineering for programmable mutagenesis in Escherichia coli. We here address two important issues with DGRec: the dependence of mutagenesis efficiency on the dgrRNA secondary structure and the variability of the reverse-transcription biases with sequence context and position. First, we introduce and validate a method to recode non-functional templates, i.e. with low mutagenesis efficiency, into highly functional ones through synonymous mutations. Second, we develop a Long Short-Term Memory (LSTM) model to predict DGRec mutational profiles for any given template sequence. By integrating this LSTM model with our recoding method, we establish a comprehensive workflow for customized directed evolution, enabling researchers to precisely fine-tune DGRec in vivo mutagenesis to their engineering needs.

24.
arXiv (CS.CL) 2026-06-12

Causal Inference with Generative Artificial Intelligence: Application to Texts as Treatments

In this paper, we demonstrate how to enhance the validity of causal inference with unstructured high-dimensional treatments like texts, by leveraging the power of generative Artificial Intelligence (GenAI). Specifically, we propose to use a deep generative model such as large language models (LLMs) to efficiently generate treatments and use their internal representation for subsequent causal effect estimation. We show that the knowledge of this true internal representation helps disentangle the treatment features of interest, such as specific sentiments and certain topics, from other possibly unknown confounding features. Unlike existing methods, the proposed GenAI-Powered Inference (GPI) methodology eliminates the need to learn causal representation from the data, and hence produces more accurate and efficient estimates. We formally establish the conditions required for the nonparametric identification of the average treatment effect, propose an estimation strategy that avoids the violation of the overlap assumption, and derive the asymptotic properties of the proposed estimator through the application of double machine learning. Finally, using an instrumental variables approach, we extend the proposed GPI methodology to the settings in which the treatment feature is based on human perception. The GPI is also applicable to text reuse where an LLM is used to regenerate existing texts. We conduct simulation and empirical studies, using the generated text data from an open-source LLM, Llama 3, to illustrate the advantages of our estimator over state-of-the-art causal representation learning algorithms.

25.
medRxiv (Medicine) 2026-06-23

A pharmacometric grey zone reconciles high metronidazole resistance rates with bismuth quadruple therapy efficacy in Helicobacter pylori

Summary Background Metronidazole (MET) resistance in Helicobacter pylori (H. pylori) exceeds 50-60% globally, yet MET-containing bismuth quadruple therapy (BQT) achieves &gt90% eradication in MET-resistant infections. We hypothesise this discordance stems from a structural limitation of two-fold dilution: a pharmacometric grey zone between the 128 and 256 &microg/mL breakpoints where treatable isolates are systematically misclassified as high-level resistance. Methods In a real-world cohort of 4610 treatment-na&iumlve children (2019-2024), checkerboard assays determined the bismuth-MET synergy factor (SF). Population PK/PD modelling simulated gastric MET exposure (AUC