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01.
arXiv (CS.AI) 2026-06-24

Can Scale Save Us From Plasticity Loss in Large Language Models?

arXiv:2606.24752v1 Announce Type: new Abstract: The loss of plasticity - the ability of a network to learn new information after having already learned older information - is a fundamental challenge in creating artificial neural networks capable of continual learning. Although this phenomenon has been known for decades, it has mostly been studied in older, relatively small architectures and rarely in natural-language domains. To determine whether loss of plasticity remains a problem in the modern transformer-based LLM paradigm, we study plasticity loss in GPT-style Transformer models trained on a multilingual continual learning problem. Consistent with prior work, we find evidence of plasticity loss across models ranging from 5M to 314M non-embedding parameters, as measured by deterioration on a held-out Vietnamese probing task. We further find that the onset of plasticity loss follows a predictable scaling law, growing sublinearly with model size. These results suggest that larger models may delay the measurable effects of plasticity loss, but that increasing parameter count alone is likely to be insufficient to completely prevent it. We also find evidence of plasticity loss under stationary multilingual training, challenging the view that the phenomenon is exclusive to continual learning with abrupt task changes. Overall, our results suggest that even large Transformer language models trained on natural-language will eventually lose the ability to efficiently adapt to new data after sufficiently long training, in both continual and stationary settings.

02.
arXiv (CS.CV) 2026-06-24

DiffusionBench: On Holistic Evaluation of Diffusion Transformers

Diffusion transformer (DiT) research on image generation has converged to a single evaluation setup: class-conditional generation on ImageNet. While methods improve the FID and related metrics, it is increasingly unclear whether they reflect real progress in generative modeling. The natural alternative, i.e., text-to-image (T2I) generation, is perceived as too costly or inconvenient to train and evaluate and is often skipped. We argue that this perception no longer holds. We introduce NanoGen, a unified DiT training and evaluation framework. NanoGen matches state-of-the-art DiT baselines on ImageNet and, with 12 lines of configuration change, also trains competitive text-to-image models. It currently supports RAE, VAE, pixel-space, and MeanFlow diffusion methods under both ImageNet and T2I setups. Under NanoGen, training T2I requires comparable compute to ImageNet. After training 21 latent diffusion models with NanoGen, we observe that method ranking shows no strong correlation between ImageNet and T2I generation: Pearson correlation is between -0.377 and -0.580 across three metrics. This suggests that a method which improves class-conditional ImageNet FID may show no corresponding improvement on T2I, clearly indicating the necessity of evaluating DiTs on both tasks. To this end, we summarize ImageNet and text-to-image results, which yields DiffusionBench, a holistic benchmark for DiT research. We recommend reporting DiffusionBench in place of ImageNet alone: methods that improve DiffusionBench are more likely to reflect broader progress.

03.
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.

04.
arXiv (CS.AI) 2026-06-11

Improving Generalization and Data Efficiency with Diffusion in Offline Multi-agent RL

arXiv:2307.01472v2 Announce Type: replace Abstract: We present a novel Diffusion Offline Multi-agent Model (DOM2) for offline Multi-Agent Reinforcement Learning (MARL). Different from existing algorithms that rely mainly on conservatism in policy design, DOM2 enhances policy expressiveness and diversity based on diffusion model. Specifically, we incorporate a diffusion model into the policy network and propose a trajectory-based data-reweighting scheme in training. These key ingredients significantly improve algorithm robustness against environment changes and achieve significant improvements in performance, generalization and data-efficiency. Our extensive experimental results demonstrate that DOM2 outperforms existing state-of-the-art methods in all multi-agent particle and multi-agent MuJoCo environments, and generalizes significantly better to shifted environments {(in $28$ out of $30$ settings evaluated)} thanks to its high expressiveness and diversity. Moreover, DOM2 is ultra data efficient and requires no more than $5\%$ data for achieving the same performance compared to existing algorithms (a $20\times$ improvement in data efficiency).

05.
arXiv (CS.CV) 2026-06-12

Cross-Modal Masked Compositional Concept Modeling for Enhancing Visio-Linguistic Compositionality

Contrastively trained vision-language models like CLIP, have made remarkable progress in learning joint image-text representations, but still face challenges in compositional understanding. They often exhibit a "bag-of-words" behavior–struggling to capture the object relations, attribute-object bindings, and word order dependencies. This limitation arises not only from the reliance on global, single-vector representations for optimization, but also from the insufficient exploitation and modeling of the rich compositional information inherently present in paired image text data. In this work, we propose MACCO (MAsked Compositional Concept MOdeling), a framework that masks compositional concepts in one modality and reconstructs them conditioned on the full contextual information from the other, enabling the model to capture and align cross-modal compositional structures more effectively. To facilitate this process, we introduce two auxiliary objectives that jointly align and regularize masked features both inter-modally and intra-modally. Extensive experiments on five compositional benchmarks, along with in-depth analyses, demonstrate that our approach not only significantly enhances compositionality in VLMs but also improves their ability to capture syntactic structure and linguistic information. Additionally, the improved compositionality also benefits text-to-image generation and multimodal large language model. Code is available at https://github.com/hiker-lw/MACCO.

06.
medRxiv (Medicine) 2026-06-12

Design, Implementation, and Evaluation of a Shadowing Program for Medical Students in the Basic Sciences Phase

Introduction Shadowing, as an educational method based on active observation, can foster a realistic understanding of professional roles and enhance the communication skills of medical students. This study aimed to design, implement, and evaluate a shadowing program for basic sciences medical students. Methods This development study was conducted based on the ADDIE model in five phases. The study population consisted of 799 medical students in semesters 2 to 5. The stages included Analysis (determining needs through literature review and expert panels), Design (specifying learning environments and evaluation methods), Development (preparing guides and educational tools), Implementation (within the Medical Ethics course), and Evaluation (using questionnaires and reflection forms). Findings This study aimed to design and evaluate an educational shadowing program based on the ADDIE model. In the Analysis phase, the profiles of 799 students and learning objectives were determined. In the Design phase, a structured program for four types of shadowing was designed. In the Development phase, all guides and educational tools were prepared. In the Implementation phase, the program was carried out with complete coverage and adherence to ethical considerations. Finally, the program evaluation showed that "Motivation to become a good physician" (3.75-3.95) and "Enhancing empathy" (3.50-3.94) received the highest scores, while "Increasing understanding of the basic science-clinical connection" (2.53-2.89) and "Willingness to attend on holidays" (1.87-2.31) received the lowest scores. Conclusion The findings indicate that implementing the shadowing program is an effective method for strengthening the professional attitudes and academic motivation of medical students. However, the program did not significantly improve students perception of the basic science-clinical connection, indicating a need for curricular refinement. The continuation and extension of this program to other levels and fields of medical sciences are recommended.

07.
arXiv (CS.LG) 2026-06-18

Point-Cloud-Assistant Localized Statistical Channel Prediction by Tangent Gaussian Splatting

arXiv:2606.18734v1 Announce Type: cross Abstract: Accurate, site-specific channel information is crucial for optimizing next-generation wireless networks. Among various approaches, localized statistical channel modeling (LSCM), which models the channel multipath angular power spectrum (APS) from the reference signal received power (RSRP) measurement, has emerged as a state-of-the-art method tailored for efficient network optimization. However, despite its effectiveness, LSCM cannot predict APS at the vast majority of locations where no measurements are available, which significantly restricts its applicability in large-scale, real-world scenarios. To address this challenge, we present point-cloud-assisted tangent Gaussian splatting (PC-TGS), the first framework to extrapolate APS to unmeasured outdoor grids by integrating sparse radio measurements with dense LiDAR-based geometry. PC-TGS represents environmental scatterers as anisotropic 3D Gaussians, initialized and refined through a relaxed-mean reparameterization of the raw point cloud. A tangent-plane projection accurately maps each Gaussian into the local angular domain, while a depth-aware electromagnetic splatting process aggregates their contributions. To ensure practical deployment, we derive a closed-form Gaussian-weighted average (GWA) for APS bin integration and provide a provable error bound. { Evaluations on a LiDAR-scanned city-scale dataset (5M points, 6,310 RSRP samples) demonstrate that PC-TGS achieves better APS and RSRP prediction performance compared to state-of-the-art baselines and faster inference time for APS extrapolation task. These results highlight the potential of PC-TGS to enable geometry-aware and data-efficient channel prediction in large-scale wireless digital twins.

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

LLM-as-Code Agentic Programming for Agent Harness

arXiv:2606.15874v1 Announce Type: new Abstract: Every major LLM agent framework gives the LLM the role of orchestrator; the model decides what to do next, when to call tools, and when to stop. We argue that token explosion, control-flow hallucination, and unreliable completion are not implementation bugs but architectural consequences of assigning the deterministic work of looping, branching, and sequencing to a probabilistic system. A better prompt or a stronger model cannot guarantee the reliability of the LLM agent. We therefore propose Agentic Programming, in which the program governs all control flow, and the LLM is itself part of it, an adaptive component we call LLM-as-Code and invoke only where a task calls for reasoning or generation. Within each call the model keeps full flexibility, but it cannot alter the program's execution path. With control in the program, the LLM's context is built from the execution history's call tree and forms a directed acyclic graph (DAG). Each call's context length is then determined by its call depth rather than by accumulation over steps. A case study of computer-use agents shows that the design is practical, not just a theoretical stance, substantially improving the stability of long visual operation sequences.

09.
arXiv (CS.AI) 2026-06-24

SAFARI: Scaling Long Horizon Agentic Fault Attribution via Active Investigation

arXiv:2606.24626v1 Announce Type: new Abstract: As autonomous agents tackle increasingly complex multi-step, multi-agent tasks, their execution trajectories have scaled beyond the constraints of even the largest context windows. Current methods for effectively diagnosing agent failures load the full trajectory into an LLM's context window, which suffers from attention dilution and fails when agentic traces inevitably exceed context limits. To address this, we introduce SAFARI (Scaling long-horizon Agentic Fault AttRibution via active Investigation), a framework that replaces linear context loading with a tool-augmented diagnostic loop. By equipping LLMs with a specialized toolbox to read and search trajectory segments alongside a persistent Short-Term Memory (STM) for cross-turn reasoning, SAFARI effectively decouples diagnostic accuracy from architectural context limits. Our experiments demonstrate that SAFARI outperforms state-of-the-art results by 20% on the Who&When dataset within a 1M token budget, and by 19% on TRAIL GAIA subset on a 25K token budget. Most significantly, SAFARI maintains a 0.58 precision even when the target fault resides 5x beyond the model's native context window, a scenario where traditional evaluators fail entirely.

11.
arXiv (CS.LG) 2026-06-12

A Privacy-Preserving Framework Using Remote Data Science for Inter-Institutional Student Retention Prediction

arXiv:2606.12845v1 Announce Type: cross Abstract: This study explores privacy-preserving machine learning (PPML) techniques using the PySyft platform to enable collaborative prediction of student retention between institutions. We developed a remote data science (RDS) framework with a semi-air-gapped architecture consisting of high-side and low-side servers, allowing researchers from three universities to build predictive models on sensitive student data without direct data access. Using historical data from a small private university (N=720), we evaluated three synthetic data generation approaches and validated the framework through inter-institutional collaboration. The results demonstrate consistent classification performance across institutions (Macro F1: 0.690–0.695) while maintaining strict Family Educational Rights and Privacy Act (FERPA) compliance. We also propose Data-Type-Aware Templates, a novel synthetic data method that prioritizes privacy over distributional fidelity. Our findings confirm that RDS-based PPML is technically feasible for educational settings and offers a practical alternative to federated learning for small-scale inter-institutional collaborations. The code is available at https://github.com/jtfields/NAIRR240195-Privacy-Preserving-Machine-Learning.

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

Resurgence of the Thermal Transition between Bounce and Sphaleron

arXiv:2606.13778v1 Announce Type: cross Abstract: We study the thermal transition between the bounce and the sphaleron in quantum mechanics with a metastable vacuum from the viewpoint of Borel resurgence. For two models representing a second-order and a first-order transition, we compute the perturbative expansion of the thermal free energy to high orders and extract the leading Borel singularity data $(A,b,S)$ as functions of temperature. The Borel singularity location $A$ reproduces the on-shell action of the dominant saddle on both sides of the transition, joining smoothly in the second-order case and developing a kink in the first-order case. The characteristic exponent $b$ jumps between $0$ and $1/2$ across the transition, counting the zero modes of the corresponding saddle. The Stokes constant $S$ matches the one-loop determinant around the saddle. The perturbative expansion around the false vacuum thus determines the transition temperature, the order of the transition, and the decay rate including the one-loop prefactor without relying on semiclassical inputs.

13.
arXiv (quant-ph) 2026-06-16

Interaction-enabled topological pumping of Rydberg electrons

arXiv:2606.15126v1 Announce Type: cross Abstract: Topological pumping is a paradigmatic realization of quantized transport in band systems, yet its fate in strongly correlated regimes, especially with long-range interactions, remains largely unexplored. Here we report the experimental observation of interaction-enabled topological pumping of correlated Rydberg electrons in a synthetic lattice. We show that dipolar exchange interactions induce a controllable shift of the underlying topological singularity in parameter space, such that a fixed pumping trajectory can be driven through successive topological transitions by tuning the interaction strength alone. This leads to the emergence and breakdown of quantized transport. The observations are consistent with an effective Rice-Mele description with interaction-renormalized onsite potentials and are supported by characterizing the adiabaticity and robustness to control trajectory imperfections. Our results establish a platform for exploring interaction-controlled topological transport beyond perturbative regimes and open a route toward engineering correlated topological matter in synthetic quantum systems.

14.
arXiv (CS.AI) 2026-06-18

Engagement Intensity as a Learner-Modeling Signal for Adaptive AI Ethics Instruction

arXiv:2606.18548v1 Announce Type: cross Abstract: Adaptive AI ethics instruction in graduate research training benefits from intake measures that reflect differences in prior LLM experience. Prior coursework or workshop attendance is an obvious candidate, but it is not clear whether it is associated with pre-instruction ratings on key AI perception items. We compare three candidate intake features, self-reported usage frequency, self-rated LLM familiarity, and prior AI education, across five baseline perception outcomes in 93 bioscience graduate and postdoctoral trainees enrolled in a required research ethics course. Usage frequency shows Holm-corrected associations with all five outcomes, self-rated familiarity with three, and prior AI education with none. A threshold-like pattern at the lower end of the scale is most visible for training interest and accuracy trust rather than appearing as a uniform gradient across all five outcomes. In a short intake survey, reported LLM use is more consistently associated with these perceptions than prior coursework or workshops, with self-rated familiarity serving as a secondary indicator. These results suggest that simple pre-instruction behavioral signals can inform lightweight intake profiling for adaptive AI ethics education.

15.
arXiv (CS.AI) 2026-06-24

Alternate loss functions and regression models that achieve robustness to outliers by modulating the learning rate

arXiv:2606.22068v2 Announce Type: replace-cross Abstract: Most real-world datasets used for training supervised learning models are contaminated with noisy data and outliers leading to large prediction errors. This paper proposes a new approach for achieving robustness where the learning rate is modulated by a factor that is sensitive to outliers. In this approach a reduction of the learning rate is shown to be achieved by using alternate loss functions that are infinitely differentiable, strictly convex or quasiconvex and more closely approximate the absolute error than Huber and log-cosh losses. A comparison of the performance of regression models trained with different loss functions on a wide variety of benchmarks and datasets is presented to demonstrate the superior performance of the Square Root Loss (SRL) and Smooth Mean Absolute Error (SMAE) losses proposed in this paper. Two new robust linear regression models are presented. Highly vectorized robust parameter update formulae that take advantage of modern GPUs for both stochastic and batch gradient descent are presented.

16.
arXiv (CS.CL) 2026-06-15

SANA: What Matters for QA Agents over Massive Data Lakes?

Exploratory question answering (EQA) over data lakes requires an LLM agent to discover relevant sources, analyze retrieved data, and adapt its actions based on intermediate results. End-to-end accuracy alone cannot distinguish failures in search, planning, data analysis, or the agent's Action Policy: its decisions about what to do next and when to submit an answer. We present SANA (Search Agent Navigation Ablation framework), a diagnostic ablation framework that transforms EQA tasks into runtime profiles containing gold source sequence, sanitized subquestions, and execution records. SANA uses these profiles to construct idealized search, planning, and data-analysis tools, allowing each component to be ablated; the residual gap is diagnostic evidence for policy failures. To illustrate SANA as a reusable evaluation framework, we adapted two recent EQA benchmarks, LakeQA and KramaBench, and evaluated lightweight and mid-sized agents under fixed prompts, budgets, data lakes, and runtimes. Across both benchmarks, data analysis is a consistent bottleneck while planning is less so. Search is a major limitation in LakeQA's large data-lake setting, but less so for the smaller-scale KramaBench. SANA thus deconstructs end-to-end task accuracies into a diagnosis of where data-lake agents fail, and allows for systematic comparisons of progress in search, planning, data analysis, and agent design.

17.
arXiv (math.PR) 2026-06-16

Pricing Excess-of-Loss Reinsurance and CAT Bonds under Climate Uncertainty: A Cox Process Framework with Temperature-Dependent Stochastic Intensity

arXiv:2606.14830v1 Announce Type: cross Abstract: This paper develops a climate-aware pricing framework for excess-of-loss (XL) reinsurance contracts and catastrophe (CAT) bonds under non-stationary catastrophe risk. Catastrophe arrivals are modeled as a Cox process whose stochastic intensity depends exponentially on a temperature-related climate index. To represent climate dynamics, the index is modeled as a mean-reverting Ornstein–Uhlenbeck process around a time-dependent warming trend. Within this setting, aggregate losses follow a compound Cox structure with lognormal severities. Pricing is performed under a reduced-form risk-adjusted measure, which provides a tractable valuation approach for XL reinsurance layers and binary zero-coupon CAT bond payoffs in an incomplete market setting. Because catastrophe losses are not dynamically replicable, the framework emphasizes scenario-based valuation rather than model-independent no-arbitrage bounds. A Monte Carlo valuation scheme is implemented to quantify the economic implications of climate-dependent catastrophe intensity. The numerical results show that climate dependence materially changes the loss-generation mechanism and affects the valuation of catastrophe-linked contracts. In the baseline calibration, the climate-aware model increases the excess-of-loss reinsurance premium and lowers the CAT bond price relative to the stationary benchmark. Furthermore, our analysis of the 99.5\% Tail Value-at-Risk (TVaR) indicates that stationary benchmarks may underestimate economic capital requirements by approximately 13.7\% compared to the climate-aware framework, highlighting the potential regulatory relevance of the proposed model. This finding highlights that benchmark design is critical for interpreting climate-pricing effects.

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

Positional Encoding in the Context of Memristor-Based Analog Computation for Automatic Speech Recognition

arXiv:2606.13379v1 Announce Type: new Abstract: Memristors provide a new chance for resource-efficient computation of neural models for natural language processing by enabling analog execution of vector-matrix-multiplication. Yet, computations on these devices are currently subject to larger distortion, both in weight programming and execution. In this work, we identify large output values of transformed positional encodings to cause major degradation within analog-to-digital conversion (ADC) as part of memristor-based computation. By adjusting the proportion of weight and precision bits of the ADC of specific memristor layers, we reduce the degradation of the execution by ~50% relative, while keeping the estimated energy consumption stable. Additionally, we investigate scenarios where the ADC cannot be modified. In that case the degradation can be reduced by ~30% relative after removing encoding-related linear transformations.

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

Clustering and Pruning in Causal Data Fusion

arXiv:2505.15215v3 Announce Type: replace-cross Abstract: Data fusion, the process of combining observational and experimental data, can enable the identification of causal effects that would otherwise remain non-identifiable. Although identification algorithms have been developed for specific scenarios, do-calculus remains the only general-purpose tool for causal data fusion, particularly when variables are present in some data sources but not others. However, approaches based on do-calculus may encounter computational challenges as the number of variables increases and the causal graph grows in complexity. Consequently, there exists a need to reduce the size of such models while preserving the essential features. For this purpose, we propose pruning (removing unnecessary variables) and clustering (combining variables) as preprocessing operations for causal data fusion. We generalize earlier results on a single data source and derive conditions for applying pruning and clustering in the case of multiple data sources. We give sufficient conditions for inferring the identifiability or non-identifiability of a causal effect in a larger graph based on a smaller graph and show how to obtain the corresponding identifying functional for identifiable causal effects. Examples from epidemiology and social science demonstrate the use of the results.

20.
arXiv (CS.AI) 2026-06-11

Engineering Robustness into Personal Agents with the AI Workflow Store

arXiv:2605.10907v3 Announce Type: replace-cross Abstract: The dominant paradigm for AI agents is an "on-the-fly" loop in which agents synthesize plans and execute actions within seconds or minutes in response to user prompts. We argue that this paradigm short-circuits disciplined software engineering (SE) processes – iterative design, rigorous testing, adversarial evaluation, staged deployment, and more – that have delivered the (relatively) reliable and secure systems we use today. By focusing on rapid, real-time synthesis, are AI agents effectively delivering users improvised prototypes rather than systems fit for high-stakes scenarios in which users may unwittingly apply them? This paper argues for the need to integrate rigorous SE processes into the agentic loop to produce production-grade, hardened, and deterministically-constrained agent *workflows* that substantially outperform the potentially brittle and vulnerable results of on-the-fly synthesis. Doing so may require extra compute and time, and if so, we must amortize the cost of rigor through reuse across a broad user community. We envision an *AI Workflow Store* that consists of hardened and reusable workflows that agents can invoke with far greater reliability and security than improvised tool chains. We outline the research challenges of this vision, which stem from a broader flexibility-robustness tension that we argue requires moving beyond the ``on-the-fly'' paradigm to navigate effectively.

21.
medRxiv (Medicine) 2026-06-10

Towards the Virtual Amyotrophic Lateral Sclerosis Patient: Inferring Cortical Excitability through Whole-Brain Dynamical Modeling

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem neurodegenerative disorder in which motor-neuron degeneration is accompanied by widespread alterations in cortical dynamics. Among its most reproducible neurophysiological signatures is cortical hyperexcitability, yet how this local excitability imbalance shapes distributed whole-brain activity remains poorly understood. Here, we combined source-reconstructed resting-state MEG data, tractography-informed whole-brain modeling, and simulation-based inference to investigate whether ALS-related alterations in large-scale brain dynamics can be mechanistically explained by changes in cortical excitability. First, we characterized empirical brain dynamics using complementary features spanning regional activity amplitude and variability, functional connectivity, and avalanche-based metrics. These analyses revealed significant alterations in ALS patients relative to healthy controls, as well as associations with clinical impairment and disease staging. To mechanistically interpret these changes, we employed a reduced Wong-Wang whole-brain model in which local recurrent excitation modulates emergent large-scale neural dynamics. Simulations showed that increasing excitability systematically reproduced the empirical dynamical signatures observed in ALS. We then applied a simulation-based inference framework to estimate latent excitability parameters directly from empirical observations. Whole-brain model inversion revealed increased excitability in ALS patients compared with controls. The recovered excitability parameter was associated with disease staging, supporting its clinical relevance as a model-derived descriptor of ALS progression. Finally, by extending the model to estimate frontal and non-frontal excitability separately, we found that ALS-related alterations were predominantly associated with increased frontal excitability, whereas non-frontal regions appeared comparatively less affected. The recovered parameters related to disease staging. Together, these findings provide a mechanistic framework linking altered large-scale brain dynamics in ALS to selective cortical hyperexcitability, explaining how local excitability changes can give rise to global network reorganization. More broadly, they show how computational model inversion can recover latent multiscale pathophysiological processes from empirical neural recordings, offering a non-perturbative alternative to complex experimental paradigms typically required to causally probe local-to-global mechanisms.

22.
arXiv (CS.LG) 2026-06-15

Denoising Score Matching with Random Features: Insights on Diffusion Models from Precise Learning Curves

arXiv:2502.00336v3 Announce Type: replace Abstract: We theoretically investigate the phenomena of generalization and memorization in diffusion models. Empirical studies suggest that these phenomena are influenced by model complexity and the size of the training dataset. In our experiments, we further observe that the number of noise samples per data sample ($m$) used during Denoising Score Matching (DSM) plays a significant and non-trivial role. We capture these behaviors and shed insights into their mechanisms by deriving asymptotically precise expressions for test and train errors of DSM under a simple theoretical setting. The score function is parameterized by random features neural networks, with the target distribution being $d$-dimensional Gaussian. We operate in a regime where the dimension $d$, number of data samples $n$, and number of features $p$ tend to infinity while keeping the ratios $\psi_n=\frac{n}{d}$ and $\psi_p=\frac{p}{d}$ fixed. By characterizing the test and train errors, we identify regimes of generalization and memorization as a function of $\psi_n,\psi_p$, and $m$. Our theoretical findings are consistent with the empirical observations.

23.
medRxiv (Medicine) 2026-06-16

The biological clock of multimorbidity: temporal dynamics of disease co-occurrence in primary care

Multimorbidity is the dominant clinical reality of primary care, yet the temporal dynamics governing when and how persistent comorbidity associations emerge remain poorly characterised. Most large-scale comorbidity studies adopt a single observation window after an index diagnosis, implicitly assuming that associations detectable at one year are equally detectable at five. Using 11 years of electronic health records from 5,821,197 individuals in Catalan primary care, we applied a matched cohort design across nine complementary follow-up windows, five cumulative (0-1 to 0-5 years) and four conditional (1-2 to 4-5 years), to 1,315 index diseases, identifying 144,030 significant directed comorbidity associations in the five-year network. We found that 60.1% of these associations required at least three years of follow-up and were undetectable in shorter-window analyses, demonstrating that observation window length is a primary determinant of which comorbidities can be observed. To organise this temporal heterogeneity, we introduce the biological clock of multimorbidity: a two-dimensional framework that positions ICD-10 disease categories according to their rates of cumulative signal attenuation and the persistence of conditional risk. This framework identifies four reproducible temporal patterns (episodic, chronic stable, chronic progressive, and transient-persistent) that are robust under bootstrap resampling, leave-one-disease-out sensitivity analysis, and alternative clustering approaches. The biological clock is systematically modulated by sex, with Blood/Immune and Musculoskeletal disorders showing the largest sex differences in temporal dynamics. Network analysis identified 19 disease "initiators" that generate broad downstream comorbidity burdens and 21 "sinks" representing convergent endpoints of multiple disease trajectories. Comparison with hospital-based Danish data from 6,909,676 individuals showed that shared associations were 2.7-fold enriched over chance expectation (hypergeometric test, p

24.
bioRxiv (Bioinfo) 2026-06-22

HTS-Oracle X: AI-Guided Prospective Discovery of Small Molecule Immune Checkpoint Binders

Targeting immune checkpoint protein-protein interactions (PPIs) using small molecules remains limited by the shallow, featureless binding surfaces of co-stimulatory and co-inhibitory receptors and the characteristically low hit rates of conventional high-throughput screening against these interfaces. Here we report HTS-Oracle X, a multimodal deep learning platform that integrates bidirectional cross-attention fusion of ChemBERTa SMILES embeddings with extended RDKit descriptors, trains on continuous biophysical binding signals rather than binary labels, and employs Monte Carlo Dropout uncertainty quantification for uncertainty-adjusted compound selection. Trained on 45,760 Dianthus TRIC-screened compounds per target under scaffold-aware cross-validation, HTS-Oracle X was applied prospectively to a 100,160-compound Enamine library against CD28, TIM-3, and VISTA. From 150 model-selected compounds, 45 dose-response confirmed binders were identified (30.0% overall hit rate), yielding enrichment factors of 234-408x over experimentally established random prospective baselines and 16 sub-micromolar hits. The top hits, HX-CD28-1 (KD = 233 nM), HX-TIM3-1 (KD = 249 nM), and HX-VISTA-1 (KD = 345 nM), demonstrated on-target functional activity in immune cell and tumor co-culture assays. HTS-Oracle X represents a scalable AI-guided framework for small molecule discovery against non-enzymatic immune checkpoint targets.

25.
arXiv (CS.AI) 2026-06-17

Sustainable Metal-Organic Framework Water Harvesters in the Artificial Intelligence Era

arXiv:2605.29179v2 Announce Type: replace-cross Abstract: Metal-organic frameworks (MOFs) are excellent candidates for water harvesting due to their tunable pore environments, which can be precisely engineered to capture and release water in arid conditions. Integrating artificial intelligence (AI) into MOF discovery can further accelerate the design of high-performance sorbents by identifying structural features that enhance atmospheric water harvesting (AWH), stability, and cycling efficiency. In this Perspective, we examine key MOF design principles, including cooperative adsorption, operational relative humidity (RH), uptake capacity, hysteresis, and scalability. We highlight recent design advancements such as multivariate strategies and long-arm linker extension, and examine how these principles tune pore capacity and hydrophilicity, while preserving stability and crystallinity. Furthermore, we discuss how AI, large language models (LLMs), and data mining can accelerate the discovery process through predictive synthesis, inverse design, and elucidating synthesis-structure-property relationships for the next generation of MOF water harvesters.