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01.
arXiv (CS.CL) 2026-06-18

Sumi: Open Uniform Diffusion Language Model from Scratch

Diffusion models have become a promising alternative to autoregressive models. Among these, uniform diffusion language models (UDLMs) permit any token to be updated at any step, in principle enabling more flexible generation. However, no UDLM has yet been pretrained from scratch at both large parameter scale and large token budget. Both autoregressive modeling and masked diffusion modeling already have capable models at scale that the community can study and build on; uniform diffusion has none. A scratch-pretrained UDLM at scale would provide a clean reference point for studying scaling behavior, generation dynamics, controllability, and trade-offs against established autoregressive and masked diffusion models. To this end, we introduce Sumi ("ink" in Japanese), a fully open 7B uniform diffusion language model pretrained from scratch on 1.5T tokens. Sumi performs competitively with autoregressive models trained at comparable token budgets on knowledge, reasoning, and coding benchmarks, while under-performing on commonsense benchmarks, where our education-heavy data mixture is a likely contributor. We release our model weights, checkpoints, and full training recipe, including a complete specification of the data mixture over publicly available corpora. We hope this release enables the community to study native uniform diffusion at scale and catalyzes work on its as-yet poorly understood aspects.

02.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

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

Entropy-Aware On-Policy Distillation of Language Models

On-policy distillation is a promising approach for transferring knowledge between language models, where a student learns from dense token-level signals along its own trajectories. This framework typically uses reverse KL divergence, encouraging the student to match the teacher's high-confidence predictions. However, we show that the mode-seeking property of reverse KL reduces generation diversity and yields unstable learning signals when the teacher distribution has high entropy. To address this, we introduce Entropy-Aware On-Policy Distillation. Our key idea is augmenting the standard reverse KL objective with forward KL when teacher entropy is high, capturing the full range of plausible outputs while retaining precise imitation elsewhere. It balances mode-seeking precision with mode-covering robustness without sacrificing on-policy training efficiency. Experiments show that our method maintains generation diversity (sustained token-level entropy) and improves student-teacher alignment (lower forward KL on high-entropy tokens). Across six math reasoning benchmarks, this yields Pass@8 accuracy gains of +1.37 for Qwen3-0.6B-Base, +2.39 for Qwen3-1.7B-Base, and +5.05 for Qwen3-4B-Base compared to baseline on-policy distillation methods. These results demonstrate that accounting for teacher uncertainty is essential for maintaining diversity and achieving effective knowledge transfer.

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

CRC-Screen: Certified DNA-Synthesis Hazard Screening Under Taxonomic Shift

Authors:

arXiv:2605.00074v2 Announce Type: replace-cross Abstract: DNA-synthesis providers screen incoming orders by searching the requested sequence against curated hazard lists. We show that this baseline collapses to a 100% false-flag rate when the hazardous sequence comes from a taxonomic family absent from the reference set: under Conformal Risk Control's certified miss-rate constraint, a low-discrimination signal forces the threshold below the entire test-benign mass. We compose three signals derived from a synthesis order's public annotation: $k$-mer Jaccard similarity to known toxins, the trimmed-mean score of a five-LLM judge panel, and cosine similarity to clustered embedding centroids. Fused under a monotone logistic aggregator and calibrated by Conformal Risk Control, the resulting screener certifies $\mathbb{E}[\mathrm{FNR}] \le \alpha + \mathrm{TV}$, where the additive term is the calibration-to-test distribution shift under family holdout (a certified ceiling of 24-49% across folds). Across ten leave-one-taxonomic-family-out folds at $\alpha=0.05$ on UniProt KW-0800 reviewed toxins, the calibrated screener achieves 0% empirical test miss rate on every fold and 0% test false-flag rate on nine of ten folds. The bound's finite-sample slack $1/(n_{\mathrm{cal}}+1)$ caps the certifiable miss rate at 1.77% on our 200-hazard subsample; reaching procurement-grade $\alpha=10^{-3}$ requires an $18\times$ larger calibration set, which the full reviewed UniProt KW-0800 corpus is large enough to deliver. The binding constraint on certifiable DNA-synthesis screening is calibration data, not algorithms. Code: https://github.com/najmulhasan-code/crc-screen

05.
arXiv (CS.CL) 2026-06-19

MENTOR: Reinforcement Learning via Flexible Teacher-Optimized Rewards for Tool-Use Distillation

Distilling the tool-use capabilities of large language models (LLMs) into small language models (SLMs) is essential for their practical application. The predominant approach, supervised fine-tuning (SFT), suffers from poor out-of-domain (OOD) generalization due to its rigid alignment with static teacher trajectories. While reinforcement learning (RL) offers an alternative, the capacity limitations of SLMs pose a severe dilemma: sparse outcome rewards provide insufficient guidance, whereas strict trajectory matching imposes overly restrictive constraints. To bridge this capacity-driven gap, we propose MENTOR, which introduces a flexible yet process-aware reward structure. Instead of enforcing rigid replication, MENTOR uses the teacher's reference to guide tool-use behavior, balancing behavioral alignment with downstream performance. Extensive experiments on controlled executable-tool benchmarks demonstrate that MENTOR improves OOD tool-use performance compared to SFT and strict RL baselines. Our findings suggest that within verifiable tool-use environments, flexible tool-use alignment offers a more effective approach than strict trajectory replication for developing adaptable small models.

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

Multi-Agent Systems are Mixtures of Experts: Who Becomes an Influencer?

arXiv:2605.25929v2 Announce Type: replace-cross Abstract: The effectiveness of multi-agent LLM deliberation depends not only on the agents' individual predictions, but also on how they communicate and collaborate. We study this mechanism through the lens of Friedkin-Johnsen (FJ) opinion dynamics, a tractable model for analyzing stubbornness, influence, and opinion change in multi-agent systems that captures empirically observed deliberation patterns. We show that the FJ parameters are input-dependent, turning multi-agent deliberation into a mixture of experts. This perspective implies that multi-agent systems can outperform single agents and static ensembles when routing reflects agent competence. Since competence is latent in practice, we analyze how influence is established through observable proxies: agents' self-assessed confidence, their perceived confidence, and initial alignment with other agents' views.

07.
arXiv (CS.CV) 2026-06-11

Semantic search for 100M+ galaxy images using AI-generated captions

Finding scientifically interesting phenomena through slow manual labeling campaigns severely limits our ability to explore the billions of galaxy images produced by telescopes. In this work, we develop a pipeline to create a semantic search engine from completely unlabeled image data. Our method leverages Vision-Language Models (VLMs) to generate descriptions for galaxy images, then contrastively aligns a pre-trained astronomy foundation model with these embedded descriptions to produce searchable embeddings at scale. We find that current VLMs provide descriptions that are sufficiently informative to train a semantic search model that outperforms direct image similarity search. Our model, AION-Search, achieves state-of-the-art zero-shot performance on finding rare phenomena despite training on randomly selected images with no deliberate curation for rare cases. Furthermore, we introduce a VLM-based re-ranking method that nearly doubles the recall for our most challenging targets in the top-100 results. For the first time, AION-Search enables flexible semantic search for over 100 million galaxy images, enabling discovery from previously infeasible searches, including the identification of 36 new extragalactic stellar stream candidates. More broadly, our work provides an approach for making large, unlabeled scientific image archives semantically searchable, expanding data exploration capabilities in fields from Earth observation to microscopy. The code, data, and app are publicly available at https://github.com/NolanKoblischke/AION-Search

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

CyberEvolver: Structured Self-Evolution for Cybersecurity Agents On the Fly

arXiv:2605.26195v2 Announce Type: replace-cross Abstract: LLM-based agents are increasingly used for cybersecurity tasks, but most existing systems rely on fixed, human-designed scaffolds that struggle to adapt across diverse targets and failure modes. We introduce \textsc{CyberEvolver}, a self-evolving cybersecurity agent framework that iteratively revises its own scaffold based on experience from failed execution attempts. Self-evolution in cybersecurity is challenging because the space of possible scaffold changes is largely unstructured, execution feedback is sparse and often obscured by the environment, and low-diversity updates can cause errors to compound over repeated iterations. \textsc{CyberEvolver} addresses these challenges with a four-layer evolvable agent architecture that decomposes scaffold optimization into structured components, a trace-to-diagnosis mechanism that converts noisy execution logs into actionable revision signals, and a population-based beam search strategy that preserves diverse agent variants during evolution. We evaluate \textsc{CyberEvolver} on CTF challenges, vulnerability exploitation, and penetration-testing tasks using four open-source LLMs. Across these settings, \textsc{CyberEvolver} improves the seed agent's success rate by $13.6$\,\% on average, and outperforms six human-designed cybersecurity agents as well as two self-improvement methods adapted from other domains. These results suggest that scaffold self-evolution is a promising direction for building adaptive LLM agents for security testing.

09.
arXiv (CS.CV) 2026-06-11

Wild3R: Feed-Forward 3D Gaussian Splatting from Unconstrained Sparse Photo Collection

Feed-forward 3D Gaussian Splatting (3DGS) removes the need for time-consuming per-scene optimization required by traditional 3DGS. However, existing feed-forward approaches struggle with real-world photo collections that include diverse lighting conditions and transient objects. In this paper, we present Wild3R, a feed-forward approach for unconstrained sparse photo collections. The main bottleneck is the lack of training data that provides multiple viewpoints, a variety of illuminations, and transient variations necessary for learning robust scene representations. To address this, we introduce the WildCity dataset, which comprises 200 scenes, 170 lighting conditions, and transient objects, resulting in 337,500 images in total. By leveraging the dataset, our model learns appearance consistency across viewpoints conditioned on reference views, while removing transient content. Extensive experiments demonstrate that our method outperforms existing feed-forward approaches and achieves results competitive with prior per-scene optimization-based methods.

10.
arXiv (CS.LG) 2026-06-19

Evolutionary Two-Stage Hyperparameter Optimization Strategies for Physics-Informed Neural Networks

arXiv:2606.20442v1 Announce Type: new Abstract: Physics-Informed Neural Networks (PINNs) solve Partial Differential Equations (PDEs) by embedding physical laws into neural network training. However, their performance suffers from unstable convergence, training plateaus, and strong sensitivity to architectural and optimization hyperparameters due to the highly non-convex and multi-term structure of the physics-informed loss. In this setting, the outer-loop hyperparameter search is a noisy and black-box optimization problem over heterogeneous parameters, where classical local or gradient-based strategies are easily trapped in suboptimal regions. Evolutionary algorithms, with their population-based exploration and ability to handle mixed, non-differentiable search spaces, provide a more robust mechanism for discovering promising configurations. We propose and investigate a two-stage approach based on evolutionary algorithms that combines exploration and exploitation parts of PINNs training to improve solution accuracy and robustness under fixed computational budgets. In the first stage, we perform low-fidelity training runs with truncated epochs to rapidly screen candidate configurations, treating hyperparameter selection as a black-box outer-loop problem. In the second stage, only the most promising candidates are fully trained with standard gradient-based optimizers to refine the solution. Evaluated on three popular problems, namely Advection, Klein-Gordon and Helmholtz equations, our method consistently outperforms standard training and achieves significantly lower mean error within constrained computational resources.

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

Stabilizing Bandits using Regularization: Precise Regret and A Quantitative Central Limit Theorem

arXiv:2603.10184v2 Announce Type: replace-cross Abstract: Statistical inference with bandit data presents fundamental challenges owing to adaptive sampling, which violates the independence assumptions underlying classical asymptotic theory. Recent work has identified stability~\citep{laiwei82} as a sufficient condition for valid inference under adaptivity. This paper first provides a refined stability condition, stated in terms of the iterates of an online algorithm, and shows that a large class of regularized stochastic-mirror-descent-style algorithms satisfy it. This refined condition allows us to strengthen the asymptotic results of~\citet{laiwei82} in several ways. First, we derive a non-asymptotic Berry–Esseen bound for the empirical reward estimates under adaptive sampling. Second, we derive matching non-asymptotic upper and lower bounds on the regret of the proposed algorithm, yielding a precise characterization of its regret. Third, we show that these regularized algorithms preserve asymptotic normality and valid inference under a prescribed level of adversarial corruption. Finally, we show that regularization is necessary rather than incidental: Lai–Wei stability is incompatible with the optimal $O(\sqrt{T})$ regret rate – the rate attained by unregularized algorithms such as EXP3 – so that a controlled, polylogarithmic inflation in regret is the price of valid inference.

12.
arXiv (math.PR) 2026-06-16

Exact Label Recovery in Euclidean Random Graphs

arXiv:2407.11163v3 Announce Type: replace-cross Abstract: In this paper, we propose a family of label recovery problems on weighted Euclidean random graphs. The vertices of a graph are embedded in $\mathbb{R}^d$ according to a Poisson point process, and are assigned to a discrete community label. Our goal is to infer the vertex labels, given edge weights whose distributions depend on the vertex labels as well as their geometric positions. Our general model provides a geometric extension of popular graph and matrix problems, including submatrix localization and $\mathbb{Z}_2$-synchronization, and includes the Geometric Stochastic Block Model (proposed by Sankararaman and Baccelli) as a special case. We study the fundamental limits of exact recovery of the vertex labels. Under a mild distinctness of distributions assumption, we determine the information-theoretic threshold for exact label recovery, in terms of a Chernoff-Hellinger divergence criterion. Impossibility of recovery below the threshold is proven by a unified analysis using a Cramér lower bound. Achievability above the threshold is proven via an efficient two-phase algorithm, where the first phase computes an almost-exact labeling through a local propagation scheme, while the second phase refines the labels. The information-theoretic threshold is dictated by the performance of the so-called genie estimator, which decodes the label of a single vertex given all the other labels. This shows that our proposed models exhibit the local-to-global amplification phenomenon.

13.
arXiv (math.PR) 2026-06-11

Markov property and path regularity for the solutions to SPDEs driven by cylindrical-martingale valued measures

arXiv:2606.12381v1 Announce Type: new Abstract: In this paper we prove the Markov property for the solution to stochastic partial differential equations driven by a cylindrical orthogonal martingale-valued measure. We assume our coefficients are time-dependent and satisfy some growth and Lipschitz conditions. We also prove that for time-independent coefficients and under mild assumptions on the cylindrical orthogonal martingale-valued measure, the solutions to our stochastic partial differential equations are Feller. Finally, in the case that the $C_{0}$-semigroup is quasi-contraction, we show that the solution to our stochastic partial differential equation possesses a càdlàg version.

14.
arXiv (CS.CL) 2026-06-16

PreLort: Prefix-Nested LoRA for Federated Fine-Tuning under Rank Heterogeneity

Federated fine-tuning of large language models using parameter-efficient methods such as LoRA enables privacy-preserving adaptation of foundation models. Heterogeneous hardware resources introduce challenges, as clients with different adapter ranks cannot be directly aggregated. While existing methods enable aggregation under heterogeneous ranks, they fail to control how information is distributed across rank dimensions, leading to suboptimal use of shared low-rank representations. Instead, we propose PreLort: a nested low-rank formulation for federated LoRA that organizes adapter dimensions into a prefix hierarchy. Our approach ensures that lower-rank dimensions encode task-relevant information, while higher-rank dimensions capture additional capacity. Building on this, we introduce (i) a segment-wise aggregation rule that averages only over clients contributing to each rank segment, avoiding dilution from zero-padded lower-rank clients, and (ii) a prefix-nested training strategy that optimizes each adapter under multiple rank truncations, encouraging useful signal to concentrate in low-rank prefix dimensions. Together, these components encourage a consistent low-rank prefix capturing the most task-relevant information, while higher-rank dimensions learn additional capacity. This allows low-rank clients to benefit from richer information contributed by higher-rank clients, as prefix dimensions are consistently learned and aggregated. Experiments demonstrate that our method consistently outperforms prior heterogeneous federated LoRA methods in accuracy and ROUGE-L, while achieving lower or comparable perplexity across multiple base models.

15.
bioRxiv (Bioinfo) 2026-06-11

VFUSE: Virulent Feature Understanding with Sparse autoEncoders

Generative models have shown remarkable progress in a variety of domains such as protein design, but such power enables the opaque generation of hazardous proteins. In this work, we introduce VFUSE (Virulent Feature Understanding with Sparse autoEncoders), a mechanistic interpretability approach that trains SAEs on diffusion-transformer activations to audit protein models for hazard-aware features. We apply VFUSE to RoseTTAFold3 and RFDiffusion3, popular open-weight models for protein folding and synthesis. We find that for certain blocks, linear probes detect hazardous designs significantly better when fit in the SAE latent space over the original model's representations: improving interpretability without sacrificing model performance. Furthermore, we identify monosemantic features from the SAE that fire only on hazardous designs at up to AUROC 0.84 (q < 10-13).

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

Clusters are All You Need: Pre-Training the Tsetlin Machine with Semantic Clusters from Language Models for Interpretability

Pre-trained language models such as BERT achieve strong text classification performance but lack transparency, limiting their use in high-stakes settings. The Tsetlin Machine (TM) offers fully interpretable, clause-based reasoning but captures little semantic information, and prior attempts to bridge the two rely on static word embeddings that miss contextual meaning. We propose a semantic pre-training framework that transfers knowledge from a pre-trained language model into a TM without using embeddings. Text samples are grouped into semantically coherent clusters with K-means or Top2Vec, and the resulting cluster-sample pairs pre-train a non-negated TM with enhanced Type I feedback. The TM thereby learns interpretable semantic keywords that are fine-tuned on downstream tasks. Across five datasets, our method substantially outperforms vanilla and embedding-based TMs and reaches performance competitive with BERT while remaining interpretable.

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

Geometric and Stochastic Analysis of Discontinuities in Sparse Mixture-of-Experts

arXiv:2606.19036v1 Announce Type: new Abstract: Sparse Mixture-of-Experts (SMoE) architectures are now widely deployed in state-of-the-art language and vision models, where conditional routing allows scaling to very large networks. However, this very Top-$k$ expert selection that enables conditional routing also renders the SMoE map inherently discontinuous. In the vicinity of these discontinuity surfaces, even inputs that are arbitrarily close may activate substantially different sets of experts resulting in significantly different outputs. In this work we give a rigorous geometric and stochastic analysis of these discontinuities. We first classify them by order, determined by the number of tied experts at a switching event. Using measure-theoretic slicing arguments, we establish asymptotic volume estimates for the thickened discontinuity surfaces, showing that lower-order discontinuity sets dominate, whereas higher-order ones occupy a vanishingly small relative volume. Next, modeling random perturbations in the input space via a diffusion process, we prove that the path eventually encounter a discontinuity, and moreover that the first hit almost surely occurs on an order-1 discontinuity with explicit finite-time probability bounds. We further derive occupation-time bounds that quantify the duration the random path spend in the neighborhoods of each discontinuity order. These theoretical results imply that inputs are more likely to lie near lower order discontinuities. Motivated by this insight, we propose a simple smoothing mechanism that can be directly applied to existing SMoEs, softly incorporating experts near discontinuities; our analysis guarantees that the added computational overhead remains small while providing localized smoothing near discontinuities, and experiments across language and vision tasks show that smoothing not only enforces continuity of the SMoE map but also enhances empirical performance.

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

BASENet: Band-Adapted Speech Enhancement Network with Cross-Band Attention

arXiv:2606.12662v1 Announce Type: cross Abstract: Speech enhancement models typically apply uniform capacity across all frequencies, disregarding the non-uniform spectral resolution of human hearing. We propose BASENet, a frequency-adapted architecture that partitions the spectrum into Bark-scale bands and assigns each a scaled-capacity encoder derived from critical-band density, automatically granting deeper branches to perceptually dense low frequencies and lighter ones to high frequencies. A cross-band attention module captures harmonic dependencies across bands through compact frequency-pooled representations at linear complexity. Built on inverted residual blocks with dense connectivity and a convolutional recurrent network, BASENet achieves 3.55 PESQ and STOI~96% on VoiceBank+DEMAND with only 0.83M parameters and 7.3 G~MACs, the fewest parameters among all methods with PESQ > 3.50. A causal variant (3.44 PESQ) surpasses several non-causal baselines, confirming suitability for real-time streaming on resource-constrained devices.

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

Why Low-Precision Transformer Training Fails: An Analysis on Flash Attention

arXiv:2510.04212v4 Announce Type: replace-cross Abstract: The pursuit of computational efficiency has driven the adoption of low-precision formats for training transformer models. However, this progress is often hindered by notorious training instabilities. This paper provides the first mechanistic explanation for a long-standing and unresolved failure case where training with flash attention in low-precision settings leads to catastrophic loss explosion. Our in-depth analysis reveals that the failure is not a random artifact but caused by two intertwined phenomena: the emergence of similar low-rank representations within the attention mechanism and the compounding effect of biased rounding errors inherent in low-precision arithmetic. We demonstrate how these factors create a vicious cycle of error accumulation that corrupts weight updates, ultimately derailing the training dynamics. To validate our findings, we introduce a minimal modification to the flash attention that mitigates the bias in rounding errors. This simple change stabilizes the training process, confirming our analysis and offering a practical solution to this persistent problem. Code is available at https://github.com/ucker/why-low-precision-training-fails.

20.
medRxiv (Medicine) 2026-06-16

Presurgical immune biomarkers associated with pain intensity and pain interference recovery after total knee arthroplasty: findings from the PRIME-KNEE study

Chronic postsurgical pain (CPSP) prevalence after total knee arthroplasty (TKA) is >20%. Circulating immune biomarkers are known factors of musculoskeletal pain but poorly understood as CPSP predictors. This prospective, longitudinal study of 203 patients s/p TKA tested presurgical plasma biomarkers associated with 6-month CPSP, using promising approaches from geriatrics biomarker research: expected recovery differential (ERD; resilience outcome) and penalized, machine-learning regularization modeling (elastic net and LASSO regression). Forty-nine presurgical candidate biomarkers were considered. CPSP was operationalized using ERDs built around PROMIS pain intensity and pain interference, which quantified the difference between observed and expected recovery after accounting for demographic, comorbidity, reserve, and perioperative factors. Plasma/ERDs from ~130 patients revealed 13 biomarkers with the highest selection stability criteria, and either positive or negative (+/-) associations with ERDs. Interleukin (IL) 5 (-) and Lipopolysaccharide-Binding Protein (LBP; +) were associated with both ERDs. Unique associations with pain intensity ERD included Cytomegalovirus-Specific IgG Negative (CMV IGg-; -), Macrophage Inflammatory Protein-1 Beta (MIP1b; -), IL12p70 (-, Cluster of Differentiation 30 (sCD30;-), Interferon alpha 2a (IFN2a;+), and Leukemia Inhibitory Factor (LIF;+). Unique associations with pain interference ERD included Lipopolysaccharide (LPS;-), Activin A (-), IL8 (-), Serum Amyloid A (SAA;-), and IL7 (+). Protein-protein interaction analyses and topology motifs suggest a centralized network with higher-than-expected connectivity, involving IL5, IL7, IL8, MIP1{beta}, and IFN2a, among others. This study proposes rigorous yet feasible approaches to expedite pain biomarker research, and introduces presurgical biomarkers t0 consider in future TKA-CPSP biosignature derivation.

21.
arXiv (quant-ph) 2026-06-15

Landscape-Similarity-Guided Optimization in Divide-and-Conquer QAOA

arXiv:2602.21689v3 Announce Type: replace Abstract: Divide-and-conquer strategies mitigate hardware constraints for the Quantum Approximate Optimization Algorithm (QAOA) on Noisy Intermediate-Scale Quantum (NISQ) devices by partitioning large interaction graphs into smaller, hardware-compatible sub-problems. However, this approach introduces a severe classical training bottleneck: a decomposition across $m$ boundary nodes generates $2^m$ distinct sub-problems that typically require independent optimization. In this work, we demonstrate that across diverse synthetic and real-world interaction graphs, the variational landscapes of these reduced QAOA instances actually exhibit a robust universality. Adapting the replica-overlap framework of spin-glass physics, we define a landscape-overlap order parameter $q$ to quantify geometric correlations between energy landscapes, revealing a sharp landscape-similarity transition as graph connectivity is tuned. Exploiting this, we introduce Doubly Optimized QAOA (DO-QAOA), an adaptive pipeline that collapses the sub-problems from $2^m$ distinct sub-problems into $K=\mathcal{O}(1)$ effective landscape classes. By performing optimization on a single representative sub-problem and dynamically transferring parameters to remaining sub-problems, DO-QAOA lowers runtime and quantum measurement overhead by orders of magnitude while maintaining a competitive Approximation Ratio Gap (ARG).

22.
medRxiv (Medicine) 2026-06-22

Pump-Free Patient-Derived Human Proximal Tubule Microphysiological System for Modeling Flow-Dependent Epithelial Maturation and Cisplatin Injury

Recent initiatives by the U.S. Food and Drug Administration and the National Institutes of Health to reduce animal testing in drug development have highlighted the need for in vitro platforms that better recapitulate human biology for preclinical safety assessment. Drug-induced nephrotoxicity remains a major cause of drug attrition, underscoring the need for human-relevant kidney models. To address this, a pump-free human patient-derived proximal tubule microphysiological system was developed by integrating human renal proximal tubular epithelial cells (hRPTECs), isolated from non-tumorous nephrectomy cortex, with a porous membrane-based microfluidic device. Expanded hRPTECs were cultured for 10 days under static conditions or rocker-driven shear stress approximating physiological proximal tubular flow. Shear stress increased epithelial density, enhanced proximal tubule marker expression (Na+/K+-ATPase and aquaporin-1), and improved Zonula occludens-1 and occludin localization. Bulk RNA sequencing demonstrated transcriptomic changes associated with enhanced apical maturation and epithelial signature. In cisplatin-induced injury assays, shear-conditioned epithelia exhibited reduced cell density and increased {gamma}H2AX staining, indicating greater sensitivity to nephrotoxicity. These findings demonstrate that rocker-driven shear stress promotes epithelial maturation in patient-derived hRPTECs. The pump-free human patient-derived proximal tubule microphysiological system offers a practical, scalable, and physiologically relevant platform for modeling flow-dependent proximal tubule biology and assessing human-relevant nephrotoxicity.

23.
arXiv (CS.LG) 2026-06-16

Self-Supervised Learning of Iterative Solvers for Constrained Optimization

arXiv:2409.08066v3 Announce Type: replace Abstract: The real-time solution of parametric optimization problems is critical for applications that demand high accuracy under tight real-time constraints, such as model predictive control. To this end, this work presents a learning-based iterative solver for constrained optimization, comprising a neural network predictor that generates initial primal-dual solution estimates, followed by a learned iterative solver that refines these estimates to reach high accuracy. We introduce a novel loss function based on Karush-Kuhn-Tucker (KKT) optimality conditions, enabling fully self-supervised training without pre-solved optimizer solutions. Theoretical guarantees ensure that the training loss function attains minima exclusively at KKT points. A convexification procedure enables application to nonconvex problems while preserving these guarantees. Experiments on two nonconvex case studies demonstrate speedups of up to one order of magnitude compared to state-of-the-art solvers such as IPOPT, while achieving orders of magnitude higher accuracy than competing learning-based approaches.

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

Applicability Condition Extraction for Therapeutic Drug-Disease Relations

arXiv:2606.14031v1 Announce Type: new Abstract: Identifying conditions that a certain drug takes therapeutic effect on a target disease is crucial for clinical decision-making support. However, most existing biomedical information extraction methods have focused on identifying only relations between drugs and diseases, while largely overlooking the context-specific conditions where such relations can apply. To address this problem, we introduce the task of applicability condition extraction for therapeutic drug–disease relations from biomedical research literature. We create the first dataset that has manually annotated triples of drugs, diseases, and applicability conditions on biomedical paper abstracts with 1,119 drug-disease pairs. Using this dataset, we systematically evaluate the performance of a range of existing methods. In addition, we propose a new method that enhances LoRA to consider relations between drugs and diseases. Our method consistently outperforms strong baselines across different evaluation settings. The source code and dataset of this paper can be obtained from: https://github.com/guantingluo98/Drug-ACE

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

Search Discipline for Long-Horizon Research Agents

arXiv:2606.11522v1 Announce Type: new Abstract: Autoresearch agents now propose, evaluate, and select scientific candidates against a metric, and that metric is usually an aggregate reduced over a heterogeneous space of regions, slices, or cohorts. We show that when scientific validity lives in that disaggregated structure, the aggregate can rank the wrong candidate first. The headline number improves while the structure underneath inverts, so a decision made on the number accepts a candidate that quietly breaks the model. The failure is not domain-specific. It appears wherever a candidate's validity is multi-dimensional but its verifier is a single reduction. We demonstrate the inversion on a fire-model task in the Ecosystem Demography model. The highest-scoring candidate and a slightly lower one are within noise of each other on global score, yet the top-scoring one collapses the protected boreal regions while the other preserves them. What separates them is the per-region behavior, not the headline number. This decision should not be left to the agent that produced the candidates. The agent optimizing the score is the last party likely to catch the score being wrong, and a prompt has no remaining turn once the agent has stopped. We move the decision to an external control loop that audits each candidate on its disaggregated behavior and acts after the agent has decided. It can demote a candidate the agent would have accepted, and it can reopen a run the agent had declared finished. Our contribution is the inversion finding itself, and a search-discipline protocol that decides on reviewable candidate-effect evidence instead of the score.