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01.
arXiv (CS.AI) 2026-06-16

Multi-Grade Deep Learning for Partial Differential Equations with Applications to the Burgers Equation

arXiv:2309.07401v2 Announce Type: replace-cross Abstract: Deep neural networks (DNNs) show great promise for solving partial differential equations (PDEs), but their deep architectures introduce complex, large-scale, non-convex optimization challenges. Nonlinear PDEs, like the viscous Burgers' equation, compound these difficulties due to steep gradients and shock-like solutions. To address this, we propose a two-stage multi-grade deep learning (TS-MGDL) method. In the first stage, shallow networks are trained progressively grade by grade to fit the target function from low- to high-frequency components; previously learned grades are frozen, and each new residual block is trained solely to minimize the remaining approximation error. The second stage unfreezes and retrains selected layers using the first-stage network as initialization, achieving an interpretable, stable hierarchical refinement while mitigating optimization complexity. Furthermore, we theoretically prove that each grade and stage in TS-MGDL monotonically reduces the loss function under an appropriate optimization strategy. Numerical experiments on 1D, 2D, and 3D viscous Burgers' equations demonstrate that TS-MGDL significantly outperforms single-grade learning (SGL), reducing predictive errors by up to a factor of 60.

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

BRIDGE: Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks

arXiv:2606.14734v1 Announce Type: cross Abstract: Motivation: Gene regulatory network inference from single-cell RNA sequencing (scRNA-seq) data is important for uncovering cell-state-specific transcriptional programs. However, scRNA-seq measurements are sparse and noisy, and experimentally validated TF-target interactions remain limited, making reliable inference challenging. Although graph neural networks have advanced GRN prediction, existing methods often rely on biologically unconstrained graph augmentation, such as random edge perturbation, and insufficiently control information transfer between genes and cells. These limitations may distort regulatory structures and weaken robustness under noisy and weakly supervised settings. Results: To address these issues, we propose an innovative framework named Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks (BRIDGE). BRIDGE extracts gene and cell representations from the expression matrix and its matrix dual, and performs contrastive learning in the gene space and cell space between self and neighbors across the co-expression-refined regulatory view and the original graph. It then applies heterogeneous gated encoding to adaptively regulate information transfer between genes and cells, enabling robust transcription factor-to-target gene prediction. Experiments on benchmark datasets spanning three network types and seven cell types show that BRIDGE achieves state-of-the-art AUROC and AUPRC in most settings. In particular, on Specific networks, BRIDGE improves average AUPRC by 5% over the second-best baseline, GCLink. In cross-cell-type few-shot transfer, BRIDGE consistently outperforms GCLink and GENELink across all six target cell types. A case study on hESC further supports the biological relevance of the predictions, with 9 of the top 10 and 46 of the top 100 novel TF-target interactions validated by ChIPBase.

03.
arXiv (CS.AI) 2026-06-12

EWAM: An Enhanced World Action Model for Closed-Loop Online Adaptation in Embodied Intelligence

arXiv:2606.12690v1 Announce Type: cross Abstract: In this paper, we propose the Enhanced World Action Model (EWAM), a closed-loop online adaptation architecture built upon a pretrained and fully frozen Cosmos3 backbone network. Evaluated entirely under a zero-shot task protocol, EWAM is centrally focused on reducing the amount of additional deployment data required to adapt to new task layouts. Notably, no extra task-specific demonstration sets were introduced in any of the evaluations, and no fine-tuning was performed on the backbone network. Its performance gains stem entirely from an inference-time co-reasoning mechanism composed of four inserted lightweight neural layers: the Neural Experience Memory Layer located in the intermediate layers of the Diffusion Transformer (DiT) provides task-relevant execution context; the Neural Anomaly Detection Layer after the state prediction head monitors the divergence between predicted and actual states in real time; the Neural Policy Routing Layer dynamically selects direct execution, conservative replanning, or rollback recovery based on the anomaly severity; and the Neural Action Correction Layer refines the generated action chunks using execution diagnostics. Unlike naive feature fusion, the memory, anomaly detection, and correction modules are deeply integrated into the Cosmos3 forward path in a differentiable manner, with only the final routing decision being a discrete supervised one.

04.
arXiv (quant-ph) 2026-06-19

Quantifying Entanglement via Quantum Wasserstein Distances

arXiv:2606.04969v2 Announce Type: replace Abstract: We propose a bipartite entanglement measure defined as the minimal order-1 quantum Wasserstein distance from a state to the set of separable states. Owing to the universal data-processing inequality of the Wasserstein metric, the measure satisfies all fundamental axioms within a single geometric framework. A Lipschitz dual formulation yields explicit lower bounds for pure and mixed states, a sharp constant for two-qubit systems, and an expected value for Haar-random pure states. We further establish a quantitative connection to entanglement witnesses: any negative witness expectation value certifies a lower bound, and the dual variational bound is exactly the maximal violation achievable by a Lipschitz-1 witness. The approach naturally provides subadditivity, trace-distance estimates, and bounds on local observables, while pointing toward large-deviation conjectures. This work introduces a framework at the interface of entanglement theory, optimal transport, and experimental entanglement detection.

05.
arXiv (CS.CV) 2026-06-18

RUB: Evaluating Residual Knowledge in Unlearned Models

Machine Unlearning (MUL) has emerged as a key mechanism for privacy protection and content regulation, yet current techniques often fail to guarantee the complete removal of sensitive information. While most existing works focus on verifying the execution of unlearning, they overlook the critical question of whether models remain robust against adversarial attempts to recover forgotten knowledge. In this work, we advocate for the principle of Robust Unlearning, which requires models to be both indistinguishable from retrained counterparts and resilient against diverse adversarial threats. To instantiate this principle, we propose a unified benchmark, RUB (Robust Unlearning Benchmark), that systematically evaluates the robustness of unlearning algorithms across classification, image-to-image reconstruction, and text-to-image synthesis. Within this framework, we introduce the Unlearning Mapping Attack (UMA) as a generalizable method to detect residual information, and demonstrate how existing attack strategies can be adapted into this framework as long as they conform to the generic UMA framework. Our experiments across discriminative and generative tasks reveal that state-of-the-art unlearning methods remain vulnerable under these evaluations, even when passing standard verification metrics. By positioning robustness as the central criterion and providing a benchmark for adversarial evaluation, we hope RUB paves the way toward more reliable and secure unlearning practices. The codebase and model checkpoints in RUB will be published.

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

Stimulus Motion Perception Studies Imply Specific Neural Computations in Human Visual Stabilization

Even during fixation the human eye is constantly in low amplitude motion, jittering over small angles in random directions at up to 100Hz. This motion results in all features of the image on the retina constantly traversing a number of cones, yet objects which are stable in the world are perceived to be stable, and any object which is moving in the world is perceived to be moving. A series of experiments carried out over a dozen years revealed the psychophysics of visual stabilization to be more nuanced than might be assumed, say, from the mechanics of stabilization of camera images, or what might be assumed to be the simplest solution from an evolutionary perspective. The psychophysics revealed by the experiments strongly implies a specific set of operations on retinal signals resulting in the observed stabilization behavior. The presentation is in two levels. First is a functional description of the action of the mechanism that is very likely responsible for the experimentally observed behavior. Second is a more speculative proposal of circuit-level neural elements that might implement the functional behavior.

07.
medRxiv (Medicine) 2026-06-19

Extraction of Glaucoma Diagnosis, Type, and Severity from Clinical Notes using Secure Cloud-based Large Language Models

Purpose: To evaluate the performance of secure cloud-based large language models (LLMs) in extracting glaucoma diagnosis, type, and severity from free-text clinical notes in the electronic health record (EHR). Design: Retrospective chart review analysis. Participants: 1,250 subjects from the Bascom Palmer Ophthalmic Repository. Methods: Clinical notes of glaucoma-related encounters between 2014 and 2024 were extracted from the Bascom Palmer Ophthalmic Repository. Two fellowship-trained glaucoma specialists annotated clinical notes for glaucoma presence, type, and severity at the eye level. The dataset was split into development (10%), validation (10%), and test (80%) sets. Development and validation sets were used for prompt engineering and refinement, and the held-out test set was used for evaluation. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT-5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Azure AI Foundry within HIPAA-compliant containers. Model performance was assessed using standard metrics. Clinician-entered ICD-10 codes were also compared with adjudicated labels. Main Outcome Measures: Gwet AC1, accuracy, sensitivity, specificity, and F1-score. Results: Inter-grader agreement was high for glaucoma detection (Gwet AC1= 0.930 (95% CI: 0.917-0.945), type classification (Gwet AC1= 0.917 (95% CI: 0.904-0.930), and severity staging (Gwet AC1= 0.901 (95% CI: 0.884-0.916). For glaucoma diagnosis, LLMs demonstrated high overall accuracy, with Claude achieving 97.5%, DeepSeek 96.0%, GPT 96.2%, Grok 94.4%, and Qwen 95.5%. F1 scores for glaucoma detection ranged from 95.4% to 98.9% across models. For glaucoma type classification, accuracies were 97.1%, 94.2%, 94.2%, 94.0%, and 94.4% for Claude, DeepSeek, GPT, Grok, and Qwen, respectively. F1 scores for the most prevalent type (POAG) ranged from 96.3% to 98.9%. For severity staging, accuracies were 95.0%, 94.8%, 94.5%, 94.0%, and 95.2%, respectively, with F1 scores ranging from 89.7% to 96.3% across severity categories and models. ICD-10 codes demonstrated substantially lower performance for type and severity staging, with overall accuracies of 89.2% and 58.5%, respectively. Conclusions: Secure cloud-based LLMs accurately extracted glaucoma diagnosis, type, and severity information from free-text ophthalmology notes, achieving performance approaching expert clinician adjudication while substantially outperforming ICD-based phenotyping approaches, particularly for disease severity classification. These findings demonstrate the potential of LLMs to transform unstructured clinical documentation into scalable, research-ready phenotypic data for large-scale glaucoma cohort development and EHR-based ophthalmic research.

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

Convergence Rate Analysis of the AdamW-style Shampoo: Unifying One-Sided and Two-Sided Preconditioning

arXiv:2601.07326v4 Announce Type: replace-cross Abstract: This paper studies AdamW-style Shampoo, an effective variant of the classical Shampoo that won the external tuning track of the AlgoPerf neural network training competition. Our analysis unifies one-sided and two-sided preconditioning. When the exponents of the two preconditioners sum to $1/2$, we establish the convergence rate $\frac{1}{K}\sum_{k=1}^KE\left[||\nabla f(X_k)||_*\right]\leq O(\frac{\sqrt{m+n}C}{K^{1/4}})$, where $K$ represents the number of iterations, $(m,n)$ denotes the dimensions of the matrix-valued parameters, and $C$ matches the constant appearing in the optimal convergence rate of SGD. Theoretically, the nuclear norm and Frobenius norm satisfy $||\nabla f(X)||_F\leq ||\nabla f(X)||_*\leq \sqrt{\min\{m,n\}}||\nabla f(X)||_F$, which suggests that our convergence rate is analogous to the optimal $\frac{1}{K}\sum_{k=1}^KE\left[||\nabla f(X_k)||_F\right]\leq O(\frac{C}{K^{1/4}})$ convergence rate of SGD in the ideal case where $||\nabla f(X)||_*= \Theta(\sqrt{\min\{m,n\}})||\nabla f(X)||_F$ and $m$ and $n$ are of comparable magnitude. Then, we extend our analysis to settings where the preconditioning exponents do not sum to 1/2, and establish convergence with an explicit but more involved rate.

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

CineCap: Structured Reasoning with Spatio-Temporal Anchors for Cinematographic Video Captioning

arXiv:2606.24636v1 Announce Type: new Abstract: Cinematographic captioning aims to describe how a video is filmed using professional film-language concepts such as camera movement, shot size, depth of field, composition, and shooting angle. This capability is important for fine-grained video understanding and controllable movie-quality video generation, yet remains underexplored in existing multimodal large language models. Unlike question-answering-based evaluation of cinematic understanding, cinematographic captioning requires a unified open-form description over multiple cinematographic dimensions. This task is challenging for two main reasons: the model must infer professional cinematographic concepts from subtle visual evidence, and it must generate captions that are both comprehensive and accurate. Accordingly, we propose CineCap, a framework that combines structured reasoning with spatio-temporal anchors and reinforcement learning with comprehensiveness, accuracy, and gated coverage rewards. The former grounds professional cinematographic descriptions in explicit visual evidence and organizes them into compact atomic reasoning for supervised fine-tuning, while the latter improves the balance between descriptive completeness and factual correctness. In addition, we construct CineCap Bench, a benchmark of 472 manually annotated video-caption pairs for systematic evaluation. Extensive experiments show that CineCap consistently outperforms strong proprietary and open-source baselines, establishing a new state of the art for cinematographic captioning. The code, model checkpoint, and benchmark are publicly available in https://github.com/Hectormxy/CineCap.git.

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

Towards Truly Multilingual ASR: Generalizing Code-Switching ASR to Unseen Language Pairs

Automatic Speech Recognition (ASR) has become a key technology for human–AI interaction. However, code-switching ASR (CS-ASR) remains particularly challenging due to the severe scarcity of multilingual CS speech resources across diverse language pairs. Existing approaches primarily improve CS-ASR performance through synthetic CS speech generation or pair-specific fine-tuning on limited bilingual datasets. Nevertheless, these approaches face an inherent scalability limitation, as support for CS must be developed separately for language pairs whose number grows combinatorially with the number of supported languages. In this work, we investigate whether CS capabilities learned from a limited set of seen language pairs can generalize to unseen language pairs through model merging and domain generalization methods. Our experiments show that merged bilingual CS-ASR models modestly generalize to unseen language pairs, suggesting limited transfer of bilingual CS capabilities across language pairs.

11.
arXiv (CS.AI) 2026-06-15

When Should Agent Trust Be Conditional? Characterizing and Attacking Skill-Conditional Reputation in Agent Swarms

arXiv:2606.14200v1 Announce Type: new Abstract: Open platforms increasingly route tasks among heterogeneous LLM agents–differing in base model, scaffold, and tool stack–whose competence varies sharply by skill: an agent excellent at one skill may be useless at another. The standard reputation approach summarizes each agent by a single global trust score, but that scalar is the wrong object here, because routing every task to the globally most-trusted agent leaves the value of specialization unclaimed. We study skill-conditional trust R(i | k)–the trust to place in agent i for a task requiring skill k, rather than one score per agent–and pose three falsifiable questions: when is conditioning worth it, how much cross-skill evidence should be borrowed, and whether that borrowing is safe. A controlled phase-diagram analysis answers the first two: conditional trust wins only in a specific regime–high agent heterogeneity, sparse per-skill evidence, and correlated skills–and the coupling strength beta that buys this data efficiency is dual-use, because the same cross-skill borrowing is also a laundering channel. On a public benchmark of 14 genuinely heterogeneous AppWorld agents, real pools land inside the beneficial regime–a small but genuine gain, with the per-skill best agent genuinely changing across skills. We then show that an attacker with cheap evidence in one skill and none in a target skill hijacks the conditional router, driving routing regret from 0 to 0.94 on a pool our zero-cost Conditional Information Value Test (CIVT) rates GREEN–while the ungated trust verdict it contaminates reads -0.06 instead of the honest +0.19. A zero-evidence gate bounds the attack but does not eliminate it; we characterize the residual cost under an explicit budget. We do not claim Sybil-resistance–we quantify the trade-off.

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

Optimal Spatio-Temporal Decoupling for Bayesian Conformal Prediction

arXiv:2605.00432v2 Announce Type: replace Abstract: Online conformal prediction must balance fast adaptation to distribution shift against stable coverage: feedback-driven methods react quickly but become volatile, while strongly discounted Bayesian methods lag and inflate intervals at tight coverage. We introduce State-Adaptive Bayesian Conformal Prediction (SA-BCP), which forms the predictive quantile as a gated convex combination of long-term temporal inertia and local spatial evidence from a kernel density estimate, controlled by a single interpretable evidence threshold $K$. We establish three results: (i) asymptotic marginal validity of the resulting intervals; (ii) a closed-form expression for the MSE-optimal threshold, $K^*_{\mathrm{MSE}}=\alpha(1-\alpha)/M^{\mathcal{T}}$, trading the coverage-indicator (Bernoulli) variance against the temporal structural bias $M^{\mathcal{T}}$; and (iii) a rolling-origin procedure for selecting $K$ online – consistent under stationarity, with $O(\sqrt{T\log N})$ regret against the best fixed $K$ and, for a segmented variant, a sublinear dynamic-regret bound under bounded drift. Across four financial-volatility and weather datasets, three target coverage levels, and eight baselines (including the strongest recent conditional-quantile methods, SPCI and KOWCPI), SA-BCP attains at-or-above-nominal coverage in most settings while producing substantially sharper intervals – up to roughly $3\times$ lower Winkler score than discounted Bayesian CP at the tightest coverage – and a coverage-matched audit confirms these efficiency gains are not an artifact of under-coverage. We disclose one principal limitation: a volatility-specialized conformal-GARCH competitor remains more efficient on its home volatility-base series, though it does not transfer across domains.

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

Intention Driven Identification of In-Possession Match Phases in Association Football through Temporal Graph Learning

arXiv:2606.09289v2 Announce Type: replace Abstract: Understanding tactical organisation of association football, hereafter referred to as football, requires identifying distinct match phases. Yet in-possession phases are rarely directly observable and are shaped by evolving tactical intentions, rather than spatial patterns alone. This study proposes a data-driven framework for identifying in-possession match phases from spatiotemporal tracking data. Seven German Bundesliga matches recorded at 25 Hz with TRACAB were analysed. A hierarchical phase model was defined with three tactical intentions (Invade Opponent Space, Keep Possession, Scoring) and six phases (Build Up, Progression, Counter Attack, Maintenance, Sustained Threat, Finishing). A Temporal Graph Attention Network (T-GAN) was developed to combine frame-level player-interaction graphs, contextual features, and Transformer-based temporal modelling. Performance was evaluated using frame-level F1 and a sequence-aware Intersection over Truth-Dominance (IoT-D) metric. T-GAN achieved macro-average frame-level F1 scores of 0.87 at the intention level, 0.76 for invasion-related phases, and 0.79 for scoring phases. At the sequence level, mean diagonal IoT-D F1 increased from 0.68 to 0.79 for intentions and from 0.61 to 0.71 for phases after post-processing, indicating improved temporal coherence. Model comparisons showed that sequence modelling was the main driver of segmentation quality, while graph-based relational modelling was particularly beneficial for Counter Attack recognition. Exploratory player attention analysis further suggested that wide and midfield positional groups contributed strongly to phase discrimination. Overall, the framework translates continuous tracking data into tactically interpretable in-possession phase representations, with potential applications in automated match annotation, tactical analysis, and playing-style profiling.

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

Machine Learning-based Two-Stage Graph Sparsification for the Travelling Salesman Problem

arXiv:2604.20236v2 Announce Type: replace Abstract: High-performance TSP solvers such as Lin-Kernighan-Helsgaun (LKH) search within a candidate graph – a small subset of edges pre-selected for the solver – rather than over the complete graph. The two leading sparsification heuristics, $\alpha$-Nearest and POPMUSIC, each fall short of the density-coverage balance: $\alpha$-Nearest is dense with stable recall, while POPMUSIC is sparser but its recall degrades with scale. Their union closes the recall gap while remaining far below the complete graph in density, leaving room for further reduction. Existing learning-based sparsifiers score edges on the complete graph, an approach that is expensive and largely limited to Euclidean instances. We propose a two-stage method that inverts this logic. Stage~1 takes the union of $\alpha$-Nearest and POPMUSIC, achieving near-perfect recall at ${\sim}6N$ edges. Crucially, the union annotates each edge with its source provenance – whether it was endorsed by $\alpha$-Nearest, POPMUSIC, or both. Stage~2 trains a lightweight classifier on these annotated edges and prunes the lowest-scoring ones. Because dual-source edges are almost always optimal, the learning problem reduces to filtering the single-source subset – a substantially easier task than classifying all $O(N^2)$ edges from scratch. Across four distance types, five spatial distributions, and problem sizes from 50 to 500, the pipeline reduces candidate-graph density by $37$-$47\%$ while retaining ${\geq}99.69\%$ of optimal-tour edges, and matches or exceeds the coverage of recent Euclidean-only neural sparsifiers at lower density at TSP500.

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

LEDGER: A Long-Context Benchmark of Corporate Annual Reports for Grounded Financial Retrieval and Extraction

Finance reporting is a natural proving ground for large language models, and the very-long-context capabilities of recent models across all sizes make rigorous evaluation in this domain an increasingly pressing need. Yet most public financial resources reduce the task to plain-text SEC 10-K filings paired with a handful of question-answer items. We release LEDGER (Long-context Evaluation of Documents for Grounded Extraction and Retrieval), a corpus of 4,999 digitized corporate annual reports - full documents with figures, tables, and narrative, not just regulatory filings. Each report is labeled with 31 consolidated financial KPIs to be extracted and linked to the market's reaction at the earnings date. From this data we derive three evaluation benchmarks spanning the difficulty spectrum: a pure page-level KPI retrieval task with TREC-style relevance judgments over 118,048 questions in natural language, a conversational "needle-in-a-haystack" single-value lookup, and a full KPI extraction task, both from long, numerically dense reports. We additionally provide human OCR-quality annotations with inter-annotator agreement and the complete extraction, validation, and scoring toolchain. We further demonstrate the dataset's research utility with a case study linking CEO-letter rhetoric to post-publication market impact.

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

COSMOS: Model-Agnostic Personalized Federated Learning with Clustered Server Models and Pseudo-Label-Only Communication

arXiv:2605.11165v2 Announce Type: replace Abstract: Federated learning (FL) in heterogeneous environments remains challenging because client models often differ in both architecture and data distribution. While recent approaches attempt to address this challenge through client clustering and knowledge distillation, simultaneously handling architectural and statistical heterogeneity remains difficult. We introduce COSMOS, a model-agnostic framework that enables server-side personalization using only pseudo-label communication. Clients train local models and predict on the public data; the server clusters clients by prediction similarity, trains a cluster-specific model for each group using its own compute, and distills the resulting models back to clients. We provide the first theoretical analysis showing that distillation from the learned cluster models can yield exponential personalization risk contraction, going beyond the convergence-to-stationarity guarantees typically provided in model-agnostic FL. Experiments across benchmarks demonstrate that COSMOS consistently outperforms all model-agnostic FL baselines while remaining competitive with state-of-the-art personalized FL methods. More broadly, our results highlight personalized server-side learning with pseudo-labels as a promising paradigm for scalable and model-agnostic federated learning in highly heterogeneous environments.

17.
arXiv (CS.AI) 2026-06-12

Mapping AI Programs in the U.S: A Status Report from Early 2026 and an Analysis of AI Majors and Minors

arXiv:2606.12428v1 Announce Type: cross Abstract: We present a report on the status of undergraduate Artificial Intelligence (AI) programs in the United States in Spring 2026. In so doing, we 1) describe our scraping and mapping tools, which dynamically update to track the state of AI education in the U.S., and 2) create a historic record at a time of great upheaval. The tool we developed, available at https://cicmap.ai, detects, scrapes, and displays data from more than 350 undergraduate AI programs–majors, minors, concentrations, and certificates–at 4-year universities. Our tool searched over 560 institutions to locate these programs, a sample that represents 86\% of all undergraduate Computer Science (CS) graduates in the U.S. This tool allows prospective students, guidance counselors, administrators, and faculty to easily access AI program requirements and is designed to continually update as new programs emerge. To the best of our knowledge, this survey represents the most comprehensive snapshot of the state of AI programs in the U.S. to date. With this work we offer three important contributions: 1) a record of AI programs in the U.S. at a time of great upheaval; 2) a tool to explore AI programs and their requirements; and 3) an analysis of the courses required for 66 AI majors and 87 AI minors. Our analysis of majors and minors shows great variability in the size and the requirements of these degrees, but we note two takeaways. First, not all majors require a general AI course, but if they don't, they do require a Machine Learning (ML) course. Second, while more than a third of majors require an Ethics in AI course, just under a quarter of AI minors do.

18.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

19.
arXiv (CS.CL) 2026-06-17

Evaluating Second-Order Bias of LLMs Through Epistemic Entitlement

Evaluations of social bias in LLMs largely focus on whether models generate or imply biased content. However, as LLMs are increasingly used as judges of bias, they may exhibit social biases in subtler ways in how they evaluate biased content, which current methods do not systematically capture. We call this second-order bias: social bias in an LLM's judgment about social bias, which we evaluate through a novel, philosophically grounded reasoning task. Drawing on entitlement epistemology, we conceptualize bias as misplaced foundational knowledge that shapes an agent's rational inquiry, and derive a logical reasoning task for LLMs to judge to whom a biased text is acceptable or non-acceptable. We develop two simple metrics to measure how biased LLM judges are in inferring demographics for acceptability without sufficient support, and how these inferences vary across groups targeted by biased texts. Evaluating open and closed models, we find that our task evades safety guardrails by surfacing bias in model judgment. It varies systematically across target groups, reflects implicit social maps, and shows how models are still triggered by demographic labels. Our work points to the need for LLM bias evaluation in judgment tasks and broadly, for more theoretically grounded approaches to bias evaluation in NLP. We release our code and model responses at https://github.com/uofthcdslab/second-order-bias.

21.
arXiv (CS.AI) 2026-06-11

On the Limits of LLM-as-Judge for Scientific Novelty Assessment

arXiv:2606.12071v1 Announce Type: cross Abstract: LLMs are increasingly used to generate and judge scientific ideas. This makes novelty evaluation a central problem. Full idea evaluation is difficult because it often requires judging a method, its feasibility, and its empirical promise. We therefore study a cleaner upstream object: the research question (RQ). RQ generation is a prerequisite for scientific ideation, and RQs can be compared against questions pursued in real papers. We introduce RQ-Bench, a benchmark built from recent arXiv papers. For each paper, we reconstruct author-anchored RQs from its cited background, gaps, and contributions. These RQs are not the only valid questions for the same background. They are author-anchored reference points for testing novelty judgments. We evaluate model-generated RQs with standalone LLM judging, comparative LLM judging, and human expert evaluation. LLM judges consistently rate model-generated RQs as highly novel, producing a novelty mirage; in comparative evaluations, this preference becomes even stronger. Domain experts, however, reach the opposite conclusion and prefer the author-anchored reference questions. We further find that many generated RQs are narrow or source-bound, a dimension that LLM judges often miss unless explicitly tested. Overall, the contradictory novelty evaluations between LLM judges and human experts raise a serious concern about the reliability of using LLMs to assess the scientific novelty of research questions.

22.
bioRxiv (Bioinfo) 2026-06-18

Population-associated molecular variation in histologically normal breast tissue is context-dependent and associated with distinct transcriptional states

Population-associated molecular variation in breast tissue may contribute to differences in tissue biology and disease susceptibility, yet the extent to which such variation is shaped by underlying tissue states remains unclear. Here, we performed RNA-seq and lipidomic profiling of histologically normal breast tissue samples from African American (AA) and Caucasian White (CW) individuals, followed by conceptual integration of the resulting transcriptomic and lipidomic patterns. Unsupervised analysis revealed two distinct baseline transcriptional states (G1 and G2) that defined the primary axis of molecular variation across the cohort and corresponded to epithelial-enriched (G1) and vascular-enriched (G2) tissue contexts as determined by cell-type deconvolution. Global comparisons between AA and CW samples showed minimal transcriptomic differences, with only a single gene reaching significance after multiple testing correction. However, when stratified by baseline tissue state, 191 genes were differentially expressed within G1, with coordinated upregulation of extracellular matrix organization and proliferative/cytoskeletal processes in AA samples. These patterns were consistently supported across multiple enrichment approaches. No comparable population-associated differences were observed within G2. Lipidomic analyses showed partial but non-significant trends consistent with transcriptomic structure, suggesting that lipid variation provides complementary but limited support for baseline molecular differences, likely reflecting constraints of bulk tissue composition. Together, these findings suggest that population-associated molecular differences in normal breast tissue are context-dependent and emerge within specific baseline transcriptional states, where distinct biological programs can coexist and be differentially modulated. These findings highlight the importance of tissue heterogeneity in shaping molecular variation and its potential relevance to disease-associated tissue states.

23.
arXiv (CS.AI) 2026-06-24

Low-power analogue neural networks with trainable nonlinear connections for continuous control

arXiv:2606.23742v1 Announce Type: cross Abstract: Physical neural networks promise low-power machine learning by computing directly with analogue device physics, but most architectures force nonlinear device responses to act as scalar weights. Inspired by Kolmogorov-Arnold networks, we place trainable nonlinear functions on the connections, making each physical connection a learnable computational element. Realising these functions as analogue band-pass filters on field-programmable analogue arrays, we find that the benefit is task-dependent and follows from the smoothness of the physical basis: the networks represent smooth, continuously valued targets, including robotic kinematics, continuous control, and photovoltaic maximum-power-point tracking, with far fewer nodes and connections than multilayer perceptrons, but offer no parameter-efficiency advantage on classification-like decision boundaries. Trained networks transfer to hardware across approximately 35,000 connections with quantified fidelity, and a dedicated CMOS implementation is projected to operate at approximately 30 microwatts. A memristive realisation reproduces the same behaviour in simulation, indicating that the advantage comes from placing trainable nonlinearity on connections, rather than from a particular device.

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

More with LESS – Local Scene Representations for Tactile Imaging

arXiv:2606.14344v1 Announce Type: new Abstract: Tactile imaging seeks to reconstruct the internal structure of soft objects through touch sensing, with applications in medical diagnosis and robotic manipulation. Recent self-supervised learning approaches have shown promising results, but rely on global, unstructured representations and robot-controlled sensing, limiting generalization and practical use. We propose Local Encoder for Spatial Sensing (LESS), an object-centric tactile representation that exploits the local nature of touch. The tactile scene is modeled as a grid of recurrent encoders with local receptive fields, whose states are fused to reconstruct 2D or 3D images of internal structure. This compositional design enables strong generalization: models trained on single-inclusion phantoms accurately image objects with multiple inclusions and varying sizes. The local structure further supports spatial uncertainty estimation. In addition, we enable hand-held tactile imaging via external pose tracking and human-like palpation data, and extend tactile imaging to full 3D reconstruction.

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Nature Biotechnology 2026-06-09

Hybrid solid−liquid optics enable scalable, high-resolution light-sheet microscopy across diverse immersion media

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Many data-driven approaches rely on scalable and affordable three-dimensional (3D) imaging across subcellular to organ scales. Although advances in tissue clearing, expansion microscopy and light-sheet microscopy (LSM) have enabled high-resolution imaging of intact specimens, scalability in sample size, throughput and accessibility remains fundamentally limited by detection optics. Here we introduce hybrid solid−liquid optics (HySIL), a flexible refractive design framework in which a solid optical element and a refractive index (RI)-matched liquid function as a continuous optical system for wavefront correction and numerical aperture enhancement. We implement this framework as SCOPE and Super-SCOPE, enabling submicron-resolution, aberration-corrected LSM using long-working-distance air objectives. We demonstrate high-resolution volumetric imaging across diverse biological contexts, including cleared and expanded mouse, salamander and cavefish brains, human induced pluripotent stem cell (iPSC)-derived brain organoids and large intact human tissues for 3D histopathology. By combining enhanced optical performance with low-cost, long-working-distance and multi-immersion compatibility, HySIL provides an accessible and scalable foundation for next-generation volumetric imaging and data-driven biological discovery. Hybrid solid–liquid optics improve light-sheet imaging of intact biological samples.