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01.
medRxiv (Medicine) 2026-06-17

Wearable-Grade Lead Reduction Disproportionately Degrades ECG AI Performance in Elderly Patients: Evidence from PTB-XL and MIT-BIH

Consumer wearable devices increasingly use single-lead electrocardiograms (ECGs) for cardiac monitoring, but these signals contain substantially less spatial information than the clinical 12-lead standard. Whether this reduction dispro- portionately affects older adults, who often present with more complex cardiac conditions, remains poorly understood. In this study, we evaluated the impact of lead reduction on AI-ECG diagnostic performance across age groups. A 1D resid- ual neural network was trained on 21,091 PTB-XL ECG recordings spanning five diagnostic superclasses and assessed using 12-, 6-, 2-, and 1-lead configurations. Under the full 12-lead setting, model accuracy declined from 84.5% in patients younger than 40 years to 66.2% in patients aged 75 years or older. Progressive lead reduction further widened this gap. Under the 1-lead configuration, accuracy decreased by 14.1 percentage points in the 75+ group but by only 0.4 percent- age points in the

02.
Nature (Science) 2026-06-17

Navigating a crowded developing brain leaves neurons with broken DNA

As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails. As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails.

03.
bioRxiv (Bioinfo) 2026-06-21

OracleScreen-LILRB4: Machine Learning-Guided Discovery of Myeloid Immune Checkpoint Binders Validated in Patient-Derived Cells

The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit rates observed in conventional high-throughput screening campaigns. Here we report OracleScreen-LILRB4, an ensemble machine learning framework trained on quantitative biophysical screening data from two structurally diverse compound libraries (19,800 compounds total) screened against the myeloid immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3). By formulating binding prediction as a regression task targeting continuous {Delta}Fnorm values rather than binary hit classifications, OracleScreen-LILRB4 achieved a mean Spearman R of 0.61 and ROC-AUC of 0.86 under scaffold-aware cross-validation. Prospective virtual screening of a 45,760-member compound library and experimental validation of the top 200 predictions yielded a 28.5% hit rate, representing a 15.0-fold enrichment over baseline, with 16 compounds demonstrating nanomolar-affinity LILRB4 (ILT3) engagement. Lead compounds ORS-22 and ORS-14 restored anti-tumor immune activity across patient-derived colorectal cancer and acute myeloid leukemia co-culture systems, reversing SCG2-mediated immunosuppression and recovering cytotoxic T-cell function. These findings establish OracleScreen-LILRB4 as an effective computational framework for accelerating small molecule discovery against non-enzymatic immune checkpoint targets.

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

Large-scale semantic mapping of learner agency and autonomy reveals what measurement and generative AI research overlook

arXiv:2606.10881v2 Announce Type: replace Abstract: Learner agency and autonomy are foundational to personal development, yet a pervasive "jingle-jangle" fallacy (i.e. identical terms denoting different constructs, distinct terms denoting identical ones) has substantially hindered cumulative knowledge. Treating meaning as a phenomenon constituted through use in linguistic practice, we extracted 8,954 definitions and 2,700 scale items from over 14,000 publications, to investigate how researchers actually used learner agency and autonomy with a semantic analysis pipeline. The definitional landscape of two constructs resolves into three dimensions: regulation and control of learning (task), intrinsic motivation and internal decision-making (person), and social-relational action (sociocultural), thereby empirically quantifying the jingle-jangle fallacy. Existing scales, however, systematically underrepresent the sociocultural dimension. Critically, current generative AI research in education concentrates on learning regulation and control, narrowing the behavioral repertoire that AI-mediated learning environments are designed to cultivate. Beyond conceptual clarification, this work carries direct implications for conceptualization, measurement, and practice towards supporting the multidimensional learner agency and autonomy.

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

Not Just How Much, But Where: Decomposing Epistemic Uncertainty into Per-Class Contributions

arXiv:2602.21160v3 Announce Type: replace-cross Abstract: In safety-critical classification, the cost of failure is often asymmetric, yet Bayesian deep learning summarises epistemic uncertainty with a single scalar, mutual information (MI), that cannot distinguish whether a model's ignorance involves a benign or safety-critical class. We decompose MI into a per-class vector $C_k(x)=\sigma_k^{2}/(2\mu_k)$, with $\mu_k{=}\mathbb{E}[p_k]$ and $\sigma_k^2{=}\mathrm{Var}[p_k]$ across posterior samples. The decomposition follows from a second-order Taylor expansion of the entropy; the $1/\mu_k$ weighting corrects boundary suppression and makes $C_k$ comparable across rare and common classes. By construction $\sum_k C_k \approx \mathrm{MI}$, and a companion skewness diagnostic flags inputs where the approximation degrades. After characterising the axiomatic properties of $C_k$, we validate it on three tasks: (i) selective prediction for diabetic retinopathy, where critical-class $C_k$ reduces selective risk by 34.7\% over MI and 56.2\% over variance baselines; (ii) out-of-distribution detection on clinical and image benchmarks, where $\sum_k C_k$ achieves the highest AUROC and the per-class view exposes asymmetric shifts invisible to MI; and (iii) a controlled label-noise study in which $\sum_k C_k$ shows less sensitivity to injected aleatoric noise than MI under end-to-end Bayesian training, while both metrics degrade under transfer learning. Across all tasks, the quality of the posterior approximation shapes uncertainty at least as strongly as the choice of metric, suggesting that how uncertainty is propagated through the network matters as much as how it is measured.

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

Efficient time-series prediction on NISQ devices via time-delayed quantum extreme learning machine

arXiv:2602.21544v2 Announce Type: replace Abstract: We proposed a time-delayed quantum extreme learning machine (TD-QELM) for efficient time-series prediction on noisy intermediate-scale quantum (NISQ) devices. By encoding multiple past inputs simultaneously, TD-QELM achieves shallow circuit depth independent of sequence length, thereby, mitigating noise accumulation and reducing computational complexity. Experiments using the NARMA benchmark on both noiseless simulations and IBM's 127-qubit processor demonstrate that TD-QELM consistently outperforms conventional quantum reservoir computing in prediction accuracy and noise robustness. These results highlight TD-QELM as a practical and scalable framework for time-series learning on current NISQ hardware.

07.
arXiv (quant-ph) 2026-06-19

Fidelity bounds for adiabatic gates and other quantum operations with time-dependent dissipation

arXiv:2606.20501v1 Announce Type: new Abstract: As quantum-computing platforms are susceptible to noise, the fidelity of quantum operations is limited by decoherence. Understanding this limitation is crucial for building utility-scale quantum processors. In previous works [Phys. Rev. Lett. 129, 150504 (2022); Quantum 9, 1684 (2025)], we presented analytical formulae for the average gate fidelity of multi-qubit operations under static Markovian noise processes, including operations that temporarily leave the computational subspace. However, some quantum-computing architectures dynamically modulate qubit or coupler frequencies to implement two-qubit gates, e.g., baseband flux gates; such modulation can lead to dissipation rates varying in time. In this Letter, we therefore generalize the fidelity-reduction formulae to encompass time-dependent dissipation. Applying our generalized formula, we obtain a fidelity bound for adiabatic operations and demonstrate that flux-dependent noise sensitivity, combined with qubit-coupler hybridization, significantly reduces the fidelity of adiabatic controlled-Z (CZ) gates in superconducting quantum computers. Our work thus provides essential theoretical tools for evaluating error budgets and optimizing the design of quantum operations in tunable quantum-computing architectures, and may also find applications in quantum-sensing and quantum-communication protocols that are affected by time-dependent dissipation.

08.
arXiv (quant-ph) 2026-06-12

Spectral analysis of equilibration: information leakage in isolated quantum systems

arXiv:2606.12545v1 Announce Type: new Abstract: We develop a unified dynamical-spectral framework for equilibration in isolated quantum systems based on a subspace coarse-graining approach. Central to our formulation is the Leakage Fidelity Function (LFF), defined as the probability that a unitarily evolving state escapes the support of its initial subspace. This quantity provides a direct, operational measure of information flow and memory loss without invoking ensemble assumptions or perturbative arguments. We derive universal bounds on temporal fluctuations of the LFF, in terms of the spectral gap structure and the square of the effective dimension, evincing that large spectral delocalization suppresses fluctuations and guarantees equilibration on average. By introducing spectral power distributions and associated entropic measures, we establish a quantitative link between phase mixing, gap participation, and dynamical stability. We further investigate the equilibration timescale by connecting the LFF to quantum speed limits, thereby revealing the average time required for equilibration. Our results provide a state-dependent, geometrically transparent perspective on how spectral complexity and subspace information leakage jointly govern irreversibility in closed quantum many-body systems.

09.
Nature (Science) 2026-06-10

A 5.3-million-year-old deep-sea whale necropolis in the Diamantina Zone

Whale falls are biodiversity oases at seabeds1–6, yet their record from the oceans has remained sparse and fragmentary6,7. Here we report the discovery of a vast whale necropolis in the Diamantina Zone (4,616- to 7,001-m depth), extending about 1,200 km along the sea floor of the southeastern Indian Ocean. This area has a deep and extensive accumulation comprising five modern natural whale-fall communities and 476 fossil cetaceans recorded. We show that carcasses host specialized communities dominated by brittle stars, bone-boring worms and chemosynthesis-based bivalves and that the fossil record in this area comprises both extant and extinct deep-diving beaked whales. Isotopic dating shows that whale falls in this region have occurred since at least 5.3 million years ago. These findings reshape the understanding of the limits and biogeography of whale-fall ecosystems and establish some deep sea floors as a fossil archive for tracing cetacean evolution over geological time. Researchers uncovered an enormous deep-sea accumulation of whale remains in the southeastern Indian Ocean, showing long-term, specialized ecosystems and an extensive fossil record that offers new insight into deep-ocean biodiversity and whale evolutionary history.

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

CountZES: Counting via Zero-Shot Exemplar Selection

Object counting in complex scenes is particularly challenging in the zero-shot (ZS) setting, where instances of unseen categories are counted using only a class name. Existing ZS counting methods that infer exemplars from text often rely on off-the-shelf open-vocabulary detectors (OVDs), which in dense scenes suffer from semantic noise, appearance variability, and multi-instance proposals. Alternatively, random image-patch sampling is employed, which fails to accurately delineate object instances. Since counting is sensitive to exemplar quality, such selection strategies often yield poorly representative exemplars, leading to inaccurate count estimation. To address these issues, we propose CountZES, an inference-only approach for object counting via ZS exemplar selection. CountZES discovers diverse exemplars through three synergistic stages: Detection-Anchored Exemplar (DAE), Density-Guided Exemplar (DGE), and Feature-Consensus Exemplar (FCE). DAE refines OVD detections to isolate precise single-instance exemplars. DGE introduces a density-driven, self-supervised paradigm to identify statistically consistent and semantically compact exemplars, while FCE reinforces visual coherence through feature-space clustering. Together, these stages yield a complementary exemplar set that balances textual grounding, count consistency, and feature representativeness. Experiments on diverse datasets demonstrate CountZES superior performance among ZOC methods while generalizing effectively across domains.

11.
Nature (Science) 2026-06-10

In situ nanocrystal confinement for efficient blue perovskite LEDs

Metal halide perovskites have emerged as promising semiconductors for light-emitting diodes (LEDs) owing to their excellent luminescence properties1. However, their performance remains limited, primarily owing to the inherent contradiction between ‘high crystallinity’ and ‘small size’ in the in situ synthesis of perovskite nanocrystals on substrates. Here we report efficient blue perovskite LEDs (PeLEDs) achieved via in situ polymerization-driven nanocrystal confinement to synthesize perovskite films composed of high-quality nanocrystals. The in situ-formed polymer network imposes nanoscale spatial constraints during perovskite nanocrystal growth, enabling nanocrystals with small sizes and a high photoluminescence quantum yield of 83%. Furthermore, polymerizable monomers with sufficient coordination sites allow a prolonged lattice rearrangement of perovskite clusters, promoting the crystallinity of the nanocrystals. The synthesized perovskite nanocrystals are utilized in the fabrication of PeLEDs, resulting in an external quantum efficiency of 21.8% at 491 nm, which is among the highest performances in blue PeLEDs. This work simultaneously controls the thermal dynamics of perovskite crystallization and organic ligand reactions, which helps to advance understanding of the effect of ligand engineering on nanocrystal synthesis, benefiting the development of efficient PeLEDs and other optoelectronic technologies. Efficient blue perovskite light-emitting diodes with an external quantum efficiency of 21.8% are achieved through in situ polymerization-driven nanocrystal confinement.

12.
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.

13.
arXiv (CS.AI) 2026-06-12

Position: Generative Engine Optimization Creates Underexamined Risks, Governance Must Target Concentration, Disclosure, and Academic Blind Spots

arXiv:2606.12439v1 Announce Type: cross Abstract: Large language model (LLM) answer engines are increasingly used for information seeking, shifting visibility from ranked lists to synthesized answers. This enables Generative Engine Optimization (GEO), which targets LLM answer engines' evidence pool and generation. We analyze the search engine optimization (SEO) to GEO transition to identify two risks: (i) concentrated influence from low contestability and system sensitivity, and (ii) undisclosed commercial influence embedded in evidence and reasoning. We then formalize a general GEO pipeline to locate where optimization acts and compare academic and industry practices, revealing a third risk: (iii) academic-industry blind spots driven by visibility and evaluation asymmetries between offline setups and deployed systems. This position argues the need for answer-level governance and measurement: stronger contestability, high-precision disclosure, black-box auditing of material influence, and deployment-aligned metrics for exposure persistence.

14.
arXiv (CS.CV) 2026-06-11

Understanding Cross-Sensor Feature Variations for Generalizable 3D Perception

Radar-camera BEV perception often suffers from degraded performance when evaluated across datasets, as changes in driving scenes, sensor configurations, and environmental conditions can alter both the input observations and the internal fused representations. This work studies this issue from the perspective of source-domain variation modeling, aiming to improve the robustness of BEV-based 3D detectors without relying on target-domain samples. We introduce a framework that characterizes visual scene variations in the frequency domain and uses them to synthesize diverse source-domain views. By comparing the resulting fused BEV representations, the framework further captures how image-level variations influence multi-modal BEV features. These variation patterns are then used to regularize the detector, encouraging the learned fusion space to remain stable under latent scene changes. The proposed method is applied only during training and leaves the inference pipeline unchanged. Experiments on cross-dataset radar-camera 3D detection between View-of-Delft and TJ4DRadSet demonstrate consistent improvements over multiple BEV fusion backbones, and the gains remain effective when a small amount of target-domain data is available.

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

Orchestrated Reality: From Role-Play to Living, Playable Game Worlds – LLM-Driven World Simulation as a Parameterized-Action POMDP

arXiv:2606.16014v1 Announce Type: cross Abstract: Many games rely on storytelling combined with systems that track levelling, NPC behaviour, and consequence simulation; bridging tightly-authored narrative with deeply-simulated worlds – most acute in sandbox and open-world settings – has been prohibitively expensive. LLM-driven worlds open a new path: a single harness can coordinate numerical state, narrative voice, storytelling pacing, and rule logic together. Realising this requires the LLM system to sustain a persistent world (who is where, what has just happened, what is currently true), which today's deployed systems do not: the narrative voice asserts state in free prose without any validated representation, so a fully autonomous game engine remains infeasible. We treat this as an architectural choice, not a limitation of language models, and report work in progress on a framework – orchestrated reality – that makes the world a canonical object owned by a singleton orchestration agent analogous to the tabletop-RPG Game Master (GM). We formalise an LLM-driven game world for a human player as a Parameterized-Action POMDP: state is a tree of canonical JSON entities, actions decompose as $a=(k, x_k)$ (a discrete intent kind plus structured JSON parameters), the agent observes only a narrative projection $o=O(s)$ of state, and the transition kernel $F$ is an LLM-driven Plan-Diff-Validate-Apply (PDVA) pipeline that commits schema-validated, content-hashed JSON deltas. We give the formal model, a JSON-state example, a worked single-turn example, and a catalogue of 15 illustrative incidents drawn from a real deployment showing the framework in action. Empirical validation through a planned human player study – together with multi-NPC concurrent agency and deployment as an RL environment – is situated as future work.

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

Can Factual Opinions Be Edited (Manipulated) in Large Language Models?

Large Language Models (LLMs) are increasingly integrated into various domains, making knowledge editing techniques crucial yet potentially hazardous. Current editing methods primarily target atomic facts, overlooking the significant risks associated with manipulating factual opinions, e.g., documented stances of public figures on societal issues. Such manipulation could reshape public images, influence elections, and alter societal views. To systematically assess this threat, we introduce the Factual Opinion Editing with Evidence (FOE) benchmark, which encompasses 261 public figures, 19 issue categories, and 2,178 complete opinion records. Our evaluations demonstrate that current editing techniques struggle significantly with factual opinions, often achieving only superficial changes while failing to preserve consistency between the edited opinion and the supporting evidence generated by the model. To address this limitation, we further propose a simple yet effective Self-Generated Evidence-Aligned method that achieves opinion-evidence alignment without relying on explicit instructions. Together, our benchmark and method provide a foundation for understanding the emerging security implications of factual opinion editing in LLMs.

17.
arXiv (math.PR) 2026-06-12

Sphere Packings in Higher Dimension (after Boaz Klartag)

arXiv:2606.13313v1 Announce Type: cross Abstract: Let $\delta_n^L$ be the maximal density of a lattice sphere packing in the $n$-dimensional Euclidean space. We explain how Boaz Klartag proved the inequality $\delta_n^L \geq c n^2 2^{-n}$ where $c>0$ is a universal constant. In higher dimension, even for non-lattice sphere packings, this new lower bound is a substantial improvement. Klartag's proof uses the probabilistic method in two different ways. The first, very standard, relies on the statistical properties of a uniformly chosen random lattice. The second, completely new, studies the stochastic evolution of an ellipsoid constrained to contain non nonzero lattice points in the interior.

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

FeedEval: Pedagogically Aligned Evaluation of LLM-Generated Essay Feedback

Going beyond the prediction of numerical scores, recent research in automated essay scoring has increasingly emphasized the generation of high-quality feedback that provides justification and actionable guidance. To mitigate the high cost of expert annotation, prior work has commonly relied on LLM-generated feedback to train essay assessment models. However, such feedback is often incorporated without explicit quality validation, resulting in the propagation of noise in downstream applications. To address this limitation, we propose FeedEval, an LLM-based framework for evaluating LLM-generated essay feedback along three pedagogically grounded dimensions: specificity, helpfulness, and validity. FeedEval employs dimension-specialized LLM evaluators trained on datasets curated in this study to assess multiple feedback candidates and select high-quality feedback for downstream use. Experiments on the ASAP++ benchmark show that FeedEval closely aligns with human expert judgments and that essay scoring models trained with FeedEval-filtered high-quality feedback achieve superior scoring performance. Furthermore, revision experiments using small LLMs show that the high-quality feedback identified by FeedEval leads to more effective essay revisions. We release our code and curated datasets at: https://github.com/BBeeChu/FeedEval.git.

20.
arXiv (CS.CL) 2026-06-18

Evaluating Prompting-Based Defenses Against Domain-Camouflaged Injection Attacks

作者:

Domain-camouflaged injection attacks embed malicious instructions in retrieved content using domain-appropriate vocabulary, evading standard detectors that rely on syntactic injection markers. When detection fails, practitioners need to know which defense architectures reduce attack success. We evaluate five prompting-based defenses (spotlighting, paraphrasing, prompt sandwiching, and two combinations) against domain-camouflaged injection across three model families (Claude Haiku, Llama 3.1 8B, Gemini 2.0 Flash) and three deployment domains (financial, legal, general) using 3,510 trials. Paraphrasing retrieved content before agent processing is the most consistently effective defense in this benchmark, reducing camouflage attack success rate by 55-84\% depending on model, and achieves lower attack success rates than our Llama Guard 4 configuration on every model tested. Defense effectiveness is strongly model-dependent: spotlighting halves attack success on Claude Haiku but provides no benefit on Llama 3.1 8B. Financial domain deployments face the highest residual risk at 26-33\% baseline attack success rate, with no prompting-based defense fully eliminating the threat on weaker models. These results provide the first systematic evaluation of prompting-based defenses specifically against camouflage-class injection attacks and establish benchmark-based recommendations for practitioners. All tasks use synthetically constructed professional documents; whether these benchmark rankings generalize to real enterprise documents remains an open question.

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

World Model Self-Distillation: Training World Models to Solve General Tasks

Pretrained video generators are promising visual world models that exhibit emergent task-solving abilities; however, their reliance on detailed textual descriptions limits their direct use for planning and decision-making. Existing approaches either outsource this reasoning to language or vision-language models, or rely on supervised fine-tuning with paired task-execution videos, which are costly to collect and difficult to scale. We propose a scalable framework that elicits task-solving ability in such models by combining self-distillation with reinforcement learning. Given an unlabeled scene image, a vision-language model generates a candidate task and a detailed step-by-step solution. The solution conditions a pretrained video diffusion model, the Demonstrator; we distill its behavior into an Executor conditioned only on the image and a short task prompt. This transfers execution knowledge from caption-guided generation to instruction-conditioned task solving without curated task-video supervision. We further improve the Executor with reinforcement learning from VLM feedback, exploiting the asymmetry between judging whether a sampled video satisfies a task and generating the solution. Experiments on our proposed WorldTasks-Benchmark and the DreamGen robotics benchmark show that the Executor surpasses the Demonstrator under our VLM-based evaluation protocol and transfers competitively to robotic tasks.

22.
bioRxiv (Bioinfo) 2026-06-10

Pseudoperplexity Probes Memorization in Protein Language Models

Protein Language Models (pLMs) have significantly advanced computational biology. Yet their scale and reliance on redundant training data raise a fundamental question: do pLMs generalize the statistical grammar of proteins, or do they simply memorize their training data? To investigate this, we used pseudoperplexity as a probe for sequence-level memorization, comparing ProtT5's pseudoperplexity on a pre-training proxy dataset against a post-training holdout of genuinely novel sequences. To ensure a valid comparison, we matched the datasets by sequence length, cluster size, and taxonomic family. As a statistical baseline, we trained n-gram language models; analysis of higher-order n-gram composition and a statistically significant divergence in perplexity confirmed that the post-training sequences were genuinely novel at the local sequence level. ProtT5 showed a statistically significant difference in pseudoperplexity between seen and unseen sequences, though further analysis revealed this memorization signal to be modest. These findings suggest that ProtT5 exhibits detectable but limited memorization of its training data as measured by a pseudoperplexity-based probe.

23.
arXiv (CS.CL) 2026-06-15

Cross-Dataset Bloom Question Classification: Supervised Models and Prompted LLMs

Automatic Bloom's taxonomy classification of assessment questions can substantially reduce instructor workload, but labeling is subjective and teacher-dependent. Prior machine learning (ML) and deep learning (DL) approaches reported strong within-dataset results, yet were rarely evaluated in cross-dataset settings, leaving real-world generalizability unclear; meanwhile, LLM effectiveness for Bloom question classification has not been systematically studied. We evaluated the cross-dataset generalization of existing ML/DL methods and assessed LLMs with multiple prompting strategies on five datasets; the best prompting strategy combined in-context examples with course-specific action verbs. Supervised ML/DL models degraded substantially on unseen datasets, whereas LLMs were more stable, suggesting a robust alternative across diverse educational contexts. Based on the best prompting strategy, we also presented a lightweight UI that supports instructors in automatically classifying large question banks; a usability study indicated low workload and high usability.

24.
Nature (Science) 2026-06-10

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1–3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC). The purified AMC enables RNA loading and AGO folding, faithfully recapitulating de novo RISC assembly. Using cryogenic electron microscopy, we determined the structure of AMC bound to a microRNA duplex. In contrast to its conformation in the RISC, AGO adopts a highly open conformation in the AMC: the N domain and the RNA-binding module (PAZ–MID–PIWI) are fully detached and anchored to opposite sides of the HSP90 dimer, connected solely by the unfolded L1 linker. This arrangement exposes a positively charged cleft that accommodates an RNA duplex. AGO folding is facilitated by a small RNA duplex containing a 5′-terminal phosphate—but not by single-stranded RNAs—revealing a role for the RNA duplex as a chaperone-like cofactor that directs AGO domain assembly. These findings elucidate the RISC assembly mechanism and establish the AMC as a molecular tool for probing optimal RNA features and chemical modifications for the rational design of small interfering RNA therapeutics. Our study also sheds light on how chaperones, together with ligands, can guide the folding of client proteins. Structures of the AGO maturation complex reveal how chaperones and an RNA duplex drive assembly of the RNA-induced silencing complex.

25.
arXiv (CS.CV) 2026-06-12

LaME: Learning to Think in Latent Space for Multimodal Embedding via Information Bottleneck

Reasoning-driven universal multimodal embedding has advanced rapidly by introducing Chain-of-Thought (CoT) reasoning into the embedding pipeline. Despite the strong performance across both general and complex tasks, this paradigm suffers from two core limitations: (i) autoregressive CoT reasoning incurs high computational cost, making it impractical for low-latency retrieval; and (ii) embedding performance is heavily coupled with CoT annotation quality, making large-scale training unreliable. These raise fundamental questions: Is textual CoT the optimal form of reasoning for embedding, and can effective embedding reasoning be accomplished in latent space? To this end, we propose LaME (Latent Reasoning Multimodal Embedding), which formulates embedding-oriented latent reasoning as a weakly supervised information bottleneck. LaME employs K learnable reason tokens as a fixed-capacity bottleneck, completing all reasoning within a single forward pass. The two weak supervision signals structurally decouple contrastive from autoregressive objectives and eliminate dependence on CoT annotations, while a two-stage training pipeline ensures stable convergence. Experiments on MMEB-v2 and MRMR show that LaME achieves competitive performance, surpassing some explicit CoT-based models, while delivering 60x faster inference than explicit CoT methods and 2x faster than latent baselines with throughput comparable to discriminative embedding models. Code will be released.