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01.
arXiv (CS.AI) 2026-06-12

Two-Layer Linear Auto-Regressive Models Estimate Latent States

arXiv:2606.12691v1 Announce Type: cross Abstract: Auto-regressive models have emerged as powerful tools for sequential data, from language to video. Understanding how and why these models learn latent representations remains an open theoretical question. In this work, we demonstrate that when trained by empirical risk minimization on data from partially observed linear dynamical systems, two-layer linear auto-regressive models naturally learn to approximate Kalman filtering. In particular, we show that the learned hidden representation coincides, up to a similarity transformation, with the state estimates produced by the optimal (Kalman) filter, even though the model has no explicit knowledge of the underlying dynamics or state. The result follows from three main insights. First, we establish that the Kalman filter is well approximated by an auto-regressive model with bounded truncation error. Second, we show that despite non-convexity, the two-layer optimization landscape is benign, i.e., all stationary points are either strict saddles or global minima. Finally, as our main contributions, we provide finite-sample guarantees on prediction error, parameter estimation error, and latent state recovery. Numerical simulations support the theoretical results and demonstrate that the latent representations of auto-regressive models recover state estimates.

02.
arXiv (CS.CV) 2026-06-19

Evaluation of Image Matching for Art Skills Assessment

While some individuals possess a natural talent for drawing, mastering this skill requires dedicated training and practice. Determining one's skill in the art of drawing requires proper comprehensive assessment. In this paper, we propose a method to measure drawing skill by by matching the hand-drawn image with the original template. Existing techniques often involve complex processes. However, advancements in computer vision allow us to train computers to perform these comparisons at a human-like level, thereby resolving the tedious and overwhelming traditional process. Using computer vision applications, determining image similarity involves identifying the level of similarities in an image with a reference image. We have implemented and analyzed the SIFT feature and Siamese network to measure image similarity. Our results indicate that it is feasible to assess art skill levels. Through feature analysis, we found that SIFT-based key point matching provides a more effective means of detecting drawing skills.

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

A post-selected quantum model of cosmic acceleration

arXiv:2606.12297v1 Announce Type: cross Abstract: The origin of cosmic acceleration remains a central problem in cosmology, commonly attributed to a cosmological constant within the $\Lambda$CDM model or to dynamical dark energy. Here, we develop an alternative approach in which acceleration emerges from quantum post-selection, a standard feature of quantum theory that is not usually incorporated into cosmological modelling. While quantum theory admits both pre-selected and post-selected ensembles, quantum cosmological models are almost exclusively formulated in terms of initial conditions. Building on previous work on post-selected quasiclassical dynamics, we construct a minimal predictive cosmological model in which post-selection and coarse-graining generate effective late-time acceleration without introducing a cosmological constant, dark energy, or modifications of general relativity. The resulting expansion history is highly constrained theoretically and depends on at most two parameters beyond standard Friedmann evolution. Confrontation with type Ia supernova and cosmic chronometer data yields statistically competitive fits while naturally avoiding the coincidence problem. The model also reproduces the standard radiation- and matter-dominated behaviour at early times and predicts a present-day jerk parameter significantly different from the $\Lambda$CDM value. These results suggest that cosmic acceleration may arise as a macroscopic quantum cosmological effect rather than from additional cosmological fluids or modified gravitational dynamics.

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

Finite-Time Queue Peak Laws in Stochastic Networks: Logarithmic Scaling After Geometric Thresholds

arXiv:2606.18218v1 Announce Type: cross Abstract: We study finite-horizon queue peaks in generalized switches, a standard stochastic-network model in which many queues share constrained service resources. Arrivals may be dependent, time-varying, and adapted to the past; the standing load condition is uniform interior slack, meaning the conditional mean arrival vector stays in a fixed contraction of the capacity region. We show that this slack reshapes the finite-time peak law for drift-minimizing scheduling policies such as MaxWeight. The square-root envelope that is sharp without slack persists only up to a geometry-dependent threshold; beyond that threshold, the running maximum grows only logarithmically with the horizon, both with high probability and in expectation. The mechanism is self-normalization: in the current queue direction, the projected fluctuation scale is normalized by the stabilizing drift scale. This removes capacity geometry from the logarithmic coefficient, while geometry remains in the threshold. Matching lower bounds show that both the logarithmic term and a geometric threshold are unavoidable. When finite-time state-space collapse is available, the threshold can be sharpened using local bottleneck geometry. For generalized input-queued switches, we obtain finite-time peak bounds with tight logarithmic coefficients. Simulations illustrate the two-phase envelope, local geometric refinements, and variance-sensitive improvements predicted by the theory.

05.
medRxiv (Medicine) 2026-06-12

Association of circulating endothelial progenitor cell count and functional outcome in patients with acute ischemic stroke due to intracranial large vessel occlusion

Background: Circulating endothelial progenitor cells (cEPCs) contribute to vascular repair following an ischemic stroke. The aim of the study was to evaluate the association between cEPCs and functional outcomes in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) who received endovascular therapy (EVT). Methods: Prospective study of patients with LVO-AIS who received EVT. Blood samples were obtained within 24 +- 12 hours and on day 7+-1 from stroke onset. cEPCs were detected using flow cytometry (CD34+/VEGFR2+/CD133+). The primary endpoint was a favourable functional outcome (modified Rankin Scale 0-2) at three months of follow-up. Secondary endpoints include baseline to 24 hours/day 7 changes in the National Institutes of Health Stroke Scale (NIHSS) score and collateral circulation (CC) status. Bivariate and multivariable logistic regression analyses were performed. Results: Included were 90 patients (73.2+-12.7 years, 41.1% women) in 42 of whom (46.7%) cEPCs were detected at 24 hours. On day 7, cEPCs were detected in 27 (43.6%) of 62 patients for which this information was available. Atrial fibrillation, prior anticoagulant treatment and stroke onset-to-door time

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

Grounded Inference: Principles for Deterministically Encapsulated Generative Models

Authors:

arXiv:2606.19753v1 Announce Type: new Abstract: The incorporation of generative models into traditional computational systems presents both enormous opportunity and tremendous peril. Although many early adopters have realized these perils at great expense, the field still requires foundational frameworks to de-risk incorporation of AI into traditional systems. This manuscript establishes this foundation through the definition of four specific primitives of AI blended architecture, designed to enable deterministic encapsulation of probabilistic models. It further establishes two overarching anti-patterns broadly represented across industry to serve as warnings for engineers in this field. This framework was designed to enable successful integration of AI into traditional systems while providing a foundation upon which generative model providers could build the next generation of generative model interfaces.

07.
arXiv (CS.CL) 2026-06-19

Token-Operations-Oriented Inference Optimization Techniques for Large Models

Large model inference optimization serves as a key foundation for supporting the scalable, low-cost, and highly stable operation of large model services. Centered on token-oriented inference optimization technology, this paper proposes for the first time a four-layer technical architecture consisting of Multi-model Fusion, Model Optimization, Compute-Model Fusion, and Compute-Network-Model Fusion. It systematically reviews the key technologies and current industry status across these four levels and analyzes the application value of related technologies in real-world business scenarios. This paper provides a practical technical path for reducing token production costs, improving token service efficiency, ensuring the stability of token supply, and driving the transition of large model services from being merely callable to being operable.

08.
arXiv (math.PR) 2026-06-18

Stability of Khintchine-type inequalities via log-monotonicity

arXiv:2606.19313v1 Announce Type: new Abstract: We investigate Khintchine-type inequalities for the weighted sums $S=\sum_ka_kX_k$ of independent copies of a symmetric random variable $X$. We show how log-monotonicity of the sequence $r_k(X)=k! \mathbb{E}[X^{2k}]/(2k)!$ implies sharp comparisons between the $L_p$ and $L_2$ norms of $S$ for every even integer $p\geq 2$, extending classic Khintchine-type inequalities and yielding new results in the log-convex setting. We also investigate the stability of our inequalities. Our first stability inequality sharpens the classic inequality by a deviation of the coefficient vector from the coordinate extremizers, while the second quantifies deviation from the Gaussian limit. Our results recover recent stability inequalities for random signs and apply to a broad class of distributions, including type-$\mathscr{L}$ random variables, ultra sub-Gaussian random variables and Gaussian mixtures.

09.
arXiv (CS.CL) 2026-06-16

Creative Collision: Directorial Persona Steering and Competition in Large Language Models

Activation steering has emerged as a powerful tool for shaping the behaviour of large language models at inference time, yet most prior work injects a single semantic direction into the residual stream. We study the richer setting in which two semantically opposing steering vectors are superimposed – a regime we call Creative Collision. Concretely, we construct directorial persona vectors for Steven Spielberg (optimistic, redemptive moral valence) and Martin Scorsese (dark, morally ambiguous) via mean-difference activation contrast on curated screenplay-derived corpora, then interpolate between them with a scalar mixing parameter $\alpha \in [0,1]$ and a steering coefficient $\lambda$. Across five evaluation axes – moral valence, generation coherence, surface style, directional dominance, and vector geometry – three principal findings emerge: (i)~Spielberg's representational signature exhibits robust directional dominance, suppressing Scorsese's moral influence across almost the entire interpolation range; (ii)~intermediate collision points paradoxically improve generation coherence relative to pure single-director steering at high $\lambda$; and (iii)~both personas localise maximally to layer~28 of a 40-layer decoder-only transformer, revealing a shared moral-tone substrate. These results illuminate the geometry of competing semantic directions in transformer residual streams and have direct implications for controllable creative generation and value-aligned narrative synthesis.

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

Scalable Training of Spatially Grounded 2D Vision-Language Models for Radiology

We study how to train visually grounded vision-language models (VLMs) for radiology without manual spatial annotations. We introduce RefRad2D, a large-scale bilingual (German/English) dataset of 1.2M CT and MR image-text pairs derived from clinical practice, with task-specific VQA and spatial grounding subsets generated automatically via LLM-based curation and automated segmentation. Trained on this data, our model RadGrounder jointly performs report generation, visual question answering, and spatial grounding via bounding-box detection or segmentation. On external VQA benchmarks (Slake, VQA-RAD), RadGrounder achieves competitive results with specialized medical VLMs. Adding our clinical data to the training mixture improves open-ended VQA over fine-tuning on the downstream datasets alone, showing the transferability of our dataset. Crucially, adding grounding supervision does not degrade language quality, enabling spatially verifiable outputs at no cost to VQA performance.

11.
arXiv (CS.AI) 2026-06-16

Minimalist Genetic Programming

arXiv:2606.10237v2 Announce Type: replace Abstract: Genetic programming (GP) is based on two important insights. First, that any learning task can fundamentally be posed as a program induction problem, where the goal is to construct a symbolic hierarchical model that is expressed as a syntax tree. Second, to pose this task as a search problem, and use evolution to locate the desired model. Since it was proposed, GP has produced notable results in a wide range of tasks and problem domains. This work presents an alternative view by modifying the second core insight of GP, posing the problem as a syntactic derivation task instead. In particular, this paper presents Minimalist Genetic Programming (MGP), an algorithm that like GP is biologically inspired, but instead of evolution it takes inspiration from the Minimalist Program to human language, in which syntax is understood as an optimal solution to the problem of linking two other mental systems. In minimalism, the core computational process is a binary set formation operator called $MERGE$, than can be used to incrementally construct complex syntactic structures using a simple Markovian process. MGP is able to discover the core building blocks of the symbolic expressions, and to incrementally combined them using $MERGE$. The proposed system is benchmarked on symbolic regression tasks that are known to be difficult to solve with standard GP systems because of the propensity for bloat. Results show that when a proper lexicon of atomic syntactic objects are chosen, MGP is able to consistently produce the exact ground truth model on a set of symbolic regression tasks where standard GP struggles to do the same. The insights provided by minimalism are shown to be relevant to the problem of program induction, and should be explored further based on the potential exhibited by MGP in this work.

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

Beyond the Commitment Boundary: Probing Epiphenomenal Chain-of-Thought in Large Reasoning Models

Chain-of-thought (CoT) reasoning is the dominant paradigm for inference-time scaling in language models, yet the causal influence of individual steps on the final answer poorly understood. We estimate each step's causal importance via early exit and use this measure to study how answers form across the reasoning traces of several model families. Across diverse tasks, we find that reasoning typically crosses a commitment boundary – a sharp transition from transient intermediate guesses to a stable, high-confidence answer. This transition often happens in a single step, well before the model's reasoning block ends, and is followed by epiphenomenal CoT steps that leave the final answer probability unaltered. Using attention probes, we show that answer-formation stages can be linearly decoded from intermediate reasoning steps with high accuracy and generalize robustly to unseen reasoning tasks. We exploit this signal to early-exit reasoning blocks at the commitment boundary, reducing the length of CoTs up to 55\% on average with negligible impact on model performance.

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

Nonlinear cascaded quantum network with giant emitters

arXiv:2404.09829v2 Announce Type: replace Abstract: Chiral quantum optics is central to developing scalable quantum networks, yet existing approaches rely predominantly on linear single-photon regimes. It remains unclear how to generate directional multiphotons. Here we show that giant emitters coupled to nonlinear quantum optical baths enable tunable directional correlated photons, revealing a mechanism for multiphoton directional emission. We demonstrate that the propagation phases of correlated photons, together with the coupling phases of giant emitters, can generate destructive interference in one direction while enhancing emission in the opposite direction, making directionality fully tunable. Building on this mechanism, we introduce a nonlinear cascaded quantum network paradigm mediated by correlated flying qubits, providing a configurable building block enabling distinct many-body applications beyond linear unidirectional setups. These results reveal a rich landscape for engineering multiphoton propagation and correlations through interference in giant emitter-nonlinear bath architectures, offering pathways for quantum networks and strongly correlated light-matter platforms.

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

Improving Scientific Document Retrieval with Academic Concept Index

arXiv:2601.00567v2 Announce Type: replace-cross Abstract: Adapting general-domain retrievers to scientific domains is challenging due to the scarcity of large-scale domain-specific relevance annotations and the substantial mismatch in vocabulary and information needs. Recent approaches address these issues through two independent directions that leverage large language models (LLMs): (1) generating synthetic queries for fine-tuning, and (2) generating auxiliary contexts to support relevance matching. However, both directions overlook the diverse academic concepts embedded within scientific documents, often producing redundant or conceptually narrow queries and contexts. To address this limitation, we introduce an academic concept index, which extracts key concepts from papers and organizes them guided by an academic taxonomy. This structured index serves as a foundation for improving both directions. First, we enhance the synthetic query generation with concept coverage-based generation (CCQGen), which adaptively conditions LLMs on uncovered concepts to generate complementary queries with broader concept coverage. Second, we strengthen the context augmentation with concept-focused auxiliary contexts (CCExpand), which leverages a set of document snippets that serve as concise responses to the concept-aware CCQGen queries. Extensive experiments show that incorporating the academic concept index into both query generation and context augmentation leads to higher-quality queries, better conceptual alignment, and improved retrieval performance.

15.
medRxiv (Medicine) 2026-06-22

Panel-level multilocus methylation quantification in native cell-free DNA by PCR-compatible sequential enzymatic processing

DNA methylation is informative for liquid biopsy, but low template abundance, distributed methylation signals and workflow complexity limit implementation. Here we present Delta-HLD, a PCR-compatible methylation assay platform that quantifies methylation directly in native DNA through sequential hybridization, ligation and methylation-sensitive digestion. The assay co-reports methylation-dependent signals from multiple loci through a shared amplification architecture, generating a single panel-level PCR readout. We established the chemistry, optimized panel size and composition through model-guided experiments, and implemented the assay as a triplex qPCR workflow with per-sample internal process controls. Plasma proof-of-concept analyses showed discriminatory signal in CRC and proof-of-concept transferability to hepatocellular carcinoma. Additional platelet-retaining experiments identified a strategy to increase recovery of analyzable circulating templates while reducing genomic DNA recognition. Delta-HLD provides a compact PCR-compatible framework for low-input methylation analysis without base conversion.

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

G-Loss: Graph-Guided Fine-Tuning of Language Models

Traditional loss functions, including cross-entropy, contrastive, triplet, and su pervised contrastive losses, used for fine-tuning pre-trained language models such as BERT, operate only within local neighborhoods and fail to account for the global semantic structure. We present G-Loss, a graph-guided loss function that incorporates semi-supervised label propagation to use structural relationships within the embedding manifold. G-Loss builds a document-similarity graph that captures global semantic relationships, thereby guiding the model to learn more discriminative and robust embeddings. We evaluate G-Loss on five benchmark datasets covering key downstream classification tasks: MR (sentiment analysis), R8 and R52 (topic categorization), Ohsumed (medical document classification), and 20NG (news categorization). In the majority of experimental setups, G-Loss converges faster and produces semantically coherent embedding spaces, resulting in higher classification accuracy than models fine-tuned with traditional loss functions.

17.
arXiv (CS.AI) 2026-06-15

The Accountability Paradox: How Platform API Restrictions Undermine AI Transparency Mandates

arXiv:2505.11577v5 Announce Type: replace-cross Abstract: Recent application programming interface (API) restrictions on major social media platforms challenge compliance with the EU Digital Services Act [20], which mandates data access for algorithmic transparency. We develop a structured audit framework to assess the growing misalignment between regulatory requirements and platform implementations. Our comparative analysis of X/Twitter, Reddit, TikTok, and Meta identifies critical ``audit blind-spots'' where platform content moderation and algorithmic amplification remain inaccessible to independent verification. Our findings reveal an ``accountability paradox'': as platforms increasingly rely on AI systems, they simultaneously restrict the capacity for independent oversight. We propose targeted policy interventions aligned with the AI Risk Management Framework of the National Institute of Standards and Technology [80], emphasizing federated access models and enhanced regulatory enforcement.

18.
arXiv (CS.CV) 2026-06-15

A Lightweight Fiducial-Based Pipeline for 3D Hyperspectral Mapping of ex-vivo Lumpectomy Specimens

Hyperspectral Imaging (HSI) is a promising modality for intraoperative assessment of resection margins in Breast-Conserving Surgery (BCS), but its clinical translation requires aligning the inherently 2D spectral information onto the 3D shape of the excised tissue so that suspicious regions can be precisely localized for targeted follow-up. We present a fully automated, calibration-free pipeline that produces a 3D hyperspectral point cloud of an ex-vivo lumpectomy specimen from a set of consumer-camera RGB images and a single top-down HSI acquisition. The 3D geometry is reconstructed with a deep-learning Structure-from-Motion backbone, stabilized in a metric reference frame by a custom bundle adjustment that enforces consistency on the corners of four ArUco markers placed around the specimen. The HSI cube is then registered to the reconstruction without recovering the HSI camera pose: the markers, visible in both modalities, define 16 corner correspondences that drive a planar homography, and 3D coordinates are recovered by lookup on an orthographically rendered depth map. Evaluated on two ex-vivo lumpectomy specimens, the pipeline achieves a median 3D registration error below 1~mm and a 2D reprojection error below 0.02 mm, with a total per-specimen processing time under 4 minutes on accelerated hardware. These results support the feasibility of integrating HSI-guided spatial localization into intraoperative margin assessment workflows for breast-conserving surgery.

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

LedgerAgent: Structured State for Policy-Adherent Tool-Calling Agents

Policy-adherent tool-calling agents in customer-service domains must maintain task states across turns while calling tools and obeying domain policies. Task states consist of relevant facts, identifiers, constraints, and conditions observed through user interaction and tool calls. In standard agents, task states are not represented separately. Observations, tool returns, and policy instructions are placed in the prompt, leaving agents to reconstruct the relevant states from the prompt each time they decide what to do next. This design makes state management implicit, creating two common failure modes. An agent may retrieve the right facts but later ground its decision in stale, missing, or incorrect information; and a syntactically valid tool call may still violate a domain policy that depends on the current task state. We introduce \textsc{LedgerAgent}, an inference-time method for tool-calling agents that maintains observed task states in a separate ledger and renders the states into the prompt. The ledger is also used to check state-dependent policy constraints before environment-changing tool calls are executed, blocking policy violations. Across four customer-service domains and a mixed panel of open- and closed-weight models, \textsc{LedgerAgent} improves average pass\textasciicircum{}k over a standard prompt-based tool-calling approach, with the largest gains under stricter multi-trial consistency metrics.

20.
arXiv (CS.AI) 2026-06-12

Competition and Diversity in Generative AI

arXiv:2412.08610v3 Announce Type: replace-cross Abstract: Recent evidence, both in the lab and in the wild, suggests that the use of generative artificial intelligence reduces the diversity of content produced. The use of the same or similar AI models appears to lead to more homogeneous behavior. Our work begins with the observation that there is a force pushing in the opposite direction: competition. When producers compete with one another (e.g., for customers or attention), they are incentivized to create novel or unique content. We explore the impact competition has on both content diversity and overall social welfare. Through a formal game-theoretic model, we show that competitive markets select for diverse AI models, mitigating monoculture. We further show that a generative AI model that performs well in isolation (i.e., according to a benchmark) may fail to provide value in a competitive market. Our results highlight the importance of evaluating generative AI models across the breadth of their output distributions, particularly when they will be deployed in competitive environments. We validate our results empirically by using language models to play Scattergories, a word game in which players are rewarded for answers that are both correct and unique. Overall, our results suggest that homogenization due to generative AI is unlikely to persist in competitive markets, and instead, competition in downstream markets may drive diversification in AI model development.

21.
arXiv (CS.CV) 2026-06-16

Text region detection in historical astronomical diagrams

Text detection is a crucial task in the analysis of historical documents. While datasets and benchmarks exist for text detection in manuscripts and maps, the study of text in mathematical diagrams has received little attention. To address this, we introduce a large-scale, diverse, open-access dataset of 948 historical astronomical diagrams containing 10,940 oriented polygonal text regions. Our dataset spans ten centuries (8th to 18th) and seven main linguistic traditions: Arabic and Persian (115), Chinese (332), Byzantine (233), Latin (185), Hebrew (48), and Sanskrit (35). It captures a wide range of diagram styles and textual content, from symbols to multi-line paragraphs. Each text instance is annotated with ordered polygons that precisely delineate text regions and encode the reading direction. In addition, we annotated the 2,293 regions in Latin diagrams with 20 class labels. We evaluated several strong baselines on our dataset, including TESTR, DeepSolo++, and Poly-DETR, a simple extension of DINO-DETR that we design to predict ordered polygon vertices. Poly-DETR achieves state-of-the-art performance on the MTHv2 and cBAD2019 benchmarks and provides a solid, simple baseline on our dataset. Code and dataset available online.

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

Transforming Shape Schemas with Composable Property-Graph Queries (Extended Version)

arXiv:2606.14309v1 Announce Type: cross Abstract: Property graphs may be constrained by schemas that inform both query engines and human users about the shape of valid data, enforcing a contract between data provider and consumer. Composable property-graph queries transform input graphs into output graphs. Then, the question arises of which schema can be expected after one (or several) transformation steps. We investigate how schema constraints can be inferred given an input schema and a transforming query. Specifically, we propose a reasoning procedure that, given an input schema in ProGS and a query in G-CORE infers an output schema. Since graph updates will happen frequently, our inference procedure does not rely on graph instances, such that the computed output schema applies to all graphs originating from any input graph complying with the input schema. Related work has addressed this problem for SPARQL CONSTRUCT queries, encoding it in Description Logics (DLs) so that the output schema is entailed by axioms inferred from input schema and queries. Property graphs and their queries, however, complicate the matter, as property graphs feature label and property annotations as well as first-class edges. Thus, reification has to be used in one way or another, though available DLs lack the means to encode such features directly. We approach this novel challenge via a family of mappings for i) property graphs reified in RDF, aligned with ii) a mapping from ProGS to SHACL and iii) a mapping from G-CORE to SPARQL CONSTRUCT queries. In this manner, schema inference for property graphs becomes manageable, as we break apart the problem through the extra mapping layer and utilize efficient DL reasoners. We develop the metatheory regarding the soundness of inferred schema constraints and the semantic equivalence of mapped schemas and queries.

23.
Nature (Science) 2026-06-22

Why heritage sites are at risk in a warming world — and how to save them

As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently. As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently.

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.CL) 2026-06-12

G-Long: Graph-Enhanced Memory Management for Efficient Long-Term Dialogue Agents

While Large Language Models (LLMs) have advanced open-domain dialogue systems, maintaining long-term consistency remains a challenge due to inherent limitations in long-context reasoning and the inefficiency of processing extensive raw text. Existing approaches typically rely on either unstructured memory storage, which is prone to information loss, or computationally expensive LLMs that incur high latency. To address these limitations, we propose G-Long, a graph-enhanced framework that utilizes a fine-tuned small Language Model (sLM) for structured triplet extraction and associative retrieval, significantly reducing operational costs. Furthermore, we introduce the novel attention-aware importance scoring mechanism that leverages the intrinsic cross-attention signals of a T5 summarizer to identify salient memories. Extensive experiments across diverse benchmarks demonstrate that G-Long achieves state-of-the-art performance in both response generation and memory retrieval, yielding performance gains of up to 9.8% in response quality on MSC and 40.8% in retrieval recall on LME, while significantly minimizing computational overhead.