Long-horizon egocentric memory transforms continuous first-person video and audio into a searchable record of past experiences. We demonstrate two bottlenecks in existing systems: indices built from context-poor captions are unreliable for agentic search, while retrieval ignores a question's temporal intent. To address both bottlenecks, we introduce EgoCITE (Egocentric Context-augmented Indexing and Time-aware Evidence retrieval), a long-horizon agentic memory framework for egocentric QA. EgoCITE comprises three components. EgoScheme uses local multimodal context to turn fragmentary video captions and speech transcripts into self-contained atomic memory indices. EgoIndex organizes complementary action, activity, utterance, and conversation representations into searchable multi-view memory indices at multiple granularities. EgoRetrv combines semantic search with question-conditioned temporal relevance scoring and curation of retrieved evidence. We evaluate EgoCITE on EgoLifeQA, EgoMem, and EgoR1-Bench in terms of answer accuracy and target-event retrieval alignment. EgoCITE improves accuracy over agentic memory baselines by at least 4.4--14.2\% while achieving 36$\times$ lower cost than long-context LLM agents.
https://arxiv.org/abs/2608.12627
Cashew production is a widespread economic activity in Guinea-Bissau, as well as other countries in West Africa. However, unregulated cashew production can be directly associated with increasing regionwide deforestation rates, biodiversity losses, and a fragile economic structure. There is no nationwide database for listing or georeferencing cashew orchards, so there is a clear need to remotely map their locations. In recent years, multiple methods for detecting orchards have been developed, though they have only been applied on a regional level. This work expands regional analyses to a nationwide scale. It develops a scalable and cost-effective remote approach, based on Sentinel-2 satellite imagery, using Machine Learning techniques to detect cashew orchards automatically. Margin-based Active Learning techniques were employed to develop an optimal training set in terms of the number of points and their informativeness, leading to a cashew map with 94.0% balanced accuracy obtained entirely off-site. We created two datasets and a 2021 cashew map with 10m spatial resolution that are openly accessible through GitHub. The results demonstrate the possibility of a broader cashew orchard mapping, creating a new stepping stone for this environmental application.
https://arxiv.org/abs/2608.11996
Robots operating in human environments need memories that capture not only what objects exist and where, but also how people use them over time and how individual interactions compose into goal-directed activities. Existing 4D scene graphs preserve object and place histories but omit activity structure, whereas activity representations are either not grounded in persistent 3D scenes or rely on externally provided event boundaries and object associations. We present GESTO (Grounded Event and Spatio-Temporal memOry), a spatio-temporal memory that couples a persistent 4D scene graph with a two-level hierarchy of atomic human--object interactions and goal-driven events. From an RGB-D observation stream, GESTO automatically extracts timestamped interactions, grounds them to persistent scene entities, groups them into events, and uses event context to refine uncertain object associations. A relation-aware tool-calling agent queries the resulting memory for activity-centric spatio-temporal reasoning. We evaluate GESTO on the reproducible text, binary, and time categories of an existing benchmark, together with 40 new Space2Event and Event2Space queries. GESTO achieves scores of 0.71, 0.75, and 0.70 on the standard categories, approaching a method supplied with ground-truth event and object grounding, while substantially outperforming the same reasoning framework when these inputs are removed. It further achieves 0.73 and 0.75 on Space2Event and Event2Space queries. Ablations show that hierarchical event structure and context-aware grounding refinement provide complementary benefits, supporting activity-grounded hierarchical memory for retrospective reasoning in dynamic human environments.
https://arxiv.org/abs/2608.10886
Recognizing human behavior across levels of abstraction, from atomic actions to long-horizon intentions, requires data annotated along a semantic hierarchy. Large corpora provide isolated, atomically labeled clips without temporal composition, whereas recorded composite-activity corpora offer shallow, domain-narrow, fixedhierarchies. A benchmark-generation and evaluation frameworkis proposed that synthesizes a four-level hierarchical-intention benchmark, spanning actions, activities, low-level intentions (LLIs), and high-level intentions (HLIs), from a flat single-label action corpus while retaining real pre-extracted features at the action level. Episodes are assembled by a transition model under a subject-consistency constraint, and a coverage-aware sampler reduces the subject usage Gini from 0.566 to 0.248. Synthesizing such a benchmark raises a circular-supervision risk that recorded datasets avoid: if the rules generating the episodes also govern the evaluation, models can succeed by recovering the generator rather than through genuine reasoning. Validity is addressed by design, holding sequence-generation rules disjoint from the first-order-logic rules used at evaluation. The instantiation yields 15,002 episodes. Four reference baselines from different model families characterize difficulty, not as recognition methods. A compositional held-out gap of 0.13 to 0.17 macro-F1 appears across all baselines, including a graph-aware model that recognizes best yet does not close the gap, indicating a structural property of the benchmark rather than a model artifact. A logic-free baseline still violates the held-out semantic rules above their intrinsic data rate, and the order-destroying control changes macro-F1 within seed variation, serving as a generator-consistency check. Theontology, transition model, and generator are released so the benchmark can beregenerated and extended.
https://arxiv.org/abs/2608.10765
Terminal interfaces to conversational agents report rich internal state (listening, thinking, executing tools, awaiting input, failing) almost entirely through text, while the motion channel beside it, the one peripheral vision monitors without reading, carries a single bit: alive. We present the Signal Rail, a one-row terminal status instrument that gives that channel a grammar. Four ideas govern it: spatial semantics (input, processing, and output zones, with direction as meaning), a motion grammar (one kinetic rule per state, never color alone), determinism (frames as a pure function of explicit inputs, golden-frame testable), and honesty (no invented progress or activity). We contribute a 45-section normative specification and a reference implementation inside a working full-duplex local voice agent driven by real signals.
https://arxiv.org/abs/2608.10689
Proteolysis-targeting chimeras (PROTACs) induce protein degradation by recruiting a target protein to an E3 ubiquitin ligase, making degradation a joint outcome of the degrader molecule and its biological context. Although public databases contain thousands of structured molecule-target-E3 records, degradation measurements are available for only a small fraction of them. Existing supervised approaches therefore leave most recorded chemical-biological relationships unused. We introduce DegradeQuery, a context-aware prediction framework that converts these label-missing records into a pretraining signal. Its counterfactual tuple pretraining objective contrasts recorded tuples with alternatives formed by replacing the target, the E3 ligase, or both, enabling the model to learn contextual associations without assigning activity pseudo-labels. The resulting representation is then fine-tuned to predict degradation from the complete molecule-target-E3 context. On the official PROTAC-8K benchmark, DegradeQuery achieves an area under the receiver operating characteristic curve of 0.9065 and an accuracy of 0.8500, outperforming the compared methods. Controlled analyses further show that the improvement is primarily attributable to tuple-level pretraining, can be recovered using only label-missing records, and remains complementary to protein language model representations. These findings demonstrate that incompletely labeled PROTAC databases contain useful relational supervision and provide a practical route for learning context-aware degradation predictors from scarce experimental labels.
https://arxiv.org/abs/2608.10595
The emergence of language-based AI agents promises to transform the scope of machine economic activity. Instead of just proposing bids or following hard-coded protocols, such agents can be used to negotiate and execute agreements in open-ended natural language. However, most evaluations of these abilities have focused on one-off exchanges or simple economic games, leaving open the rich space of time-extended, contingent, and incomplete contracts made expressible by language; they also focus on raw profit, without measuring the qualities required for trustworthy contracting. We address this by formulating a rational framework for how agents should negotiate and perform natural language contracts in uncertain multi-step environments. Within this framework, we develop metrics and baselines for quantifying rational and cooperative play. To evaluate how agents perform at such contracting, we instantiate our framework in ContractSim, an evaluation suite where two players negotiate and execute a multi-turn supplier contract under environmental and inter-player uncertainty. Across six environments and three supplier settings (catering, hotel cleaning, and AI hosting) we find that current LLM-based agents reach agreement reliably, and negotiate efficient contracts when environmental uncertainty is low. However, under high uncertainty, they often fail to negotiate satisfiable, efficient, or mutually beneficial contracts. They are also frequently uncooperative when executing contracts, violating contract terms for additional profit even when contracts are easy to satisfy. These findings highlight room for improvement in the design of language agents that can negotiate, interpret, and execute contracts both rationally and cooperatively.
https://arxiv.org/abs/2608.10475
Deep learning models that synthesize PET from CT or MRI can reduce patient dose and scanner demand, but are typically optimized with global losses such as L1 or mean squared error (MSE) that treat all voxels similarly. In whole-body PSMA-PET, tumor voxels occupy only a small fraction of the volume, yet carry the clinically relevant activity signal; as a result, models can achieve high structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) while still underestimating lesion activity or failing to preserve tumor-specific structure. Radiomics provides biologically meaningful descriptors of tumor intensity and texture, but direct radiomics conditioning is time-consuming because it requires feature extraction from delineated lesion regions. We propose LAFNO, a Lesion-Aware Adaptive Fourier Neural Operator for CT-to-PSMA-PET synthesis that replaces high-dimensional radiomics conditioning with two efficient CT-derived proxy channels. Motivated by radiomics analysis of PSMA-avid tumor core and peritumoral regions, LAFNO uses a contrast proxy for local density variation and a disorder proxy for local texture heterogeneity, both injected into the model bottleneck. LAFNO combines whole-volume reconstruction with lesion-level total lesion activity (TLA), tumor-core contrast, and peritumoral supervision. We evaluated LAFNO against four baseline architectures on the TCIA PSMA-PET-CT-Lesions dataset. LAFNO remained competitive on whole-volume image quality, achieving SSIM of 0.960 and 0.938 for 18F- and 68Ga-PSMA, respectively, while reducing per-patient TLA error to 48.3% and 64.0% for 18F- and 68Ga-PSMA, respectively, and achieving the highest tumor-core radiomics reproducibility across all feature classes for both tracers. Peritumoral reproducibility remained tracer-dependent, indicating that biological fidelity in synthetic PSMA-PET remains challenging.
https://arxiv.org/abs/2608.10429
Many studies have shown that specially crafted inputs can induce large language models (LLMs) to generate excessively long outputs, resulting in significant computational overhead and resource consumption. While most existing denial-of-service (DoS) attacks target text-only LLMs, end-to-end (E2E) speech LLMs are rapidly emerging. Existing text-based DoS attacks primarily rely on prompt engineering, such as adversarial suffixes or semantic inducement, which exploit the discrete nature of text inputs and therefore cannot be directly transferred to continuous speech inputs. Moreover, prior studies on speech model security mainly focus on ASR or TTS systems, leaving the DoS vulnerability of E2E speech LLMs largely unexplored. To address this gap, we propose the perturbation-based DoS attack targeting E2E speech models. Instead of inducing long outputs through prompt manipulation, our method optimizes imperceptible acoustic perturbations to directly influence the model's autoregressive generation process while preserving the original input length. Specifically, we formulate the attack as a composite optimization objective that jointly suppresses EOS generation, encourages prolonged decoding, and largely preserves semantic consistency by integrating weighted EOS loss, top-k logit loss, length loss, and semantic alignment loss. To further improve stealthiness, we employ voice activity detection (VAD) to inject perturbations only into voiced regions. Extensive experiments on three open-source E2E speech LLMs demonstrate that our method achieves stable attack success rate while significantly increasing generation length and GPU resource consumption, revealing security risks in modern ALLMs.
https://arxiv.org/abs/2608.10405
Bus bunching degrades service regularity and increases passenger waiting in high-frequency transit. Existing reinforcement-learning-based holding controllers primarily rely on instantaneous operational variables or route-specific stop identifiers, which provide limited information about the functional and operational context of individual stops and constrain policy reuse across routes. This study introduces an LLM-assisted semantic stop representation for event-driven bus holding control. An LLM is used offline to transform heterogeneous stop information, including physical attributes, surrounding activity context, and historical operational characteristics, into fixed semantic embeddings that are incorporated into a deep Q-learning controller without requiring real-time LLM inference. Experiments are conducted in stochastic simulations calibrated with observed data from two bus routes. Compared with the best calibrated Daganzo baseline, the semantic controller reduces headway variability, bunching events, and passenger waiting time by 32.0%, 69.2%, and 24.0%, respectively. A route-specific stop identifier does not improve the spacing-only controller, whereas semantic stop information improves headway regularity, waiting time, and holding effort, providing a more favorable overall trade-off across control objectives. Cross-route experiments further show that zero-shot transfer provides limited immediate generalization, while warm-start fine-tuning accelerates early-stage learning and improves transferred policies; cold-start training nevertheless achieves the best final performance. These findings suggest that semantic state representations can complement conventional operational states and support adaptation-based policy reuse across related transit routes.
https://arxiv.org/abs/2608.10207
Autonomous Unmanned Aerial Vehicles (UAVs) are complex cyber-physical systems that require the coordinated integration of flight control, navigation, perception, communication, power management, and mission-level decision-making under safety, timing, and reliability constraints. However, many autonomous UAV development workflows still rely on document-centric requirements, separated architectural descriptions, and software implementation artifacts, which can lead to ambiguity, interface inconsistencies, and weak traceability during early design. This paper presents a Model-Based Systems Engineering (MBSE) design framework for the SysML-driven development of autonomous UAVs. The proposed framework uses the Systems Modeling Language (SysML) as a formal design backbone to structure UAV development across four connected layers: stakeholder requirements, functional decomposition, logical architecture, and physical/software allocation. SysML requirement diagrams, activity diagrams, block definition diagrams, internal block diagrams, state machine diagrams, and parametric diagrams are used to capture the functional, structural, behavioral, interface, and performance aspects of the UAV system. The logical architecture is then systematically mapped to a Robot Operating System 2 (ROS 2) software architecture by relating SysML blocks to ROS 2 nodes, flow ports and connectors to topics, request-response interactions to services, and goal-oriented behaviors to actions. The framework is illustrated at the design level using representative autonomous UAV mission scenarios, including autonomous take-off, waypoint navigation, hover stabilization, obstacle avoidance, return-to-home, and emergency handling. The resulting model supports requirement allocation, interface definition, subsystem responsibility assignment, and verification planning before simulation or physical deployment.
https://arxiv.org/abs/2608.09547
Wearable human activity recognition (HAR) remains challenging due to the computational and energy constraints of deep learning models on resource-limited devices. Existing lightweight approaches often rely on recurrent architectures (e.g., GRU and LSTM), limiting parallelism and increasing inference latency. We propose LITEWAY, a modality-agnostic, fully convolutional framework for multichannel sensor time series that replaces recurrent temporal modeling with structured convolutional decomposition. LITEWAY combines lightweight convolutional blocks, strided temporal processing, and convolution-attention pooling to efficiently capture temporal dependencies while reducing computational complexity. We evaluate LITEWAY on 16 HAR datasets against TinyHAR, TinierHAR, and MLP-HAR. LITEWAY achieves competitive macro F1 while reducing model size by 4.06x-9.52x (Light) and 3.87x-9.07x (Full) compared with TinyHAR and TinierHAR. Deployment experiments further show energy reductions of 2.29x-3.14x (Light) and 1.46x-2.01x (Full) compared with TinierHAR and MLP-HAR, highlighting efficient fully convolutional temporal modeling for wearable HAR. The source code is publicly available at this https URL.
https://arxiv.org/abs/2608.09421
The demand for maritime surveillance has given rise to the need for monitoring fishing vessel activities, particularly in addressing the challenge of "dark vessels" that operate without Automatic Identification System (AIS) transmission. This study presents a novel approach for detecting small-scale fishing vessels using nighttime light (NTL) imagery from the SDGSAT-1 satellite, combined with deep learning techniques to enhance fishing monitoring awareness along the western coast of India. A dual-branch YOLO11 architecture was developed to exploit both the 10-meter panchromatic and 40-meter RGB imagery from SDGSAT-1. The custom model architecture was specifically optimized for small object detection in NTL imagery, featuring parallel convolutional backbones that process both modalities before concatenation for enhanced feature extraction. The dual-branch YOLO11 model demonstrated optimal performance with a precision of 0.99, recall of 0.93, F1-score of 0.96, and mAP@50 of 0.96, significantly outperforming single-branch implementations of YOLOv5s, YOLOv8s, and standard YOLO11s architectures. When applied to the western coast of India, the model detected 31525 vessel instances across the temporal dataset spanning 2022-23. Cross-matching analysis with AIS data revealed that only 7146 (22.7%) of detected vessels had corresponding AIS transmissions, while 24379 (77.3%) were identified as potential dark vessels. Spatio-temporal analysis showed peak fishing activity during January-April, with a primary activity corridor parallel to the coastline within 50-100 km, corresponding to productive continental shelf areas. This research contributes to maritime surveillance capabilities by highlighting the effectiveness of nighttime lights satellite imagery for fishing vessel detection and provides valuable insights into fishing patterns and potential regulatory compliance issues in Indian waters.
https://arxiv.org/abs/2608.09360
Mixed emotions represent a clinically relevant but still underexplored target for automatic emotion recognition. EEG provides millisecond-level access to neural activity, yet most EEG pipelines analyze the signal through a single temporal window, thereby fixing the temporal structure available to the model. This study introduces a multi-scale temporal framework for EEG-based emotion recognition. The EEG waveform is decomposed into windows of one or several durations, processed by a shared attention-based encoder, and integrated through a dynamic fusion module that assigns sample-specific weights across temporal scales. The framework is evaluated under a subject-independent protocol in binary and three-class settings, with the three-class task including the mixed affective category. The best results are 65.22% for the two-class task and 45.43% for the three-class task. Both are obtained with three-scale dynamic-fusion configurations and remain substantially above the full-signal baseline. The best-performing temporal scales differ between the two tasks. Dynamic fusion outperforms concatenation in the highest-scoring two-class configuration and slightly exceeds it in the highest-scoring three-class configuration, although these multi-scale settings require substantially more computation than the full-signal baseline.
https://arxiv.org/abs/2608.09088
Cognitive decision-making research depends on diverse scenarios with carefully controlled complexity, yet manual production is slow, inconsistent, and biased. We developed an automated pipeline that uses LLms to generate structured decision scenarios and validates their complexity through a composite framework rooted in established task-complexity theory. We evaluated 4,238 scenarios across multiple domains and complexity tiers. Measurement validation met rigorous psychometric standards. Agreement among five independent model families was nearly perfect, with an intraclass correlation coefficient of 0.997 and a kappa of 0.971. Known-groups validity demonstrated large separation between tiers, with an eta-squared of 0.587 and all pairwise comparisons significant at p less than .001. Factor analysis revealed a dominant complexity construct, with loadings between 0.87 and 0.96 across three frameworks, while interactivity formed a weaker secondary dimension at 0.34. Discriminant validity was limited by a strong relationship between complexity and text length that persisted after controlling for tier, yielding a partial correlation of 0.86. This constrains construct purity but does not undermine the instrument's tier-grading function. Model analyses showed a negative association between throughput and schema pass rate (r = -0.967, p = .007, n = 5), suggesting a speed-quality trade-off, though largely driven by one high-throughput model. Llama 4 Maverick generated scenarios fastest at 134 per minute versus 25 for DeepSeek Chat V3.2, but underproduced complex-tier scenarios, whereas DeepSeek Chat V3.2 balanced domain coverage with high schema compliance. The system demonstrated strong psychometric properties, enabling reliable classification into Simple, Moderate, and Complex tiers and providing the measurement infrastructure needed for downstream cognitive assessment of AI systems
https://arxiv.org/abs/2608.08822
In an era defined by escalating climate change and the pervasive deployment of edge intelligence, the environmental cost of semiconductor manufacturing and operation has reached a critical threshold. As Deep Learning (DL) accelerators dominate System-on-Chip (SoC) die area, achieving true sustainability requires a paradigm shift from static worst-case efficiency to dynamic energy-proportionality. This paper introduces Eco-SoC, a highly scalable VLSI architecture co-designed specifically for sustainable artificial intelligence. We propose a hardware-level Dynamic Precision-Scaling Logic (DPSL) framework that adaptively modulates bit-width precision based on real-time activation sparsity, successfully reducing switching activity by up to 42% on a commercial 7nm FinFET process node. Furthermore, we transcend traditional Power-Performance-Area (PPA) metrics by providing a comprehensive Life Cycle Assessment (LCA) using the Architectural Carbon footprint Tool (ACT). Our synthesis demonstrates that Eco-SoC offsets its increased embodied carbon footprint (a marginal 4.8% area overhead) within 1.1 years of edge deployment. Finally, by introducing a thermal-aware power gating mechanism that mitigates localized hotspots, Eco-SoC doubles the projected Mean Time To Failure (MTTF) of the silicon, providing a tangible, scalable strategy for electronic waste (e-waste) mitigation in next-generation computing systems.
https://arxiv.org/abs/2608.08761
Motivated by the IEEE 802.11bf effort to standardize advanced WLAN sensing, interest in Wi-Fi Channel State Information (CSI) for passive, device-free, and privacy-preserving activity and gesture recognition has grown rapidly. Recent studies have shown that Doppler velocity projections extracted from CSI, which directly reflect human-motion velocity, enable more robust human activity recognition (HAR) and stronger generalization across users and unseen conditions. Nevertheless, reliable generalization under real-world variability remains a major challenge, hindering the adoption of Wi-Fi sensing in real-world applications. To address this challenge, we introduce Doppler Radiance Fields (DoRF), bringing the concept of neural radiance fields (NeRF) from computer vision into Wi-Fi sensing. DoRF models Doppler velocity projections extracted from Wi-Fi CSI as sparse and diverse virtual-camera views of human motion. It then infers a latent 3D motion sequence whose projections along learned effective Doppler directions explain the CSI-derived Doppler observations. The recovered motion is subsequently projected onto an equiangular grid of directions on the unit sphere, producing a spherical representation of the underlying motion. Since DoRF naturally defines the Doppler representation on spheres, we further introduce DoRF++, a spherical-learning design that applies spherical Transformers for activity classification. Experiments on our collected hand-gesture dataset show that DoRF++ significantly outperforms state-of-the-art Wi-Fi-based HAR methods in cross-user generalization accuracy, especially for difficult gestures in settings with a single multi-antenna receiver access point (AP).
https://arxiv.org/abs/2608.08381
Multimodal LLMs that recognise events reliably still fail to say when they happen. Prompted for timestamps, strong VLMs reach as little as $3.8\%$ R@0.5 on Charades-STA, and $77$ to $80\%$ of their wrong predictions carry low output entropy: the models are confidently wrong, and entropy-based error detection stays below a random classifier. We show that this failure lives in the task interface, not in perception. Holding the weights fixed, replacing timestamp regression with a coarse-to-fine scan of binary questions, whose first-token probabilities are consumed only as a ranking, raises R@0.5 by $28$ to $50$ points across four frozen backbones. The residual failures decompose into two measurable axes: a perception axis that moves with the backbone, and a geometry axis that is analytically predictable from the ratio of the output-window and event widths. FV-Action, the training-free method built on this analysis, reaches $56.8\%$ R@0.5 on Charades-STA, above the same backbone's native grounding pipeline and the strongest training-free result on this benchmark; it surpasses every TVG-trained model evaluated zero-shot on TACoS, and improves over direct prediction on ActivityNet Captions and QVHighlights, with no temporal supervision at any stage.
https://arxiv.org/abs/2608.08315
General wearable foundation models are pretrained across broad sensor streams and populations, but are not designed around women's-health tasks. We introduce FemWear, a specialized wearable foundation model that parameter-efficiently repurposes a pretrained multimodal wearable backbone. FemWear retains the patch projection and Transformer encoder, training 239,236 parameters (1.11% of a 21.54M-parameter encoder) through low-rank residual adapters and causal task-family heads. It learns one shared longitudinal representation for menstrual, symptom, affective, sleep/recovery, autonomic, activity, and pregnancy-related outcomes. We evaluate six cohorts with 63 comparable primary metrics, including 33 from women's-health cohorts, while retaining the 32-task OpenMHC ability-retention benchmark. On a fixed participant split over three seeds, FemWear improved cycle-phase macro-F1 by 8.15% and reduced mean absolute error for cramps, mood symptoms, and sleep problems by 9.32%, 5.80%, and 9.43%, respectively. In a stricter 42-participant nested leave-one-participant-out audit, 24-hour onset, 72-hour onset, and cramps retained positive changes of 2.87%, 6.35%, and 2.19%; phase, mood, and sleep were neutral or negative, and no endpoint had a strictly positive corrected confidence interval. Capacity-matched experiments outperformed a latest-day multilayer perceptron but not shared-GRU or multi-gate mixture-of-experts baselines. Train-only calibration reduced onset expected calibration error by 84.2--88.2% with zero temporal-nesting violations. FemWear enables targeted transfer and coherent probability outputs for women's-health research, but does not establish universal performance dominance or clinical validity.
https://arxiv.org/abs/2608.08244
The total synthesis of a complex molecule is among the most demanding intellectual and experimental feats in chemistry: a chemist must plan many steps ahead for how to assemble simple building blocks into an intricate target, devise backup strategies, and anticipate procedural challenges. It is also a profoundly creative activity. For half a century, efforts to automate the retrosynthetic design of natural products and other complex molecules have drawn on catalogued reactions, and the resulting tools now report near-complete success on benchmarks built from that same source. But these tools were shaped to fit benchmarked chemistry, and they falter on many natural products, the frontier of the field, whose densely functionalized, polycyclic architectures demand precisely the inventive chemistry the record contains least. Whether a machine could reasonably design such syntheses like an expert chemist does has remained unclear. Here, we show that SynthEx, an agentic framework built on large language models, plans routes to complex natural products that lie beyond the reach of conventional design algorithms. SynthEx proposes competing strategies, assembles a sequence of routine and key steps into a cohesive route, and critiques and improves its own design; the chemistry it favours is more convergent than existing tools produce, and spans a region of reaction space that catalogue-based tools cannot match. Most notably, in blinded assessments, expert chemists judged its key steps comparable to those of published human syntheses and engaged with them as genuine synthesis plans, a response algorithmic route prediction has not previously accomplished. We release routes to more than a thousand natural products as SynthAtlas, an open, interactive database, and anticipate it will become a shared resource for a collection of complex target molecules that lack existing literature routes.
https://arxiv.org/abs/2608.07454