Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (CS.AI) 2026-06-19

Dual-Agent Framework for Cross-Model Verified Translation of Natural-Language Protocols into Robotic Laboratory Platform

arXiv:2606.20120v1 Announce Type: cross Abstract: Biological experiment protocols are written in natural language, whereas automation systems rely on predefined control commands, creating a semantic gap that limits autonomous execution. Microplate-based automatic experiments are particularly challenging due to the need to simultaneously control well mapping, sample-reagent combinations, replicate placement, and parallel dispensing. This study proposes an agent-based protocol translation framework that converts natural-language microplate-based protocols into executable control commands for a robotic laboratory platform. A Parser Agent formalizes the natural-language protocol into a structured representation, and a rule-based mapping engine deterministically incorporates the operational constraints of the robotic laboratory platform to generate device-level control commands. A heterogeneous LLM Validation Agent verifies completeness, parameter accuracy, and execution order, and triggers a self-correction loop with structured feedback when errors are detected. A sweep involving 7 Parsers and 3 Validators on randomly selected ELISA protocols evaluates how model scale and Validator type affect translation accuracy and pass rates under cross-model verification. The accuracy-latency trade-off is further verified by comparing the rule-based mapping of the proposed framework with LLM end-to-end direct mapping. Finally, Bradford assay-based protein quantification using a microplate was demonstrated on a robotic laboratory platform, validating end-to-end autonomous execution from natural-language protocols to real-world experiments. The proposed framework provides a flexible approach to narrowing the semantic gap between natural-language protocols and microplate-based self-driving laboratories.

02.
bioRxiv (Bioinfo) 2026-06-22

From hotspot dependence to distributed robustness in resistance-aware lead optimization

Drug resistance remains a recurrent failure mode in targeted anticancer and antiviral therapy, and resistance evidence often enters only after compound selection. ResistAgent is an evidence-constrained framework that converts mutational liabilities into design-time objectives through site- and combo-aware resistance mapping, deterministic mechanism diagnosis and robust counter-design. In EGFR-Erlotinib and HIV-RT-Rilpivirine, the framework separated residue-level liabilities from observed HIV combination liabilities and linked prioritized mutations to anchor loss, pocket rearrangement, electrostatic shifts and contact redistribution. Same-budget paired searches showed that robust objectives changed lower-tail mutant-panel behavior and interaction-dependence profiles while prioritizing robustness over average-affinity behavior. Under predefined liability panels, selected robust-best trajectories shifted support away from mutable hotspot contacts toward more distributed interaction networks. Supplementary physical summaries and ranking-first benchmarks support the scope of this resistance-aware design strategy while preserving clear boundaries for prospective validation.

03.
arXiv (CS.AI) 2026-06-17

AnalogFed: Privacy-Preserving Discovery of Analog Circuits at Scale with Federated Generative AI

arXiv:2507.15104v2 Announce Type: replace-cross Abstract: Recent advances in generative AI (GenAI) have shown transformative potential for modern hardware design. However, existing GenAI-driven approaches fall short of enabling large-scale electronic design automation (EDA) due to the proprietary and siloed nature of hardware datasets, which cannot be centralized for model training. Achieving at-scale GenAI-driven EDA, therefore, requires a novel privacy-preserving framework that can leverage distributed data without compromising confidentiality. This work introduces AnalogFed, the first privacy-preserving framework for large-scale analog circuit topology discovery using federated learning (FedL) and GenAI. AnalogFed establishes the feasibility of collaborative analog topology design while addressing key security challenges: it mitigates membership inference attacks (MIAs) through a novel input perturbation strategy based on dummy token injection, and defends against model inversion attacks with customized, efficient homomorphic encryption. Extensive experiments demonstrate AnalogFed's effectiveness and efficiency, achieving strong privacy protection without degrading model utility. This framework lays the foundation for scalable, multi-party collaboration in next-generation hardware design automation with GenAI.

04.
medRxiv (Medicine) 2026-06-15

Neural Correlates of Human Food Memory link to Microbial, Homeostatic, and Hedonic Signals: Evidence from a Prebiotic Randomized Clinical Trial

Background Homeostatic and hedonic brain circuits regulate eating behavior but also shape how food memories are encoded and retrieved. Objective We examined neural correlates during food memory encoding and retrieval during functional MRI before and after a 14-day prebiotic intervention in a preregistered, double-blind crossover trial (NCT03829189). Design 55 healthy adults with overweight (19 females, age 28{+/-}6.5, BMI 25-30 kg/m2) underwent 3 Tesla task-based functional MRI before and after dietary intervention of prebiotic (30g inulin/day) or equicaloric placebo for 14 days. Peripheral metabolic, short-chain fatty acids (SCFA), and microbial markers using 16S rRNA analysis were assessed in fasting blood and feces. Results Food memory was enhanced by assigned reward value and engaged brain activity in hedonic regions, including the nucleus accumbens, orbitofrontal cortex, caudate, cingulate, dorsomedial prefrontal cortex, and ventral tegmental area, as well as homeostatic and memory-related such as the hypothalamus and the hippocampus. Higher neural activations during food encoding were related to higher Actinobacteriota abundance, fecal SCFA acetate, and creatinine levels, and lower ghrelin levels. Activations in reward-related and homeostatic brain areas partially correlated with insulin, glucagon-like peptide-1, leptin, and thyroid-stimulating hormone levels. Neural activations related to food memory decreased after prebiotic intervention. The prebiotic supplementation induced decrease of hippocampal activity during food encoding related to changes in gut microbiota Firmicutes abundance. Conclusions This study indicates that neuronal food-related memory processes depend on homeostatic and hedonic brain signals modulated by the gut-brain axis. Our findings raise implications for the treatment of obesity and substance use disorder.

05.
arXiv (CS.CV) 2026-06-11

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

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

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

Breaking the Solver Bottleneck: Training Task Generators at the Learnable Frontier

The limiting resource for training agents via reinforcement learning (RL) is increasingly frontier task supply: valid, solvable tasks just difficult enough to train the current model. As reasoning and agentic models improve, fixed task distributions saturate, while naive synthetic generation yields tasks that are trivial, impossible, or ill-posed. Training a task generator with RL to optimize validity and learnability can address this bottleneck, but direct optimization requires repeated solver rollouts per candidate. For software-engineering (SWE) tasks, a single rollout can take tens of minutes; solver-in-the-loop generator training is intractable. We introduce PROPEL, a solver-amortized framework for training task generators at the targeted solve rate. PROPEL trains a lightweight activation probe on a one-time labeled corpus of generated tasks and solver outcomes. The probe predicts target-solver pass rate from a frozen generator reference model and serves as a proxy for solve rate during generator optimization, reducing generator evaluation to a single forward pass. Across math, code, and software-engineering at multiple model scales, PROPEL shifts generation toward the targeted solve rate: for coding, tasks generated at the learnable frontier increase from $10.1\% \rightarrow 20.0\%$ for a Qwen2.5-3B-Instruct solver and from $5.3\% \rightarrow 12.6\%$ for a Qwen2.5-7B-Instruct solver. For SWE, PROPEL increases the share of generations at the targeted solve rate from $9.8\% \rightarrow 19.6\%$ for Qwen3.5-27B on repositories not seen during training of probe and generator.

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

Point-Identification of a Robust Predictor Under Latent Shift with Imperfect Proxies

arXiv:2603.15158v2 Announce Type: replace Abstract: Addressing the domain adaptation problem becomes more challenging when distribution shifts across domains stem from latent confounders that affect both covariates and outcomes. Existing proxy-based approaches that address latent shift rely on a strong completeness assumption to uniquely determine (point-identify) a robust predictor. Completeness requires that proxies have sufficient information about variations in latent confounders. For imperfect proxies the mapping from confounders to the space of proxy distributions is non-injective, and multiple latent confounder values can generate the same proxy distribution. This breaks the completeness assumption and observed data are consistent with multiple potential predictors (set-identified). To address this, we introduce latent equivalent classes (LECs). LECs are defined as groups of latent confounders that induce the same conditional proxy distribution. We show that point-identification for the robust predictor remains achievable as long as multiple domains differ sufficiently in how they mix proxy-induced LECs to form the robust predictor. This domain diversity condition is formalized as a cross-domain rank condition on the mixture weights, which is substantially weaker assumption than completeness. We introduce the Proximal Quasi-Bayesian Active learning (PQAL) framework, which actively queries a small, targeted set of diverse domains that satisfy this rank condition. PQAL can recover the point-identified predictor, demonstrates robustness to varying degrees of shift and outperforms previous methods on synthetic data and semi-synthetic dSprites, IHDP, ACS Folktables datasets.

08.
arXiv (quant-ph) 2026-06-16

Optimizing Wigner Negativity in Scattering Processes Using Energetic Cost Functions

arXiv:2606.15101v1 Announce Type: new Abstract: Wigner negativities (WNs) are key signatures of non-Gaussian bosonic states and essential resources for quantum technologies. We study their generation in the scattering of coherent pulses by a two-level atom coupled to a one-dimensional reservoir, a unitary and energy-preserving platform. Optimization in this multimode setting is hindered by the complexity of evaluating Wigner functions. We overcome this challenge by introducing energetic cost functions that identify output modes most likely to host large negativities. First using incoherent energy and then isolating a genuinely non-Gaussian contribution, we demonstrate a strong correlation between these quantities and WNs. This correlation extends beyond short, intense pulses to encompass pulses of finite energy, where photons are scattered while the two-level atom is driven. Focusing on the energy-efficiency of the process, we show that maximally efficient generation takes place for one input photon, on average, spectrally mode-matched with the atom.

09.
arXiv (CS.LG) 2026-06-15

Cluster LOCO: Feature Importance For Interpreting Clusters

arXiv:2606.14592v1 Announce Type: cross Abstract: Clustering is widely used for exploratory analysis and scientific discovery, driving insights from market segmentation to biological data analysis, but its outputs can be difficult to interpret, audit, and reproduce as modern datasets become increasingly large and complex. Reliable use of clustering requires understanding which features drive the discovered structure, yet feature-level explanations for clustering remain scarce compared with methods in supervised learning. Furthermore, existing clustering feature importance scores are often tied to specific algorithms and data assumptions. To address these challenges, we propose Cluster LOCO (Leave-One-Covariate-Out), a family of model-agnostic feature importance scores for clustering. Cluster LOCO is built on feature occlusion and clustering generalizability, defined as whether cluster labels learned on one subset of the data can be accurately predicted on held-out samples. For any chosen clustering algorithm, Cluster LOCO quantifies a feature's importance by measuring how much its removal degrades generalizability. We first introduce Cluster LOCO-Split, which relies on data splitting, and then extend it to Cluster LOCO-MP, a minipatch ensemble-based version designed for large-scale data. Across synthetic simulations and an application to cell-type discovery in single-cell transcriptomics, we show that Cluster LOCO more reliably recovers informative features than existing clustering feature importance methods.

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

eCNNTO: A Highly Generalizable ConvNet for Accelerating Topology Optimization

arXiv:2606.19921v1 Announce Type: new Abstract: This work proposes an element-based Convolutional Neural Network (CNN) to accelerate density-based Topology Optimization (TO), termed eCNNTO. TO generally undergoes a large number of iterations, where finite element analysis is performed in every iteration, leading to the efficiency bottleneck especially when dense meshes are used to achieve high-resolution designs. To address this limitation, eCNNTO is proposed to build upon Kallioras et al. (2020), where a Deep Belief Network (DBN) was trained for every element to predict its near-optimal density from its early history, thereby skipping the great majority of iterations and significantly accelerating the TO procedure. However, the method lacks spatial correlations among neighboring elements and may lead to disconnected features in the final structure. The proposed method employs CNN with residual connections to address this issue. On top of it, a novel training strategy is introduced to further enhance the optimization efficiency, where the training dataset consists of the final stage density histories rather than early ones. This change can also help reduce the required training data size. eCNNTO requires only a small dataset to train and yet it can be generalized to problems with largely different boundary conditions, loading cases, design domain geometries, mesh resolutions, as well as non-design domains. In the end, the generalization capabilities and efficiency of eCNNTO are demonstrated through a variety of examples in two and three dimensions, achieving up to 90% and 97% reduction of iterations, respectively.

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

SPADE: Split-and-Delay Embeddings for Autoregressive High-Granularity Calorimeter Simulation

arXiv:2606.11304v1 Announce Type: cross Abstract: We introduce SPADE (SPlit And Delay Embeddings), an autoregressive transformer for sequences whose tokens carry multiple features. Rather than embedding these features jointly, SPADE embeds them independently. Delaying each feature stream relative to the previous one allows intra-token correlations to be learned by the standard self-attention mechanism. Applied to point-cloud calorimeter shower generation in the highly granular ILD detector, SPADE is competitive with the state of the art AllShowers model on photon showers, and substantially outperforms its VQ-VAE-based predecessor OmniJet-$\alpha_C$. The mechanism is applicable to any generative task with multi-feature tokens, enabling LLM-style pretraining workflows for higher-dimensional data.

12.
arXiv (CS.LG) 2026-06-11

Least-Action-Guided Diffusion for Physical Extrapolation

arXiv:2606.11277v1 Announce Type: new Abstract: Reliable extrapolation remains a central challenge for generative models in computational physics, because models trained over finite ranges of time, parameters, or geometries may produce physically inconsistent predictions outside the training distribution. We introduce a least-action-principle-guided diffusion, LAPG, a framework that promotes physical consistency during inference rather than relying solely on constraints imposed during training. The method combines a conditional score-based diffusion model with an action-derived physical guidance score. In the first stage, the learned score model generates an in-distribution proposal; in the second, an action-based variational prior refines this proposal toward the target out-of-distribution condition. This formulation turns the principle of least action into a differentiable inference-time correction mechanism and provides an alternative to pointwise residual penalties that often require empirical loss balancing. We evaluate LAPG on representative ordinary- and partial-differential-equation systems, including free fall, conservative and dissipative spring-mass dynamics, interacting point vortices, and potential flow over parameterized airfoils. In temporal, parameter, and geometric extrapolation tests, LAPG reduces phase drift, preserves dissipative decay, captures vortex motion, and improves the lift response of airfoil flows compared with training-time physics-informed baselines.

13.
medRxiv (Medicine) 2026-06-22

Effect of Lowering the Drink-Driving Blood Alcohol Limit in Scotland on Road Traffic Crashes: a Synthetic Difference-in-Differences Study

Objective: To evaluate the road safety impact arising from Scotlands 2014 reduction in the legal blood alcohol concentration (BAC) limit for drivers, and to assess whether the effect of the reform varied across different spatial contexts. Design: A quasi-experimental statistical longitudinal study using a Synthetic Difference-in-Differences (SDID) approach. Setting: Small-area panel data for Great Britain, with areas (Middle-layer Super Output Areas, MSOAs, in England and Wales and Intermediate Zones, IZs, in Scotland) classed into control and treatment groups according to whether they were exposed to Scotlands BAC reform. The control and treatment groups comprise 7088 spatial units in England and Wales and 852 spatial units in Scotland, respectively, observed over the period 2008-2019. Participants: The study primarily analyses police-reported road traffic collision data from the UK Department for Transports STATS19 system. Data were analysed at the MSOA/IZ level. This is a secondary dataset, and we therefore did not involve patients or the public in formulating the research question, determining outcome measures, or designing and conducting the study. Main Outcome Measures: The main outcome measures were log-transformed rates of total road traffic crashes, and (weekend) night-time crashes (22:00-04:00) per 100,000 population. The latter is used as a proxy measure for drunk driving. Results: Our results indicate that the reduction in the legal BAC limit led to statistically significant declines in road traffic crash rates. Aggregate estimates suggest reductions of 12.0% (95% confidence interval (CI): [-13.7%, -10.3%]) in total crashes, 15.6% (95% CI: [-20.7%, -10.2%]) in night-time crashes, and 12.4% (95% CI: [-16.7%, -7.9%]) in weekend night-time crashes. We also find substantial heterogeneity in treatment effects across spatial contexts. Effects were strongest in rural and less densely populated areas, where reductions exceeded 16% (95% CI: [-18.7%, -13.9%]) for total crashes and reached up to 29.6% (95% CI: [-35.8%, -22.8%]) for night-time and 21.4% (95% CI: [-28.3%, -13.9%]) for weekend night-time crashes. Moderate but statistically significant effects were also observed in dense urban areas, whereas effects in suburban and transitional areas were smaller and not statistically significant. Conclusions: Our analysis suggests that lowering the legal BAC limit in Scotland led to meaningful reductions in road traffic crashes, particularly during higher-risk periods and in rural areas. The findings further suggest that the effectiveness of BAC regulation may vary across local contexts, highlighting the importance of accounting for spatial heterogeneity when evaluating road safety policies.

14.
arXiv (CS.CV) 2026-06-19

Through the PRISM: Preference Representation in Intermediate States of Video Diffusion Models

Evaluating video generation with clean, pixel-based reward models disconnects evaluation from the noisy diffusion process and incurs massive VAE decoding costs. In this paper, we challenge this paradigm by asking a fundamental question: Can a powerful video generator inherently discriminate preferences directly from noisy latents? To answer this, we introduce PRISM (Preference Representation in Intermediate States of Diffusion Models). PRISM employs a lightweight Query-based Aggregation head with a frozen video diffusion backbone to decode preference signals from noisy latents. Surprisingly, PRISM not only achieves SOTA preference accuracy but also unlocks strong noise-robustness, which enables early-stage Best-of-$N$ sampling. This allows for filtering suboptimal candidates at the very beginning of denoising, drastically reducing computation while boosting video quality. We also reveal a strong positive correlation between a backbone's generative performance and its inherent evaluative power, enabling self-improving video backbones.

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

Variational Test-time Optimization for Diffusion Synchronization

Collaborative generation, which coordinates multiple diffusion trajectories to extend the capabilities of pretrained priors, has emerged as a powerful paradigm for extending the applicability of diffusion models. Among existing approaches, diffusion synchronization provides a scenario-agnostic solution by introducing general guidance mechanisms. However, current synchronization approaches rely heavily on heuristics and still require task-specific tailoring, which limits their generalizability and performance. In this work, we mathematically derive a synchronization framework based on optimal control, providing a principled explanation of diffusion synchronization. During sampling, we optimize control variables to guide multiple trajectories toward coherent solutions while remaining close to the underlying diffusion prior. Our method operates entirely at test-time without additional training, thereby enabling broad applicability across diverse generation scenarios when combined with strong pretrained priors. We demonstrate consistent improvements over baselines on three representative collaborative generation tasks, covering a wide range of modalities and applications. Beyond performance gains, our work establishes a novel foundation for collaborative generation, opening a principled path toward extending pretrained generative models to new collaborative generation settings.

16.
arXiv (CS.CV) 2026-06-25

Dual Agreement Consistency Learning for Semi-Supervised Fetal Ultrasound Segmentation

Maternal-fetal US is the primary imaging modality for monitoring fetal development, yet accurate automated segmentation remains challenging due to the scarcity of pixel-level annotations. To address this issue, we propose DACL, a semi-supervised framework for robust fetal US image segmentation. DACL jointly trains a deployment-oriented lightweight convolutional network (1.47\thinsp\mathrm{M} parameters) and a Transformer-based network, leveraging labeled data for supervised learning and unlabeled data via CPS. To enhance prediction stability, we introduce a dual-agreement consistency loss that couples pixel-wise probabilistic divergence with entropy-guided confidence alignment. Unlike conventional CPS methods that enforce agreement only at the prediction level, DACL explicitly regularizes both distributional alignment and uncertainty, thereby suppressing unreliable pseudo-labels and enabling stable cross-architecture pseudo-label learning under extreme annotation scarcity. Furthermore, an interpolation-based consistency strategy using mixup is applied to unlabeled samples to enhance robustness. Under 5% labeled data, DACL improves Dice by up to 2.77% and reduces HD95 by up to 14.69 mm compared with the strongest recent semi-supervised methods, demonstrating significant improvements in boundary accuracy on both fetal head and abdomen datasets. These results demonstrate the effectiveness of agreement-based consistency learning for annotation-efficient fetal US segmentation. Our code is on GitHub.

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

Impulse Decoding of Quantum LDPC Codes: Equivalence of Degeneracy and Code-Shortening

arXiv:2606.18240v1 Announce Type: new Abstract: Quantum error correction is essential for building scalable quantum computers. Within the stabilizer formalism, the Calderbank-Shor-Steane framework constructs quantum codes from pairs of classical linear codes. A distinctive feature in this setting is degeneracy, where multiple equivalent error estimates exist-a phenomenon that has no classical counterpart, and the lack of a meaningful classical coding-theoretic interpretation of which has remained a gap in the literature. In this paper, we demonstrate that degeneracy is closely related to the classical operation of shortening of a linear block code. Interestingly, the shortening here takes place at the decoder rather than at the encoder. Leveraging this insight, we present a parallel decoding scheme for quantum low-density parity-check codes, which we term impulse decoding, that significantly outperforms belief propagation with ordered statistics decoding, as well as several other existing techniques, under both code-capacity and circuit-level noise, with significantly lesser complexity. We then present another algorithm based on decoding of residual errors, which when combined with impulse decoding achieves further performance improvement under circuit-level noise.

18.
arXiv (CS.AI) 2026-06-16

Phys-JEPA: Physics-Informed Latent World Models for Multivariate Time-Series Forecasting

arXiv:2606.16076v1 Announce Type: cross Abstract: Multivariate forecasting in physical systems requires models that predict coupled temporal variables while preserving meaningful state evolution. Deep forecasters can fit temporal correlations, and physics-informed models can regularize predictions with scientific constraints, but these directions are often connected only at the decoded-output level. As a result, the hidden predictive state that generates future trajectories may remain statistically useful but physically unstructured. We introduce Phys-JEPA, a physics-informed joint-embedding predictive architecture for multivariate time-series forecasting. Phys-JEPA learns a latent world model in which predictive states are decomposed into physical and residual components, and physical consistency is imposed directly on latent states and latent transitions rather than only on decoded forecasts. This formulation uses known physical variables to organize the representation space while retaining residual capacity for unresolved dynamics. On Jena Climate 2009–2016, Phys-JEPA reduces aggregate MSE from 0.12482 to 0.12273 and temperature MSE from 0.01892 to 0.01831 at H=24. On Traffic, full Phys-JEPA improves aggregate MSE over the supervised baseline across all tested horizons, reducing H=192 MSE from 0.800784 to 0.773873. On Electricity, the best variant depends on horizon: static latent consistency is strongest at H=24 and H=48, while full Phys-JEPA gives the best aggregate and target-variable MSE at H=192. These initial results suggest that moving physics-informed learning from output space to latent predictive state space is a promising direction for interpretable temporal world models.

19.
arXiv (quant-ph) 2026-06-24

Quantum algorithm for Valiant-Vazirani reduction

arXiv:2606.18428v2 Announce Type: replace Abstract: There is growing interest in extensions of the standard model of gate-based quantum computation to include auxiliary degrees of freedom evolving according to a nonlinear Schrödinger equation. By reducing the Boolean satisfiability problem SAT to quantum state discrimination, Abrams and Lloyd argued that the right type of nonlinearity can be used to solve NP and #P problems in polynomial time, at least in an idealized noise-free limit. For practical implementation, however, we are restricted to simulated and emergent nonlinearities, such as that appearing in mean field models for ultracold atoms and similar ensembles. A prominent example is the torsion model, which arises in two-component Bose-Einstein condensates and spin models with all-to-all Ising interaction. But torsion-based state discrimination appears to fall short of solving SAT. Here we close this gap by constructing the filtered oracle of the Valiant-Vazirani theorem, providing a randomized polynomial-time reduction from SAT to UNIQUE SAT, a promise problem where there is at most 1 satisfying assignment. In the noise-free limit, the UNIQUE SAT problem can be solved in polynomial time using torsion nonlinearity. Quantum Valiant-Vazirani reduction is no faster than the efficient classical version, but a fault-tolerant implementation coupled to a nonlinear quantum coprocessor simulating torsion would enable polynomial time solution to NP (but not #P) problems.

20.
arXiv (quant-ph) 2026-06-17

Time-spectral control of accidental coincidences in daylight entanglement-based free-space QKD

arXiv:2606.17365v1 Announce Type: new Abstract: Daylight entanglement-based free-space quantum key distribution (QKD) is limited by accidental coincidences from receiver-admitted background light. We develop and experimentally validate a receiver-level framework linking receiver bandwidth, accepted temporal width, and background-noise density to Bob singles, sifted-key rate, error rate, and quantum bit error rate (QBER) in telecom-wavelength BBM92 QKD. Indoor sweeps show that useful sifted counts saturate near the source-matched bandwidth, whereas broader bandwidth or higher background mainly increases accidental contamination. Increasing the accepted temporal width leaves Bob singles nearly unchanged but directly raises QBER by enlarging the random-overlap probability. A two-dimensional design map shows that the temporal-window margin contracts rapidly with increasing background-to-signal ratio, while the bandwidth margin remains comparatively broad near source-matched filtering. A 10 m rooftop daylight experiment demonstrates operation in the predicted low-accidental regime, yielding a mean sifted-key rate of 2,811 cps and a mean QBER of 4.43%.

21.
arXiv (quant-ph) 2026-06-25

Many-Body Second Order Green's Function Theory for Ab Initio Molecular Quantum Electrodynamics

arXiv:2606.26076v1 Announce Type: new Abstract: In this work, we develop two many-body quantum electrodynamic methods to calculate the ground-state energies of strongly coupled light-matter molecular systems. Specifically, we extend the second-order many-body Green's function theory (GF2) for electronic systems to incorporate electron-boson couplings. We employ two ansätze to treat the bosonic part of the system, namely the coherent-state (CS) and Lang-Firsov (LF) transformed vacuum state. These are combined with the GF2 method to construct two new approaches, which we refer to as CS-GF2 and LF-GF2. We benchmark CS- and LF-GF2 by studying various molecular systems inside an optical cavity. We investigate $\mathrm{H}_2$ and $\mathrm{LiH}$ potential energy surfaces, keto-eneol tautomerization energy barrier, van-der Waals interactions between two $\mathrm{H_2}$ molecules and the torsional potential energy surface of the ethylene molecule, $\mathrm{C_2H_4}$. Both methods provide highly accurate energies, with only modest additional improvement observed in LF-GF2.

22.
arXiv (CS.CL) 2026-06-19

Thermodynamic Signatures of Reasoning: Free-Energy and Spectral-Form-Factor Diagnostics for Hallucination Detection in Large Language Models

作者:

Hallucination detection in large language models (LLMs) is deployment-critical, and recent work shows that the spectrum of attention-derived graph Laplacians carries strong signal about reasoning quality. Prior spectral diagnostics, however, summarize the Laplacian spectrum by a handful of eigenvalues or hand-picked scalars, leaving most of its structure unused. We propose Free-Energy Signatures (Fes), a spectral descriptor that treats each layer's attention Laplacian as a Hamiltonian and extracts its thermodynamic potentials partition function, free energy, spectral entropy, heat capacity together with the random-matrix-theory (RMT) spectral form factor. We prove three results: (i)~Lipschitz stability of Fes under attention perturbation; (ii)~an expressiveness result showing that Fes enriches finite spectral summaries and approximates moment-derived spectral functionals under explicit regularity and grid-resolution assumptions; and (iii)~a finite-sample PAC bound on the AUROC of a training-free detector built from Fes. Empirically, across six open-weight LLMs and six benchmarks, a lightweight probe on Fes descriptors achieves the strongest aggregate AUROC among attention-spectral baselines, improving over LapEig by $+6.5$ AUROC points and over GoR-4 by $+2.4$ points on average, while requiring no update to the underlying LLM. In the fully unsupervised setting, an RMT-deviation score achieves mean AUROC $0.71$, providing a label-free but weaker detector. A complementary RMT analysis shows that correct generations exhibit more Wigner-Dyson like spectral statistics, whereas hallucinations exhibit more Poisson-like statistics. The anonymized code and config are provided in the supplementary material.

23.
Nature (Science) 2026-06-24

Zero-shot design of drug-binding proteins via neural iterative selection−expansion

作者:

The design of proteins that bind to small molecules has been challenging because it requires simultaneous optimization of the protein sequence, protein structure and ligand conformation1–7. Current deep-learning algorithms have struggled to navigate this landscape, precluding the zero-shot design of binders. Here we show that by combining two neural networks in an iterative design algorithm, small-molecule binding proteins can be created from scratch with high accuracy. We trained a graph neural network—ligand-aware sequence engineering message-passing neural network (LASErMPNN)—to design compatible protein sequences for an input protein backbone and docked ligand. We paired  LASErMPNN with a structure predictor that models a three-dimensional protein–ligand complex for an input protein sequence and ligand identity. The closed-loop iteration of these reciprocal networks optimized sequence–structure–ligand compatibility, and outperformed a comparable design loop using a physics-based energy function. We used our strategy, termed neural iterative selection–expansion (NISE), to design proteins that, using different folds, specifically bind to two chemically distinct small-molecule drugs, exatecan and apixaban, with success rates of 100% and 83%, respectively. The tightest NISE binders had nanomolar-to-picomolar affinities, surpassing those of the next-leading method by 70-fold for exatecan and nearly 10,000-fold for apixaban. LASErMPNN then suggested two amino-acid substitutions that improved the affinity of the tightest exatecan binder by 100-fold without any experimental input. The optimized binder protected the labile lactone ring of exatecan from hydrolysis for days. Our work describes a general recipe for using neural networks to automate the design of small-molecule binding proteins for applications in drug delivery, sensing and catalysis.  By pairing two neural networks in an iterative optimization algorithm, small-molecule binding proteins can be designed from scratch with high accuracy, affinity and success rates, showing promise for applications in drug delivery and sequestration.

24.
PLOS Computational Biology 2026-06-18

Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation

作者:

by Martin Lardy, Leqi Wang, Claire Guerrier, Veronica T. Cheli, Pablo M. Paez, Anmar Khadra Calcium (Ca2+) signaling has emerged as a central regulator of activity-dependent myelination in oligodendrocytes. These Ca2+ signals encompass both the stimulus-independent spontaneous Ca2+ local transients (SCaLTs) generated intrinsically in a voltage-independent manner or facilitated by the membrane voltage, as well as evoked responses triggered by ATP and glutamate release. To investigate the regulatory mechanisms underlying this combined spiking activity, we developed a stochastic spatiotemporal flux-balance model of Ca2+ transients in oligodendrocyte precursor cells (OPCs). The model incorporates all the relevant fluxes in these cells and integrates membrane voltage dynamics with a Ca2+-induced Ca2+-release (CICR) mechanism using parameters fitted to Ca2+ fluorescence recordings. The model reproduced the intrinsic and voltage-facilitated SCaLTs in OPCs in the absence of purinergic and glutamatergic receptors, and captured the three distinct patterns of evoked Ca2+ responses induced by prolonged ATP and glutamate stimulations identified using machine classifier. The model highlighted the role of ATP and glutamate in generating these clusters, and showed that the fast dynamics of CICR is key to producing these evoked responses. Further analysis of the model also revealed that voltage-gated L- and T-type Ca2+ channels slightly increase the frequency of SCaLTs, while stimulation with ATP and glutamate, using randomly distributed pulses mimicking in vivo conditions, leads to an increase in both the amplitudes of Ca2+ spikes (i.e., the combination of SCaLTs and evoked responses) and the prevalence of wide spikes, especially upon glutamate stimulation. Bifurcation analysis of the deterministic version of the model, in the absence of diffusion, demonstrated that ATP and glutamate stimulation can shift the system into an oscillatory regime, thereby increasing the deterministic component of SCaLT dynamics. This study thus offers a comprehensive representation of OPC Ca2+ transients linking recorded in vitro behaviors to in vivo dynamics.

25.
arXiv (quant-ph) 2026-06-11

Invariants of Sequential Circuits and Generalized Non-Abelian Statistics

arXiv:2606.11527v1 Announce Type: cross Abstract: Non-invertible symmetries in quantum many-body systems generally give rise to sequential unitary circuits that move symmetry defects. In this paper, we investigate invariants defined by sequences of such circuits, which move non-invertible defects and generate a Berry phase evaluated on quantum states with defects. We show that this Berry phase generally defines an invariant under local deformations, provided that the sequential circuits preserve the locality of those deformations. This invariant also rules out a short-range-entangled state that preserves the non-invertible symmetry, thereby signaling the 't Hooft anomaly of a non-invertible symmetry purely in terms of unitary operators acting on a state. We then apply this framework to loop excitations in three spatial dimensions and identify a new loop excitation in the (3+1)D $\mathbb{D}_4$ topological order, which we dub a non-Abelian fermionic loop. Using the invariant of sequential circuits, we characterize the statistics of non-Abelian fermionic loops. In addition, we find a new (3+1)D mixed topological order with a single non-Abelian fermionic loop, whose long-range entanglement is protected by an invariant of sequential circuits.