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01.
arXiv (quant-ph) 2026-06-16

Bath memory as a precision resource in quantum transport

arXiv:2606.17026v1 Announce Type: new Abstract: Structured baths can reshape transport fluctuations in mesoscopic quantum devices, yet a predictive criterion for when this enhances precision has been lacking. We propose a route towards such precision advantages by utilizing bath memory in coherent fermionic transport through a noninteracting quantum-dot chain. Using the Landauer-Büttiker formalism, we derive a dual impedance-matching condition that synchronizes the conductor mode splitting, boundary dissipation, and bath bandwidth, and sustains constructive multimode interference across the transmission window. The analytical predictions for the optimal bath bandwidths show excellent agreement with exact nonequilibrium Green's function calculations of the transport for Lorentzian, Gaussian, and Newns spectral densities. The prescription yields an optimal bath bandwidth at which the current Fano factor is minimized and the thermodynamic and kinetic precision coefficients are simultaneously enhanced beyond their Markovian limits. The alignment of the optimal precision regime with the experimentally accessible current Fano factor minimum thus provides a practical strategy for designing precision-enhanced transport in mesoscopic platforms such as semiconductor quantum-dot arrays and ultracold fermionic channels.

02.
arXiv (CS.CV) 2026-06-18

HACMatch Semi-Supervised Rotation Regression with Hardness-Aware Curriculum Pseudo Labeling

Regressing 3D rotations of objects from 2D images is a crucial yet challenging task, with broad applications in autonomous driving, virtual reality, and robotic control. Existing rotation regression models often rely on large amounts of labeled data for training or require additional information beyond 2D images, such as point clouds or CAD models. Therefore, exploring semi-supervised rotation regression using only a limited number of labeled 2D images is highly valuable. While recent work FisherMatch introduces semi-supervised learning to rotation regression, it suffers from rigid entropy-based pseudo-label filtering that fails to effectively distinguish between reliable and unreliable unlabeled samples. To address this limitation, we propose a hardness-aware curriculum learning framework that dynamically selects pseudo-labeled samples based on their difficulty, progressing from easy to complex examples. We introduce both multi-stage and adaptive curriculum strategies to replace fixed-threshold filtering with more flexible, hardness-aware mechanisms. Additionally, we present a novel structured data augmentation strategy specifically tailored for rotation estimation, which assembles composite images from augmented patches to introduce feature diversity while preserving critical geometric integrity. Comprehensive experiments on PASCAL3D+ and ObjectNet3D demonstrate that our method outperforms existing supervised and semi-supervised baselines, particularly in low-data regimes, validating the effectiveness of our curriculum learning framework and structured augmentation approach.

03.
arXiv (CS.AI) 2026-06-19

The Autonomy Tax: Defense Training Breaks LLM Agents

arXiv:2603.19423v2 Announce Type: replace-cross Abstract: Large language model (LLM) agents increasingly rely on external tools (file operations, API calls, database transactions) to autonomously complete complex multi-step tasks. Practitioners deploy defense-trained models to protect against prompt injection attacks that manipulate agent behavior through malicious observations or retrieved content. We reveal a fundamental capability-alignment paradox: defense training designed to improve safety systematically destroys agent competence while failing to prevent sophisticated attacks. Evaluating defended models against undefended baselines across 97 agent tasks and 1,000 adversarial prompts, we uncover three systematic biases unique to multi-step agents. Agent incompetence bias manifests as immediate tool execution breakdown, with models refusing or generating invalid actions on benign tasks before observing any external content. Cascade amplification bias causes early failures to propagate through retry loops, pushing defended models to timeout on 99\% of tasks compared to 13\% for baselines. Trigger bias leads to paradoxical security degradation where defended models perform worse than undefended baselines while straightforward attacks bypass defenses at high rates. Root cause analysis reveals these biases stem from shortcut learning: models overfit to surface attack patterns rather than semantic threat understanding, evidenced by extreme variance in defense effectiveness across attack categories. Our findings demonstrate that current defense paradigms optimize for single-turn refusal benchmarks while rendering multi-step agents fundamentally unreliable, necessitating new approaches that preserve tool execution competence under adversarial conditions.

04.
arXiv (CS.CV) 2026-06-11

Atlas H&E-TME: Scalable AI-Based Tissue Profiling at Expert Pathologist-Level Accuracy

Hematoxylin and eosin (H&E) staining is the cornerstone of histopathology, yet scalable, quantitative analysis of H&E whole-slide images (WSIs) remains a central challenge in computational pathology. We present Atlas H&E-TME, an AI-based system built on the Atlas family of pathology foundation models that predicts tissue quality, tissue region, and cell type labels across multiple cancer types, yielding over 4,500 quantitative readouts per slide at cell-level resolution. A key challenge to validating such systems is overcoming morphological ambiguity inherent to H&E-only ground truth and the limited scalability of more informed references drawing on modalities such as immunohistochemistry (IHC). We address this with a dual validation framework combining biologically grounded depth with technical and morphological breadth. For depth, we propose an IHC-informed multi-pathologist consensus protocol that substantially improves inter-rater agreement over conventional H&E-only annotation. This yields a molecularly grounded reference against which we compare Atlas H&E-TME and pathologists working from H&E alone. For breadth, we benchmark Atlas H&E-TME on over 200,000 high-confidence H&E-only pathologist annotations across 1,500+ cases spanning eight cancer types and their most common metastatic sites, with subtypes covering >90% of clinical cases per cancer type, drawn from 25+ sources and 8+ scanner models. Benchmarked against the IHC-informed consensus, Atlas H&E-TME matches or exceeds pathologist H&E-only performance and generalizes consistently and robustly across this broad morphological and technical scope. In doing so, Atlas H&E-TME turns the H&E slide – the most ubiquitous data in pathology – into a scalable, quantitative window into the tumor and its microenvironment, laying a foundation for the next generation of tissue-based biomarkers in translational and clinical research.

05.
arXiv (CS.CV) 2026-06-12

VietFashion: Benchmarking Sketch-Text Composed Image Retrieval for Cultural Outfits

Cultural garments pose a unique challenge for visual retrieval systems, as their identity often depends on subtle structural and symbolic details that are poorly captured by standard AI models. We introduce VietFashion, a new benchmark for sketch-text composed image retrieval centered on the Ao Dai, a traditional Vietnamese garment. VietFashion enables designers and researchers to retrieve culturally meaningful outfits using a combination of hand-drawn sketches, which convey garment structure, and textual descriptions, which encode cultural semantics. The dataset is initialized with 650 sketches and expanded using generative models to produce over 21,000 photorealistic images with aligned captions. Textual prompts that describe detailed outfit attributes, which are extracted from fashion magazines to ensure authenticity and diversity. To better reflect the inherent ambiguity of design intent, VietFashion adopts a multi-target retrieval setting, where a single query may correspond to multiple valid results. We establish standardized evaluation protocols and benchmark state-of-the-art composed image retrieval methods. Experimental results reveal significant performance gaps in modeling fine-grained cultural semantics and multi-modal composition, positioning VietFashion as a challenging benchmark for fine-grained fashion retrieval. The dataset is publicly available at: https://hng0303.github.io/VietFashion.

06.
Nature (Science) 2026-06-17

Optical metasurfaces for general vision processing on the edge

作者:

Large-scale artificial intelligence (AI) models achieve notable performance in computer vision but require substantial computational resources, limiting their deployment on edge devices1,2. Optical neural networks (ONNs) promise reduced latency and energy consumption by making use of the inherent parallelism of light3. However, present ONNs struggle to scale and are confined to simple tasks, owing to the challenges of replicating exact algebraic operations of digital models using physical (analogue) systems. This work introduces a new paradigm that directly embeds core computer vision principles, including similarity-based recognition, attention-guided perception and detail–context fusion, into a large-scale optical metasurface. By unifying optical physics with these computer vision fundamentals, we develop a photonic–electronic engine that overcomes scalability and generality barriers, enabling high-accuracy, general-purpose computer vision at the edge. The resulting system combines a 41-million-parameter optical metasurface front end with a co-designed, ultraefficient 87,000-parameter digital back end, outperforming many digital models with tens of millions of parameters across object detection, segmentation, 3D reconstruction and video understanding. We build a deployable prototype and demonstrate real-time edge visual processing in natural scenes. This work represents a path towards practical optical computing for general vision tasks in complex natural environments, enabling a new paradigm for low-energy, low-latency, real-time on-device vision intelligence. By embedding core computer vision principles into a large-scale optical metasurface, an efficient vision processing system using far fewer parameters is demonstrated to outperform many digital models and enables deployment on edge devices.

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

Cross-Modal Benchmarking for Robotic Perception in Natural Environments

Natural environments present a complex challenge to robotics perception systems. Current models, particularly vision foundation models, are largely trained on structured, urban environments leading to weaknesses in their perception for field robotics tasks. We showcase the limitations of current models using our recently released WildCross benchmark, a new cross-modal benchmark for place recognition and metric depth estimation in large-scale natural environments. WildCross comprises over 476K sequential RGB frames with semi-dense depth and surface normal annotations, each aligned with accurate 6DoF pose and synchronized dense lidar submaps. In this work, we provide an expanded analysis of the benchmark results from the recent WildCross benchmark, with particular emphasis on expanded metric depth estimation experiments. Access to the code repository and dataset for this work can be found at https://csiro-robotics.github.io/WildCross.

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

Ultra Flash: Scaling Real-Time Streaming Video Generation to High Resolutions

While recent autoregressive video diffusion models achieve remarkable streaming quality, they remain confined to low resolutions (e.g., 480P), leaving efficient, scalable, real-time high-resolution video generation a fundamental open challenge. To bridge this gap, we present Ultra Flash, a cascaded streaming framework capable of real-time high-resolution video generation. Ultra Flash achieves ~30 FPS at 1K resolution and ~18 FPS at 2K resolution on a single GPU through three key contributions: (1) an architecture-preserving T2V-to-TV2V super-resolution training paradigm coupled with an AIGC-oriented data degradation pipeline that effectively preserves the generative capability of the base model, enabling enhanced high-resolution detail when cascaded after mainstream low-resolution generative models; (2) a causal streaming latent upsampler paired with a high-resolution decoder, which enhances spatiotemporal coherence while enabling efficient latent spatial scaling and precise high-resolution decoding with negligible computational overhead; and (3) a cascade high-resolution streaming video generation optimization scheme that first performs hybrid-reward-enhanced sparse causalization and single-step distillation of the super-resolution model, then introduces cascaded streaming self-forcing preference optimization with dynamic cache management, jointly enhancing overall coherence, improving quality, and enabling real-time high-resolution streaming video generation. Extensive experiments demonstrate that Ultra Flash reliably produces ultra-high-resolution streaming video while maintaining state-of-the-art visual quality and superior efficiency. Project Page: https://xin1u.github.io/UltraFlash/

09.
arXiv (CS.CV) 2026-06-11

XPR: An Extensible Cross-Platform Point-Based Differentiable Renderer

Point-based differentiable rendering underpins modern 3D reconstruction, novel-view synthesis, and learning-based graphics pipelines, but developing new rendering methods often requires extensive low-level implementation, hardware-specific kernels, and manually written backward passes. This limits rapid prototyping, reproducibility, exploration, and deployment, especially across diverse hardware platforms. This paper presents XPR, an extensible cross-platform framework for point-based differentiable rendering. XPR introduces a high-level programming interface that separates method-specific logic from the shared rendering pipeline, allowing users to implement new methods in a few lines of code. Its pipeline decomposes rendering into modular, statically shaped parallel operations that can be lowered by a cross-platform compiler to GPUs, TPUs, CPUs, and other ML accelerators. We demonstrate implementations of 3DGS, 3DGUT, and LinPrim, with only a few 100s lines of Python code, each of which can be compiled to a range of hardware platforms with the XLA compiler. These results show that XPR enables fast experimentation and portable execution for emerging point-based differentiable rendering systems.

10.
arXiv (CS.LG) 2026-06-16

Dynestyx: A Probabilistic Programming Library for Dynamical Systems

arXiv:2606.16985v1 Announce Type: cross Abstract: State-space models (SSMs) are the standard formalism for Bayesian treatment of dynamical systems, with natural applications in statistics, signal processing, and machine learning. Despite their importance in both theory and application, dynamical systems have proven difficult to incorporate in modern probabilistic programming languages (PPLs), making state-of-the-art methods less accessible to practitioners and introducing friction in following the "Bayesian workflow." We introduce dynestyx, a probabilistic programming library with first-class support for SSMs, including state-of-the-art methods in the estimation of both states and parameters. Through a single, unified interface, users may specify arbitrary priors for discrete-time or continuous-time dynamical systems, perform inference over mixed-effect data, and make state and parameter estimates with principled uncertainty quantification.

11.
arXiv (quant-ph) 2026-06-19

On chip, multifunctional quantum sensing using single spins in a van der Waals crystal

arXiv:2606.19978v1 Announce Type: new Abstract: Nanoscale thermometry and magnetometry are in high demand across a wide range of scientific and technological applications. In this context, optically addressable spins in solids have emerged at the forefront of on-chip quantum sensing. However, simultaneous quantum sensing of multiple parameters (e.g., temperature and magnetic field) using the same spin sensor remains challenging due to cross-sensitivity to multiple physical quantities. Here, we demonstrate independent dual sensing of temperature and magnetic field using single quantum emitters in hexagonal boron nitride (hBN). We experimentally verify the independent response of the zero-phonon line (ZPL) position to temperature and of optically detected magnetic resonance (ODMR) to magnetic fields. Furthermore, we demonstrate local temperature sensing of a microcircuit while simultaneously measuring an external magnetic field. Our results establish quantum emitters in hBN as a robust platform for multifunctional quantum sensing under realistic operating conditions.

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

Hidden Ghost Hand: Unveiling Backdoor Vulnerabilities in MLLM-Powered Mobile GUI Agents

Graphical user interface (GUI) agents powered by multimodal large language models (MLLMs) have shown greater promise for human-interaction. However, due to the high fine-tuning cost, users often rely on open-source GUI agents or APIs offered by AI providers, which introduces a critical but underexplored supply chain threat: backdoor attacks. In this work, we first unveil that MLLM-powered GUI agents naturally expose multiple interaction-level triggers, such as historical steps, environment states, and task progress. Based on this observation, we introduce AgentGhost, an effective and stealthy framework for red-teaming backdoor attacks. Specifically, we first construct composite triggers by combining goal and interaction levels, allowing GUI agents to unintentionally activate backdoors while ensuring task utility. Then, we formulate backdoor injection as a Min-Max optimization problem that uses supervised contrastive learning to maximize the feature difference across sample classes at the representation space, improving flexibility of the backdoor. Meanwhile, it adopts supervised fine-tuning to minimize the discrepancy between backdoor and clean behavior generation, enhancing effectiveness and utility. Extensive evaluations of various agent models in two established mobile benchmarks show that AgentGhost is effective and generic, with attack accuracy that reaches 99.7\% on three attack objectives, and shows stealthiness with only 1\% utility degradation. Furthermore, we tailor a defense method against AgentGhost that reduces the attack accuracy to 22.1\%. Our code is available at \texttt{anonymous}.

13.
arXiv (CS.AI) 2026-06-19

Class-Incremental Motion Forecasting

arXiv:2603.09420v3 Announce Type: replace-cross Abstract: Motion forecasting enables autonomous vehicles to anticipate scene evolution by predicting the future trajectories of dynamic agents. However, existing approaches typically assume a closed-world setting with a fixed object taxonomy and access to high-quality perception, limiting their applicability in the real world where perception is imperfect, and new object classes may emerge over time. In this work, we introduce class-incremental motion forecasting, a novel setting in which new object classes are sequentially introduced over time and future object trajectories are predicted directly from camera images. We propose the first end-to-end framework for this setting, which adapts to newly introduced classes while mitigating catastrophic forgetting of previously learned ones. Our method generates motion forecasting pseudo-labels for known classes and matches them with 2D instance masks from an open-vocabulary segmentation model. This 3D-to-2D keypoint voting mechanism filters inconsistent and overconfident predictions, while a query feature variance-based replay strategy samples informative past sequences to preserve prior knowledge. Extensive evaluations on nuScenes and Argoverse 2 show that our approach successfully preserves performance on known classes while effectively adapting to novel ones. We further demonstrate zero-shot transfer to real-world driving and show that the framework extends naturally to open- and closed-loop end-to-end class-incremental planning on nuScenes and NeuroNCAP. Code and models will be made publicly available at https://omen.cs.uni-freiburg.de.

14.
PLOS Computational Biology 2026-06-01

Histology-informed spatial domain identification through multi-view graph convolutional networks

作者:

by Huihui Zhang, Jiaxing Chang, Zirong Li, Yue Sun, Pinli Hu, Haoxiu Wang, Hang Yang, Yonglin Ren, Xingtan Zhang, Zehua Chen, Kok Wai Wong, Haojing Shao Identifying spatial domains is crucial in spatial transcriptomics, yet effectively integrating gene expression, spatial location, and histology remains challenging. We present STESH, a Spatial Transcriptomics clustering method that combines Expression, Spatial information and Histology. STESH extracts histological features using a convolutional neural network and generates expression, histology, spatial, and collaborative convolution modules for a multi-view graph convolutional network with a decoder and attention mechanism. We evaluated STESH on multiple tissue types and technology platforms. STESH consistently outperformed ten state-of-the-art methods, achieving superior clustering accuracy with the highest scores in adjusted Rand index, normalized mutual information, and Fowlkes-Mallows index.

16.
arXiv (CS.AI) 2026-06-17

Ensemble RL through Classifier Models: Enhancing Risk-Return Trade-offs in Trading Strategies

作者:

arXiv:2502.17518v3 Announce Type: replace-cross Abstract: This paper presents a comprehensive study on the use of ensemble Reinforcement Learning (RL) models in financial trading strategies, leveraging classifier models to enhance performance. By combining RL algorithms such as A2C, PPO, and SAC with traditional classifiers like Support Vector Machines (SVM), Decision Trees, and Logistic Regression, we investigate how different classifier groups can be integrated to improve risk-return trade-offs. The study evaluates the effectiveness of various ensemble methods, comparing them with individual RL models across key financial metrics, including Cumulative Returns, Sharpe Ratios (SR), Calmar Ratios, and Maximum Drawdown (MDD). Our original experimental results demonstrate that ensemble methods often outperform base models in terms of risk-adjusted returns, providing better management of drawdowns and overall stability. However, both the original analysis and the additional reproduction reported in this version show that ensemble performance is sensitive to the choice of variance threshold \(\tau\), classifier group, RL-agent pair, and market universe. The reproduction evidence strengthens the conclusion that classifier-assisted ensemble selection can improve robustness, while also clarifying that the advantage is conditional rather than automatic across all datasets. This study emphasizes the value of combining RL with classifiers for adaptive decision-making, with implications for financial trading, robotics, and other dynamic environments.

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

Distributional Loss for Robust Classification

This paper proposes a novel loss concept for supervised classification tasks. Rather than enforcing a direct mapping from each input sample to a single assigned label, we define an optimization objective over all classifier outputs as a bimodal Gaussian distribution. This softer target formulation implicitly captures class ambiguity, mitigates overfitting, and encourages the learning of more robust decision boundaries, all without requiring additional label information. Experimental results demonstrate consistent improvements in robustness, with particularly pronounced gains in low-data regimes, while requiring only minimal modifications to standard training pipelines.

18.
arXiv (CS.CV) 2026-06-11

SpecLoR: Spectral Lookahead Rectification for Motion-Coherent Text-to-Video Generation

Flow Matching has enabled robust text-to-video generation via latent ODE sampling. However, velocity approximation and numerical discretization errors inevitably accumulate, causing sampling trajectories to drift. Consequently, generated videos often suffer from severe spatiotemporal inconsistencies. Nevertheless, directly correcting these drifted, noisy latents is challenging: (i) timestep-dependent noise obscures reliable structural cues; (ii) spatial interventions risk disrupting intricate local geometry while incurring heavy computational costs. To address this, we propose Spectral Lookahead Rectification (SpecLoR), a plug-and-play inference method that bypasses noise via lookahead prediction, and circumvents spatiotemporal entanglement by shifting corrections to the frequency domain, where universal statistical priors of natural videos are readily available. First, during early sampling stages, SpecLoR looks ahead to estimate the clean latent $z_{t,0}$ and computes its 3D spatiotemporal spectrum. Next, SpecLoR rectifies the amplitude spectrum to match the prior, leaving the phase intact. Finally, the corrected state is re-noised to resume ODE integration. Experiments on Wan2.2 demonstrate that SpecLoR significantly reduces physical artifacts and enhances motion coherence across multiple benchmarks with minimal computational overhead (4 additional NFEs).

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

Local controllability of heralded quantum linear optics

arXiv:2606.19470v1 Announce Type: new Abstract: Photonic linear optical networks provide a versatile platform for quantum information processing and quantum state engineering. However, the set of states that can be generated using passive linear optics alone is fundamentally constrained by bosonic symmetries. Heralding, based on conditional measurements on auxiliary modes, is a widely used technique to overcome these limitations and effectively enlarge the set of accessible states. Despite the widespread use of heralding, it is often unclear how specific ancillary resources impact the overall reachability of the target space. In this work, we investigate the local controllability of photonic states in linear optical networks by analyzing the rank of the Jacobian of the output state with respect to the underlying unitary circuit, which provides a quantitative measure of the dimension of the accessible tangent space at a given configuration. Our analysis ranges from passive linear optics to heralded linear optics, where auxiliary resources and conditional measurements are included. Within this framework, we quantify how different resources enlarge the locally accessible state space beyond that of passive linear optics and determine the resources required for the Jacobian rank to reach its maximal value, thereby achieving full local controllability. As maximal local rank is a necessary condition for global reachability, our framework offers a systematic tool to assess and compare the accessible state space of measurement-based photonic architectures, and to establish practical criteria for the resources needed in high-dimensional quantum state engineering.

20.
Nature (Science) 2026-06-09

People are turning to AI chatbots to plug gaps in health information

A systematic assessment of health-related queries to a chatbot powered by artificial intelligence highlights shortfalls in health-care provision and the responsibilities of AI companies. A systematic assessment of health-related queries to a chatbot powered by artificial intelligence highlights shortfalls in health-care provision and the responsibilities of AI companies.

21.
medRxiv (Medicine) 2026-06-17

Reverse engineering of motor unit discharge in multiple sclerosis reveals heterogeneity of voluntary motor commands

Central nervous system injury causes motor deficits through derangement of excitatory, inhibitory, and/or neuromodulatory inputs to motoneurons, the three fundamental components of motor commands. Typically, study of pathologic neural control in humans is restricted to only one of the three. Chardon et al. (2024) presented a fundamentally new approach to comprehensively study all components by reverse engineering motor unit firing patterns. We apply their framework to motor unit firing patterns from 89 people with multiple sclerosis (MS) and 34 controls to study excitatory, inhibitory, and neuromodulatory contributions to pathologic motor output. Disruptions to all components are plausible in MS, a disease hallmarked by heterogeneity in nearly all aspects. Accordingly, we found abnormalities in MS for all three components. Notably, neuromodulation included both high and low extremes. Our results suggest that pathophysiology of motor commands in MS varies among patients, a finding fundamentally different from other studied populations showing relative consistency.

22.
arXiv (CS.CL) 2026-06-11

Organize then Retrieve: Hierarchical Memory Navigation for Efficient Agents

Large language model (LLM) agents struggle with long-horizon tasks due to their inherent statelessness, requiring all task-relevant information to be encoded in growing input contexts. The resulting degraded reasoning quality, increased inference cost, and higher latency necessitate efficient working memory mechanisms. However, existing approaches either rely on lossy compression or similarity-based retrieval, which often fail to capture temporal structure and causal dependencies required for multi-step agentic tasks. In this work, we present HORMA, a Hierarchical Organize-and-Retrieve Memory Agent that organizes experience into a file-system-like hierarchical structure, where summarized entities are linked to the corresponding raw trajectories, enabling efficient access without losing detailed information. HORMA decomposes working memory into two stages: structured memory construction and navigation-based retrieval. The construction module iteratively refines how experiences are structured by distinguishing between failures caused by missing information and those caused by misleading or overloaded context. The navigation module retrieves task-relevant context by traversing the hierarchy using a lightweight agent trained with reinforcement learning to select minimal yet sufficient context, thereby reducing latency along the critical execution path. Across ALFWorld, LoCoMo, and LongMemEval, HORMA improves task performance under constrained context budgets while requiring at most 22.17% of the baseline token usage in long conversation tasks. Compared to existing methods, it consistently achieves better efficiency-performance trade-offs and generalizes effectively to unseen tasks.

23.
bioRxiv (Bioinfo) 2026-06-18

A data-driven rediscovery of the specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that assemble structurally diverse peptides, many of pharmacological importance, including antibiotics and immunosuppressants. Within each NRPS module, the adenylation (A) domain selects the substrate to be incorporated, a choice governed by a small set of residues lining the binding pocket. For two decades, computational prediction of A-domain substrate specificity has relied on residue sets - most prominently the Stachelhaus code and the 34-residue "8 Angstrom code" - that were defined by spatial proximity to the substrate rather than by demonstrated predictive value. Here we revisit which residues govern substrate specificity from a purely data-driven perspective. We assembled a non-redundant dataset of 5,366 A-domain sequences (4,693 bacterial and 673 fungal) and used information-theoretic measures to rank alignment positions by their statistical association with substrate identity, without restricting candidate positions to any predefined structural shell. This procedure yielded two compact, kingdom-specific codes: IG15B (15 positions) for bacterial and IG13F (13 positions) for fungal A-domains. Both match or exceed the predictive accuracy of the 34-residue 8 Angstrom code while using fewer than half its positions, and both independently recover the majority of the classical Stachelhaus positions. Notably, our analysis identifies four positions (242, 280, 281, and 284) that lie outside all conventional codes yet carry non-redundant specificity information and co-localize with classical determinants on two helices flanking the binding pocket. These positions provide new candidate sites for the rational engineering of A-domain specificity.

24.
arXiv (quant-ph) 2026-06-11

On-Chip Quantum Randomness Amplification

arXiv:2606.12173v1 Announce Type: new Abstract: Randomness amplification, the task of extracting uniform private bits from biased seeds that may be partly known by a malicious third party, is of central importance in cryptography. The highest security in this task is provided by a class of quantum protocols known as device-independent, which however are challenging to integrate into scalable devices. Semi-device-independent (SDI) protocols are a promising alternative that guarantees security under few natural assumptions, such as bounds on the amount of energy used by the devices. Here, we provide the first demonstration of SDI randomness amplification on an integrated silicon photonic chip, achieving a throughput rate of 20 Mbps suitable for practical applications. This rate is achieved through a novel technique for SDI entropy certification, which delivers strictly tighter von Neumann entropy bounds compared to existing methods and remains valid even if the preparation and measurement devices share quantum correlations. Overall, the methods developed in this work enable the integration of SDI technology into portable telecom devices, opening up a new generation of quantum cryptographic hardware.

25.
arXiv (CS.LG) 2026-06-11

Why Depth Matters in Parallelizable Sequence Models: A Lie Algebraic View

arXiv:2603.05573v2 Announce Type: replace Abstract: Scalable sequence models, such as Transformer variants and structured state-space models, often trade expressivity power for sequence-level parallelism, which enables efficient training. Here we examine the bounds on error and how error scales when models operate outside of their expressivity regimes using a Lie-algebraic control perspective. Our theory formulates a correspondence between the depth of a sequence model and the tower of Lie algebra extensions. Echoing recent theoretical studies, we characterize the Lie-algebraic class of constant-depth sequence models and their corresponding expressivity bounds. Furthermore, we analytically derive an approximation error bound and show that error diminishes exponentially as the depth increases, consistent with the strong empirical performance of these models. We validate our theoretical predictions using experiments on symbolic word and continuous-valued state-tracking problems.