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01.
arXiv (quant-ph) 2026-06-15

Spin counting via projection noise measurement of mesoscopic solid-state spin ensemble

arXiv:2606.14437v1 Announce Type: new Abstract: Quantum projection noise is the fundamental noise source for the population measurement of spin ensembles. While projection-noise-limited measurements have been extensively studied in atomic systems, corresponding experiments on solid-state spin ensembles remain challenging due to dominant classical readout noise. Here, we report direct measurement of the quantum projection noise of mesoscopic ensembles of nitrogen-vacancy (NV) spin defects at room temperature. Our experiment is enabled by a high optically-detected magnetic resonance (ODMR) contrast of over 20% for a single crystallographic orientation of the defect spins, obtained by combining polarization-selective optical excitation with spin-to-charge conversion. We use our protocol to demonstrate projection noise measurements and spin counting from nanoscale NV ensembles of up to 43 spins. We further demonstrate that the protocol allows for significant gains in sensitivity for magnetometry applications without need for cryogenic operation or high bias magnetic fields.

02.
bioRxiv (Bioinfo) 2026-06-11

OCOO-T : A SIMPLE AND SCALABLE VIRTUAL CELL MODEL FOR TRANSCRIPTIONAL PERTURBATION RESPONSE PREDICTION

Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

03.
arXiv (CS.CL) 2026-06-11

Neural FOXP2 – Language Specific Neuron Steering for Targeted Language Improvement in LLMs

LLMs are multilingual by training, yet their lingua franca is often English, reflecting English language dominance in pretraining. Other languages remain in parametric memory but are systematically suppressed. We argue that language defaultness is governed by a sparse, low-rank control circuit, language neurons, that can be mechanistically isolated and safely steered. We introduce Neural FOXP2, that makes a chosen language (Hindi or Spanish) primary in a model by steering language-specific neurons. Neural FOXP2 proceeds in three stages: (i) Localize: We train per-layer SAEs so each activation decomposes into a small set of active feature components. For every feature, we quantify English vs. Hindi/Spanish selectivity overall logit-mass lift toward the target-language token set. Tracing the top-ranked features back to their strongest contributing units yields a compact language-neuron set. (ii) Steering directions: We localize controllable language-shift geometry via a spectral low-rank analysis. For each layer, we build English to target activation-difference matrices and perform layerwise SVD to extract the dominant singular directions governing language change. The eigengap and effective-rank spectra identify a compact steering subspace and an empirically chosen intervention window (where these directions are strongest and most stable). (iii) Steer: We apply a signed, sparse activation shift targeted to the language neurons. Concretely, within low to mid layers we add a positive steering along the target-language dominant directions and a compensating negative shift toward the null space for the English neurons, yielding controllable target-language defaultness.

04.
arXiv (CS.AI) 2026-06-19

TerraMind: Large-Scale Generative Multimodality for Earth Observation

arXiv:2504.11171v5 Announce Type: replace-cross Abstract: We present TerraMind, the first any-to-any generative, multimodal foundation model for Earth observation (EO). Unlike other multimodal models, TerraMind is pretrained on dual-scale representations combining both token-level and pixel-level data across modalities. On a token level, TerraMind encodes high-level contextual information to learn cross-modal relationships, while on a pixel level, TerraMind leverages fine-grained representations to capture critical spatial nuances. We pretrained TerraMind on nine geospatial modalities of a global, large-scale dataset. In this paper, we demonstrate that (i) TerraMind's dual-scale early fusion approach unlocks a range of zero-shot and few-shot applications for Earth observation, (ii) TerraMind introduces "Thinking-in-Modalities" (TiM) – the capability of generating additional artificial data during finetuning and inference to improve the model output – and (iii) TerraMind achieves beyond state-of-the-art performance in community-standard benchmarks for EO like PANGAEA. The pretraining dataset, the model weights, and our code are open-sourced under a permissive license.

05.
arXiv (CS.LG) 2026-06-19

Reinforcement Twinning for Hybrid Control of Flapping-Wing Drones

arXiv:2505.18201v2 Announce Type: replace-cross Abstract: Controlling flapping-wing drones requires controllers that handle time-varying, nonlinear, underactuated dynamics from incomplete, noisy sensor data. Recent advances in artificial intelligence (AI), particularly reinforcement learning (RL), have opened new perspectives for addressing such complex control problems through data-driven policy optimization from interaction with the environment. Yet purely data-driven methods are sample-inefficient, demanding extensive, sometimes unsafe exploration, especially without guiding physical models. This motivates hybrid AI-physics frameworks. This article proposes a hybrid model-free/model-based flight-control approach using the reinforcement twinning algorithm. The model-based (MB) component uses an adjoint formulation and an adaptive digital twin continuously identified from live trajectories; the model-free (MF) component uses RL. The two agents share knowledge via transfer learning, imitation learning, and shared experience between the real environment and the digital twin, coordinated by a policy referee that selects which agent acts in reality based on digital-twin performance and a real-to-virtual consistency ratio. The framework is evaluated for the longitudinal control of a flapping-wing drone, modelled as a nonlinear time-varying system driven by quasi-steady aerodynamic forces. The hybrid strategy is tested under three adaptive-model initializations: (1) offline identification from existing data, (2) random initialization with fully online identification, and (3) offline pre-training with biased parameters followed by online adaptation. In all cases, the hybrid framework improves performance, robustness, and sample efficiency over purely model-free and purely model-based approaches.

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

The Register Gap: A Meaning Intelligence Framework for Nigerian Public Discourse

We introduce the Meaning Intelligence Framework (MIF), a nine-dimension annotation and evaluation schema for Nigerian public discourse that separates surface sentiment from true communicative intent. Existing benchmarks for Nigerian languages, including NaijaSenti and AfriSenti, treat sentiment classification as a three-way polarity task (positive, negative, neutral). We argue that the dominant failure mode of AI systems on Nigerian discourse is not translation failure but context failure: the same utterance carries opposite pragmatic force depending on speaker, audience, and situation. The MIF operationalises this insight across nine scored dimensions: register, surface sentiment, true intent, irony, coded subtext, risk tier, annotator confidence, speaker emotion, and recommended communications action. We construct a 30-item calibration dataset spanning Standard English, Nigerian English, Nigerian Pidgin, and code-mixed registers, and evaluate a frontier language model (Gemini 2.5 Flash) under zero-shot and schema-informed prompting conditions. The headline finding is the Register Gap: zero-shot register classification accuracy is 33.3%, rising to 73.3% (+40 points) when the model receives the MIF schema in-context. The composite Meaning Intelligence Score increases by 5.4 points (73.2 to 78.6) under schema-informed prompting, with the largest practical gains in register identification, coded-subtext detection (+10 points), and strategic action recommendation (+10.3 points). We release the framework specification, annotation guidelines, and the 30-item public calibration set to support reproducibility, while retaining a private holdout corpus for contamination-protected evaluation.

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

QueryGaussian: Scalable and Training-Free Open-Vocabulary 3D Instance Retrieval

arXiv:2606.19733v1 Announce Type: cross Abstract: Efficiently retrieving specific 3D instances from large-scale scenes via natural language prompts remains a formidable challenge in multimedia analysis. Existing approaches predominantly follow a "scene-level embedding" paradigm, which requires distilling high-dimensional semantic features into every 3D primitive. This strategy suffers from a fundamental architectural bottleneck: memory and computational costs scale linearly with scene complexity, inevitably triggering out-of-memory (OOM) failures in city-scale environments. To address this barrier, we propose QueryGaussian, a training-free framework for expeditious and scalable open-vocabulary 3D instance retrieval. Unlike holistic semantic distillation, QueryGaussian employs an instance-level query mechanism that decouples semantic understanding from geometric representation. Specifically, we leverage pre-trained 2D vision models to interpret user prompts and lift segmentation masks into 3D via a concurrent maximum-weight association strategy, ensuring semantic-visual consistency. To mitigate projection ambiguity, we introduce a temporal fusion module with multi-stage adaptive density clustering. Experimental results demonstrate that QueryGaussian not only matches the accuracy of state-of-the-art methods but also delivers a decisive efficiency leap, reducing GPU memory usage by over 70% and accelerating inference by 180x. Crucially, QueryGaussian enables expeditious instance retrieval on city-scale scenes containing tens of millions of Gaussians using consumer-grade hardware.

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

Characterizing the functional role of quantum coherence in energy transfer

arXiv:2606.13404v1 Announce Type: new Abstract: Quantum coherence is understood to play a role in excitation energy transfer in open quantum systems, yet a quantitative approach to assessing its influence on the transfer process is still missing. Using Nakajima-Zwanzig projection operators, we derive a general memory kernel identity that enables us to characterize and quantify the impact of coherence in the eigenenergy basis on a generalized rate of energy transfer. Applying our approach to the electronic dynamics of a dimer coupled to a structured phonon bath, we demonstrate how quantum coherence acts to modulate energy transfer.

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

Misinformation Propagation in Benign Multi-Agent Systems

Multi-agent systems, in which multiple large language model agents solve problems through turn-based interaction, are increasingly deployed in high-stakes settings such as medical diagnosis, legal analysis, and forensic decision-making. Their reliability can be at risk when single agents reason from incorrect or misleading context, e.g., from tool calls, since errors may propagate through agent interactions. This work studies this risk by injecting intent-based misinformation into benign single-agent and multi-agent systems across reasoning, knowledge, and alignment tasks. We find that misinformation can degrade single-agent performance and persists across multi-agent debate, with agents often retaining answers introduced by misinformed peers. Nevertheless, multi-agent debate reduces the resulting performance degradation compared to single-agent prompting, especially when most agents are not exposed to misinformation. Robustness depends on group composition and decision protocol. Consensus can be more stable than voting under peer pressure, while majorities can often steer misinformed agents back toward correct answers. Our results show that misinformation robustness in multi-agent systems depends on the underlying model and also on how agents exchange information and aggregate decisions.

10.
arXiv (quant-ph) 2026-06-12

Steady-State Noise Signatures of Lindbladian Exceptional Points

arXiv:2606.13377v1 Announce Type: new Abstract: Exceptional points (EPs) are non-Hermitian degeneracies at which two or more eigenvalues and their corresponding eigenvectors coalesce. In open quantum systems, exceptional points can arise in the Lindbladian governing the dissipative dynamics. Their signatures have so far been mainly identified in finite-time observables, such as transient currents, while steady-state average currents generally provide no direct evidence of the underlying exceptional-point structure. In this work, we demonstrate that signatures of Lindbladian EPs can nevertheless be accessed in the steady-state regime through current noise. We derive general expressions for current correlation functions within a Lindblad master-equation framework and show, in particular, how exceptional points affect their behaviour as a function of the time delay. We illustrate these results with the paradigmatic example of two interacting qubits coupled to two reservoirs, where the steady-state noise clearly distinguishes overdamped, underdamped, and critical regimes. Our results establish current correlation functions as a steady-state probe of Lindbladian EPs in open quantum systems.

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

Sparse positive maps on qutrits with exact nondecomposability thresholds and PPT-entanglement transitions

arXiv:2606.19765v1 Announce Type: new Abstract: We study a family of sparse positive maps on qutrits for which positivity, decomposability, and PPT entanglement can all be analysed explicitly. The block structure of the associated Choi matrices reduces positivity to a Hermitian biquadratic form and leads to exact positivity boundaries for three representative parametric families. For the same families we determine the exact transition between decomposable and non-decomposable maps and construct associated PPT states of two classes. The first consists of witness-adapted deformations naturally tied to the non-decomposability analysis. The second consists of analytically tractable families whose full PPT-entangled branch is detected by fixed positive maps, yielding exact thresholds between separability and bound entanglement. For the trace-preserving subclass, we further compare positivity with a recent eigenvalue bound for 2-positive maps, thereby making the gap between positivity and higher-order positivity fully explicit within this family.

12.
medRxiv (Medicine) 2026-06-22

Burden of Cardiovascular Disease in Brazil, 1996-2023: A Retrospective Descriptive Study of the Epidemiology and Impact on Public Healthcare with Emphasis on Acute Myocardial Infarction

Background Cardiovascular diseases (CVD) are the leading cause of death worldwide, and their epidemiology is correlated with genetic predisposition, exposure to risk factors, sex, age, access to medical care, and other sociodemographic characteristics. Brazil is a developing country with a vast territory, which leads to structural inequalities. Estimates of CVD in Brazil, in its regions, and in its population are poorly evaluated and analysed. Methods We obtained CVD-related data from the Brazilian Unified Health System (SUS) and analysed mortality and morbidity from 1996 to 2023 by sex, race/ethnicity, age, and region. We calculated the risk of death from the most prevalent diseases, the average length of hospital stay, and the costs associated with heart transplantation. Findings In Brazil, acute myocardial infarction was the pathology that led to the highest number of deaths across all variables analysed during the evaluated period. Other CVD were also related to causes of death and morbidity, such as hypertensive diseases and heart failure. Interpretation Brazil presents a serious challenge to the public health system due to the high number of deaths and the progressive mortality rate. This study represents a fundamental contribution to the basis for formulating public health policies aimed at reducing the growing impact associated with these diseases. Funding CNPq, CAPES, FAPEMIG, INCT

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

Preparation of Fractional Quantum Hall States on Quantum Computers

arXiv:2606.16548v1 Announce Type: new Abstract: The realization of fractional quantum Hall (FQH) states, characterized by fractional charge and intrinsic topological order, on quantum computers represents a central challenge at the interface of condensed matter physics and quantum information science. Current methods are grouped into two types: methods based on (quasi-)adiabatic evolution of complex parent Hamiltonians to yield target states, and circuit-based approaches for direct state preparation, which are confined to effectively one-dimensional systems near the thin cylinder or torus limit. We introduce a complementary scheme relying on direct quantum circuit construction, which works for arbitrary geometries. Specifically, we present a method to precisely prepare the $\nu=1/3$ Laughlin state on the sphere geometry and demonstrate that it significantly reduces the required number of two-qubit gates and circuit depth, compared to variational quantum circuit approaches. In addition, we employ optimal control techniques to design control pulses for both superconducting and Rydberg atom platforms, identifying experimentally feasible protocols for state preparation. Our results provide an efficient and hardware-relevant pathway for realizing generic FQH states on both noisy intermediate-scale and fault-tolerant quantum devices.

14.
arXiv (CS.AI) 2026-06-17

ParkingTransformer: LLM-Enhanced End-to-End Trajectory Planning for Autonomous Parking

arXiv:2606.17082v1 Announce Type: cross Abstract: End-to-end autonomous parking has emerged as a critical task within the realm of autonomous driving. However, existing methods suffer from black-box characteristics, lacking high-level semantic understanding and interpretability, which impedes the realization of seamless long-distance autonomous parking from the road to the target spot. To address these limitations, we propose ParkingTransformer, a novel framework that leverages multi-view perception and the scene understanding capability of Large Language Models (LLMs). By combining trajectory queries with LLMs implicit state features, our method interacts directly with historical information and raw sensor data to output planning trajectories, eliminating the need for dense Bird's-View (BEV) representations. To compensate for the inadequate spatial reasoning ability of LLMs, we introduce 3D positional encoding to explicitly inject spatial geometric awareness. Furthermore, a fixed-window streaming mechanism is designed for historical information processing, significantly improving long-term temporal processing efficiency and inference speed. Additionally, a coarse-to-fine decoding strategy is employed to progressively enhance trajectory precision. Extensive closed-loop experiments are conducted on the CARLA simulator and real-world vehicle platforms. The results demonstrate that our method achieves a driving score of 61.32 in CARLA simulator and an average success rate of 88.70% in real-world experiments, validating the feasibility and effectiveness of the proposed algorithms.

15.
arXiv (quant-ph) 2026-06-12

Squeezing Enhancement in Lossy Multi-Path Atom Interferometers

arXiv:2409.04091v3 Announce Type: replace Abstract: This paper explores the sensitivity gains afforded by spin-squeezed states in atom interferometry, in particular using Bragg diffraction. We introduce a generalised input-output formalism that accurately describes realistic, non-unitary interferometers, including losses due to velocity selectivity and scattering into undesired momentum states. This formalism is applied to evaluate the performance of one-axis twisted spin-squeezed states in improving phase sensitivity. Our results show that by carefully optimising the parameters of the Bragg beam splitters and controlling the degree of squeezing, it is possible to improve the sensitivity of the interferometer by several dB with respect to the standard quantum limit despite realistic levels of losses in light pulse operations. However, the analysis also highlights the challenges associated with achieving these improvements in practice, most notably the impact of finite temperature on the benefits of entanglement. The results suggest ways of optimising interferometric setups to exploit quantum entanglement under realistic conditions, thereby contributing to advances in precision metrology with atom interferometers.

16.
arXiv (CS.LG) 2026-06-24

Debate2Create: Robot Co-design via Multi-Agent LLM Debate

arXiv:2510.25850v3 Announce Type: replace-cross Abstract: We introduce Debate2Create (D2C), a multi-agent LLM framework that formulates robot co-design as structured, iterative debate grounded in physics-based evaluation. A design agent and control agent engage in a thesis-antithesis-synthesis loop, while criterion-specific LLM judges provide multi-objective feedback to steer exploration. Across five MuJoCo locomotion benchmarks, D2C achieves the highest default-normalized score among the evaluated LLM-based and black-box baselines, with gains up to 3.2x on Ant and nearly 9x on Swimmer. Iterative debate yields 18-35% gains over compute-matched zero-shot generation, and D2C-generated rewards transfer to default morphologies in 4/5 tasks. These results suggest that structured, simulator-grounded multi-agent interaction is a useful mechanism for joint morphology-reward optimization under a fixed-topology, per-candidate-RL protocol. Project page: debate2create.github.io.

17.
arXiv (quant-ph) 2026-06-24

Augmenting Imaginary-Time Evolution with Local Geometric Information

arXiv:2606.23934v1 Announce Type: new Abstract: Imaginary-time evolution (ITE) underpins a broad family of algorithms for ground-state preparation in quantum simulation and quantum many-body physics. In these methods, convergence is governed by the energy variance of the instantaneous state, causing the flow to approach the ground state only asymptotically. We introduce an augmented imaginary-time evolution (AITE) framework that replaces the standard gradient flow on the energy landscape with a geometrically informed descent along locally optimal directions, which are identified by exploiting the higher-order statistical structure of the instantaneous energy distribution. The resulting flow strictly outperforms standard ITE throughout the entire evolution and exhibits two qualitatively distinct regimes: a superlinear convergence regime, followed by an extinction regime in which the energy error vanishes exactly at a finite imaginary time, in sharp contrast to the asymptotic exponential decay of ITE. Standard ITE is recovered in the zero-skewness limit of AITE, implying that the acceleration extends naturally across the broader ITE algorithmic family.

18.
arXiv (CS.CV) 2026-06-19

Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank

The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.

19.
arXiv (CS.LG) 2026-06-12

Physics-Aware Auxiliary Losses Improve Out-of-Distribution Generalization of a GNN Synthesizability Filter

arXiv:2606.12651v1 Announce Type: new Abstract: Machine-learning drug-discovery pipelines increasingly rely on generative models that propose molecules far from the data used to train downstream synthesizability filters. Existing filters (SAScore, SCScore, RAscore, DeepSA) are purely statistical and degrade in exactly this out-of-distribution (OOD) regime. We ask whether cheap, closed-form physical priors, used as auxiliary supervision on a graph neural network (GNN), improve OOD generalization. We add two auxiliary losses to a GINE backbone: a topological complexity regression supervised by the Bertz index, and a strain-energy soft penalty supervised by MMFF94 force-field energy. On a 65,177-molecule corpus (HIV, Tox21, COCONUT) labeled by SAScore thresholds we reproduce a strong in-distribution baseline, then evaluate a 4-way ablation (baseline / +complexity / +strain / +both) on a single-source OOD split (train on drug-like HIV+Tox21, test on COCONUT natural products), repeated over 5 seeds with paired bootstrap confidence intervals. All three physics-aware variants give a small but statistically significant OOD improvement over the baseline (mean OOD AUC 0.9774): +complexity Delta = +0.0060 (95% CI [+0.0023, +0.0102]), +strain Delta = +0.0032 ([+0.0008, +0.0052]), +both Delta = +0.0066 ([+0.0038, +0.0093]); every interval excludes zero, and the combination is best. The variants are indistinguishable in-distribution, so the effect is visible only under OOD evaluation. We are explicit that the effects are modest, and we report a cautionary methodological finding: a single-seed version of this experiment produced a qualitatively different (non-monotone) story that did not survive multi-seed evaluation.

20.
arXiv (CS.LG) 2026-06-24

Precision Physical Activity Prescription via Reinforcement Learning for Functional Actions

arXiv:2605.19208v2 Announce Type: replace-cross Abstract: Physical activity (PA) plays an important role in maintaining and improving health. Daily steps have been a key PA measure that is easily accessible with common wearable devices. However, methods are lacking to recommend a personalized optimal distribution of daily steps over a period of time for the best of certain health biomarkers. In this paper, we fill this void based on the data from the All of Us Research Program which includes months of step counts as well as repeated measurements of key health biomarkers. We develop a new offline reinforcement learning (RL) algorithm to learn personalized and optimal PA distributions associated with cardiometabolic risk, where the action is a function representing the daily step distribution over a period of time. Simulation studies demonstrate the advantage of the proposed approach over existing continuous-action RL methods. The learned optimal policy from the All of Us data generally suggests people take more daily steps and also follow a more consistent pattern of PA over time while offering tailored recommendations for subgroups in blood glucose level, body mass index, blood pressure, age, and sex.

21.
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.

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

Visualizing LLM Latent Space Geometry Through Dimensionality Reduction

arXiv:2511.21594v3 Announce Type: replace Abstract: Large language models (LLMs) achieve state-of-the-art results across many natural language tasks, but their internal mechanisms remain difficult to interpret. In this work, we extract, process, and visualize latent state geometries in Transformer-based language models through dimensionality reduction. We capture layerwise activations at multiple points within Transformer blocks and enable systematic analysis through Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP). We demonstrate experiments on GPT-2 and LLaMa models, where we uncover interesting geometric patterns in latent space. Notably, we identify a clear separation between attention and MLP component outputs across intermediate layers, a pattern not documented in prior work to our knowledge. We also characterize the high norm of latent states at the initial sequence position and visualize the layerwise evolution of latent states. Additionally, we demonstrate the high-dimensional helical structure of GPT-2's positional embeddings and the sequence-wise geometric patterns in LLaMa. We make our code available at https://github.com/Vainateya/Feature_Geometry_Visualization. A better formatted blog-post with identical content is available at https://iclr-blogposts.github.io/2026/blog/2026/vis-llm-latent-geometry/.

23.
arXiv (CS.LG) 2026-06-16

Towards a Unified Generative Model for Scarce Time Series with Domain Experts

arXiv:2606.15172v1 Announce Type: new Abstract: Synthesizing realistic time series with generative models has wide-ranging applications in real-world scenarios. Despite recent progress, most existing methods are trained under the assumption of abundant training data, which substantially limits their effectiveness in data-scarce settings. In this paper, we propose TimeMoDE, a novel framework that integrates Diffusion Transformers with Mixture-of-Experts to exploit both domain adaptability and diffusion-stage awareness for time series generation under data scarcity. It is pre-trained on a large-scale collection of multi-domain datasets to extract domain-agnostic temporal representations and domain-specific information benefiting generalization during fine-tuning. We propose Domain Prompts to condition expert assignment for indistinguishable noised tokens, mitigating the limitations of capturing inter-dataset relationships. Moreover, we incorporate diffusion timestep signals to equip the experts with awareness of time series degradation variations, facilitating adaptive calibrate to stage-dependent denoising requirements. Extensive experiments demonstrate that TimeMoDE outperforms existing methods under diverse low-data settings. It establishes an innovative paradigm for advanced time series few-shot generation.

24.
arXiv (CS.CL) 2026-06-12

From Benchmarks to Skills: Low-Rank Factors for LLM Evaluation

Current evaluations of large language models (LLMs) rely heavily on a growing collection of benchmarks and on aggregate benchmark scores, yet it remains unclear what this comparison actually captures, and what these scores reveal about models' underlying capabilities. Here, we propose a new paradigm for LLM evaluation, by asking whether benchmark performance reflects many independent abilities, or rather relies on a small number of shared dimensions. To answer this, we apply Factor Analysis (FA) to a massive performance matrix of LLMs versus benchmarks \((60\times44)\) revealing an intrinsically low-rank structure of that matrix. That is, a small number of latent factors captures most of the structure in the full task space. This low-rank geometry reveals substantial redundancy across existing tasks and explains why many benchmarks appear to be measuring overlapping abilities. We further show that these latent factors correspond to coherent, skill-like, dimensions of LLM behavior. Leveraging this latent skill-space, we deliver three practical tools for LLM evaluation and downstream users: (i)~identifying redundant tasks, (ii)~profiling new models using a small subset of tasks, and (iii)~selecting models aligned with desired skill profiles. Our method provides a solid alternative to the de-facto standard of a single aggregate score, and establishes an interpretable and practical framework for understanding and benchmarking LLM core capabilities.

25.
Nature Biotechnology 2026-06-11

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

Authors:

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in situ. In a human cancer metastatic colonization model, we applied large (80,000+) sgRNA panels across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes. We linked perturbations affecting long noncoding RNA covariation, microRNA–mRNA interactions and distinct amino acid-specific tRNA alterations to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, investigation of the tumor immune microenvironment indicated distinct, synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of perturbation responses in complex tissues, including small and large RNA regulation, tumor proliferation, migration, metastasis and immune interactions. In vivo CRISPR genetic perturbations are spatially mapped at scale.