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01.
arXiv (CS.AI) 2026-06-18

Benchmarking Action Spaces in Reinforcement Learning for Vision-based Robotic Manipulation

arXiv:2606.18594v1 Announce Type: cross Abstract: In real-world reinforcement learning (RL), the choice of action space can play a key role in shaping motion smoothness, safety, and overall task performance. In this study, we evaluate pose increment, pose velocity, joint position increment, and joint velocity across two vision-based manipulation tasks: object picking and pushing. We train policies in simulation and deploy them to the real world using sim-to-real transfer. We find that action-space representation indeed significantly affects sim-to-real performance. In particular, we find that the joint velocity action space is best for the vision-based picking and pushing tasks in terms of smoothness and final task performance. We also provide practical guidance for RL practitioners in choosing action spaces for both simulation and real-world experiments.

02.
arXiv (quant-ph) 2026-06-16

Nonlinear cascaded quantum network with giant emitters

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

03.
arXiv (CS.CV) 2026-06-15

Connections Between Pairs of Filters Improve the Accuracy of Convolutional Neural Networks

While researchers continue to find new and improved network structures for CNNs, most of the newly invented architectures still rely on the traditional pattern of stacking convolutional blocks and separating them with pointwise activation functions. However, there are drawbacks to a network purely building on pointwise nonlinearities. One alternative is to introduce a pairwise connection between two filters of a network. Typical connection functions use multiplications or the minimum operation to realize logical AND connections. In this paper, we go one step further by demonstrating that CNNs can benefit from more general connections, which include parameters that are learned. With such parameters, the network is able to implement different connections in different network layers and better adapt the connection function to the task at hand.

04.
arXiv (CS.LG) 2026-06-15

A Stationarity-and-Coupling Criterion for Training-Free Time-Lagged Spectral Embeddings of Multivariate Time Series

arXiv:2606.13823v1 Announce Type: new Abstract: We study training-free fixed-length descriptors for multivariate time series and ask not merely whether such a descriptor performs well, but when it can be expected to work at all. Our object of study is $D(\tau)$, built from a time-lagged correlation matrix truncated at the Marchenko-Pastur edge so that only signal-bearing eigenvalues survive and classified by cosine similarity to class centroids with zero learned parameters. The central contribution is not the descriptor but a falsifiable applicability criterion for it. Working from a stationary Gaussian VAR(1) model, we argue that $D(\tau)$ separates two classes when the signals are approximately stationary and the class information lives in their cross-channel temporal coupling rather than in marginal per-channel power. We derive, semi-formally, three consequences: a distinguishability condition, why the static ($\tau=0$) covariance collapses to chance, and why a stationary but power-discriminated paradigm defeats the descriptor. The criterion is operational: a two-part pre-flight test – an augmented Dickey-Fuller stationarity check and a power-baseline saturation check – predicts applicability before any training. We validate both halves on a mixed assortment. On four paradigms that satisfy the criterion (Sleep-EDF, BCI-IV-2a, MIT-BIH, ESC-50) the descriptor is competitive with strong baselines at a fraction of their cost, reaching $88.5\pm4.5\%$ under 20-subject leave-one-subject-out on Sleep-EDF on a single CPU thread. On three that violate it – non-stationary ERPs, and financial-volatility and wearable-stress regimes that are power-discriminated – it fails exactly as the pre-flight predicts, and these negatives are the more informative half. We are explicit that $D(\tau)$ is not the most accurate representation; its value is a compact, training-free embedding whose domain of validity is known in advance.

05.
bioRxiv (Bioinfo) 2026-06-20

SAbDab2: The structural antibody database in the age of machine learning

The Structural Antibody Database (SAbDab) is a publicly available repository of experimentally determined antibody structures, first released in 2013. Explicit support for single-domain antibodies was added in 2021, with SAbDab-nano. Recently, increasing interest in antibodies has led to a proliferation of novel antibody formats, while simultaneous advances in machine learning have increased demand for standardised, high-quality structure data. Here, we present SAbDab2, re-engineered for the machine-learning age. It introduces support for a variety of new formats, and makes it easy to retrieve and compare all known structures of a given antibody. In addition, SAbDab2 provides ready access to ML-grade structures of antibody and antibody–antigen-complexes, with standardised, versioned train/test splits. These will be updated every six months going forward, and are available at https://zenodo.org/records/20083995. SAbDab2 itself is updated weekly and is freely available at https://sabdab2.opig.stats.ox.ac.uk.

06.
Science (Express) 2026-05-21

DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3′–guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

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

Higher order PCA-like rotation-invariant features for detailed shape descriptors modulo rotation

作者:

PCA can be used for rotation invariant features, describing a shape with its $p_{ab}=E[(x_i-E[x_a])(x_b-E[x_b])]$ covariance matrix approximating shape by ellipsoid, allowing for rotation invariants like its traces of powers. However, real shapes are usually much more complicated, hence there is proposed its extension to e.g. $p_{abc}=E[(x_a-E[x_a])(x_b-E[x_b])(x_c-E[x_c])]$ order-3 or higher tensors describing central moments, or polynomial times Gaussian allowing decodable shape descriptors of arbitrarily high accuracy, and their analogous rotation invariants. Its practical applications could be rotation-invariant features to include shape modulo rotation e.g. for molecular shape descriptors, or for up to rotation object recognition in 2D images/3D scans maybe also for 3D scene understanding, or shape similarity metric allowing inexpensive comparison of objects modulo rotation avoiding costly optimization over rotations.

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

SceneConductor: 3D Scene Generation from a Single Image with Multi-Agent Orchestration

Generating complete 3D scenes from a single image requires inferring globally consistent geometry, object relationships, and environmental context from inherently ambiguous visual evidence. Despite recent progress in joint layout-and-mesh generation, existing methods often rely on holistic or weakly decomposed pipelines that entangle many factors at once and demand extensive scene-level supervision, limiting their generalization to complex real-world environments. We propose a multi-agent orchestration framework that decomposes single-image 3D scene generation into three structured stages: scene initialization, environment construction, and multi-agent refinement. The initialization stage extracts image-derived object masks, builds object-level 3D representations, and predicts an initial spatial layout to form a coarse 3D scene. The environment-construction stage then leverages this initialization together with point-map geometry to build an environmental scaffold of supporting surfaces, room boundaries, materials, and illumination. Finally, in the refinement stage, a planner agent identifies structural and visual inconsistencies, applies simple corrections directly, and dispatches specialist agents for complex localized revisions that are reintegrated into the global scene. To provide reliable structural initialization while reducing reliance on scene-level annotations, we further introduce a geometry-aware layout predictor supervised by sparse geometric priors derived from point maps. Unlike fully supervised layout generators, the predictor can be trained from segmentation-level data and generalizes robustly to diverse real-world scenes. Extensive experiments on benchmark datasets show that our method consistently outperforms prior approaches in geometric accuracy, spatial consistency, and perceptual realism.

09.
arXiv (quant-ph) 2026-06-16

Inflationary branch decoherence and the cosmological arrow of time

作者:

arXiv:2602.21263v3 Announce Type: cross Abstract: We analyze branch decoherence in inflationary quantum cosmology by computing reduced density matrices and branch-overlap factors for long-wavelength perturbations. The Hartle-Hawking no-boundary state is real in the semiclassical regime and contains both expanding and contracting WKB components, whereas the tunneling state is selected as an outgoing complex WKB branch; expanding-contracting decoherence is therefore central for the former and mainly diagnostic for the latter. Using the influence-functional formalism, we derive the noise kernel for a light spectator environment and evaluate decoherence under horizon-based and EFT-motivated coarse grainings. We then compute the single-mode branch overlap directly from the Bunch-Davies mode functions, obtaining $|\mathcal{D}_k(z)|=[z^2/(z^2+1)]^{1/4}$ in the massless limit and $|\mathcal{D}_k(z)|\sim z^\nu$ on superhorizon scales for massive fields, where $z=-k\eta$ is the dimensionless wavenumber with $\eta$ the conformal time. In the massless case, the accumulated geometric branch functional is evaluated in closed form, with a leading cutoff-sensitive phase-space term and a universal subleading contribution. The calculation provides an explicit quantitative bridge between quantum-cosmological boundary conditions, inflationary squeezing, and the emergence of effectively classical cosmological histories.

10.
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.

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

PHINN: Persistent Homology Inspired Neural Network for Rare-Event Time Series Generation

arXiv:2606.15452v1 Announce Type: new Abstract: Rare events in time series are critical to model but hard to learn due to data scarcity. Current generative models struggle with extreme values. We observe that rare events leave distinct topological fingerprints - transitions in Betti numbers from point-cloud embeddings - that are more stable and discriminative than statistical moments. We introduce PHINN, a flow-matching framework using dynamic Betti curves as conditioning signals and a persistence landscape loss for homology consistency. It scales to multivariate data, includes a natural-language interface to set Betti targets, supports cross-domain meta-learning and few-shot generation, and provides certified adversarial robustness. On financial, epidemiological, and multi-modal benchmarks, PHINN outperforms statistical and diffusion baselines in topological fidelity (beta-RMSE down 41-63%, transition accuracy up 84%) and matches jump-diffusion models in tail coverage while exceeding them in shape fidelity. All results have 95% confidence intervals.

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

MolGraphBench: A Benchmark of GNN Architectures for Molecular Regression Tasks

arXiv:2602.20573v3 Announce Type: replace Abstract: Molecules are often represented as SMILES strings, which can be readily converted to hand-crafted descriptors or fingerprints (FP) for molecular property prediction. Research has demonstrated that SMILES can be converted to molecular graphs $G = (V, E)$, with atoms as nodes $(V)$ and bonds as edges $(E)$. These molecular graphs can subsequently be used to train graph neural networks (GNN) models. Despite the recent surge in application of GNN (existing and novel architectures) for molecular property prediction, a rigorous benchmark is still lacking. We propose MolGraphBench, a comprehensive benchmark of four commonly used GNN models for molecular property prediction. Benchmarking results demonstrate graph convolutional network (GCN) and graph isomorphism networks (GIN) as the optimal GNN architectures for molecular graph regression tasks, based on absolute performance, training efficiency, transfer learning and prediction quality. The study also indicates the non-complementary nature of molecular fingerprints in the fusion (GNN-FP) framework. Furthermore, our GNN models achieved performance superior or comparable performance to current state-of-the-art GNN baselines across three datasets (GCN with RMSE of $0.518$ on B3DB, GIN-FP with RMSE of $1.022$ on FreeSolv and GIN with MAE of $63.783$ on RT datasets). Findings from this study indicate that type of GNN-layer, should be treated as a tunable hyperparameter rather than a fixed design choice to achieve superior performance.

14.
arXiv (quant-ph) 2026-06-12

Path integral control of open quantum systems

arXiv:2410.18635v4 Announce Type: replace Abstract: We investigate open-loop quantum state preparation for a class of open quantum systems whose dynamics follow a Gorini-Kossakowski-Lindblad-Sudarshan (GKLS) master equation that admits a trajectory-based stochastic representation. The deterministic control objective is reformulated as a stochastic optimal control problem – interpreting stochasticity as a methodological tool akin to stochastic Schrödinger equation unravelings – which situates the problem within the path integral control framework. For the class of GKLS generators under consideration, this reformulation leads to an explicit expression for the optimal control as a weighted average over stochastic quantum trajectories, thereby eliminating the need for gradient evaluations. Building on this theoretical result, we derive a control update rule for piecewise-constant control pulses and demonstrate that adaptive importance sampling progressively enhances the control estimator during optimization, culminating in the algorithm we term Path integral Quantum Control (PiQC). We further introduce an annealed variant of PiQC, wherein a synthetic noise schedule gradually steers open-system trajectories toward closed-system dynamics, enabling high-fidelity unitary state preparation. Numerical studies on a dissipative single-qubit system and a multi-qubit Nuclear Magnetic Resonance model verify that PiQC yields precise open-loop controls and displays robustness to Hamiltonian perturbations. We propose PiQC as a trajectory-based alternative to gradient-based approaches, which might offer a viable solution in quantum control problems where gradient computation is infeasible or computationally demanding.

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

Risk-Aware LLM Agents for Geospatial Data Retrieval: Design and Preliminary Adversarial Evaluation

We present an LLM-driven framework for retrieving remote sensing data from cloud-based geospatial catalogues using natural language queries. The system converts user intent into structured API calls, enabling efficient access to satellite imagery and environmental datasets. The architecture integrates three agents: Guardrail for safety and policy enforcement, General-QA for intent interpretation, and Recommender-Analyst for schema-aware API call generation. This coordinated design ensures reliable, semantically aligned interaction with external data services. The modular framework is portable across platforms through API schema substitution and supports applications in environmental monitoring, disaster response, and climate analysis. It establishes a scalable interface between user intent and geospatial infrastructure, enabling streamlined and automated Earth observation workflows. Preliminary experiments under adversarial multi-turn settings show that prompt-level safety instructions improve robustness, although rare high-impact failures persist in API manipulation scenarios and highlight the need for adaptive, system-level defenses that balance safety, usability, and cost efficiency, which motivates the use of our intercept-level Guardrail agent.

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

Bridging Day and Night: Unsupervised Cross-Domain Re-Identification with Synergistic Prompt and Prototype Learning

Cross-domain day-night re-identification (ReID) is fundamentally challenged by the substantial visual appearance discrepancies between daytime and nighttime scenes. Existing fully supervised methods rely heavily on labor-intensive annotations, which are costly and exhibit limited generalization across domains. In this work, we investigate unsupervised day-night ReID and propose a novel framework that synergistically combines prompt learning and prototype-based representation learning to associate identities across domains without requiring manual labels. Our approach follows a progressive two-stage training strategy. In the first stage, we exploit the vision-language model to generate instance-specific textual prompts in an annotation-free manner. We employ an instance-level alignment mechanism to embed visual features and textual prompts into a unified semantic space, aligning unlabeled day/night images with learnable prompts via instance-aware dynamic-bias adaptation. In the second stage, we construct domain-specific prototype memory banks and introduce two complementary modules: i) an intra-domain identity association module to enhance feature discriminability within each domain, and ii) a cross-domain prototype matching module to reliably identify positive and negative prototype pairs, thereby establishing robust identity correspondences across day and night. Extensive experiments on public benchmarks validate the effectiveness of our method. Under the unsupervised setting, our framework attains Rank-1 accuracy comparable to state-of-the-art fully supervised methods.

17.
arXiv (CS.AI) 2026-06-11

Model-Based and Data-Driven Hierarchical Control and Topology Co-Design for Robust Networked Systems

arXiv:2606.11596v1 Announce Type: cross Abstract: In this paper, we consider a class of networked systems comprising an interconnected set of linear subsystems, disturbance inputs, and performance outputs. Using dissipativity theory, we first propose a model-based hierarchical control design strategy to ensure the closed-loop networked system is dissipative from its disturbance inputs to performance outputs. This involves designing local controllers for each subsystem to enforce local dissipativity guarantees, which are then exploited to co-design distributed global controllers and the interconnection topology to enforce global dissipativity guarantees while optimizing interconnection topology costs. The overall design process requires only solving a sequence of linear matrix inequality (LMI) problems, thereby retaining compositionality and decentralizability while avoiding non-convex, iterative design processes that are inefficient and centralized. This model-based hierarchical control design strategy assumes the knowledge of the subsystem dynamics, which may not hold in many real-world networked systems. Motivated by this, we also propose a data-driven hierarchical control design strategy that assumes only the availability of rich input-state-output trajectory data from the subsystems. The proposed data-driven design process assumes that the unknown disturbances affecting the subsystem dynamics are bounded by a quadratic matrix inequality (relaxing conventional bounds) and accounts for this by using the matrix S-lemma. Finally, the effectiveness of the proposed model-based and data-driven hierarchical control designs is illustrated for a networked system representing a DC microgrid, with the aim of enforcing robust (dissipative) voltage regulation and current sharing.

18.
arXiv (CS.AI) 2026-06-17

Belief-Space Control for Personalized Cancer Treatment via Active Inference

arXiv:2606.10376v2 Announce Type: replace Abstract: Cancer treatment is at the core a sequential decision-making problem with partial observability, latent patient heterogeneity, and explicit constraints on the budget for medical measurements. Unlike standard Reinforcement Learning (RL) approaches that control state trajectories, cancer treatments permanently modify patients' transition dynamics, changing how states evolve over time. We model cancer treatment as a belief-space planning problem using active inference, deriving an expected free-energy objective that unifies goal-directed control and information acquisition under measurement budgets without. We implement this framework using real clinical cancer data from the AACR Project GENIE Biopharma Collaborative dataset. Results on clinical data demonstrate a simultaneous patient categorization and high treatment efficacy, under real measurement and treatment constraints.

19.
arXiv (CS.CV) 2026-06-15

TSA: Temporal Slot Activation for Persistent Object-Centric Video Representation

Unsupervised video object-centric learning aims to decompose dynamic scenes into temporally persistent entity representations. Existing recurrent video slot-attention methods propagate a fixed set of slots across frames, but typically assume unconditional slot propagation: every slot is updated and decoded at every frame, regardless of whether its corresponding object is visible. We show that this design violates a basic lifecycle requirement for persistent slots: when an object is absent or fully occluded, its slot should preserve its previous state and avoid explaining unrelated visible content. Instead, unconditional propagation creates two failure pathways: update-induced state drift, where current-frame evidence overwrites the absent object's representation, and decoder-induced reconstruction interference, where the inactive slot remains coupled to reconstruction through decoder attention. We propose Temporal Slot Activation (TSA), a mechanism that learns a per-slot, per-frame activation score $\alpha_{k,t} \in (0, 1)$ without visibility supervision. TSA uses this activation as a shared latent control variable for slot lifecycle modeling. When a slot is inactive, TSA anchors its state to the previous slot via activation-gated updating and suppresses its decoder participation through an activation-dependent additive bias on attention logits before softmax normalization. This jointly reduces state drift and reconstruction-driven interference. To improve decisions under partial occlusion and gradual reappearance, TSA further conditions activation prediction on a per-slot temporal memory produced by a Temporal Context Encoder. We evaluate TSA on MOVi-C/E, YT-VIS, and OVIS benchmarks using both standard and tracking-based metrics (FG-ARI, mBO, IDF1, HOTA). TSA consistently improves object decomposition and temporal identity preservation, with large gains on long, heavily occluded videos.

20.
arXiv (CS.CL) 2026-06-16

Fast When, Careful Who: Dual-Process Multiparty Turn-Taking with Diffusion Augmentation

Reliable turn-taking is essential for spoken dialogue systems. However, most existing methods are designed for two-speaker interaction and struggle with realistic multiparty audio containing overlap and rapid speaker changes. We study multiparty turn-taking on the VoxConverse dataset and propose an audio-only two-stage pipeline that separates when to trigger a turn boundary from whether the floor is actually transferring. A fast trigger scans the audio and proposes candidate end-of-turn times, while a lightweight verifier runs only at those times to decide \textsc{Hold} or \textsc{Shift} and support next-speaker prediction. We report results in the full multiparty setting and a controlled dyadic top-2 projection for comparability. We also investigate diffusion-based, label-preserving background-audio mixing as a data augmentation strategy. Results show improved shift detection over a baseline, with further improvements from diffusion augmentation.

21.
medRxiv (Medicine) 2026-06-15

Supporting people to access social security payments through the Special Rules for End of Life: a qualitative study of the perspectives of patients, carers and health care professionals

Background: People living with terminal illness face a double financial burden from additional costs and loss of earning for themselves and their carers. Social security benefits are intended to help alleviate some of this financial pressure, and in the UK and other countries people are eligible for fast-tracked access to financial support via the Special Rules for End of Life. One in 3 people who are eligible miss out on this support, yet there is limited evidence on the reasons for this take-up deficit. Objectives: The aim of this study is to understand the barriers and facilitators to claiming benefits for terminally ill people from the perspectives of patients, carers, and health care professionals. Methods: This is a qualitative study combining i) focus groups with healthcare professionals recruited via professional networks and social media, and ii) interviews with patients and carers recruited in hospital and hospice settings. We analysed the data using Practical Thematic Analysis Results: Fifty-five multidisciplinary healthcare professionals participated in 11 focus groups, and we interviewed 10 patients and carers. We constructed five descriptive themes to summarise the data: Navigating priorities and uncertainty; positive impacts alongside a sense of shame and stigma; talking about money, difficulties and dividends; everybodys, yet nobodys, responsibility; and sticking points in the system. Conclusion: The themes reveal several challenges that may contribute to people not taking up this financial support. However, discussions about access to benefits were also seen as a core part of holistic care, a positive way to offer support and a gateway to other discussions about end-of-life care preferences and decisions. Recommendations for policy and practice include evaluating the adoption of a diagnostic rather than a prognostic eligibility criteria, integrating discussions about benefits into existing processes such as advance care planning, and improving education and support for clinicians.

22.
arXiv (CS.CV) 2026-06-16

Navigating Distribution Shifts in Medical Image Analysis: A Survey

Medical Image Analysis (MedIA) has become indispensable in modern healthcare, enhancing clinical diagnostics and personalized treatment. Despite the remarkable advancements supported by deep learning (DL) technologies, their practical deployment faces challenges posed by distribution shifts, where models trained on specific datasets underperform on others from varying hospitals, or patient populations. To address this issue, researchers have been actively developing strategies to increase the adaptability of DL models, enabling their effective use in unfamiliar environments. This paper systematically reviews approaches that apply DL techniques to MedIA systems affected by distribution shifts. Rather than organizing existing methods by technical characteristics, we explicitly bridge real-world clinical constraints – such as limited data accessibility, strict privacy requirements, and heterogeneous collaboration protocols – with the technical paradigms able to address them. By establishing this connection between operational constraints and methodological evolution, we categorize existing works into Joint Training, Federated Learning, Fine-tuning, and Domain Generalization, each aligned with specific healthcare scenarios. Beyond this taxonomy, our empirical analysis suggests that, as domain information becomes progressively less accessible across these paradigms, performance improvements become increasingly constrained, and further uncovers a gradual shift in methodological focus from explicit distribution alignment toward uncertainty-aware modeling, ultimately pointing to the need for more deployability-aware design in real-world MedIA.

23.
bioRxiv (Bioinfo) 2026-06-21

Antibody-Antigen Affinity Prediction with Chain-Aware Protein Language Modeling

Motivation: Antibody-antigen affinity determines which antibodies advance in therapeutic discovery, repertoire analysis and affinity maturation, but experimental measurements are sparse relative to the scale of sequence libraries. Structure-based predictors can exploit interface geometry when reliable complexes are available, yet early discovery often requires ranking many heavy-light chain pairs against antigens for which no complex structure exists. Existing sequence-based models are scalable, but frequently compress heavy and light chains into a single antibody representation or concatenate antibody and antigen features obscuring the chain-specific and epitope-specific signals that drive binding. Results: We present AbAffinity, a sequence-only chain-aware three-stream architecture that maintains heavy chain, light chain and antigen as distinct streams. It integrates frozen ESM-2 embeddings with heavy-chain CDR-focused pooling, heavy-light self-attention, adaptive fusion gating and gated cross-attention, training only a compact interaction module. On the SAAINT-DB benchmark, AbAffinity achieves strong predictive performance under ten-fold cross-validation and maintains robust accuracy on novel antigens. It consistently outperforms recent sequence-based models across external benchmarks including SAbDab, AB-Bind and SKEMPI 2.0. Ablation studies highlight the contributions of chain-specific representations, CDR-focused pooling and the gated interaction pathway. Integrated Gradients attributions recover known paratope and epitope residues at structurally validated interfaces. AbAffinity provides a lightweight, explainable sequence-first framework for antibody triage and prioritisation when structural information is limited or unavailable.

24.
medRxiv (Medicine) 2026-06-23

Uptake of minimal intervention dentistry among Romanian dental professionals and trainees: an exploratory cluster and network analysis

Background Minimal intervention dentistry (MID) is promoted as a prevention-oriented approach to caries management, but its integration into routine practice remains uneven. Existing research often examines MID-related knowledge, attitudes, or practices separately, offering limited insight into how these dimensions co-occur within individuals or are conditionally associated. Methods This exploratory cross-sectional survey examined multidimensional MID uptake among 327 Romanian dental students, residents, and specialists from five university centers. Ten MID-related scores were analyzed, including nine formative composites and one single-item peer-norm indicator. K-means clustering examined uptake profiles, and Gaussian graphical model network analysis with stepwise BIC selection examined conditional associations among constructs. Results A two-cluster solution was highly reproducible but modestly separated (n = 144 vs n = 183; average silhouette width = 0.13; mean Jaccard similarities = 0.92 and 0.94). The profiles reflected broadly lower versus higher uptake across knowledge-, belief-, and practice-related dimensions, while perceived peer norms for hygiene instruction showed the opposite pattern. Profile membership was not clearly patterned by gender, age band, professional status, or clinical experience. The primary network included 14 non-zero edges out of 36 possible edges, all positive; the strongest partial association linked diagnostic knowledge to diagnostic methods used in practice (partial r = .22). Familiarity, diagnostic knowledge, and general practices occupied more interconnected positions descriptively, but limited centrality stability precluded interpreting them as intervention targets. Conclusions MID uptake in this sample was better represented as a continuum of modestly differentiated profiles than as sharply separated participant types. The findings provide an exploratory map of multidimensional MID uptake and may inform future survey validation, implementation research, and dental education studies. Because the study was cross-sectional, convenience-sampled, and based on self-report, findings should be interpreted as hypothesis-generating rather than causal or population-representative.

25.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.