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01.
arXiv (CS.AI) 2026-06-12

Fault Lines: Navigating Ethics and Responsible AI Where National Policy Meets Local Practice in Public Sector Transformation

arXiv:2606.13039v1 Announce Type: cross Abstract: The UK government has adopted a pro-AI stance to help transform public service delivery in the face of severe financial pressures, but the path to translate this vision into responsible AI practice remains ill-defined. While UK policy is often set at the national level, local authorities are responsible for most public service delivery, and the rapid advance of AI-first narratives in the public sector is exposing fault lines in knowledge and practice at this national-local interface. This paper examines how responsible AI is interpreted and implemented at the interface between the UK's central government and local authorities, taking the high-stakes area of Special Educational Needs and Disabilities (SEND) as a case study. We present a thematic analysis of 17 semi-structured interviews with policymakers, practitioners, and third-sector professionals to identify barriers and enabling conditions for responsible AI where national policy meets local practice. We identify five interconnected challenges facing local authorities: shadow usage of AI and data privacy risks, market-government asymmetry in AI provision, insufficient workforce readiness, a lack of standardised definitions and measurements, and gaps in human accountability. For each, participants proposed actionable steps, from strengthening data protection frameworks and rebalancing the market-government relationship to enhancing workforce capacity. Our examination of SEND brings these challenges into sharper focus, showing how high-stakes decisions affecting vulnerable children and families intensify tensions around accountability, fairness, and human oversight, exposing the limits of a principle-based regulatory approach. We argue that responsible public sector AI requires both national policy adjustments and structural reforms to institutional capacity, values, and governance mechanisms at the local level.

02.
arXiv (CS.CV) 2026-06-16

LOCUS: Local Visual Cue Search for Enhancing Fine-Grained Perception in Multimodal Large Language Models

Multimodal Large Language Models (MLLMs) remain unreliable on fine-grained visual perception, even when high-resolution inputs preserve the necessary local details. We identify this limitation as visual context rot: decisive evidence may exist in the full image, yet fail to be reliably selected and used amid redundant visual context. We propose LOCUS (LOcal visual CUe Search), a training framework that teaches MLLMs to internalize local evidence search through a verifiable proxy task. During training, LOCUS provides a local crop as a visual cue and optimizes the model to recover its spatial support in the full image using an IoU-based reward. The visual cue is used only during training, leaving the standard image-question inference interface unchanged. Experiments across fine-grained perception, hallucination, general understanding, and reasoning benchmarks show that LOCUS improves localization-sensitive visual understanding while preserving broad capabilities. Attention analyses further indicate stronger focus on task-relevant evidence regions, suggesting that training-time visual cue search provides an effective route to internalized fine-grained evidence selection.

03.
arXiv (CS.CV) 2026-06-16

Reasoning in Computer Vision: Taxonomy, Models, Tasks, and Methodologies

Visual reasoning matters for many computer vision tasks that go beyond surface-level object detection and classification. Despite progress in relational, symbolic, temporal, causal, and commonsense reasoning, existing surveys typically cover only one part of the problem, such as visual question answering, scene-graph generation, neuro-symbolic AI, or multimodal chain-of-thought, and rarely analyze reasoning types, methodologies, and evaluation protocols together. This survey addresses that gap. Following a structured literature review, we group visual reasoning into five major types (relational, symbolic, temporal, causal, and commonsense) and examine how each is implemented across methods that range from graph-based models, memory networks, attention mechanisms, and neuro-symbolic systems to reasoning with vision-language models (VLMs) and multimodal large language models (MLLMs), including visual chain-of-thought, visual programming, and tool-augmented and test-time reasoning. We then review evaluation protocols for functional correctness, structural consistency, and causal validity, and we analyze their limits in generalizability, reproducibility, faithfulness, and explanatory power. We also identify open challenges: scaling to complex scenes, integrating symbolic and neural paradigms more deeply, the shortage of comprehensive benchmarks, language-prior shortcuts and hallucination in foundation models, and reasoning under weak supervision. Finally, we set out a research agenda for vision systems and argue that connecting perception and reasoning is necessary for transparent, trustworthy, and cross-domain models, especially in high-stakes settings such as autonomous driving and medical diagnostics.

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

What sentiment analysis can't see: Measuring whether customers were helped, and what went wrong, across 70,000 support conversations

Most companies read their customer support data at scale using sentiment analysis, which measures how customers sound rather than whether they were satisfied with the result. We tested a richer alternative on 70,450 support conversations from a leading online fundraising platform: alongside tone, we used GPT-5.4 to estimate each customer's satisfaction and to flag whether they reported a concrete problem, then validated all three readings against the 1-to-5 ratings customers left on the conversations they rated. The satisfaction estimate tracked those ratings far better than sentiment did, correlating at 0.47 against 0.36 and flagging unhappy customers with far fewer false alarms. The structured read also sees what sentiment cannot: tone and satisfaction disagree in 44% of conversations, a single "Neutral" label hides everything from quietly satisfied customers to ones who quietly gave up, and the largest group of all is "tolerated friction," customers who are satisfied but still reporting a fixable problem, a standing issue that no sentiment-based dashboard can surface. The broader finding is that LLM-based annotation can capture far more than the tonality of a customer's language, offering strong potential for new business metrics grounded instead in the customer's state (whether they were satisfied) and the cause of their problem extracted directly from the raw textual data of interactions and feedback.

05.
arXiv (quant-ph) 2026-06-25

Folds of one curve: the superradiant phase diagram of Dicke modes with interacting matter

arXiv:2606.26081v1 Announce Type: cross Abstract: We give a thermodynamic-limit account of Dicke models with one cavity mode coupled collectively to interacting matter. Integrating out the cavity yields an exact self-consistent functional of the magnetisation $m$, $\tilde e(m) = \lambda m^2/2 + e_mat(\lambda m)$: a classical penalty on the bare-matter energy $e_mat$ in the self-consistent field $h = \lambda m$, with $\lambda = g^2/(2\omega_c)$ the collective coupling. Supplying only that scalar field, the photon creates no phase the matter does not already possess. States holding a minimum form one connected curve, $\lambda(m) = \mu_mat^{-1}(m)/m$, so superradiant first-order transitions are folds of one equation of state not crossings of disjoint sheets, and a fold can straighten into a continuous line. The remaining rules are local, each with a spectral counterpart: onset by the leading singularity of $e_mat$ (a softening polariton), order by one bare response – the Landau quartic, or a divergent susceptibility forcing a Larkin-Pikin (LP) fold. For the Dicke-Ising model the Landau coefficients are exact, giving in closed form the second-order boundary and both zero-quartic fields, one tricritical; a $1/d$ expansion maps all four phases, with the AS-PS transition first order for $d\le d_{uc}=3=4-z$ (LP) and tricritical points in the $(d,\epsilon)$ plane above. At the degenerate quadruple point the matter is a Rydberg-blockade chain, solved by strict-blockade iDMRG: the antiferromagnetic superradiant (AS) phase persists as a finite 1D wedge, first order into the corner. Other magnets: the triangular antiferromagnet keeps a continuous superradiant-superradiant line (3D-XY, no fold forced); the compass chain a BKT-functional onset; the Heisenberg and XX chains, via a conserved operator, a spectrally silent first-order onset; and the Dicke-Heisenberg diagram an exact tricritical point at the saturation corner.

06.
arXiv (math.PR) 2026-06-17

Critical spectral behavior and large deviations for geometric $\alpha$-stable processes

arXiv:2606.17501v1 Announce Type: new Abstract: In this paper, we study the Schrödinger-type operator associated with geometric stable processes on $\mathbb{R}^{d}$, especially the differentiability of spectral function. Let $\mathcal{H}$ be the generator of the geometric stable process and $\mu$ a smooth measure on $\mathbb{R}^{d}$. Then the spectral function $C(\theta)$ is defined as $C(\theta) = -\inf \sigma(-\mathcal{H} - \theta \mu)$, where $\sigma(\mathcal{A})$ denotes the spectrum of $\mathcal{A}$ and $\theta$ is a real parameter. Since the geometric stable process exhibits severe local singularities in its Lévy measure, its transition semigroup lacks ultracontractivity, which invalidates classical methods for proving the differentiability. To overcome this obstacle, we use the compact embedding of the extended Dirichlet space into $L^2(\mu)$. As a primary application of this differentiability, we establish a large deviation principle for a positive continuous additive functional associated with the smooth measure $\mu$.

07.
arXiv (CS.AI) 2026-06-15

Regional Climate Model Emulation with Diffusion Approaches: What is the Added Value of Generative Machine Learning?

arXiv:2606.14570v1 Announce Type: cross Abstract: Emulators provide a cost-effective alternative to regional climate models (RCMs) by capturing their dynamical downscaling function. They link large-scale predictors simulated by global climate models (GCMs) to RCM-simulated high-resolution fields of the target variable, here precipitation. Machine learning methods, typically deep learning, are cheaper than running RCMs in computation time and energy. Among them, generative models are appealing because they can simulate ensembles of local high-resolution fields consistent with the predictors. This ensemble, which we call the uncertainty envelope, remains to be properly assessed for added value. Here, we make three contributions. First, we introduce ParamDiffusion, a new two-stage diffusion-based framework, and compare it with a state-of-the-art diffusion approach. Second, we expand standard validation through a comprehensive framework aligned with climate-science needs, examining specific precipitation events, including extremes. Third, within this framework, we assess the added value of diffusion approaches relative to deterministic methods. We intercompare four deep-learning models: a deterministic model designed to capture the precipitation tail; a parametric probabilistic model based on it; a recently proposed diffusion approach; and ParamDiffusion, which couples the parametric model with a diffusion model. Our results show that diffusion-based approaches reproduce climatological precipitation statistics with high skill, including distributional tails and spatially compounded extremes, while generating spatially detailed fields. However, none of the assessed models consistently accounts for the most extreme RCM-simulated events within its uncertainty envelope. Diffusion models are therefore promising for probabilistic RCM emulation, but progress is still required before they can reliably represent high-impact precipitation extremes.

08.
arXiv (CS.AI) 2026-06-17

MIVE: A Minimalist Integer Vector Engine for Softmax LayerNorm and RMSNorm Acceleration

arXiv:2606.17781v1 Announce Type: cross Abstract: The rapid growth of Large Language Models (LLMs) has intensified the need for specialized hardware accelerators that can satisfy stringent inference latency and power constraints. Although matrix multiplications dominate the overall computational workload, non-linear vector normalization operations, such as LayerNorm, RMSNorm and Softmax can become critical hardware bottlenecks. Existing accelerators typically implement these functions using dedicated hardware blocks, leading to duplicated resources and inefficient silicon utilization. To address this limitation, we propose a Minimalist Integer Vector Engine (MIVE), a programmable architecture capable of executing all three operations within a unified datapath. By exploiting common computational patterns across LayerNorm, RMSNorm and Softmax the proposed vector engine maximizes hardware sharing while reducing implementation overhead. Physical ASIC implementation results show that MIVE provides comprehensive multi-function support while achieving higher area and hardware efficiency than most state-of-the-art standalone accelerators.

09.
PLOS Computational Biology 2026-06-15

Fung-AI: An AI/ML-driven pipeline for antifungal peptide discovery

by Daniel S. Berman, Libby M. Lewis, Tom D. Curtis, Olivia N. Tiburzi, Daniel F. Q. Smith, Arturo Casadevall, Laura J. Dunphy Emerging fungal pathogens represent a concerning threat to both global health and food security. In this study, we aimed to address our rising vulnerability to fungal pathogens through the development of the Fung-AI pipeline: an AI/ML-driven approach for antifungal discovery. A generative adversarial network (GAN) was trained to generate novel candidate antifungal peptide sequences. Next, in silico antifungal and hemolytic classifiers were built to further prioritize AI-generated peptides for experimental validation. From a pool of ~10,000 candidates, thirteen peptides were selected for testing over two-stages of experimentation. Five peptides were found to display mild antifungal activity against the wheat pathogen, Fusarium graminearum, with minimal inhibitory concentrations (MICs) ranging from 250 µg/mL to 500 µg/mL. Four of the five peptides also showed activity against the human pathogen, Candida albicans (MIC: 500 µg/mL). Two of our AI-generated antifungal peptides additionally demonstrated low cytotoxicity in HepG2 human liver carcinoma cells (LC50 > 704.2 µg/mL) indicating that they may be useful as scaffolds for future optimization for therapeutic applications. None of our peptides were found to considerably inhibit the emerging pathogen C. auris, suggesting the need for pathogen-specific down-selection of candidate peptides. Overall, we present a proof-of-principle, generative-AI-based approach for the rapid design of de novo antifungal peptides.

10.
arXiv (CS.LG) 2026-06-18

Unsupervised Diffusion Solver for Combinatorial Optimization via Combinatorial Adjoint Matching

arXiv:2605.30920v2 Announce Type: replace Abstract: Diffusion-based neural solvers have shown strong promise for combinatorial optimization (CO), but existing methods typically rely on supervised training with large collections of near-optimal solutions. In this work, we extend adjoint-based trajectory optimization methods to discrete combinatorial domains. We formulate diffusion-based CO as a stochastic control problem over Continuous-Time Markov Chains and introduce discrete adjoint dynamics for propagating optimization signals through discrete generative trajectories. Building on this formulation, we propose Combinatorial Adjoint Matching (CAM), an unsupervised training framework for discrete diffusion solvers with structured and low-variance trajectory-level optimization signals. Empirically, CAM consistently outperforms existing unsupervised diffusion baselines and achieves performance competitive with strong supervised diffusion solvers and even traditional solvers across diverse combinatorial optimization problems. Our code is available at https://github.com/Shengyu-Feng/CAM.

11.
arXiv (CS.CV) 2026-06-15

Conditioning Matters: Stabilizing Inversion and Attention in Diffusion Image Editing

Inversion-based image editing offers flexible and training-free control but still struggles with inversion accuracy and the trade-off between editing fidelity and background preservation. While recent methods improve inversion formulations or attention interactions, the role of textual conditioning in shaping diffusion dynamics and editing behavior remains underexplored. We show both empirically and theoretically that the precision of textual conditioning influences inversion stability by modulating the geometry of the diffusion velocity field, while also affecting the consistency of cross-branch attention during editing. These effects directly impact background preservation and semantic fidelity. Building on this analysis, we propose SimEdit, a conditioning-aware framework with two complementary components: (a) conditioning refinement, which constructs conditioning signals with improved semantic precision and structural alignment to facilitate stable inversion and consistent attention manipulation, and (b) token-wise cross-branch attention control, which separates edit-relevant and structure-preserving components and modulates them asymmetrically during attention manipulation. Extensive experiments on PIE-Bench demonstrate that SimEdit consistently improves both inversion reconstruction quality and editing performance over previous attention-manipulation approaches. Our code is available at https://github.com/zju-pi/SimEdit.

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

A specialized reasoning large language model for accelerating rare disease diagnosis: a randomized AI physician assistance trial

Rare diseases affect millions of individuals worldwide, yet timely diagnosis remains a major public health challenge due to scarcity of specialized clinical expertise. While large language models (LLMs) show promise to support rare disease diagnosis, current models are constrained by insufficient clinical deployability, limited clinically grounded evidence, and scarcity of training data. Here we present RaDaR (Rare Disease navigatoR), an open-source, compact reasoning LLM (32B parameters) for rare disease diagnosis. RaDaR was trained with 49,170 publicly available free-text cases and 104,666 synthetic cases with reasoning-enhanced training. RaDaR showed the strongest performance among evaluated open-source models, including the 671B DeepSeek-R1, across public benchmarks and four external validation centers. In a retrospective cohort, RaDaR prioritized the final diagnosis before documented clinical suspicion in 61.06 percent of cases, corresponding to a potential lead time of 1.87 months and 50.18 percent of the within-center interval. In a randomized physician-assistance trial, RaDaR assistance improved physicians' rare-disease diagnostic accuracy by 21.44 percentage points compared with internet search alone. Synthetic-data ablations suggested that phenotype-anchored narratives provide useful training signal for long-tail rare diseases, with a monotonic scaling trend within the tested data range. Together, RaDaR and its development and validation framework provide a deployable rare-disease reasoning model and a reproducible development framework for diagnostic AI under data scarcity.

13.
arXiv (CS.CL) 2026-06-25

Why Multi-Step Tool-Use Reinforcement Learning Collapses and How Supervisory Signals Fix It

Tool use enables large language models (LLMs) to perform complex tasks, and recent agentic reinforcement learning (RL) methods show promise for enhancing model capabilities. However, RL alone often leads to instability or limited gains in tool-use tasks. In our experiments, some models exhibit catastrophic collapse, where performance abruptly drops and tool-invocation structures fail. The analysis reveals that these failures stem from unexpected probability spikes in specific control tokens, disrupting structured execution, yet the underlying tool-use capability remains intact, merely obscured by specific formats. To address this, we systematically investigate a diverse set of supervisory signals, including off-policy supervision, hint-based guidance, erroneous example supervision, and others, applied under both synchronous and interleaved training schemes. We find that interleaving supervised fine-tuning (SFT) with RL substantially improves stability, but exhibits degraded performance under format and content out-of-distribution (OOD) evaluation. We also analyze the impact of learning rates and generalization across settings. These results highlight the importance of understanding RL failures and demonstrate how diverse supervisory signals can guide exploratory learning, enabling robust training of LLMs for complex, multi-step tool-use tasks. Our Code is available at https://github.com/hypasd-art/Tool-RL-Box.

14.
arXiv (CS.AI) 2026-06-16

Safe Exploration via Policy Priors

arXiv:2601.19612v3 Announce Type: replace-cross Abstract: Safe exploration is a key requirement for reinforcement learning (RL) agents to learn and adapt online, beyond controlled (e.g. simulated) environments. In this work, we tackle this challenge by utilizing suboptimal yet conservative policies (e.g., obtained from offline data or simulators) as priors. Our approach, SOOPER, uses probabilistic dynamics models to optimistically explore, yet pessimistically fall back to the conservative policy prior if needed. We prove that SOOPER guarantees safety throughout learning, and establish convergence to an optimal policy by bounding its cumulative regret. Extensive experiments on key safe RL benchmarks and real-world hardware demonstrate that SOOPER is scalable, outperforms the state-of-the-art and validate our theoretical guarantees in practice.

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

EM-NeSy: Expectation Maximization for Neurosymbolic Learning

arXiv:2606.14463v1 Announce Type: new Abstract: Neurosymbolic (NeSy) models integrate neural networks and symbolic reasoning for robust and interpretable AI. State-of-the-art NeSy models require that the symbolic component is expressed in a differentiable way, often complicating the use of approximate inference. We propose EM-NeSy which casts probabilistic NeSy learning as an instance of the Expectation-Maximization (EM) algorithm. In the expectation step, we compute the posterior over the neurally predicted symbols conditioned on the label via probabilistic inference. In the maximization step, we update the neural parameters based on this posterior using gradient descent only through the neural component. This formulation unlocks the full potential of the EM algorithm for NeSy learning. It allows NeSy to extend naturally to approximate reasoning without any additional modifications or differentiability requirements of the symbolic component. Furthermore, it recovers the standard end-to-end gradient-based NeSy setting under exact inference. Our experimental results demonstrate the scalability and computational efficiency of EM-NeSy.

16.
arXiv (quant-ph) 2026-06-24

Passive Polarization Stabilization for Robust Entanglement Distribution via Cross-Aligned Polarization Maintaining Fiber Pairs

arXiv:2512.01229v2 Announce Type: replace Abstract: Maintaining stable entanglement distribution through perturbed fiber links is essential for practical quantum-optics experiments, yet it remains challenging because of polarization fluctuations and phase or temporal-delay variations. We demonstrate stable entangled-photon transmission using a cross-aligned polarization-maintaining fiber (CAPMF) structure composed of two polarization-maintaining fiber sections with mutually orthogonal principal axes. The CAPMF configuration passively compensates polarization fluctuations without real-time active polarization control. We theoretically analyze the CAPMF structure and experimentally verify its stabilization performance under external mechanical perturbations. In the experiment, the single-mode fiber configuration yields an average visibility of $0.7655$ and a CHSH value of $S=1.7714$, whereas the CAPMF configuration maintains an average visibility of $0.9843$ and a CHSH value of $S=2.6838$. These results show that CAPMF offers a simple and robust architecture for stabilizing fiber-interface sections in practical entanglement-distribution systems.

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

Membership Inference Attacks against Large Audio Language Models

arXiv:2603.28378v2 Announce Type: replace-cross Abstract: We present the first systematic Membership Inference Attack (MIA) evaluation of LALMs. Using Multi-modal Blind Baselines based on textual, spectral and prosodic features, we demonstrate that common audio datasets exhibit near-perfect train/test separability (AUC ~ 1.0) even without model inference, thus MIA may primarily detect distribution shift. We therefore introduce a blind-baseline protocol to control for this confound. Under this protocol, we identify that the distribution-matched datasets enable reliable MIA evaluation without distribution-shift artifacts. We benchmark multiple MIA methods and conduct modality disentanglement experiments on these datasets. The results reveal that LALM memorization is cross-modal, arising only from binding a speaker's vocal identity with its text. These findings establish a principled standard for auditing LALMs beyond spurious correlations. Our codebase is available at https://github.com/snooow1029/ALM_MIA.

18.
arXiv (CS.AI) 2026-06-25

Agentic evolution of physically constrained foundation models

arXiv:2606.25532v1 Announce Type: new Abstract: Artificial intelligence increasingly drives automated scientific discovery, yet contemporary generalist agents lack physical grounding, frequently hallucinating hardware-incompatible designs. Here, we present a physically grounded, multi-agent discovery engine that autonomously architects hardware-compliant computing systems. Anchored by an Evolutionary Knowledge Graph structuring past scientific innovations, the framework extracts an "algorithmic Chain-of-Thought" to transform blind stochastic search into directed structural evolution. Applied to the extreme testbed of foundation model deployment, the engine evolved two hardware-aware compression methodologies surpassing human-engineered heuristics: Q-Enhance mitigates long-context accuracy loss in dense models, and MoE-Salient-AQ outperforms state-of-the-art manual sparse Mixture-of-Experts designs by 3.7% at sub-3-bit regimes. Utilizing a bandwidth-efficient Sensitivity Profile, we successfully deployed a massive 235-billion-parameter model onto a constrained dual-A100 server, reducing memory requirements by 75% with a marginal 0.64% accuracy degradation. By transforming unconstrained combinatorial search into knowledge-driven autonomy, this establishes a scalable hardware-software co-design paradigm for machine-driven discovery within strict physical boundaries.

19.
arXiv (CS.CV) 2026-06-24

D3Seg: Dependency-Aware Diffusion for Brain Tumor Segmentation with Missing Modalities

Accurate brain tumor segmentation using multi-parametric MRI is critical for effective treatment planning. However, in clinical settings, complete acquisition of all MRI sequences is not always possible. The absence of certain MRI modalities results in substantial performance degradation in existing segmentation methods, which typically rely on naive feature concatenation or direct fusion strategies. To address this limitation, we propose a novel segmentation model D3Seg which is designed to maintain stable performance under missing-modality settings. D3Seg introduces Multi-hop Modality Graph Fusion (MMGF) to model higher-order inter-modality dependencies, a lightweight diffusion-based imputation mechanism to compensate for missing T1ce and FLAIR feature representations in latent space, and probability-space decision refinement to mitigate dominant-class overconfidence and improve delineation of underrepresented tumor subregions. We evaluate the proposed D3Seg model on BraTS 2023 Glioma as the primary benchmark and further test it on a subset of the external BraTS 2023 Meningioma cohort to assess generalization across tumor pathologies. The results are compared with the state-of-the-art models under different missing-modality conditions. The proposed model achieves approximately 1.5-2.0% Dice improvement on enhancing tumor (ET) and around 1.0% on tumor core (TC) across multiple missing-modality configurations compared to the current state-of-the-art model on BraTS Glioma dataset. Cross-cohort evaluation on BraTS Meningioma dataset demonstrates the generalizability of the proposed model, showing consistent improvements in the challenging TC and ET regions, with approximately 1.5-3.0% and 1.5-6.5% gains respectively across several missing-modality configurations.

20.
Nature Biotechnology 2026-06-23

Efficient generation of epitope-targeted antibodies with Germinal

Obtaining antibodies to specific protein targets is a widely important yet experimentally laborious process. Meanwhile, computational methods for antibody design have been limited by low success rates that require resource-intensive screening. Here we introduce Germinal, a broadly enabling generative pipeline that designs antibodies against specific epitopes with nanomolar binding affinities while requiring only low-n experimental testing. Our method co-optimizes antibody structure and sequence by integrating a structure predictor with an antibody-specific protein language model to perform de novo design of functional complementarity-determining regions onto a user-specified structural framework. When tested against four diverse protein targets, Germinal designed functional antibodies across all targets and binder formats, testing only 43–101 designs for each antigen. Validated designs also exhibited robust expression in mammalian cells and high sequence and structural novelty. We provide open-source code and full computational and experimental protocols to facilitate wide adoption. Germinal achieves epitope-targeted, de novo complementarity-determining region design with high experimental success rates.

21.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

22.
bioRxiv (Bioinfo) 2026-06-24

Generative Modeling of Mouse Embryogenesis for Fate and Disease Prediction

Embryonic development is orchestrated by complex gene regulatory networks, and learning regulatory dynamics from developmental data could allow us to understand, predict, and ultimately engineer cell fates. Here we introduce Navigo (https://github.com/aristoteleo/Navigo-release), a biologically grounded generative modeling framework that learns a developmental vector field by integrating flow matching at the population level with RNA kinetics modeling at the molecular level. Navigo accurately maps developmental trajectories across lineages on a mouse embryogenesis scRNA-seq atlas spanning 43 time points and comprising 12.4 million cells. Applied to cardiac development, Navigo enables disease modeling by mechanistically resolving regulatory networks that distinguish congenital heart disease subtypes. Navigo also predicts perturbation effects in a zero-shot manner, as validated on independent in vivo data from six knockout genotypes without perturbation-specific training, uncovering lineage-specific gene-compensation mechanisms. Moreover, Navigo guides rational cell-fate engineering, exemplified by fibroblast reprogramming analyses, including identifying pro-fibrotic barriers to cardiac fates and evaluating hundreds of pairwise transcription factor combinations for neuronal fate, each consisting of one bHLH factor and one POU factor. Overall, Navigo provides a generalizable AI platform for perturbation-effect prediction, disease modeling, and rational cell-fate engineering, advancing toward AI-based virtual embryos for developmental biology and regenerative medicine.

23.
arXiv (CS.CV) 2026-06-24

Bridging the Manifold Gap: Riemannian Residual Line Search for One-Step Image Editing

One-step diffusion editors are fast because they avoid inversion and iterative optimization, but a single transport update must be aggressive enough to realize the target prompt and conservative enough to preserve the source image–and no fixed update strength satisfies both demands across edit types. We treat this tension as a post-hoc candidate-selection problem on top of energy-field transport rather than as a new editing model. Our proposed method, Riemannian Residual Line Search, first builds a stronger edit by estimating the local time curvature of the prompt-delta field and projecting the corrected direction back onto the update norm of the original first-order energy-field transport estimation. It then forms a small residual path from the source image to this strong edit, retains the original first-order output as one candidate, and picks the final image by maximizing target-prompt CLIP alignment. On a 700-sample PIE-Bench++ evaluation across 10 edit type IDs, our method achieves state-of-the-art (SOTA) performance among current one-step update algorithms.

24.
arXiv (math.PR) 2026-06-17

Absolute continuity, supports and idempotent splitting in categorical probability

arXiv:2308.00651v5 Announce Type: replace Abstract: Markov categories have recently turned out to be a powerful high-level framework for probability and statistics. They accommodate purely categorical definitions of notions like conditional probability and almost sure equality, as well as proofs of fundamental results such as the Hewitt–Savage 0/1 Law, the de Finetti Theorem and the Ergodic Decomposition Theorem. In this work, we develop additional relevant notions from probability theory in the setting of Markov categories. This comprises improved versions of previously introduced definitions of absolute continuity and supports, as well as a detailed study of idempotents and idempotent splitting in Markov categories. Our main result on idempotent splitting is that every idempotent measurable Markov kernel between standard Borel spaces splits across another standard Borel space, and we derive this as an instance of a general categorical criterion for idempotent splitting in Markov categories.

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

Consistent Evaluation of Operators Involving the Position Operator in the Bloch Representation: Application to the Orbital Moment

arXiv:2606.11679v1 Announce Type: cross Abstract: The position operator plays a central role in condensed-matter observables such as velocity, orbital moment, and electric polarization. In solid-state physics, the evaluation of operators incorporating the position operator has not reached a consensus, as observed in the operator-level discrepancy between the local circulation of Wannier functions and the self-rotation of wave packets. Here, to achieve a consistent evaluation of such operators, we propose three rules for evaluating operators involving the position operator in the Bloch representation. The rules are devised to satisfy physical conditions: independence from the choice of unit cell, preservation of Hermitian conjugacy for the product of operators, and recovery of the correct intraband velocity. We further address the gauge dependence of the position operator and introduce a scheme termed gauge filtration, which systematically removes gauge-dependent contributions from the operators containing the position operator. This methodology ensures that the quantities obtained from the operator evaluation correspond to observable physical phenomena. By applying our framework, we reconcile the results concerning the self-rotation of the wave packet and the local circulation of the Wannier function. We expect our proposal to establish a consistent framework for evaluating operators involving the position operator.