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01.
Nature Medicine 2026-06-17

Why large-scale randomized trials of live-attenuated shingles vaccination for dementia prevention are urgently needed

In my view, we have never had as robust a body of evidence from observational data on an intervention for dementia as we do for live-attenuated shingles vaccination. Both a recent US National Institutes of Health expert workshop and an international expert consensus on Alzheimer’s disease drug repurposing identified large-scale randomized trials of shingles vaccination for dementia prevention as the crucial next step for the field.

02.
arXiv (CS.AI) 2026-06-17

KANLib – An Modular, Extensible and Fast Kolmogorov-Arnold Network Implementation

arXiv:2606.17927v1 Announce Type: cross Abstract: Kolmogorov-Arnold Networks (KANs) have recently emerged as a promising alternative to traditional multilayer perceptrons by replacing linear weights with learnable univariate functions. Despite their theoretical advantages in interpretability and expressiveness, practical research of KANs remains difficult due to high computational costs and inconsistent feature support across existing frameworks. This paper introduces KANLib, a modular, extensible, and computationally efficient framework for developing and evaluating KAN architectures. KANLib unifies core concepts from existing implementations, including PyKAN, EfficientKAN, and FastKAN, within a consistent software architecture that emphasizes flexibility, feature parity, and high performance. The framework supports two basis function types, adaptive grid rescaling, grid extension, and fine-grained architectural customization while maintaining compatibility with standard PyTorch workflows. Experimental evaluation on the California Housing benchmark demonstrates that KANLib reproduces the predictive behavior of established reference KAN implementations while achieving competitive computational efficiency. Furthermore, the framework enables the exploration of architectural variations beyond standard KAN formulations with only minor impacts on predictive performance. Overall, KANLib provides a robust foundation for future research on scalable and extensible KAN architectures.

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

Scalar-pathway fidelity improves physical accuracy in short-range equivariant interatomic potentials

arXiv:2606.15892v1 Announce Type: new Abstract: Accurate interatomic potentials enable molecular dynamics of materials, molecules, and interfaces beyond density-functional-theory length and time scales. Equivariant neural network potentials have improved the representation of local geometry. However, their deployable energy surfaces ultimately manifest through invariant scalar channels, whose aggregation and spectral resolution remain comparatively underexamined. Here we use Physics-Aware Neighborhood (PAN) pooling and Physics-Guided Spectral (PGS) mixers as controlled scalar-pathway probes: lightweight, symmetry-preserving modifications that act only on \(\ell=0\) channels while leaving the equivariant tensor backbone unchanged. Using MACE as a high-body-order mechanistic scaffold, PAN adds coordination-sensitive amplitude modulation, whereas PGS augments edge and readout scalar features with radial and tapered spectral bases. Across metallic Ag, covalent Si, a short-range ionic LiF/Li–F subset, and MD17/rMD17 molecules, this scalar-pathway correction reduces MACE force errors by 22–27\% and energy errors by 19–22\%; on systems with stress labels, stress errors decrease by 27–28\%, at approximately 5\% additional inference-FLOPs cost. Directionally consistent gains in Allegro and NequIP further indicate that the correction is portable across distinct short-range equivariant backbones, although effect sizes remain architecture-dependent. These results identify scalar-pathway fidelity as a practical design dimension for short-range equivariant interatomic potentials.

04.
arXiv (math.PR) 2026-06-15

Stability of Synthetic Ricci Curvature Lower Bounds for Inverse Limit Extended Metric Measure Spaces

arXiv:2606.14322v1 Announce Type: cross Abstract: We show that every Polish extended metric measure space arises as an inverse limit of metric measure spaces up to isomorphism. We then prove that synthetic Ricci curvature lower bounds and several functional inequalities, including the log-Sobolev, Talagrand, Poincaré, and dimension-free Harnack inequalities are stable under inverse limit. We discuss applications to infinite-dimensional spaces, including abstract Wiener spaces and their quotient spaces.

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

Intention Driven Identification of In-Possession Match Phases in Association Football through Temporal Graph Learning

arXiv:2606.09289v2 Announce Type: replace Abstract: Understanding tactical organisation of association football, hereafter referred to as football, requires identifying distinct match phases. Yet in-possession phases are rarely directly observable and are shaped by evolving tactical intentions, rather than spatial patterns alone. This study proposes a data-driven framework for identifying in-possession match phases from spatiotemporal tracking data. Seven German Bundesliga matches recorded at 25 Hz with TRACAB were analysed. A hierarchical phase model was defined with three tactical intentions (Invade Opponent Space, Keep Possession, Scoring) and six phases (Build Up, Progression, Counter Attack, Maintenance, Sustained Threat, Finishing). A Temporal Graph Attention Network (T-GAN) was developed to combine frame-level player-interaction graphs, contextual features, and Transformer-based temporal modelling. Performance was evaluated using frame-level F1 and a sequence-aware Intersection over Truth-Dominance (IoT-D) metric. T-GAN achieved macro-average frame-level F1 scores of 0.87 at the intention level, 0.76 for invasion-related phases, and 0.79 for scoring phases. At the sequence level, mean diagonal IoT-D F1 increased from 0.68 to 0.79 for intentions and from 0.61 to 0.71 for phases after post-processing, indicating improved temporal coherence. Model comparisons showed that sequence modelling was the main driver of segmentation quality, while graph-based relational modelling was particularly beneficial for Counter Attack recognition. Exploratory player attention analysis further suggested that wide and midfield positional groups contributed strongly to phase discrimination. Overall, the framework translates continuous tracking data into tactically interpretable in-possession phase representations, with potential applications in automated match annotation, tactical analysis, and playing-style profiling.

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

Stalls and Spequlation: Pipelined Execution for Fault Tolerant Quantum Computation

arXiv:2606.19593v1 Announce Type: new Abstract: Fault-tolerant quantum computation requires the coordinated action of three distinct systems: classical control logic, quantum hardware, and classical error decoders. Current scheduling models treat logical operations as atomic, hiding the fact that these subsystems operate sequentially and spend significant time idle. We present a pipelined execution framework that decomposes each logical operation into its component stages i.e. Control, Execute, and Decode. Building on this, we discuss some speculation strategies that allow successor operations to begin processing before their predecessors have completed decoding. We evaluate our framework on several common benchmarks and show that pipelining with speculation reduces total pipeline steps by 20-40% compared to a no-speculation baseline. The most aggressive strategy consistently outperforms conservative alternatives, even though partial rollback is needed at times, because the per-rollback penalty is small relative to the parallelism gained. We further show that speculation facilitates load balancing by distributing work more evenly across the heterogeneous subsystems of a fault-tolerant quantum computer, converting idle time into useful computation while also saving on execution time.

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

Lighting-aware Unified Model for Instance Segmentation

Foundation models like the Segment Anything Model (SAM) demonstrate impressive zero-shot generalization but frequently degrade under diverse real-world illumination, particularly for instance segmentation. In this work, we address this limitation by developing Lighting Convolutional-Attention (\lca{)}, an adapter module that enhances segmentation robustness without fine-tuning the heavy backbone. \lca{} employs a dual-branch architecture to process RGB features alongside contrast maps, enabling physically motivated sensitivity to structural changes rather than illumination artifacts. We optimize \lca{} through a pairwise training strategy, introducing a targeted loss term that explicitly penalizes discrepancies between clean images and their corresponding illumination variants. To evaluate and support this architecture, we conduct a comprehensive empirical study across multiple existing benchmarks and present a novel Unity-based synthetic dataset specifically designed to accurately replicate complex real-world lighting conditions. Extensive experimental results demonstrate that our approach successfully bridges the domain gap, delivering superior lighting-robust segmentation.

08.
arXiv (CS.CL) 2026-06-24

A P\={a}ninian Foundation for Indic Language Processing

More than a billion people communicate in Indic languages, yet the natural language processing infrastructure serving them remains fragmented and underdeveloped. The cause is structural: the field organizes its tools and benchmarks around individual languages or small subsets of genealogical language families, building separate analyzers, parsers, and datasets for each language and starting over for the next. This overlooks a deep regularity. Through more than two millennia of convergence around Sanskrit, Indic languages came to share a morphosyntactic architecture formalized in P\={a}nini's grammar, the Ast\={a}dhy\={a}y\={i}. This cuts across genealogical lines, uniting languages through a common framework. We argue that this P\={a}ninian framework supplies a unifying computational architecture the field has lacked, and that benchmarks grounded explicitly in it would make Indic language systems more accurate, more data-efficient, and more transferable, effectively merging many apparently disparate and sparse Indic language resources into a single high-resource metalanguage bedrock. We propose a four-part benchmark suite to render this shared architecture explicit, measurable, and ready to be leveraged for practical applications. Moreover, we underscore the question it raises for interpretability research: whether neural models trained on these languages come to represent P\={a}nini's categories on their own.

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

Physics-Driven Spatiotemporal Modeling for AI-Generated Video Detection

AI-generated videos have achieved near-perfect visual realism (e.g., Sora), urgently necessitating reliable detection mechanisms. However, detecting such videos faces significant challenges in modeling high-dimensional spatiotemporal dynamics and identifying subtle anomalies that violate physical laws. In this paper, we propose the first physics-driven AI-generated video detection paradigm based on probability flow conservation principles. Specifically, we propose a statistic called Normalized Spatiotemporal Gradient (NSG), which quantifies the ratio of spatial probability gradients to temporal density changes, explicitly capturing deviations from natural video dynamics. Leveraging pre-trained diffusion models, we develop an NSG estimator through spatial gradients approximation and motion-aware temporal modeling without complex motion decomposition while preserving physical constraints. Building on this, we propose an NSG-based video detection method (NSG-VD) that computes the Maximum Mean Discrepancy (MMD) between NSG features of the test and real videos as a detection metric. Last, we derive an upper bound of NSG feature distances between real and generated videos, proving that generated videos exhibit amplified discrepancies due to distributional shifts. Extensive experiments confirm that NSG-VD outperforms state-of-the-art baselines by 16.00% in Recall and 10.75% in F1-Score, validating the superior performance of NSG-VD. The source code is available at https://github.com/ZSHsh98/NSG-VD.

10.
arXiv (math.PR) 2026-06-11

Instability of a nonlinear oscillator with small friction and small additive noise

arXiv:2606.11389v1 Announce Type: new Abstract: Let $\lambda = \lambda(\beta,\sigma,a,b)$ denote the top Lyapunov exponent for the linearization along trajectories of the noisy damped non-linear oscillator $\ddot{x}+\beta \dot{x} + ax+bx^3 = \sigma \dot{W}_t$, where $a$, $b$ and $\beta$ are all positive and $\sigma \neq 0$. In 2004 Arnold, Imkeller and Sri Namachchivaya stated without proof that $\lambda(\varepsilon^2 \beta,\varepsilon \sigma,a,b) \sim \overline{\lambda} \varepsilon^{2/3}$ as $\varepsilon \to 0$ with $\overline{\lambda} > 0$. This paper contains a proof of this assertion.

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

Neural ARFIMA model for forecasting BRIC exchange rates with long memory

arXiv:2509.06697v3 Announce Type: replace-cross Abstract: Exchange rate forecasting remains a challenging problem, particularly for emerging economies, where the observed time series exhibit pronounced long-memory dependence, nonlinear dynamics, and sensitivity to macro-financial drivers. Classical models such as ARFIMA capture long-range persistence but fail to adequately represent nonlinear relationships, while modern machine learning approaches often neglect the underlying long-memory structure in macroeconomic series. To address this gap, we propose a Neural AutoRegressive Fractionally Integrated Moving Average (NARFIMA) model that integrates ARFIMA-based long-memory modeling with neural networks for nonlinear function approximation, while incorporating exogenous macroeconomic and uncertainty indicators. The framework provides a unified approach for capturing persistence, nonlinear dynamics, and external shocks. We establish asymptotic stationarity of the NARFIMA process and develop conformal prediction intervals for distribution-free uncertainty quantification. Empirical results for BRIC exchange rates show that NARFIMA consistently outperforms a broad range of forecasting benchmarks across multiple horizons, underscoring the importance of explicitly modeling long-memory dependence in exchange rate dynamics. The `narfima' R package provides an implementation of our approach.

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

Leveraging Social Media Data for COVID-19 Studies

Nowadays, social media networks have become widely preferred sources of information. Especially during the time of the Coronavirus disease 2019 COVID 19 pandemic, social media has been one of the most used platforms to get the latest news and information related to COVID 19. Social media are popular because they offer free access to their registered users and allow them to do posting, disseminate information, and respond to others postings. With almost 4.6 billion social media users worldwide, it is not surprising the significant amount of information shared through these platforms could affect how people perceive and cope with the pandemic that we are facing right now. With decent use, social media can be a beneficial digital tool to spread reliable news and public awareness for patients, clinicians, and society. Specifically, this chapter describes linguistic, visual, and emotional indicators expressed in user disclosures. Thus, in this chapter, the related studies of social media platforms usage during the COVID 19 pandemic are explored and discussed in detail. This chapter also categorizes social media data used, introduces different deployed machine learning, feature engineering, natural language processing, and survey methods, and outlines directions for future research.

13.
arXiv (CS.CL) 2026-06-18

Structured Inference with Large Language Gibbs

The knowledge encoded in large language models (LLMs) can serve as a substrate for structured reasoning over variables describing a complex world, but accessing this knowledge in a probabilistically coherent manner poses a difficult inference problem. We propose Large Language Gibbs, a scheme for structured probabilistic inference that uses conditional distributions of an LLM as transition operators. Rather than sampling structured objects through single-pass autoregressive generation, we iteratively resample individual variables conditioned on others using an LLM's next-token conditionals. This approach avoids order-dependent biases and produces a stationary distribution that reflects a compromise between all local conditionals. We apply this approach to sampling from synthetic distributions, consistent reasoning tasks, and Bayesian structure learning. The results suggest that the use of LLM conditionals in MCMC is a practical alternative to one-pass generation for structured probabilistic inference under a world prior accessible through noisy LLM conditionals.

14.
arXiv (CS.CV) 2026-06-18

Moving Beyond Diversity: Visual Token Pruning as Subspace Reconstruction for Efficient VLMs

Despite their remarkable performance, Vision Language Models (VLMs) incur substantial computational overhead due to the large number of visual tokens. While diversity maximization has become a dominant strategy for token reduction, existing methods rely on cosine-based normalized similarity that discards magnitude information, failing to faithfully approximate the original feature representation and leading to suboptimal performance, particularly on compositional multi-skill reasoning tasks. In this paper, we introduce SPARE, a subspace reconstruction method that reformulates token pruning as a column subset selection problem and explicitly minimizes reconstruction error. By iteratively selecting tokens with large projection residuals, SPARE performs reconstruction-driven pruning beyond angular diversity. Moreover, we reveal a counterintuitive anti-relevance phenomenon: tokens with lower image-text relevance score can better preserve contextual information. Based on this finding, we incorporate anti-relevance into SPARE as an additional selection criterion to promote context-aware token selection. Extensive experiments across multiple VLMs and benchmarks demonstrate that SPARE consistently achieves state-of-the-art performance, with strong gains on compositional tasks. When applied to LLaVA, SPARE removes up to 94% of visual tokens while retaining 95% of the baseline performance, all in a fully training-free manner.

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

To Cool, or Not to Cool? Displacement Sensing with Hot Quantum States

arXiv:2606.13650v1 Announce Type: new Abstract: Quantum-enhanced displacement sensing with bosonic systems is typically formulated assuming that the oscillator is cooled close to its ground state before nonclassical probe preparation. We investigate whether such near-ground-state initialization is necessary, or whether sensitive probes can instead be generated directly from thermal states. We analyze hot quantum probes produced by squeezing, number-raising, and Schrödinger-cat-state generation applied to thermal inputs. We identify two distinct mechanisms by which thermal mixedness can remain compatible with enhanced displacement sensitivity. First, projecting a mixed probe onto a definite parity sector removes the usual thermal suppression of the displacement quantum Fisher information, which can then increase with initial thermal occupation. Second, coherent superpositions of opposite displacements can retain sensitivity through coherence between their displaced components, even when the underlying state is mixed. We use these two mechanisms to classify hot-state protocols according to whether their sensitivity comes from parity selection, coherence between displaced components, or both. Finally, we formulate an experimentally relevant optimization problem comparing initial cooling with direct hot-state preparation under realistic decoherence and show that complete cooling is not universally optimal. Our results establish hot-state engineering as a route to quantum-enhanced bosonic displacement sensing without mandatory ground-state initialization.

16.
arXiv (math.PR) 2026-06-12

On McDiarmid's Inequality under Dependence via Approximate Tensorization of Entropy

Authors:

arXiv:2606.12720v1 Announce Type: new Abstract: We argue that dependent versions of McDiarmid's inequality are a useful but underutilized tool in mathematical statistics, learning theory and theoretical computer science. To make this point, we first highlight that approximate tensorization of entropy (ATE) implies McDiarmid's via the Entropy Method. Second, we derive McDiarmid's inequality for non-isotropic Gaussian random vectors $X \sim \mathcal N(\mu, \Sigma)$ through ATE with a constant of the order of the condition number of $\Sigma$. We both independently obtain this ATE through a simple application of stochastic localization and also discuss how a more general ATE for the Gibbs sampler due to Ascolani et al., 2026 generalizes McDiarmid's-like concentration to strongly log-concave and log-smooth probability measures. We then apply the resulting concentration inequalities to resolve a question on the concentration of $\operatorname{sign}(X)$ posed by Simone Bombari, investigate Erdős-Rényi graphs under dependence and prove a Dvoretzky-Kiefer-Wolfowitz-type inequality for observations from a joint measure fulfilling ATE and continuous marginal CDFs. For the class of strongly log-concave and log-smooth measures, this result improves upon a prior Dvoretzky-Kiefer-Wolfowitz-type inequality for non-i.i.d. observations due to Bobkov and Götze, 2010, by establishing the expected $1/\sqrt{n}$-rate of convergence under weak dependence instead of $n^{-1/3}$.

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

Persistent Homology as a Theory of Emergent Structure

Authors:

arXiv:2507.03065v2 Announce Type: replace Abstract: Why do some macroscopic structures remain identifiable even though their microscopic constituents continually change? Vortices persist while fluid parcels turn over, neural memories persist while spikes and synapses fluctuate, and institutions persist while individuals enter and leave. We propose a scale-relative answer: an emergent property is a persistent nontrivial homology class $[z]\in H_p=\ker\partial_p/\im\partial_{p+1}$, a macro-feature that is closed but not exact across a filtration of descriptions. This identification turns emergence into a measurement problem. Persistent bars detect stable macro-features, and we introduce a contractive-similarity (CS) graph operator to supply scaffold spectral gaps that predict robustness. Hodge decomposition separates harmonic macro-scaffold from exact and co-exact micro-flow; and functorial condensation explains when one level's emergent class becomes a unit for the next. The resulting scaffold-flow framework expresses six familiar signatures of emergence (i.e., inevitability, coherence, irreducibility, complementarity, robustness, and hierarchy) within one mathematical language. It also yields falsifiable predictions across atmospheric, neural, and social systems: genuine emergent structures should persist across filtrations, remain spectrally stable, respond disproportionately to harmonic interventions, and require timescale separation for hierarchical autonomy.

18.
arXiv (math.PR) 2026-06-24

Variational Tail Bounds for Norms of Random Vectors and Matrices

arXiv:2503.17300v5 Announce Type: replace Abstract: We propose a variational tail bound for norms of random vectors and matrices under moment assumptions on their one-dimensional marginals. A simplified version of the bound that parametrizes the ``aggregating distribution'' using a certain pushforward of the Gaussian distribution is also provided. We apply the proposed method to reproduce some of the well-known bounds on norms of Gaussian random vectors, and also obtain dimension-free tail bounds for the Euclidean norm of random vectors with arbitrary moment profiles. Furthermore, we reproduce a dimension-free concentration inequality for sum of independent and identically distributed positive semidefinite matrices with sub-exponential marginals, and obtain a concentration inequality for the sample covariance matrix of sub-exponential random vectors. We also obtain a tail bound for the operator norm of a random matrix series whose random coefficients may have arbitrary moment profiles. Furthermore, we use coupling to formulate an abstraction of the proposed approach that applies more broadly. As a corollary, we derive a PAC-Bayesian-style bound in terms of a certain combination of the KL and R\'{e}nyi divergences between the prior and posterior distributions.

19.
medRxiv (Medicine) 2026-06-23

Sex-Specific TMPRSS2 Response and Reduced Peripheral RNA Concentration Following AstraZeneca COVID-19 Vaccination in Nigeria.

Background: ChAdOx1 nCoV-19 remains a cornerstone COVID-19 vaccine in sub-Saharan Africa, yet population-specific molecular responses are understudied. We examined peripheral blood ACE2 and TMPRSS2 expression, total RNA concentration, and coagulation indices in Nigerians >=6 months post-vaccination. Methods: In a case-control study in Port Harcourt, Nigeria, 51 ChAdOx1-vaccinated adults and 51 age/sex-matched unvaccinated controls provided venous blood for RNA extraction, qRT-PCR, and coagulation assays. Multivariable linear models assessed effects of vaccination, sex, and age on molecular parameters. Results: Vaccinated participants had 37% lower total RNA concentration than controls (4.02 +/- 0.09 vs 6.38 +/- 0.14 ng/uL, p=6 months post-ChAdOx1, Nigerians show reduced peripheral blood RNA without sustained ACE2/TMPRSS2 upregulation. The sex-specific TMPRSS2 pattern suggests hormone and vaccine interactions previously unreported in African cohorts and highlights the need for sex-disaggregated molecular surveillance. Region-specific reference gene validation is recommended for Nigerian transcriptomic studies.

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

Pathway-Structured Privileged Distillation for Deployable Computational Pathology

Integrating transcriptomics and histopathology can improve cancer risk modelling, yet practical use is constrained by the limited availability of RNA profiling in routine settings. Here we introduce Mixture of Pathway Experts (MoPE), a knowledge-distillation framework that reframes multimodal learning as privileged distillation for histology-only inference. MoPE is motivated by the partial observability between RNA profiles and whole-slide images: histology can capture morphology-linked consequences of certain molecular programmes, but cannot be expected to reconstruct the full transcriptomic state. MoPE encodes RNA-derived pathways and transfers the molecular supervision to pathway-indexed pathology experts through memory-usage alignment. Across diverse public benchmarks and two independent breast cancer cohorts, MoPE consistently improved WSI-only inference performance relative to baseline methods. Pathway-usage analyses and human-audited visual inspection provide bounded inspection of model behaviour and candidate morphology-linked readouts. These results support pathway-structured privileged distillation as a promising route to using molecular information during training while preserving RNA-free inference.

21.
arXiv (CS.LG) 2026-06-15

Machine Learning for Biomedical Raman Spectroscopy: From Spectral Acquisition to Clinical Translation

arXiv:2606.14169v1 Announce Type: new Abstract: Raman spectroscopy provides label-free, chemically specific characterization of biological systems and has become an important tool for cancer diagnosis, molecular subtyping, microbiological identification, and intraoperative decision support. Biomedical Raman spectra are, however, high-dimensional, noisy, and affected by fluorescence background, acquisition variability, and biological heterogeneity, making robust computational analysis essential. This review examines the role of machine learning across the biomedical Raman spectroscopy pipeline, from preprocessing and signal correction to unsupervised structure discovery, supervised diagnosis and molecular stratification, representation and transfer learning, explainability, biomarker discovery, and multimodal integration with imaging, pathology, and molecular profiling. Emphasis is placed on the use of machine learning not only for diagnostic classification, but also for biologically interpretable and clinically actionable analysis. We also discuss the main barriers to clinical translation, including limited dataset sizes, inter-instrument variability, inconsistent preprocessing, insufficient external validation, reproducibility concerns, and limited sharing of software, data, and metadata. We argue that progress will require methodological advances together with standardization, robust validation, explainability, and deployment-ready analytical frameworks. By integrating methodological, biomedical, and translational perspectives, this review outlines key directions for developing reliable and clinically deployable Raman-AI systems.

22.
bioRxiv (Bioinfo) 2026-06-18

Elucidating the Design Space of Generative Models for Single-Cell Perturbation Prediction

Next-token prediction has produced predictable scaling in language, but the recipe presumes a sequence of tokens with a meaningful order. Single-cell RNA-seq counts have no natural gene ordering, so applying the recipe directly to raw expression fails under an ill-suited left-to-right bias. We instead ask whether a learned latent can supply the structure the recipe needs. We introduce texttt{ExpressionVAE} (eVAE), a discrete-latent perturbation model that compresses each cell into a short sequence of discrete codes through a finite-scalar-quantization (FSQ) bottleneck and trains a perturbation-conditioned discrete prior over those codes. On Replogle and Parse~1M, eVAE sets a new state of the art on every distributional metric and leads on most cell-eval perturbation metrics, with Fr'echet distance and $mathrm{MMD}^2$ roughly $3$ to $20times$ lower than the strongest continuous-latent baseline. Swapping the prior between autoregressive and masked discrete diffusion leaves performance near-identical, isolating the gain to the discrete latent itself rather than the prior family. A decoder-head ablation then exposes a single design axis, the richness of the predictive distribution at inference, that splits the standard metrics into two groups, variance-sensitive and mean-sensitive, which move in opposite directions along the axis. Finally, on a held-out CRISPRi reversion benchmark of $1{,}732$ perturbations under inflammatory cytokine stress, the frozen eVAE encoder outperforms UMAP and differential expression and matches scGPT on perturbation ranking at a fraction of the data.

23.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

24.
arXiv (CS.LG) 2026-06-18

On Local Population-Risk Certificates

Authors:

arXiv:2606.19147v1 Announce Type: cross Abstract: This paper develops local certificates for population-risk increments around a current model. For a local candidate set \(\mathcal D\), the certificate is a two-sided confidence band for \(P({\ell_{\theta+v}-\ell_\theta})\) over \(v\in\mathcal D\). As an application, the upper endpoint of this band yields a risk-controlled update rule: an update is accepted only when its certified upper endpoint is nonpositive; otherwise the current model is retained.

25.
arXiv (quant-ph) 2026-06-17

Stochastic signal sensing with finite energy and dead time at the fundamental quantum limit

arXiv:2606.18133v1 Announce Type: new Abstract: State preparation, measurement, and reset operations take finite time and use finite energy in realistic experiments, yet the impact of this on optimal quantum metrological protocols is not properly understood. We study the effect on sensing a stochastic signal, relevant for the detection of ultralight dark matter and other searches for fundamental physics. We prove that two-mode squeezed vacuum is the optimal probe state given a finite mean-energy constraint for a family of incoherent sensing problems, including noise sensing and quantum illumination. For estimating a gain independent of a loss, we show that entanglement is a required resource to achieve the fundamental quantum limit and observe a non-Gaussian to Gaussian transition in the optimal unentangled state as the dead time increases. We apply our results to bulk acoustic wave resonators.