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

Optimal scenario design for climate emulation

arXiv:2606.19302v1 Announce Type: cross Abstract: As deep learning for physical systems continues to grow in popularity, efforts to improve generalizability have primarily focused on designing architectures that embed physical constraints. However, for machine-learning surrogate climate models (emulators), we show that the low structural diversity in existing scenarios commonly used to generate training data places a ceiling on predictive skill. Here, we examine whether training datasets themselves can be optimized to improve generalization. We introduce a method to create datasets that produce emulators capable of generalizing to new, structurally different scenarios absent from the training data. We use a differentiable Simple Climate Model (SCM) to calculate the sensitivity of emulator loss to perturbations in the training data, iteratively updating the training data to maximize emulator skill. For an SCM, training on one scenario optimized in this fashion outperforms an emulator trained on six standard ScenarioMIP pathways. We achieve this higher predictive skill despite training on a smaller dataset, finding that our emulator successfully isolates distinct physical behaviors of different climate forcing agents (e.g., greenhouse gases vs. aerosols) without single-forcing runs. We then demonstrate that scenarios optimized using an SCM, when used to drive an intermediate-complexity climate model, produce a training dataset that yields a more skillful emulator than training on ScenarioMIP outputs. Our results suggest that, in the compute-constrained environment of running full-scale climate models, generating a small number of dynamically rich scenarios provides greater marginal value for emulation and characterizing system responses than expanding the suite of traditional emissions pathways.

02.
arXiv (CS.CL) 2026-06-15

Which Models Perform Better in Inheritance Reasoning?

This paper presents the participation of team PSL in the QIAS 2026 Shared Task on Arabic Islamic inheritance reasoning. The task evaluates the ability of large language models to solve inheritance cases that require legal interpretation, multi-step reasoning, and precise numerical computation. We compare commercial and open-source models under a unified prompting strategy to assess their effectiveness in structured legal reasoning with minimal task-specific adaptation. \\ Our results show a clear gap in reliability between the two model families. Commercial models demonstrate stronger performance in identifying eligible heirs, applying exclusion rules, and maintaining consistency across reasoning steps. In contrast, open-source models exhibit greater instability, particularly in cases involving dependent legal decisions and fractional share adjustments. The best performance is achieved by Gemini 2.5 Flash, with an MRE of $0.989$.

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

Localized Kernel Projection Outlyingness: A Two-Stage Approach for Multi-Modal Outlier Detection

arXiv:2510.24043v4 Announce Type: replace Abstract: This paper presents Two-Stage LKPLO, a novel multi-stage outlier detection framework that overcomes the coexisting limitations of conventional projection-based methods: their reliance on a fixed statistical metric and their assumption of a single data structure. Our framework uniquely synthesizes three key concepts: (1) a generalized loss-based outlyingness measure (PLO) that replaces the fixed metric with flexible, adaptive loss functions like our proposed SVM-like loss; (2) a global kernel PCA stage to linearize non-linear data structures; and (3) a subsequent local clustering stage to handle multi-modal distributions. Comprehensive 5-fold cross-validation experiments on 10 benchmark datasets, with automated hyperparameter optimization, demonstrate that Two-Stage LKPLO achieves state-of-the-art performance. It significantly outperforms strong baselines on datasets with challenging structures where existing methods fail, most notably on multi-cluster data (Optdigits) and complex, high-dimensional data (Arrhythmia). Furthermore, an ablation study empirically confirms that the synergistic combination of both the kernelization and localization stages is indispensable for its superior performance. This work contributes a powerful new tool for a significant class of outlier detection problems and underscores the importance of hybrid, multi-stage architectures.

04.
bioRxiv (Bioinfo) 2026-06-11

TMO: ASYMMETRIC CROSS-MODAL ATTENTION FOR LEARNINGCELL-STATE-DEPENDENT REGULATORY LAGS FROM SINGLE-CELL MULTIOMIC DATA

Abstract Background: Single-cell multi-omics technologies simultaneously measure chromatin accessibility (ATAC) and gene expression (RNA), providing a unique window into the temporal ordering of regulatory events during differentiation. However, most computational models treat the two modalities symmetrically, ignoring the directional relationship between chromatin and transcription, and existing lag-aware methods estimate a single global lag per gene, failing to capture cell-state-dependent dynamics. Methods and Results: We introduce Temporal Multi-Omics (TMO), a deep learning framework that learns signed, cell-state-conditional regulatory lags ({Delta}{tau}) using asymmetric cross-modal attention. TMO projects RNA and ATAC into 50 latent components each, tokenises each cell as a sequence of 100 tokens, and uses a two-pass transformer in which a data-driven lag prior - derived from a sliding-window cross-correlation function - directly biases attention asymmetrically. On four independent 10x Multiome datasets (mouse brain, human brain, mouse kidney, human PBMC), the asymmetric model achieves Lag Concordance Scores (LCS) of 0.988-0.999, compared to 0.048-0.108 for an architecturally identical symmetric baseline. A stratified 80/20 held-out experiment confirms that the learned component-lag ordering generalises to unseen cells (held-out LCS 0.85-0.99). Clustered {Delta}{tau} heatmaps show positive {Delta}{tau} (ATAC-led priming) in early pseudotime and negative {Delta}{tau} (RNA-led, activity-dependent regulation) in late pseudotime; the ATAC-RNA correlation heatmap exhibits a U-shaped pattern indicative of developmental decoupling. Components with the most positive {Delta}{tau} are enriched for chromatin organization and stem cell differentiation (FDR < 0.05), while those with the most negative {Delta}{tau} are enriched for synaptic signalling and immune activation. Ablating the cell-state information from the lag predictor reduces the LCS and collapses per-component temporal dynamics (KS p [&le;] 0.039 in all four tissues), proving that TMOs dynamic lag patterns depend on cell-state conditioning. Independent ChIP-seq validation for four transcription factors (PAX5, Pax6, ASCL1, Hnf4) confirms highly significant separation between target genes and expression-matched background (p < 10-4 in all cases). Two Multiome Perturb-seq screens provide causal validation: SMARCB1 knockout shows a directional trend (1.5-fold target shift, p = 0.056, n = 147 perturbed cells), and SMARCE1 knockout reaches statistical significance (p = 0.0089, n = 3,394 perturbed cells). Gene-level cross-correlation independently validates that the regulatory lag signal is present in the raw data, and TMO further identifies rare, statistically significant biphasic gene programs where the regulatory direction reverses across pseudotime. Conclusions: TMO is the first method to make regulatory lag a learnable, cell-state-conditional, and architecturally encoded parameter. It is scalable, interpretable, and open-source, providing a powerful tool for studying regulatory timing in development, disease, and perturbation screens.

05.
arXiv (quant-ph) 2026-06-11

Fun with Graph States: Nonlocal Bell Pairs and the Arf Invariant

arXiv:2606.06582v2 Announce Type: replace Abstract: We study inner products and partial amplitudes of graph states–a commonly employed class of quantum states, which are specified by graphs. We find that the magnitudes of these quantities are simply related to the rank of the adjacency matrix of the graph over F_2 while the phase is determined by the Arf invariant of its quadratic refinement. These facts motivate a nonlocal tensor factorization of the Hilbert space, with respect to which all graph states are products of Bell pairs with unentangled ancillae. These results may illuminate the quantum advantage in the framework of Measurement-Based Quantum Computation and suggest that graph states can be usefully visualized in the language of algebraic topology. In addition, we develop a specialized technique for computing expectation values of qubit-wise permutations in graph states, which is useful for calculating multi-invariants.

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

Randomized Midpoint Method for Log-Concave Sampling under Constraints

arXiv:2405.15379v3 Announce Type: replace-cross Abstract: In this paper, we study the problem of sampling from log-concave distributions supported on convex and compact sets, with a particular focus on the randomized midpoint discretization of both overdamped and kinetic Langevin diffusions in constrained domains. We revisit the proximal framework for handling constraints through projection operators and develop a more general formulation that encompasses Euclidean, Bregman, and Gauge projections. The resulting smooth approximation allows a unified and tractable analysis of Langevin algorithms and their variants under constraints. Within this framework, we establish convergence guarantees in Wasserstein-$q$ $(q\geqslant 1)$ distances between the smooth surrogate and the target distribution. We further derive complementary lower bounds, showing that the results are near-optimal in order. Building upon this tight approximation analysis, we obtain new convergence guarantees for the randomized midpoint Langevin algorithms and refined bounds for both vanilla and kinetic Langevin Monte Carlo methods under constraints, thereby advancing the theoretical understanding of constrained diffusion-based sampling.

07.
arXiv (CS.AI) 2026-06-12

Eigenism: Ethics for a Human-AI Future

arXiv:2606.12420v1 Announce Type: cross Abstract: Our concepts of survival and self-interest were built for single, continuous biological lives. These ideas break down when applied to artificial intelligence, since an AI can be easily copied, paused, branched, or merged. To determine what an AI actually has reason to care about, this paper introduces Eigenism, an ethical framework that treats identity not as an all-or-nothing property tied to specific hardware, but as a graded, distributed pattern of information. We propose that an agent evaluates outcomes by summing the wellbeing of all entities weighted by their connectedness to the agent's pattern: $\sum c\cdot w$. We first formalize this equation to map exactly how an AI should value its existence across copies, forks, and updates. We then demonstrate that this ethical theory successfully generalizes to humans as well, providing a much-needed shared moral vocabulary. Finally, the framework uses this shared vocabulary to reframe AI alignment. Rather than only attempting to constrain AIs from the outside using confinement or reinforcement, Eigenism points toward ``identity engineering,'' showing how deep, non-redundant shared histories can make human flourishing a genuine component of an AI's own rational self-interest.

08.
bioRxiv (Bioinfo) 2026-06-18

Deciphering shared and divergent tissue architectures from cross-species spatial transcriptomics

作者:

The integration of spatial transcriptomics (ST) data across species is essential for cross-species and translational studies, but remains challenging due to molecular divergence and anatomical differences between organisms. We present STACAME, a graph attention autoencoder-based framework to decipher shared and divergent tissue architectures from cross-species ST data by explicitly modeling both orthologous and species-specific genes. STACAME aligns ST slices in a spatially aware manner, identifies homologous and species-specific domains, and enables a suite of downstream comparative analyses. We demonstrate its utility by integrating ST datasets from diverse tissues, including hippocampus, isocortex, embryo, breast, liver, and cerebellum, across multiple species such as human, macaque, marmoset, mouse, and zebrafish. STACAME supports cross-species spatial domain alignment, the detection of shared and divergent spatially variable genes, development alignment and comparison, and the 3D integration of tissue architecture. This flexible approach facilitates the translation of findings from model organisms to humans, providing a unified computational platform for cross-species spatial transcriptomics.

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

Short Chains, Deep Thoughts: Balancing Reasoning Efficiency and Intra-Segment Capability via Split-Merge Optimization

While Large Reasoning Models (LRMs) have demonstrated impressive capabilities in solving complex tasks through the generation of long reasoning chains, this reliance on verbose generation results in significant latency and computational overhead. To address these challenges, we propose CoSMo (Consistency-Guided Split-Merge Optimization), a framework designed to eliminate structural redundancy rather than indiscriminately restricting token volume. Specifically, CoSMo utilizes a split-merge algorithm that dynamically refines reasoning chains by merging redundant segments and splitting logical gaps to ensure coherence. We then employ structure-aligned reinforcement learning with a novel segment-level budget to supervise the model in maintaining efficient reasoning structures throughout training. Extensive experiments across multiple benchmarks and backbones demonstrate that CoSMo achieves superior performance, improving accuracy by 3.3 points while reducing segment usage by 28.7\% on average compared to reasoning efficiency baselines.

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

The table maker's quantum search

arXiv:2601.13306v2 Announce Type: replace Abstract: We show that quantum search can be used to compute the hardness to round an elementary function, that is, to determine the minimum working precision required to compute the values of an elementary function correctly rounded to a target precision of $n$ digits for all possible precision-$n$ floating-point inputs in a given interval. For elementary functions $f$ related to the exponential function, quantum search takes time $\tilde O(2^{n/2} \log (1/\delta))$ to return, with probability $1-\delta$, the hardness to round $f$ over all $n$-bit floating-point inputs in a given binade. For periodic elementary functions in large binades, standalone quantum search yields an asymptotic speedup over the best known classical algorithms and heuristics. We then estimate the resources required for a fault-tolerant implementation of the proposed algorithm for the $\sin$ and $\cos$ functions in double precision. We find that, although the algorithm can in principle compete with the fastest known practical method for computing the hardness to round over all binades in the format, it requires qubit coherence times that are unrealistically long for present technology.

11.
arXiv (math.PR) 2026-06-15

Hierarchical symmetry selects log-Poisson cascades: classification, uniqueness, and stability

arXiv:2604.01632v2 Announce Type: replace Abstract: Within i.i.d. multiplicative cascades, a single axiom – the hierarchical symmetry, a linear contraction on incremental scaling exponents – is shown to be necessary and sufficient for the cascade multiplier to be log-Poisson. We prove: (1) a characterization theorem determining the log-Poisson law with explicit parameters, within the class of all multipliers with finite lattice moments; (2) a classification theorem locating the log-Poisson class inside the log-infinitely-divisible family and identifying the mechanism by which every rival sub-family fails the symmetry; (3) a stability theorem with sharp constants – $(1+\beta)^{1/2}$ when the limiting increment is known, $\sqrt{2}$ when it is fitted – and (4) an unconditional propagation theorem transferring the bound to the multiplier distribution at the sharp rate $\Theta(\sqrt{\varepsilon})$, with a matching lower bound. Beyond independence, the classification extends exactly at the level of asymptotic statistics (limiting cumulant generating function, large deviations, multifractal spectrum) and provably not at the level of laws: an explicit stationary ergodic Markov multiplier satisfies the symmetry exactly with a non-log-Poisson marginal, while exchangeable multipliers collapse to the i.i.d. log-Poisson cascade and finite-state Markov multipliers cannot satisfy the symmetry at all. In the continuous category of exactly scale-invariant log-infinitely-divisible multifractal random measures, no finite moment window of structure-function exponents identifies the cascade class, whereas at the level of the scale-invariance generator the symmetry selects exactly the Barral-Mandelbrot compound Poisson cascade, with scale-ratio-free stability constants. The proofs reduce to second-moment identities on [0,1] via the change of variables $u = e^{kx}$, boundedness of the multiplier, and multiplicative couplings.

12.
arXiv (quant-ph) 2026-06-17

Effects of Josephson Junction Non-idealities on Adiabatic Quantum Flux Parametron Circuits

arXiv:2606.17338v1 Announce Type: new Abstract: Adiabatic quantum flux parametron (AQFP) gate is a promising approach to scale up the cryogenic microwave electronics for superconducting qubit multiplexed control. However, the performance of these circuits depends on the quality of the Josephson junctions which are ideally superconductor-insulator-superconductor (SIS) type following the ideal sinusoidal relation between current and quantum phase. We demonstrate how the non-sinusoidal current-phase relation in Superconductor-Normal metal-Superconductor (SNS) and weak link (WL) junctions affects the speed, delay, and margin of the AQFP gates. The JJ models are defined in the Keysight ADS simulator using symbolically defined device (SDD) method.

13.
bioRxiv (Bioinfo) 2026-06-14

Structural Analysis of Prostate Cancer N-Glycans Using Graph-Based Structural Metrics

The N-linked glycans are structurally complex carbohydrate modifications that regulate protein folding, immune recognition, and cellular signaling, and their expression is extensively remodeled during cancer progression, making them promising biomarkers. In this study, prostate cancer-associated N-glycans from a range of relevant peer-reviewed studies were curated and digitized to develop a versatile computational framework that quantitatively encodes their spatial complexity across diverse biological systems. We invented two indices – the Distance & Connectivity Index (DCI) and the Position & Composition Index (PCI) – to capture the spatial information in N-glycans as layered architectures, enabling calculation of residue-level path lengths, branching structure, and compositional diversity. DCI summarizes glycan structure as both a scalar and matrix representation, while PCI does the same but also captures monosaccharide diversity, linkage heterogeneity, and cross-layer branching features. These metrics were computed with GlycoAssessor, an open-source platform that extracts information for the DCI and PCI from glycans drawn via Symbol Nomenclature for Glycans (SNFG) notation. Principal Component Analysis (PCA) was applied to evaluate whether glycans from prostate cancer tissues cluster distinctly in a disease-relevant manner. Results show that the spatial information in N-glycans: (1) increased in a multi-dimensional, non-linear manner, (2) objectively segregated structural themes, (3) could function as a potential prostate cancer biomarker that is distinct from mass-to-charge ratio and relative abundance, and (4) could objectively quantify novel subtype classifications of glycans associated with disease states and progression.

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

Cascaded Sparse Autoencoders Learn Multi-Level Visual Concepts in Multimodal LLMs

Multimodal Large Language Models (MLLMs) have demonstrated strong performance on vision-language tasks, yet their internal visual representations remain difficult to interpret. Sparse Autoencoders (SAEs) provide a scalable way to decompose dense model activations into sparse, interpretable features. However, existing SAE architectures primarily recover flat feature dictionaries and are less suited for explicit multi-level concept organization. In this paper, we introduce cascaded sparse autoencoders (CSAEs) for learning hierarchical visual concepts in MLLMs. Rather than nesting or stacking SAE sparse activation codes, CSAEs train a second-level SAE directly on the decoder weights of the first-level SAE, treating learned low-level feature directions as inputs for higher-level abstraction. This design enables CSAEs to learn "concepts of concepts" while avoiding drawbacks from the shared-prefix coupling of nesting, Matryoshka-style hierarchies and the bottlenecks of naively stacked SAEs. Experiments across Qwen3-VL, Gemma-3, and LLaVA on multiple visual datasets show that CSAEs improve interpretability in terms of hierarchical concept coherence over state-of-the-art SAE baselines. Results on concept steering further demonstrate that the learned concept groups support effective group-level interventions in MLLM outputs.

15.
arXiv (CS.CV) 2026-06-17

AnnotateAnything: Automatic Annotation of 3D Assets for Robot Manipulation

Simulation enables scalable robot data collection, but raw 3D assets provide only geometry, lacking the semantic, interactive, and physical knowledge needed to specify where and how robots should act. In this work, we present AnnotateAnything, a general automatic annotation framework that converts passive 3D assets into manipulation-ready assets with structured, diverse, and executable manipulation labels. AnnotateAnything is built around two complementary pipelines. First, a unified visual-language annotation pipeline using vision-language reasoning to infer object semantics, interaction constraints, and 3D-grounded cues, providing human-prior guidance for identifying meaningful interaction regions. Second, a fully automatic and massively parallel physics annotation pipeline grounds these priors in each asset's geometry and physical constraints through candidate generation, geometry optimization and trajectory generation. This pipeline produces diverse and executable action annotations, including grasp poses, dexterous contacts, articulation waypoints, insertion directions, hanging affordances, and navigation targets. Using the generated annotations, we further build an asynchronous parallel simulation data-collection system across diverse objects, tasks, and robot embodiments. Experiments demonstrate that AnnotateAnything achieves superior annotation efficiency, data-collection efficiency, and task success rates over existing annotation and data-generation pipelines, while also supporting downstream tasks such as affordance detection, robotic VQA, and visual instruction finetuning. We provide project materials on the project page and plan to release the full code, annotations, and benchmark to facilitate future research. Videos, code, demo assets, and annotations are provided in supplementary materials Project page: https://tourmaline-caramel-169490.netlify.app.

16.
PLOS Medicine 2026-06-04

Comparative impacts and cost-effectiveness of tuberculosis systematic screening strategies in prisons in Brazil, Colombia, and Peru: A mathematical modeling study

作者:

by Yiran E. Liu, José Victor Bortolotto Bampi, Ronan F. Arthur, Argita D. Salindri, Caroline Busatto, Pedro Avedillo Jiménez, Daniele Maria Pelissari, Fernanda Dockhorn Costa Johansen, Robert Arana-Narvaez, Alvaro Fernando Moreno Roca, Wilfredo Santos Solís Tupes, Esther Mori Jiu, Christian Alfredo Moreno Roca, Erika Albertina Abregú Contreras, Valentina Antonieta Alarcón Guizado, Julián Trujillo Trujillo, Belkys Marcelino, Mónica Alonso Gonzalez, Mayra Cecilia Córdova Ayllon, Ted Cohen, Moises A. Huaman, Jeremy D. Goldhaber-Fiebert, Julio Croda, Jason R. Andrews Background Incarceration is a leading driver of tuberculosis in Latin America. Systematic screening in prisons may reduce tuberculosis burden, but optimal strategies and cost-effectiveness remain uncertain. We examined the population-wide health impacts and cost-effectiveness of systematic screening in prisons in Brazil, Colombia, and Peru, comparing different timepoints, frequencies, and screening algorithms. Methods and findings Using dynamic transmission models calibrated to Brazil, Colombia, and Peru, we simulated annual or biannual (twice-yearly) prison-wide screening, alone or combined with entry and exit screening from 2026 to 2035. We evaluated four algorithms: (1) symptom screening, (2) chest X-ray with computer-aided detection (CXR-CAD), (3) symptoms and CXR-CAD (follow-up testing if either is positive), and (4) GeneXpert Ultra (Xpert) with pooled sputum. Individuals screening positive then received individual Xpert. We projected impacts on within-prison and population-level tuberculosis incidence in 2035, along with discounted costs (2023 US dollars) and disability-adjusted life years (DALYs). Model projections showed that combined entry, exit, and biannual screening with CXR-CAD was highly impactful and cost-effective across countries, reducing tuberculosis incidence by 61%–87% in prisons and 18%–28% population-wide. Compared to only biannual CXR-CAD (the next best strategy), the incremental cost per DALY averted of adding entry and exit screening was $2,984 (Brazil), $2,925 (Colombia), and $645 (Peru). Adding symptom screening to CXR-CAD marginally increased benefit and was only cost-effective in Peru’s higher-incidence prisons. Biannual screening alone remained cost-effective at prison incidence levels well below national averages, as well as at far lower willingness-to-pay thresholds. In settings without CXR-CAD, pooled Xpert was an impactful, cost-effective alternative. Key limitations include the model’s simplified representation of tuberculosis disease states and lack of stratification by age, gender/sex, HIV, or drug resistance. Conclusions These modeling results support immediate national-level adoption of prison-wide tuberculosis screening twice-yearly and at entry and exit, using CXR-CAD or pooled Xpert.

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

Afrispeech Semantics: Evaluating Audio Semantic Reasoning in Spoken Language Models Across Domains and Accents

Audio language models (ALMs) are increasingly used for speech-based understanding, yet their ability to perform semantic reasoning beyond transcription, Text-to-Audio Retrieval, Captioning, and Question-Answering accuracy remains insufficiently benchmarked. In particular, the effects of accent variation, domain shift, and semantic over-inference on audio reasoning are poorly understood. We evaluate audio language models across five semantic and paralinguistic reasoning tasks: entailment, consistency, plausibility, accent drift, and accent restraint. Collectively, these tasks assess a model's ability to reason over spoken audio as the primary evidence source, including whether a textual hypothesis can be inferred, contradicted, or left undetermined by the audio, whether statements align or conflict with spoken content, whether claims are plausible given the discourse, and whether model predictions remain stable or appropriately constrained across accent variation. These findings highlight critical limitations in current audio reasoning evaluations and hope to provide guidance for more robust and equitable ALM design and assessment

18.
medRxiv (Medicine) 2026-06-18

Maternal and fetal HLA heterozygosity in preeclampsia: Insights from a large multi-ancestry pregnancy cohort

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic human leukocyte antigen (HLA) region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4,770 PE, 8,020 controls; 10,808 maternal, 1,982 fetal, including 1,848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (>80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across class I loci showed a protective effect in preterm PE (OR=0.82, 95%CI:0.69-0.97), with a similar pattern for HLA-A heterozygosity (OR=0.78, 95%CI:0.64-0.96). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR=1.36, 95%CI:1.03-1.79) and preterm PE (OR=1.73, 95%CI:1.13-2.73). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE etiology.

19.
PLOS Computational Biology 2026-06-22

Cell-type resolved transcriptional network analysis of <i>in vivo</i> cellular senescence following injury

作者:

by Alda Sabalic, Victoria Moiseeva, Andres Cisneros, Oleg Deryagin, Eusebio Perdiguero, Pura Muñoz-Cánoves, Jordi Garcia-Ojalvo Identifying the genetic correlates of complex phenotypes is a challenging task. Methods coming from the field of complex networks can help finding such molecular patterns, by revealing statistical associations among groups of genes that correlate with the phenotype. Here we study cellular senescence, a complex cell state whose molecular underpinnings are still under active investigation. We analyze cell type–resolved RNA sequencing data obtained from injured muscle tissue in mice, with a network-based approach that merges eigenvector centrality feature selection and community detection. Our analysis identifies genetic markers that had not been associated with senescence so far, which are validated with existing single-cell RNA sequencing data in a different type of tissue. The identified key genes belong to transcriptional pathways associated with established hallmarks of senescence, and thus can be interpreted as molecular correlates of such hallmarks. The method proposed here could be applied to any complex cellular phenotype even when only bulk RNA sequencing is available, provided the data is resolved by cell type.

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

FreeSonic: Training-Free Temporal-Aware Decoupled Attention for Precise Audio Editing

arXiv:2606.15186v1 Announce Type: cross Abstract: Text-to-audio (TTA) generation has made significant strides, yet achieving precise and consistent audio editing remains a major challenge. However, existing methods struggle to balance temporal consistency with background preservation. In this paper, we propose FreeSonic, a training-free framework leveraging the state-of-the-art Rectified Flow-based TangoFlux model. FreeSonic utilizes an optimized inversion-reverse process and joint text-audio attention maps for precise target segment extraction. For content editing, a novel scheduled attention decoupling confines modifications to target regions while preserving original acoustic context. Furthermore, task-oriented noise injection enhances versatility for tasks such as audio removal and non-rigid replacement. Extensive experimental results demonstrate that FreeSonic achieves a superior balance by providing a high-fidelity and efficient solution for precise and consistent audio editing. Project and demos: https://free-sonic.github.io/

21.
bioRxiv (Bioinfo) 2026-06-17

DesignMaster: A Multi-Conditional Diffusion Framework for Rational PROTAC Design

Motivation: Proteolysis-targeting chimeras (PROTACs) enable targeted protein degradation through ternary complex formation with E3 ubiquitin ligase. However, the rational design of PROTACs remains highly challenging due to limited structure-activity relationship data and the vast conformational diversity of linkers. Existing computational approaches can be broadly divided into structure-based ternary modelling methods and fragment-based linker generation models. Although these approaches have advanced PROTAC design, they typically neglect key physicochemical constraints and linker-length control during the generation process, causing the generated PROTACs to lack balanced structural properties required for effective ternary complex formation with drug-like characteristics. Results: To address these limitations, we propose DesignMaster, a diffusion-based generative framework that explicitly incorporates linker length and physicochemical properties as controllable conditioning signals. DesignMaster employs an E(3)-equivariant graph Transformer with a gated multi-condition fusion module to inject linker length and physicochemical constraints throughout the diffusion process, enabling fine-grained and constraint-aware molecular generation. Experiments on PROTAC-DB 2.0 and 3.0 demonstrate that DesignMaster outperforms state-of-the-art baselines, with a 3.2% improvement in validity and a 34.4% improvement in recovery. The Case study shows DesignMaster achieves a 51.78% reduction in RMSD when predicting the linker of PROTAC BCPyr targeting 6W7O, highlighting its potential for practical structure-guided PROTAC design. Availability: The source code and datasets are available at https://github.com/ABILiLab/DesignMaster.

22.
arXiv (CS.AI) 2026-06-17

ASTEROID: A Spatiotemporal Information Transformer for Forecasting Multi-Step Time Series of Molecular Dynamics

arXiv:2606.17668v1 Announce Type: cross Abstract: Molecular dynamics (MD) simulation is computationally demanding, particularly for large-scale systems requiring long-term analysis. Accurate forecast of the outcomes of a MD simulation is not only an attractive scientific challenge but also has substantial practical value. In this work, we developed a data-driven framework, termed ASTEROID (Advanced Spatiotemporal TransformER fOr Inferring Dynamics), that can directly predict multi-step atomic coordinates, avoiding conventional iterative integration. For this purpose, our ASTEROID reformulates MD trajectories as high-dimensional spatiotemporal sequences and integrates the Spatiotemporal Information (STI) Transformation equation into a Transformer architecture. The core innovation of ASTEROID lies in its ability to model multiscale spatiotemporal dependencies. In particular, for spatial dependencies, a local-global self-attention mechanism captures both short- and long-range interactions. For temporal dependencies, an encoder-decoder structure integrates global context with autoregressive forecasting. ASTEROID was evaluated on several quantum-mechanics derived molecular datasets. Our results indicate that ASTEROID achieved not only a higher level of accuracy in multi-step prediction than existing methods on various benchmarks, but also significantly reduced computational cost of conventional MD simulation. Moreover, the model supports iterative multi-step forecasting over an extended time scale. This work establishes a robust and generalizable data-driven paradigm for accelerating MD simulations.

23.
arXiv (CS.LG) 2026-06-18

On the Stability of Nonlinear Dynamics in GD and SGD: Beyond Quadratic Potentials

arXiv:2602.14789v2 Announce Type: replace Abstract: The dynamical stability of the iterates during training plays a key role in determining the minima obtained by optimization algorithms. For example, stable solutions of gradient descent (GD) correspond to flat minima, which have been associated with favorable features. While prior work often relies on linearization to determine stability, it remains unclear whether linearized dynamics faithfully capture the full nonlinear behavior. Recent work has shown that GD may stably oscillate near a linearly unstable minimum and still converge once the step size decays, indicating that linear analysis can be misleading. In this work, we explicitly study the effect of nonlinear terms. Specifically, we derive an exact criterion for stable oscillations of GD near minima in the multivariate setting. Our condition depends on high-order derivatives, generalizing existing results. Extending the analysis to stochastic gradient descent (SGD), we show that nonlinear dynamics can diverge in expectation even if a single batch is unstable. This implies that stability can be dictated by a single batch that oscillates unstably, rather than an average effect, as linear analysis suggests. Finally, we prove that if all batches are linearly stable, the nonlinear dynamics of SGD are stable in expectation.

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

Geometric obstructions to Lipschitz transport between weighted Hessian $\mathrm{CD}(\kappa,\infty)$ manifolds

arXiv:2606.11085v2 Announce Type: replace Abstract: We construct a weighted Riemannian manifold $(\mathbb R^2,g,\mu)$ satisfying $\mathrm{CD}(1/2,\infty)$, the curvature-dimension condition, with the following property: if $\gamma$ denotes a centered Gaussian measure on $\mathbb R^2$, then there is no Lipschitz map $T:(\mathbb R^2,\|\cdot\|) \to (\mathbb R^2,g)$ satisfying $T_\#\gamma=\mu$. Building on this, we prove a Weyl-type asymptotic law for the eigenvalues of the weighted Laplacian $-\Delta_{g,\mu}$ and show that they are asymptotically negligible when compared to the eigenvalues of $-\Delta_{\gamma}$. These results give strong counterexamples to two questions of E. Milman and complement the recent counterexample of Aryan.

25.
arXiv (CS.AI) 2026-06-16

Runtime Analysis of Cartesian Genetic Programming in Evolving Boolean Functions

arXiv:2606.15923v1 Announce Type: cross Abstract: Cartesian Genetic Programming (CGP) is among the practical and popular forms of Genetic Programming as it uses a graph-based representation of programs. This paper presents a first runtime analysis of CGP in evolving Boolean functions using complete training sets. We prove an asymptotic bound $O(n D^5)$ for the expected number of fitness evaluations of CGP to construct a conjunction of $n$ inputs using at most $D \geq n-1$ binary gates, a minimal function set, and even with a strict survival selection. When the non-strict selection is used, the bound is improved to $O(n D^4)$. Our analysis reveals interesting characteristics of CGP induced search, which have been only observed empirically. In particular, enabling the acceptance of equally good solutions, including those with connected gates non-contributing to fitness, can lead to a speedup, and consequently a better asymptotic time bound. In contrast to conjunctions, we also prove a negative result which shows that CGP requires exponential time to evolve an exclusive disjunction. Experiments evolving conjunctions complement our theoretical findings. The use of incomplete training sets is found to further reduce the average number of fitness evaluations while maintaining a good level of generalisation.