Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (quant-ph) 2026-06-12

Spectral analysis of equilibration: information leakage in isolated quantum systems

arXiv:2606.12545v1 Announce Type: new Abstract: We develop a unified dynamical-spectral framework for equilibration in isolated quantum systems based on a subspace coarse-graining approach. Central to our formulation is the Leakage Fidelity Function (LFF), defined as the probability that a unitarily evolving state escapes the support of its initial subspace. This quantity provides a direct, operational measure of information flow and memory loss without invoking ensemble assumptions or perturbative arguments. We derive universal bounds on temporal fluctuations of the LFF, in terms of the spectral gap structure and the square of the effective dimension, evincing that large spectral delocalization suppresses fluctuations and guarantees equilibration on average. By introducing spectral power distributions and associated entropic measures, we establish a quantitative link between phase mixing, gap participation, and dynamical stability. We further investigate the equilibration timescale by connecting the LFF to quantum speed limits, thereby revealing the average time required for equilibration. Our results provide a state-dependent, geometrically transparent perspective on how spectral complexity and subspace information leakage jointly govern irreversibility in closed quantum many-body systems.

02.
arXiv (quant-ph) 2026-06-17

Quantum Routers: A Switching-Fabric Framework for Quantum-Native Forwarding

arXiv:2606.17773v1 Announce Type: new Abstract: Forwarding in quantum networks cannot be realized by directly transposing classical switching fabrics, since the no-cloning theorem and the quantum measurement postulate constrain the direct relay of quantum information while ruling out copy-based buffering and inspection. In this paper, we propose a switching-fabric framework for quantum routers based on multipartite entanglement. Specifically, we formalize the notion of an entanglement-based switching fabric, in which a graph state acts as the forwarding resource and entanglement forwarding is realized through local Pauli measurements. We translate the classical notions of blocking and non-blocking operation into structural conditions for entanglement-based fabrics, by deriving the edge-controlled (EC) design principle for non-blocking operation. We instantiate this principle through a monolithic EC crossbar and a modular Clos-type EC fabric, for which we characterize resource scaling and identify the regime where the modular design becomes more resource-efficient than the monolithic one. Finally, a forwarding-latency analysis establishes a fundamental distinction between matching-oblivious and matching-driven forwarding: the proposed EC fabrics realize all requested input-output entanglement links with constant forwarding depth under sufficient measurement parallelism, whereas matching-driven EPR-based fabrics exhibit latency that scales with the number of requested connections. The proposed framework provides a hardware-agnostic foundation for quantum-router switching fabrics.

03.
arXiv (CS.AI) 2026-06-19

Information Lattice Learning as Probabilistic Graphical Model Structure Learning

arXiv:2606.19366v1 Announce Type: cross Abstract: Information lattice learning (ILL) learns interpretable rules of a signal by alternately projecting the signal onto a partition lattice that encodes a hierarchy of abstractions and lifting selected rules back to the signal domain. When the signal is a probability mass function, we show the probabilistic rules learned by ILL admit a natural probabilistic graphical model (PGM) interpretation and develop this interpretation in detail. A partition in ILL induces a deterministic quotient variable, and a rule is the marginal law of that quotient variable. A rule set is therefore a collection of marginal constraints over interpretable abstractions. General lifting is the feasible family of all joint distributions satisfying those constraints, while special lifting chooses a maximum-ignorance reconstruction, implemented in ILL by an L2 uniformity principle closely related to maximum entropy. Under a Shannon-entropy lifting, the same constraints yield a log-linear factor graph whose factors are indexed by learned abstractions. The information lattice itself, however, is not a Bayesian network: its edges encode refinement and coarsening of abstractions, not conditional dependence. Thus ILL is best viewed as structure learning for interpretable constraint-based factor graphs over quotient variables. This view clarifies how ILL relates to graphical models and maximum entropy models, while suggesting new directions for inference, identifiability, and hybrid symbolic-probabilistic learning.

04.
arXiv (math.PR) 2026-06-12

Voronoi Percolation: Topological Stability and Giant Cycles

arXiv:2601.00793v2 Announce Type: replace Abstract: We study the topological stability of Voronoi percolation in higher dimensions. We show that slightly increasing p allows a discretization that preserves increasing topological properties with high probability. This strengthens a theorem of Bollobás and Riordan and generalizes it to higher dimensions. As a consequence, we prove a sharp phase transition for the emergence of i-dimensional giant cycles in Voronoi percolation on the 2i-dimensional torus.

05.
arXiv (CS.CL) 2026-06-16

Depth-Attention: Cross-Layer Value Mixing for Language Models

Self-attention selects information freely across the sequence, but across depth, Transformers merely add each layer's output to the residual stream, so later layers cannot selectively reuse earlier-layer representations. Recent cross-layer methods improve this flow but operate on hidden states outside attention, adding state beyond the key-value cache at inference–a cost that becomes increasingly salient as modern LLMs compress the cache with grouped-query and multi-head latent attention. We introduce Depth-Attention, which performs this selection inside the attention module itself: before a layer attends over the sequence, its query attends over the keys of earlier layers at the same token position and mixes their values into the value that self-attention then reads. Because Depth-Attention reuses the standard attention queries, keys, and value-cache slots, storing depth-mixed values in place of the original values, it adds no parameters and introduces no persistent inference state beyond the standard key-value cache–the same cache size as a vanilla decoder and less than hidden-state-based cross-layer methods. On Qwen3-style decoders at 1.5B and 3B parameters, Depth-Attention attains the lowest perplexity and the highest average downstream accuracy, improving over the vanilla Transformer by up to 2.3 accuracy points and surpassing strong cross-layer baselines in perplexity and average accuracy, while adding under 0.01% extra arithmetic FLOPs and no additional persistent inference state. The gains hold from 360M to 3B parameters and extend to looped Transformers.

06.
bioRxiv (Bioinfo) 2026-06-15

oxo-flow: compiled, memory-safe bioinformatics workflow orchestration

作者:

Bioinformatics analyses depend on workflow engines to coordinate dozens of computational tools across complex dependency chains. The most widely adopted engines-Snakemake, Nextflow, the Common Workflow Language (CWL), and the Workflow Description Language (WDL)-run on interpreted or just-in-time (JIT) compiled language runtimes, incurring hundreds of milliseconds of startup latency and providing no compile-time safety guarantees from the host language. We developed oxo-flow, a workflow engine written in Rust that compiles to a single native binary. On an Apple M5 processor, oxo-flow parses, validates, and dry-runs a production-scale workflow in roughly 22 milliseconds-before Snakemake or Nextflow have finished loading their runtime environments. Peak memory usage is 16 megabytes, representing six- to seven-fold reductions relative to Snakemake and Nextflow. Dry-run latency is essentially independent of workflow size: a hundred-fold increase in rule count adds approximately 0.4 milliseconds. oxo-flow integrates 31 command-line tools, a REST interface with 60 endpoints, an embedded web application, and native cluster submission into a single 10-megabyte binary. It provides per-rule environment isolation across seven backends, checkpoint-based fault tolerance with cryptographic output verification, and a formal installation and operational qualification protocol for regulated laboratory environments. Ten curated workflows and three demonstration pipeline repositories are available. oxo-flow is freely available under Apache License 2.0 at https://github.com/Traitome/oxo-flow.

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

StanceNakba Shared Task: Actor and Topic-Aware Stance Detection in Public Discourse

We present StanceNakba 2026, a shared task on stance detection in polarized social media discourse related to the Palestinian-Israeli conflict, organized as part of Nakba-NLP 2026 at LREC-COLING 2026. The task introduces two subtasks: Subtask A (Actor-Level Stance Detection), which classifies English social media posts as Pro-Palestine, Pro-Israel, or Neutral; and Subtask B (Cross-Topic Stance Detection), which identifies Favor, Against, or Neither stances in Arabic posts toward two conflict-related topics, normalization with Israel and refugee presence in Jordan. The task is grounded in an annotated dataset of 2,606 social media posts. A total of 7 teams participated in Subtask A and 6 teams in Subtask B. Participating systems primarily fine-tuned Arabic and multilingual transformer-based models, including MARBERT, AraBERT, and DeBERTa-v3 variants, with several teams employing cross-validation, ensemble methods, and topic-conditioned architectures. The best-performing systems achieved a Macro F1 of 0.9620 on Subtask A and 0.8724 on Subtask B, demonstrating that transformer-based approaches are highly effective for conflict-domain stance detection while highlighting persistent challenges in cross-topic generalization and neutral class prediction.

08.
arXiv (CS.CV) 2026-06-12

Masked and Predictive Self-Supervised Foundation Models for 3D Brain MRI

Self-supervised foundation models have shown strong promise in medical imaging. However, existing MRI foundation-model studies have primarily emphasized segmentation and dense prediction tasks, while systematic investigation of self-supervised foundation models for MRI-based disease detection remains limited. In this work, we investigate two major self-supervised pretraining paradigms for MRI-based disease detection: reconstruction-based learning via Masked Autoencoders (MAE) and predictive representation learning via Joint Embedding Predictive Architectures (JEPA). We study the role of auxiliary objectives by introducing a novel spectral-domain reconstruction loss for MAE to enhance sensitivity to fine-grained anatomical structure, and by integrating variance–covariance regularization (VCR) within our JEPA framework to encourage decorrelated latent representations. Our models are pretrained on heterogeneous single-contrast MRI volumes in a contrast-agnostic setting, without modality concatenation. Across five downstream disease detection tasks, our results highlight the importance of self-supervised objective design for medical foundation model pretraining, demonstrating that the downstream benefit of each objective is determined by its relevance to the task's structure. Specifically, spectral regularization yields the largest improvements when the downstream discriminative signal is characterized by strong high-frequency anatomical structures, while covariance regularization is most beneficial when discriminative information spans multiple decorrelated feature dimensions. MAE with spectral-domain supervision consistently achieves superior downstream performance for MRI-based disease detection. These findings suggest that self-supervised objectives in medical imaging encode specific biases, and their downstream benefit is fundamentally conditioned on the task's structure.

09.
arXiv (CS.AI) 2026-06-19

Execution-bound advisory automation for agentic AI: a reproducible AIBOM-driven CSAF-VEX framework

arXiv:2606.19390v1 Announce Type: cross Abstract: A protocol driven framework is presented that binds SBOM and AIBOM artefacts to deterministic environment capture and structured runtime telemetry. Exploitability is computed from declared artefacts, observed activation conditions, and enforced execution policies. CSAF VEX advisories are generated from combined static and runtime evidence, cryptographically signed, and validated through deterministic replay. Evaluation uses approximately 10000 component entries across synthetic Agentic AI workloads 50 to 5000 components, incorporating OSV, GitHub Advisory, KEV, and EPSS datasets.

10.
arXiv (CS.CV) 2026-06-12

Augmentation techniques for video surveillance in the visible and thermal spectral range

In intelligent video surveillance, cameras record image sequences during day and night. Commonly, this demands different sensors. To achieve a better performance it is not unusual to combine them. We focus on the case that a long-wave infrared camera records continuously and in addition to this, another camera records in the visible spectral range during daytime and an intelligent algorithm supervises the picked up imagery. More accurate, our task is multispectral CNN-based object detection. At first glance, images originating from the visible spectral range differ between thermal infrared ones in the presence of color and distinct texture information on the one hand and in not containing information about thermal radiation that emits from objects on the other hand. Although color can provide valuable information for classification tasks, effects such as varying illumination and specialties of different sensors still represent significant problems. Anyway, obtaining sufficient and practical thermal infrared datasets for training a deep neural network poses still a challenge. That is the reason why training with the help of data from the visible spectral range could be advantageous, particularly if the data, which has to be evaluated contains both visible and infrared data. However, there is no clear evidence of how strongly variations in thermal radiation, shape, or color information influence classification accuracy. To gain deeper insight into how Convolutional Neural Networks make decisions and what they learn from different sensor input data, we investigate the suitability and robustness of different augmentation techniques...

11.
arXiv (CS.CL) 2026-06-12

Keep Policy Gradient in Charge: Sibling-Guided Credit Distillation for Long-Horizon Tool-Use Agents

Long-horizon tool-use reinforcement learning can learn from outcome verification, but its trajectory-level advantage is broadcast across many reasoning, API, and answer tokens. Self-distillation promises a denser signal by reusing a policy's own rollouts or a privileged teacher. We show, however, that direct token-level self-distillation can silently destroy tool use: it rehearses teacher behavior without knowing which actions the verifier rewards, so useful skills and harmful shortcuts are amplified together. We introduce Sibling-Guided Credit Distillation (SGCD), which uses distillation for credit assignment rather than as a competing actor loss. Dynamic sampling produces mixed successful and failed sibling rollouts; an external LLM summarizes their contrast into a training-only stepwise credit reference; dense teacher/student divergence drives credit reassignment; and bounded detached credit weights reshape GRPO token advantages. The deployed student sees no external LLM, sibling evidence, or oracle. Across AppWorld and $\tau^3$-airline, SGCD improves over matched GRPO comparators: AppWorld TGC $42.9 \to 45.6$ on test_normal and $24.7 \to 27.0$ on test_challenge, and $\tau^3$-airline pass@1 $0.583 \to 0.602$.

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

The Hidden Power of Scaling Factor in LoRA Optimization

arXiv:2606.12883v1 Announce Type: new Abstract: In Low-Rank Adaptation (LoRA), the scaling factor $\alpha$ is often treated as a mere complement to the learning rate, yet its role in optimization remains poorly understood. In this paper, we reveal that the scaling factor $\alpha$ and the learning rate function differently, with $\alpha$ emerging as the dominant driver of effective optimization, delivering gains that cannot be replicated by learning rate scaling alone. Through the synergy of extensive empirical analysis and a theoretical Signal-Drift framework, we uncover three findings into LoRA's scaling mechanism: First, LoRA's spectral suppression smooths the optimization landscape, rendering standard hyperparameters overly conservative and creating an optimization gap. Second, when leveraging this smoothness to accelerate convergence, $\alpha$ outperforms the learning rate by amplifying the task signal without increasing the drift ratio. Third, the optimal scaling factor follows a sublinear relationship with the rank, well characterized by a square-root law with an unexpectedly large coefficient, revealing the insufficient scaling of existing rank-tied heuristics. Based on these insights, we propose LoRA-$\alpha$, a minimalist framework that restores $\alpha$ to its principled regime, making LoRA compatible with standard small learning rates. Extensive evaluations across diverse tasks demonstrate that LoRA-$\alpha$ consistently improves performance while streamlining hyperparameter search, unleashing the learning potential of LoRA.

13.
arXiv (math.PR) 2026-06-12

(Non)-hyperuniformity of perturbed lattices

arXiv:2405.19881v3 Announce Type: replace Abstract: We ask whether a stationary lattice in dimension $d$ whose points are shifted by identically distributed but possibly dependent perturbations remains hyperuniform. When $d = 1$ or $2$, we show that it is the case when the perturbations have a finite $d$-moment, and that this condition is sharp. When $d \geq 3$, we construct arbitrarily small perturbations such that the resulting point process is not hyperuniform. As a side remark of independent interest, we exhibit hyperuniform processes with arbitrarily slow decay of their number variance.

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

Co-PLNet: A Collaborative Point-Line Network for Prompt-Guided Wireframe Parsing

Wireframe parsing aims to recover line segments and their junctions to form a structured geometric representation useful for downstream tasks such as Simultaneous Localization and Mapping (SLAM). Existing methods predict lines and junctions separately and reconcile them post-hoc, causing mismatches and reduced robustness. We present Co-PLNet, a point-line collaborative framework that exchanges spatial cues between the two tasks, where early detections are converted into spatial prompts via a Point-Line Prompt Encoder (PLP-Encoder), which encodes geometric attributes into compact and spatially aligned maps. A Cross-Guidance Line Decoder (CGL-Decoder) then refines predictions with sparse attention conditioned on complementary prompts, enforcing point-line consistency and efficiency. Experiments on Wireframe and YorkUrban show consistent improvements in accuracy and robustness, together with favorable real-time efficiency, demonstrating our effectiveness for structured geometry perception. Our code is available at https://github.com/GalacticHogrider/Co-PLNet.

15.
arXiv (CS.CV) 2026-06-12

World Tracing: Generative Pixel-Aligned Geometry Beyond the Visible

Image-to-3D methods often trade off faithfulness and completeness: depth estimators are anchored to input pixels but stop at the visible surface, while image-to-3D models generate complete shapes that are often misaligned with the input. We introduce World Tracing, a generative pixel-aligned geometry representation that predicts 3D points aligned with observed pixels while completing geometry beyond the visible surface. For each input pixel, World Tracing predicts an ordered stack of camera-space 3D points, where the first layer represents the visible surface and subsequent layers represent front-to-back intersections with occluded surfaces. We instantiate this representation with a world-tracing diffusion transformer, WT-DiT, which treats multiple geometry layers as separate denoising tokens coupled through factorized and global attention. WT-DiT is trained with pixel-space flow matching and a mixed noise schedule that balances visible-surface reconstruction with occluded-geometry generation. World Tracing achieves strong performance on visible-surface reconstruction and complete geometry generation across object, scene, and dynamic benchmarks, outperforming both depth predictors and image-to-3D generators. It also preserves 2D-to-3D correspondence, enabling text-driven 3D scene editing, geometry-conditioned novel-view video synthesis, and training-free integration with textured-mesh generators.

17.
medRxiv (Medicine) 2026-06-19

A soluble bi-specific fusion protein for the improved expansion of human CD8+ CAR-T cells

The success of Chimeric Antigen Receptor (CAR) T cell therapy is heavily dependent on the quality of the final cellular product. Current expansion protocols often rely on reagents that require removal from cell culture media, posing logistical challenges in manufacturing, and can also lead to terminal differentiation. Here, we evaluate the use of a soluble, bead-free T cell activator, T cell expansion protein (T-CEP), as a streamlined alternative for generating potent CAR-T cells. Human T cells were activated with T-CEP or known T cell activators (Dynabeads and TransAct) and transduced with either CD19 or interleukin-13 (IL-13) mutein (tetravariant-13; TV-13)-based CAR lentiviral vectors. Our results demonstrate that T-CEP supports robust CAR-T cell expansion and achieves transduction efficiencies comparable to commercial reagents for both types of CAR-T cells. Notably, T-CEP significantly favored the expansion of CD8+ T cells, yielding an enhanced CD27+ phenotype and a lower CD4:CD8 ratio compared to TransAct. Cytotoxicity assays confirmed that T-CEP-expanded CAR-T cells possess cytolytic function equivalent to commercial reagents for both CARs, while exhibiting lower levels of inflammatory cytokine secretion. In summary, T-CEP represents a competitive alternative to existing expansion agents, as it does not require its removal during CAR-T manufacturing and generates a CD8+ dominant, less-differentiated phenotype without compromising efficacy.

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

TRACE: Learning to Compute on Circuit Graphs

arXiv:2509.21886v3 Announce Type: replace Abstract: Learning to compute, the ability to model the functional behavior of a circuit graph, is a fundamental challenge for graph representation learning. Yet, the dominant paradigm is architecturally mismatched for this task. This flawed assumption, central to mainstream message passing neural networks (MPNNs) and their conventional Transformer-based counterparts, prevents models from capturing the position-aware, hierarchical nature of computation. To resolve this, we introduce TRACE, a new paradigm built on an architecturally sound backbone and a principled learning objective. First, TRACE employs a Hierarchical Transformer that mirrors the step-by-step flow of computation, providing a faithful architectural backbone that replaces the flawed permutation-invariant aggregation. Second, we introduce function shift learning, a novel objective that decouples the learning problem. Instead of predicting the complex global function directly, our model is trained to predict only the function shift, the discrepancy between the true global function and a simple local approximation that assumes input independence. We validate this paradigm on various circuits modalities, including Register Transfer Level graphs, And-Inverter Graphs and post-mapping netlists. Across a comprehensive suite of benchmarks, TRACE substantially outperforms all prior architectures. These results demonstrate that our architecturally-aligned backbone and decoupled learning objective form a more robust paradigm for the fundamental challenge of learning the functional behavior of a circuit graph.

19.
arXiv (quant-ph) 2026-06-15

Tamed Feynman-Kac diffusion processes: Killing-branching intertwine

arXiv:2605.07824v2 Announce Type: replace-cross Abstract: Relaxation to equilibrium of a drifted Brownian motion is quantified by a transition probability density function, whose main (multiplicative) entry is an inferred Feynman-Kac kernel of the Schr\"{o}dinger semigroup operator. Although seemingly devoid of a natural probabilistic significance (except for its explicit path integral definition), the pertinent kernel relaxes to equilibrium as well. The implicit Feynman-Kac potential ${\cal{V}}(x)$, continuous, confining and bounded from below, may take negative values. If positive, ${\cal{V}}(x)$ can be interpreted as the killing rate of the decaying diffusion process. In case of relaxing F-K kernels the killing effects are tamed (often overcompensated). The taming inavoidably appears in conjunction with the existence of the negativity subdomains of ${\cal{V}}(x)$ in $R$. If locally ${\cal{V}}(x) < 0$, its sign inversion $- {\cal{V}}(x)$ can be interpreted as the branching (cloning, alternatively bifurcation) rate in the course of the other wise free random motion. The arising killed diffusion processes with branching, we interpret as the possible path-wise background of tamed (relaxing) Feynman-Kac diffusions. We present acomputer-assisted path-wise arguments, towards a consistency of the killing/branching taming scenario, for a number of nonlinear model systems in one space dimension. Special attention is paid to Feynman-Kac potential shapes in the double well form, where an analytic access to eigenvalues and eigenfunctions is scarce. Throughout the paper the dynamics refers to the positive real time. Since the Newton-type equations of motion for admissible classical trajectories have a Euclidean form (due to the sign inverted force term), we give a brief resume of a couple of their explicit solutions, without recourse to the Euclidean time intuitions, and the instanton lore of related quantum model systems.

20.
medRxiv (Medicine) 2026-06-16

Preventing postpartum depression through mitigating breastfeeding grief: A convergent parallel mixed methods study

Background: Women who did not meet their breastfeeding goals often experience breastfeeding grief (BG) and may be likely to have postpartum depression (PD). Furthermore, PD is nearly twice as common in African American (AA) women as in Non-Hispanic White women. No research exists on BG and its role in PD. This study examined the BG experiences of AA women and its possible contributions to PD symptoms. Methods: A convergent parallel mixed methods design was used. A purposive sample of 16 AA women with children aged 6 months to 2 years with BG participated in individual semi-structured interviews about their experiences of BG and completed an online survey including the Edinburgh Postnatal Depression Scale (EPDS). Qualitative and quantitative data were analyzed using reflexive thematic analysis and descriptive statistics, respectively. Both data were integrated using joint display of data and side-by-side comparison. Results: The mean age of participants was 29.5 years. Four meaning-based themes about BG were generated including: We looked forward to breastfeeding, But it did not go as expected, So we grieve, and These would have helped. From quantitative results, 87.5% of participants reported a history of PD symptoms and almost 44% had EPDS scores >11. All participants reported that experiencing BG contributed to their PD symptoms. Findings suggest that BG influenced PD symptoms in AA women without prior diagnosis of depression. Conclusions: Qualitative and quantitative findings from this novel exploratory study revealed an overlap that AA women with BG report PD symptoms. Clinicians should support women to achieve their breastfeeding goals to prevent BG and PD. Keywords: African American; Breastfeeding grief; Mental health; Mixed methods; Postpartum depression

21.
arXiv (CS.CL) 2026-06-17

Do Large Language Models Always Tell The Same Stories?

Recent advances in large language models (LLMs) have enabled the generation of high-quality prose, yet the question of whether these models are capable of generating diverse outputs remains contested. In this work, we investigate the diversity of LLM-generated stories through the framework of narrative similarity. Using a contrastive framework and a dataset of human-written stories and prompts from r/WritingPrompts, we collect narrative similarity judgments across 10 representative LLMs, utilizing both human evaluations and three different automatic annotation methods. Our findings reveal a consistent trend: LLM-generated narratives are consistently more similar to each other than human-written stories are. We demonstrate that frontier models in particular converge on a ``mean'' generic narrative that approximates individual human stories but lacks the collective diversity of human authors. Finally, we show that common mitigation strategies, including negative prompting and temperature scaling, fail to meaningfully address this homogeneity.

22.
medRxiv (Medicine) 2026-06-15

Long-read sequencing enables high-accuracy mitochondrial heteroplasmy detection in Parkinson's disease

Background: Low-frequency heteroplasmic mitochondrial DNA (mtDNA) variants are associated with aging and neurological diseases, including Parkinson's disease (PD). Targeted deep mtDNA sequencing using PacBio HiFi long reads has the potential to resolve heteroplasmy across the full mitochondrial genome with high accuracy. Methods: To validate Vega PacBio sequencing for detecting mtDNA heteroplasmy, we analyzed four predefined mixtures of two mtDNA haplotypes. We generated a single long-range PCR amplicon covering the entire mitochondrial genome. These amplicons were mixed at predefined ratios (minor mixture haplotype component: 5%, 2%, 1%, and 0.1%). Variant calling was performed using Mutserve2, and accuracy was assessed by calculating the F1 score from comparisons between expected and detected variants. Full-length mtDNA PacBio sequencing was applied to investigate heteroplasmy across fibroblast passages derived from five LRRK2 p.Gly2019Ser variant carriers (n=3 affected with PD and n=2 unaffected carriers). Changes in mtDNA heteroplasmy level and variant load were assessed longitudinally using a linear mixed model. Results: The single-amplicon approach enabled full-length haplotype resolution without amplification bias associated with overlapping PCR strategies. The F1 score of the predefined mixtures was 1.0 for heteroplasmy levels between 5% and 1% and remained high (0.91) at 0.1%. We detected n=10/62 variants discordant with the Illumina reference at the 0.1% mixture, but sensitivity remained very high at 1.00 in that mixture. Detected minor variants closely matched expected heteroplasmy levels, with average variant levels of 0.057 (5%), 0.022 (2%), 0.011 (1%), and 0.001 (0.1%). Across twelve fibroblast passages, we observed fewer mtDNA heteroplasmic variants ({beta}=-3.2, p=0.026). Increased heteroplasmic variant load over time was also associated with older age ({beta}=1.50, p=0.001) and PD affection status ({beta}=5.0, p=1.0 x 10-4) in LRRK2 variant carriers. Notably, we observed distinct patterns of heteroplasmic variants that either increased or decreased in heteroplasmy level across passages. Conclusion: PacBio HiFi sequencing, combined with a single-amplicon strategy, enables accurate full-length mtDNA heteroplasmy detection and longitudinal analysis, providing a valuable tool for studying mitochondrial variation and dynamics in disease.

23.
arXiv (CS.LG) 2026-06-19

A Solver-Free Training Method for Predict-then-Optimize

arXiv:2606.19587v1 Announce Type: cross Abstract: We propose a scalable method for training prediction (machine learning) models in the predict-then-optimize paradigm, where model outputs serve as coefficients for a subsequent linear optimization task. Directly minimizing the empirical decision regret is intractable for linear programming and combinatorial optimization since the decision mapping is piecewise constant, and the gradients are zero almost everywhere. While existing methods address this by smoothing the differentiation process, they suffer from scalability issues, since a computationally expensive solver call is required for every gradient evaluation. To address this, we propose a decision-focused learning pipeline based on a measure transformation principle, which yields a new surrogate loss that is completely optimization-solver-free during training. We establish theoretical guarantees, including Fisher consistency and excess risk bounds. Empirically, our method achieves decision quality competitive with state-of-the-art methods while reducing training time by orders of magnitude.

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

MegaFold: Efficient Training of Next-Generation 3D Attention Protein Models on Cross-Platform GPUs

arXiv:2506.20686v2 Announce Type: replace-cross Abstract: Recent advances in biomolecular modeling have been catalyzed by models such as AlphaFold3 (AF3), which introduce science-informed changes to the transformer architecture. Unlike transformers, a defining characteristic of AF3-style models is their 3D attention over 2D pairwise representations which produces tensors whose computation and memory costs scale cubically with sequence length. As a result, despite moderate parameter counts, AF3-style models are far more expensive to train than size-equivalent transformers, and are severely constrained by GPU memory capacity. Our characterization shows 3D attention fundamentally changes the training workload, causing massive 3D attention maps, complex inter-operator dependencies, kernel fragmentation, and heavy host-side data pipelines which differ substantially from LLM training, leading to poor utilization on modern GPU systems. Moreover, existing GPU optimizations do not adequately address these challenges due to complex cross-layer inter-operator dependencies introduced by 3D attention. Motivated by these challenges, we introduce MegaFold, a novel cross-platform system for efficient training of next-generation 3D-attention protein models. MegaFold combines a memory-efficient 3D-attention kernel, a communication-efficient sharding strategy for quadratic representations, fused operator implementations for critical execution paths, and a determinism-aware host-device pipeline that eliminates preprocessing stalls. Evaluation on both NVIDIA H200 and AMD MI250 GPUs shows that MegaFold enables training with up to 3.36$\times$ longer sequence lengths on 32 GPUs while reducing end-to-end execution time by up to 1.73$\times$ (NVIDIA) and 1.62$\times$ (AMD).

25.
Science (Express) 2026-06-18

Dynamic asymmetric strain imprinted into substrates by an oxide thin film | Science

作者: 未知作者

In film-substrate systems, the substrate role is often considered to be limited to providing static mechanical constraints. Dynamic film-substrate interactions when a structural change in the film modifies the substrate are generally disregarded. Using combined X-ray and electron microscopies, we observed that the electrically induced filament in a VO 2 film created strong asymmetric strain in the underlying Al 2 O 3 substate. This asymmetric substrate strain fed back into the film and defined the filament expansion direction, revealing the importance of film-substrate dynamic interactions in determining film functionality. Furthermore, the strain imprint propagated at least tens of microns deep into the substrate, exceeding the film thickness more than 200 times, potentially enabling substrate functionalization as an active mechanical coupling media in 3D-integrated microelectronics architectures.