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01.

arXiv (CS.CL) 2026-06-19 DOI: arXiv:2606.19379

How Linear Is a Transformer Feed-Forward Block? Per-Block Linear Recoverability Is Learned, Not Architectural

作者:

Stuart Whipp↗

Transformer feed-forward networks (FFNs) are often treated as nonlinear stores of computation, yet how nonlinear a trained FFN block actually is has rarely been measured. We treat each FFN as a position-wise input-to-output map and split it into the exact least-squares linear approximation plus a residual. The held-out variance the closed-form linear map explains defines a block's linear recoverability (R^2_lin), an optimiser-free measure of its linearity. Across all twelve blocks of GPT-2, Pythia-160m, and llama-160m, R^2_lin is highly heterogeneous and non-monotone with depth, ranging from near-linear (>0.99) to strongly nonlinear (

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02.

arXiv (CS.LG) 2026-06-16 DOI: arXiv:2602.14154

A Penalty Approach for Differentiation Through Black-Box Quadratic Programming Solvers

作者:

Yuxuan Linghu↗Zhiyuan Liu↗Qi Deng↗

arXiv:2602.14154v3 Announce Type: replace Abstract: Differentiating through the solution of a quadratic program (QP) is a central problem in differentiable optimization. Most existing approaches differentiate through the Karush–Kuhn–Tucker (KKT) system, but their computational cost and numerical robustness can degrade at scale. To address these limitations, we propose dXPP, a penalty-based differentiation framework that decouples QP solving from differentiation. In the solving step (forward pass), dXPP is solver-agnostic and can leverage any black-box QP solver. In the differentiation step (backward pass), we map the solution to a smooth approximate penalty problem and implicitly differentiate through it, requiring only the solution of a much smaller linear system in the primal variables. This approach bypasses the difficulties inherent in explicit KKT differentiation and significantly improves computational efficiency and robustness. We evaluate dXPP on various tasks, including randomly generated QPs, large-scale sparse projection problems, and a real-world multi-period portfolio optimization task. Empirical results demonstrate that dXPP is competitive with KKT-based differentiation methods and achieves substantial speedups on large-scale problems. Our implementation is open source and available at https://github.com/mmmmmmlinghu/dXPP.

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03.

bioRxiv (Bioinfo) 2026-06-17 DOI: HASH:d8812c8582e5e570d59a82a72aa54231

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

作者:

Shi↗Liu↗Pan↗Hao↗Isbel↗Roy↗M. J↗Ng↗A. P↗Shang↗Li↗

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.

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04.

arXiv (CS.AI) 2026-06-17 DOI: arXiv:2606.17830

Functional Equivalence in Attention: A Comprehensive Study with Applications to Linear Mode Connectivity

作者:

Viet-Hoang Tran↗Vinh Khanh Bui↗Van-Hoan Trinh↗Tan Lai Ngoc↗Tan M. Nguyen↗

arXiv:2606.17830v1 Announce Type: cross Abstract: Neural network parameter spaces are inherently non-injective, as distinct parameter configurations can realize identical functions through functional equivalence. While this symmetry is well understood in classical fully connected and convolutional models, it becomes substantially more intricate in modern attention-based architectures. Existing analyses of multihead attention have largely focused on the vanilla formulation, overlooking positional encodings that fundamentally reshape architectural symmetries. In this work, we provide a formal study of functional equivalence in Transformers with positional encodings. Focusing on the two most widely used variants–sinusoidal and rotary positional encodings (RoPE)–we show that sinusoidal encodings preserve the equivalence structure of vanilla attention, whereas rotary encodings significantly reduce the symmetry group, thereby enhancing expressivity. This offers a principled explanation for the growing prominence of RoPE in practice. We further examine how positional encodings affect linear mode connectivity, and through an alignment algorithm, empirically demonstrate that the presence and variability of connectivity across Transformer settings crucially depend on the positional encoding.

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05.

arXiv (CS.AI) 2026-06-24 DOI: arXiv:2606.24808

Large-Language-Model Discovery of Quantum LDPC Codes through Structured Concept Evolution

作者:

Zidu Liu↗Florian Marquardt↗

arXiv:2606.24808v1 Announce Type: cross Abstract: Quantum computers could outperform classical machines on important problems, but only if the errors that pervade quantum hardware can be corrected at scale. Quantum low-density parity-check (qLDPC) codes offer a promising route to this goal by combining sparse parity checks with finite encoding rate and growing distance, but their construction remains a challenging discrete design problem. Here we introduce structured concept evolution (SCE), a search framework that pairs a large language model with a structured algebraic mutation grammar to discover lifted-product code families, a class of CSS qLDPC codes. Instead of asking the LLM to design codes from first principles, SCE evolves structured concepts consisting of algebraic specifications paired with executable programs that realize them, using hierarchical mutations that modify the group algebra, protograph geometry, or base space. Running SCE, we discover a diverse set of competitive code families, ranging from abelian constructions to families over non-abelian groups beyond those underlying standard designs such as bivariate-bicycle codes, and characterize them under code-capacity depolarizing noise with BP+OSD decoding. These results are obtained with lightweight models (GPT-5.4-mini and GPT-5.4-nano).

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06.

arXiv (CS.AI) 2026-06-19 DOI: arXiv:2606.20381

Rethinking Shrinkage Bias in LLM FP4 Pretraining: Geometric Origin, Systemic Impact, and UFP4 Recipe

作者:

Qian Zhao↗Kunlong Chen↗Changxin Tian↗Zhonghui Jiang↗Haitao Zhang↗Chaofan Yu↗Peijie Jiang↗Mingliang Gong↗Jia Liu↗Ziqi Liu↗Zhiqiang Zhang↗Jun Zhou↗…

arXiv:2606.20381v1 Announce Type: new Abstract: FP4 training promises substantial reductions in memory and computation cost for LLM pretraining, yet current FP4 hardware paths and recipes, including NVIDIA Blackwell/Rubin-class systems and AMD MI350-series GPUs, remain centered on E2M1 data elements. In this study, we identify a fundamental limitation of that choice: non-uniform formats such as E2M1 inherently suffer from Shrinkage Bias, a systematic negative rounding error caused by the geometric asymmetry of their representable bins. We show that this bias accumulates multiplicatively across layers and is amplified by the Random Hadamard Transform (RHT), providing a unified explanation for the training instability observed in existing E2M1-based FP4 recipes. In contrast, uniform grids (E1M2/INT4) bypass this grid-geometry error and better convert the improved bucket utilization from RHT into higher quantization quality. Based on this finding, we propose UFP4, a uniform 4-bit training recipe that applies RHT to all three training GEMMs while restricting stochastic rounding to dY alone. On Dense 1.5B, MoE 7.9B, and MoE 124B long-run pretraining, UFP4 consistently achieves lower BF16-relative loss degradation than strong E2M1-based baselines, supported by scaling-law analysis and ablation studies. Our results suggest that future accelerators should support E1M2/INT4-style uniform 4-bit grids as first-class training primitives alongside E2M1.

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07.

arXiv (CS.CL) 2026-06-24 DOI: arXiv:2501.11790

Benchmarking LLMs' Mathematical Reasoning with Unseen Random Variables Questions

作者:

Zijin Hong↗Hao Wu↗Su Dong↗Junnan Dong↗Yilin Xiao↗Yujing Zhang↗Zhu Wang↗Feiran Huang↗Linyi Li↗Hongxia Yang↗Xiao Huang↗

Recent studies have raised significant concerns regarding the reliability of current mathematics benchmarks, highlighting issues such as simplistic design and potential data contamination. Consequently, developing a reliable benchmark that effectively evaluates large language models' (LLMs) genuine capabilities in mathematical reasoning remains a critical challenge. To address these concerns, we propose RV-Bench, a novel evaluation methodology for Benchmarking LLMs with Random Variables in mathematical reasoning. Specifically, we build question-generating functions to produce random variable questions (RVQs), whose background content mirrors original benchmark problems, but with randomized variable combinations, rendering them "unseen" to LLMs. Models must completely understand the inherent question pattern to correctly answer RVQs with diverse variable combinations. Thus, an LLM's genuine reasoning capability is reflected through its accuracy and robustness on RV-Bench. We conducted extensive experiments on over 30 representative LLMs across more than 1,000 RVQs. Our findings propose that LLMs exhibit a proficiency imbalance between encountered and ``unseen'' data distributions. Furthermore, RV-Bench reveals that proficiency generalization across similar mathematical reasoning tasks is limited, but we verified it can still be effectively elicited through test-time scaling.

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08.

arXiv (CS.CL) 2026-06-16 DOI: arXiv:2606.15079

Ling and Ring 2.6 Technical Report: Efficient and Instant Agentic Intelligence at Trillion-Parameter Scale

作者:

Ang Li↗Ben Liu↗Bin Han↗Bin Hu↗Bin Jing↗Binbin Hu↗Bing Li↗Cai Chen↗Caizhi Tang↗Changxin Tian↗Chao Huang↗Chao Zhang↗…

Efficient and scalable agentic intelligence requires models that can deliver both low-latency responses and strong reasoning capabilities while remaining practical to train, serve, and deploy. In this report, we present Ling-2.6 and Ring-2.6, a family of models designed to address this challenge at scale. Ling-2.6 is optimized for instant response generation and high capability per output token, whereas Ring-2.6 is tailored for deeper reasoning and more advanced agentic workflows. Instead of training from scratch, we upgrade the Ling-2.0 base model through architectural migration pre-training and large-scale post-training. This upgrade is guided by a unified co-design of model architecture, optimization objectives, serving systems, and agent training environments, enabling improvements in both model capability and deployment efficiency. At the architectural level, we introduce a hybrid linear attention design that integrates Lightning Attention with MLA, improving the efficiency of long-context training and decoding. To further enhance token efficiency, we optimize capability per output token through Evolutionary Chain-of-Thought, Linguistic Unit Policy Optimization, bidirectional preference alignment, and shortest-correct-response distillation. For agentic capabilities, we propose KPop, a reinforcement learning framework designed to support stable training of Ring-2.6-1T on large-scale environment-grounded data. KPop improves training efficiency through asynchronous scheduling across coding, search, tool use, and workflow execution, enabling scalable learning from complex agent-environment interactions. Together, Ling-2.6 and Ring-2.6 provide a practical pathway toward efficient, scalable, and open agentic systems. We open-source all checkpoints in the 2.6 family to support further research and development in practical agentic intelligence.

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09.

arXiv (CS.AI) 2026-06-18 DOI: arXiv:2606.18327

Self-CTRL: Self-Consistency Training with Reinforcement Learning

作者:

Itamar Pres↗Laura Ruis↗Melat Ghebreselassie↗Belinda Z. Li↗Jacob Andreas↗

arXiv:2606.18327v1 Announce Type: cross Abstract: Language models (LMs) that faithfully describe their own behavior can more easily be audited, understood, and trusted by users. This paper describes Self-Consistency Training with Reinforcement Learning (Self-CTRL), a method that optimizes for consistency between a LM's self-explanations and behavior on related inputs by updating explanations to better predict behavior or updating behavior to better match explanations. We apply our method in two domains. First, we study a formal probabilistic reasoning task in which LMs must learn to imitate a family of biased samplers and evaluated on their ability to report the associated biases. We find that consistency training improves the correlation between self-reported and behaviorally-measured latent biases from $R^2=0.24$ to $R^2=0.64$ on a set of held-out distributions, matching the generalization of direct ground-truth supervision. Second, we study a constitutional AI domain in which LMs must describe when they will refuse or comply with user requests. Here, Self-CTRL produces rules that faithfully describe the model's behavior on held-out requests, improving the refusal predictions of a third-party auditor model from $36\%$ to $92\%$. In the other direction, behavior updates improve alignment, reducing HarmBench failure rate from $15.0\%$ to $0.5\%$ without substantially increasing refusal on harmless prompts. By aligning explanations and behavior, our work provides a general recipe for training AI models to be safer, more transparent, and more controllable.

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10.

arXiv (quant-ph) 2026-06-19 DOI: arXiv:2602.04550

Locally Gentle State Certification for High Dimensional Quantum Systems

作者:

Cristina Butucea↗Jan Johannes↗Henning Stein↗

arXiv:2602.04550v3 Announce Type: replace Abstract: Standard approaches to quantum statistical inference rely on measurements that induce a collapse of the wave function, effectively consuming the quantum state to extract information. In this work, we investigate the fundamental limits of locally-gentle quantum state certification, where the learning algorithm is constrained to perturb the state by at most $\alpha$ in trace norm, thereby allowing for the reuse of samples. We analyze the hypothesis testing problem of distinguishing whether an unknown state $\rho$ is equal to a reference $\rho_0$ or $\epsilon$-far from it. We derive the minimax sample complexity for this problem, quantifying the information-theoretic price of non-destructive measurements. Specifically, by constructing explicit measurement operators, we show that the constraint of $\alpha$-gentleness imposes a sample size penalty of $\frac{d}{\alpha^2}$, yielding a total sample complexity of $n = \Theta(\frac{d^3}{\epsilon^2 \alpha^2})$. Our results clarify the trade-off between information extraction and state disturbance, and highlight deep connections between physical measurement constraints and privacy mechanisms in quantum learning. Crucially, we find that the sample size penalty incurred by enforcing $\alpha$-gentleness scales linearly with the Hilbert-space dimension $d$ rather than the number of parameters $d^2-1$ typical for high-dimensional private estimation.

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11.

arXiv (CS.AI) 2026-06-19 DOI: arXiv:2606.19769

Data Standards for Humanoid Robotics: The Missing Infrastructure for Physical AI

作者:

Shaoshan Liu↗Xiugong Qin↗Xuan Wu↗Xuan Xia↗Ning Ding↗Jialu Liu↗Jie Tang↗

arXiv:2606.19769v1 Announce Type: cross Abstract: The scalability of humanoid robots will depend not only on models and hardware, but also on whether physical experience can accumulate across robots, tasks, organizations, and time. Drawing on the authors' work in developing ISO/WD 26264-1, Humanoid robot datasets – Part 1: General requirements, within ISO/TC 299/WG 16, this article argues that data standards are becoming foundational infrastructure for Physical AI. We develop three insights. First, humanoid robot data is embodied interaction data, not a collection of isolated digital samples; a useful dataset must preserve the relationship among robot body, action, task, scene, execution trace, and outcome. Second, its value depends on physical coherence: multimodal streams are reusable only when timing, coordinate frames, calibration, kinematics, units, and synchronization assumptions remain inspectable. Third, the main bottleneck is not only data scarcity, but non-cumulative data caused by high collection costs, data silos, and inconsistent evaluation. We argue that humanoid robot data standards address these bottlenecks by making embodied experience interpretable, shareable, traceable, and reusable. A general standard should provide horizontal infrastructure for lifecycle management, metadata, provenance, quality, versioning, and traceability, while capability-specific parts should define domain grammar for manipulation, locomotion, human-robot interaction, cognition, and future humanoid capabilities. As AI moves from screens into bodies, data standards must evolve from organizing digital information to structuring physical interaction.

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12.

arXiv (CS.CV) 2026-06-24 DOI: arXiv:2606.24253

TuringViT: Making SOTA Vision Transformers Accessible to All

作者:

Qiman Wu↗Hanlin Chen↗Lyujie Chen↗Rui Xin↗Jianlei Zheng↗Mingyuan Wang↗Jiahui Hu↗Da Zhu↗Yuecheng Ma↗Yuhua Wei↗Yizhao Wang↗Hua Zhou↗…

Modern VLMs and VLA systems commonly adopt off-the-shelf ViTs such as SigLIP2 as visual encoders, but diverse downstream requirements in latency, temporal modeling, and VLM integration often call for customized SOTA-level ViTs. Training such encoders remains beyond the reach of much of the community, as it requires massive image-text data, while standard softmax attention makes high-resolution or dynamic-resolution pretraining prohibitively costly and often forces low-resolution pretraining followed by post-hoc adaptation. TuringViT addresses these challenges with three key designs: Turing Linear Attention (TLA) for efficient sequence modeling, VISTA-Curation to construct supervision-rich image-video training data, and native dynamic-resolution pretraining that supports flexible inputs from the start and transfers seamlessly to downstream VLMs. As a result, TuringViT outperforms leading open-source ViT baselines with only 10% of the data, achieves stronger downstream VLM performance, and delivers substantially better latency scaling on high-resolution inputs. Our scaling-law analysis further shows that TuringViT continues to improve predictably with curated data scale, far from saturation. Its fast adaptation, hardware-friendly design, and efficient deployment have made it a unified visual foundation across XPeng's AI systems. More broadly, TuringViT provides a reproducible pipeline that dramatically lowers the cost for the community to train, customize, and deploy SOTA-level ViTs, moving toward making such Vision Transformers accessible to all.

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13.

medRxiv (Medicine) 2026-06-22 DOI: HASH:47a4cec2ba15812df4ec230d2bb6b20e

A Drug-Specific, Half-Life-Adjusted Framework for Classifying CNS-Active Systemic Therapy Exposure During and After Radiotherapy

作者:

Pari Mitre↗Drapkin↗Dohopolski↗

Clinical oncology datasets often store systemic therapy as a regimen label with a start date and an end date. Those records are clinically recognizable but can be analytically incomplete when the research question concerns whether a patient was exposed to a concurrent CNS-active drug (cCNS-aD) or an adjuvant CNS-active drug (aCNS-aD) around radiotherapy. Contemporary CNS-oncology studies usually define CNS activity by empiric drug lists and define concurrency by fixed calendar windows, although the literature shows substantial heterogeneity across both concepts. This paper proposes a generalizable framework for converting raw systemic therapy records into reproducible cCNS-aD and aCNS-aD variables, useful in subgrouping for clinical studies. The framework uses a transparent CNS scoring model based on three clinical evidence components: intracranial objective response rate, consensus CNS endorsement, and intrathecal route of administration. It then defines a pharmacokinetic exposure proxy as the recorded end date plus five half-lives. Concurrent exposure is classified by overlap with the radiotherapy interval, while post-radiotherapy exposure is classified by overlap with a prespecified post-RT attribution window. The framework separately identifies post-RT pharmacokinetic persistence and post-RT treatment initiation, allowing investigators to distinguish continued exposure from true adjuvant initiation. This is a methodological framework and reference implementation. Implementation audits and endpoint-specific sensitivity analyses remain necessary before use as a definitive exposure classifier

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14.

arXiv (CS.CV) 2026-06-19 DOI: arXiv:2606.19849

ViCoStream: Streaming VideoLLMs Can Run Beyond 100 FPS with Stage-Wise Coordinated Inference

作者:

Yang Tan↗Junlong Tong↗Linan Yue↗Hao Wu↗Pengfei Fang↗Xiaoyu Shen↗

Streaming VideoLLMs must continuously process incoming video while maintaining low query latency, making both video-ingestion throughput and query-time responsiveness critical for real-time deployment. Existing methods largely focus on accelerating individual modules, such as visual encoding, token pruning, or KV-cache compression, but provide limited insight into whether the resulting system can sustain real-time streaming performance. We formulate streaming VideoLLM inference as a coordinated pipeline spanning visual preprocessing, visual encoding, token dropping, and LLM prefilling/decoding. Building on this formulation, we propose ViCoStream (Video Coordinated Streaming), a stage-wise coordinated streaming framework that combines chunk-wise execution, CUDA-stream overlap, visual token control, bounded visual attention, and query-side retrieval to bound per-chunk computation and memory costs. We further provide a systematic study of bottleneck migration, revealing how chunk size, token retention, attention locality, and retrieval scope shape the throughput-accuracy trade-off. Experiments with Qwen2.5-VL-3B/7B-Instruct across multiple streaming benchmarks show that ViCoStream achieves 134 FPS video throughput and less than 50 ms TTFT on a single A100 GPU while maintaining accuracy close to full-history baselines.

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15.

arXiv (CS.AI) 2026-06-12 DOI: arXiv:2605.08116

The Safety-Aware Denoiser for Text Diffusion Models

作者:

Amman Yusuf↗Zhejun Jiang↗Mijung Park↗

arXiv:2605.08116v2 Announce Type: replace-cross Abstract: Recent work on text diffusion models offers a promising alternative to autoregressive generation, but controlling their safety remains underexplored. Existing safety approaches are geared toward autoregressive models and typically rely on post-hoc filtering or inference-time interventions. These are inadequate for effectively addressing safety risks in text diffusion models. We propose the Safety-Aware Denoiser (SAD), a safety-guidance framework in text diffusion models. The SAD modifies the iterative denoising process such that the text sample at the final denoising step is steered toward provably safe regions of the text space. This inference-time method can integrate safety constraints into the denoiser, avoiding computationally expensive retraining of the underlying diffusion model and enabling flexible, lightweight safety guidance. We evaluate the safety of the generated text using the SAD, with respect to hazard taxonomy, memorization, and jailbreak. Experimental results show that SAD substantially reduces unsafe generations while preserving generation quality, diversity, and fluency, outperforming existing methods. These results demonstrate that our safety guidance during denoising provides an effective and scalable mechanism for enforcing safety in text diffusion models.

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16.

arXiv (CS.LG) 2026-06-17 DOI: arXiv:2606.17659

Physics-Constrained Neural Networks for Improved Short-Term Weather Forecasting: A Case Study over the South Pacific

作者:

Egor Bugaev↗Fedor Buzaev↗Dmitry Efremenko↗Denis Derkach↗Fedor Ratnikov↗

arXiv:2606.17659v1 Announce Type: new Abstract: This study introduces enhancements to physics-constrained neural networks (PCNNs) that improve the accuracy and stability of hybrid short-term weather forecasting models. Building on the WeatherGFT architecture, three innovations are proposed. First, an upgraded numerical solver, combining a fifth-order weighted essentially non-oscillatory scheme (WENO-5), a beta-plane approximation, and subgrid-scale viscosity, permits a fourfold increase in the integration time step to 1200 s while reducing the daily mean squared error by up to 26%. Second, a unified autoregressive hybrid block replaces the original chain of 24 specialised modules, eliminating overfitting to specific lead times. Third, the physical core is integrated with two state-of-the-art neural backbones, resulting in PI-PredFormer and PI-IAM4VP. Evaluation on the WeatherBench South Pacific subset from 2000 to 2004 shows that these hybrids reduce root mean squared error at 1-12 h lead times by 8-22% compared to purely neural counterparts, while better preserving physical consistency. These results demonstrate that incremental refinement of hybrid components offers a practical route toward more accurate and efficient short-range weather forecasting.

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17.

PLOS Medicine 2026-05-26 DOI: HASH:7f406689d6b83c002181d9d5c56bb6c1

Requiring code sharing to strengthen transparency and trust in research

作者:

Helen Lumbard↗

by Helen Lumbard, Lauren Cadwallader, Devin Soper, on behalf of the PLOS Medicine Staff Editors PLOS Medicine has always championed open science and data transparency. Now, recognizing that code is as essential a research artifact as the data it analyzes, we are strengthening our code sharing policy to further ensure reproducibility and trust in the scientific record. Recognizing that code is as essential a research artifact as the data it analyzes, this Editorial outlines how PLOS Medicine is strengthening its code sharing policy to further ensure reproducibility and trust in the scientific record.

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18.

medRxiv (Medicine) 2026-06-24 DOI: HASH:b4751877bbc3e2075d6bc22f709847bc

Differential COVID-19 Outcomes Across Lysosomal Disorders

作者:

Byer↗B. K↗Butzin-Dozier↗McGrath↗B. M↗Muenzer↗Clarke↗Haendel↗M. A↗O'Neil↗S. T↗

Background Lysosomal disorders (LDs) are a heterogeneous group of rare inherited disorders characterized by multi-system involvement and high comorbidity burden, which raises concerns about severe COVID-19 outcomes. Conversely, because SARS-CoV-2 relies on endolysosomal pathways for cellular entry and replication, certain LDs may exert a protective effect against viral pathogenesis. Prior clinical evidence investigating LDs and severe SARS-CoV-2 infection has been limited by small sample sizes and inconsistent findings. Therefore, to resolve these conflicting biological hypotheses and estimate population-level outcomes, we conducted a large-scale retrospective cohort study using nationwide U.S. harmonized electronic health record data from the National Clinical Cohort Collaborative (N3C). This design utilized longitudinal records starting January 1, 2018, to evaluate COVID-19 infections captured between January 1, 2020, and July 11, 2024. Results The study included 16,380 individuals, comprising 5,460 patients with lysosomal disorders and 10,920 matched controls. Patients with LDs had significantly higher odds of COVID-19 hospitalization compared with controls (OR = 1.86, 95% CI: 1.70-2.04). Elevated odds were observed across the evaluated categories, but varied substantially. Notably, neurodegenerative LDs such as neuronal ceroid lipofuscinosis (OR = 9.32) and metachromatic leukodystrophy (OR = 2.33) remained associated with hospitalization after adjustment for comorbidities. Contrarily, the elevated odds for Fabry disease and Gaucher disease were no longer significant after adjustment. Mortality among hospitalized patients with LDs was comparable to that of matched controls (one-year survival: 82.1% vs 82.0%), suggesting that LD status does not independently worsen survival once hospitalization occurs. Conclusions Patients with LDs were at an increased odds of COVID-19 hospitalization, driven by a combination of elevated comorbidity burden and disorder-specific effects, which vary significantly across LD categories. This study clarifies that excess risk is concentrated in the transition to hospitalization. These patients may thus require personalized clinical care to mitigate the negative consequences of COVID-19.

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19.

medRxiv (Medicine) 2026-06-22 DOI: HASH:27e222c43fb222f9f6728da3d9ef5ed1

A Controlled Human Malaria Infection model for relapsing Plasmodium vivax

作者:

Duncan↗A. D. S↗Geraedts↗T. J. M↗Manlutac↗Baker↗E. C↗van Heerden↗J. K↗Roberts↗T. W↗Rigby↗…

Background Plasmodium vivax malaria relapses are a major source of morbidity and onward transmission of infection. The underlying mechanisms are poorly understood and current therapies sub-optimal. We examined the safety and feasibility of a controlled human malaria infection (CHMI) model for relapsing P. vivax. Methods We conducted an open-label, proof-of-concept, CHMI study of relapsing P. vivax. Healthy, malaria-naive, Duffy-positive adults aged 18-45 years with extensive CYP2D6 metaboliser phenotype and normal blood glucose-6-phosphate dehydrogenase (G6PD) levels were recruited in Oxford, UK. Mosquito-bite CHMI was performed in Nijmegen, The Netherlands, using Anopheles stephensi mosquitoes infected with PvW1, a clonal isolate of P. vivax from Thailand. All follow-up visits were conducted in Oxford, UK. Primary P. vivax infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine (80mg/480mg at 8, 24, 36, 48 and 60 hours). From Day 28 following CHMI, participants attended a fortnightly clinic for clinical review and qPCR blood sampling, with additional assessments performed for any reported symptoms. P. vivax relapse infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine as per primary infection. Definitive anti-malarial treatment with atovaquone-proguanil (1000mg/400mg once daily for three days) and primaquine (0{middle dot}5 mg/kg/day for 14 days) was administered six months following CHMI, regardless of parasitaemia or symptoms. The primary objective was to assess the safety, feasibility and frequency of relapsing P. vivax after CHMI. Remote follow-up (5 years) is ongoing. The study is registered with ISRCTN registry (ISRCTN48625883). Findings 20 participants were screened for eligibility from 21 January 2025. Five participants (median age 22 years) underwent CHMI (five infected mosquitoes per participant) on 15 April 2025. All participants developed primary P. vivax infection and experienced at least one relapse infection. Two participants experienced a second relapse. Overall incidence rate was 3{middle dot}6 relapse infections per person-year. Solicited adverse events were mild or moderate and there were no serious adverse events. Definitive anti-malarial treatment was administered to all participants. One participant experienced primaquine-induced methaemoglobinaemia, resolving with early discontinuation of treatment (total dose 5{middle dot}3 mg/kg). To date, more than six months after primaquine treatment, no further relapses have been recorded. Interpretation CHMI of relapsing P. vivax is safe and feasible, allowing exploration of the mechanisms underlying relapse infections and providing a platform for future anti-relapse efficacy studies. Funding European Union Horizon Europe programme and UK Research and Innovation (UKRI) via OptiVivax consortium; UK National Institute for Health and Care Research Biomedical Research Centre: Oxford; and UK Medical Research Council.

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20.

Nature (Science) 2026-06-24 DOI: HASH:7de4970ddb50064211c19d526d16a20f

Optical cooling by interfacial charge transfer in 2D heterostructures

作者:

Jiamin Lin↗

Optical refrigeration, or laser cooling of solids1, offers a cryogen-free route to temperature control for quantum and electronic systems. Existing progress2–8 relies on a phonon-assisted up-conversion photoluminescence approach, which remains constrained by stringent material and excitation requirements. Here we demonstrate a distinct route, interfacial-charge-transfer-driven optical cooling, in two-dimensional semiconductor heterostructures. Photo-excited carriers in WSe2 cross a type-II junction into MoSe2 or WS2, extracting lattice energy nonradiatively—through a phonon-assisted interfacial charge transfer process. Raman and photoluminescence measurements show prominent low-temperature signatures in the WSe2 layer, with transient absorption spectroscopy identifying a phonon-assisted, barrier-activated interlayer charge transfer. Molecular dynamics simulations show a prominent interfacial thermal resistance sustaining the temperature gradient. This barrier-mediated phonon extraction bypasses the need for near-unity quantum efficiency or resonant excitation, offering a promising strategy for cryogen-free refrigeration and thermal management in quantum, optoelectronic and nanoscale systems. Optical cooling in two-dimensional semiconductor heterostructures is demonstrated through phonon-assisted interfacial charge transfer, enabling cryogen-free thermal management without stringent quantum-efficiency requirements.

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21.

arXiv (CS.LG) 2026-06-16 DOI: arXiv:2602.03293

Anomaly Detection via Mean Shift Density Enhancement

作者:

Pritam Kar↗Rahul Bordoloi↗Olaf Wolkenhauer↗Saptarshi Bej↗

arXiv:2602.03293v2 Announce Type: replace Abstract: Unsupervised anomaly detection stands as an important problem in machine learning. Existing unsupervised anomaly detection algorithms rarely perform well across different anomaly types, often excelling only under specific structural assumptions. This lack of robustness also becomes particularly evident under noisy settings. We propose Mean Shift Density Enhancement (MSDE), a fully unsupervised framework that detects anomalies through their geometric response to density-driven manifold evolution. MSDE is designed as a general purpose anomaly detection framework, based on the principle that normal samples, being well supported by local density, remain stable under iterative density enhancement, whereas anomalous samples undergo large cumulative displacements as they are attracted toward nearby density modes. To operationalize this idea, MSDE employs a weighted mean-shift procedure with adaptive, sample-specific density weights derived from a manifold learning-based fuzzy neighborhood graph. We evaluate MSDE on an anomaly detection benchmark comprising 46 real-world tabular datasets, four realistic anomaly generation mechanisms, and six noise levels. Compared to 13 established unsupervised baselines, MSDE achieves consistently strong, balanced and robust performance for several standard classification metrics, at several noise levels and on average over several types of anomalies. These results demonstrate that displacement-based scoring provides a robust alternative to the existing state-of-the-art for unsupervised anomaly detection.

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22.

arXiv (CS.AI) 2026-06-17 DOI: arXiv:2606.18186

Kolmogorov Regression for Robust Diffusion Policies

作者:

Lekan Molu↗

arXiv:2606.18186v1 Announce Type: cross Abstract: Finite-dimensional (FD) diffusion policies exhibit temporal drift owing to discretization artifacts that degrade long-horizon performance (when deployed on physical systems). We introduce a backward Kolmogorov equation that lifts diffusion policies to a Cameron-Martin space – a subset of the Hilbert space. Essentially, replacing stochastic score matching with a deterministic boundary-value PDE problem. Our core innovation thrives on Gaussian measure theory whereupon the diffusion noise covariance operator is realized from a colored noise distribution which prescribes a notion of regularity on samples from the model at inference time. We train the diffusion model with a derived precision-weighted Cameron- Martin loss and a Kolmogorov residual is introduced as a PDE diagnostic during inference. These substitutions yield (i) convergence guarantees where the bound's constants depend on the effective rank of the kernel rather than action dimension, (ii) improved trajectory regularity via spectral weighting, and (iii) a deterministic failure detector without reward signals. Validation across two application domains demonstrates substantial improvements: on the PushT manipulation benchmark, the Cameron-Martin loss achieves a 17% improvement in maximum episode reward (0.95 vs. 0.78 for MSE) and 67.6% reduction in inter-step drifts during inference via the introduced residual magnitude. Similarly, on a 6-station manufacturing line with constant work-in-process (CONWIP) flow control, we achieve 28.4% lower RMSE than classical LSTM baselines; a high starvation-event recall (1.0 in test cycles), and effective bottleneck identification (Precision@1 = 1.0 in test set, 13x signal-to-noise ratio). We then certify the dispatch policies with Hamilton-Jacobi reachability theory which reduces deadlock events by 96% compared to uncontrolled dispatch over 100 simulated runs (351 events prevented).

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23.

arXiv (CS.LG) 2026-06-18 DOI: arXiv:2606.19147

On Local Population-Risk Certificates

作者:

Mingzhi Song↗

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.

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24.

arXiv (CS.LG) 2026-06-24 DOI: arXiv:2606.24340

Managing Task Execution for Unknown Workloads in Batteryless IoT: A Hardware-Agnostic Evaluation

作者:

Samer Nasser↗Henrique Duarte Moura↗Ritesh Kumar Singh↗Maarten Weyn↗Jeroen Famaey↗

arXiv:2606.24340v1 Announce Type: new Abstract: In recent years, the Internet of Things (IoT) paradigm has been shifting toward batteryless, energy-harvesting architectures. Sustaining reliable operation in these systems requires intelligent management of highly volatile stored energy. As edge applications grow in complexity, traditional energy-aware schedulers struggle with unpredictable workloads due to their reliance on static execution thresholds or pre-measured, hardware-specific task profiles. To overcome this, we propose two novel, hardware-agnostic dynamic scheduling strategies treating applications as a "black box," requiring no prior energy information: a model-free Reinforcement Learning (RL) agent and an on-the-fly Approximated Prediction (AP) method. We evaluate these methods against an adaptive task rate approach (AsTAR) and optimized static thresholds using a custom-built, physically accurate simulation framework driven by real-world solar data and dynamic LoRa transmission profiles. Rather than claiming universal superiority, our analysis exposes the distinct operational trade-offs of each method: the AP approach delivers lightweight, near-oracle task throughput; the RL agent provides tunable survival-execution balancing; and AsTAR excels at execution pacing across long energy gaps. Finally, we demonstrate that while these advanced strategies provide critical resilience for severely constrained systems with small capacitors, devices with larger energy buffers can efficiently rely on simpler, less computationally expensive static policies.

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25.

arXiv (CS.CV) 2026-06-16 DOI: arXiv:2606.15796

DifFRACT: Diffusion Feature Reconstruction and Attribution for Circuit Tracing

作者:

Artyom Mazur↗Nina Konovalova↗Aibek Alanov↗

Mechanistic interpretability seeks to explain neural network behavior by decomposing model computations into interpretable features and circuits. While transcoder-based circuit tracing has recently enabled detailed causal analyses of large language models, multimodal diffusion transformers for image generation remain comparatively opaque. We still lack tools for understanding how semantic information propagates across denoising steps and how text and image representations interact within double-stream MM-DiT architectures. Existing methods provide only partial insight: attention maps expose a limited view of token interactions, while sparse autoencoders can discover interpretable features but do not directly reveal how these features are transformed and composed through nonlinear MLP layers. In this work, we extend transcoder-based circuit tracing to multimodal diffusion transformers. We train timestep-conditioned transcoders that faithfully approximate the input-output behavior of MLP sublayers in FLUX.1[schnell]. By replacing MLPs with transcoders and linearizing the remaining computation, we obtain exact feature-to-feature attribution and recover compact, interpretable circuits. Empirically, our transcoders match or slightly outperform sparse autoencoders on the sparsity-faithfulness tradeoff. The resulting circuits reveal mechanisms underlying attribute binding and cross-stream semantic propagation, and provide causal explanations for systematic generation errors. Moreover, circuit-guided interventions are substantially more precise and effective than standard SAE-based steering. Our results demonstrate that transcoder-based circuit analysis is feasible for state-of-the-art diffusion transformers and provides a powerful framework for understanding and controlling multimodal generative models. The code is available at https://github.com/Artalmaz31/DifFRACT

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