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01.
arXiv (math.PR) 2026-06-17

Analysis of the asymmetric shelf shuffle

arXiv:2606.18047v1 Announce Type: new Abstract: In an asymmetric shelf shuffle, a deck of $n$ cards is dealt sequentially from the bottom and assigned one of the $m$ shelves uniformly at random. The card is placed at the top of the assigned shelf with probability $p$, and at the bottom of the assigned shelf with probability $(1-p)$. Analysis of the shelf shuffle has gained much attention recently, and the case $p=1/2$ was first treated by Diaconis–Fulman–Holmes [Ann. Appl. Prob. 23 (2013), no. 4, 1692–1720]. In this paper, we extend the analysis of the shelf shuffle to general $p\in (0, 1)$. In particular, we study the distribution of cycles, cycle lengths, number of descents, number of valleys, number of inversions, and the RSK shape of a permutation obtained from an asymmetric shelf shuffle. Our results extend the analysis of Diaconis–Fulman–Holmes to arbitrary $p$. Furthermore, our analysis of the distribution of descents and inversions is new even for $p=1/2$.

02.
arXiv (math.PR) 2026-06-17

Cutoff for asymmetric shelf shuffle

arXiv:2606.18039v1 Announce Type: new Abstract: A mechanical shuffler consists of $m$ shelves. A deck of $n$ cards, arranged in increasing order, is dealt from the bottom sequentially. Each card is assigned a shelf uniformly at random and placed on the top (bottom) of the existing pile with probability $p$ ($1-p$) independently. We refer to this as asymmetric shelf-shuffle. We find the law $\nu_{n, m}^{(p)}$ of the permutation induced by the asymmetric shelf-shuffle and show that the pair consisting of the number of descents and the number of valleys is a sufficient statistic. This generalizes a result of Diaconis, Fulman, and Holmes (Ann. Appl. Prob., 2013) corresponding to the case $p=1/2$. For $p=1/2$, Chen and Ottolini (ECP, 2025) established the cutoff in the total variation distance near $\lfloor n^{5/4}\rfloor$. We establish the cutoff for the asymmetric shelf shuffle. Let $\nu_n$ be the uniform measure on the set of all permutations $S_n$ of $\{1, \ldots, n\}$. For a fixed $p\neq 1/2$ and $c>0$, we show that \[\operatorname{TV}\left(\nu_{n, \lfloor cn^{3/2}\rfloor }^{(p)}, \nu_n\right)=1-2\Phi\left(-\frac{|2p-1|}{4\sqrt{3}c}\right)+O_{c, p}(n^{-1/2})\;.\] We also establish the cutoff in the separation distance near $m\approx n^{2}$ and in the relative entropy near $m=n^{3/2}$. In both cases, we also obtain the cutoff profile explicitly.

03.
arXiv (CS.AI) 2026-06-12

Prefill Awareness in Large Language Models

arXiv:2606.12747v1 Announce Type: new Abstract: Safety-relevant studies of language models, including alignment and jailbreaking evaluations and AI control protocols, often rely on prefilling model outputs. If AI models can recognize and act on the fact their prior assistant messages have been inserted or edited, the effectiveness and validity of these methods could be compromised. We investigate whether frontier language models can distinguish between tampered and untampered assistant-side context, a capability we call prefill awareness. To do so, we construct a binary preference benchmark across three prefill mechanisms, filtering for cases where models show consistent stances. We find that frontier models show substantial prefill awareness: Claude Opus 4.5 detects prefills opposing its preferences in 9-35% of cases with a 0% false positive rate when prompted; additionally, models often revert towards baseline behavior without explicitly reporting that the prefill was foreign. Controlled ablations later also show that detection and resistance rely on different cues, where stylistic mismatch mainly affects whether models flag a prefill as foreign, while preference mismatch mainly affects whether they revert toward their baseline answer. We also examine more realistic agentic settings such as misalignment-continuation evaluations and SWE-bench trajectories, where frontier models sometimes disavow prefilled assistant turns in ways that depend strongly on dataset, task success, and hidden formatting artifacts. Our results indicate that prefill awareness is already a substantial confound for some prefill-based methods. We recommend that model developers track this capability in frontier systems.

04.
arXiv (CS.LG) 2026-06-17

A Generalized Sinkhorn Algorithm for Mean-Field Schrödinger Bridge

arXiv:2604.06531v3 Announce Type: replace-cross Abstract: The mean-field Schrödinger bridge (MFSB) problem concerns designing a minimum-effort controller that guides a diffusion process with nonlocal interaction to reach a given distribution from another by a fixed deadline. Unlike the standard Schrödinger bridge, the dynamical constraint for MFSB is the mean-field limit of a population of interacting agents with controls. It serves as a natural model for large-scale multi-agent systems. The MFSB is computationally challenging because the nonlocal interaction makes the problem nonconvex. We propose a generalization of the Hopf-Cole transform for MFSB and, building on it, design a Sinkhorn-type recursive algorithm to solve the associated system of integro-PDEs. Under mild assumptions on the interaction potential, we discuss convergence guarantees for the proposed algorithm. We present numerical examples with repulsive and attractive interactions to illustrate the theoretical contributions.

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

Understanding, Detecting, and Repairing Real-World In-Context-Learning-Based Text-to-SQL Errors

Large language models (LLMs) have been adopted for text-to-SQL tasks, utilizing their in-context learning (ICL) capability to translate natural language questions into SQL queries. However, such a technique faces correctness problems. In this paper, we conduct the first comprehensive study of text-to-SQL errors of ICL-based techniques. Our study covers four representative ICL-based techniques, five basic repairing methods, two benchmarks, and two LLM settings. We find that text-to-SQL errors are widespread and summarize 27 error types of 7 categories. We also find that existing repairing attempts have limited correctness improvement while having high computational overhead and many mis-repairs. Based on these findings, we propose MapleDoctor, a novel text-to-SQL error detection and repairing framework. The evaluation demonstrates that MapleDoctor outperforms existing solutions by repairing 13.8% more queries with a negligible number of mis-repairs and reducing 67.4% repair latency. The artifact is publicly available at GitHub.

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

Beyond Uniform Tokens: Adaptive Compression for Time Series Language Models

Large language models (LLMs) have enabled time series (TS) analysis by jointly modeling numerical observations and textual context through a shared token interface. However, TS tokens and prompt tokens exhibit fundamentally different information structures, making uniform token processing inefficient. In this paper, we study token efficiency in TS language modeling from an asymmetric-token perspective. We show that TS tokens have highly uneven spectral contributions, where many tokens share redundant frequency patterns while a small subset preserves critical temporal evidence. We also observe that prompt-token influence attenuates with model depth, suggesting that full prompt retention across all layers is unnecessary. Based on these findings, we develop an adaptive token budgeting framework that compresses TS tokens via frequency-domain structure and progressively reduces prompt tokens across layers. Experiments across forecasting, classification, imputation, and anomaly detection demonstrate up to 7.68$\times$ inference acceleration and performance gains in 78\% of evaluated settings, showing the effectiveness of asymmetric token compression for scalable TS foundation models.

07.
arXiv (CS.AI) 2026-06-16

PrologMCP: A Standardized Prolog Tool Interface for LLM Agents

arXiv:2606.14935v1 Announce Type: new Abstract: Frontier reasoning-tuned language models still fail on deductive tasks at depth, and the cost of improved performance through extended internal reasoning scales poorly. Symbolic delegation offers a complementary route: a language model translates the problem, while a solver performs the inference. However, current autoformalization pipelines for logic programming are typically bespoke integrations tied to particular tasks or agents. We introduce PrologMCP, a task-agnostic, open-source server that exposes Prolog as a stateful tool through the Model Context Protocol (MCP). Its compact tool interface, structured error reporting, and per-session isolation make the translate-run-inspect-repair loop a reusable primitive for MCP-capable agents. We evaluate a formalizer agent enhanced with PrologMCP against standard and reasoning LLMs (Claude Sonnet 4.6, GPT-4.1, and o4-mini) on two subsets of PARARULE-Plus: a general-purpose sample and a more challenging one targeting a specific failure mode of natural-language reasoning. On the general sample, the formalizer matches or exceeds reasoning LLMs (accuracy 1.00 vs.\ 1.00 / 0.998), with the largest gains over standard models (0.762 for GPT-4.1). On the challenging subset, the formalizer remains near-perfect (1.00 / 0.99) while reasoning LLMs drop to 0.95 / 0.94. These results suggest that delegating inference to Prolog via MCP is a robust and inspectable alternative to extended natural-language reasoning.

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

Edit3DGS: Unified Framework for Dynamic Head Editing via 2D Instruction-Guided Diffusion and 3D Gaussian Splatting

We present Edit3DGS, a unified framework for dynamic 3D head editing that integrates 2D instruction-guided diffusion with 3D Gaussian splatting. Unlike prior approaches that separately address frame-based edits or static 3D reconstruction, our method couples semantic controllability in the image domain with photorealistic, temporally consistent 3D representations. Given an input video, editable facial regions are masked and modified using a text-conditioned diffusion model to support fine-grained operations such as expression transformation, attribute modification, and appearance refinement. The edited frames are then aggregated through 3D Gaussian splatting to produce a coherent, high-fidelity avatar that preserves both identity and motion dynamics. To enforce consistency, Edit3DGS incorporates multi-view batch editing and lightweight inpainting strategies that recover lost expressions across timesteps. Experimental results demonstrate that our framework enables controllable, artifact-free head editing with smooth temporal transitions, offering practical applications in virtual avatars, immersive communication, film production, and interactive media.

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

When to Trust, How to Distill: Multi-Foundation Model Guidance for Lightweight, Robust Scientific Time Series Forecasting

arXiv:2606.19363v1 Announce Type: new Abstract: The deployment of Time-Series Foundation Models (TSFMs) in physical sciences is hindered by a critical trade-off: while these models encode rich, universal temporal dynamics, they suffer from severe distributional misalignment when applied zero-shot to specific scientific domains, and their computational cost prohibits deployment in edge-computing sensor networks. We address a fundamental challenge: How can we extract latent structural knowledge from misaligned foundation models (FM) to train lightweight, specialized forecasters? We propose Gated Uncertainty-Aware Routing for Distillation (Guard), a novel framework that reframes multiteacher distillation as an instance-wise decision process with two adaptive mechanisms: (1) a Contextual Router that dynamically selects the most relevant teacher based on local input statistics, exploiting complementarity across diverse foundation models; and (2) an Uncertainty-Gated Temperature mechanism that acts as a "circuit-breaker," automatically attenuating distillation strength when teacher confidence diverges from domain reality. We evaluate our proposed lightweight framework on four climate-critical domains: meteorology, ecosystem carbon flux, soil moisture, and energy grids. Our method significantly reduces RMSE relative to a fixed-weight multi-teacher distillation baseline, successfully distilling knowledge from pretrained FMs (teachers) even when they exhibit suboptimal zero-shot accuracy due to distribution shift between the original and target data domains. We demonstrate that these domain-misaligned teachers can still serve as critical correctives, outperforming the globally superior FMs on 28.5% of the hardest instances. Ultimately, this enables high-precision scientific forecasting suitable for resource-constrained edge deployment. Code is available at https://github.com/RupasreeDey/GUARD-KDD2026.

10.
arXiv (CS.CV) 2026-06-11

Latent Geometric Chords for Query-Efficient Decision-Based Adversarial Attacks

While decision-based black-box adversarial attacks present a severe security threat, current methodologies suffer from fundamental limitations. Pixel-wise attacks frequently introduce unnatural, high-frequency visual artifacts, while latent-space frameworks are confined by the limited search space of low-dimensional manifolds and inherent reconstruction flaws. To resolve these limitations, we propose Latent Geometric Chords (LGC) for Query-Efficient Decision-Based Adversarial Attacks alongside a variant, LGC-H. At its core, LGC navigates decision boundaries by executing a curvature-aware geometric search within a compressed semantic manifold. To guarantee high visual fidelity and circumvent dimensionality bottlenecks, we introduce a Residual-based Adversarial Generation (RAG) mechanism. RAG isolates semantic perturbations as geometric chords and superimposes them directly onto the original source image. RAG substantially resolves baseline reconstruction flaws and effectively doubles the permissible search space dimensions. Experimental results demonstrate that LGC achieves robust cross-dataset transferability and substantially outperforms state-of-the-art baselines. Notably, our method, LGC, minimizes perturbation magnitudes while achieving state-of-the-art visual fidelity–with a Structural Similarity Index Measure (SSIM) exceeding 0.99 and a Learned Perceptual Image Patch Similarity (LPIPS) below 0.01 at 5000 queries–and sustaining high attack success rates under stringent perceptual constraints, successfully compromising adversarially trained robust models. The source code is available at: https://github.com/eihmuekhine/Latent-Geometric-Chords.

11.
arXiv (CS.LG) 2026-06-19

MassSpecGym in the Wild: Uncovering and Correcting Evaluation Pitfalls in AI-Driven Molecule Discovery

arXiv:2606.19624v1 Announce Type: new Abstract: Reliable benchmarking is critical for developing machine learning models for tandem mass spectrometry (MS/MS) based molecule discovery. Subtle issues in experimental design and model evaluation procedures can degrade the trustworthiness of such benchmarks and lead to erroneous conclusions. We conduct a thorough review of model evaluation issues in the recent MS/MS machine learning literature, using the standard MassSpecGym benchmark suite as a case study to illustrate the impact of these issues. We find evaluation issues in at least 17 of 26 papers reporting MassSpecGym benchmark results in the first year of its adoption. We isolate three classes of failures: (i) data leakage, (ii) shortcut learning, and (iii) implementation bugs and metric divergence. Through extensive experimentation and code replication, we quantify the impact of these issues and show how they corrupt the evaluation standards MassSpecGym was designed to enforce. We distill our findings into recommendations generalizable to MS/MS challenges, benchmarks, and custom evaluation setups. We also release MassSpecGym v1.5, an implementation of our recommendations in the MassSpecGym benchmarking suite which addresses the failure modes identified in this audit. MassSpecGym v1.5 is publicly available at https://github.com/pluskal-lab/MassSpecGym.

12.
arXiv (CS.LG) 2026-06-16

How to Score Experts for One-Shot MoE Expert Pruning: A Unified Formulation and Selection Principle

arXiv:2606.15716v1 Announce Type: new Abstract: Mixture-of-Experts (MoE) language models reduce per-token computation through sparse expert activation, yet deployment still requires storing the full expert pool, making one-shot expert pruning a practical approach for reducing memory usage. Although effective, existing criteria are largely heuristic, and no single criterion is universally optimal. Thus, establishing a principle for selecting pruning criteria suited to different deployment objectives remains an important yet largely underexplored problem in one-shot expert pruning. To this end, we introduce a unified formulation for one-shot MoE expert pruning organized around three factors: routing frequency, gate weighting, and activation strength. The formulation yields a criteria selection principle: task-agnostic pruning should favor routed-token-averaged, gate-free activation-based criteria, whereas task-specific pruning can benefit from retaining routing-frequency and gate-weight information. Beyond this principle, the formulation also provides a systematic view of existing heuristic criteria and gives rise to two new task-agnostic criteria, Mean Activation Norm (MAN) and Mean Squared Activation Norm (MSAN). Across four representative MoE models and 16 diverse benchmarks, MAN and MSAN are consistently strong in the task-agnostic setting, obtain the top-two average ranks, and improve average performance by up to 8.8 points over the strongest baseline.

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

On the Residual Scaling of Looped Transformers: Stability and Transferability

arXiv:2606.18524v1 Announce Type: new Abstract: Looped (weight-tied) Transformers apply a shared residual block $N$ times ($h \leftarrow h + \varepsilon\,f(h)$, same $f$ at each step), increasing effective depth without adding parameters. Prior depth-scaling analyses prescribe $\varepsilon = 1/\!\sqrt{L}$ for depth-$L$ residual networks. We show that this is insufficient for looped architectures: weight sharing makes residual updates correlated across iterations, requiring the stronger scaling $\varepsilon = 1/N$. For multi-layer blocks ($L$ unique layers looped $N$ times), we derive a factored parameterization $\varepsilon = \lambda/(N\!\sqrt{L})$ that separates the two sources of growth: $1/N$ controls the within-layer loop correlation, and $1/\!\sqrt{L}$ controls the across-layer variance. A key consequence is that the optimal learning rate depends only on the number of unique layers $L$, not on the loop count $N$, enabling direct hyperparameter transfer from small to large $N$ without retuning. Experiments on looped Transformers confirm that $1/N$ scaling improves trainability and yields better loss than $1/\!\sqrt{N}$ scaling across loop counts.

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

The Vision Encoder as a Privacy Boundary: Visual-Token Side Channels in Encoder-Free Vision-Language Models

A vision encoder compresses image pixels into semantic embeddings, implicitly acting as a privacy boundary by preserving semantic content while attenuating pixel-local detail required for exact text recovery. Encoder-free vision-language models (VLMs) remove this boundary by routing image patches directly into the language-model token stream, thereby exposing an architectural privacy attack surface: intermediate visual tokens become a pre-output side channel. Under a token-access adversary, decoders invert visual-token streams from two encoder-free VLMs, Gemma4 and Fuyu, recovering recognizable image structure and readable held-out access codes, whereas matched encoder-based controls localize target regions but recover no exact strings. Within-model ablations show that the operative factor is spatial sampling fidelity of the visual-token grid, especially character-direction sampling density, rather than token or value count. The leakage is not limited to exported tokens: Gemma4 layer-0 key-value cache tensors are directly invertible, placing the side channel within KV caches commonly persisted by production serving stacks for decoding efficiency. The attack survives clutter, realistic document degradation, and zero-shot transfer to public document images, and it resists value-level defenses such as additive noise and quantization. Effective mitigation must therefore reduce spatial sampling, making removal of the vision encoder a first-class privacy decision in VLM deployment.

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

NOVA: NOise-aware Verbal Confidence CAlibration for Robust Large Language Models in RAG Systems

Accurately assessing model confidence is essential for deploying large language models (LLMs) in mission-critical factual domains. While retrieval-augmented generation (RAG) is widely adopted to improve grounding, confidence calibration in RAG settings remains poorly understood. We conduct a systematic study across four benchmarks, revealing that LLMs exhibit poor calibration performance especially when noisy contexts are retrieved. Specifically, contradictory or irrelevant evidence tends to exacerbate the model's overconfidence issue. To address this, we propose NOVA Rules (NOise-Aware Verbal Confidence CAlibration Rules) to provide a principled foundation for resolving overconfidence under noise. We further design NOVA, a noise-aware calibration framework that synthesizes supervision from ~2K HotpotQA examples guided by these rules. By performing supervised fine-tuning (SFT) with this data, NOVA equips models with intrinsic noise awareness without relying on stronger teacher models. Empirical results show that NOVA yields substantial gains, improving ECE scores by 10.9% in-domain and 8.0% out-of-domain. By bridging the gap between retrieval noise and verbal calibration, NOVA paves the way for both accurate and epistemically reliable LLMs.

16.
arXiv (CS.AI) 2026-06-17

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

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.

17.
arXiv (CS.CL) 2026-06-16

Symbolic Informalization: Fluent, Productive, Multilingual

作者:

Symbolic informalization enables a reliable conversion of formal mathematics to natural language. It has the potential to make machine-checked content human-readable without loss of precision. In a traditional proof system usage, symbolic informalization generalizes the limited mechanisms of syntactic sugar into the ordinary language of mathematics. In a setting where proofs are constructed by artificial intelligence and autoformalization, symbolic informalization can explain what precisely has been constructed. This paper outlines the project Informath, which aims to show how symbolic informalization can produce fluent text with a reasonable development effort and address multiple formal and natural languages. Informath is based on an interlingual architecture, where Dedukti works as a hub between different proof systems (Agda, Lean, Rocq) and Grammatical Framework (GF) takes care of linguistic correctness and variation in different natural languages.

18.
arXiv (CS.CV) 2026-06-16

Learning Fine-Grained Correspondence with Cross-Perspective Perception for Open-Vocabulary 6D Object Pose Estimation

Open-vocabulary 6D object pose estimation empowers robots to manipulate arbitrary unseen objects guided solely by natural language. However, a critical limitation of existing approaches is their reliance on unconstrained global matching strategies. In open-world scenarios, trying to match anchor features against the entire query image space introduces excessive ambiguity, as target features are easily confused with background distractors. To resolve this, we propose Fine-grained Correspondence Pose Estimation (FiCoP), a framework that transitions from noise-prone global matching to spatially-constrained patch-level correspondence. To systematically eliminate background interference, FiCoP first employs an object-centric disentanglement step to isolate the target from macro-level environmental noise. Building upon this localized region, our core methodological innovations are twofold. Firstly, a Cross-Perspective Global Perception (CPGP) module is proposed to fuse dual-view features, establishing structural consensus through explicit context reasoning and text-guided semantic injection. Secondly, we design a Patch Correlation Predictor (PCP) that leverages a patch-to-patch correlation matrix as a structural prior. This generates a precise block-wise association map, acting as a spatial filter to enforce fine-grained, noise-resilient matching. Experiments on the REAL275 and Toyota-Light datasets demonstrate that FiCoP improves Average Recall by 8.0% and 6.1%, respectively, compared to the state-of-the-art method, highlighting its capability to deliver robust and generalized perception for robotic agents operating in complex, unconstrained open-world environments. The source code will be made publicly available at https://github.com/zjjqinyu/FiCoP.

19.
arXiv (CS.AI) 2026-06-11

nD-RoPE: A Generalized RoPE for n-Dimensional Position Embedding

arXiv:2606.12146v1 Announce Type: cross Abstract: Rotary Position Embedding (RoPE) is widely adopted in Transformer models, yet its extension to high-dimensional domains lacks a unified theoretical formulation. Most existing approaches either apply rotations independently along each axis or empirically mix frequencies, which limits cross-dimensional interactions and yields direction-dependent representations. To address these limitations, we propose nD-RoPE, a decomposition-free generalization of RoPE to arbitrary dimensions. From a translation-invariant formulation in continuous Hilbert space, we derive a spectral condition for isotropy that requires treating positions and frequencies as coupled \(n\)-dimensional vectors. We instantiate this formulation with a multi-scale regular-simplex wave-vector design, which provides non-degenerate spatial coverage and a symmetric, directionally balanced second-order response. Experiments across images, videos, and point clouds demonstrate consistent performance gains and improved generalization in high-dimensional settings.

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

HRIR-Former: Grid-Free Time-Domain Reconstruction of Head-Related Impulse Responses with a Spatially Encoded Transformer

arXiv:2603.27998v2 Announce Type: replace-cross Abstract: Individualized head-related impulse responses (HRIRs) enable binaural rendering, but dense per-listener measurements are costly. We address HRIR spatial up-sampling from sparse per-listener measurements: given a few measured HRIRs for a listener, predict HRIRs at unmeasured target directions. Prior learning methods often work in the frequency domain, rely on minimum-phase assumptions or separate timing models, and use a fixed direction grid, which can degrade temporal fidelity and spatial continuity. We propose HRIR-Former, a time-domain, grid-free binaural Transformer for reconstructing HRIRs at arbitrary directions from sparse inputs. It uses sinusoidal spatial features, a Conv1D refinement module, and auxiliary interaural time difference (ITD) and interaural level difference (ILD) heads. On SONICOM, it improves normalized mean squared error (NMSE), cosine distance, and ITD/ILD errors over prior methods; ablations validate modules and show minimum-phase preprocessing is unnecessary.

21.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

22.
arXiv (CS.LG) 2026-06-11

Trajectory Geometry of Transformer Representations Across Layers

arXiv:2606.09287v2 Announce Type: replace Abstract: Understanding how transformer representations evolve across layers, not merely what they encode, remains an open problem in mechanistic interpretability. We recast the transformer forward pass as a discrete population trajectory through a high-dimensional representation manifold, drawing on geometric tools from computational neuroscience. Rather than probing for pre-specified features, we characterize trajectory geometry using five metrics computed directly in the ambient space: trajectory length, curvature, a semantic convergence index, layerwise cosine similarity, and representational stability. Across three model families (GPT-2, TinyLlama, Qwen2.5) and five controlled prompt families, we report four findings. First, semantically related prompts converge significantly in middle-to-late layers (peak CI 0.41–0.58, p

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

Investigating Inductive Biases for Machine Learning Emulation of Sudden Stratospheric Warmings in Idealised Isca Simulations

arXiv:2606.18857v1 Announce Type: new Abstract: Machine-learning emulators are increasingly used for weather prediction and have the potential to extend skill on subseasonal-to-seasonal timescales by learning dynamically important sources of predictability. A key challenge is whether the models can exploit predictability anchors, such as stratospheric variability, that influence tropospheric circulation beyond short lead times. We test how architectural inductive bias affects emulation of sudden stratospheric warming (SSW) dynamics using paired idealised Isca simulations that differ only in an imposed wave-2 heating perturbation. Across convolutional, transformer, and graph-based architectures trained for one-step prediction, model differences are modest when the stratosphere is dynamically quiet but widen substantially when SSW-like variability is active. Our results identify explicit three-dimensional vertical coupling as a key inductive bias for machine-learning emulation of stratospheric dynamics. However, Eliassen-Palm flux diagnostics show that low forecast error does not guarantee physically faithful wave-mean-flow interaction, with coherent errors remaining in stratospheric wave-driving structure.

24.
arXiv (CS.AI) 2026-06-11

Grounding Computer Use Agents on Human Demonstrations

arXiv:2511.07332v2 Announce Type: replace-cross Abstract: Building reliable computer-use agents requires grounding: accurately connecting natural language instructions to the correct on-screen elements. While large datasets exist for web and mobile interactions, high-quality resources for desktop environments are limited. To address this gap, we introduce GroundCUA, a large-scale desktop grounding dataset built from expert human demonstrations. It covers 87 applications across 12 categories and includes 56K screenshots, with every on-screen element carefully annotated for a total of over 3.56M human-verified annotations. From these demonstrations, we generate diverse instructions that capture a wide range of real-world tasks, providing high-quality data for model training. Using GroundCUA, we develop the GroundNext family of models that map instructions to their target UI elements. At both 3B and 7B scales, GroundNext achieves state-of-the-art results across five benchmarks using supervised fine-tuning, while requiring less than one-tenth the training data of prior work. Reinforcement learning post-training further improves performance, and when evaluated in an agentic setting on the OSWorld benchmark using o3 as planner, GroundNext attains comparable or superior results to models trained with substantially more data,. These results demonstrate the critical role of high-quality, expert-driven datasets in advancing general-purpose computer-use agents.

25.
arXiv (CS.LG) 2026-06-15

Beyond a Single Explanation of the Adam–SGD Gap

arXiv:2606.14259v1 Announce Type: new Abstract: Prior work has identified several factors that can contribute to the performance gap between Adam and SGD, spanning data aspects, architecture design, and optimization properties. Yet these explanations are often studied in isolation, leaving their relative importance unclear. In this work, we revisit these hypotheses through a controlled empirical study across vision, language, genomics, and graph tasks, spanning modern and classical architectures, and carefully designed training setups. Our results suggest that no single factor consistently explains the Adam–SGD gap. For instance, the Adam advantage can (1) persist under a uniform vocabulary distribution yet nearly disappear under a heavy-tailed one; (2) reverse in favor of SGD in softmax-attention models; and (3) become larger under soft architectural modifications, e.g., when ReLU is replaced by a GeLU nonlinearity. This suggests that the gap arises from nontrivial data and architecture interactions, rather than from a single common factor. Yet, we observe a pattern across our settings: a crossover batch size at which the relative advantage shifts from SGD to Adam as the batch size scales. These empirical results are captured by our theoretical gap model, which predicts this batch-size-dependent crossover. Our perspective helps reconcile several existing hypotheses while offering practical insights across domains.