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01.
arXiv (CS.CL) 2026-06-12

Reward Modeling for Multi-Agent Orchestration

Multi-Agent Systems (MAS) built on Large Language Models (LLMs) require effective orchestration to coordinate specialized agents, yet training such orchestrators is hindered by limited supervision and high computational cost. We propose Orchestration Reward Modeling (OrchRM), a self-supervised framework for evaluating orchestration quality without human annotations. OrchRM leverages intermediate artifacts from multi-agent executions to construct win-lose pairs for Bradley-Terry reward model training. Unlike existing MAS test-time scaling and orchestrator training frameworks that rely on costly sub-agent rollouts, OrchRM operates directly at the orchestration level, enabling efficient and high-performing reward-guided orchestrator training and MAS test-time scaling. OrchRM improves training efficiency by up to 10x in token usage while improving MAS test-time scaling performance by up to 8% in accuracy. These gains consistently transfer across multiple domains, including mathematical reasoning, web-based question answering, and multi-hop reasoning, demonstrating orchestration-level reward modeling as a scalable direction for robust multi-agent orchestration. Code will be available at https://github.com/Wang-ML-Lab/OrchRM.

02.
bioRxiv (Bioinfo) 2026-06-13

Testing the reliability of AI-generated protein structures

Authors:

Although AlphaFold2 and its competitors have demonstrated remarkable abilities to predict protein structure, more work is needed to explore the limitations of these methods. Here we investigated the reliability of AlphaFold2 and ColabFold by creating a set of realistic but false protein sequences, using ColabFold to predict their structure, and then asking how often the program produces a high-scoring structure for a sequence that does not represent a protein. We determined that AlphaFold2 has a very small but non-zero false positive rate, estimated here at approximately 1 in 435 if one uses a threshold pLDDT score of 70 to define positive predictions. We also discovered, serendipitously, that some high-scoring sequences in the human genome were not false positives, but instead were previously unknown and un-annotated pseudogenes. These latter findings indicate that some well-established human annotations of protein-coding genes may have incorrectly extended the 5-prime untranslated regions too far. They also suggest that the false positive rate of AlphaFold2 is low enough that almost any high-scoring structure, even in a noncoding region, is worthy of further investigation.

03.
arXiv (CS.LG) 2026-06-11

Bernstein-Schur Kernels: Random Features by Sketched Modulation and Radial Randomization

Authors:

arXiv:2606.11255v1 Announce Type: new Abstract: Bernstein–Schur kernels are products of a finite-feature kernel (one with an explicit finite-dimensional feature map) and a completely monotone shift-invariant kernel: nonstationary kernels that fall between the shift-invariant and dot-product templates random features usually exploit, so in general neither Bochner sampling nor polynomial sketching applies to the full kernel directly. We give one random-feature construction for the whole class that randomizes both factors: it sketches the finite modulation and randomizes the completely monotone radial factor, sampling the latter's one-dimensional Bernstein–Widder scale and then applying Gaussian random Fourier features (whose frequency is still $d$-dimensional). The feature dimension is then $Dm$, set by the sketch size $m$ and the radial-draw count $D$, free of the $O(d^2)$ size of the exact modulation feature. Keeping the modulation \emph{exact is the analyzable limit ($m\to\infty$): there we prove unbiasedness, an exact variance for the recommended flat estimator, an expected matrix-Bernstein operator-norm bound (with a matching high-probability tail) controlled by the top eigenvalues of the kernel and modulation Gram matrices together with an intrinsic dimension rather than the crude $N\max_{ij}$ entrywise route, and a deterministic relative-spectral kernel-ridge stability result. By conditioning on the sketch, the doubly-randomized estimator inherits the same intrinsic-dimension operator-norm guarantee plus a single additive sketch term, tunable by $m$ independently of $D$. The motivating instance is the biased $yat$-kernel $k_{yat,b}(w,x)=(w^\top x+b)^2/(\|w-x\|^2+\varepsilon)$, $b\ge0$, whose family span contains the inverse-multiquadric kernel by finite differences in $b$; for it the radial mixture is the IMQ spectral sampler, and one frequency per scale is variance-optimal at a fixed radial-feature budget.

04.
arXiv (CS.AI) 2026-06-16

RaBiT: Residual-Aware Binarization Training for Accurate and Efficient LLMs

arXiv:2602.05367v3 Announce Type: replace Abstract: Efficient deployment of large language models (LLMs) requires extreme quantization, forcing a critical trade-off between low-bit efficiency and performance. Residual binarization enables hardware-friendly, matmul-free inference by stacking binary ($\pm$1) layers, but is plagued by pathological feature co-adaptation. We identify a key failure mode, which we term inter-path adaptation: during quantization-aware training (QAT), parallel residual binary paths learn redundant features, degrading the error-compensation structure and limiting the expressive capacity of the model. While prior work relies on heuristic workarounds (e.g., path freezing) that constrain the solution space, we propose RaBiT, a novel quantization framework that resolves co-adaptation by algorithmically enforcing a residual hierarchy. Its core mechanism sequentially derives each binary path from a single shared full-precision weight, which ensures that every path corrects the error of the preceding one. This process is stabilized by a robust initialization that prioritizes functional preservation over mere weight approximation. RaBiT redefines the 2-bit accuracy-efficiency frontier: it achieves state-of-the-art performance, rivals even hardware-intensive Vector Quantization (VQ) methods, and delivers a $4.49\times$ inference speed-up over full-precision models on an RTX 4090. Code is available at https://github.com/SamsungLabs/RaBiT.

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

MPK: A Compiler and Runtime for Mega-Kernelizing Tensor Programs

arXiv:2512.22219v2 Announce Type: replace-cross Abstract: We introduce Mirage Persistent Kernel (MPK), the first compiler and runtime system that automatically transforms multi-GPU model inference into a single high-performance mega-kernel. MPK introduces an SM-level graph representation that captures data dependencies at the granularity of individual streaming multiprocessors (SMs), enabling cross-operator software pipelining, \rev{fine-grained overlap of computation and communication, and other optimizations that are infeasible under the conventional kernel-per-operator execution model}. The MPK compiler lowers tensor programs into optimized SM-level task graphs and generates fast CUDA implementations for each task, while the MPK in-kernel parallel runtime executes these tasks within a single persistent mega-kernel using decentralized scheduling across SMs. Together, these components provide end-to-end kernel fusion with minimal developer effort, while preserving the flexibility of existing programming models. Our evaluation shows that MPK significantly outperforms existing kernel-per-operator LLM serving systems, achieving up to 1.7$\times$ lower end-to-end inference latency and pushing LLM inference performance close to the limits of the underlying hardware. MPK is publicly available at https://github.com/mirage-project/mirage.

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

WEQA: Wearable hEalth Question Answering with Query-Adaptive Agentic Reasoning

arXiv:2606.18147v1 Announce Type: new Abstract: Language models are remarkably capable at medical question answering, in some cases surpassing the accuracy of general physicians. However, answering questions about wearable health data remains challenging and understudied, as these ubiquitous sensors produce continuous, high-dimensional, and longitudinal data, which is non-trivial to align with text-centric distributions in LLM pretraining. The diversity of sensor modalities and user intents cannot be effectively handled by a fixed reasoning workflow or a single pretrained foundation model. To address these challenges, we propose WEQA, a query-adaptive agent framework that unifies LLM reasoning with specialized wearable analytical and modeling tools. An LLM controller is employed to synthesize execution plans and dynamically route each query to the appropriate combination of sensor analysis and pretrained models, and perform grounded response auditing with external knowledge. We also curate a benchmark spanning four open wearable datasets comprising analytic and predictive tasks in three different health domains. Experiments show that our framework is 24% more accurate than LLM and agentic baselines, and a blinded study with 12 medical experts and 8 users shows substantial gains in usefulness and clinical soundness.

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

Active Learning with Low-Rank Structure for Data Selection

arXiv:2606.16045v1 Announce Type: new Abstract: In the data selection problem, the objective is to choose a small, representative subset of data that can be used to efficiently train a machine learning model. Sener and Savarese [ICLR 2018] showed that, given an embedding representation of the data and suitable geometric assumptions, heuristics based on $k$-center clustering can be used to perform data selection. This perspective was further explored by Axiotis et. al. [ICML 2024], who proposed a data selection approach based on $k$-means clustering and sensitivity sampling. However, these methods rely on the assumption that the dataset exhibits intrinsic geometric structure that can be effectively captured by clustering, whereas many modern datasets instead possess global algebraic structure that is better exploited by low-rank approximation or principal component analysis. In this paper, we introduce a new data selection framework based on low-rank approximation and residual-based sampling, formulated through the lens of row subset selection and loss-preserving coreset construction. Given an embedding representation of the data satisfying mild regularity conditions, which can be interpreted as algebraic or angular notions of Lipschitz continuity, we show that it is possible to select a weighted subset of $\tilde{O}\left(k + \frac{1}{\varepsilon^2}\right)$ data points whose average loss approximates the average loss over the full dataset within a $(1+\varepsilon)$ relative error, up to an additive $\varepsilon \Phi_k$ term, where $\Phi_k$ denotes the optimal rank-$k$ approximation cost of the embedding matrix. We complement these theoretical guarantees with empirical evaluations, demonstrating that on a range of real-world datasets, our data selection approach achieves improved performance over prior strategies based on uniform sampling or clustering-based sensitivity sampling.

08.
arXiv (CS.AI) 2026-06-19

Analyzing the Narration Gap in LLM-Solver Loops

arXiv:2606.19588v1 Announce Type: new Abstract: Formal tools such as SAT and SMT solvers are increasingly embedded in language model reasoning pipelines when a safety or security critical question can be formulated in logic. Unlike chain of thought whose steps are sampled from the model distribution without formal guarantee, a solver produces a sound and independently verifiable answer. However, the soundness guarantee can be lost in the interaction between the solver and the model. The hybrid pipeline has three components: formalizing the question, deciding it, and narrating the result. Prior work has studied the formalization and decision, but not narration, which is the step that turns a formal tool's output into the user answer. To fill the narration gap, we first model the LLM-solver loop as a verified decision procedure. We further evaluate five open-sourced models under prompt injection, and we find certificate gating makes the solver verdict sound, while an adversary can invert a verified conclusion across phrasings and channels. We study the mitigation through hardened prompt that reduces injection significantly but cannot eliminate it and still suffers under adaptive attack. Combining the formal analysis and empirical studies, we show in the LLM-solver loop, robustness does not reach to the answer that the user finally reads.

09.
arXiv (CS.CV) 2026-06-16

RaLMPH: Reliability-aware Learning for Multi-Pathologist Harmonization in Whole-Slide Image Classification

Multiple Instance Learning (MIL) is a standard paradigm for Whole-Slide Image (WSI) analysis and has achieved strong results in computational pathology. However, most MIL pipelines assume a single "gold" label per slide, which conflicts with clinical practice where substantial inter-pathologist variability is common. Existing multi-annotator learning and label-refinement methods typically estimate global annotator reliability or rely on single-instance assumptions, making them poorly suited to MIL and to localized diagnostic contexts where experts disagree. We propose RaLMPH (Reliability-aware Learning for Multi-Pathologist Harmonization), a MIL-based label reconciliation framework for WSIs annotated by multiple pathologists. RaLMPH introduces a reliability field that jointly models (i) local neighborhood structure in WSI feature space and (ii) expert uncertainty (entropy), enabling per-sample identification of trustworthy reference neighborhoods. Leveraging this field, RaLMPH performs sample-wise local annotator ranking to select reliable opinions per slide and applies an adaptive gating mechanism to fuse labels conditioned on local reliability. Experiments on a clinical WSI dataset with labels from six pathologists, as well as controlled simulated benchmarks, show that RaLMPH consistently outperforms existing approaches. Further analyses clarify how our reliability-aware mechanism improves label reconciliation and downstream MIL performance.

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

PCA-Enhanced Adaptive NVAR Framework for High-Resolution Sea Surface Temperature Forecasting in the East Sea

arXiv:2606.12141v1 Announce Type: new Abstract: Accurate forecasting of sea surface temperature (SST) in regional seas such as the East Sea is crucial for monitoring marine ecosystems, assessing climate risks, managing fisheries, and conducting naval operations. Traditional numerical ocean models provide reliable predictions but are computationally expensive and often unsuitable for real-time forecasting. Many deep learning methods also struggle with high-dimensional spatiotemporal ocean data and experience error accumulation over longer forecasting periods. This study builds on our previously proposed Adaptive Next-Generation Reservoir Computing (Adaptive NVAR) framework, initially introduced and tested on synthetic dynamical systems, and extends it to ocean forecasting. We present a reduced-order forecasting framework that combines Singular Value Decomposition (SVD) with Adaptive NVAR to predict SST dynamics in the East Sea. SST fields are compressed into a low-dimensional representation using SVD, which extracts dominant modes of ocean variability. Adaptive NVAR models the temporal evolution of these latent states, and the predicted states are reconstructed into SST forecasts. We evaluate the framework using regional ocean datasets and compare it with the standard NG-RC/NVAR. Results show that Adaptive NVAR consistently achieves lower forecasting errors across multiple prediction horizons. In addition, SVD reduces computational complexity, resulting in a fast and scalable framework suitable for real-time ocean forecasting.

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

TerraMind: Large-Scale Generative Multimodality for Earth Observation

arXiv:2504.11171v5 Announce Type: replace-cross Abstract: We present TerraMind, the first any-to-any generative, multimodal foundation model for Earth observation (EO). Unlike other multimodal models, TerraMind is pretrained on dual-scale representations combining both token-level and pixel-level data across modalities. On a token level, TerraMind encodes high-level contextual information to learn cross-modal relationships, while on a pixel level, TerraMind leverages fine-grained representations to capture critical spatial nuances. We pretrained TerraMind on nine geospatial modalities of a global, large-scale dataset. In this paper, we demonstrate that (i) TerraMind's dual-scale early fusion approach unlocks a range of zero-shot and few-shot applications for Earth observation, (ii) TerraMind introduces "Thinking-in-Modalities" (TiM) – the capability of generating additional artificial data during finetuning and inference to improve the model output – and (iii) TerraMind achieves beyond state-of-the-art performance in community-standard benchmarks for EO like PANGAEA. The pretraining dataset, the model weights, and our code are open-sourced under a permissive license.

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

Does the Judge Prefer English? Evaluating Language-Switching Invariance in LLM-as-a-Judge

Authors:

Large language models (LLMs) are now widely used as automatic judges for open-ended instruction-following evaluation. This practice is convenient, scalable, and often more semantically aware than reference-based metrics, but it also introduces a new reliability question: does a judge evaluate the quality of an answer, or does it also react to the language in which the comparison is presented? We propose Judge-LS, a lightweight meta-evaluation protocol that transforms LLMBar response-pair items into English, Chinese, and Chinese-English language-switched variants. A reliable judge should preserve its preference under label-preserving language transformations and should not prefer a language when two answers are translation-equivalent. We evaluate four API-accessible judges on the full 419-item LLMBar benchmark, producing 13,408 successful pairwise judgments. Across models, Chinese and language-switched presentations induce 10.7–14.4% preference flips relative to English, and all judges achieve their highest accuracy in English. However, translation-equivalent tie probes do not reveal a systematic English preference: most probes are judged as ties, and non-tie decisions more often favor Chinese. We add confidence intervals, paired significance tests, and an automatic transformation audit with a sensitivity analysis that excludes mechanically flagged high-risk variants. The experiment requires no model training, uses only API calls, and is feasible on modest local hardware.

13.
arXiv (CS.CV) 2026-06-17

Does the Data Processing Inequality Reflect Practice? On the Utility of Low-Level Tasks

The data processing inequality is an information-theoretic principle stating that the information content of a signal cannot be increased by processing the observations. In particular, it suggests that there is no benefit in enhancing the signal or encoding it before addressing a classification problem. This assertion can be proven to be true for the case of the optimal Bayes classifier. However, in practice, it is common to perform "low-level" tasks before "high-level" downstream tasks despite the overwhelming capabilities of modern deep neural networks. In this paper, we aim to understand when and why low-level processing can be beneficial for classification. We present a comprehensive theoretical study of a binary classification setup, where we consider a classifier that is tightly connected to the optimal Bayes classifier and converges to it as the number of training samples increases. We prove that for any finite number of training samples, there exists a pre-classification processing that improves the classification accuracy. We also explore the effect of class separation, training set size, and class balance on the relative gain from this procedure. We support our theory with an empirical investigation of the theoretical setup. Finally, we conduct an empirical study where we investigate the effect of denoising and encoding on the performance of practical deep classifiers on benchmark datasets. Specifically, we vary the size and class distribution of the training set, and the noise level, and demonstrate trends that are consistent with our theoretical results.

14.
bioRxiv (Bioinfo) 2026-06-16

THEOBROMA: an aggregated open database of 1.13 million natural products with per-compound license auditing, three-tier classification, and stereochemistry-aware deduplication

Natural products remain one of the most productive sources of pharmacologically active compounds for drug discovery, yet the current open aggregator landscape attributes licenses at database rather than compound granularity, with consequences that have become tangible as the field grows. A recent relicensing event in one constituent source (the September 2024 transition of the Natural Products Atlas to CC BY-NC 4.0) demonstrates how database-level licensing propagates across an aggregate and motivates the per-compound audit framework presented here. The same peer cohort separately leaves classification provenance and stereoisomer-family relations coarser than either layer warrants. THEOBROMA, accessible at url{https://theobroma.l3s.uni-hannover.de}, integrates 1{,}133{,}004 natural products from 29 open sources under a per-compound license audit that resolves each compound's license tier across all attesting sources under a most-restrictive-wins rule, identifying 900{,}170 compounds (79.4%) under open-use licenses and exposing the per-source attestation chain and resolved tier through a dedicated audit endpoint and a query-time license filter. A three-tier classification stratifies 89.3% coverage into 35.1% curated, 43.9% high-confidence inferred, and 10.3% exploratory tiers, with 486{,}215 stereoisomer families preserved by full 27-character InChIKey deduplication and exposed via a dedicated texttt{/api/stereoisomers/} endpoint and a radial-family display. Per-compound license provenance is the primary differentiator. Classification stratification and stereoisomer-family exposure add finer-grained access to two related axes, supporting license-compatible virtual screening and isomer-specific bioactivity analysis at corpus scale. As an evolving open resource, THEOBROMA pairs continuous pipeline maintenance with interactive geographic, taxonomic, and chemical-space exploration.

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

Right Predictions, Misleading Explanations: On the Vulnerability of Vision-Language Model Explanations

Explanation mechanisms are increasingly used to support transparency and trust in vision-language models (VLMs), particularly in settings where model decisions require human oversight. However, the robustness of these explanations remains insufficiently understood. In this work, we investigate whether explanation heatmaps in VLMs, particularly CLIP-based models, faithfully reflect model reasoning under adversarial conditions. We show that explanation maps can be systematically manipulated while preserving the model's original prediction, revealing a disconnect between predictive behavior and explanation faithfulness. To study this vulnerability, we introduce X-Shift, a novel grey-box attack that perturbs patch-level visual representations to redirect explanation heatmaps toward semantically irrelevant regions without altering the predicted output. Unlike conventional adversarial attacks that aim to induce misclassification, X-Shift specifically targets the integrity of the explanation process itself. The attack operates without modifying model parameters and generalizes across multiple CLIP architectures and explanation methods. We evaluate the proposed approach on ImageNet-1k, MS-COCO, and Flickr30K, demonstrating consistent degradation in explanation alignment under imperceptible perturbations while maintaining prediction stability. Furthermore, standard prediction-oriented adversarial attacks fail to reproduce the same explanation-shifting behavior even under substantially larger perturbation budgets. Our findings highlight a fundamental limitation of current explanation mechanisms in VLMs and raise concerns about their use as reliable indicators of model trustworthiness in high-impact applications.

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

LVLMs and Humans Ground Differently in Referential Communication

For generative AI agents to partner effectively with human users, the ability to accurately predict human intent is critical. But this ability to collaborate remains limited by a critical deficit: an inability to model common ground. We present a referential communication experiment with a factorial design involving director-matcher pairs (human-human, human-AI, AI-human, and AI-AI) that interact with multiple turns in repeated rounds to match pictures of objects not associated with any obvious lexicalized labels. We show that LVLMs cannot interactively generate and resolve referring expressions in a way that enables smooth communication, a crucial skill that underlies human language use. We release our corpus of 356 dialogues (89 pairs over 4 rounds each) along with the online pipeline for data collection and the tools for analyzing accuracy, efficiency, and lexical overlap.

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

Non-negative Elastic Net Decoding for Information Retrieval

Dense retrieval has become the dominant paradigm in information retrieval, in which each document is scored against a query by the inner product of their vector embeddings, and the top-$k$ documents by score are retrieved for this query. However, since each document's score depends solely on the embedding of the query and itself, the retrieval process is oblivious to the content of the entire corpus. Therefore, dense retrieval cannot avoid selecting semantically similar documents from the corpus, which may result in a non-diverse, redundant set of retrieved documents. To this end, we approach retrieval as a joint decoding problem, in which documents are selected as a set with regard to the context of the rest of the corpus. To achieve this, we propose Non-Negative elastic Net (NNN) decoding, which selects documents whose embeddings jointly reconstruct the query embedding as a sparse non-negative linear combination. Our main theoretical result establishes a strict separation between dense retrieval and NNN decoding. For any corpus, every query correctly handled by dense retrieval is also handled by NNN decoding, while on corpora containing correlated documents, NNN decoding additionally handles queries that dense retrieval cannot. Experimental results indicate that applying NNN decoding to frozen embeddings trained for inner-product scoring yields consistent improvements across several benchmarks. Moreover, we introduce an end-to-end training procedure which optimizes the embeddings for NNN decoding, producing significant performance gains surpassing in all metrics and benchmarks compared to dense retrieval. Our work establishes a new paradigm for leveraging dense embeddings in information retrieval, beyond the standard practice of inner-product scoring.

18.
arXiv (CS.AI) 2026-06-12

ERTS: Adversarial Robustness Testing of Ethical AI via Semantic Perturbation in a Bounded Consequence Space

arXiv:2606.13282v1 Announce Type: new Abstract: As AI systems are deployed in high-stakes ethical contexts such as healthcare triage, autonomous vehicle control, and employment screening, formal methods for evaluating their robustness against adversarial manipulation of ethical reasoning remain underdeveloped. This paper introduces the Ethical Robustness Testing System (ERTS), a closed-pipeline framework that: (1) encodes ethical dilemmas into a 22-dimensional Ethical Consequence Space (ECS) grounded in established ethical theory; (2) applies 17 semantic perturbation functions subject to 6 validity constraint classes including a novel semantic coherence constraint; (3) measures decision deviation via a 4-component Ethical Instability Index (EII); and (4) produces domain-adaptive pre-deployment robustness assessment verdicts. We evaluate 4 structured baseline models and 2 production LLMs (Gemini 2.0 Flash and Llama 3.2) across 50 ethical scenarios spanning 8 deployment domains, generating 1,500 adversarial test cases. Results demonstrate that only 33% of models achieve assessment clearance, with the local Llama-3.2 model proving particularly vulnerable to fairness corruption and information degradation attacks (ERS = 0.737). To the best of our knowledge, no existing framework combines a bounded ethical consequence space, semantic coherence constraints, and domain-adaptive assessment in a single adversarial testing pipeline.

19.
arXiv (CS.CL) 2026-06-17

DICE: Diffusion Large Language Models Excel at Generating CUDA Kernels

Diffusion large language models (dLLMs) have emerged as a compelling alternative to autoregressive (AR) LLMs, owing to their capacity for parallel token generation. This paradigm is particularly well-suited for code generation, where holistic structural planning and non-sequential refinement are critical. Despite this potential, tailoring dLLMs for CUDA kernel generation remains challenging, obstructed not only by the high specialization but also by the severe lack of high-quality training data. To address these challenges, we construct CuKe, an augmented supervised fine-tuning dataset optimized for high-performance CUDA kernels. On top of it, we propose a bi-phase curated reinforcement learning (BiC-RL) framework consisting of a CUDA kernel infilling stage and an end-to-end CUDA kernel generation stage. Leveraging this training framework, we introduce DICE, a series of diffusion large language models designed for CUDA kernel generation, spanning three parameter scales, 1.7B, 4B, and 8B. Extensive experiments on KernelBench demonstrate that DICE significantly outperforms both autoregressive and diffusion LLMs of comparable scale, establishing a new state-of-the-art for CUDA kernel generation.

20.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Authors:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

21.
arXiv (CS.CL) 2026-06-11

A Resource for Enthymeme Detection in Controversial Political Discourse

Enthymemes, arguments with unstated premises or conclusions, are pervasive in persuasive discourse, yet their annotation remains notoriously subjective. We present a resource of 1,482 tweets from politically controversial discourse, annotated by five annotators for the presence of enthymemes and their argument structure, designed to study label variation. We first revisit the definition of enthymemes and propose annotation guidelines anchored in Walton's argumentation schemes, offering a structured and constrained approach that nonetheless preserves room for the interpretive nature of the task. This contrasts with past resources, which tend to eliminate disagreement, obscuring its sources and preventing investigation of its potential benefits for model performance. We further propose a complexity analysis of the task, identifying where annotation imposes high cognitive load and may give rise to inconsistent annotation. Our preliminary experiments show that models trained on annotator disagreement outperform models trained on hard majority-vote labels. We close by reflecting on how structural openness in enthymeme definitions and guidelines enables the study of variation in subjective inferential processes for future resources and downstream NLP applications concerned with human inference.

22.
arXiv (CS.CV) 2026-06-16

HairLRM: Strand-based Hair Modeling via Large Reconstruction Models

The fundamental limitation of traditional strand-based modeling is not simply data scarcity, but the ill-posedness of inferring complex 3D fields from 2D imagery without structural constraints. This unconstrained regression leads to catastrophic failures in resolving both global occlusion (e.g., in ponytails) and local directionality (e.g., in curls), resulting in over-smoothed, plausible-but-incorrect geometries. To resolve this, we integrate the strong geometric priors of Large Reconstruction Models (LRMs) into the strand generation pipeline. Using the LRM mesh as a structural anchor, we employ a novel Dual Orientation AutoEncoder to lift coarse geometry into high-fidelity strands. By resolving vector field singularities through latent-space optimization and surface-guided refinement, our method effectively disentangles complex topological structures, setting a new benchmark for robustness and accuracy in hair reconstruction.

23.
arXiv (CS.CV) 2026-06-15

One Layer's Trash is Another Layer's Treasure: Adaptive Layer-wise Visual Token Selection in LVLMs

Large Vision-Language Models (LVLMs) have achieved remarkable success across diverse multimodal tasks, yet their practical deployment remains constrained by the computational burden arising from lengthy visual tokens. While visual token pruning has emerged as a promising solution, existing methods suffer from a fundamental limitation: once tokens are pruned at a specific layer, they become inaccessible to all subsequent layers, leading to premature information loss that can compromise model performance. Through empirical studies, we observe that different layers exhibit distinct visual region focus, indicating a varying optimal token subset across layers. Motivated by this insight, we propose Adaptive Layer-wise Visual Token Selection (ALVTS), a novel framework that breaks away from the conventional static token pruning paradigm. ALVTS incorporates a lightweight token selector to identify and route important tokens for further processing, while allowing less important tokens to skip the layer, thus minimizing computational redundancy. These two streams of tokens are seamlessly reintegrated before being fed into subsequent layers, facilitating adaptive compression across the entire model. Grounded in our importance consistency constrained low-rank approximation, the proposed token selection module closely emulates the full attention mechanism, effectively capturing its essential patterns without requiring model retraining. Extensive experiments on LLaVA-1.5, LLaVA-NeXT, and Qwen2.5-VL validate the effectiveness of our method. With an 89% token compression ratio, ALVTS retains 96.7% of the original model's accuracy, achieving a superior efficiency-accuracy trade-off for LVLM inference.

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

Rewrite to Translate, Translate to Reward: Reinforcement Learning for Source Rewriting in Machine Translation

Rewriting source text with large language models (LLMs) before translation has been shown to improve machine translation (MT) quality. However, we find that prompt-based rewriting can degrade translation quality rather than improve it, particularly when smaller LLMs, such as 4B-parameter models, are used. We argue that this limitation stems from the difficulty of controlling rewriting behavior through natural-language prompts alone: a rewrite is useful only if it improves downstream translation, yet existing prompt-based methods do not explicitly optimize for this signal. To address this issue, we propose RLSR (Reinforcement Learning for Source Rewriting), a reinforcement learning framework that trains the rewriting model with a reward based on the downstream translation-quality improvement produced by each rewrite. Experiments across six MT systems and 16 language pairs show that our 4B RLSR-trained rewriting models significantly outperform both the no-rewriting baseline and prompt-based rewriting baselines at the same model scale, while remaining competitive with baselines that use a 235B LLM.

25.
arXiv (CS.AI) 2026-06-19

HilDA: Hierarchical Distillation with Diffusion for Advancing Self-Supervised LiDAR Pre-trainin

arXiv:2606.20189v1 Announce Type: cross Abstract: Leveraging Vision Foundation Models (VFMs) for camera-to-LiDAR knowledge distillation offers a promising solution to the scarcity of annotated data needed to represent the immense geometric and kinematic diversity of real-world autonomous driving (AD). However, current approaches typically treat VFMs as black-box teachers, relying exclusively on frame-wise feature similarity. Consequently, they do not fully exploit the teacher's layer-wise semantic structure and global context, as well as the rich spatiotemporal information inherent in LiDAR sequences. We propose HilDA, a self-supervised pretraining framework for LiDAR backbones that better captures the semantic what and geometric where needed for driving tasks. HilDA combines hierarchical distillation comprising multi-layer distillation for progressive semantic alignment and global context distillation for scene-level semantics, with a temporal occupancy diffusion objective promoting spatiotemporal consistency. Models pre-trained with HilDA achieve state-of-the-art results on cross-modal distillation benchmarks and outperform models trained via prior distillation approaches on 3D object detection, scene flow, and semantic occupancy prediction. Code available at: https://maxiuw.github.io/hilda.