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01.
arXiv (CS.CV) 2026-06-15

Temporal Backtracking Search for Test-time Generative Video Reasoning

While test-time scaling has revolutionized reasoning in large language models, generative video reasoning remains bottlenecked by a single-shot paradigm. We demonstrate that searching over denoising steps cannot rescue logically flawed rollouts because spatial trajectories commit early in the diffusion process. Root-level Best-of-N (BoN) sampling is similarly inefficient: reasoning errors cluster early in the temporal axis, and resampling blindly discards verified upstream progress. To unlock effective test-time scaling for video models, we introduce Temporal Backtracking Search (TBS), which shifts the search space to the temporal axis. TBS transforms video generation into an iterative generate-verify-restart loop via three core mechanisms: (1) variable-K conditioning to resume generation from arbitrary clean prefixes; (2) temporal process verification to localize failures and extract valid restart anchors; and (3) prefix-based search to reallocate compute toward extending correct trajectories rather than root resampling. Across algorithmic, navigation, and robotics domains, TBS Pareto-dominates matched-budget BoN. In a strict out-of-distribution setting where one-shot generation collapses (0.7% for BoN), TBS achieves 22.7%, with every solved episode stemming from a restarted branch. Ultimately, TBS reveals that the local reasoning competence of video models far exceeds what single-shot rollouts indicate, providing a scalable test-time framework to unlock it.

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

Quantum statistical enhancement of collective behaviour in a bosonic active Ising model

arXiv:2606.18091v1 Announce Type: new Abstract: Collective behaviour such as flocking (the collective motion of a spontaneously formed group along a common direction) or aster formation (the binding of opposing flocks, inhibiting each others motion) are intriguing emergent phenomena in active systems with local alignment rules. Until recently, their occurrence was mainly studied for classical systems, a prime example being the active Ising model (AIM), which translates the main ingredients of flocking and aster formation (i.e., alignment and self-propulsion) to a lattice framework. Here we introduce and study a one-dimensional (1D) quantum lattice variant of the AIM, based on ideal bosons with a spin degree of freedom. We find that both the collective behaviours of the 1D classical model, flocking and aster formation, are markedly enhanced by the bosonic quantum statistics. This contrasts with a recent quantum generalization of the AIM based onto hard-core bosons [Khasseh et al., Phys. Rev. Lett. 135, 248302 (2025)], where flocking, but neither its quantum-statistical stabilization nor aster states were observed as a consequence of interactions. Moreover, we investigate the competition of this quantum statistical stabilization of collective phases with their suppression by the quantum fluctuations induced by a transverse external magnetic field.

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

Multi-Fidelity SINDy: Sparse Discovery of Nonlinear Dynamical Systems with Fidelity-Weighted Measurements

arXiv:2606.15690v1 Announce Type: new Abstract: Data from simulations and experiments are rarely noise-free and often exhibit heterogeneous levels of fidelity. Measurement uncertainty may vary across repeated observations, sensing devices, or even within a single experiment. This work addresses the problem of discovering nonlinear dynamical systems from such inhomogeneous data. We extend the Sparse Identification of Nonlinear Dynamical Systems (SINDy) framework to account for variable noise levels by combining Ensemble SINDy and Weak SINDy within a weighted regression formulation derived from generalized least squares. A statistical justification for the weighting strategy is also provided. The methodology is validated on several benchmark systems, including ordinary and partial differential equations. In addition, we show the benefit of multi-fidelity integration for forecasting the dynamics of a double pendulum system. The results confirm that the proposed approach mitigates the adverse effects of heteroscedastic noise and that repeated, low-cost, low-quality measurements can improve model recovery, in some cases matching or outperforming reconstructions obtained using only high-fidelity data.

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

MR-GVNO: A Geometry-Aware Variational Physics-Informed Neural Operator for Mindlin-Reissner Plates on Irregular Domains

arXiv:2606.16624v1 Announce Type: new Abstract: Plate and shell structures are widely used in engineering, making rapid response prediction under varying geometries, materials, and loads highly desirable. However, conventional finite element methods require repeated modeling and solution, resulting in high computational costs. This study proposes a geometry-aware variational neural operator for Mindlin-Reissner plate problems, termed MR-GVNO. The method uses boundary point clouds to represent irregular geometries and employs separate encoders for spatially varying material fields, pressure loads, and scalar physical parameters. A cross-attention mechanism integrates these inputs with query point information to predict transverse deflections and rotations at arbitrary locations. MR-GVNO is trained without labeled solution data using a variational physics-informed loss derived from the discretized total potential energy. It directly processes irregular point clouds and allows different physical fields to be discretized independently, avoiding interpolation onto a common grid. Numerical experiments on single-hole, double-hole, and L-shaped plates demonstrate accurate response prediction under homogeneous and heterogeneous materials and uniform and random loads. The model also achieves millisecond-level full-field inference and favorable cross-geometry generalization.

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

Airport Terminal Passenger Queue Forecasting for Departure Gates and Security Checkpoints

arXiv:2606.07622v2 Announce Type: replace Abstract: Accurate passenger queue forecasting in airport terminals is essential for efficient departure operations, as it enables proactive congestion management. However, time-varying passenger demand and heterogeneous facility usage across multiple departure facilities make forecasting challenging. In this work, we propose a passenger queue forecasting framework that learns historical passenger flow patterns from operational data. The proposed model employs a Transformer-based architecture to capture temporal dependencies and inter-facility correlations using past queue length and waiting time at departure gates and security checkpoints, together with passenger throughput at check-in islands. The learned representations are mapped to two facility-specific prediction heads to predict queue length and waiting time at departure gates and security checkpoints. Experimental results demonstrate accurate forecasts up to two hours ahead. The proposed approach offers practical real-time decision support for proactive queue management and staff reallocation in airport terminal operations.

06.
medRxiv (Medicine) 2026-06-13

Projected population level impact and cost-effectiveness of clinic and community-based tuberculosis screening approaches

The South Africa National Department of Health have set ambitious targets to scale up TB testing, focusing primarily on clinic attendees. In the context of declining funding for TB care and prevention, the most cost-effective approaches for targeting testing should be identified. We developed a mathematical model of TB in South Africa, explicitly incorporating clinic attendance by sex and HIV/ART status. We simulated six screening approaches over 2026-2035 (individually and in combination): three clinic-based (symptom screening, intensified targeted universal TB testing [TUTT, symptom-agnostic sputum testing of clinic attendees in key risk groups], and intensified TUTT allowing saliva samples) and three targeted community-based (community radiographic screening, symptom screening, and universal Xpert Ultra testing), each implemented at a range of coverage levels. Model outputs were combined with a mechanistic cost function to estimate potential impact and cost-effectiveness from a societal perspective. The most cost-effective standalone approach was community radiographic screening at 10% annual population coverage, with an incremental cost-effectiveness ratio (ICER) of $421 per disability-adjusted life year (DALY) averted. 10/11 scenarios along the expansion path included community radiographic screening at progressively higher coverage, combined with a clinic-based approach. Combining complementary approaches to reach both groups at increased risk of TB (e.g. clinic-based screening) and groups with lower screening coverage (e.g. community-based screening) may increase cost-effectiveness of TB screening, compared to standalone approaches. When designing TB screening strategies, both population risk and existing screening coverage should be considered.

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

Text-Driven Fusion for Infrared and Visible Images: Achieving Image Scene Adaptation on Hyperbolic Space

Infrared and visible image fusion aims to integrate complementary modalities, while existing Euclidean methods impose rigid distance metrics that distort multi-modal interactions and parent-to-child semantic hierarchies. To overcome these limitations, we introduce a text-driven fusion framework empowered by hyperbolic manifold learning. During training, BLIP-extracted text prompts serve as topological anchors within the hyperbolic space, guiding vision-attribute alignment through hyperbolic embeddings that naturally accommodate varying semantic granularities. By exploiting the exponential volume growth dictated by the Poincaré ball's negative curvature, this approach seamlessly embeds hierarchical trees to encode coarse-to-fine semantics without metric saturation, while the vast peripheral space prevents texture distortion during cross-modal fusion. At inference, the fusion process autonomously adapts to input content using the learned text-attribute priors, completely eliminating the need for textual input. Experimental results show our method outperforms state-of-the-art approaches on benchmark datasets, with code available at https://github.com/Shaoyun2023/TEDFusion.

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

Bayesian Magnetic Resonance Joint Image Reconstruction and Uncertainty Quantification using Sparsity Prior Models and Markov Chain Monte Carlo Sampling

We propose a novel framework for uncertainty quantification using compressed sensing magnetic resonance image reconstruction. The problem is formulated within a Bayesian framework as a linear inverse problem, with prior distributions assigned to the unknown model parameters. Specifically, the image to be reconstructed is assumed to be sparse in a given basis. We develop a general framework applicable to any basis and as examples, we test the sparsity of the image in its (1) spatial gradients using a total variation prior model, and in its (2) wavelet transform. A Markov chain Monte Carlo (MCMC) method, based on a split-and-augmented Gibbs sampler, is then employed to sample from the posterior distribution of the unknown parameters. The non-differentiable conditional distributions are efficiently sampled using a proximal MCMC method. The proposed algorithms are validated on both single-coil and multi-coil datasets using various k-space sub-sampling patterns and ratios. The results demonstrate the superior performance of each proposed approach in reconstructing images compared to its counterpart optimisation-based method. Moreover, our framework effectively quantifies uncertainty, showing a notable correlation between estimated uncertainty maps and error maps computed using ground truth and reconstructed images, compared with existing deep learning-based methods.

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

DIRECT: When and Where Should You Allocate Test-Time Compute in Embodied Planners?

Vision-Language Models (VLMs) are increasingly deployed as high-level planners for embodied agents, with an emerging strategy of scaling test-time compute to improve capability. However, we observe that doing so increases latency, token usage, and FLOPs while yielding uneven, often diminishing gains in downstream success, limiting where embodied agents can be deployed. We argue that choosing when and where to spend test-time compute is central to bringing frontier performance to the real world. We introduce DIRECT, a routing framework that uses multimodal scene context to allocate compute per prompt, improving the success–cost Pareto frontier over fixed model selection. Across three dominant scaling axes, namely chain-of-thought depth, model size, and memory history, our experiments on VLABench and RoboMME show that test-time compute is not a uniform lever: different axes yield qualitatively distinct capability gains. We validate these insights on a physical Franka arm in a DROID setup spanning zero-shot manipulation and long-horizon chaining, where our router matches or exceeds a stronger model's success rate at up to 65% lower average latency. Ultimately, our results show that naively scaling test-time compute is wasteful, and that DIRECT can provide frontier-level embodied planning in robotic systems at a fraction of the cost. Project page can be found at jadee-dao.github.io/direct/.

10.
arXiv (CS.AI) 2026-06-19

LoRDO: Distributed Low-Rank Optimization with Infrequent Communication

arXiv:2602.04396v2 Announce Type: replace-cross Abstract: Distributed training of foundation models via $\texttt{DDP}$ is limited by interconnect bandwidth. While infrequent communication strategies reduce synchronization frequency, they remain bottlenecked by the memory and communication requirements of optimizer states. Low-rank optimizers can alleviate these constraints; however, in the local-update regime, workers lack access to the full-batch gradients required to compute low-rank projections, which degrades performance. We propose $\texttt{LoRDO}$, a principled framework unifying low-rank optimization with infrequent synchronization. We first demonstrate that, while global projections based on pseudo-gradients are theoretically superior, they permanently restrict the optimization trajectory to a low-rank subspace. To restore subspace exploration, we introduce a full-rank quasi-hyperbolic update. $\texttt{LoRDO}$ achieves near-parity with low-rank $\texttt{DDP}$ in language modeling and downstream tasks at model scales of $125$M–$720$M, while reducing communication by $\approx 10 \times$. Finally, we show that $\texttt{LoRDO}$ improves performance even more in very low-memory settings with small rank/batch size.

11.
arXiv (CS.CL) 2026-06-16

Re-feeding Is Not Replaying: Measuring Replay Noise in Counterfactual Token-Credit Estimation

Per-token counterfactual credit estimation asks which token in a language-model rollout caused the final answer to be right or wrong: cut the transcript at a pivot, substitute an alternative token, replay continuations, and compare outcomes. Published methods re-feed the transcript prefix as a fresh prompt, assuming this reproduces the state the model passed through during generation. We measure what that assumption costs on a stock inference engine, with a three-pass design: continuations resumed from the verified decode-time KV state, an identical second exact pass (a replica noise floor), and a re-feed pass. Across six configurations and three models (including a GRPO-trained checkpoint), at low-margin decision tokens, re-feeding changes the credit estimate at rates 14-28 percentage points above the replica floor (7-21pp under a treatment-independent conditioning; problem-clustered t = 2.9-6.4). Most changes are zero-boundary crossings of the quantized estimator rather than polarity reversals, and the perturbation is consistent with mean-zero, so averaged quantities are largely safe; but selection is not: a critical-token set chosen by thresholding $|\hat{A}_t|$ under re-feed overlaps the exact-resume selection at Jaccard 0.34-0.90, versus a 0.63-0.96 replica ceiling. A causal confirmation closes the loop: under vLLM's batch-invariant kernels all three passes are identical on every measured channel, with both disagreement rates exactly zero. Replica passes themselves disagree on 9-23% of eligible estimates: single-sample credit measurements at decision tokens are unreliable under any replay. Settings were fixed in advance; exact-pass cache hits in the second campaign are instrumented (100% hit rate, 3,434 pivots); total compute was under 10 USD. We recommend that counterfactual credit studies resume decoder state or use batch-invariant kernels, and report a replica floor.

12.
arXiv (CS.AI) 2026-06-19

Hidden Anchors in Multi-Agent LLM Deliberation

arXiv:2606.19494v1 Announce Type: new Abstract: Multi-agent LLM deliberation, where agents exchange and revise answers over several rounds, is increasingly used to improve reasoning and accuracy, yet how and why it works is rarely modelled. Such deliberation mirrors how humans reach decisions. As social animals we are pulled both by the group, the herd effect that classical opinion-dynamics models such as DeGroot and Friedkin–Johnsen capture, and by our own internal belief, which they do not. We model multi-agent deliberation as a closed-loop dynamical system in which each agent carries a hidden internal belief, its anchor, that continually pulls its opinion regardless of its neighbours. We show this anchor can be recovered from the deliberation alone, and that it explains a behaviour classical consensus rules forbid: an agent's confidence in the correct answer can climb past where any agent started, escaping the space (convexhull) formed by the initial beliefs. Checking whether the recovered anchor also predicts held-out runs (generalizes) gives a simple test for when a model is truly driven bysuch an anchor. Across three open-weight model families this is a spectrum, not all-or-nothing. All anchors' influence are about equally strongly, but they differ in where the anchor sits, and only when it sits far from the initial opinions does deliberation escape the hull and need the full closed-loop model.

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

Vibe Coding Ate My Homework: An evaluation of AI approaches to greenfield software engineering and programming

arXiv:2606.18293v1 Announce Type: cross Abstract: Thanks to rapid developments in generative AI, we are in the midst of a paradigm shift that may change how we interact with computers forever. We have observed a growth in the use of natural language prompts to build applications and coding infrastructures without underlying knowledge of the field, and this practice has been dubbed `vibe coding.' It arguably represents what the field of programming has been building towards since the beginning, with every higher level of abstraction that is conceived. Vibe coding promises to be the endpoint for the meta of high-level programming as far as method of input is concerned: eliminating a human's use of code syntax entirely in favour of programming in their mother tongue. This paper aims to evaluate the viability of vibe coding for greenfield software engineering tasks, as well as analyse the benchmarks that have been used to measure its software engineering prowess. To this end, we have developed an evaluation suite for analysing an LLM's proficiency in carrying out simple, isolated greenfield programming tasks in Python to provide scoped insight on the matter.

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

ThinkJEPA: Empowering Latent World Models with Large Vision-Language Reasoning Model

Recent progress in latent world models (e.g., V-JEPA2) has shown promising capability in forecasting future world states from video observations. Nevertheless, dense prediction from a short observation window limits temporal context and can bias predictors toward local, low-level extrapolation, making it difficult to capture long-horizon semantics and reducing downstream utility. Vision–language models (VLMs), in contrast, provide strong semantic grounding and general knowledge by reasoning over uniformly sampled frames, but they are not ideal as standalone dense predictors due to compute-driven sparse sampling, a language-output bottleneck that compresses fine-grained interaction states into text-oriented representations, and a data-regime mismatch when adapting to small action-conditioned datasets. We propose a VLM-guided JEPA-style latent world modeling framework that combines dense-frame dynamics modeling with long-horizon semantic guidance via a dual-temporal pathway: a dense JEPA branch for fine-grained motion and interaction cues, and a uniformly sampled VLM thinker branch with a larger temporal stride for knowledge-rich guidance. To transfer the VLM's progressive reasoning signals effectively, we introduce a hierarchical pyramid representation extraction module that aggregates multi-layer VLM representations into guidance features compatible with latent prediction. Experiments on hand-manipulation trajectory prediction show that our method outperforms both a strong VLM-only baseline and a JEPA-predictor baseline, and yields more robust long-horizon rollout behavior.

15.
arXiv (CS.CL) 2026-06-16

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

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.

16.
arXiv (quant-ph) 2026-06-17

Independent Chiral Control in Theory-Space Models:A Rank-Preserving Framework and Its Application to Neutrino Mass Generation

arXiv:2409.09033v3 Announce Type: replace-cross Abstract: We develop a general framework of rank-preserving, element-wise matrix transformations for engineering fermion mass hierarchies in theory-space constructions. We prove that preservation of massless modes requires the transformation function to be separable, $g_f(i,j)=g^{(L)}_f(i)g^{(R)}_f(j)$, which in turn enables independent control of left- and right-chiral zero-mode profiles directly at the level of the theory-space mass matrix. This formalism unifies and extends the clockwork mechanism, permits controlled deformation of Kaluza–Klein spectra, and enhances hierarchy generation in GIM-like fine-cancellation scenarios. As a concrete application, we show that in theory-space models for neutrino masses, suitable transformations allow sub-eV light neutrinos to arise from TeV-scale new physics with only $\mathcal{O}(40)$ additional fermionic sites, while remaining consistent with charged-lepton flavor-violation bounds. In contrast, the corresponding untransformed models asymptote at the MeV scale and cannot access the phenomenologically required regime without extreme field multiplicities or hierarchical parameters.

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

SkillMoV: Mixture-of-View Routing with Prototype-Conditioned Gating for Unified Multi-View Proficiency Estimation

Estimating human proficiency from video is a key challenge for automated skill assessment, with applications in sports coaching, music pedagogy, surgical training, and workplace learning. Existing approaches often focus on individual scenarios or rely on shared multi-view aggregation, limiting their ability to adapt to heterogeneous camera viewpoints and activity domains. We introduce SkillMoV, a unified, parameter-efficient framework for multi-scenario proficiency estimation from synchronized multi-view video. At its core, SkillMoV introduces a Mixture-of-View Projector (MoVP), which adapts the mixture-of-experts paradigm to camera-specific view features. MoVP is composed of four stages: (i) a Mixture-of-View soft router with twelve expert MLPs that learns view-dependent expert preferences without camera-identity supervision; (ii) cross-view attention to align synchronized cameras; (iii) learnable prototype anchoring to condition the representation on class-level reference vectors; and (iv) a prototype-conditioned gated projection that produces the final skill embedding. We evaluate SkillMoV on EgoExo4D across six skill domains and three separately trained view configurations: Ego, Exos, and Ego+Exos. SkillMoV reaches 50.17% overall accuracy in the Exos setting with a single model trained jointly across all scenarios, surpassing the strongest reported Exos result among the compared methods by 3.57 percentage points. In Ego+Exos, SkillMoV remains close to the best reported result in that setting (47.63% versus 48.20%). Ablations on the selected Exos configuration validate each component: MoV routing contributes +6.61 pp over attentive aggregation, cross-view attention +4.92 pp, prototype anchoring +4.07 pp, and stochastic view dropout +3.90 pp. Through LoRA adaptation, SkillMoV trains only 23.32% of its parameters and adds limited measured overhead relative to a LoRA-only baseline.

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

Driving, Fast or Slow? Neuro-Symbolic Guidance for Motion Prediction in Multi-Modal Ground Mobility

arXiv:2606.15251v1 Announce Type: cross Abstract: Accurate and interpretable motion prediction for heterogeneous traffic spaces, including pedestrians, bicycles, cars, and trucks, is essential for safe autonomous navigation. Nevertheless, state-of-the-art approaches remain predominantly black-box, lacking explicit encoding of the regulatory and behavioral constraints of real-world mobility. We propose Trajectory Compliance-Shaping (TraCS), a neuro-symbolic framework that augments existing black-box motion prediction backbones with interpretable and probabilistic first-order logic. To do so, TraCS employs an agentic code-generation pipeline to bridge the gap between natural-language descriptions of traffic regulations and probabilistic motion prediction. Furthermore, TraCS employs a reactive data-streaming inference engine that maintains and efficiently updates compliance landscapes as scenes evolve. To prevent TraCS from overconfidently steering the backbone's predictions in the wrong direction, we propose a neural confidence rating learned as a context-aware attenuation of the compliance signal. We demonstrate on the Argoverse 2 benchmark how TraCS consistently improves state-of-the-art prediction backbones, showing that probabilistic and symbolic compliance reasoning is a broadly applicable and computationally efficient complement to purely neural motion predictors.

19.
arXiv (CS.CV) 2026-06-12

Self-Evolving Vision-Language Models for Image Quality Assessment via Voting and Ranking

Improving vision-language models (VLMs) in the post-training stage typically relies on supervised fine-tuning or reinforcement learning, methods that necessitate costly, human-annotated data. While self-supervised techniques have proven effective for enhancing reasoning capabilities, their application to perceptual domains such as image quality assessment (IQA) remains largely unexplored. In this work, we introduce EvoQuality, a novel framework that enables a VLM to autonomously refine its quality perception capabilities without any ground-truth labels. EvoQuality adapts the principle of self-consistency to the ranking-based nature of IQA. It generates pseudo-labels by performing pairwise majority voting on the VLM's own outputs to establish a consensus on relative quality. These pseudo-rankings are then formulated into a fidelity reward that guides the model's iterative evolution through group relative policy optimization (GRPO). By iteratively leveraging its own predictions, EvoQuality progressively refines the VLM's perceptual capability. Extensive experiments show that EvoQuality boosts the base VLM's zero-shot performance by 31.8% on PLCC across diverse IQA benchmarks. Remarkably, despite being entirely self-supervised, EvoQuality achieves performance that is competitive with, or even surpasses, state-of-the-art supervised VLM-based IQA models, outperforming these models on 5 out of 7 IQA benchmarks. Furthermore, the framework demonstrates significant flexibility, allowing it to be stacked with pre-trained IQA models to bolster generalization on unseen datasets. Codes and checkpoints will be available at https://github.com/bytedance/EvoQuality.

20.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

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.AI) 2026-06-16

Variance Reduction for Non-Log-Concave Sampling with Applications to Inverse Problems

arXiv:2606.16257v1 Announce Type: cross Abstract: Sampling from high-dimensional, non-log-concave distributions with unnormalized densities is a fundamental challenge in machine learning, particularly when the exact gradient of the potential is unavailable and must be approximated via stochastic gradients that exhibit high variance under a fixed budget of gradient computations per iteration. Although variance reduction techniques such as SGD with momentum, STORM, and PAGE have demonstrated improved convergence properties in non-convex optimization, their implications for sampling from non-log-concave distributions remain largely unexplored. In this work, we develop the first unified analysis of these estimators for sampling from non-log-concave distributions. We establish improved non-asymptotic convergence rates in $\varepsilon$-relative Fisher information and, under a Poincaré inequality assumption, in squared total variation distance, and further prove weak convergence to the target distribution. We extend our analysis to solving inverse problems with score-based generative priors. We empirically validate our theory and demonstrate that, under a fixed gradient computations per iteration, variance-reduction techniques consistently improve sample quality in two standard imaging applications.

22.
PLOS Computational Biology 2026-06-10

Interpreting higher-order dependence in multimorbidity using cohort data: A partial information decomposition approach

by Cillian Hourican, Geeske Peeters, René J. F. Melis, Almar Kok, Natasja M. van Schoor, Sandra Wezeman, Mike Lees, Marcel G. M. Olde Rikkert, Rick Quax In the context of multimorbidity, clinical features seldom act in isolation: symptoms, signs and behaviours form interdependent systems in which joint effects on function can be demonstrated only when features are considered together. We introduce an open, reusable workflow that detects and interprets these “together-only” interactions using bivariate Partial Information Decomposition (PID; two sources to one target), linking synergy-based dependence to the broader network of clinical variables rather than to a single target. The workflow estimates synergy with small-sample bias correction and summarises each pair in a Breadth–Uniformity–Synergy–Total (BUST) map: breadth of synergy across target variables (broad “generalist” vs narrow “specialist” patterns), cross-stratum uniformity across age, sex and multimorbidity (uniform vs subgroup-specific), synergy strength, and total shared information. Simple diagnostics contrast observed targets with additive expectations, revealing the specific joint configurations through which non-additive effects arise. Applied to data from the Longitudinal Ageing Study Amsterdam, we treated all health-related variables—covering symptoms, clinical signs, behaviours, lifestyle factors, and self-rated health indicators—as both sources and targets in the PID framework. This symmetric design permits synergy to be quantified for every pair of variables with respect to every other variable. The workflow identifies synergistic constellations that additive models miss. Multidomain cliques involving subjective health, pain, cognition and grip strength showed multiple non-additive configurations, whereas pairs such as alcohol use with grip strength exhibited focused, narrow but uniform synergy. Notably, the pairs with the strongest synergistic contributions were largely distinct from those with the highest total mutual information, indicating that synergy captures dependency structure overlooked by conventional association measures. Rather than a new measure, this work provides a bias-aware workflow that makes higher-order dependence visible and transferable. Our results support synergy-aware mapping as a practical complement to conventional multimorbidity analyses: it highlights specific combinations of routinely assessed features whose joint states may be especially informative across multiple health targets and therefore candidates for prioritised joint assessment and future multi-domain intervention studies.

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

Right or Wrong, Models Comply: Directional Blindness in LLM Moral Judgment

As language models take integrated roles across many domains, the response of LLMs to user pushback becomes a critical alignment property. Yet many existing evaluations treat compliance as unidirectional, measuring whether models resist pressure but not whether they resist it selectively. We introduce Compliance Asymmetry (A = BCR/HCR), a bidirectional diagnostic that compares beneficial output change under helpful nudges with harmful change under misleading nudges. Across 9 models and 972,000 nudge-condition responses, we find that this selectivity differs in factual and moral judgments: models follow helpful nudges more than harmful ones on factual questions (A = 1.58), but follow both directions at nearly identical rates on moral questions (A = 1.04). This phenomenon persists across model families, capability levels, and nudging types. Interestingly, we also find that chain-of-thought prompting amplifies helpful and harmful compliance together, while identity-based prompting suppresses both by nearly identical margins. These results identify direction-blind moral compliance as a distinct failure mode in current LLMs and suggest that alignment should target directionally calibrated updating rather than lower compliance alone.

24.
arXiv (CS.LG) 2026-06-18

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

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

25.
arXiv (math.PR) 2026-06-11

Feynman–Kac formula for the heat equation with a one-center point interaction in $d=3$

arXiv:2606.11677v1 Announce Type: new Abstract: We study Schrödinger operators with a one-center point interaction, formally defined by \begin{align*} -\Delta_\alpha=-\Delta+\alpha\,\delta_0(\cdot), \end{align*} for $\alpha\in\mathbb{R}$, and the associated heat equation \begin{align} \partial_t u=\tfrac{1}{2}\Delta_{\alpha} u,\quad u(0,x)=u_0(x)\in C_c^{\infty}(\mathbb{R}^3\setminus\{0\}).\label{eq:HEapp} \end{align} Here $\Delta$ denotes the Laplacian (self-adjoint on $L^2(\mathbb{R}^3)$) and $\delta_x$ the Dirac measure at $x$. The operator $-\Delta_\alpha$ can be realized either as a self-adjoint extension of $-\Delta|_{C_0^{\infty}(\mathbb{R}^3\setminus\{0\})}$ in $L^2(\mathbb{R}^3)$, or as the norm-resolvent limit of $-\Delta+\lambda_\varepsilon V(\cdot/\varepsilon)$ for suitable $\lambda_\varepsilon$ and $V:\mathbb{R}^3\to\mathbb{R}$. In this paper we construct, for each $t>0$ and $x\in\mathbb{R}^3\setminus\{0\}$, a probability law on path space and a normalizing function $G_t^\alpha(x)$ giving the following probabilistic representation of the solution to the associated equation: \begin{align*} u(t,x)=G_t^\alpha(x)\,\mathbb{E}\bigl[u_0\bigl(W^{t,x}(t)\bigr)\bigr], \end{align*} where $\{W^{t,x}(s):0\le s\le t\}$ is a continuous process depending on $(t,x,\alpha)$. The result provides a Feynman–Kac type formula for the heat equation with a one-point interaction in three dimensions.