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

LoMC: Localized Multidirectional Correction for Refusal Suppression in Routed Foundation Models

arXiv:2606.13709v1 Announce Type: cross Abstract: We study controlled post-training refusal suppression in routed MoE and hybrid-MoE foundation models, aiming to increase non-refusal target-response behavior while preserving general capability under a compact intervention footprint. Existing broad direction-based edits can perturb general-purpose computation, whereas support-only expert edits often lack sufficient capacity to correct heterogeneous refusal representations. To address this limitation, we introduce Localized Multidirectional Correction (LoMC), a support-gated intervention framework that follows a support-then-correction execution order: it first identifies a compact edit support, then aggregates prototype correction directions into layer-wise correction directions, and finally applies rank-one layer-wise correction only within the selected support. By using the edit support as a structural gating constraint, LoMC increases correction capacity without expanding the intervention scope. Experiments on text-only and multimodal safety benchmarks across four routed backbones show that LoMC substantially improves non-refusal target-response behavior while maintaining general capability under a compact intervention footprint.

02.
arXiv (CS.CL) 2026-06-16

LLM Judges Have Dark Current: A Psychometric Datasheet for LLM-as-a-Judge Evaluation

LLM-as-a-judge systems are now routinely used for open-ended model evaluation, where human preference annotation is costly, slow, and difficult to reproduce. Yet these judges are often reported as scalar accuracy, win-rate, or agreement devices. We argue that a judge should instead be reported as a measurement instrument. We introduce a Judge Datasheet protocol that measures dark current under true-vacuum inputs, stable cross-sensitivity to same-quality surface variation, positional false preference, target sensitivity on a controlled quality ladder, and the criterion or operating point induced by tie instructions. The direction-stability decomposition reveals that apparent Delta0 preference can be stable surface response or disguised position bias. In a three-judge open-weight case study, Llama-3.1-8B shows high dark current and presentation-conflicted Delta0 behavior, Qwen2.5-14B is vacuum-clean and target-sensitive but mixes stable and positional over-discrimination, and Qwen2.5-32B is vacuum-clean with low stable cross-sensitivity and low positional false preference. A strict tie criterion eliminates Qwen32B Delta0 false preference but absorbs marginal Delta1 target signals into ties while preserving Delta5 sensitivity. The results show that prompting moves the criterion, not the resolution. We do not claim that the downstream mechanism hypothesis that motivated this work is confirmed; the contribution is a metrological protocol for measuring the measuring device before downstream claims are made.

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

Using Seismic Statistical Features and VQ-VAE to Improve Spatiotemporal Seismicity Predictability

arXiv:2606.10069v2 Announce Type: replace Abstract: In this paper we build upon a previous study in which we demonstrated, using XGBoost and earthquake catalogue data from Japan and Chile, that a set of 60 seismic statistical features (SSFs) had much greater predictive value than a set of 428 generic time series features from the tsfresh package. We here extend this previous work in two key ways, focusing on data from Japan as a large dataset is necessary in order to allow for the training of a deep learning (autoencoder) model. First, we move from whole-region prediction (considering, for each candidate event, the likelihood of an event M $\geq$ 5.0 anywhere in the region in the next 15 days) to localised predictions in which both the region of feature computation and the region of prediction are restricted to a circle of radius 24 km around the candidate event, and we show that performance remains excellent, similar to our previous whole-region study for the same area. Second, we here couple this proven set of SSFs, based on one-dimensional (catalogue) data, with a novel feature based on two-dimensional seismic maps, obtained by training a VQ-VAE model to reproduce such maps as output and identifying a measure of its error in doing so with a localised build-up of crustal stress. We show that while localised prediction based on SSFs can be effective alone, with test AUC values as high as those obtained in the case of Japan in our previous whole-region study, the inclusion of the new natively-spatial VQ-VAE-derived feature, top-ranked by SHAP analysis, can enhance performance and additionally appears to near-wholly replace the traditionally-computed $b$-value in terms of feature usage.

05.
arXiv (CS.LG) 2026-06-12

Data-driven Lake Water Quality Forecasting for Time Series with Missing Data using Machine Learning

arXiv:2601.15503v2 Announce Type: replace Abstract: Volunteer-led lake monitoring yields irregular, seasonal time series with many gaps arising from ice cover, weather-related access constraints, and occasional human errors, complicating forecasting and early warning of harmful algal blooms. We study Secchi Disk Depth (SDD) forecasting on a 30-lake, data-rich subset drawn from three decades of in-situ records collected across Maine lakes. Missingness is handled via Multiple Imputation by Chained Equations (MICE), and we evaluate performance with a normalized Mean Absolute Error (nMAE) metric for cross-lake comparability. Among six candidates, ridge regression provides the best mean test performance. Using ridge regression, we then quantify the minimal sample size, showing that under a backward, recent-history protocol, the model reaches within 5% of full-history accuracy with approximately 176 training samples per lake on average. We also identify a minimal feature set, where a compact four-feature subset matches the thirteen-feature baseline within the same 5% tolerance. Bringing these results together, we introduce a joint feasibility function that identifies the minimal training history and fewest predictors sufficient to achieve the target of staying within 5% of the complete-history, full-feature baseline. In our study, meeting the 5% accuracy target required about 64 recent samples and just one predictor per lake, highlighting the practicality of targeted monitoring. Hence, our joint feasibility strategy unifies recent-history length and feature choice under a fixed accuracy target, yielding a simple, efficient rule for setting sampling effort and measurement priorities for lake researchers.

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

Topological Flow Matching

arXiv:2606.15897v1 Announce Type: cross Abstract: Flow matching is a powerful generative modeling framework, valued for its simplicity and strong empirical performance. However, its standard formulation treats signals on structured spaces, such as fMRI data on brain graphs, as points in Euclidean space, overlooking the rich topological features of their domains. To address this, we introduce topological flow matching, a topology-aware generalization of flow matching. We interpret flow matching as a framework for solving a degenerate Schrödinger bridge problem and inject topological information by augmenting the reference process with a Laplacian-derived drift. This principled modification captures the structure of the underlying domain while preserving the desirable properties of flow matching: a stable, simulation-free objective and deterministic sample paths. As a result, our framework serves as a drop-in replacement for standard flow matching. We demonstrate its effectiveness on diverse structured datasets, including brain fMRIs, ocean currents, seismic events, and traffic flows.

07.
Nature Medicine 2026-06-15

Long-term independent use of an intracortical brain–computer interface for speech and cursor control

Brain–computer interfaces (BCIs) can provide naturalistic communication and digital access to people with severe paralysis by decoding neural activity associated with attempted speech and movement. Recent work has demonstrated highly accurate intracortical BCIs for speech and cursor control, but two critical capabilities needed for practical viability were unmet: independent at-home operation without researcher assistance and reliable long-term performance supporting accurate speech and cursor decoding. Here we demonstrate the independent and near-daily use of a multimodal BCI with novel brain-to-text speech and computer cursor decoders by a man with paralysis and severe dysarthria due to amyotrophic lateral sclerosis. Over nearly 2 years, the participant used the BCI for more than 3,800 h at home with no researchers present to maintain rich interpersonal communication with his family and friends, independently control his personal computer and sustain full-time employment—despite being paralyzed. He communicated 183,060 sentences—totaling 1,960,163 words—at an average rate of 56 words per minute. He labeled 92% of sentences as being decoded at least mostly correctly. In formal quantifications of performance where he was asked to say words presented on a screen, attempted speech was consistently decoded with more than 99% word accuracy (125,000 word vocabulary). The participant also used the speech BCI as keyboard input and the cursor BCI as mouse input to control his personal computer, enabling him to send text messages and emails and to browse the internet. These results demonstrate that intracortical BCIs have the potential to support independent use in the home, marking a critical step toward practical assistive technology for people with severe motor impairment. An automated intracortical brain–computer interface, used at home with no researcher intervention, provides long-term and accurate restoration of speech-based communication and cursor-based computer usage in a person with severe dysarthria due to amyotrophic lateral sclerosis.

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

Structure-Oriented Randomized Neural Networks for Poisson-Nernst-Planck and Poisson-Nernst-Planck-Navier-Stokes Systems

arXiv:2606.19912v1 Announce Type: cross Abstract: We develop a structure-oriented randomized neural network framework, termed SO-RaNN, for the Poisson-Nernst-Planck (PNP) system and the Poisson-Nernst-Planck-Navier-Stokes (PNP-NS) system. The decoupled linearized subproblems are solved iteratively by randomized neural networks in a space-time framework. For the concentration variables, a pointwise cut-off is used to enforce positivity at the value level, and discrete mass-scaling factors are computed at selected correction instants and interpolated in time, so as to ensure exact mass matching at those instants and to promote approximate mass preservation between them. To introduce an auxiliary discrete dissipation mechanism, we further employ an SAV-type post-processing correction, which yields monotonicity of the SAV auxiliary variable under the ideal SAV update. For the PNP-NS system, a structure-preserving randomized neural network (SP-RaNN) is used for the velocity field, so that the velocity approximation satisfies the incompressibility constraint pointwise by construction. On the theoretical side, we derive residual-based estimates for the raw, uncorrected RaNN solvers of the linearized subproblems, formulate a conditional local-in-time convergence result for the raw outer Picard iteration of the PNP system, and analyze the value-level positivity correction together with the mass-correction and SAV post-processing steps. For the PNP-NS system, we establish an approximation result for the SP-RaNN space and provide a conditional error statement for the corresponding linearized Oseen-type problem. Numerical experiments demonstrate approximation accuracy in the source-driven manufactured tests and illustrate the intended value-level positivity correction, selected-time mass matching, computed free-energy curves based on the final gauge-fixed potential, and divergence-free approximation in benchmark tests.

09.
bioRxiv (Bioinfo) 2026-06-10

Bias-mitigated microbiome inference refines coronary artery disease signature

作者:

Roughly half the cells in the human body are microbial, and changes in these communities are increasingly implicated in cardiovascular, metabolic, and oncological diseases. Yet identifying which taxa truly differ in abundance, differential abundance (DA), is distorted by four major sources of bias: loss of total microbial load, taxa measurement efficiencies, arbitrary pseudocounts required to handle pervasive zeros, and contamination which has recently driven retractions. No existing DA method accounts for all four. Here we introduce BootDA, a non-parametric bootstrap-based method that explicitly models each bias source without data transformations, pseudocounts, parametric assumptions, or assuming that most taxa are non-DA. In semi-parametric simulations preserving the sparsity (>70% zeros) and correlation structure of real 16S amplicon data, BootDA achieved the highest sensitivity among tested methods, including ANCOM-BC2, LinDA, MaAsLin 3, and Wilcoxon tests, while controlling the false discovery rate. Performance was retained in low biomass settings when contamination contributed ~50% of counts, and without negative controls, indicating de novo decontamination capability. Applied to a coronary artery disease cohort, BootDA refined the original signature to two co-enriched genera, Klebsiella and Gemmiger, and excluded likely contaminants. BootDA is available as an R package and could generalise to other sparse, high dimensional biological data.

10.
arXiv (quant-ph) 2026-06-17

Acceleration-induced spectral blind spots in stimulated atomic transitions

arXiv:2606.17396v1 Announce Type: cross Abstract: Stimulated transitions are among the most fundamental processes in light-matter interaction, underlying resonant absorption and emission in atomic systems. Here we show that uniform acceleration can convert this familiar response into a frequency-selective absence of response. Specifically, when an incident photon has a nonzero momentum component transverse to the acceleration, the stimulated transition probability vanishes at a discrete set of frequencies fixed by the acceleration, the atomic transition frequency, and the photon propagation angle. At these spectral blind spots, both ordinary stimulated absorption and acceleration-induced excitation are simultaneously suppressed, rendering the atom effectively unresponsive to the incident radiation. The effect arises from the nontrivial response of accelerated atoms to quantum vacuum fluctuations and provides a distinctive signature of the Unruh effect through the absence, rather than the enhancement, of stimulated transitions. We further provide an order-of-magnitude estimate showing that an electron-based implementation with spin splitting in combined electric and magnetic fields could access the required parameter regime. These results reveal an unexplored form of acceleration-modified light-matter interaction and identify spectral blind spots as a new manifestation of the Unruh effect.

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

How Fragile Are Training-Free AI-Generated Image Detectors? A Controlled Audit of Score Direction, Preprocessing, and Compression

Training-free detectors of AI-generated images promise generator-agnostic deployment without classifier training, yet their reported numbers are rarely compared under a single controlled protocol. We audit two representative training-free scores – an autoencoder-reconstruction score (AEROBLADE-style) and a noise-perturbation feature-similarity score (RIGID-style) – plus a naive feature-kNN control, on a common 1,500-image GenImage-derived benchmark spanning seven generators and JPEG compression at quality 70 and 50. The audit yields three cautionary findings. (i) Implementation details masquerade as method differences: replacing the LPIPS backbone (AlexNet -> VGG-16) changes overall AUROC by +0.085, and switching between resize-to-512 and native-resolution preprocessing flips per-generator conclusions by up to 0.38 AUROC. (ii) Score direction is not a property of the method but of its hyperparameters: the RIGID-style score is inverted (AUROC < 0.5) on SD1.5 and Wukong at noise level sigma=0.05, recovers to >0.5 for every generator at sigma=0.01, and collapses to 0.15 at sigma=0.3. (iii) Dataset format bias inflates robustness claims: without unified re-encoding, AUROC under JPEG-50 exceeds the clean condition for the AlexNet-backbone reconstruction score; after bias correction the residual anomaly localizes to a single generator (BigGAN). The audited scores have complementary per-generator failure sets, but naive z-score fusion does not beat the best single score, indicating that exploiting complementarity requires direction-aware combination.

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

A Formal Framework for Declarative Agentic AI in Business Process Analysis

arXiv:2606.15291v1 Announce Type: new Abstract: Agentic AI opens new opportunities for automating Business Process (BP), enabling autonomous decision-making and dynamic adaptation. However, realising this potential requires BP entities and their interactions to be defined with formal precision. This paper presents a formal framework for Agentic BP analysis through the AGO methodology. AGO captures the modelling perspective in terms of who is acting (Agents), why it is carried out (Goals), and what the relevant entities are (Objects). Grounded in set theory and mathematical logic, we formally define the AGO entity types and their interactions, organising all definitions into a BP Knowledge Base (BPKB). The resulting BPKB supports structured querying, incremental updates, and automatic generation of BP workflows, while ensuring soundness and completeness of the derived paths.

13.
arXiv (CS.CL) 2026-06-16

DoubtProbe: Black-Box Jailbreak Defense via Structural Verification and Semantic Auditing

As large language models (LLMs) are increasingly deployed in user-facing systems, black-box jailbreak defense has become an important practical problem. Existing defenses often rely on known-attack coverage, prompt-level semantic judgment, or local runtime control, yet these paths can become unstable under evolving prompt packaging, expression rewriting, and structure manipulation. We observe that many black-box jailbreaks do not remove the harmful goal, but reorganize the information needed to express and execute it, thereby evading safety alignment while remaining recoverable during generation. Motivated by this observation, we propose DoubtProbe, a dual-branch inference-time defense framework that combines structural verification with semantic auditing and formulates black-box jailbreak defense as consistency checking under controlled transformation. The structural branch extracts a structured representation from the original request, reconstructs the request under representation constraints, and detects information-preservation failures between the original and reconstructed requests; the semantic branch audits the original prompt directly. We evaluate DoubtProbe against representative black-box defenses on jailbreak and benign-request benchmarks, and further test backbone transfer from Qwen2.5-72B to Llama-3.1-70B. Results show that DoubtProbe achieves a stronger and more stable defense-utility trade-off: on Qwen2.5-72B, it reduces the JBB attack success rate from 0.293 to 0.100 and the CodeAttack attack success rate from 0.152 to 0.001, while maintaining false positive rates of 0.022 and 0.016 on AlpacaEval and OR-Bench; the same pattern remains stable on Llama-3.1-70B. These findings show that structural inconsistency signals provide a practical and generalizable basis for black-box jailbreak defense, especially when combined with semantic auditing.

14.
arXiv (CS.AI) 2026-06-19

Protein Representation Learning with Secondary-Structure and Energy-Filtered Hydrogen-Bond Graphs

arXiv:2606.19374v1 Announce Type: cross Abstract: Graph-based representations are widely used in protein modeling, yet many existing approaches rely primarily on sequence adjacency or geometric proximity, which only partially reflect the principles governing protein folding. Proteins instead adopt complex three-dimensional conformations organized around secondary structure elements, such as $\alpha$-helices and $\beta$-sheets, which encode recurring local motifs and stabilizing hydrogen-bond interactions. In this work, we introduce a secondary-structure-aware graph neural network for protein representation learning. Residue-level node representations are augmented with secondary structure assignments, and graph edges are constructed from hydrogen-bond interactions filtered by their energetic strength. This design enables the model to capture both local structural context and long-range couplings that are central to protein stability and function. We evaluate the proposed approach on commonly used protein benchmarks and observe consistent improvements over existing graph-based methods. In addition, the resulting graph representations offer enhanced biological interpretability, as the learned connectivity aligns with established structural motifs. These findings suggest that incorporating secondary structure and energy-filtered hydrogen-bond topology provides an effective inductive bias for protein representation learning. The code is released at https://github.com/mohamedmohamed2021/SSProNet

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

The Safety-Aware Denoiser for Text Diffusion Models

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

16.
medRxiv (Medicine) 2026-06-22

AI-Assisted Longitudinal Analyses of Environmental and Psychosocial Determinants of Subjective Cognitive Difficulties

作者:

Short-term environmental exposures have been linked to cognitive and behavioral outcomes, although many reported associations may reflect broader geographic and contextual differences. Using longitudinal data from the All of Us Research Program (2018–2024), we linked daily weather and air-pollution exposures to repeated attention-related and subjective cognitive outcomes. Associations were evaluated using pooled, fixed-effects, lagged, and event-study analyses. Additional machine-learning analyses were conducted to explore potential heterogeneity and latent psychosocial structure. Replication analyses were performed using the 2024 Behavioral Risk Factor Surveillance System (BRFSS). Several environmental exposure measures showed small associations with cognitive outcomes in pooled analyses, but most attenuated substantially after accounting for within-location temporal variation. Mediation, sensitivity, and machine-learning analyses yielded similar conclusions. In contrast, mental-health burden, loneliness, and social functioning were consistently associated with subjective cognitive difficulty and exhibited substantially larger effect sizes than environmental exposures. Similar patterns were observed in BRFSS. Exploratory AI-assisted analyses yielded findings broadly consistent with the primary longitudinal analyses. These findings suggest that short-term environmental perturbations may have limited associations with cognitive outcomes after accounting for within-location variation, whereas psychosocial factors appear to be more consistently associated with subjective cognitive burden.

17.
arXiv (CS.LG) 2026-06-11

Quantum Occam Learning: Sample-Supported Expressibility for Circuit-Based Quantum Learning

arXiv:2606.12211v1 Announce Type: cross Abstract: A central principle in quantum machine learning is that an ansatz should be expressive enough to represent the quantum data of interest. Yet, the expressibility is statistically meaningful only insofar as it can be learned from finitely many copies of an unknown quantum state. In this work, we develop an information-theoretic Occam theory for quantum data generated by finite-size quantum circuits. For the class $S_{n,G}$ of $n$-qubit pure states preparable with at most $G$ two-qubit gates, a metric-entropy argument gives the realizable sample law $\widetilde{\Theta}(G/\epsilon^2)$ in the circuit-limited regime. For an arbitrary source $\hat{\rho}$, we introduce the best $G$-gate approximation error $d_G(\hat{\rho})$ and the approximate circuit complexity $C_\eta(\hat{\rho})$. We prove an agnostic quantum Occam theorem: with $M$ copies, one can learn up to the best $G$-gate approximation error plus a statistical penalty $\widetilde{O}(\sqrt{G/M})$. We then remove the need to know $G$ in advance through an adaptive model-selection theorem whose oracle inequality selects the circuit complexity justified by the data. Matching lower bounds yield a sample-supported expressibility law: at trace-distance accuracy $\epsilon$, $M$ samples can support only $G_supported \simeq M\epsilon^2$ gates, up to logarithmic factors and tomography saturation at $2^n$. Thus, the circuit complexity becomes an adaptive statistical resource rather than a static promise. Our framework turns bounded circuit complexity into a model-selection principle for quantum machine learning.

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

High-Fidelity 4D Hand-Object Capture via Multi-View Spatiotemporal Tracking and Physics-Aware Gaussians

The growing demand for high-fidelity 4D hand-object interaction (HOI) data in embodied AI and spatial computing is currently bottlenecked by the reliance on pre-scanned object templates and physical markers. While recent methods have demonstrated promising results in reconstructing 4D hand-object interaction from videos, they are highly sensitive to initial estimates of hand and object poses. Yet, estimating these poses from images is challenging, in particular under severe occlusion which is inherent in hand-object interaction scenarios. We propose a novel system for the robust and accurate reconstruction of hands and objects from synchronized and calibrated multi-view videos without requiring any templates or markers. Our system consists of two main components with key innovations: (1) a multi-view feed-forward transformer model that aggregates cross-view geometry and temporal cues to provide a reliable, metric-consistent initialization for both poses and dense object geometry, and (2) a hand-object physics-aware Gaussian-based optimization framework to refine the initial estimates, integrating tetrahedral constraints, collision refinement, and appearance decomposition to produce physically plausible and visually accurate reconstruction. Validated on public benchmarks and an extensive internal dataset, our pipeline achieves highly robust, artifact-free reconstruction, providing an efficient foundation for automated 4D asset generation. Our project page are available at https://zyshen021.github.io/HOSTPG/.

19.
arXiv (CS.CV) 2026-06-18

A Unified Framework for Efficient Remote Sensing Visual Question Answering: Adapting Dual, Hybrid, and Encoder-Decoder Architectures

Visual Question Answering (VQA) in the Remote Sensing (RS) domain presents unique challenges due to the high resolution, multi scale object distribution, and semantic complexity of aerial imagery. While general domain Foundation Models have achieved remarkable success, their direct application to RSVQA is hindered by massive domain shifts and the computationally prohibitive nature of full fine tuning. This study presents a comparative analysis of RS Adapter, a Parameter Efficient Fine Tuning (PEFT) strategy, applied across three distinct Vision Language Model (VLM) architectures: the Dual Encoder CLIP, the Encoder Decoder BLIP, and the Hybrid FLAVA. We introduce a unified architectural surgery pipeline that injects lightweight bottleneck adapters into the attention and MLP layers of frozen backbones, enabling rapid adaptation with less than 5 percent of trainable parameters. Experimental results on the high resolution RSVQA x dataset demonstrate that while all adapted models achieve convergence, the Hybrid FLAVA architecture offers a superior balance of multimodal reasoning and retrieval capabilities compared to its unimodal counterparts. Our findings establish a new baseline for resource efficient VQA in disaster assessment and urban monitoring.

20.
arXiv (CS.LG) 2026-06-12

Uncertainty Estimation for Molecular Diffusion Models

arXiv:2606.13451v1 Announce Type: new Abstract: Diffusion models have seen wide adoption for 3D molecular generation, yet they offer no principled signal of when a generated molecule is likely to be of low quality. We propose a post-hoc method for estimating per-sample uncertainty in pretrained molecular diffusion models. Building on a Laplace approximation of the denoising network, we measure the variability of the noise prediction across the generation trajectory. Empirically, we show that the resulting uncertainty score is informative of sample quality, exhibiting a negative correlation with established sample-level quality metrics. We further study how the proposed uncertainty score can be used to filter generated samples, improving model performance via test-time scaling.

21.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.

22.
arXiv (CS.AI) 2026-06-15

Position: Align AI to Our Aspirations, Not Our Flaws

arXiv:2606.13755v1 Announce Type: cross Abstract: We argue that aligning AI to aggregated human preferences is the wrong target. With current technology, one can train AIs to share the values of a Silicon Valley techno-optimist, a degrowth environmentalist, a national-conservative culture warrior, a single-party state cadre, or a devout religious traditionalist. We should not. Human values produce societies that thrive or fail on the merits of those values - from failed states and extreme inequality to declining happiness, political polarization, and government dysfunction in the world's wealthiest democracies. The pluralistic-alignment program correctly diagnoses that there is no single "humanity" to align with, but is dangerous if taken as the main directive. We argue that AI should be trained to a non-negotiable floor of objective alignment goals - competence, bounded by the constraints of factual accuracy, honesty, and lawfulness and that pluralism belongs at the surface (language, register, conventions, missing-context defaults) and across the wide band of legitimate value tradeoffs that respect the floor, but not at the level of values that violate it. We highlight the empirical reality of unfiltered pluralistic values, propose four commitments as a constructive alternative, and engage six credible objections: commercial pressure and practical feasibility, democratic legitimacy, regulatory compliance, over-reliance on institutionalist explanations, the charge that the floor itself is culturally laden, and the limits of Coherent Extrapolated Volition.

23.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

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

Breaking the Solver Bottleneck: Training Task Generators at the Learnable Frontier

The limiting resource for training agents via reinforcement learning (RL) is increasingly frontier task supply: valid, solvable tasks just difficult enough to train the current model. As reasoning and agentic models improve, fixed task distributions saturate, while naive synthetic generation yields tasks that are trivial, impossible, or ill-posed. Training a task generator with RL to optimize validity and learnability can address this bottleneck, but direct optimization requires repeated solver rollouts per candidate. For software-engineering (SWE) tasks, a single rollout can take tens of minutes; solver-in-the-loop generator training is intractable. We introduce PROPEL, a solver-amortized framework for training task generators at the targeted solve rate. PROPEL trains a lightweight activation probe on a one-time labeled corpus of generated tasks and solver outcomes. The probe predicts target-solver pass rate from a frozen generator reference model and serves as a proxy for solve rate during generator optimization, reducing generator evaluation to a single forward pass. Across math, code, and software-engineering at multiple model scales, PROPEL shifts generation toward the targeted solve rate: for coding, tasks generated at the learnable frontier increase from $10.1\% \rightarrow 20.0\%$ for a Qwen2.5-3B-Instruct solver and from $5.3\% \rightarrow 12.6\%$ for a Qwen2.5-7B-Instruct solver. For SWE, PROPEL increases the share of generations at the targeted solve rate from $9.8\% \rightarrow 19.6\%$ for Qwen3.5-27B on repositories not seen during training of probe and generator.

25.
arXiv (CS.CV) 2026-06-16

MeshFlow: Efficient Artistic Mesh Generation via MeshVAE and Flow-based Diffusion Transformer

We present MeshFlow, a new method for generating artist-like 3D meshes. Current mesh generators often adopt Auto-Regressive (AR) next-token prediction, a natural choice given the discrete nature of mesh topology. However, AR methods scale poorly because the inference cost is quadratic in mesh size. They also require discretizing the vertex coordinates, which introduces quantization errors. To address these challenges, we introduce a Variational Autoencoder (VAE) that, supervised with a contrastive loss, represents both continuous vertex positions and discrete connectivity in a continuous latent space. This latent space is significantly more compact than prior token-based mesh representations. We then build a 3D generator based on a Rectified Flow transformer, generating all mesh vertices and edges in parallel. Our model generates meshes 18x faster than the fastest AR generator while also achieving excellent accuracy across standard mesh-generation metrics. Homepage: https://mesh-flow.github.io/, Code: https://github.com/facebookresearch/meshflow