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01.
arXiv (CS.LG) 2026-06-24

Machine Learning and Deep Learning for Exoplanet Detection and Atmospheric Characterization with JWST and the Upcoming Ariel Mission

arXiv:2606.23766v1 Announce Type: cross Abstract: The detection and atmospheric characterization of exoplanets have entered a new data-intensive era driven by the James Webb Space Telescope and the upcoming Ariel mission. Modern surveys produce millions of light curves and high-resolution spectra that overwhelm traditional pipelines, motivating the rapid integration of Machine Learning and Deep Learning methods into the exoplanet workflow. This review synthesizes the latest progress in applying ML/DL techniques to exoplanet detection (transit identification, candidate vetting, false-positive rejection) and atmospheric characterization (retrieval, detrending, cross-correlation, surrogate modelling) in the context of JWST and Ariel. We start with classical algorithms such as Random Forests and Convolutional Neural Networks, move through Transformers and Recurrent architectures, then survey modern simulation-based inference using Neural Posterior Estimation and Flow Matching Posterior Estimation with normalizing or continuous normalizing flows. We discuss benchmark efforts, including the Ariel Machine Learning Data Challenges (2019 to 2025) hosted with NeurIPS, and key JWST case studies such as the WASP-39b Early Release Science programme. Results indicate that DL approaches consistently match or exceed traditional pipelines in both speed and accuracy, while ML-driven retrievals reduce inference time from CPU-hours to seconds and can accelerate nested-sampling retrievals by factors of 3-8 without compromising Bayesian evidence. We identify outstanding challenges interpretability, calibration of uncertainties under noisy data, hybrid modelling, and the generalization of models across instruments and planet populations and outline a research roadmap spanning the JWST era and beyond into Ariel's launch in 2029.

02.
arXiv (CS.CV) 2026-06-11

Learning Instance-Adaptive Low-Rank Orthogonal Subspaces for Clothes-Changing Person Re-Identification

Clothes-changing person re-identification (CC-ReID) aims to recognize individuals despite drastic appearance changes caused by clothing variation. While existing methods rely on adversarial learning to disentangle clothing features, we propose Ortho-ReID, which explicitly models a low-rank clothing subspace from VLM text descriptions and extracts clothing-invariant representations via direct geometric constraints. A critical component is our transformer-based Basis Maker, which refines a shared, low-dimensional clothing prior into an instance-adaptive low-rank subspace through cross-attention with image patches, enabling robust clothing feature extraction even under varying visibility conditions. This instance-adaptive subspace is supervised via alignment with clothing text embeddings, while identity features are extracted via a learnable projection head and geometrically constrained to be strictly orthogonal to it. Extensive experiments demonstrate state-of-the-art performance on PRCC (+5.9% top-1), Celeb-reID-light (+3.5%), and LaST (+5.3%), with competitive results on LTCC.

04.
arXiv (quant-ph) 2026-06-19

Single-Step Phase-Engineered Pulse for Active Readout Cavity Reset in Superconducting Circuits

arXiv:2512.08393v2 Announce Type: replace Abstract: In a circuit QED architecture, we experimentally demonstrate a hardware-efficient and qubit-state-dependent Single-Step Phase-Engineered (SSPE) pulse scheme for actively depopulating a readout cavity. The protocol appends a reset segment with tailored amplitude and phase to a standard square readout pulse. Within the linear-response regime, the optimal reset amplitude scales proportionally with the readout amplitude, while the optimal reset phase remains invariant, significantly simplifying the experimental calibration procedure. Time-resolved measurements of the cavity photon number dynamics demonstrate that the SSPE scheme significantly outperforms the CLEAR protocol in terms of reset speed. Crucially, this approach enables arbitrarily fast, overshoot-free depletion of the cavity photon population, with the ultimate reset rate constrained by the finite analog bandwidth of the measurement chain. Furthermore, a comprehensive evaluation of the QND nature demonstrates that the SSPE scheme introduces no additional non-QND measurement errors. It exhibits non-QNDness comparable to both the free-decay and CLEAR protocols, with residual errors predominantly governed by state switching induced by qubit relaxation during the readout process. Thses results establish the SSPE scheme as a practical and scalable approach for achieving rapid and smooth cavity reset in superconducting quantum circuits.

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

Uncertainty Quantification of Engineering Structures by Polynomial Chaos Expansion and Multivariate Active Learning

arXiv:2606.17233v1 Announce Type: new Abstract: In many engineering applications, a single high-fidelity model produces multiple quantities of interest (QoIs) under the same input parameters, e.g. finite element models of complex physical systems. To alleviate the high computational cost of direct model evaluations, surrogate models are widely used to construct efficient approximations of model responses. Naturally, the accuracy of surrogates strongly depends on the quality of the experimental design (ED). However, a single ED may not provide an adequate representation for all outputs simultaneously, especially when different outputs exhibit varying sensitivities to the input variables. A straightforward solution is to perform separate sampling for each output, but this results in increased sampling complexity and computational cost. From a statistical perspective, such an approach also ignores potential correlations among all outputs and may compromise data consistency. To address this issue, an adaptive sequential sampling method for constructing polynomial chaos expansion surrogate models is generalized for vector valued QoIs. The method sequentially selects new samples from a candidate pool based on their local contribution to the output variance, while balancing distance-based exploration of the input space and exploitation of aggregated variance information across all outputs. Its performance is compared with non-sequential Latin Hypercube Sampling through several numerical examples from engineering problems. Numerical results demonstrate that the proposed strategy improves both surrogate accuracy and stability, and provides a more reliable estimation of second-order statistics.

08.
arXiv (CS.CV) 2026-06-24

3D Masked Autoencoders are Robust Learners of Volumetric and Multimodal Cellular Representations for Microscopy

Self-supervised learning in fluorescence microscopy often relies on 2D projections, despite the inherently three-dimensional nature of cells. We present a systematic comparison of 2D and 3D masked autoencoders (MAE-2D vs. MAE-3D) on volumetric microscopy data. Under matched architectures and training protocols, MAE-3D consistently outperforms 2D max-projection and slice-based variants on downstream single-cell tasks. We further align visual representations with a pretrained protein language model (ESM2) and show that cross-modal supervision yields larger gains for volumetric models. Channel cross-attention and frequency-domain regularization are critical for leveraging 3D spatial context. On a protein–protein interaction task, MAE-3D achieves a ROC–AUC of 0.865, outperforming prior methods by up to +0.025. For protein localization, our best 3D model attains state-of-the-art AUC$_{micro}$ (0.952) and F1$_{micro}$ (0.742), improving over previous approaches by +0.003 and +0.010 absolute, respectively. Overall, these results demonstrate the advantages of native 3D modeling and multimodal alignment for representation learning in single-cell microscopy.

09.
arXiv (CS.LG) 2026-06-17

Constrained Diffusion Models with Primal-Dual Inference

arXiv:2606.17192v1 Announce Type: new Abstract: This paper develops constrained diffusion models with primal-dual inference (PDI) to sample from optimal distributions of entropy-regularized optimization problems with average constraints. We formalize constrained sampling in the Lagrangian dual domain, where the optimal distribution takes the form of a Gibbs distribution indexed by the optimal dual variable. Rather than estimating this dual multiplier before sampling and freezing it throughout generation, PDI jointly infers the optimal primal distribution and its parametrizing dual variable. Each reverse diffusion step denoises using the score field associated with the current multiplier and then updates the multiplier through dual ascent using the estimated constraint violation of the denoised samples. To enable this conditional score field, we train a single dual-conditioned score network over the family of Gibbs distributions induced by the dual variables encountered during inference. We prove that the time average of the dual variables generated along the inference trajectory converges to a neighborhood of the dual optimum and bound the effect of residual dual mismatch on the terminal distribution through schedule-dependent stability factors. We evaluate PDI on constrained sampling from a mixture of Gaussians, wireless resource allocation, and portfolio management.

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

Closing the Calibration Gap in Semantic Caching

Semantic caching cuts LLM inference costs by serving a cached response to semantically similar queries. Standard practice evaluates these systems using PR-AUC, a metric that only measures how well scores rank and ignores whether they are usable at a fixed threshold. We show this mismatch leads to systematically poor deployment choices, as models with the highest PR-AUC are often the worst in operation. We introduce Precision-Cache Hit Ratio (P-CHR) AUC, a cache-aware metric that measures precision across cache utilization levels, and Calibration Retention Rate (CRR), which captures how much offline ranking quality survives at deployment. We decompose the operational gap between offline and deployed quality into a recoverable calibration component and an irreducible structural component fixed by the dataset's positive rate. Our experiments show that the calibration gap is governed by the training objective rather than data scale, and post-hoc calibration only partially closes it. Ultimately, model selection for semantic caching is a calibration problem, not a ranking one, and measuring it is the first step to closing the gap.

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

CzechDocs: A Multiway Parallel Dataset of Formatted Documents for Minority Languages in Czechia

We present CzechDocs, a multiway parallel dataset of formatted documents (HTML, DOCX, and PDF) covering Czech and minority languages used in Czechia-primarily Ukrainian and English, with smaller portions of Vietnamese, Russian and other languages. The dataset is designed to support the evaluation of machine translation systems that aim to preserve document formatting during translation. We provide a comparison of the most common approaches to format-preserving machine translation on a validation subset of the dataset. This validation split, together with the evaluation toolkit, is publicly released for further research. A held-out test split will be reserved for a future shared task focused on document-level translation with formatting preservation.

12.
arXiv (CS.LG) 2026-06-17

Domain-Validity-Gated Metamorphic Testing of Scientific ML Surrogates

arXiv:2606.17529v1 Announce Type: cross Abstract: Scientific machine-learning (SciML) surrogates approximate expensive simulations, but exact expected outputs for arbitrary inputs are unavailable (the oracle problem). Metamorphic testing checks relations across executions, yet a candidate relation is not automatically valid: its preconditions, output mapping, and the numerical floor of the scoring operator determine whether a violation is meaningful. We study how candidate metamorphic relations (MRs) can be screened for domain validity and turned into executable, oracle-free test assets for SciML surrogates. We propose (i) a domain-validity rubric that admits a candidate only when its tolerance dominates the operator's numerical floor and its preconditions hold; (ii) an MR-card executable-asset format recording source cases, transformations, metrics, tolerances, and typed relation-level verdicts; and (iii) a case-study protocol on MeshGraphNets cylinder-flow surrogates, with a claim ledger binding every result to a tracked artifact. On a MeshGraphNets checkpoint, node permutation holds to machine precision, mirror-y is a bounded out-of-distribution stress finding rather than an exact symmetry, and absolute conservation stays deferred while a reference-relative guard passes. The same readings hold across held-out trajectories, a checkpoint roster, three further architectures, and PhysicsNeMo. On a second CFD task (compressible airfoil) the predicate instead rejects incompressible continuity on physical grounds, showing it reasons about domain validity rather than running a fixed checklist. On a second PDE family, FNO Burgers and heat surrogates run full admit/reject/execute verdicts. The evidence spans two CFD tasks and a second PDE family, supporting a validity-aware bridge from candidate MRs to auditable SciML test assets that separates model-level violations from out-of-domain applications.

13.
arXiv (CS.AI) 2026-06-12

PolyFlow: Safe and Efficient Polytope-Constrained Flow Matching with Constraint Embedding and Projection-free Update

arXiv:2606.13400v1 Announce Type: cross Abstract: While flow-based generative models have demonstrated strong performance across a wide range of domains, deploying them in safety-critical physical systems remains challenging due to strict constraint requirements. Existing approaches typically enforce safety through post-hoc corrections, which incur substantial computational overhead and may distort the learned distribution. We propose PolyFlow, a polytope-constrained flow matching framework that embeds constraints directly into the model and flow dynamics. PolyFlow introduces a discrete-time flow formulation and a projection-free architecture, which eliminate the discretization error and guarantee strict satisfaction of arbitrary polyhedral constraints, without the need for expensive iterative solvers. Experimental results show that PolyFlow achieves zero constraint violation while maintaining high distributional fidelity across a range of planning and control tasks. Compared to state-of-the-art constrained generation baselines, PolyFlow significantly reduces inference latency and demonstrates a favorable trade-off between safety, efficiency, and generative quality. Code is available on https://github.com/MJianM/PolyFlow.

14.
arXiv (CS.CL) 2026-06-12

SupraBench: A Benchmark for Supramolecular Chemistry

Supramolecular chemistry, which includes the study of non-covalent host-guest assemblies, has advanced various applications. However, designing host-guest systems remains time-consuming, requiring days of dry-lab verification per candidate pair. Although LLMs have emerged as a fast alternative with strong performance on molecular binding tasks, no benchmark currently systematically evaluates LLMs for host-guest reasoning across fundamental supramolecular chemistry tasks, e.g., binding affinity prediction. To this end, we collaborate with domain experts to release the first Supramolecular Benchmark, called SupraBench, to evaluate LLMs in chemistry reasoning. Specifically, we design four fundamental tasks, i.e., binding affinity prediction, top-binder selection, solvent identification, and host-guest description, plus an auxiliary vision-based task for molecular identification. We also release SupraPMC, a curated 16M-token corpus of Supramolecular chemistry articles distilled from Europe PMC, to support the adaptation to the supramolecular domain. We benchmark a broad range of open and proprietary LLMs and find that LLMs leave substantial headroom across all tasks. Domain adaptation pretraining over SupraPMC transfers cleanly to in-distribution regression but trades off against strict letter-format output. Moreover, the difficulty profile differs sharply across task families, revealing distinct failure modes that indicate specific gaps in current supramolecular chemistry reasoning. Our source codes and benchmark datasets are available at https://github.com/Tianyi-Billy-Ma/SupraBench.

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

LapidaryEngine: Fully Conversational Crystal Generation

arXiv:2606.14215v1 Announce Type: new Abstract: The emergence of Large Language Models (LLMs) has inspired the vision of generating bespoke crystal materials directly from natural-language instructions, enabling users to design materials through intuitive, conversational interaction. Existing text-to-crystal generative models represent important early steps toward this goal, but they suffer from two critical limitations: (i) restricted input formats that require highly structured descriptions (e.g., chemical formulas), and (ii) one-directional generation, where models can map text to crystal but cannot perform the inverse. These limitations prevent fully conversational workflows and hinder alignment with users' inherently ambiguous and evolving desiderata. We address these challenges with LapidaryEngine, the first model to support fully conversational crystal generation. LapidaryEngine accepts free-form natural-language requests and performs iterative refinement and editing in a dialogue-like manner. The key innovation is a pivot representation, a third, intermediate form that enables bidirectional translation between text and crystal structures despite the absence of direct paired datasets. Leveraging this pivot allows robust interpretation of user feedback and precise structural control. We demonstrate LapidaryEngine across diverse tasks, including insulator discovery, stability optimization, compositional modification, and structural editing, showcasing its ability to align generated materials with user intent in an interactive manner.

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

Rethinking Groups in Critic-Free RLVR

Reinforcement learning (RL) has become a central paradigm for post-training large language models. Existing critic-free RL methods typically generate a group of rollouts for the same question to estimate value baselines for advantage computation. However, this design suffers from data inefficiency, group synchronization barriers, and inflexibility with structured rollouts. In this work, we revisit the role of the ``group'' and show that its underlying function is not merely to estimate baselines but to prevent false penalties on negative samples. Building on this insight, we propose negative token filtering, a simple and effective strategy that enables stable single-rollout training. We apply it to two batch-level advantage methods, achieving comparable performance on reasoning tasks and stronger performance on agentic tasks relative to group-based RL techniques.

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

G2IA: Geometry-Guided Instance-Aware Retrieval and Refinement for Cross-Modal Place Recognition

Cross-modal place recognition (CMPR) enables camera-only robots to localize against pre-built LiDAR maps in autonomous navigation scenarios. This image-to-point-cloud setting is challenged by two coupled ambiguities: the modality gap between perspective RGB appearance and sparse metric geometry, and perceptual aliasing among urban places with similar roads, facades, intersections, and object arrangements. Instead of treating CMPR as a single global descriptor matching problem, we argue that reliable retrieval requires both geometry-aware representation alignment and fine-grained candidate verification. In this paper, we propose G2IA, a geometry-guided instance-aware framework for image-to-point-cloud place recognition. In the retrieval stage, visual geometry priors from VGGT and instance features are integrated to construct place descriptors that are more compatible with LiDAR-derived map representations. In the refinement stage, the retrieved candidates are re-ranked by explicitly verifying whether local instance shapes and their relative spatial layouts are consistent across modalities. Experiments on public benchmarks demonstrate that G2IA consistently improves image-to-point-cloud place recognition under different localization thresholds, and exhibits strong cross-dataset generalization.

18.
arXiv (CS.CV) 2026-06-17

Geometric Consistency Protocol for Foundation Model Features in Multi-View Satellite Imagery

Standardized evaluation protocols are indispensable for robust benchmarking in remote sensing, particularly as foundation features are increasingly transferred across diverse sensors and complex imaging geometries. In satellite multi-view reconstruction, conventional evaluations relying on unconstrained 2D global matching are often misleading. The Rational Function Model (RFM) and its Rational Polynomial Coefficients (RPC) dictate a curved, height-dependent epipolar geometry that render flat 2D search spaces physically inconsistent. We propose a geometry-faithful and reproducible protocol tailored for the RPC framework. Our approach integrates an RPC-projected 3D consistency metric with a geometry-constrained dense matching proxy, specifically evaluating whether similarity responses remain localized and unique under physically plausible search manifolds. A pivotal finding of our joint reporting strategy is the decoupling of semantic agreement and geometric localization: high cross-view similarity at a projected 3D point does not guarantee reliable matchability in practical inference. Our benchmark demonstrates that incorporating geometric constraints is fundamental to the problem definition in satellite imagery. Furthermore, we show that state-of-the-art 2D backbones remain remarkably competitive against specialized 3D-aware models when subjected to this RPC-consistent evaluation.

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

CMIP-Forge: An Agentic System that Retrieves, Computes, and Self-Reviews Climate Science

arXiv:2606.17076v1 Announce Type: cross Abstract: The Coupled Model Intercomparison Project Phase 6 (CMIP6) has generated thousands of peer-reviewed publications documenting model configurations, evaluation procedures, emergent constraints, and projection uncertainties. As the community transitions toward CMIP7, efficiently extracting and operationalizing this unstructured knowledge alongside live data analysis represents a critical bottleneck. Here we present CMIP-Forge, a hybrid retrieval-augmented generation (RAG) and autonomous analysis system that bridges the gap between scientific literature and Earth System Grid Federation (ESGF) data archives. The system pairs a curated corpus of 6,581 CMIP6-related open-access publications (101,828 indexed chunks) with an agentic pipeline in which a tool-augmented worker plans and executes Python workflows over live climate data, while a panel of independent reviewer models audits its methodology end to end. CMIP-Forge introduces a multi-layered Defense-in-Depth architecture that enforces physical and methodological invariants through executable mechanisms: Abstract Syntax Tree (AST) static analysis, audited scientific primitives, and an autonomous adversarial peer-review protocol. We demonstrate the system's capabilities through end-to-end autonomous research pipelines spanning atmospheric teleconnections, ocean dynamics, regional extremes, and global warming projections. An agentic analysis system grounded in peer-reviewed literature, constrained by automated code guardrails, and audited by an independent adversarial review loop can complete complex climate-research workflows autonomously. The same experiments expose concrete failure modes of the review loop (sycophantic regression, REVISE verdicts that are never resolved, and the submission of stub code for review), each diagnosable from the immutable telemetry and provenance record released with the article.

20.
arXiv (CS.AI) 2026-06-17

From Paper to Program: Knowledge Externalization for AI-Assisted Quantum Many-Body Code Generation

Authors:

arXiv:2604.04089v3 Announce Type: replace-cross Abstract: Large language models can write scientific code, but direct paper-to-program translation remains fragile when correctness depends on tacit conventions in the literature. We identify this bottleneck as knowledge externalization: converting implicit computational assumptions – index conventions, gauge choices, fermionic signs, contraction order, and memory constraints – into an explicit technical specification before implementation. We evaluate a multi-stage, human-in-the-loop workflow that inserts such a specification, with validation and stop gates, between theory extraction and code generation. The workflow is tested on two algorithmically distinct quantum many-body tasks: variational sweep-based Density-Matrix Renormalization Group (DMRG) from a pedagogical review and constructive Pfaffian conversion of Hartree–Fock–Bogoliubov states to matrix product states from the five-page Letter by Jin et al., Phys. Rev. B 105, L081101 (2022), for which no public code is available. For DMRG, all 16 specification-guided model pairings in a $4\times4$ grid satisfy physics-validation criteria, compared with 6/13 direct attempts. A prose-specification ablation indicates that externalized content, not \LaTeX{} formatting, is the essential ingredient. For Pfaffian-MPS, the workflow succeeds in 11/26 archived attempts, whereas direct prompting yields zero audited passes. Cross-specification transfer is asymmetric: non-GPT specifications implemented by GPT~5.5 pass 4/4, while GPT~5.5 specifications implemented by weaker models fail 4/4, indicating a residual implementation-model bottleneck. The resulting Paper-to-Program Many-Body skill provides an auditable protocol for AI-assisted implementation of many-body algorithms and for diagnosing where externalization succeeds or fails.

21.
arXiv (CS.AI) 2026-06-17

Visual Verification Enables Inference-time Steering and Autonomous Policy Improvement

arXiv:2606.18247v1 Announce Type: cross Abstract: Robots deployed in the real world should learn from their experience and improve over time. This requires a mechanism of practicing and learning from feedback. In this paper, we propose VERITAS, a generator-verifier framework for generalist robot policies for inference-time policy steering and self-improvement. We use a pre-trained generalist robot policy as a ``generator'' and pair it with a gradient-free ``visual verifier'' that evaluates actions at inference time. This framework enables inference-time steering that improves policy performance without additional training. We demonstrate that inference-time verification consistently outperforms vanilla generalists without training on additional demonstration data. Additionally, we demonstrate that the verified rollouts provide effective supervision for offline policy improvement: policies fine-tuned on verified self-generated trajectories achieve consistent performance gains. Notably, we find that post-training with verified rollouts achieves comparable efficiency to expert demonstrations, while requiring no human interventions. Our results highlight inference-time verification as a practical and scalable mechanism for improving robotic policies during deployment.

22.
arXiv (CS.LG) 2026-06-18

TS-Fault: Benchmarking Time Series Forecasters Against Structural Faults

arXiv:2606.18539v1 Announce Type: new Abstract: Time series forecasting (TSF) underpins consequential decisions in energy, transportation, finance, and healthcare, yet TSF models are almost universally ranked by a single number (e.g., average error) on clean held-out data, under the implicit assumption that it predicts deployed reliability. However, real faults are not i.i.d noise but structured events with temporal shape, broken cross-variable dependencies, regime change coupled with missingness, and causal propagation across a sensing pipeline. Treating TSF robustness as a data-quality problem, we present TS-Fault, a benchmark that evaluates forecasting models under explicit, parameterized fault scenarios with controllable semantic difficulty. TS-Fault organizes recurring failures into four modes along two orthogonal axes (observation- vs mechanism-level; univariate vs multivariate) and injects each fault into the most prediction-critical window via a unified importance score. This design enables robustness to be tested against the structures models actually rely on, rather than reduced to generic noise sensitivity. We evaluate 21 models across 6 datasets, 4 modes, and 5 difficulty levels under a paired clean/corrupt protocol. The results reveal three findings that contradict common leaderboard intuition: (i) clean-data accuracy anti-correlates with robustness; (ii) clean rankings are preserved under observation-level faults but reshuffled under mechanism-level faults; and (iii) all catastrophic failures occur under mechanism-level faults, with foundation models achieving the highest clean-data accuracy yet exhibiting the greatest fragility. The code is publicly available at https://github.com/Ray-zyy/TS-Fault.

23.
arXiv (CS.AI) 2026-06-17

First, do NOHARM: towards clinically safe large language models

arXiv:2512.01241v3 Announce Type: replace-cross Abstract: Large language models (LLMs) are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a 1,100-task benchmark of primary care-to-specialist consultation cases to measure the frequency and severity of harm from LLM-generated medical recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 28 LLMs, recommendations carried the potential for severe harm in up to 22.6% of cases, with errors of omission accounting for more than 80% of severe errors. In a randomized trial of 101 generalist physicians, human benchmark performance significantly improved with AI assistance, yet physicians remained far from realizing the potential of AI tools, frequently ignoring essential advice surfaced by AI. Safety performance tracked general-intelligence and medical-knowledge benchmarks across the full range of models but decoupled at the frontier. Despite strong performance on existing evaluations, widely used AI models can produce medical advice with the potential for severe harm at non-trivial rates, highlighting the importance of explicit measurement of clinical safety.

24.
medRxiv (Medicine) 2026-06-23

The Target ALS Global Natural History Study: Cross-platform proteomics to accelerate biofluid biomarker and drug target discovery in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease of motor neurons for which therapeutics are limited. Improved biomarkers are imperative to improve patient care and therapeutic development. Here, we employed 35-plex isobaric tandem mass tag labeling based on isobutyl-proline reporter group (TMTpro) to perform unbiased proteomic analysis of cerebrospinal fluid (CSF) and plasma from control (n= 28, n= 31) and sporadic ALS (sALS) (n= 39, n= 41), from the Target ALS Global Natural History Study (TALS GNHS). We identified 2,875 proteins in CSF and 1,118 proteins in plasma and identified known and novel differentially expressed proteins (DEPs) between controls and sALS, some of which were orthogonally validated using immunoassay. Comparison of TMTpro-MS and Olink proximity extension assay proteomics revealed common and non-overlapping differentially expressed proteins illustrating strengths unique to each platform. This initial cross-sectional proteomic study of biofluids from the TALS GNHS, with unrestricted availability of study results to the research community, highlights the potential of this resource as a potent platform for ALS biomarker discovery.

25.
bioRxiv (Bioinfo) 2026-06-11

VFUSE: Virulent Feature Understanding with Sparse autoEncoders

Generative models have shown remarkable progress in a variety of domains such as protein design, but such power enables the opaque generation of hazardous proteins. In this work, we introduce VFUSE (Virulent Feature Understanding with Sparse autoEncoders), a mechanistic interpretability approach that trains SAEs on diffusion-transformer activations to audit protein models for hazard-aware features. We apply VFUSE to RoseTTAFold3 and RFDiffusion3, popular open-weight models for protein folding and synthesis. We find that for certain blocks, linear probes detect hazardous designs significantly better when fit in the SAE latent space over the original model's representations: improving interpretability without sacrificing model performance. Furthermore, we identify monosemantic features from the SAE that fire only on hazardous designs at up to AUROC 0.84 (q < 10-13).