Protein language models (PLMs) learn probability distributions over natural protein sequences. By learning from hundreds of millions of natural protein sequences, protein understanding and design capabilities emerge. Recent works have shown that scaling these models improves structure prediction, but does not seem to improve mutation understanding and representation quality for protein function prediction. We introduce PoET-2, a multimodal, retrieval-augmented protein foundation model that incorporates in-context learning of family-specific evolutionary constraints with optional structure conditioning to learn generative distributions over protein sequences. PoET-2 uses a hierarchical transformer encoder that is equivariant to sequence context ordering and a dual decoder architecture with both causal and masked language modeling objectives, allowing PoET-2 to operate in both fully generative and bidirectional representation learning modes. PoET-2 achieves state-of-the-art performance on zero-shot variant effect prediction, excelling at scoring variants with multiple mutations and challenging indel mutations. In supervised settings, PoET-2 embeddings outperform previous methods for learning sequence-function relationships, especially with small datasets. This work highlights the benefits of combining retrieval augmentation with multimodal, family-centric modeling for advancing protein foundation models.

Predicting protein complex structures is essential for protein function analysis, protein design, and drug discovery. While AI methods like AlphaFold can predict accurate structural models for many protein complexes, reliably estimating the quality of these predicted models (estimation of model accuracy, or EMA) for model ranking and selection remains a major challenge. A key barrier to developing effective machine learning-based EMA methods is the lack of large, diverse, and well-annotated datasets for training and evaluation. To address this gap, we introduce PSBench, a benchmark suite comprising five large-scale, labeled datasets, four of which were generated during the 15th and 16th community-wide Critical Assessment of Protein Structure Prediction (CASP15 and CASP16), and one curated for new Protein Data Bank (PDB) entries deposited between July 2024 and August 2025. PSBench includes over 1.4 million structural models covering a wide range of protein sequence lengths, complex stoichiometries, functional classes, and modeling difficulties. Each model is annotated with multiple complementary quality scores at the global, local, and interface levels. PSBench also provides multiple evaluation metrics and baseline EMA methods to facilitate rigorous comparisons. To demonstrate PSBench's utility, we trained and evaluated GATE, a graph transformer-based EMA method, on the CASP15 data. GATE was blindly tested in CASP16 (2024), where it ranked among the top-performing EMA methods.

Options markets represent one of the most sophisticated segments of the financial ecosystem, with prices that directly reflect market uncertainty. In this paper, we introduce the first reinforcement learning (RL) framework specifically designed for volatility trading through options, focusing on profit from the difference between implied volatility and realized volatility. Our multi-agent architecture consists of an Option Position Agent (OP-Agent) responsible for volatility timing by controlling long/short volatility positions, and a Hedger Routing Agent (HR-Agent) that manages risk and maximizes path-dependent profits by selecting optimal hedging strategies with different risk preferences. Evaluating our approach using cryptocurrency options data from 2021-2024, we demonstrate superior performance on BTC and ETH, significantly outperforming traditional strategies and machine learning baselines across all profit and risk-adjusted metrics while exhibiting sophisticated trading behavior.

Brain disorders have been consistently associated with abnormalities in specific brain regions or neural circuits. Identifying key brain regional activities and functional connectivity patterns is essential for discovering more precise neurobiological biomarkers. However, previous studies have primarily emphasized alterations in functional connectivity while overlooking abnormal neuronal population activity within brain regions. To bridge this gap, we propose a novel Local-Global Coupling Spiking Graph Transformer (LGC-SGT) that jointly models both inter-regional connectivity differences and deviations in neuronal population firing rates within brain regions, enabling a dual-perspective neuropathological analysis. The global pathway leverages spike-based computation in LGC-SGT to model biologically plausible aberrant neural firing dynamics, while the local pathway adaptively captures abnormal graph-based representations of brain connectivity learned by local plasticity in the liquid state machine module. Furthermore, we design a shortcut-enhanced output strategy in LGC-SGT with the hybrid loss function to suppress outlier interference caused by inter-individual and inter-center variability, enabling a more robust decision boundary. Extensive experiments on three brain disorder datasets demonstrate that our model consistently outperforms state-of-the-art graph methods in brain disorder diagnosis.

Accurate 3D reconstruction of hands and instruments is critical for vision-based analysis of ophthalmic microsurgery, yet progress has been hampered by the lack of realistic, large-scale datasets and reliable annotation tools. In this work, we introduce OphNet-3D, the first extensive RGB-D dynamic 3D reconstruction dataset for ophthalmic surgery, comprising 41 sequences from 40 surgeons and totaling 7.1 million frames, with fine-grained annotations of 12 surgical phases, 10 instrument categories, dense MANO hand meshes, and full 6-DoF instrument poses. To scalably produce high-fidelity labels, we design a multi-stage automatic annotation pipeline that integrates multi-view data observation, data-driven motion prior with cross-view geometric consistency and biomechanical constraints, along with a combination of collision-aware interaction constraints for instrument interactions. Building upon OphNet-3D, we establish two challenging benchmarks--bimanual hand pose estimation and hand-instrument interaction reconstruction--and propose two dedicated architectures: H-Net for dual-hand mesh recovery and OH-Net for joint reconstruction of two-hand-two-instrument interactions.

Data deviations in electronic health records (EHR) refer to discrepancies between recorded entries and a patient's actual physiological state, indicating a decline in EHR data fidelity. Such deviations can result from pre-analytical variability, documentation errors, or unvalidated data sources. Effectively detecting data deviations is clinically valuable for identifying erroneous records, excluding them from downstream clinical workflows, and informing corrective actions. Despite its importance and practical relevance, this problem remains largely underexplored in existing research. To bridge this gap, we propose a bi-level knowledge distillation approach centered on a task-agnostic formulation of EHR data fidelity as an intrinsic measure of data reliability. Our approach performs layered knowledge distillation in two levels: from a computation-intensive, task-specific data Shapley oracle to a neural oracle for individual tasks, and then to a unified EHR data fidelity predictor. This design enables the integration of task-specific insights into a holistic assessment of a patient's EHR data fidelity from a multi-task perspective. By tracking the outputs of this learned predictor, we detect potential data deviations in EHR data.

Patent examination remains an ongoing challenge in the NLP literature even after the advent of large language models (LLMs), as it requires an extensive yet nuanced human judgment on whether a submitted $\textit{claim}$ meets the statutory standards of $\textit{novelty}$ and $\textit{non-obviousness}$ against previously granted claims--$\textit{prior art}$--in expert domains. Previous NLP studies have approached this challenge as a prediction task (e.g., forecasting grant outcomes) with high-level proxies such as similarity metrics or classifiers trained on historical labels. However, this approach often overlooks the step-by-step evaluations that examiners must make with profound information, including rationales for the decisions provided in $\textit{office actions}$ documents, which also makes it harder to measure the current state of techniques in patent review processes. To fill this gap, we construct PANORAMA, a dataset of 8,143 U.S. patent examination records that preserves the full decision trails, including original applications, all cited references, $\textit{Non-Final Rejections}$, and $\textit{Notices of Allowance}$. Also, PANORAMA decomposes the trails into sequential benchmarks that emulate patent professionals' patent review processes and allow researchers to examine large language models' capabilities at each step of them. Our findings indicate that, although LLMs are relatively effective at retrieving relevant prior art and pinpointing the pertinent paragraphs, they struggle to assess the novelty and non-obviousness of patent claims. We discuss these results and argue that advancing NLP, including LLMs, in the patent domain requires a deeper understanding of real-world patent examination.

We propose and analyze a new class of unbalanced weak optimal transport (OT) problems with total variation penalties, motivated by spatial resource allocation tasks. Unlike classical OT, our framework accommodates general unbalanced nonnegative measures and incorporates cost objectives that directly capture operational trade-offs between transport cost and supply-demand mismatch. In the general setting, we establish the existence of optimal solutions and a dual formulation. We then focus on the semi-discrete setting, where one measure is discrete and the other is absolutely continuous, a structure relevant to applications such as service area partitioning for facilities like schools or medical stations. Exploiting a tessellation-based structure, we derive the corresponding explicit optimality conditions. We further address a quantization problem that jointly optimizes the locations and weights of discrete support points, applicable to facility location tasks such as the cost-efficient deployment of battery swap stations or e-commerce warehouses, informed by demand-side data. The dual-tessellation structure also yields explicit gradient expressions, enabling efficient numerical optimization in finite dimensions.

Oligonucleotide therapeutics offer great potential to address previously undruggable targets and enable personalized medicine. However, their progress is often hindered by insufficient safety and efficacy profiles. Predictive modeling and machine learning could significantly accelerate oligonucleotide drug discovery by identifying suboptimal compounds early on, but their application in this area lags behind other modalities. A key obstacle to the adoption of machine learning in the field is the scarcity of readily accessible and standardized datasets for model development, as data are often scattered across diverse experiments with inconsistent molecular representations. To overcome this challenge, we introduce OligoGym, a curated collection of standardized, machine learning-ready datasets encompassing various oligonucleotide therapeutic modalities and endpoints. We used OligoGym to benchmark diverse classical and deep learning methods, establishing performance baselines for each dataset across different featurization techniques, model configurations, and splitting strategies. Our work represents a crucial first step in creating a more unified framework for oligonucleotide therapeutic dataset generation and model training.

Apple's Camera Chief Thinks AI Can Give You Superpowers The generative features in iOS 27's new Photos app will add fake pixels to some of your shots, but Apple's Jon McCormack says the company isn't using AI "for the sake of AI." What even is a photograph these days? As tech giants pack generative AI capabilities into our phones and their camera software, the line between what is a real image and what isn't continues to blur. Phones from Google and Samsung, for example, now come with features that let you drastically alter a photo by erasing people, moving people around in the shot, and even adding new objects to the scene. Apple is getting in on the action by adding new generative features to its Photos app, though the company's iPhone camera chief, Jon McCormack, stresses that Apple is taking a more measured approach than its competitors and isn't "doing AI for the sake of AI."