Kunyang Sun

Peter Eckmann, Kunyang Sun, Bo Zhao et al.

Generation of drug-like molecules with high binding affinity to target proteins remains a difficult and resource-intensive task in drug discovery. Existing approaches primarily employ reinforcement learning, Markov sampling, or deep generative models guided by Gaussian processes, which can be prohibitively slow when generating molecules with high binding affinity calculated by computationally-expensive physics-based methods. We present Latent Inceptionism on Molecules (LIMO), which significantly accelerates molecule generation with an inceptionism-like technique. LIMO employs a variational autoencoder-generated latent space and property prediction by two neural networks in sequence to enable faster gradient-based reverse-optimization of molecular properties. Comprehensive experiments show that LIMO performs competitively on benchmark tasks and markedly outperforms state-of-the-art techniques on the novel task of generating drug-like compounds with high binding affinity, reaching nanomolar range against two protein targets. We corroborate these docking-based results with more accurate molecular dynamics-based calculations of absolute binding free energy and show that one of our generated drug-like compounds has a predicted $K_D$ (a measure of binding affinity) of $6 \cdot 10^{-14}$ M against the human estrogen receptor, well beyond the affinities of typical early-stage drug candidates and most FDA-approved drugs to their respective targets. Code is available at https://github.com/Rose-STL-Lab/LIMO.

Yiyou Sun, Xinyang Han, Weichen Zhang et al.

Recent AI systems have achieved strong results on a wide range of benchmarks, yet these gains have not translated into economically meaningful deployment across many professional domains. We argue that this gap is largely an evaluation problem: widely used benchmarks lack sustained performance measurement on real and economically valuable workflows. This paper introduces Agents' Last Exam (ALE), a benchmark designed to evaluate AI agents on long-horizon, economically valuable, real-world tasks with verifiable outcomes. Developed in collaboration with 250+ industry experts, ALE covers non-physical industries defined with reference to O*NET / SOC 2018 (the U.S. federal occupational taxonomy). It is organized around a task taxonomy with 55 subfields grouped into 13 industry clusters covering 1K+ tasks. Current results show that the hardest tier remains far from saturated: across mainstream harness and backbone configurations, the average full pass rate is 2.6%. ALE is designed as a living benchmark: its task pool grows continuously as new workflows and industries are onboarded. More broadly, ALE is intended not merely as another leaderboard, but as an instrument for closing the gap between benchmark success and GDP-relevant impact.

M. Jehanzeb Mirza, Inkyu Shin, Wei Lin et al.

Our MATE is the first Test-Time-Training (TTT) method designed for 3D data, which makes deep networks trained for point cloud classification robust to distribution shifts occurring in test data. Like existing TTT methods from the 2D image domain, MATE also leverages test data for adaptation. Its test-time objective is that of a Masked Autoencoder: a large portion of each test point cloud is removed before it is fed to the network, tasked with reconstructing the full point cloud. Once the network is updated, it is used to classify the point cloud. We test MATE on several 3D object classification datasets and show that it significantly improves robustness of deep networks to several types of corruptions commonly occurring in 3D point clouds. We show that MATE is very efficient in terms of the fraction of points it needs for the adaptation. It can effectively adapt given as few as 5% of tokens of each test sample, making it extremely lightweight. Our experiments show that MATE also achieves competitive performance by adapting sparsely on the test data, which further reduces its computational overhead, making it ideal for real-time applications.

Zhicheng Li, Kunyang Sun, Rui Yao et al.

Video shadow detection confronts two entwined difficulties: distinguishing shadows from complex backgrounds and modeling dynamic shadow deformations under varying illumination. To address shadow-background ambiguity, we leverage linguistic priors through the proposed Vision-language Match Module (VMM) and a Dark-aware Semantic Block (DSB), extracting text-guided features to explicitly differentiate shadows from dark objects. Furthermore, we introduce adaptive mask reweighting to downweight penumbra regions during training and apply edge masks at the final decoder stage for better supervision. For temporal modeling of variable shadow shapes, we propose a Tokenized Temporal Block (TTB) that decouples spatiotemporal learning. TTB summarizes cross-frame shadow semantics into learnable temporal tokens, enabling efficient sequence encoding with minimal computation overhead. Comprehensive Experiments on multiple benchmark datasets demonstrate state-of-the-art accuracy and real-time inference efficiency. Codes are available at https://github.com/city-cheng/DTTNet.

Joseph M. Cavanagh, Kunyang Sun, Andrew Gritsevskiy et al.

Here we show that a general-purpose large language model (LLM) chatbot, Llama-3.1-8B-Instruct, can be transformed via supervised fine-tuning of engineered prompts into a chemical language model (CLM), SmileyLlama, for molecule generation. We benchmark SmileyLlama by comparing it to CLMs trained from scratch on large amounts of ChEMBL data for their ability to generate valid and novel drug-like molecules. We also use direct preference optimization to both improve SmileyLlama's adherence to a prompt and to generate molecules within the iMiner reinforcement learning framework to predict new drug molecules with optimized 3D conformations and high binding affinity to drug targets, illustrated with the SARS-Cov-2 Main Protease. This overall framework allows a LLM to speak directly as a CLM which can generate molecules with user-specified properties, rather than acting only as a chatbot with knowledge of chemistry or as a helpful virtual assistant. While our dataset and analyses are geared toward drug discovery, this general procedure can be extended to other chemical applications such as chemical synthesis.

Kunyang Sun, Wei Lin, Haoqin Shi et al.

Unsupervised domain adaptive object detection is a challenging vision task where object detectors are adapted from a label-rich source domain to an unlabeled target domain. Recent advances prove the efficacy of the adversarial based domain alignment where the adversarial training between the feature extractor and domain discriminator results in domain-invariance in the feature space. However, due to the domain shift, domain discrimination, especially on low-level features, is an easy task. This results in an imbalance of the adversarial training between the domain discriminator and the feature extractor. In this work, we achieve a better domain alignment by introducing an auxiliary regularization task to improve the training balance. Specifically, we propose Adversarial Image Reconstruction (AIR) as the regularizer to facilitate the adversarial training of the feature extractor. We further design a multi-level feature alignment module to enhance the adaptation performance. Our evaluations across several datasets of challenging domain shifts demonstrate that the proposed method outperforms all previous methods, of both one- and two-stage, in most settings.

Hancheng Zhu, Xinyu Liu, Rui Yao et al.

Image retouching has received significant attention due to its ability to achieve high-quality visual content. Existing approaches mainly rely on uniform pixel-wise color mapping across entire images, neglecting the inherent color variations induced by image content. This limitation hinders existing approaches from achieving adaptive retouching that accommodates both diverse color distributions and user-defined style preferences. To address these challenges, we propose a novel Content-Adaptive image retouching method guided by Attribute-based Text Representation (CA-ATP). Specifically, we propose a content-adaptive curve mapping module, which leverages a series of basis curves to establish multiple color mapping relationships and learns the corresponding weight maps, enabling content-aware color adjustments. The proposed module can capture color diversity within the image content, allowing similar color values to receive distinct transformations based on their spatial context. In addition, we propose an attribute text prediction module that generates text representations from multiple image attributes, which explicitly represent user-defined style preferences. These attribute-based text representations are subsequently integrated with visual features via a multimodal model, providing user-friendly guidance for image retouching. Extensive experiments on several public datasets demonstrate that our method achieves state-of-the-art performance.

Yuanqi Du, Botao Yu, Tianyu Liu et al.

There has been unprecedented interest in developing agents that expand the boundary of scientific discovery, primarily by optimizing quantitative objective functions specified by scientists. However, for grand challenges in science , these objectives are only imperfect proxies. We argue that automating objective function design is a central, yet unmet requirement for scientific discovery agents. In this work, we introduce the Scientific Autonomous Goal-evolving Agent (SAGA) to amend this challenge. SAGA employs a bi-level architecture in which an outer loop of LLM agents analyzes optimization outcomes, proposes new objectives, and converts them into computable scoring functions, while an inner loop performs solution optimization under the current objectives. This bi-level design enables systematic exploration of the space of objectives and their trade-offs, rather than treating them as fixed inputs. We demonstrate the framework through a broad spectrum of applications, including antibiotic design, inorganic materials design, functional DNA sequence design, and chemical process design, showing that automating objective formulation can substantially improve the effectiveness of scientific discovery agents.

Long Phan, Alice Gatti, Ziwen Han et al. · amazon-science, apple-ml

Benchmarks are important tools for tracking the rapid advancements in large language model (LLM) capabilities. However, benchmarks are not keeping pace in difficulty: LLMs now achieve over 90\% accuracy on popular benchmarks like MMLU, limiting informed measurement of state-of-the-art LLM capabilities. In response, we introduce Humanity's Last Exam (HLE), a multi-modal benchmark at the frontier of human knowledge, designed to be the final closed-ended academic benchmark of its kind with broad subject coverage. HLE consists of 2,500 questions across dozens of subjects, including mathematics, humanities, and the natural sciences. HLE is developed globally by subject-matter experts and consists of multiple-choice and short-answer questions suitable for automated grading. Each question has a known solution that is unambiguous and easily verifiable, but cannot be quickly answered via internet retrieval. State-of-the-art LLMs demonstrate low accuracy and calibration on HLE, highlighting a significant gap between current LLM capabilities and the expert human frontier on closed-ended academic questions. To inform research and policymaking upon a clear understanding of model capabilities, we publicly release HLE at https://lastexam.ai.

Shenglan Li, Rui Yao, Yong Zhou et al.

To reduce the reliance on large-scale annotations, self-supervised RGB-T tracking approaches have garnered significant attention. However, the omission of the object region by erroneous pseudo-label or the introduction of background noise affects the efficiency of modality fusion, while pseudo-label noise triggered by similar object noise can further affect the tracking performance. In this paper, we propose GDSTrack, a novel approach that introduces dynamic graph fusion and temporal diffusion to address the above challenges in self-supervised RGB-T tracking. GDSTrack dynamically fuses the modalities of neighboring frames, treats them as distractor noise, and leverages the denoising capability of a generative model. Specifically, by constructing an adjacency matrix via an Adjacency Matrix Generator (AMG), the proposed Modality-guided Dynamic Graph Fusion (MDGF) module uses a dynamic adjacency matrix to guide graph attention, focusing on and fusing the object's coherent regions. Temporal Graph-Informed Diffusion (TGID) models MDGF features from neighboring frames as interference, and thus improving robustness against similar-object noise. Extensive experiments conducted on four public RGB-T tracking datasets demonstrate that GDSTrack outperforms the existing state-of-the-art methods. The source code is available at https://github.com/LiShenglana/GDSTrack.

Tianyu Liu, Sihan Jiang, Fan Zhang et al.

Large language models (LLMs) are in the ascendancy for research in drug discovery, offering unprecedented opportunities to reshape drug research by accelerating hypothesis generation, optimizing candidate prioritization, and enabling more scalable and cost-effective drug discovery pipelines. However there is currently a lack of objective assessments of LLM performance to ascertain their advantages and limitations over traditional drug discovery platforms. To tackle this emergent problem, we have developed DrugPlayGround, a framework to evaluate and benchmark LLM performance for generating meaningful text-based descriptions of physiochemical drug characteristics, drug synergism, drug-protein interactions, and the physiological response to perturbations introduced by drug molecules. Moreover, DrugPlayGround is designed to work with domain experts to provide detailed explanations for justifying the predictions of LLMs, thereby testing LLMs for chemical and biological reasoning capabilities to push their greater use at the frontier of drug discovery at all of its stages.

Wei Lin, Anna Kukleva, Kunyang Sun et al.

Although action recognition has achieved impressive results over recent years, both collection and annotation of video training data are still time-consuming and cost intensive. Therefore, image-to-video adaptation has been proposed to exploit labeling-free web image source for adapting on unlabeled target videos. This poses two major challenges: (1) spatial domain shift between web images and video frames; (2) modality gap between image and video data. To address these challenges, we propose Cycle Domain Adaptation (CycDA), a cycle-based approach for unsupervised image-to-video domain adaptation by leveraging the joint spatial information in images and videos on the one hand and, on the other hand, training an independent spatio-temporal model to bridge the modality gap. We alternate between the spatial and spatio-temporal learning with knowledge transfer between the two in each cycle. We evaluate our approach on benchmark datasets for image-to-video as well as for mixed-source domain adaptation achieving state-of-the-art results and demonstrating the benefits of our cyclic adaptation. Code is available at \url{https://github.com/wlin-at/CycDA}.

Hao Chen, Kunyang Sun, Zhi Tian et al.

Instance segmentation is one of the fundamental vision tasks. Recently, fully convolutional instance segmentation methods have drawn much attention as they are often simpler and more efficient than two-stage approaches like Mask R-CNN. To date, almost all such approaches fall behind the two-stage Mask R-CNN method in mask precision when models have similar computation complexity, leaving great room for improvement. In this work, we achieve improved mask prediction by effectively combining instance-level information with semantic information with lower-level fine-granularity. Our main contribution is a blender module which draws inspiration from both top-down and bottom-up instance segmentation approaches. The proposed BlendMask can effectively predict dense per-pixel position-sensitive instance features with very few channels, and learn attention maps for each instance with merely one convolution layer, thus being fast in inference. BlendMask can be easily incorporated with the state-of-the-art one-stage detection frameworks and outperforms Mask R-CNN under the same training schedule while being 20% faster. A light-weight version of BlendMask achieves $ 34.2% $ mAP at 25 FPS evaluated on a single 1080Ti GPU card. Because of its simplicity and efficacy, we hope that our BlendMask could serve as a simple yet strong baseline for a wide range of instance-wise prediction tasks. Code is available at https://git.io/AdelaiDet

Kunyang Sun, Dorian Bagni, Joseph M. Cavanagh et al.

Generative machine learning models for exploring chemical space have shown immense promise, but many molecules they generate are too difficult to synthesize, making them impractical for further investigation or development. In this work, we present a novel approach by fine-tuning Meta's Llama3 Large Language Models (LLMs) to create SynLlama, which generates full synthetic pathways made of commonly accessible building blocks and robust organic reaction templates. SynLlama explores a large synthesizable space using significantly less data, and offers strong performance in both forward and bottom-up synthesis planning compared to other state-of-the-art methods. We find that SynLlama, even without training on external building blocks, can effectively generalize to unseen yet purchasable building blocks, meaning that its reconstruction capabilities extend to a broader synthesizable chemical space than the training data. We also demonstrate the use of SynLlama in a pharmaceutical context for synthesis planning of analog molecules and hit expansion leads for proposed inhibitors of target proteins, offering medicinal chemists a valuable tool for discovery.