Search

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and the expanded availability of experimental 3D protein structures have accelerated structure prediction, the dynamic nature of protein structures has received limited attention. This study introduces an innovative 4D diffusion model incorporating molecular dynamics (MD) simulation data to learn dynamic protein structures. Our approach is distinguished by the following components: (1) a unified diffusion model capable of generating dynamic protein structures, including both the backbone and side chains, utilizing atomic grouping and side-chain dihedral angle predictions; (2) a reference network that enhances structural consistency by integrating the latent embeddings of the initial 3D protein structures; and (3) a motion alignment module aimed at improving temporal structural coherence across multiple time steps. To our knowledge, this is the first diffusion-based model aimed at predicting protein trajectories across multiple time steps simultaneously. Validation on benchmark datasets demonstrates that our model exhibits high accuracy in predicting dynamic 3D structures of proteins containing up to 256 amino acids over 32 time steps, effectively capturing both local flexibility in stable states and significant conformational changes.

Despite significant progress in static protein structure collection and prediction, the dynamic behavior of proteins, one of their most vital characteristics, has been largely overlooked in prior research. This oversight can be attributed to the limited availability, diversity, and heterogeneity of dynamic protein datasets. To address this gap, we propose to enhance existing prestigious static 3D protein structural databases, such as the Protein Data Bank (PDB), by integrating dynamic data and additional physical properties. Specifically, we introduce a large-scale dataset, Dynamic PDB, encompassing approximately 12.6K proteins, each subjected to all-atom molecular dynamics (MD) simulations lasting 1 microsecond to capture conformational changes. Furthermore, we provide a comprehensive suite of physical properties, including atomic velocities and forces, potential and kinetic energies of proteins, and the temperature of the simulation environment, recorded at 1 picosecond intervals throughout the simulations. For benchmarking purposes, we evaluate state-of-the-art methods on the proposed dataset for the task of trajectory prediction. To demonstrate the value of integrating richer physical properties in the study of protein dynamics and related model design, we base our approach on the SE(3) diffusion model and incorporate these physical properties into the trajectory prediction process. Preliminary results indicate that this straightforward extension of the SE(3) model yields improved accuracy, as measured by MAE and RMSD, when the proposed physical properties are taken into consideration. https://fudan-generative-vision.github.io/dynamicPDB/ .

Large language models (LLMs) are trained on extensive text corpora, which inevitably include biased information. Although techniques such as Affective Alignment can mitigate some negative impacts of these biases, existing prompt-based attack methods can still extract these biases from the model's weights. Moreover, these biases frequently appear subtly when LLMs are prompted to perform identical tasks across different demographic groups, thereby camouflaging their presence. To address this issue, we have formally defined the implicit bias problem and developed an innovative framework for bias removal based on Bayesian theory, Bayesian-Theory based Bias Removal (BTBR). BTBR employs likelihood ratio screening to pinpoint data entries within publicly accessible biased datasets that represent biases inadvertently incorporated during the LLM training phase. It then automatically constructs relevant knowledge triples and expunges bias information from LLMs using model editing techniques. Through extensive experimentation, we have confirmed the presence of the implicit bias problem in LLMs and demonstrated the effectiveness of our BTBR approach.

We introduce Imagen 3, a latent diffusion model that generates high quality images from text prompts. We describe our quality and responsibility evaluations. Imagen 3 is preferred over other state-of-the-art (SOTA) models at the time of evaluation. In addition, we discuss issues around safety and representation, as well as methods we used to minimize the potential harm of our models.

Operational numerical weather prediction systems consist of three fundamental components: the global observing system for data collection, data assimilation for generating initial conditions, and the forecasting model to predict future weather conditions. While NWP have undergone a quiet revolution, with forecast skills progressively improving over the past few decades, their advancement has slowed due to challenges such as high computational costs and the complexities associated with assimilating an increasing volume of observational data and managing finer spatial grids. Advances in machine learning offer an alternative path towards more efficient and accurate weather forecasts. The rise of machine learning based weather forecasting models has also spurred the development of machine learning based DA models or even purely machine learning based weather forecasting systems. This paper introduces FuXi Weather, an end-to-end machine learning based weather forecasting system. FuXi Weather employs specialized data preprocessing and multi-modal data fusion techniques to integrate information from diverse sources under all-sky conditions, including microwave sounders from 3 polar-orbiting satellites and radio occultation data from Global Navigation Satellite System. Operating on a 6-hourly DA and forecasting cycle, FuXi Weather independently generates robust and accurate 10-day global weather forecasts at a spatial resolution of 0.25\textdegree. It surpasses the European Centre for Medium-range Weather Forecasts high-resolution forecasts in terms of predictability, extending the skillful forecast lead times for several key weather variables such as the geopotential height at 500 hPa from 9.25 days to 9.5 days. The system's high computational efficiency and robust performance, even with limited observations, demonstrates its potential as a promising alternative to traditional NWP systems., Comment: 34 pages, 4 figures

Large language models (LLMs) have shown exceptional performance as general-purpose assistants, excelling across a variety of reasoning tasks. This achievement represents a significant step toward achieving artificial general intelligence (AGI). Despite these advancements, the effectiveness of LLMs often hinges on the specific prompting strategies employed, and there remains a lack of a robust framework to facilitate learning and generalization across diverse reasoning tasks. To address these challenges, we introduce a novel learning framework, THOUGHT-LIKE-PRO In this framework, we utilize imitation learning to imitate the Chain-of-Thought (CoT) process which is verified and translated from reasoning trajectories generated by a symbolic Prolog logic engine. This framework proceeds in a self-driven manner, that enables LLMs to formulate rules and statements from given instructions and leverage the symbolic Prolog engine to derive results. Subsequently, LLMs convert Prolog-derived successive reasoning trajectories into natural language CoT for imitation learning. Our empirical findings indicate that our proposed approach substantially enhances the reasoning abilities of LLMs and demonstrates robust generalization across out-of-distribution reasoning tasks.

Effective collaboration in multi-agent systems requires communicating goals and intentions between agents. Current agent frameworks often suffer from dependencies on single-agent execution and lack robust inter-module communication, frequently leading to suboptimal multi-agent reinforcement learning (MARL) policies and inadequate task coordination. To address these challenges, we present a framework for training large language models (LLMs) as collaborative agents to enable coordinated behaviors in cooperative MARL. Each agent maintains a private intention consisting of its current goal and associated sub-tasks. Agents broadcast their intentions periodically, allowing other agents to infer coordination tasks. A propagation network transforms broadcast intentions into teammate-specific communication messages, sharing relevant goals with designated teammates. The architecture of our framework is structured into planning, grounding, and execution modules. During execution, multiple agents interact in a downstream environment and communicate intentions to enable coordinated behaviors. The grounding module dynamically adapts comprehension strategies based on emerging coordination patterns, while feedback from execution agents influnces the planning module, enabling the dynamic re-planning of sub-tasks. Results in collaborative environment simulation demonstrate intention propagation reduces miscoordination errors by aligning sub-task dependencies between agents. Agents learn when to communicate intentions and which teammates require task details, resulting in emergent coordinated behaviors. This demonstrates the efficacy of intention sharing for cooperative multi-agent RL based on LLMs.

Structured data, rich in logical and relational information, has the potential to enhance the reasoning abilities of large language models (LLMs). Still, its integration poses a challenge due to the risk of overwhelming LLMs with excessive tokens and irrelevant context information. To address this, we propose Struct-X, a novel framework that operates through five key phases: ``read-model-fill-reflect-reason'' efficiently enabling LLMs to utilize structured data. It begins by encoding structured data into a topological space using graph embeddings, followed by filling in missing entity information with knowledge retrieval modules, and filtering out irrelevant tokens via a self-supervised module. The final phase involves constructing a topological network with selected tokens to further reduce the total token length for more effective LLM inference. Additionally, Struct-X includes an Auxiliary Module trained to generate prompts, aiding LLMs in analyzing structured data. Extensive experiments on benchmarks, including the knowledge graph question-answer task and the long document reading comprehension task, show that Struct-X notably improves LLM reasoning, demonstrating the effectiveness of structured data augmentation in improving LLM inference with complex input context.

Graph Neural Networks (GNNs) have gained significant attention as a powerful modeling and inference method, especially for homophilic graph-structured data. To empower GNNs in heterophilic graphs, where adjacent nodes exhibit dissimilar labels or features, Signed Message Passing (SMP) has been widely adopted. However, there is a lack of theoretical and empirical analysis regarding the limitations of SMP. In this work, we unveil some potential pitfalls of SMP and their remedies. We first identify two limitations of SMP: undesirable representation update for multi-hop neighbors and vulnerability against oversmoothing issues. To overcome these challenges, we propose a novel message passing function called Multiset to Multiset GNN(M2M-GNN). Our theoretical analyses and extensive experiments demonstrate that M2M-GNN effectively alleviates the aforementioned limitations of SMP, yielding superior performance in comparison, Comment: Published as a conference paper at ICML 2024

We introduce AI2Apps, a Visual Integrated Development Environment (Visual IDE) with full-cycle capabilities that accelerates developers to build deployable LLM-based AI agent Applications. This Visual IDE prioritizes both the Integrity of its development tools and the Visuality of its components, ensuring a smooth and efficient building experience.On one hand, AI2Apps integrates a comprehensive development toolkit ranging from a prototyping canvas and AI-assisted code editor to agent debugger, management system, and deployment tools all within a web-based graphical user interface. On the other hand, AI2Apps visualizes reusable front-end and back-end code as intuitive drag-and-drop components. Furthermore, a plugin system named AI2Apps Extension (AAE) is designed for Extensibility, showcasing how a new plugin with 20 components enables web agent to mimic human-like browsing behavior. Our case study demonstrates substantial efficiency improvements, with AI2Apps reducing token consumption and API calls when debugging a specific sophisticated multimodal agent by approximately 90% and 80%, respectively. The AI2Apps, including an online demo, open-source code, and a screencast video, is now publicly accessible.

Recent advancements in deep learning have led to the development of various models for long-term multivariate time-series forecasting (LMTF), many of which have shown promising results. Generally, the focus has been on historical-value-based models, which rely on past observations to predict future series. Notably, a new trend has emerged with time-index-based models, offering a more nuanced understanding of the continuous dynamics underlying time series. Unlike these two types of models that aggregate the information of spatial domains or temporal domains, in this paper, we consider multivariate time series as spatiotemporal data regularly sampled from a continuous dynamical system, which can be represented by partial differential equations (PDEs), with the spatial domain being fixed. Building on this perspective, we present PDETime, a novel LMTF model inspired by the principles of Neural PDE solvers, following the encoding-integration-decoding operations. Our extensive experimentation across seven diverse real-world LMTF datasets reveals that PDETime not only adapts effectively to the intrinsic spatiotemporal nature of the data but also sets new benchmarks, achieving state-of-the-art results

Neural radiance field (NeRF) has achieved great success in novel view synthesis and 3D representation for static scenarios. Existing dynamic NeRFs usually exploit a locally dense grid to fit the deformation field; however, they fail to capture the global dynamics and concomitantly yield models of heavy parameters. We observe that the 4D space is inherently sparse. Firstly, the deformation field is sparse in spatial but dense in temporal due to the continuity of of motion. Secondly, the radiance field is only valid on the surface of the underlying scene, usually occupying a small fraction of the whole space. We thus propose to represent the 4D scene using a learnable sparse latent space, a.k.a. SLS4D. Specifically, SLS4D first uses dense learnable time slot features to depict the temporal space, from which the deformation field is fitted with linear multi-layer perceptions (MLP) to predict the displacement of a 3D position at any time. It then learns the spatial features of a 3D position using another sparse latent space. This is achieved by learning the adaptive weights of each latent code with the attention mechanism. Extensive experiments demonstrate the effectiveness of our SLS4D: it achieves the best 4D novel view synthesis using only about $6\%$ parameters of the most recent work., Comment: 10 pages, 6 figures

Skillful subseasonal forecasts are crucial for various sectors of society but pose a grand scientific challenge. Recently, machine learning based weather forecasting models outperform the most successful numerical weather predictions generated by the European Centre for Medium-Range Weather Forecasts (ECMWF), but have not yet surpassed conventional models at subseasonal timescales. This paper introduces FuXi Subseasonal-to-Seasonal (FuXi-S2S), a machine learning model that provides global daily mean forecasts up to 42 days, encompassing five upper-air atmospheric variables at 13 pressure levels and 11 surface variables. FuXi-S2S, trained on 72 years of daily statistics from ECMWF ERA5 reanalysis data, outperforms the ECMWF's state-of-the-art Subseasonal-to-Seasonal model in ensemble mean and ensemble forecasts for total precipitation and outgoing longwave radiation, notably enhancing global precipitation forecast. The improved performance of FuXi-S2S can be primarily attributed to its superior capability to capture forecast uncertainty and accurately predict the Madden-Julian Oscillation (MJO), extending the skillful MJO prediction from 30 days to 36 days. Moreover, FuXi-S2S not only captures realistic teleconnections associated with the MJO, but also emerges as a valuable tool for discovering precursor signals, offering researchers insights and potentially establishing a new paradigm in Earth system science research.

Semi-supervised learning has attracted much attention due to its less dependence on acquiring abundant annotations from experts compared to fully supervised methods, which is especially important for medical image segmentation which typically requires intensive pixel/voxel-wise labeling by domain experts. Although semi-supervised methods can improve the performance by utilizing unlabeled data, there are still gaps between fully supervised methods under extremely limited annotation scenarios. In this paper, we propose a simple yet efficient strategy to explore the usage of the Segment Anything Model (SAM) for enhancing semi-supervised medical image segmentation. Concretely, the segmentation model trained with domain knowledge provides information for localization and generating input prompts to the SAM. Then the generated pseudo-labels of SAM are utilized as additional supervision to assist in the learning procedure of the semi-supervised framework. Experimental results demonstrate that SAM's assistance significantly enhances the performance of existing semi-supervised frameworks, especially when only one or a few labeled images are available.

Instruction fine-tuning has conventionally been employed to adapt Large Language Models (LLMs) to a variety of tasks. Nonetheless, this technique often necessitates substantial computational resources, making it impractical for deployment by individuals or small-scale entities. Recently, Low-Rank Adaptation (LoRA) has become a promising alternative, offering high capabilities on par with full tuning with reduced resource overhead. However, attaining satisfactory performance through the fine-tuning of LoRA is a non-trivial challenge. In this paper, we propose PILLOW, which aims to improve LoRA's performance by a discrimination-based prompting method, leveraging LLMs' In-Context Learning ability. PILLOW incorporates a matching network that selects prompts from a user-defined prompt pool, concatenates the selected prompts with the user instruction as input, and performs inference using the LoRA-fine-tuned LLMs. Trained with Reinforcement Learning, PILLOW exhibits commensurate performance on various evaluation metrics compared with typical instruction fine-tuning methods, utilizing only consumer-grade GPU resources and exhibiting a large reduction in computational costs., Comment: Accepted by EMNLP 2023 (Industry Track), Oral Presentation

The Segment Anything Model (SAM) has recently emerged as a groundbreaking foundation model for prompt-driven image segmentation tasks. However, both the original SAM and its medical variants require slice-by-slice manual prompting of target structures, which directly increase the burden for applications. Despite attempts of auto-prompting to turn SAM into a fully automatic manner, it still exhibits subpar performance and lacks of reliability especially in the field of medical imaging. In this paper, we propose UR-SAM, an uncertainty rectified SAM framework to enhance the reliability for auto-prompting medical image segmentation. Building upon a localization framework for automatic prompt generation, our method incorporates a prompt augmentation module to obtain a series of input prompts for SAM for uncertainty estimation and an uncertainty-based rectification module to further utilize the distribution of estimated uncertainty to improve the segmentation performance. Extensive experiments on two public 3D medical datasets covering the segmentation of 35 organs demonstrate that without supplementary training or fine-tuning, our method further improves the segmentation performance with up to 10.7 % and 13.8 % in dice similarity coefficient, demonstrating efficiency and broad capabilities for medical image segmentation without manual prompting.

Large language models (LLMs) have proven their remarkable versatility in handling a comprehensive range of language-centric applications. To expand LLMs' capabilities to a broader spectrum of modal inputs, multimodal large language models (MLLMs) have attracted growing interest. This work delves into enabling LLMs to tackle more vision-language-related tasks, particularly image captioning, visual question answering (VQA,) and visual grounding. To this end, we implemented a three-stage training scheme: starting with lightweight alignment pretraining, then moderate-weight multitask hybrid training, and finally, LLM fine-tuning to improve instruction following capability. Throughout the training process, the requirements on GPU memory gradually increase. To effectively manage the number of visual embeddings passed to the LLM while preserving their positional information, we introduce a straightforward visual adapter module dubbed pool-adapter. Our experiments demonstrate that preserving the positional information of visual embeddings through the pool-adapter is particularly beneficial for tasks like visual grounding. We name our proposed approach InfMLLM and have evaluated it extensively on various benchmark datasets. Our results demonstrate that InfMLLM achieves either state-of-the-art (SOTA) performance or performance comparable to recent MLLMs. The code and model will be made open-source at: \url{https://github.com/mightyzau/InfMLLM}., Comment: 8

Significant advancements in the development of machine learning (ML) models for weather forecasting have produced remarkable results. State-of-the-art ML-based weather forecast models, such as FuXi, have demonstrated superior statistical forecast performance in comparison to the high-resolution forecasts (HRES) of the European Centre for Medium-Range Weather Forecasts (ECMWF). However, ML models face a common challenge: as forecast lead times increase, they tend to generate increasingly smooth predictions, leading to an underestimation of the intensity of extreme weather events. To address this challenge, we developed the FuXi-Extreme model, which employs a denoising diffusion probabilistic model (DDPM) to restore finer-scale details in the surface forecast data generated by the FuXi model in 5-day forecasts. An evaluation of extreme total precipitation ($\textrm{TP}$), 10-meter wind speed ($\textrm{WS10}$), and 2-meter temperature ($\textrm{T2M}$) illustrates the superior performance of FuXi-Extreme over both FuXi and HRES. Moreover, when evaluating tropical cyclone (TC) forecasts based on International Best Track Archive for Climate Stewardship (IBTrACS) dataset, both FuXi and FuXi-Extreme shows superior performance in TC track forecasts compared to HRES, but they show inferior performance in TC intensity forecasts in comparison to HRES.

In recent years, the explosion of web videos makes text-video retrieval increasingly essential and popular for video filtering, recommendation, and search. Text-video retrieval aims to rank relevant text/video higher than irrelevant ones. The core of this task is to precisely measure the cross-modal similarity between texts and videos. Recently, contrastive learning methods have shown promising results for text-video retrieval, most of which focus on the construction of positive and negative pairs to learn text and video representations. Nevertheless, they do not pay enough attention to hard negative pairs and lack the ability to model different levels of semantic similarity. To address these two issues, this paper improves contrastive learning using two novel techniques. First, to exploit hard examples for robust discriminative power, we propose a novel Dual-Modal Attention-Enhanced Module (DMAE) to mine hard negative pairs from textual and visual clues. By further introducing a Negative-aware InfoNCE (NegNCE) loss, we are able to adaptively identify all these hard negatives and explicitly highlight their impacts in the training loss. Second, our work argues that triplet samples can better model fine-grained semantic similarity compared to pairwise samples. We thereby present a new Triplet Partial Margin Contrastive Learning (TPM-CL) module to construct partial order triplet samples by automatically generating fine-grained hard negatives for matched text-video pairs. The proposed TPM-CL designs an adaptive token masking strategy with cross-modal interaction to model subtle semantic differences. Extensive experiments demonstrate that the proposed approach outperforms existing methods on four widely-used text-video retrieval datasets, including MSR-VTT, MSVD, DiDeMo and ActivityNet., Comment: Accepted by ACM MM 2023

Ordered electronic states have been extensively explored in cuprates and iron-based unconventional superconductors, but seldom observed in the epitaxial FeSe/SrTiO3(001) monolayer (FeSe/STO) with an enhanced superconducting transition temperature (Tc). Here, by using scanning tunneling microscopy/ spectroscopy (STM/STS), we reveal a checkerboard charge order in the epitaxial FeSe/STO monolayer, with a period of four times the inter-Fe-atom distance along two perpendicular directions of the Fe lattice. This ordered state is uniquely present in the superconducting FeSe/STO monolayer, even at liquid nitrogen temperature, but absent in the non-superconducting FeSe monolayer or bilayer. Quasiparticle interference (QPI) measurements further confirm it as a static order without an energy-dependent dispersion and gapped out within the superconductivity gap. The intensity of the charge order shows an enhancement near the superconducting transition temperature, thus implying a correlation with the high-Tc superconductivity in the FeSe/STO monolayer. This study provides a new basis for exploring the ordered electronic states and their interplay with high-Tc superconductivity in the FeSe monolayer., Comment: 22 pages, 4 figures

We consider Einstein gravity extended with Riemann-squared term and construct the leading-order perturbative solution to the rotating black hole with all equal angular momenta in $D=7$. We find that in the extremal limit, the linear perturbation involves irrational powers in the near-horizon expansion. We argue that, despite that all curvature tensor invariants are regular on the horizon, the irrational power implies that the inside of the horizon is destroyed and the horizon becomes the natural boundary of the spacetime. We demonstrate that this vulnerability of the horizon regularity is an innate part of Einstein theory, and can arise in Einstein theory with minimally coupled matter. However, in fine-tuned theories such as supergravities, the black hole inside is preserved, which may be one of the criteria for a consistent theory of quantum gravity. We also show that the vulnerability occurs in general higher dimensions, which only a few sporadically distributed dimensions can evade., Comment: Latex, 24 pages, 1 figure

Over the past few years, due to the rapid development of machine learning (ML) models for weather forecasting, state-of-the-art ML models have shown superior performance compared to the European Centre for Medium-Range Weather Forecasts (ECMWF)'s high-resolution forecast (HRES) in 10-day forecasts at a spatial resolution of 0.25 degree. However, the challenge remains to perform comparably to the ECMWF ensemble mean (EM) in 15-day forecasts. Previous studies have demonstrated the importance of mitigating the accumulation of forecast errors for effective long-term forecasts. Despite numerous efforts to reduce accumulation errors, including autoregressive multi-time step loss, using a single model is found to be insufficient to achieve optimal performance in both short and long lead times. Therefore, we present FuXi, a cascaded ML weather forecasting system that provides 15-day global forecasts with a temporal resolution of 6 hours and a spatial resolution of 0.25 degree. FuXi is developed using 39 years of the ECMWF ERA5 reanalysis dataset. The performance evaluation, based on latitude-weighted root mean square error (RMSE) and anomaly correlation coefficient (ACC), demonstrates that FuXi has comparable forecast performance to ECMWF EM in 15-day forecasts, making FuXi the first ML-based weather forecasting system to accomplish this achievement.

We discuss estimation and inference of conditional treatment effects in regression discontinuity designs with multiple scores. Aside from the commonly used local linear regression approach and a minimax-optimal estimator recently proposed by Imbens and Wager (2019), we consider two estimators based on random forests -- honest regression forests and local linear forests -- whose construction resembles that of standard local regressions, with theoretical validity following from results in Wager and Athey (2018) and Friedberg et al. (2020). We design a systematic Monte Carlo study with data generating processes built both from functional forms that we specify and from Wasserstein Generative Adversarial Networks that can closely mimic the observed data. We find that no single estimator dominates across all simulations: (i) local linear regressions perform well in univariate settings, but can undercover when multivariate scores are transformed into a univariate score -- which is commonly done in practice -- possibly due to the "zero-density" issue of the collapsed univariate score at the transformed cutoff; (ii) good performance of the minimax-optimal estimator depends on accurate estimation of a nuisance parameter and its current implementation only accepts up to two scores; (iii) forest-based estimators are not designed for estimation at boundary points and can suffer from bias in finite sample, but their flexibility in modeling multivariate scores opens the door to a wide range of empirical applications in multivariate regression discontinuity designs.