旨在找到合成靶分子的反应途径的循环合成计划在化学和药物发现中起着重要作用。此任务通常被建模为搜索问题。最近，数据驱动的方法吸引了许多研究兴趣，并显示了反递归计划的有希望的结果。我们观察到在搜索过程中多次访问了相同的中间分子，并且通常在先前基于树的方法（例如，或树搜索，蒙特卡洛树搜索）中独立处理。这样的裁员使搜索过程效率低下。我们提出了基于图的搜索策略，以消除任何中间分子的冗余探索。由于图形上的搜索比在树上更复杂，因此我们进一步采用图形神经网络来指导图形搜索。同时，我们的方法可以在图中搜索一批目标，并在基于树的搜索方法中删除目标间重复。两个数据集的实验结果证明了我们方法的有效性。尤其是在广泛使用的USPTO基准测试中，我们将搜索成功率提高到99.47％，以2.6分提高了先前的最新性能。

药物目标亲和力（DTA）预测是药物发现和药物研究的重要任务。 DTA的准确预测可以极大地受益于新药的设计。随着湿实验的昂贵且耗时，DTA预测的监督数据非常有限。这严重阻碍了基于深度学习的方法的应用，这些方法需要大量的监督数据。为了应对这一挑战并提高DTA预测准确性，我们在这项工作中提出了一个具有几种简单但有效的策略的框架：（1）多任务培训策略，该策略将DTA预测和蒙版语言建模（MLM）任务采用配对的药品目标数据集； （2）一种半监督的训练方法，通过利用大规模的未配对分子和蛋白质来赋予药物和靶向代表性学习，这与以前仅利用仅利用预训练的预训练和微调方法，这些方法仅利用前培训和微调方法训练; （3）一个交叉意见模块，以增强药物和靶代表性之间的相互作用。在三个现实世界基准数据集上进行了广泛的实验：BindingDB，Davis和Kiba。结果表明，我们的框架大大优于现有方法，并实现最先进的性能，例如，$ 0.712 $ rmse在bindingdb ic $ _ {50} $测量上，比以前的最佳工作要改善了$ 5 \％。此外，关于特定药物目标结合活动，药物特征可视化和现实世界应用的案例研究证明了我们工作的巨大潜力。代码和数据在https://github.com/qizhipei/smt-dta上发布

在本文中，我们从优化的角度研究了对比度学习，旨在分析和解决现有的对比学习方法的基本问题，这些方法依靠大批量大小或大型矢量词典。我们考虑了对比度学习的全球目标，该目标将每个正对与锚点的所有负对对比。从优化的角度来看，我们解释了为什么诸如SIMCLR之类的现有方法需要大批量大小才能获得令人满意的结果。为了消除此类要求，我们提出了一种记忆有效的随机优化算法，用于求解名为SOGCLR的对比度学习的全局目标。我们表明，在足够数量的迭代次数之后，在合理条件下，其优化误差可以忽略不计，或者对于稍有不同的全局对比目标而减少。从经验上讲，我们证明具有小批量大小的SOGCLR（例如256）可以在Imagenet-1k上的自我监督学习任务上获得与具有较大批量大小（例如8192）的SIMCLR相似的性能。我们还试图证明所提出的优化技术是通用的，可以应用于解决其他对比损失，例如双峰对比度学习的双向对比损失。提出的方法是在我们开源的图书馆libauc（www.libauc.org）中实现的。

Molecular conformation generation aims to generate three-dimensional coordinates of all the atoms in a molecule and is an important task in bioinformatics and pharmacology. Previous methods usually first predict the interatomic distances, the gradients of interatomic distances or the local structures (e.g., torsion angles) of a molecule, and then reconstruct its 3D conformation. How to directly generate the conformation without the above intermediate values is not fully explored. In this work, we propose a method that directly predicts the coordinates of atoms: (1) the loss function is invariant to roto-translation of coordinates and permutation of symmetric atoms; (2) the newly proposed model adaptively aggregates the bond and atom information and iteratively refines the coordinates of the generated conformation. Our method achieves the best results on GEOM-QM9 and GEOM-Drugs datasets. Further analysis shows that our generated conformations have closer properties (e.g., HOMO-LUMO gap) with the groundtruth conformations. In addition, our method improves molecular docking by providing better initial conformations. All the results demonstrate the effectiveness of our method and the great potential of the direct approach. The code is released at https://github.com/DirectMolecularConfGen/DMCG

差分方程管理的学习动态对于预测和控制科学和工程系统来说至关重要。神经常规方程（节点）是一种与微分方程集成的深度学习模型，最近是由于其对不规则样本的鲁棒性及其对高维输入的灵活性而流行的学习动态。然而，节点的训练对数值求解器的精度敏感，这使得节点的收敛不稳定，特别是对于不稳定的动态系统。在本文中，为了减少对数值求解器的依赖，我们建议提高节点训练中的监督信号。具体地，我们预先训练神经差分运算符（NDO）以输出衍生物的估计用作额外的监督信号。 NDO在一类基础函数上预先培训，并将这些功能的轨迹样本之间的映射学习到其衍生物。为了利用来自NDO的轨迹信号和估计的衍生工具，我们提出了一种称为NDO-Node的算法，其中损耗函数包含两个术语：真正轨迹样本的适应性以及由输出的估计衍生物的适应度预先训练的NDO。各种动力学的实验表明，我们提出的NDO-Node可以一致地用一个预先训练的NDO来改善预测精度。特别是对于僵硬的杂散，我们观察到与其他正则化方法相比，NDO-Node可以更准确地捕获动态的过渡。

本文使用移动传感器的稀疏观测来研究交通状态估计问题（TSE）问题。大多数现有的TSE方法要么依赖定义明确的物理交通流模型，要么需要大量的仿真数据作为训练机器学习模型的输入。与以前的研究不同，我们在本文中提出了纯粹的数据驱动和模型的解决方案。我们将TSE视为时空矩阵完成/插值问题，并应用时空延迟嵌入以将原始不完整的矩阵转换为四阶Hankel结构张量。通过对这种张量结构施加低级假设，我们可以以数据驱动的方式近似和表征全局和局部时空模式。我们使用平衡时空展开的截断核定标（其中每一列代表原始矩阵中小斑块的矢量化）来近似张量等级。开发了基于乘数交替方向方法（ADMM）的有效解决方案算法用于模型学习。所提出的框架仅涉及两个超参数，即空间和时间窗口长度，鉴于数据稀少度的程度，它们易于设置。我们对现实世界高分辨率轨迹数据进行数值实验，我们的结果证明了在某些具有挑战性的情况下所提出模型的有效性和优势。

Existing deep learning-based traffic forecasting models are mainly trained with MSE (or MAE) as the loss function, assuming that residuals/errors follow independent and isotropic Gaussian (or Laplacian) distribution for simplicity. However, this assumption rarely holds for real-world traffic forecasting tasks, where the unexplained residuals are often correlated in both space and time. In this study, we propose Spatiotemporal Residual Regularization by modeling residuals with a dynamic (e.g., time-varying) mixture of zero-mean multivariate Gaussian distribution with learnable spatiotemporal covariance matrices. This approach allows us to directly capture spatiotemporally correlated residuals. For scalability, we model the spatiotemporal covariance for each mixture component using a Kronecker product structure, which significantly reduces the number of parameters and computation complexity. We evaluate the performance of the proposed method on a traffic speed forecasting task. Our results show that, by properly modeling residual distribution, the proposed method not only improves the model performance but also provides interpretable structures.

We introduce the MAsked Generative VIdeo Transformer, MAGVIT, to tackle various video synthesis tasks with a single model. We introduce a 3D tokenizer to quantize a video into spatial-temporal visual tokens and propose an embedding method for masked video token modeling to facilitate multi-task learning. We conduct extensive experiments to demonstrate the quality, efficiency, and flexibility of MAGVIT. Our experiments show that (i) MAGVIT performs favorably against state-of-the-art approaches and establishes the best-published FVD on three video generation benchmarks, including the challenging Kinetics-600. (ii) MAGVIT outperforms existing methods in inference time by two orders of magnitude against diffusion models and by 60x against autoregressive models. (iii) A single MAGVIT model supports ten diverse generation tasks and generalizes across videos from different visual domains. The source code and trained models will be released to the public at https://magvit.cs.cmu.edu.

Spatiotemporal traffic data imputation is of great significance in intelligent transportation systems and data-driven decision-making processes. To make an accurate reconstruction on partially observed traffic data, we assert the importance of characterizing both global and local trends in traffic time series. In the literature, substantial prior works have demonstrated the effectiveness of utilizing low-rankness property of traffic data by matrix/tensor completion models. In this study, we first introduce a Laplacian kernel to temporal regularization for characterizing local trends in traffic time series, which can be formulated in the form of circular convolution. Then, we develop a low-rank Laplacian convolutional representation (LCR) model by putting the nuclear norm of a circulant matrix and the Laplacian temporal regularization together, which is proved to meet a unified framework that takes a fast Fourier transform solution in a relatively low time complexity. Through extensive experiments on some traffic datasets, we demonstrate the superiority of LCR for imputing traffic time series of various time series behaviors (e.g., data noises and strong/weak periodicity). The proposed LCR model is an efficient and effective solution to large-scale traffic data imputation over the existing baseline models. The adapted datasets and Python implementation are publicly available at https://github.com/xinychen/transdim.

Score-based modeling through stochastic differential equations (SDEs) has provided a new perspective on diffusion models, and demonstrated superior performance on continuous data. However, the gradient of the log-likelihood function, i.e., the score function, is not properly defined for discrete spaces. This makes it non-trivial to adapt \textcolor{\cdiff}{the score-based modeling} to categorical data. In this paper, we extend diffusion models to discrete variables by introducing a stochastic jump process where the reverse process denoises via a continuous-time Markov chain. This formulation admits an analytical simulation during backward sampling. To learn the reverse process, we extend score matching to general categorical data and show that an unbiased estimator can be obtained via simple matching of the conditional marginal distributions. We demonstrate the effectiveness of the proposed method on a set of synthetic and real-world music and image benchmarks.