A long-standing goal of machine-learning-based protein engineering is to accelerate the discovery of novel mutations that improve the function of a known protein. We introduce a sampling framework for evolving proteins in silico that supports mixing and matching a variety of unsupervised models, such as protein language models, and supervised models that predict protein function from sequence. By composing these models, we aim to improve our ability to evaluate unseen mutations and constrain search to regions of sequence space likely to contain functional proteins. Our framework achieves this without any model fine-tuning or re-training by constructing a product of experts distribution directly in discrete protein space. Instead of resorting to brute force search or random sampling, which is typical of classic directed evolution, we introduce a fast MCMC sampler that uses gradients to propose promising mutations. We conduct in silico directed evolution experiments on wide fitness landscapes and across a range of different pre-trained unsupervised models, including a 650M parameter protein language model. Our results demonstrate an ability to efficiently discover variants with high evolutionary likelihood as well as estimated activity multiple mutations away from a wild type protein, suggesting our sampler provides a practical and effective new paradigm for machine-learning-based protein engineering.

自然图像和医学图像之间的根本差异最近有利于对医学图像应用中的Imagenet转移学习使用自我监督学习（SSL）。图像类型之间的差异主要是由于成像方式和医学图像利用了广泛的基于物理的技术，而自然图像仅使用可见光捕获。尽管许多人证明了医学图像上的SSL导致了更好的下游任务绩效，但我们的工作表明可以获得更多的性能。在构建学习问题时，经常不考虑用于获取医学图像的科学原理。因此，我们建议在生成SSL期间合并定量成像原理，以提高图像质量和定量生物学准确性。我们表明，这种培训模式可为有限数据的下游监督培训提供更好的起始状态。我们的模型还生成了验证临床定量分析软件的图像。

异常气道扩张，称为牵引支气管扩张，是特发性肺纤维化（IPF）的典型特征。体积计算断层扫描（CT）成像捕获IPF中逐渐变细的丢失。我们假设气道异常的自动化量化可以提供IPF疾病程度和严重程度的估算。我们提出了一种自动化计算管道，系统地将气道树木从基于深度学习的气道分割中划分到其裂片和世代分支，从而从胸部CT获得气道结构措施。重要的是，透气阻止通过厚波传播的杂散气道分支的发生，并通过图表搜索去除气道树中的环，克服现有气道骨架算法的限制。在14名健康参与者和14名IPF患者之间比较了透气段（跨空间）和透气曲线曲线之间的逐渐变化。 IPF患者中，Airway interberering显着降低，与健康对照相比，Airway曲线曲调显着增加。差异在下叶中最大标记，符合IPF相关损伤的典型分布。透气是一种开源管道，避免了现有的气道定量算法的限制，并具有临床解释性。自动化气道测量可能具有作为IPF严重程度和疾病程度的新型成像生物标志物。

We introduce Argoverse 2 (AV2) - a collection of three datasets for perception and forecasting research in the self-driving domain. The annotated Sensor Dataset contains 1,000 sequences of multimodal data, encompassing high-resolution imagery from seven ring cameras, and two stereo cameras in addition to lidar point clouds, and 6-DOF map-aligned pose. Sequences contain 3D cuboid annotations for 26 object categories, all of which are sufficiently-sampled to support training and evaluation of 3D perception models. The Lidar Dataset contains 20,000 sequences of unlabeled lidar point clouds and map-aligned pose. This dataset is the largest ever collection of lidar sensor data and supports self-supervised learning and the emerging task of point cloud forecasting. Finally, the Motion Forecasting Dataset contains 250,000 scenarios mined for interesting and challenging interactions between the autonomous vehicle and other actors in each local scene. Models are tasked with the prediction of future motion for "scored actors" in each scenario and are provided with track histories that capture object location, heading, velocity, and category. In all three datasets, each scenario contains its own HD Map with 3D lane and crosswalk geometry - sourced from data captured in six distinct cities. We believe these datasets will support new and existing machine learning research problems in ways that existing datasets do not. All datasets are released under the CC BY-NC-SA 4.0 license.

Traditionally, data analysis and theory have been viewed as separate disciplines, each feeding into fundamentally different types of models. Modern deep learning technology is beginning to unify these two disciplines and will produce a new class of predictively powerful space weather models that combine the physical insights gained by data and theory. We call on NASA to invest in the research and infrastructure necessary for the heliophysics' community to take advantage of these advances.

Algorithms that involve both forecasting and optimization are at the core of solutions to many difficult real-world problems, such as in supply chains (inventory optimization), traffic, and in the transition towards carbon-free energy generation in battery/load/production scheduling in sustainable energy systems. Typically, in these scenarios we want to solve an optimization problem that depends on unknown future values, which therefore need to be forecast. As both forecasting and optimization are difficult problems in their own right, relatively few research has been done in this area. This paper presents the findings of the ``IEEE-CIS Technical Challenge on Predict+Optimize for Renewable Energy Scheduling," held in 2021. We present a comparison and evaluation of the seven highest-ranked solutions in the competition, to provide researchers with a benchmark problem and to establish the state of the art for this benchmark, with the aim to foster and facilitate research in this area. The competition used data from the Monash Microgrid, as well as weather data and energy market data. It then focused on two main challenges: forecasting renewable energy production and demand, and obtaining an optimal schedule for the activities (lectures) and on-site batteries that lead to the lowest cost of energy. The most accurate forecasts were obtained by gradient-boosted tree and random forest models, and optimization was mostly performed using mixed integer linear and quadratic programming. The winning method predicted different scenarios and optimized over all scenarios jointly using a sample average approximation method.

Point-of-Care Ultrasound (POCUS) refers to clinician-performed and interpreted ultrasonography at the patient's bedside. Interpreting these images requires a high level of expertise, which may not be available during emergencies. In this paper, we support POCUS by developing classifiers that can aid medical professionals by diagnosing whether or not a patient has pneumothorax. We decomposed the task into multiple steps, using YOLOv4 to extract relevant regions of the video and a 3D sparse coding model to represent video features. Given the difficulty in acquiring positive training videos, we trained a small-data classifier with a maximum of 15 positive and 32 negative examples. To counteract this limitation, we leveraged subject matter expert (SME) knowledge to limit the hypothesis space, thus reducing the cost of data collection. We present results using two lung ultrasound datasets and demonstrate that our model is capable of achieving performance on par with SMEs in pneumothorax identification. We then developed an iOS application that runs our full system in less than 4 seconds on an iPad Pro, and less than 8 seconds on an iPhone 13 Pro, labeling key regions in the lung sonogram to provide interpretable diagnoses.

Likelihood-based deep generative models have recently been shown to exhibit pathological behaviour under the manifold hypothesis as a consequence of using high-dimensional densities to model data with low-dimensional structure. In this paper we propose two methodologies aimed at addressing this problem. Both are based on adding Gaussian noise to the data to remove the dimensionality mismatch during training, and both provide a denoising mechanism whose goal is to sample from the model as though no noise had been added to the data. Our first approach is based on Tweedie's formula, and the second on models which take the variance of added noise as a conditional input. We show that surprisingly, while well motivated, these approaches only sporadically improve performance over not adding noise, and that other methods of addressing the dimensionality mismatch are more empirically adequate.

Multi-agent artificial intelligence research promises a path to develop intelligent technologies that are more human-like and more human-compatible than those produced by "solipsistic" approaches, which do not consider interactions between agents. Melting Pot is a research tool developed to facilitate work on multi-agent artificial intelligence, and provides an evaluation protocol that measures generalization to novel social partners in a set of canonical test scenarios. Each scenario pairs a physical environment (a "substrate") with a reference set of co-players (a "background population"), to create a social situation with substantial interdependence between the individuals involved. For instance, some scenarios were inspired by institutional-economics-based accounts of natural resource management and public-good-provision dilemmas. Others were inspired by considerations from evolutionary biology, game theory, and artificial life. Melting Pot aims to cover a maximally diverse set of interdependencies and incentives. It includes the commonly-studied extreme cases of perfectly-competitive (zero-sum) motivations and perfectly-cooperative (shared-reward) motivations, but does not stop with them. As in real-life, a clear majority of scenarios in Melting Pot have mixed incentives. They are neither purely competitive nor purely cooperative and thus demand successful agents be able to navigate the resulting ambiguity. Here we describe Melting Pot 2.0, which revises and expands on Melting Pot. We also introduce support for scenarios with asymmetric roles, and explain how to integrate them into the evaluation protocol. This report also contains: (1) details of all substrates and scenarios; (2) a complete description of all baseline algorithms and results. Our intention is for it to serve as a reference for researchers using Melting Pot 2.0.

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License.