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.

我们提供了PelficGridWorld软件包，为用户提供轻量级，模块化和可定制的框架，用于创建专注的电源系统的多代理体育馆环境，该环境易于与强化学习（RL）的现有培训框架集成。虽然存在许多框架用于训练多代理RL（MARL）政策，但没有可以快速原型并发开发环境，尤其是在所需电流解决方案来定义网格的异构（复合式，多器件）电力系统的背景下 - 级别变量和成本。 PowerGridWorld是一个开源软件包，有助于填补此间隙。为了突出PowerGridWorld的关键功能，我们展示了两个案例研究，并使用Openai的多代理深度确定性政策梯度（MADDPG）和RLLIB的近端策略优化（PPO）算法来演示MARL政策。在这两种情况下，至少一些代理子集合在每次作为奖励（负成本）结构的一部分中的一部分中的功率流溶液的元件。

我们仔细比较了两种无模型控制算法，演进策略和近端政策优化（PPO），具有后退地平线模型预测控制（MPC），用于操作模拟，价格响应式热水器。考虑了四个MPC变体：单次控制器，具有完美预测产生最佳控制;一个有限的地平控制器，具有完美预测;基于平均的预测控制器;使用历史情景，一个两阶段随机编程控制器。在所有情况下，水温和电价的MPC模型精确;只有水需求不确定。为了比较，ES和PPO通过在MPC使用的相同场景下直接与模拟环境直接交互来学习基于神经网络的策略。然后在需求时间序列的单独一周继续的单独一周内进行评估所有方法。我们证明了对这个问题的最佳控制是具有挑战性的，需要超过8小时的MPC寻找，具有完美预测来获得最低成本。尽管存在这一挑战，但ES和PPO都学会了在平均成本方面优于平均预测和两级随机MPC控制器的良好通用政策，并且在计算动作时速度越来越多的数量级。我们表明ES尤其可以利用并行性，使用1150 CPU核心在90秒内学习策略。

In this paper, we propose a novel technique, namely INVALIDATOR, to automatically assess the correctness of APR-generated patches via semantic and syntactic reasoning. INVALIDATOR reasons about program semantic via program invariants while it also captures program syntax via language semantic learned from large code corpus using the pre-trained language model. Given a buggy program and the developer-patched program, INVALIDATOR infers likely invariants on both programs. Then, INVALIDATOR determines that a APR-generated patch overfits if: (1) it violates correct specifications or (2) maintains errors behaviors of the original buggy program. In case our approach fails to determine an overfitting patch based on invariants, INVALIDATOR utilizes a trained model from labeled patches to assess patch correctness based on program syntax. The benefit of INVALIDATOR is three-fold. First, INVALIDATOR is able to leverage both semantic and syntactic reasoning to enhance its discriminant capability. Second, INVALIDATOR does not require new test cases to be generated but instead only relies on the current test suite and uses invariant inference to generalize the behaviors of a program. Third, INVALIDATOR is fully automated. We have conducted our experiments on a dataset of 885 patches generated on real-world programs in Defects4J. Experiment results show that INVALIDATOR correctly classified 79% overfitting patches, accounting for 23% more overfitting patches being detected by the best baseline. INVALIDATOR also substantially outperforms the best baselines by 14% and 19% in terms of Accuracy and F-Measure, respectively.

The recent increase in public and academic interest in preserving biodiversity has led to the growth of the field of conservation technology. This field involves designing and constructing tools that utilize technology to aid in the conservation of wildlife. In this article, we will use case studies to demonstrate the importance of designing conservation tools with human-wildlife interaction in mind and provide a framework for creating successful tools. These case studies include a range of complexities, from simple cat collars to machine learning and game theory methodologies. Our goal is to introduce and inform current and future researchers in the field of conservation technology and provide references for educating the next generation of conservation technologists. Conservation technology not only has the potential to benefit biodiversity but also has broader impacts on fields such as sustainability and environmental protection. By using innovative technologies to address conservation challenges, we can find more effective and efficient solutions to protect and preserve our planet's resources.

Variational autoencoders model high-dimensional data by positing low-dimensional latent variables that are mapped through a flexible distribution parametrized by a neural network. Unfortunately, variational autoencoders often suffer from posterior collapse: the posterior of the latent variables is equal to its prior, rendering the variational autoencoder useless as a means to produce meaningful representations. Existing approaches to posterior collapse often attribute it to the use of neural networks or optimization issues due to variational approximation. In this paper, we consider posterior collapse as a problem of latent variable non-identifiability. We prove that the posterior collapses if and only if the latent variables are non-identifiable in the generative model. This fact implies that posterior collapse is not a phenomenon specific to the use of flexible distributions or approximate inference. Rather, it can occur in classical probabilistic models even with exact inference, which we also demonstrate. Based on these results, we propose a class of latent-identifiable variational autoencoders, deep generative models which enforce identifiability without sacrificing flexibility. This model class resolves the problem of latent variable non-identifiability by leveraging bijective Brenier maps and parameterizing them with input convex neural networks, without special variational inference objectives or optimization tricks. Across synthetic and real datasets, latent-identifiable variational autoencoders outperform existing methods in mitigating posterior collapse and providing meaningful representations of the data.

Cashews are grown by over 3 million smallholders in more than 40 countries worldwide as a principal source of income. As the third largest cashew producer in Africa, Benin has nearly 200,000 smallholder cashew growers contributing 15% of the country's national export earnings. However, a lack of information on where and how cashew trees grow across the country hinders decision-making that could support increased cashew production and poverty alleviation. By leveraging 2.4-m Planet Basemaps and 0.5-m aerial imagery, newly developed deep learning algorithms, and large-scale ground truth datasets, we successfully produced the first national map of cashew in Benin and characterized the expansion of cashew plantations between 2015 and 2021. In particular, we developed a SpatioTemporal Classification with Attention (STCA) model to map the distribution of cashew plantations, which can fully capture texture information from discriminative time steps during a growing season. We further developed a Clustering Augmented Self-supervised Temporal Classification (CASTC) model to distinguish high-density versus low-density cashew plantations by automatic feature extraction and optimized clustering. Results show that the STCA model has an overall accuracy of 80% and the CASTC model achieved an overall accuracy of 77.9%. We found that the cashew area in Benin has doubled from 2015 to 2021 with 60% of new plantation development coming from cropland or fallow land, while encroachment of cashew plantations into protected areas has increased by 70%. Only half of cashew plantations were high-density in 2021, suggesting high potential for intensification. Our study illustrates the power of combining high-resolution remote sensing imagery and state-of-the-art deep learning algorithms to better understand tree crops in the heterogeneous smallholder landscape.

Coronary Computed Tomography Angiography (CCTA) provides information on the presence, extent, and severity of obstructive coronary artery disease. Large-scale clinical studies analyzing CCTA-derived metrics typically require ground-truth validation in the form of high-fidelity 3D intravascular imaging. However, manual rigid alignment of intravascular images to corresponding CCTA images is both time consuming and user-dependent. Moreover, intravascular modalities suffer from several non-rigid motion-induced distortions arising from distortions in the imaging catheter path. To address these issues, we here present a semi-automatic segmentation-based framework for both rigid and non-rigid matching of intravascular images to CCTA images. We formulate the problem in terms of finding the optimal \emph{virtual catheter path} that samples the CCTA data to recapitulate the coronary artery morphology found in the intravascular image. We validate our co-registration framework on a cohort of $n=40$ patients using bifurcation landmarks as ground truth for longitudinal and rotational registration. Our results indicate that our non-rigid registration significantly outperforms other co-registration approaches for luminal bifurcation alignment in both longitudinal (mean mismatch: 3.3 frames) and rotational directions (mean mismatch: 28.6 degrees). By providing a differentiable framework for automatic multi-modal intravascular data fusion, our developed co-registration modules significantly reduces the manual effort required to conduct large-scale multi-modal clinical studies while also providing a solid foundation for the development of machine learning-based co-registration approaches.

Springs are efficient in storing and returning elastic potential energy but are unable to hold the energy they store in the absence of an external load. Lockable springs use clutches to hold elastic potential energy in the absence of an external load but have not yet been widely adopted in applications, partly because clutches introduce design complexity, reduce energy efficiency, and typically do not afford high-fidelity control over the energy stored by the spring. Here, we present the design of a novel lockable compression spring that uses a small capstan clutch to passively lock a mechanical spring. The capstan clutch can lock up to 1000 N force at any arbitrary deflection, unlock the spring in less than 10 ms with a control force less than 1 % of the maximal spring force, and provide an 80 % energy storage and return efficiency (comparable to a highly efficient electric motor operated at constant nominal speed). By retaining the form factor of a regular spring while providing high-fidelity locking capability even under large spring forces, the proposed design could facilitate the development of energy-efficient spring-based actuators and robots.

Springs can provide force at zero net energy cost by recycling negative mechanical work to benefit motor-driven robots or spring-augmented humans. However, humans have limited force and range of motion, and motors have a limited ability to produce force. These limits constrain how much energy a conventional spring can store and, consequently, how much assistance a spring can provide. In this paper, we introduce an approach to accumulating negative work in assistive springs over several motion cycles. We show that, by utilizing a novel floating spring mechanism, the weight of a human or robot can be used to iteratively increase spring compression, irrespective of the potential energy stored by the spring. Decoupling the force required to compress a spring from the energy stored by a spring advances prior works, and could enable spring-driven robots and humans to perform physically demanding tasks without the use of large actuators.