This paper explores the optimization of Ground Delay Programs (GDP), a prevalent Traffic Management Initiative used in Air Traffic Management (ATM) to reconcile capacity and demand discrepancies at airports. Employing Reinforcement Learning (RL) to manage the inherent uncertainties in the national airspace system-such as weather variability, fluctuating flight demands, and airport arrival rates-we developed two RL models: Behavioral Cloning (BC) and Conservative Q-Learning (CQL). These models are designed to enhance GDP efficiency by utilizing a sophisticated reward function that integrates ground and airborne delays and terminal area congestion. We constructed a simulated single-airport environment, SAGDP_ENV, which incorporates real operational data along with predicted uncertainties to facilitate realistic decision-making scenarios. Utilizing the whole year 2019 data from Newark Liberty International Airport (EWR), our models aimed to preemptively set airport program rates. Despite thorough modeling and simulation, initial outcomes indicated that the models struggled to learn effectively, attributed potentially to oversimplified environmental assumptions. This paper discusses the challenges encountered, evaluates the models' performance against actual operational data, and outlines future directions to refine RL applications in ATM.

Binary code similarity detection (BCSD) is widely used in various binary analysis tasks such as vulnerability search, malware detection, clone detection, and patch analysis. Recent studies have shown that the learning-based binary code embedding models perform better than the traditional feature-based approaches. In this paper, we propose a novel transformer-based binary code embedding model named UniASM to learn representations of the binary functions. We design two new training tasks to make the spatial distribution of the generated vectors more uniform, which can be used directly in BCSD without any fine-tuning. In addition, we present a new tokenization approach for binary functions, which increases the token's semantic information and mitigates the out-of-vocabulary (OOV) problem. We conduct an in-depth analysis of the factors affecting model performance through ablation experiments and obtain some new and valuable findings. The experimental results show that UniASM outperforms the state-of-the-art (SOTA) approach on the evaluation dataset. The average scores of Recall@1 on cross-compilers, cross-optimization levels, and cross-obfuscations are 0.77, 0.72, and 0.72. Besides, in the real-world task of known vulnerability search, UniASM outperforms all the current baselines.

Drug discovery is vitally important for protecting human against disease. Target-based screening is one of the most popular methods to develop new drugs in the past several decades. This method efficiently screens candidate drugs inhibiting target protein in vitro, but it often fails due to inadequate activity of the selected drugs in vivo. Accurate computational methods are needed to bridge this gap. Here, we propose a novel graph multi task deep learning model to identify compounds carrying both target inhibitory and cell active (MATIC) properties. On a carefully curated SARS-CoV-2 dataset, the proposed MATIC model shows advantages comparing with traditional method in screening effective compounds in vivo. Next, we explored the model interpretability and found that the learned features for target inhibition (in vitro) or cell active (in vivo) tasks are different with molecular property correlations and atom functional attentions. Based on these findings, we utilized a monte carlo based reinforcement learning generative model to generate novel multi-property compounds with both in vitro and in vivo efficacy, thus bridging the gap between target-based and cell-based drug discovery.

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here we propose a novel framework, named AIMEE, integrating AI Model and Enzymology Experiments, to identify inhibitors against 3CL protease of SARS-CoV-2, which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value less than 3 {\mu}M. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and expanding the boundaries of drug discovery.