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Chiglitazar is a promising new-generation insulin sensitizer with low reverse effects for the treatment of type II diabetes mellitus (T2DM) and has shown activity as a nonselective pan-agonist to the human peroxisome proliferator-activated receptors (PPARs) (i.e., full activation of PPAR γ and a partial activation of PPAR α and PPAR β / δ ). Yet, it has no high-resolution complex structure with PPARs and its detailed interactions and activation mechanism remain unclear. In this study, we docked chiglitazar into three experimentally resolved crystal structures of hPPAR subtypes, PPAR α , PPAR β / δ , and PPAR γ , followed by 3  μ s molecular dynamics simulations for each system. Our MM-GBSA binding energy calculation revealed that chiglitazar most favorably bound to hPPAR γ (-144.6 kcal/mol), followed by hPPAR α (-138.0 kcal/mol) and hPPAR β (-135.9 kcal/mol), and the order is consistent with the experimental data. Through the decomposition of the MM-GBSA binding energy by residue and the use of two-dimensional interaction diagrams, key residues involved in the binding of chiglitazar were identified and characterized for each complex system. Additionally, our detailed dynamics analyses support that the conformation and dynamics of helix 12 play a critical role in determining the activities of the different types of ligands (e.g., full agonist vs. partial agonist). Rather than being bent fully in the direction of the agonist versus antagonist conformation, a partial agonist can adopt a more linear conformation and have a lower degree of flexibility. Our finding may aid in further development of this new generation of medication. 

Network disaster recovery is one of the greatest concerns for Mobile Network Operators (MNOs) and first responders during large-scale natural disasters such as earth- quakes. In many recent studies, wireless multi-hop networking has been demonstrated as an effective technique to quickly and efficiently extend the network coverage during disasters. In this paper, we specifically address the network deployment problem by proposing the Population-Aware Relay Placement (PARP) solution, which seeks the efficient deployment of a limited number of relays such that population coverage is maximized in the scenario of network disaster recovery. We provide a graph-based modeling and prove its NP-hardness accordingly. In order to efficiently solve this problem, we propose a heuristic solution, which is constructed in two steps. We first design a simple algorithm based on a disk graph to determine the Steiner locations, which is the biggest challenge in this problem. Then, we formulate the problem as an integer programming problem, which is inspired by the formulation of Prize-Collecting Steiner Tree (PCST). Thus, the integer problem is solved by exploring the similarity of the existing algorithm for PCST. To evaluate the proposed solution extensively, we present numerical results on both real-world and random scenarios, which validate the effectiveness of the proposed solution and show substantial improvement by comparing to the previous one. 

Natural disasters can result in severe damage to communication infrastructure, which leads to further chaos to the damaged area. After the disaster strikes, most of the victims would gather at the evacuation sites for food supplies and other necessities. Having a good communication network is very important to help the victims. In this paper, we aim at recovering the network from the still-alive mobile base stations to the out-of-service evacuation sites by using multi-hop relaying technique. We propose to reconstruct the post-disaster network in a capacity-aware way based on prize collecting Steiner tree. The purpose of the proposed scheme is to achieve high capacity connectivity ratio in a cost efficient way. To provide more accurate evaluation results, we evaluate the proposed scheme by using the real evacuation site and base station data in Tokyo area, and utilizing the big data analysis based post-disaster service availability model.