The GPR18 receptor, often referred to as the N-arachidonylglycine receptor, although assigned (along with GPR55 and GPR119) to the new class A GPCR subfamily-lipid receptors, officially still has the status of a class A GPCR orphan. While its signaling pathways and biological significance have not yet been fully elucidated, increasing evidence points to the therapeutic potential of GPR18 in relation to immune, neurodegenerative, and cancer processes to name a few. Therefore, it is necessary to understand the interactions of potential ligands with the receptor and the influence of particular structural elements on their activity. Thus, given the lack of an experimentally solved structure, the goal of the present study was to obtain a homology model of the GPR18 receptor in the inactive state, meeting all requirements in terms of protein structure quality and recognition of active ligands. To increase the reliability and precision of the predictions, different contemporary protein structure prediction methods and software were used and compared herein. To test the usability of the resulting models, we optimized and compared the selected structures followed by the assessment of the ability to recognize known, active ligands. The stability of the predicted poses was then evaluated by means of molecular dynamics simulations. On the other hand, most of the best-ranking contemporary CADD software/platforms for its full usability require rather expensive licenses. To overcome this down-to-earth obstacle, the overarching goal of these studies was to test whether it is possible to perform the thorough CADD experiments with high scientific confidence while using only license-free/academic software and online platforms. The obtained results indicate that a wide range of freely available software and/or academic licenses allow us to carry out meaningful molecular modelling/docking studies. 相似文献
In wireless networks, seamless roaming allows a mobile user (MU) to utilize its services through a foreign server (FS) when outside his home server (HS). However, security and efficiency of the authentication protocol as well as privacy of MUs are of great concern to achieve an efficient authentication protocol. Conventionally, authentication involves the participation of three entities (MU, HS, and FS); however, involving an HS in the authentication process incurs heavy computational burden on it due to huge amount of roaming requests. Moreover, wireless networks are often susceptible to various forms of passive and active attacks. Similarly, mobile devices have low processing, communication, and power capabilities.
In this paper, we propose an efficient, secure, and privacy-preserving lightweight authentication protocol for roaming MUs in wireless networks without engaging an HS. The proposed authentication protocol uses unlinkable pseudo-IDs and lightweight time-bound group signature to provide strong user anonymity, and a cost-effective cryptographic scheme to achieve security of the authentication protocol. Similarly, we implement a better billing system for MUs and a computationally efficient revocation scheme. Our analysis shows that the protocol has better performance than other related authentication protocols in wireless communications in terms of security, privacy, and efficiency. 相似文献
In this study, we apply the fractional Laplace variational iteration method (FLVIM), a computer methodology for exploring fractional Navier–Stokes equation solutions. In light of the theory of fixed points and Banach spaces, this paper also explores the uniqueness and convergence of the solution of general fractional differential equations obtained by the suggested method. In addition, the fractional Laplace variational iteration method solution's error analysis is covered. The computational technique also clearly demonstrates the validity and dependability of the suggested method for solving fractional Navier-Stokes equations. Furthermore, the obtained solutions are a perfect fit with previously established solutions. 相似文献
The present framework proposed the development of a Hybrid Rubber-Concrete Isolation Slab System (HRCISS) to support building structures subjected to horizontal and vertical vibration due to ground motion and machine or equipment operation in the structure. Given that the effect of the shape factor on both horizontal and vertical stiffness has yet to be reported, the proposed composite system was comprised of two layers under the nodal points of the upper layer near the slab corners with four High Damping Rubber (HDR) components positioned between the slab layers to dissipate multidirectional (horizontal and vertical directions) vibrations. The ABAQUS software was utilized to model the finite element model (FEM) and simulate the HRCISS subjected to cyclic horizontal and vertical displacements. For the optimal HDR design, the model was applied in five 3-story buildings, and the effect of distinct shape factors (0 S 2) of the HDR bearings—the ratio of bearing's loaded area to unloaded area (free to bulge)—within the hybrid system was evaluated. For each building with a specific HDR shape factor, the HRCISS was installed in the first, second, and third stories, separately, to investigate the influence of the installation level of the isolation system on the overall structural performance. The multistory buildings were subjected to two types of vibration loads: the interior machine-induced vibrations, and the exterior seismic-induced vibrations in the horizontal and vertical directions. Based on the results, the FEM results proved the significant influence of the shape factors on the dynamic response of the HRCISS under both interior and exterior 3D vibrations when applied in multistory buildings. The lateral drift of the three-story one-bay buildings decreased with the decrement of shape factor with buildings of HRCISS installed in 1st story recording more reduction. Moreover, the deflection in the structural slab under the HRCISS decreased for lower shape factor bearings. Nevertheless, the reduced deflection was less affected by the level of the machine-equipped story. The rubber layer also stiffened in shear and compression directions with a higher shape factor. 相似文献
Thrombosis and its complications are responsible for 30% of annual deaths. Limitations of methods for diagnosing and treating thrombosis highlight the need for improvements. Agents that provide simultaneous diagnostic and therapeutic activities (theranostics) are paramount for an accurate diagnosis and rapid treatment. In this study, silver-iron oxide nanoparticles (AgIONPs) are developed for highly efficient targeted photothermal therapy and imaging of thrombosis. Small iron oxide nanoparticles are employed as seeding agents for the generation of a new class of spiky silver nanoparticles with strong absorbance in the near-infrared range. The AgIONPs are biofunctionalized with binding ligands for targeting thrombi. Photoacoustic and fluorescence imaging demonstrate the highly specific binding of AgIONPs to the thrombus when functionalized with a single chain antibody targeting activated platelets. Photothermal thrombolysis in vivo shows an increase in the temperature of thrombi and a full restoration of blood flow for targeted group but not in the non-targeted group. Thrombolysis from targeted groups is significantly improved (p < 0.0001) in comparison to the standard thrombolytic used in the clinic. Assays show no apparent side effects of AgIONPs. Altogether, this work suggests that AgIONPs are potential theranostic agents for thrombosis. 相似文献
This work explores the performance of single- and multi-GPU computing on state-of-the-art NVIDIA- and AMD-based server-class hardware using various programming interfaces to accelerate a real-world scientific application for solidification modeling based on the phase-field method. The main computations of this memory-bound application correspond to 20 stencils computed across grid nodes. We investigate the application's scalability for two basic schemes of organizing computation: without and with hiding data transfers behind computation, combined with using either peer-to-peer inter-GPU data transfers through NVIDIA NVLink and AMD Infinity interconnects or communication over the PCIe and main memory. Among the studied programming interfaces is CUDA, HIP, and OpenMP Accelerator Model. While the first two are designed to write the codes for a specific hardware platform, OpenMP enables code portability between NVIDIA and AMD GPUs. The resulting performance is experimentally assessed on computing platforms containing NVIDIA V100 (up to 8 GPUs) and A100 (one GPU), as well as AMD MI210 (one device) and MI250 (up to 8 logical GPUs). 相似文献