Search Results (2,471)

In the Internet of Things (IoT) era, Mobile Edge Computing (MEC) significantly enhances the efficiency of smart devices but is limited by battery life issues. Wireless Power Transfer (WPT) addresses this issue by providing a stable energy supply. However, effectively managing overall energy consumption remains a critical and under-addressed aspect for ensuring the network’s sustainable operation and growth. In this paper, we consider a WPT-MEC network with user cooperation to migrate the double near–far effect for the mobile node (MD) far from the base station. We formulate the problem of maximizing long-term computation rates under a power consumption constraint as a multi-stage stochastic optimization (MSSO) problem. This approach is tailored for a sustainable WPT-MEC network, considering the dynamic and varying MEC network environment, including randomness in task arrivals and fluctuating channels. We introduce a virtual queue to transform the time-average energy constraint into a queue stability problem. Using the Lyapunov optimization technique, we decouple the stochastic optimization problem into a deterministic problem for each time slot, which can be further transformed into a convex problem and solved efficiently. Our proposed algorithm works efficiently online without requiring further system information. Extensive simulation results demonstrate that our proposed algorithm outperforms baseline schemes, achieving approximately 4% enhancement while maintain the queues stability. Rigorous mathematical analysis and experimental results show that our algorithm achieves $\left[O(1/V),O\left(V\right)\right]$ trade-off between computation rate and queue stability. Full article

Molecular imprinting is a promising approach for developing polymeric materials as artificial receptors. However, only a few types of molecularly imprinted polymers (MIPs) are commercially available, and most research on MIP_S is still in the experimental phase. The significant limitation has been a challenge for screening imprinting systems, particularly for weak functional target molecules. Herein, a combined method of quantum mechanics (QM) computations and molecular dynamics (MD) simulations was employed to screen an appropriate 2,4-dichlorophenoxyacetic acid (2,4-D) imprinting system. QM calculations were performed using the Gaussian 09 software. MD simulations were conducted using the Gromacs2018.8 software suite. The QM computation results were consistent with those of the MD simulations. In the MD simulations, a realistic model of the ‘actual’ pre-polymerisation mixture was obtained by introducing numerous components in the simulations to thoroughly investigate all non-covalent interactions during imprinting. This study systematically examined MIP systems using computer simulations and established a theoretical prediction model for the affinity and selectivity of MIPs. The combined method of QM computations and MD simulations provides a robust foundation for the rational design of MIPs. Full article

Device-to-device (D2D) is a pivotal technology in the next generation of communication, allowing for direct task offloading between mobile devices (MDs) to improve the efficient utilization of idle resources. This paper proposes a novel algorithm for dynamic task offloading between the active MDs and the idle MDs in a D2D–MEC (mobile edge computing) system by deploying multi-agent deep reinforcement learning (DRL) to minimize the long-term average delay of delay-sensitive tasks under deadline constraints. Our core innovation is a dynamic partitioning scheme for idle and active devices in the D2D–MEC system, accounting for stochastic task arrivals and multi-time-slot task execution, which has been insufficiently explored in the existing literature. We adopt a queue-based system to formulate a dynamic task offloading optimization problem. To address the challenges of large action space and the coupling of actions across time slots, we model the problem as a Markov decision process (MDP) and perform multi-agent DRL through multi-agent proximal policy optimization (MAPPO). We employ a centralized training with decentralized execution (CTDE) framework to enable each MD to make offloading decisions solely based on its local system state. Extensive simulations demonstrate the efficiency and fast convergence of our algorithm. In comparison to the existing sub-optimal results deploying single-agent DRL, our algorithm reduces the average task completion delay by 11.0% and the ratio of dropped tasks by 17.0%. Our proposed algorithm is particularly pertinent to sensor networks, where mobile devices equipped with sensors generate a substantial volume of data that requires timely processing to ensure quality of experience (QoE) and meet the service-level agreements (SLAs) of delay-sensitive applications. Full article

The cocrystallization of 1,3,5,7-tetranitro-1,3,5,7-tetrazolidine (HMX) with cyclopentanone was achieved via a controlled cooling method, followed by comprehensive characterization that confirmed the α-configuration of HMX within the cocrystal. The enthalpy of dissolution of HMX in cyclopentanone was assessed across a range of temperatures using a C-80 Calvert microcalorimeter, revealing an endothermic dissolution process. Subsequently, the molar enthalpy of dissolution was determined, and kinetic equations describing the dissolution rate were derived for temperatures of 303.15, 308.15, 313.15, 318.15, and 323.15 K as follows: dα⁄dt = 10^−2.46(1 − α)^0.35, dα⁄dt = 10^−2.19(1 − α)^0.79, dα⁄dt = 10^−1.76(1 − α)^1.32, dα⁄dt = 10^−1.86(1 − α)^0.46, and dα⁄dt = 10^−2.02(1 − α)^0.70, respectively. Additionally, molecular dynamics (MD) simulations investigated the intermolecular interactions of the HMX/cyclopentanone cocrystallization process, demonstrating a transformation of HMX from β- to α-conformation within the cyclopentanone environment. Theoretical calculations performed at the ωB97XD/6-311G(d,p) level affirmed that α-HMX exhibited stronger binding affinity toward cyclopentanone compared to β-HMX, corroborating experimental findings. A comprehensive understanding of the dissolution behavior of HMX in cyclopentanone holds significant implications for crystal growth methodologies and cocrystallization processes. Such insights are pivotal for optimizing HMX dissolution processes and offer valuable perspectives for developing and designing advanced energetic materials. Full article

This study evaluates radioiodinated anastrozole ([¹²⁵I]anastrozole) and epirubicin ([¹²⁵I]epirubicin) for HER2-targeted cancer therapy, utilizing radiopharmaceutical therapy (RPT) for personalized treatment of HER2-positive cancers. Through molecular docking and dynamics simulations (200 ns), it investigates these compounds’ binding affinities and mechanisms to the HER2 receptor compared to lapatinib, a known HER2 inhibitor. Molecular docking studies identified [¹²⁵I]epirubicin with the highest ΔG_bind (−10.92 kcal/mol) compared to lapatinib (−10.65 kcal/mol) and [¹²⁵I]anastrozole (−9.65 kcal/mol). However, these differences were not statistically significant. Further molecular dynamics (MD) simulations are required to better understand the implications of these findings on the therapeutic potential of the compounds. MD simulations affirmed a stable interaction with the HER2 receptor, indicated by an average RMSD of 4.51 Å for [¹²⁵I]epirubicin. RMSF analysis pointed to significant flexibility at key receptor regions, enhancing the inhibitory action against HER2. The [¹²⁵I]epirubicin complex maintained an average of four H-bonds, indicating strong and stable interactions. The average Rg values for [¹²⁵I]anastrozole and [¹²⁵I]epirubicin complexes suggest a modest increase in structural flexibility without compromising protein compactness, reflecting their potential to induce necessary conformational changes in the HER2 receptor function. These analyses reveal enhanced flexibility and specific receptor region interactions, suggesting adaptability in binding, which could augment the inhibitory action against HER2. MM-PBSA calculations indicate the potential of these radioiodinated compounds as HER2 inhibitors. Notably, [¹²⁵I]epirubicin exhibited a free binding energy of −65.81 ± 0.12 kJ/mol, which is comparable to lapatinib at −64.05 ± 0.11 kJ/mol and more favorable than [¹²⁵I]anastrozole at −57.18 ± 0.12 kJ/mol. The results suggest electrostatic interactions as a major contributor to the binding affinity. The computational analysis underscores that [¹²⁵I]anastrozole and [¹²⁵I]epirubicin may have a promising role as HER2 inhibitors, especially [¹²⁵I]epirubicin due to its high binding affinity and dynamic receptor interactions. These findings, supported by molecular docking scores and MM-PBSA binding energies, advocate for their potential superior inhibitory capability against the HER2 receptor. To validate these computational predictions and evaluate the therapeutic potential of these compounds for HER2-targeted cancer therapy, it is essential to conduct empirical validation through both in vitro and in vivo studies. Full article

The emergence of drug-resistance-inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A, including H57R and S139P within the catalytic triad. We then modelled each mutational variant for pharmacophore-based virtual screening (PBVS) followed by covalent docking towards identifying a potential covalent inhibitor, i.e., cpd-217. The binding stability of cpd-217 was then supported by molecular dynamic simulation followed by MM/GBSA binding free energy calculation. The free energy decomposition analysis indicated that the resistant mutants alter the HCV NS3/4A–ligand interaction, resulting in unbalanced energy distribution within the binding site, leading to drug resistance. Cpd-217 was identified as interacting with all NS3/4A G3 variants with significant covalent docking scores. In conclusion, cpd-217 emerges as a potential inhibitor of HCV NS3/4A G3 variants that warrants further in vitro and in vivo studies. This study provides a theoretical foundation for drug design and development targeting HCV G3 NS3/4A. Full article

Metabolomics, the study of small-molecule metabolites within biological systems, has become a potent instrument for understanding cellular processes. Despite its profound insights into health, disease, and drug development, identifying the protein partners for metabolites, especially dietary phytochemicals, remains challenging. In the present study, we introduced an innovative in silico, structure-based target prediction approach to efficiently predict protein targets for metabolites. We analyzed 27 blood serum metabolites from nutrition intervention studies’ blueberry-rich diets, known for their health benefits, yet with elusive mechanisms of action. Our findings reveal that blueberry-derived metabolites predominantly interact with Carbonic Anhydrase (CA) family proteins, which are crucial in acid-base regulation, respiration, fluid balance, bone metabolism, neurotransmission, and specific aspects of cellular metabolism. Molecular docking showed that these metabolites bind to a common pocket on CA proteins, with binding energies ranging from −5.0 kcal/mol to −9.0 kcal/mol. Further molecular dynamics (MD) simulations confirmed the stable binding of metabolites near the Zn binding site, consistent with known compound interactions. These results highlight the potential health benefits of blueberry metabolites through interaction with CA proteins. Full article

Critical blood shortages plague healthcare systems, particularly in lower-income and middle-income countries. This affects patients requiring regular transfusions and creates challenges during emergencies where universal blood is vital. To address these shortages and support blood banks during emergencies, this study reports a method for increasing the compatibility of blood group A red blood cells (RBCs) by blocking surface antigen-A using anti-A single chain fragment variable (scFv). To enhance stability, the scFv was first modified with the addition of interdomain disulfide bonds. The most effective location for this modification was found to be H44-L232 of mutant-1a scFv. ScFv was then produced from E.coli BL21(DE3) and purified using a three-step process. Purified scFvs were then used to block maximum number of antigens-A on RBCs, and it was found that only monomers were functional, while dimers formed through incorrect domain-swapping were non-functional. These antigen-blocked RBCs displayed no clumping in hemagglutination testing with incompatible blood plasma. The dissociation constant K_D was found to be 0.724 μM. Antigen-blocked RBCs have the potential to be given to other blood groups during emergencies. This innovative approach could significantly increase the pool of usable blood, potentially saving countless lives. Full article

Glucagon receptor (GCGR) is a class B1 G-protein-coupled receptor that plays a crucial role in maintaining human blood glucose homeostasis and is a significant target for the treatment of type 2 diabetes mellitus (T2DM). Currently, six small molecules (Bay 27-9955, MK-0893, MK-3577, LY2409021, PF-06291874, and LGD-6972) have been tested or are undergoing clinical trials, but only the binding site of MK-0893 has been resolved. To predict binding sites for other small molecules, we utilized both the crystal structure of the GCGR and MK-0893 complex and dynamic conformations. We docked five small molecules and selected the best conformation based on binding mode, docking score, and binding free energy. We performed MD simulations to verify the binding mode of the selected small molecules. Moreover, when selecting conformations, results of competitive binding were referred to. MD simulation indicated that Bay 27-9955 exhibits moderate binding stability in Pocket 3. MK-3577, LY2409021, and PF-06291874 exhibited highly stable binding to Pocket 2, consistent with experimental results. However, LY2409021 may also bind to Pocket 5. Additionally, LGD-6972 exhibited relatively stable binding in Pocket 5. We also conducted structural modifications of LGD-6972 based on the results of MD simulations and predicted its analogues’ bioavailability, providing a reference for the study of GCGR small molecules. Full article

Aluminium nitride (AlN) materials are widely used in heat-dissipation substrates and electronic device packages. However, the application of aluminium nitride ceramics is hindered by the obvious anisotropy and high brittleness of its crystals, leading to poor material surface integrity and high grinding force. With the rapid development of microelectronics, the requirements for the material’s dimensional accuracy, machining efficiency, and surface accuracy are increasing. Therefore, a new machining process is proposed, combining laser and ultrasonic vibration with grinding. The laser–ultrasonic-assisted grinding (LUAG) of aluminium nitride is simulated by molecular dynamics (MD). Meanwhile, the effects of different processing techniques on grinding force, stress distribution, matrix damage mechanism, and subsurface damage depth are systematically investigated and verified by experiments. The results show that laser–ultrasonic-assisted grinding produces 50% lower grinding forces compared to traditional grinding (TG). The microhardness of AlN can reach more than 1200 HV, and the coefficient of friction and wear is reduced by 42.6%. The dislocation lines of the AlN substrate under this process are short but interlaced, making the material prone to phase transformation. Moreover, the subsurface damage depth is low, realising the substrate’s material hardening and wear resistance. These studies not only enhance the comprehension of material build-up and stress damage under the synergistic impact of laser, ultrasonic, and abrasive processing but also indicate that the proposed method can facilitate and realise high-performance machining of aluminium nitride substrate surfaces. Full article

Carbon nanotubes (CNTs) are considered an advanced form of carbon. They have superior characteristics in terms of mechanical and thermal properties compared to other available fibers and can be used in various applications, such as supercapacitors, sensors, and artificial muscles. The properties of single-walled carbon nanotubes (SWNTs) are significantly affected by geometric parameters such as chirality and aspect ratio, and testing conditions such as temperature and strain rate. In this study, the effects of geometric parameters and temperature on the mechanical properties of SWNTs were studied by molecular dynamics (MD) simulations using the Large-scaled Atomic/Molecular Massively Parallel Simulator (LAMMPS). Based on the second-generation reactive empirical bond order (REBO) potential, SWNTs of different diameters were tested in tension and compression under different strain rates and temperatures to understand their effects on the mechanical behavior of SWNTs. It was observed that the Young’s modulus and the tensile strength decreases with increasing SWNT tube diameter. As the chiral angle increases, the tensile strength increases, while the Young’s modulus decreases. The simulations were repeated at different temperatures of 300 K, 900 K, 1500 K, 2100 K and different strain rates of 1 × 10⁻³/ps, 0.75 × 10⁻³/ps, 0.5 × 10⁻³/ps, and 0.25 × 10⁻³/ps to investigate the effects of temperature and strain rate, respectively. The results show that the ultimate tensile strength of SWNTs increases with increasing strain rate. It is also seen that when SWNTs were stretched at higher temperatures, they failed at lower stresses and strains. The compressive behavior results indicate that SWNTs tend to buckle under lower stresses and strains than those under tensile stress. The simulation results were validated by and consistent with previous studies. The presented approach can be applied to investigate the properties of other advanced materials. Full article

Furins are serine endoproteases that are involved in many biological processes, where they play important roles in normal metabolism, in the activation of various pathogens, while they are a target for therapeutic intervention. Dichlorophenyl-pyridine “BOS” compounds are well known drugs that are used as inhibitors of human furin by an induced-fit mechanism, in which tryptophan W254 in the furin catalytic cleft acts as a molecular transition energy gate. The binding of “BOS” drug into the active center of furin has been computationally studied using the density functional theory (DFT) and ONIOM multiscaling methodologies. The binding enthalpies of the W254 with the furin-BOS is −32.8 kcal/mol (“open”) and −18.8 kcal/mol (“closed”), while the calculated torsion barrier was found at 30 kcal/mol. It is significantly smaller than the value of previous MD calculations due to the relaxation of the environment, i.e., nearby groups of the W254, leading to the reduction of the energy demands. The significant lower barrier explains the experimental finding that the dihedral barrier of W254 is overcome. Furthermore, sartans were studied to evaluate their potential as furin inhibitors. Sartans are AT1 antagonists, and they effectively inhibit the hypertensive effects induced by the peptide hormone Angiotensin II. Here, they have been docked into the cavity to evaluate their effect on the BOS ligand via docking and molecular dynamics simulations. A consistent binding of sartans within the cavity during the simulation was found, suggesting that they could act as furin inhibitors. Finally, sartans interact with the same amino acids as W254, leading to a competitive binding that may influence the pharmacological efficacy and potential drug interactions of sartans. Full article

Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-β-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear. In this study, Gaussian accelerated molecular dynamics (GaMD) simulation was employed to elucidate the inhibitory mechanisms of NDGA and AKBA on 5LOX. It was found that the orthosteric inhibitor NDGA was tightly bound in the protein’s active pocket, occupying the active site and inhibiting the catalytic activity of the 5LOX enzyme through competitive inhibition. The binding of the allosteric inhibitor AKBA induced significant changes at the distal active site, leading to a conformational shift of residues 168–173 from a loop to an α-helix and significant negative correlated motions between residues 285–290 and 375–400, reducing the distance between these segments. In the simulation, the volume of the active cavity in the stable conformation of the protein was reduced, hindering the substrate’s entry into the active cavity and, thereby, inhibiting protein activity through allosteric effects. Ultimately, Markov state models (MSM) were used to identify and classify the metastable states of proteins, revealing the transition times between different conformational states. In summary, this study provides theoretical insights into the inhibition mechanisms of 5LOX by AKBA and NDGA, offering new perspectives for the development of novel inhibitors specifically targeting 5LOX, with potential implications for anti-inflammatory drug development. Full article

This work presents the studies of a very strong hydrogen bond (VSHB) in biologically active phthalic acids. Research on VSHB comes topical due to its participation in many biological processes. The studies cover the modelling of intermolecular interactions and phthalic acids with 2,4,6-collidine and N,N-dimethyl-4-pyridinamine complexes with aim to obtain a VSHB. The four synthesized complexes were studied by experimental X-ray, IR, and Raman methods, as well as theoretical Car–Parrinello Molecular Dynamics (CP-MD) and Density Functional Theory (DFT) simulations. By variation of the steric repulsion and basicity of the complex’ components, a very short intramolecular hydrogen bond was achieved. The potential energy curves calculated by the DFT method were characterized by a low barrier (0.7 and 0.9 kcal/mol) on proton transfer in the OHN intermolecular hydrogen bond for 3-nitrophthalic acid with either 2,4,6-collidine or N,N-dimethyl-4-pyridinamine cocrystals. Moreover, the CP-MD simulations exposed very strong bridging proton dynamics in the intermolecular hydrogen bonds. The accomplished crystallographic and spectroscopic studies indicate that the OHO intramolecular hydrogen bond in 4-nitrophthalic cocrystals is VSHB. The influence of a strong steric effect on the geometry of the studied cocrystals and the stretching vibration bands of the carboxyl and carboxylate groups was elaborated. Full article

The construction of mountain tunnels can lead to groundwater loss and severely impact plant growth. In order to study the limited discharge of groundwater in mountain tunnels for the normal growth of typical herbaceous plants, a tunnel in the alpine meadow area of Qinghai Province was taken as the research objective. Based on transplant experiments, numerical simulations, and the empirical calculation of tunnel discharge limits, the minimum water level required for the normal growth of herbaceous plants, groundwater changes, and grouting parameters during tunnel construction, as well as limited discharge values of groundwater based on the normal growth requirements of plants, were studied. The results indicate that when the groundwater level declined by 0.6–0.8 m, herbaceous plants were able to normally grow. Generally, tunnel excavation lowered the groundwater level so that the normal growth of herbaceous plants was significantly affected. The reasonable grouting parameters were obtained by numerical simulation. They were able to ensure that the groundwater level decline was less than 0.8 m and ultimately recovered to over 90% of the pre-construction level. The herbaceous plants in Qinghai’s alpine grasslands were able to normally grow when the groundwater discharge limit was 0.2~4.0 m³/(m·d). This research offers guidance and support for managing groundwater discharge during tunnel construction in ecologically fragile areas, such as the Three Rivers Source in Qinghai. Full article