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We combine on-the-fly trajectory surface hopping simulations and the doorway–window representation of nonlinear optical response functions to create an efficient protocol for the evaluation of time- and frequency-resolved fluorescence (TFRF) spectra and anisotropies of the realistic polyatomic systems. This approach gives the effective description of the proper (e.g., experimental) pulse envelopes, laser field polarizations, and the proper orientational averaging of TFRF signals directly from the well-established on-the-fly nonadiabatic dynamic simulations without extra computational cost. To discuss the implementation details of the developed protocol, we chose cis-azobenzene as a prototype to simulate the time evolution of the TFRF spectra governed by its nonadiabatic dynamics. The results show that the TFRF is determined by the interplay of several key factors, i.e., decays of excited-state populations, evolution of the transition dipole moments along with the dynamic propagation, and scaling factor of the TFRF signals associated with the cube of emission frequency. This work not only provides an efficient and effective approach to simulate the TFRF and anisotropies of realistic polyatomic systems but also discusses the important relationship between the TFRF signals and the underlining nonadiabatic dynamics. [ABSTRACT FROM AUTHOR]

This article presents methodological advances in the state-of-the-art for making time-dependent, thermochemical measurements within kilogram-scale explosive post-detonation fireballs utilizing tunable laser absorption spectroscopy. This measurement capability is critical for validating multi-scale, multi-physics models of post-detonation dynamics. The technique is based on hardened gauges built around rapidly-tunable lasers and custom post-processing algorithms that provide quantitative thermochemical data interior to large and opaque explosive fireballs. The authors present a holistic overview of the technique including gauge design, the laser absorption diagnostic, and the custom data processing algorithms. Additionally, fielding high-bandwidth laser absorption probes at stand-off ranges presents new challenges in data processing that must compensate for long distance signal transmission effects. We highlight representative data from a hardened gauge measurement at 0.81 m stand-off from a 2.78 kg LX-14 explosive charge detonated in an outdoor test arena. We discuss progress in all-optical measurement of temperature, pressure, and water vapor number density at a 100 kHz repetition rate during the first 10 ms of the fireball evolution. We conclude the article with a brief discussion on our current approach for comparing hardened gauge measurements with computational fluid dynamic simulations. [ABSTRACT FROM AUTHOR]

Modelling of many real-world processes, such as drug delivery, wastewater treatment, and pharmaceutical production, requires accurate descriptions of the dynamics of hard particles confined in complicated domains. In particular, when modelling sedimentation processes or systems with driven flows, it is important to accurately capture volume exclusion effects. This work applies Dynamic Density Functional Theory to the evolution of a particle density under diffusion, external forces, particle–particle interaction, and volume exclusion. Using a spectral element framework, for the first time it is possible to include all of these effects in dynamic simulations on complex domains. Moreover, this allows one to apply complicated no-flux, and other non-local, non-linear, boundary conditions. The methodology is also extended to control problems, addressing questions of how to enhance production set-up in industrially-motivated processes. In this work the relevant models are introduced, numerical methods are discussed, and several example problems are solved to demonstrate the methods' versatility. It is shown that incorporating volume exclusion is crucial for simulation accuracy and we illustrate that the choice of boundary conditions significantly impacts the dynamics. [ABSTRACT FROM AUTHOR]

Parkinson's disease is accompanied by the presence of amyloids in the brain that are formed of α-synuclein chains. The correlation between COVID-19 and the onset of Parkinson's disease led to the idea that amyloidogenic segments in SARS-COV-2 proteins can induce aggregation of α-synuclein. Using molecular dynamic simulations, we show that the fragment FKNIDGYFKI of the spike protein, which is unique for SARS-COV-2, preferentially shifts the ensemble of α-synuclein monomer toward rod-like fibril seeding conformations and, at the same time, differentially stabilizes this polymorph over the competing twister-like structure. Our results are compared with earlier work relying on a different protein fragment that is not specific for SARS-COV-2. [ABSTRACT FROM AUTHOR]

In this work, we investigate the water capture process for functionalized carbon nanocones (CNCs) through molecular dynamic simulations in the following three scenarios: a single CNC in contact with a reservoir containing liquid water, a single CNC in contact with a water vapor reservoir, and a combination of more than one CNC in contact with vapor. We found that water flows through the nanocones when in contact with the liquid reservoir if the nanocone tip presents hydrophilic functionalization. In contact with steam, we observed the formation of droplets at the base of the nanocone only when hydrophilic functionalization is present. Then, water flows through in a linear manner, a process that is more efficient than that in the liquid reservoir regime. The scalability of the process is tested by analyzing the water flow through more than one nanocone. The results suggest that the distance between the nanocones is a fundamental ingredient for the efficiency of water harvesting. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the ejection production from twice-shocked Sn using molecular dynamic simulations in regimes where the metal undergoes complete shock melting after the first shock. A new description form of a bubble shape is proposed to fit the interface during the whole stage, which overcomes the inapplicability of the flycut profile in later stages. We then explore the ejection on second shock with the dimensionless intervals of ∼3.8 and ∼96 between the two shocks. Surprisingly, the results show that the ejecta model can well predict the second ejecta mass with a shock interval of ∼3.8 while far underestimated that with a shock interval of ∼96. We find that in the presence of the first ejecta, the high-speed secondary interface interacts with the low-speed first ejecta, resulting in the movement of liquid metals to the secondary ejecta, thereby promoting the increase of secondary ejecta mass. These findings are further validated by our smoothed particle hydrodynamics simulations at a macroscale. [ABSTRACT FROM AUTHOR]

Large-scale nonequilibrium molecular dynamics simulation is used to study the effect of grain size and Cr segregation at the twin boundary (TB) on the spalling fracture mechanism of nickel based alloys. In particular, loading waves are designed so that the maximum tensile stress first appears in the grain interior for all the crystals with different grain sizes. In contrast to traditional understandings, no monotonous relationship between the spall strength and the grain size appears in our results. The spall strength is found to depend on the wave attenuation distance measured from the first maximum tensile stress position to the spalled TB as well as the accompanied microstructure evolutions. The number of spalling plane increases with the increase of TB or the decrease of the grain size. As the grain size continues to decrease, a greater impact strength is required to cause spallation fracture at multiple TBs. In this case, the spall strength becomes insensitive to the first maximum tensile stress position. With the increment of solute atom concentration, the number of the spalling plane increases when the solution is segregated. But it decreases when the solution is uniformly distributed. Such a result is explained by segregation-enhanced energy dissipation and interactions between the waves and the microstructures nearby TBs. In particular, the shock wave would induce a local lattice reorientation nearby the TB depending on its segregation degree and the lattice reorientation would modify the slip manner of stacking faults and, thus, affect void nucleation and growth. The lattice reorientation would also contribute to the generation of sub-grain boundaries inside the grains in terms of the movement of stacking faults. Void nucleation at the sub-GB is the main cause of fracture at the grain interior. [ABSTRACT FROM AUTHOR]

In this study, the enantioselectivity of β‐cyclodextrin and its derivatives towards propranolol enantiomers are investigated by molecular dynamic (MD) simulations. β‐cyclodextrin (β‐CD) have previously been shown to be able to recognize propranolol (PRP) enantiomers. To improve upon the enantioselectivity of β‐cyclodextrin, we propose the use of an ionic‐liquid‐modified‐β‐cyclodextrin (β‐CD‐IL). β‐CD‐IL was found to be able to complex R and S propranolol enantiomers with differing binding energies. The molecular docking study reveals that the ionic liquid chain attached to the β‐CD molecule has significant interaction with propranolol. The formation of the most stable complex occurred between (S)‐β‐CD‐IL and (S)‐propranolol with an energy of −5.80 kcal/mol. This is attributed to the formation of a hydrogen bond between the oxygen of the propranolol and the hydrogen on the primary rim of the (S)‐β‐CD‐IL cavity. This interaction is not detected in other complexes. The root mean‐squared fluctuation (RMSF) value indicates that the NH group is the most flexible molecular fragment, followed by the aromatic group. Also of note, the formation of a complex between pristine β‐CD and (S)‐propranolol is the least favorable. [ABSTRACT FROM AUTHOR]

Multiple drug-resistant fungal species are associated with the development of diseases. Thus, more efficient drugs for the treatment of these aetiological agents are needed. Rondonin is a peptide isolated from the haemolymph of the spider Acanthoscurria rondoniae. Previous studies have shown that this peptide has antifungal activity against Candida sp. and Trichosporon sp. strains, acting on their genetic material. However, the molecular targets involved in its biological activity have not yet been described. Bioinformatics tools were used to determine the possible targets involved in the biological activity of Rondonin. The PharmMapper server was used to search for microorganismal targets of Rondonin. The PatchDock server was used to perform the molecular docking. UCSF Chimera software was used to evaluate these intermolecular interactions. In addition, the I-TASSER server was used to predict the target ligand sites. Then, these predictions were contrasted with the sites previously described in the literature. Molecular dynamics simulations were conducted for two promising complexes identified from the docking analysis. Rondonin demonstrated consistency with the ligand sites of the following targets: outer membrane proteins F (id: 1MPF) and A (id: 1QJP), which are responsible for facilitating the passage of small molecules through the plasma membrane; the subunit of the flavoprotein fumarate reductase (id: 1D4E), which is involved in the metabolism of nitrogenous bases; and the ATP-dependent Holliday DNA helicase junction (id: 1IN4), which is associated with histone proteins that package genetic material. Additionally, the molecular dynamics results indicated the stability of the interaction of Rondonin with 1MPF and 1IN4 during a 10 ns simulation. These interactions corroborate with previous in vitro studies on Rondonin, which acts on fungal genetic material without causing plasma membrane rupture. Therefore, the bioprospecting methods used in this research were considered satisfactory since they were consistent with previous results obtained via in vitro experimentation. [ABSTRACT FROM AUTHOR]

Highlights: This review delves into the recent progress in high-performance and multifunctional neuromorphic devices for artificial intelligence applications from a novel perspective of plasticity modulation. It provides an in-depth discussion on the plasticity modulation strategies by chemical techniques, device structure design and physical signal modulation for advanced neuromorphic applications. It offers the prospects of exploring novel plasticity modulation mechanisms and techniques for scaled neural networks and examining their potentials in multimodal collaborative neuromorphic systems. Manipulating the expression of synaptic plasticity of neuromorphic devices provides fascinating opportunities to develop hardware platforms for artificial intelligence. However, great efforts have been devoted to exploring biomimetic mechanisms of plasticity simulation in the last few years. Recent progress in various plasticity modulation techniques has pushed the research of synaptic electronics from static plasticity simulation to dynamic plasticity modulation, improving the accuracy of neuromorphic computing and providing strategies for implementing neuromorphic sensing functions. Herein, several fascinating strategies for synaptic plasticity modulation through chemical techniques, device structure design, and physical signal sensing are reviewed. For chemical techniques, the underlying mechanisms for the modification of functional materials were clarified and its effect on the expression of synaptic plasticity was also highlighted. Based on device structure design, the reconfigurable operation of neuromorphic devices was well demonstrated to achieve programmable neuromorphic functions. Besides, integrating the sensory units with neuromorphic processing circuits paved a new way to achieve human-like intelligent perception under the modulation of physical signals such as light, strain, and temperature. Finally, considering that the relevant technology is still in the basic exploration stage, some prospects or development suggestions are put forward to promote the development of neuromorphic devices. [ABSTRACT FROM AUTHOR]

Wheel‐rail contact is a link between the vehicle system and the rail system, and the contact processing approach affects accuracy of vehicle dynamic simulation. Contact detection is usually the start of wheel‐rail contact calculation, and detecting precision of contact patch center affect accuracy of contact force calculating results, therefore it is significant to improve detecting precision of contact patch center. An alternate search method (ASM) and an extended trace line method are proposed to improve precision and efficiency of contact patch centers detection. The proposed alternate search method applies Golden Ratio Search Method and variable intervals between grids to detect contact patch centers. To make the detected contact patch centers match rail tangential directions better, an extended trace line method is constructed based on geometrical constraints between contact points and rail tangential directions. Dynamic simulations of a bogie vehicle formed by two wheelsets and a bogie frame negotiating a rail curve are conducted to evaluate effects of the proposed methods. Calculating times of the proposed methods for finishing the simulations are compared to explain computational efficiencies of the different methods. The proposed approaches are real‐time capable and can be used for vehicle dynamics simulations. [ABSTRACT FROM AUTHOR]

Background and Objectives: When a haematopoietic stem cell registry size is constrained by limits on recruiting, as in Canada, identifying the right person to recruit is a critical determinant of effectiveness. The aim of this study was to evaluate the impact of changes to donor recruitment effort, within ethnic groups, on the matching effectiveness of the Canadian registry as it evolves over time. Materials and Methods: Simulation methods are applied to create a cohort of donor recruits and patients over a 10‐year time horizon. New recruits are added to the registry each year, while some existing donors 'age‐out' upon reaching their 36th birthday. In a similar fashion, simulated patient lists are created. At the end of each simulated year, simulated patients are matched against the simulated registry. Results: There are increased matches in non‐White populations when diverse registrants are preferentially recruited, but there are larger decreases in the number of matches for Caucasian patients. Additionally, ethnic communities that have limited registrants in the Canadian registry in 2021 do not benefit from increased recruiting efforts as much as communities with a larger initial number of registrants. Conclusion: Preferentially recruiting from non‐Caucasian populations reduces the number of matches from Canadian sources because increases in non‐Caucasian populations will not fully counterbalance decreases to Caucasian patient matches. Nevertheless, more than 80% of all matches are for Caucasian patients, regardless of the donor recruiting effort within ethnic groups. [ABSTRACT FROM AUTHOR]

As one of the core transmission components, axle-box bearings have been widely applied in urban rail vehicles and played a crucial role in their safe and stable operation. No matter in the starting and stopping stage or stable operation stage of the vehicle, the skidding phenomenon in axle-box bearings exists and impacts their own dynamic characteristics. Furthermore, as one of the main shape errors of the bearing surface, waviness may cause fluctuations for skidding characteristics of axle-box bearings. This study investigates the skidding dynamic analysis of axle-box bearings, taking into account race surface waviness. Firstly, a dynamics model for double-row cylindrical roller bearings is established, considering the cage flexibility and friction forces between different components. Then, this model is coupled with a three-dimension vehicle–track model, allowing for more precise dynamic simulation of axle-box bearings under actual running conditions. Furthermore, an excitation related to race surface waviness is added to the coupling model through time-varying displacement and contact stiffness. At last, the influence of race surface waviness on skidding characteristics of axle-box bearings is analyzed. The effectiveness of the proposed model is validated through theoretical analysis and field tests. Simulation results demonstrate that race surface waviness can impact the cage and roller slip ratio of axle-box bearings. Overall, this study provides valuable insights into the skidding dynamic analysis of axle-box bearings, highlighting the importance of considering race surface waviness in designing and maintaining axle-box bearings. [ABSTRACT FROM AUTHOR]

Objective: The tandem Knoevenagel-cyclocondensation reaction of aromatic aldehydes, malonitrile, and phenylhydrazine in water and ethanol at room temperature is described as an effective, one-pot, threecomponent synthesis of many scientifically relevant heterocyclic compounds. Methods: As a part of our efforts, we have synthesized pyrazole-4-carbonitriles and characterized using various spectroscopic methods and subjected for antimicrobial analysis. Results and Discussion: From our analysis, we observed best in vitro candidate as 5-amino-3-(2,5-difluorophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile. The molecular docking analysis on common bacterial target suggested the involvement of 2,2-dialkylglycine decarboxylase (PDB ID: 1D7U) as a target for compound (IVi) (docking score: –9.32 kcal/mol). Furthermore, a molecular dynamic simulation of 100 ns resulted in the stability of best docked candidate, (IVi): 1D7U. Conclusions: We propose that best docked candidate, (IVi) as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

The shoulder joint has a high degree of freedom and an extremely complex and unstable kinematic mechanism. Coordinated contraction of the rotator cuff muscles that stop around the humeral head and the deltoid muscles and the extensibility of soft tissues, such as the joint capsule, labrum, and ligaments, contribute to shoulder-joint stability. Understanding the mechanics of shoulder-joint movement, including soft-tissue characteristics, is important for disease prevention and the development of a device for disease treatment. This study aimed to create a musculoskeletal shoulder model to represent the realistic behavior of joint movement and soft-tissue deformation as a dynamic simulation using a rigid-body model for bones and a soft-body model for soft tissues via a spring–damper–mass system. To reproduce the muscle-contraction properties of organisms, we used a muscle-expansion representation and Hill's mechanical muscle model. Shoulder motion, including the movement of the center of rotation in joints, was reproduced, and the strain in the joint capsule during dynamic shoulder movement was quantified. Furthermore, we investigated narrowing of the acromiohumeral distance in several situations to induce tissue damage due to rotator cuff impingement at the anterior–subacromial border during shoulder abduction. Given that the model can analyze exercises under disease conditions, such as muscle and tendon injuries and impingement syndrome, the proposed model is expected to help elucidate disease mechanisms and develop treatment guidelines. [ABSTRACT FROM AUTHOR]

Abnormal wear of stitch wires due to interference poses a serious threat to railway safety. To avoid this scenario, the concept of the dynamic envelope of the stitch wire was proposed, accompanied by an interference check method. A multi-node beam model of the stitch wire was established using the finite element method, employed to simulate the pantograph and catenary system, and validated by field test. The dynamic behaviour of the stitch wire was studied, and the concept of dynamic envelope was introduced. Moreover, factors affecting this envelope were analysed, and an interference check method was proposed. Results demonstrate that, the vibration of the stitch wire mainly occurs in the vertical direction and intensifies with increasing speed. Its vertical vibration increases from 70 mm to 137 mm as the train speed goes from 300 km/h to 400 km/h. Cantilever assembly errors and dropper installation issues are the main causes for the abnormal wear of stitch wires. A 100 mm assembly error reduces the clearance from 67 mm to 14 mm, while a 2 m dropper installation error eliminates the clearance entirely. This study provides valuable insights for enhancing the safety of catenary system. [ABSTRACT FROM AUTHOR]

The presented article deals with the issue of inventory management optimization through modelling and simulation in the software Tecnomatix Plant Simulation. Based on an in-depth analysis of the supply chain with an emphasis on inventory management, a simulation model was developed. It was optimized using the inventory theory methodology in combination with a discrete-event simulation approach. Dynamic simulation made it possible to perform experiments and optimize the existing state. The solution to the problem is elaborated on a case study to achieve the efficiency of the supply process of a specific operation of a clothing retail chain, which is struggling with the problems of excessive and inaccurate supply. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) has become a serious public health problem both in our country and worldwide, being the most prevalent type of diabetes. The combined use of drugs in the treatment of T2DM leads to serious side effects, including gastrointestinal problems, liver toxicity, hypoglycemia, and treatment costs. Hence, there has been a growing emphasis on drugs that demonstrate dual interactions. Several studies have suggested that dual-target agents for peroxisome proliferator-activated receptor-γ (PPAR-γ) and alpha-glucosidase (α-glucosidase) could be a potent approach for treating patients with diabetes. We aim to develop new antidiabetic agents that target PPAR-γ and α-glucosidase enzymes using molecular modeling techniques. These compounds show dual interactions, are more effective, and have fewer side effects. The molecular docking method was employed to investigate the enzyme-ligand interaction mechanisms of 159 newly designed compounds with target enzymes. Additionally, we evaluated the ADME properties and pharmacokinetic suitability of these compounds based on Lipinski and Veber's rules. Compound 70, which exhibited favorable ADME properties, demonstrated more effective binding energy with both PPAR-γ and α-glucosidase enzymes (-12,16 kcal/mol, -10.07 kcal/mol) compared to the reference compounds of Acetohexamide (-9.31 kcal/mol, -7.48 kcal/mol) and Glibenclamide (-11.12 kcal/mol, -8.66 kcal/mol). Further, analyses of MM/PBSA binding free energy and molecular dynamics (MD) simulations were conducted for target enzymes with compound 70, which exhibited the most favorable binding affinities with both enzymes. Based on this information, our study aims to contribute to the development of new dual-target antidiabetic agents with improved efficacy, reduced side effects, and enhanced reliability for diabetes treatment. [ABSTRACT FROM AUTHOR]

Nowadays, the dynamic behavior of rolling stocks is an essential problem. In dynamic simulation, the correct wheel-rail contact modeling is an important task. In this paper, the stiffness of the wheel-rail contact zone is found by a new, direct, and simplified formulation. This subject is developed by applying more details, such as surface roughness based on the surface topography and hardening effects of a real contact problem. These characteristics have not been considered altogether in other similar works. In this work, the contact stiffness and frequency results are obtained for different material properties and verified with analytical and experimental research. It is shown that the presented new direct method with an acceptable accuracy is easier to use than the complicated existing methods. This paper discusses the effects of contact parameter variations on contact stiffness and frequency. For example, it is shown that the contact stiffness decreases by increasing the surface roughness and increases by increasing the strain-hardening factor. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a new method for exact decomposition of propagating, nonlinear magnetohydrodynamic (MHD) disturbances into their component eigenenergies associated with the familiar slow, Alfvén, and fast wave eigenmodes, and the entropy and field-divergence pseudoeigenmodes. First, the mathematical formalism is introduced, where it is illustrated how the ideal-MHD eigensystem can be used to construct a decomposition of the time variation of the total energy density into contributions from the eigenmodes. The decomposition method is then demonstrated by applying it to the output of three separate nonlinear MHD simulations. The analysis of the simulations confirms that the component wave modes of a composite wavefield are uniquely identified by the method. The slow, Alfvén, and fast energy densities are shown to evolve in exactly the way expected from comparison with known linear solutions and nonlinear properties, including processes such as mode conversion. Along the way, some potential pitfalls for the numerical implementation of the decomposition method are identified and discussed. We conclude that the exact, nonlinear decomposition method introduced is a powerful and promising tool for understanding the nature of the decomposition of MHD waves as well as analyzing and interpreting the output of dynamic MHD simulations. [ABSTRACT FROM AUTHOR]

The effects of evolutionary Arias intensity are thoroughly investigated based on ground motion simulation and nonlinear dynamic response. A new methodology is developed to generate a series of spectral-equivalent synthetic motions with different energy accumulation paths using wavelet packets. Systematic studies are performed on dynamic responses of hysteretic systems and liquefiable grounds using the simulated motions and actual recordings. An attempt is made to develop the relationship between liquefaction-induced deformation and shaking intensity rate which is used to quantify the rate of Arias intensity accumulation. The results indicate the need of considering evolutionary Arias intensity in nonlinear dynamic analysis. [ABSTRACT FROM AUTHOR]

Power system simulation is vital for designing and evaluating the performance of electrical system protection and control devices. Although several commercial simulators exist, most are expensive and not open-source code. It is essential to develop educational and research simulators that can prepare students, allow researchers to develop new methodologies, and assist system operators in making decisions. This paper aims to present a computer simulation platform called AnaDyn (dynamic analysis), a non-commercial and open-source platform. AnaDyn is an educational/research platform that allows dynamic (transient stability), quasi-steady-state simulation, modal, and power flow analysis. Short- and long-term studies of voltage, frequency, and rotor angle instability problems can be performed. The main characteristics of AnaDyn are quasi-steady-state simulation, in which the equations are not simplified; easy integration with other tools and toolboxes, since AnaDyn is developing in MATLAB; flexible modeling that allows the inclusion of new devices and controller tests. The detailed modeling of various power system devices, the description of the numerical solution method, and the interface are also presented in this work. The platform is validated by comparing a test system's results with those obtained with Brazil's most popular commercial software. The main potentials of quasi-steady-state simulation are also presented. The results indicate that AnaDyn is efficient for educational and research studies on the stability of short- and long-term electrical systems. [ABSTRACT FROM AUTHOR]

Globally, rail transit is developing toward higher speeds, larger axle weights, and greater environmental friendliness. The more and more complex wheel–rail interaction will result in the dynamic responses of vehicles, tracks and other structures needing more in-depth theoretical research. However, most existing models for dynamic simulations of the vehicle–track coupling system need to extend the model on both sides of the concerned region to eliminate the boundary effect. To a certain extent, this kind of process method increases the computational effort. To overcome this disadvantage, a hybrid model combined with the analytical method and finite element method was proposed. The moving support system (including transition nodes) was specially established referring to the analytical solution of rail deflection based on the Winkler elastic foundation beam theory to realize the combination of the two methods. Two examples were presented to verify the stability and accuracy of the proposed model. The comparison results show that simulation results of vertical wheel–rail forces and track vibrations are almost consistent with the existing model. Furthermore, the calculation efficiency was discussed and certificated under different long-marshalling trains, with an obvious speedup factor that could be more than 2.5 for 16-marshalling train. The proposed model has a wide application prospect in the vehicle–track coupling analysis of long-marshalling trains, especially for heavy haul railways with hundreds of vehicles. [ABSTRACT FROM AUTHOR]

Coal-resource-based cities, as one of the important types of typical resource-based cities in China, have strong characteristics of instability, sensitivity, and fragility, exhibiting a series of vulnerability features of the human-land system. Previous studies have lacked a deeper investigation into the vulnerability of such cities from the perspective of coupling feedback mechanisms among various elements or subsystems. This paper adopts Bohle et al.'s "Dual Structure Model" of vulnerability to establish an indicator system for vulnerability warning in coal-resource-based cities. Using Fushun City as a sample, a dynamic simulation model of vulnerability in coal-resource-based cities is constructed based on system dynamics for warning simulation calculations, analyzing the evolution trend of vulnerability in Fushun City from 2010 to 2022. The results show the following: (1) from 2010 to 2022, the urban vulnerability of Fushun City transitioned from a medium warning level to a relatively safe level, showing a trend of annual reduction and improvement, undergoing three development stages of significant reduction, fluctuation stabilization, and slight rebound. (2) Due to the causal relationships among various elements within the vulnerability subsystems of Fushun City, differences exist in the contribution levels of vulnerability subsystems during the period 2010–2022, under the combined effects of sensitivity and adaptability factors. The contribution rate of the natural subsystem was the highest from 2010 to 2014, while, from 2016 to 2019, urban vulnerability began to shift towards an economically and socially dominant type. Influenced by the pandemic, Fushun City's overall vulnerability has shown an upward trend since 2020 compared to the previous stage. Finally, specific policy suggestions are proposed for Fushun City to cope with vulnerability changes based on the analysis results, providing a theoretical basis for achieving sustainable development in such coal-resource-based cities. [ABSTRACT FROM AUTHOR]

Phytophthora infestans (Mont.) de Bary, the oomycotic pathogen responsible for potato late blight, is the most devastating disease of potato production. The primary pesticides used to control oomycosis are phenyl amide fungicides, which cause environmental pollution and toxic residues harmful to both human and animal health. To address this, an antimicrobial peptide, NoPv1, has been screened to target Plasmopara viticola cellulose synthase 2 (PvCesA2) to inhibit the growth of Phytophthora infestans (P. infestans). In this study, we employed AlphaFold2 to predict the three-dimensional structure of PvCesA2 along with NoPv peptides. Subsequently, utilizing computational methods, we dissected the interaction mechanism between PvCesA2 and these peptides. Based on this analysis, we performed a saturation mutation of NoPv1 and successfully obtained the double mutants DP1 and DP2 with a higher affinity for PvCesA2. Meanwhile, dynamics simulations revealed that both DP1 and DP2 utilize a mechanism akin to the barrel-stave model for penetrating the cell membrane. Furthermore, the predicted results showed that the antimicrobial activity of DP1 was superior to that of NoPv1 without being toxic to human cells. These findings may offer insights for advancing the development of eco-friendly pesticides targeting various oomycete diseases, including late blight. [ABSTRACT FROM AUTHOR]

Water shortages and population surges pose notable challenges to food security. North China is an important grain base of the country, with limited available water resources. Therefore, it is necessary to research the patterns of photosynthate accumulation, distribution, and transfer in summer maize under water stress. On the basis of existing methods, in this study, we considered the impact of water stress with two methods, namely the distribution coefficient method and the distribution index method. The results showed that the water correction coefficient indices of the stem–leaf ratio spike–stem ratio, and root–shoot ratio were 0.2705, 0.3530, and −0.2097, respectively, which revealed that water stress caused a decrease in the stem–leaf ratio and spike–stem ratio and an increase in the root–shoot ratio. Water stress caused a reduction in the stem distribution index and leaf distribution index and a slight increase in the spike distribution index. The filling stage was the critical period for water stress to affect the distribution coefficient of each organ, while the jointing stage was the critical period for water stress to affect the leaf distribution index. During the middle growth period, water stress exerted the greatest impact on the distribution parameters. Water stress imposed a greater influence on the distribution coefficient than on the distribution index. The two methods effectively simulated the accumulation and distribution process of photosynthates under water stress conditions, and the R2, average absolute percentage and root mean square error values were 0.9358–0.9997, 4.15–22.71%, and 2.6–24.37%, respectively. The change trend of the photosynthate transfer rate calculated by the distribution coefficient method under water stress conditions was more consistent with that of the actual values. The distribution coefficient method generally performed better than the distribution index method. This study avoids the problem of solely relying on experimental data to determine crop growth dynamics and provides a way to describe crop photosynthate accumulation continuously and quantitatively. [ABSTRACT FROM AUTHOR]

To solve the problems of picking mushrooms manually in the factory mushroom growing environment with consuming time and labor, a mushroom picking robot was designed and developed. The mechanical structure of the picking robot system was designed by the modular design method, and the positive and negative kinematics solutions of the robot were deduced based on the D-H coordinate method to analyze the dynamic performance of the picking arm. The multi-objective optimization model of picking arm size structure was established for maximizing the picking efficiency, and the optimal solution was obtained with rapid iteration by genetic algorithm. The Adams virtual prototype model was established, and the picking dynamics simulation tests of the robot model before and after optimization were conducted. The simulation results show that under the same motor output torque, the maximum angular velocities of the big arm joint and the small arm joint are increased by 22.9% and 18.6%, respectively, while the single picking time is shortened from 1.60 s to 1.36 s with the picking speed increased by 15%. The developed physical prototype is suitable for the large area automatic picking operation in the sall multi- layer mushroom bed under the factory mushroom growing mode, and the single picking time is 2.0 s. [ABSTRACT FROM AUTHOR]

Motivation Simulating gut microbial dynamics is extremely challenging. Several computational tools, notably the widely used BacArena, enable modeling of dynamic changes in the microbial environment. These methods, however, do not comprehensively account for microbe–microbe stimulant or inhibitory effects or for nutrient–microbe inhibitory effects, typically observed in different compounds present in the daily diet. Results Here, we present BN-BacArena, an extension of BacArena consisting on the incorporation within the native computational framework of a Bayesian network model that accounts for microbe–microbe and nutrient–microbe interactions. Using in vitro experiments, 16S rRNA gene sequencing data and nutritional composition of 55 foods, the output Bayesian network showed 23 significant nutrient–bacteria interactions, suggesting the importance of compounds such as polyols, ascorbic acid, polyphenols and other phytochemicals, and 40 bacteria–bacteria significant relationships. With test data, BN-BacArena demonstrates a statistically significant improvement over BacArena to predict the time-dependent relative abundance of bacterial species involved in the gut microbiota upon different nutritional interventions. As a result, BN-BacArena opens new avenues for the dynamic modeling and simulation of the human gut microbiota metabolism. Availability and implementation MATLAB and R code are available in https://github.com/PlanesLab/BN-BacArena [ABSTRACT FROM AUTHOR]

In the current study, a dynamic layer freeze desalination system is simulated numerically. The computational domain is a two-dimensional rectangular channel which contains inlet and outlet flows, and the simulation is performed using computational fluid dynamics. A pre-concentrated mixture is considered as the feed solution with an initial temperature and concentration of 257 K and 0.2 kg/kg, respectively. In this work, since the simulation parameters such as temperature and species mass fraction have high importance across the entire domain, the k–ω shear stress transport turbulence model was selected. A parametric study on the effect of the heat flux of the cold wall on the ice salinity and desalination rate is performed using three cases with heat fluxes of − 1000 , − 1500 , and − 3000 W m − 2 . It is observed that the ice generation speed in the case with a heat flux of − 3000 W m − 2 is 3.28 times greater compared to the case with − 1000 W m − 2 and its desalination rate is only 2.59 % lower. The effect of the inlet velocity on the mentioned parameters is also investigated. It is observed that the cases with turbulent flow have approximately 19 % and 23 % lower ice salinity compared to the case with laminar flow. [ABSTRACT FROM AUTHOR]

Investigating immiscible displacement in fractured porous media is essential for understanding the two-phase flow behavior within pores and fractures. In this work, a three-dimensional pore-fracture network model was developed to address the influence of fracture on flow patterns and to characterize fracture-matrix crossflow under different flow conditions. Sensitivity studies at a wide range of viscosity ratios and capillary numbers underscored that fracture significantly influenced flow patterns in the capillary fingering zone. Fracture with an advantageous path effect in the displacement direction caused a shift in the boundary of capillary fingering zone toward an increase in capillary numbers. As fracture aperture decreased and aspect ratio increased, there was a discernible decline in the crossflow rate. When fracture aperture equaled average matrix throat diameter, fracture lose advantageous path effect in compact displacement zone but retained it in viscous fingering and capillary fingering zones. Distinct matrix-fracture crossflow development processes were observed in different zones: in cross zone, following displacement breakthrough, the crossflow underwent a "long-term" process to attain stability. Viscous fingering zone promptly achieved stability post-breakthrough, whereas both capillary fingering and compact displacement zones had already reached a stable state before breakthrough. Nonlinear variations in breakthrough saturation were observed in the cross zone between compact displacement and capillary fingering zones. The control process of immiscible displacement exhibited variability under different flow conditions: compact displacement zone was characterized by matrix dominance, viscous fingering zone was jointly controlled by matrix displacement and fracture-matrix crossflow, and capillary fingering zone was primarily governed by fracture-matrix crossflow. These findings enhance scholarly comprehension of immiscible displacement behavior in fractured porous media. [ABSTRACT FROM AUTHOR]

Heterotrimeric GTP-binding protein alpha subunit (Gα) and its cognate regulator of G-protein signaling (RGS) protein transduce signals in eukaryotes spanning protists, amoeba, animals, fungi, and plants. The core catalytic mechanisms of the GTPase activity of Gα and the interaction interface with RGS for the acceleration of GTP hydrolysis seem to be conserved across these groups; however, the RGS gene is under low selective pressure in plants, resulting in its frequent loss. Our current understanding of the structural basis of Gα:RGS regulation in plants has been shaped by Arabidopsis Gα, (AtGPA1), which has a cognate RGS protein. To gain a comprehensive understanding of this regulation beyond Arabidopsis, we obtained the x-ray crystal structures of Oryza sativa Gα, which has no RGS, and Selaginella moellendorffi (a lycophyte) Gα that has low sequence similarity with AtGPA1 but has an RGS. We show that the three-dimensional structure, protein-protein interaction with RGS, and the dynamic features of these Gα are similar to AtGPA1 and metazoan Gα. Molecular dynamic simulation of the Gα-RGS interaction identifies the contacts established by specific residues of the switch regions of GTP-bound Gα, crucial for this interaction, but finds no significant difference due to specific amino acid substitutions. Together, our data provide valuable insights into the regulatory mechanisms of plant G-proteins but do not support the hypothesis of adaptive co-evolution of Gα:RGS proteins in plants. [ABSTRACT FROM AUTHOR]

Investigating the resistance of materials in some applications, such as aerospace, to ballistic shocks is of great importance. This article used molecular dynamics simulation to study the effect of mechanical shock under impact loads. In the ballistic shock simulation of aluminum-graphene nanocomposites, the Mishin, Tersoff, and Lennard–Jones potentials were used for aluminum, carbon in the projectile, and aluminum-carbon nanocomposites. The study results show that the presence of graphene sheets in aluminum increases its mechanical properties, including Young's modulus and yield strength. Adding graphene prevents projectile penetration into the material, so aluminum with a higher percentage of graphene will have maximum absorption in less time. Furthermore, the effect of adding more graphene layers to aluminum was also investigated. Specifically, single to five-layer graphene sheets absorb 11, 28, 53.5, and 90% of the projectile's energy, respectively. Furthermore, some optimal configuration for withstanding along the external projectile was discussed here. [ABSTRACT FROM AUTHOR]

The manufacturing process for wrought Ti alloys with the hexagonal close-packed (HCP) structure introduces a complicated microstructure with abundant intra- and inter-grain boundaries, which greatly influence performance. In the hexagonal close-packed (HCP) structure, two types of grain boundaries are commonly observed between grains with ~90° misorientation: the basal/prismatic boundary (BPB) and the coherent twin boundary (CTB). The mechanical response of the BPB and CTB under external loading was studied through molecular dynamic simulations of HCP-Ti. The results revealed that CTB undergoes transformation into BPB through the accumulation of twin boundary (TB) steps and subsequent emission of Shockley partial dislocations. When the total mismatch vector is close to the Burgers vector of a Shockley partial dislocation, BPB emits partial dislocations and further grows along the stacking faults. When a pair of CTBs are close to each other, severe boundary distortion occurs, facilitating the emission and absorption of partial dislocations, which further assists the CTB-BPB transformation. The present results thus help to explain the frequent observation of coexisting CTB and BPB in HCP alloys and further contribute to the understanding of their microstructure and property regulation. [ABSTRACT FROM AUTHOR]

Introduction: GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in GNAO1 have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine. Methods: Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands. Results and discussion: We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in a rare neurological pediatric disease. [ABSTRACT FROM AUTHOR]

Fluid simulation is an essential tool to produce realistic looking animations. In particular, Lagrangian simulations offer interactive computation times with an easy integration of the two-way interaction with rigid bodies. However, the interactivity is lost for larger scenes even if only the areas around the bodies have any visual interest. In this paper, we present a novel approach to quickly initialize additional fluid in a rest state in simulations with any 3D boundary shape and able to preserve any already existing fluid. Our approach only uses the density property of the particles to allow compatibility with any smoothed-particle hydrodynamics (SPH) simulation scheme and any boundaries model. This initialization method is fast enough to allow the initialization of new fluid volumes interactively while the simulation is running. We showcase our approach by proposing a method to create a dynamic simulation window, allowing the restriction of simulating the fluid only around moving objects. We propose multiple experiments to demonstrate the capabilities and performance of our approach. [ABSTRACT FROM AUTHOR]

Unveiling the mechanisms and process of the interfacial reaction between transition metal oxides and metals have far-reaching implications for their superior application. Herein, the interfacial reaction between ZrO 2 and metals was comparatively studied, and the interfacial reactions between three types of ZrO 2 and Zr were systematically investigated by MD simulations. Comparative experiments show that the c -ZrO 2 reacts more vigorously with the active metal than the m -ZrO 2 under the same conditions, and modified c -ZrO 2 nanoparticles have core-shell structures due to the resulting oxygen concentration gradient. The MD simulations reveal that the crystal structure of ZrO 2 has a great influence on its oxygen loss rate (5.14 %–6.46 %) and oxygen distribution induced by the ZrO 2 /metal interface reaction. Meanwhile, the differences in ZrO 2 properties lead to two modes of ZrO 2 /metal interfacial reactions, which are distinguished by the characteristics of the oxygen distribution in the modified ZrO 2. One is that there is no obvious oxygen concentration gradient inside the ZrO 2 during the interfacial reaction, and the crystal defects in the modified ZrO 2 are uniformly distributed, such as c -ZrO 2 and t-ZrO 2. Another reaction mode is that only the region immediately adjacent to the interface in ZrO 2 undergoes diffusion of oxygen ions to the metal, and the interfacial reaction process proceeds layer by layer, such as m -ZrO 2. In addition, when the oxygen density and V O density of ZrO 2 are both low while the oxygen conductivity is high, the ZrO 2 /metal interfacial reaction tends to proceed according to mode A, resulting in modified ZrO 2 with uniformly distributed defects. [ABSTRACT FROM AUTHOR]

Food supplements have become beneficial as adjuvant therapies for many chronic disorders, including cancer. Genistein, a natural isoflavone enriched in soybeans, has gained potential interest as an anticancer agent for various cancers, primarily by modulating apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. However, in lung cancer, the exact impact and mechanism of action of genistein still require clarification. To provide more insight into the mechanism of action of genistein, network pharmacology was employed to identify the key targets and their roles in lung cancer pathogenesis. Based on the degree score, the hub genes AKT1, CASP3, EGFR, STAT3, ESR1, SRC, PTGS2, MMP9, PRAG, and AR were significantly correlated with genistein treatment. AKT1, EGFR, and STAT3 were enriched in the non-small cell lung cancer (NSCLC) pathway according to Kyoto Encyclopedia of Genes and Genomes analysis, indicating a significant connection to lung cancer development. Moreover, the binding affinity of genistein to NSCLC target proteins was further verified by molecular docking and molecular dynamics simulations. Genistein exhibited potential binding to AKT1, which is involved in apoptosis, cell migration, and metastasis, thus holding promise for modulating AKT1 function. Therefore, this study aimed to investigate the mechanism of action of genistein and its therapeutic potential for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

This study developed a finite element method (FEM) dynamic simulation to visualize the deployment behavior of thin membrane structures in the space environment. The proliferation of space debris resulting from accelerated space development threatens the future of space. Numerous researchers have explored strategies to prevent artificial structures from remaining in space and becoming space debris. One such method involves utilizing a drag sail device to de-orbit artificial structures, which reduces their kinetic energy by inducing additional atmospheric drag, allowing them to re-enter the Earth's atmosphere. Tohoku University and Nakashimada Engineering Works, Ltd. have successfully developed a deployable membrane structure for de-orbit purposes and demonstrated its effectiveness in space. Space structures, such as membranes, exhibit highly nonlinear behavior due to their flexible properties, and ground tests by actual devices cannot fully demonstrate their deployment stability in a microgravity environment. Therefore, evaluating the deployment behavior using simulation methods instead of relying solely on hardware development is crucial. In this study, we employed FEM to establish a simulation environment, which enables us to consider nonlinear oscillations of flexible structures, such as the membrane. The simulation results closely reproduce the deployment motion observed in ground tests by appropriately incorporating constraint conditions related to deployment forces and hardware interactions, such as a hub component initially wrapped by the membrane. The simulation facilitated an assessment of the impact of membrane properties on deployment without the need for physically developing an actual hardware device. We proposed evaluation methods for determining membrane properties in terms of the trend of propagation of deployed surface area and the tendency of deployment motion. This established simulation technique can be utilized to develop future flexible space structures. • De-orbit Membrane Mechanism (DOM) was developed as a satellite de-orbit application. • Formulate nonlinear FEM analysis of non-spin type deployable structures. • Modeling techniques of the membrane in simulation. • Evaluation of the membrane deployment between simulation and ground experiments. • Proposed methods can be used to predict the deployment behavior of the actual membrane. [ABSTRACT FROM AUTHOR]

The launcher recovery method known as 'In-Air Capturing' is an innovative approach where a winged rocket stage is captured mid-air by an aircraft and subsequently towed back to the launch site. To achieve this, a capturing device attached to a tether is released from the towing aircraft. This device autonomously connects the reusable launch vehicle to the aircraft, while the two vehicles are in proximity. The tether's flexible dynamics have a strong influence on the maneuverability of the capturing device. Thus, it is critical to model the dynamics of the tether to get a realistic understanding and to evaluate feasibility of the concept. However, precise modelling and control of highly flexible systems with large deformations is both challenging and computationally intensive. For engineering applications which involve closed-loop simulations, finding a trade-off between accuracy and computational effort is crucial. In this paper, the tether is modelled as a discretized chain of rigid bodies connected by rotational springs at the joints. The tether along with the capture system is integrated in a simulation model and open loop tests are performed to analyse the system characteristics. The tether properties are studied to find a suited configuration for 'In-Air Capturing'. • Multibody modelling approach for long cable like bodies with large deformation. • Capture system dynamics for the unique 'In-Air Capturing' launcher recovery concept. • Dynamic modelling for the complete capturing system including towing aircraft, capturing device and tether. • Assessment of tether properties suited for 'In-Air Capturing' with sensitivity studies. [ABSTRACT FROM AUTHOR]

Shimmy is one of the important factors affecting the ride comfort and lateral stability of straddle-type monorail vehicles with single-axle bogies (SMVS). To obtain the main parameters affecting SMVS shimmy, a global sensitivity analysis strategy for SMVS shimmy is proposed. The shimmy response surface model is constructed, and the sensitivity analysis of the shimmy response surface model is carried out by the Sobol method. Based on this, the shimmy factor model of SMVS is established by factor analysis method. A novel SMVS shimmy analysis method based on factor model is proposed. The shimmy factor model is verified by the dynamic model of SMVS. The results show that 11 main factors affecting the shimmy are obtained by sensitivity analysis. Through the dimension reduction technology of factor analysis, four main factors affecting SMVS shimmy are extracted. The complex coupling relationship between the shimmy factors of SMVS is revealed. The established shimmy factor model can effectively analyse the shimmy state of SMVS, and the dynamic simulation results also show consistency. This study not only proposes a new perspective to understand the SMVS shimmy mechanism, but also provides the foundation for further optimal design of monorail vehicle stability. [ABSTRACT FROM AUTHOR]

The scaffolds of two known CDK inhibitors (CAN508 and dinaciclib) were the starting point for synthesizing two series of pyarazolo[1,5‐a]pyrimidines to obtain potent inhibitors with proper selectivity. The study presented four promising compounds; 10d, 10e, 16a, and 16c based on cytotoxic studies. Compound 16a revealed superior activity in the preliminary anticancer screening with GI % = 79.02–99.13 against 15 cancer cell lines at 10 μM from NCI full panel 60 cancer cell lines and was then selected for further investigation. Furthermore, the four compounds revealed good safety profile toward the normal cell lines WI‐38. These four compounds were subjected to CDK inhibitory activity against four different isoforms. All of them showed potent inhibition against CDK5/P25 and CDK9/CYCLINT. Compound 10d revealed the best activity against CDK5/P25 (IC50 = 0.063 µM) with proper selectivity index against CDK1 and CDK2. Compound 16c exhibited the highest inhibitory activity against CDK9/CYCLINT (IC50 = 0.074 µM) with good selectivity index against other isoforms. Finally, docking simulations were performed for compounds 10e and 16c accompanied by molecular dynamic simulations to understand their behavior in the active site of the two CDKs with respect to both CAN508 and dinaciclib. [ABSTRACT FROM AUTHOR]

Large deformation finite element simulations of the dynamic penetration of underwater free-fall spherical penetrometers into clay are carried out using the coupled Eulerian–Lagrangian approach. Two undrained total stress analysis models are constructed and applied to simulate four well-documented centrifuge tests of sphere penetration. Model A is a new model that simulates both the free-fall process in water and the penetration process in clay. Model B, as usual, simulates only the penetration process in clay in the absence of overlying water. The simulation of the free-fall process in water is validated against an analytical solution and calibrated against the measured impact velocities of the tested spheres upon hitting the clay surface. The ability of the two models to predict the dynamic penetration behavior in clay is evaluated by comparing their results with the centrifuge test results. Model A provides a better prediction of the penetration behavior than Model B. Fully open, partially closed, and fully closed cavities formed by the passages of the sphere and water were reproduced by Model A. The water flow in the wake of the penetrating sphere is shown to have an important influence on the deformations of the clay surface and cavity wall. [ABSTRACT FROM AUTHOR]

Context: SHP2 is a non-receptor protein tyrosine phosphatase to remove tyrosine phosphorylation. Functionally, SHP2 is an essential bridge to connect numerous oncogenic cell-signaling cascades including RAS-ERK, PI3K-AKT, JAK-STAT, and PD-1/PD-L1 pathways. This study aims to discover novel and potent SHP2 inhibitors using a hierarchical structure-based virtual screening strategy that combines molecular docking and the fragment molecular orbital method (FMO) for calculating binding affinity (referred to as the Dock-FMO protocol). For the SHP2 target, the FMO method prediction has a high correlation between the binding affinity of the protein–ligand interaction and experimental values (R2 = 0.55), demonstrating a significant advantage over the MM/PBSA (R2 = 0.02) and MM/GBSA (R2 = 0.15) methods. Therefore, we employed Dock-FMO virtual screening of ChemDiv database of ∼2,990,000 compounds to identify a novel SHP2 allosteric inhibitor bearing hydroxyimino acetamide scaffold. Experimental validation demonstrated that the new compound (E)-2-(hydroxyimino)-2-phenyl-N-(piperidin-4-ylmethyl)acetamide (7188–0011) effectively inhibited SHP2 in a dose-dependent manner. Molecular dynamics (MD) simulation analysis revealed the binding stability of compound 7188–0011 and the SHP2 protein, along with the key interacting residues in the allosteric binding site. Overall, our work has identified a novel and promising allosteric inhibitor that targets SHP2, providing a new starting point for further optimization to develop more potent inhibitors. Methods: All the molecular docking studies were employed to identify potential leads with Maestro v10.1. The protein–ligand binding affinities of potential leads were further predicted by FMO calculations at MP2/6-31G* level using GAMESS v2020 system. MD simulations were carried out with AmberTools18 by applying the FF14SB force field. MD trajectories were analyzed using VMD v1.9.3. MM/GB(PB)SA binding free energy analysis was carried out with the mmpbsa.py tool of AmberTools18. The docking and MD simulation results were visualized through PyMOL v2.5.0. [ABSTRACT FROM AUTHOR]

The catalyst is crucial in enhancing productivity within the Fischer-Tropsch synthesis (FTS). The metal support interaction (MSI) plays a pivotal role in the FTS catalyst performance, impacting activity, stability, and selectivity. he configuration and composition of the catalyst dramatically impact MSI, with a strong MSI (SMSI) specified for the core-shell structure. In this study, two methods consisting of chemical treatment of etching and adding a promoter (Ru) for tuning the SMSI of the FTS catalyst are presented, and their footprints on the catalysts' performance are screened by utilizing various characterization tests, molecular dynamic simulation, and catalytic tests. It is recognized that the silica interfacial perimeter acts as a barrier that restricts the charge transfer and boosts the SMSI in the silica-coated catalyst. Conversely, the etched catalyst exhibits a moderate MSI, contributing to increased reducibility, stability, and activity. Furthermore, the Ru-doped etched catalyst represents the optimum MSI, resulting in the highest overall performance. [Display omitted] • The catalyst's structure, configuration, and composition significantly affect the metal support interaction (MSI). • Chemical etching and a promoter (Ru) are used to tune the SMSI of the FTS catalyst and intensify its performance. • The etched catalyst exhibits a moderate MSI, increasing ease of reduction, stability, and activity. • The etched catalyst undergoing doping with Ru with the outer shell of ceria promotes the formation of oxygen vacancies. • Ru NPs have a significant effect on the electron charge surface density of the catalyst. [ABSTRACT FROM AUTHOR]

Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is responsible for pancreatic cancer and is an attractive drug target. At the time of writing, no Food and Drug Administration (FDA) approved drugs are available for the KRAS G12D mutant. So, there is a need to develop an effective drug for KRAS G12D. The process of finding new drugs is expensive and time-consuming. On the other hand, in silico drug designing methodologies are cost-effective and less time-consuming. Herein, we employed machine learning algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF) for the identification of new inhibitors against the KRAS G12D mutant. A total of 82 hits were predicted as active against the KRAS G12D mutant. The active hits were docked into the active site of the KRAS G12D mutant. Furthermore, to evaluate the stability of the compounds with a good docking score, the top two complexes and the standard complex (MRTX-1133) were subjected to 200 ns MD simulation. The top two hits revealed high stability as compared to the standard compound. The binding energy of the top two hits was good as compared to the standard compound. Our identified hits have the potential to inhibit the KRAS G12D mutation and can help combat cancer. To the best of our knowledge, this is the first study in which machine-learning-based virtual screening, molecular docking, and molecular dynamics simulation were carried out for the identification of new promising inhibitors for the KRAS G12D mutant. [ABSTRACT FROM AUTHOR]

Real-time hybrid simulation (RTHS) is an economical and reliable method for the evaluation of structural dynamic performances, and the fixed analytical substructure model is often used in RTHS which may affect the accuracy of results. In this study, a real-time hybrid simulation platform (RTHSP) developed by configuring a generic National Instruments (NI) controller with hybrid programming strategy is presented in detail. The dynamic performances of a scaled base isolated structure, where the unscented Kalman filter (UKF) was used to update the analytical substructure Bouc–Wen model during the RTHSs was evaluated by presented RTHSP. RTHS of a base-isolated structure was performed where a lead rubber bearing (LRB) was tested physically as the experimental substructure of a part of the isolation layer and the superstructure with the rest of the isolation layer model updated by UKF was considered as the analytical substructure. Under the excitation of three natural earthquakes, the RTHSs with and without UKF updating were compared and analyzed the differences between the two. The results indicated that the displacements of experimental substructure generated by RTHS with UKF updating are the largest, while the relative displacements and acceleration of superstructure are the smallest overall, and the dynamic characteristics of the isolation layer of the analysis substructure updated by UKF are different from that without updated, which reflected the more authentic dynamic mechanical performance of the base-isolated structure under earthquake excitation. In addition, the RTHSP and the hybrid programming strategy are verified to be reliable in tests and experiments, and the components and implementation of a RTHSP for base-isolated structures is described in detail, providing a reference for research on RTHS method. [ABSTRACT FROM AUTHOR]

The maximum utilization of hydrocracking tail oil becomes increasingly important for petrochemical industry. The aim of this work is to develop optimized distillation processes to achieve various high‐valued qualified oil products from hydrocracking tail oil. Six different oil products is produced and the steady‐state distillation process, which aims to fractionate six qualified narrow distillates is established. The algorithm method incorporating divided‐wall column (DWC) configuration was introduced into the steady‐state design. Compared with traditional separation sequences, the DWC configuration leads to an energy‐saving potential up to 11.17%. Furthermore, effective dynamic control strategies were proposed, demonstrating precise and efficient control performance. In the presence of a 15% feed disturbance, the dynamic control structure is capable of maintaining the product distillation range near the set value. This comprehensive study provides a thorough investigation into the efficient utilization of hydrocracking tail oil, establishing a robust theoretical foundation for its industrial application. [ABSTRACT FROM AUTHOR]

Acellular fish swim bladders (AFSBs) are a promising biomaterial in tissue engineering, however, they may suffer from rapid degradation due to enzyme invasion. In this work, natural polyphenols, including epigallocatechin gallate (EGCG), proanthocyanidin (PC), tannic acid (TA) and protocatechuic acid (PCA), were utilized to improve the properties of AFSBs through crosslinking modifications. Fourier transform infrared (FTIR) results indicate that the triple helix of the collagen in AFSBs is well preserved after crosslinking. The differential scanning calorimetry (DSC), water contact angle (WCA) and in vitro degradation tests indicate that the polyphenol-crosslinked AFSBs exhibit improved thermal stability, enzymatic stability, hydrophilicity and mechanical properties. Among them, EGCG with multiple phenolic hydroxyl groups and low potential resistance is more favorable for the improvement of the mechanical properties and enzymatic stability of AFSBs, as well as their biocompatibility and integrity with the collagen triple helix. Moreover, the crosslinking mechanism was demonstrated to be due to the hydrogen bonds between polyphenols and AFSBs, and was affected by the molecular size, molecular weight and the hydroxyl groups activity of polyphenol molecules, as clarified by molecular dynamic (MD) simulations. The approach presented in this work paves a path for improving the properties of collagen materials. [ABSTRACT FROM AUTHOR]

This work deals with doubly fed induction generator (DFIG) modeling and stability when connected to weak AC grids. A detailed state-space model that includes the phase-locked loop (PLL) is developed. This work aims to determine the influence of the network's strength on DFIG stability through the short-circuit ratio (SCR). The critical values of the proportional control parameters of the grid-side and rotor-side converters (RSC and GSC), as well as PLL, which make the system unstable, are calculated for different SCR values. Finally, PSCAD/EMTDC dynamic simulations are used to validate the critical control parameters obtained by studying the eigenvalues of the DFIG state-space model regarding system stability. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the exact solutions of a modified generalized multidimensional fractional Kadomtsev–Petviashvili (KP) equation by the bifurcation method. First, the equation is converted into a planar dynamical system through fractional complex wave transformation. The phase portraits of the equation and qualitative analysis are presented under different bifurcation conditions. Then, the bounded and unbounded traveling wave solutions, including periodic, kink, anti-kink, dark-solitary, bright-solitary and breaking wave solutions, are acquired by integrating along different orbits. Finally, numerical simulations of the dynamic behaviors of the solutions obtained are graphically illustrated by choosing appropriate parameters. [ABSTRACT FROM AUTHOR]