Numerical and experimental investigation of the metering characteristic and pressure losses of the rotary tubular spool valve

This paper presents the results of numerical and experimental performance evaluation of the rotary tubular spool valve. The aim of this work is to develop further the novel design of the tubular spool valve by confirming experimentally the validity of the simulation model and its results, thereby proving the valve's potential to represent a feasible and more efficient alternative to conventionally used translation spool valves avoiding the use of two stage valve configurations. In this research the valve performance is assessed through numerical modelling and experimental studies of its metering characteristic and pressure losses. This paper demonstrates that the used valve model yields the results, which agree well with the conducted experimental study. Therefore, validation of the numerical model and the modelling results in the form of theoretical valve characteristics was accomplished. Firstly, the paper presents details of a numerical approach employed to evaluate valve performance and then analyzes the simulation results. Next, the valve performance is experimentally validated by testing a prototype valve on a hydraulic test rig capable of measuring the volume flow rate, pressure levels in up- and downstream lines of the valve across the entire spool angular stroke. Initially, average discrepancies between modelling and test results were 52.46% for the metering and 82.78% for the pressure loss characteristics. Correcting the model geometry aimed at eliminating differences between the valve model and the practically used prototype-test rig system enabled reduction of the error between experiment and modelling by 47.75% for the pressure loss function. This confirmed validity of the simulated characteristics of the valve. The benchmark comparison of pressure losses confirmed average 71.66% energy dissipation reduction compared to the industry-available analogue valve.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

BHDDF350型联轴器失效分析及改进设计

联轴器在旋转过程中连续传递扭矩且具备一定缓冲和减振的保护作用,而又不改变初始旋转方向和扭矩大小,BHDDF350型联轴器是某型矿用减速机与电机之间的扭矩传动部件。从该型联轴器的运行工况、结构分布、损坏形式等方面查找并分析了其失效原因,依据其受力分析提出了改进型设计方案,以供业内参考。改进设计后的联轴器,弹性块受力均匀,且最大受力降比30%以上,可有效延长联轴器的整体使用寿命,减少了煤矿井下日常的维护工作量。     

CFD Modeling of Active Volume Creation in a Non‐Newtonian Fluid Agitated by Submerged Recirculating Jets

Computational fluid dynamics (CFD) models were employed to investigate flow conditions inside a model reactor in which yield stress non‐Newtonian liquid is mobilized using submerged recirculating jets. The simulation results agree well with the experimental results of active volume in the reactor obtained using flow visualization by the authors in a previous study. The models developed are capable of predicting a critical jet velocity (v_c) that determines the extent of active volume obtained due to jet mixing. The v_c values are influenced both by the rheological properties of the liquid and the nozzle orientation. The liquid with higher effective viscosity leads to higher v_c for a downward facing injection nozzle. However, an upward facing injection nozzle along with a downward facing suction nozzle generates enhanced complementary flow fields which overcome the rheological constraints of the liquid and lead to lower v_c.     

Design structure matrix (DSM) method application to issue of modeling and analyzing the fault tree of a wind energy asset

The perpetual energy production of a wind farm could be accomplished (under proper weather conditions) if no failures occurred. But even the best possible design, manufacturing, and maintenance of a system cannot eliminate the failure possibility. In order to understand and minimize the system failures, the most crucial components of the wind turbines, which are prone to failures, should be identified. Moreover, it is essential to determine and classify the criticality of the system failures according to the impact of these failure events on wind turbine safety. The present study is processing the failure data from a wind farm and uses the Fault Tree Analysis as a baseline for applying the Design Structure Matrix technique to reveal the failure and risk interactions between wind turbine subsystems. Based on the analysis performed and by introducing new importance measures, the “readiness to fail” of a subsystem in conjunction with the “failure riskiness” can determine the “failure criticality.” The value of the failure criticality can define the frame within which interventions could be done. The arising interventions could be applied either to the whole system or could be focused in specified pairs of wind turbine subsystems. In conclusion, the method analyzed in the present research can be effectively applied by the wind turbine manufacturers and the wind farm operators as an operation framework, which can lead to a limited (as possible) design‐out maintenance cost, failures' minimization, and safety maximization for the whole wind turbine system.     

Ballistic behavior of plain and reinforced concrete slabs under high velocity impact

This work presents a numerical simulation of ballistic penetration and high velocity impact behavior of plain and reinforced concrete slabs. In this paper, we focus on the comparison of the performance of the plain and reinforced concrete slabs of unconfined compressive strength 41 MPa under ballistic impact. The concrete slab has dimensions of 675 mm × 675 mm × 200 mm, and is meshed with 8-node hexahedron solid elements in the impact and outer zones. The ogive-nosed projectile is considered as rigid element that has a mass of 0.386 kg and a length of 152 mm. The applied velocities vary between 540 and 731 m/s. 6 mm of steel reinforcement bars were used in the reinforced concrete slabs. The constitutive material modeling of the concrete and steel reinforcement bars was performed using the Johnson-Holmquist-2 damage and the Johnson-Cook plasticity material models, respectively. The analysis was conducted using the commercial finite element package Abaqus/Explicit. Damage diameters and residual velocities obtained by the numerical model were compared with the experimental results and effect of steel reinforcement and projectile diameter were studies. The validation showed good agreement between the numerical and experimental results. The added steel reinforcements to the concrete samples were found efficient in terms of ballistic resistance comparing to the plain concrete sample.     

Genes Identification,Molecular Docking and Dynamics Simulation Analysis of Laccases from Amylostereum areolatum Provides Molecular Basis of Laccase Bound to Lignin

An obligate mutualistic relationship exists between the fungus Amylostereum areolatum and woodwasp Sirex noctilio. The fungus digests lignin in the host pine, providing essential nutrients for the growing woodwasp larvae. However, the functional properties of this symbiosis are poorly described. In this study, we identified, cloned, and characterized 14 laccase genes from A. areolatum. These genes encoded proteins of 508 to 529 amino acids and contained three typical copper-oxidase domains, necessary to confer laccase activity. Besides, we performed molecular docking and dynamics simulation of the laccase proteins in complex with lignin compounds (monomers, dimers, trimers, and tetramers). AaLac2, AaLac3, AaLac6, AaLac8, and AaLac10 were found that had low binding energies with all lignin model compounds tested and three of them could maintain stability when binding to these compounds. Among these complexes, amino acid residues ALA, GLN, LEU, PHE, PRO, and SER were commonly present. Our study reveals the molecular basis of A. areolatum laccases interacting with lignin, which is essential for understanding how the fungus provides nutrients to S. noctilio. These findings might also provide guidance for the control of S. noctilio by informing the design of enzyme mutants that could reduce the efficiency of lignin degradation.     

Sequence-Dependent Nanofiber Structures of Phenylalanine and Isoleucine Tripeptides

The molecular design of short peptides to achieve a tailor-made functional architecture has attracted attention during the past decade but remains challenging as a result of insufficient understanding of the relationship between peptide sequence and assembled supramolecular structures. We report a hybrid-resolution model to computationally explore the sequence–structure relationship of self-assembly for tripeptides containing only phenylalanine and isoleucine. We found that all these tripeptides have a tendency to assemble into nanofibers composed of laterally associated filaments. Molecular arrangements within the assemblies are diverse and vary depending on the sequences. This structural diversity originates from (1) distinct conformations of peptide building blocks that lead to different surface geometries of the filaments and (2) unique sidechain arrangements at the filament interfaces for each sequence. Many conformations are available for tripeptides in solution, but only an extended β-strand and another resembling a right-handed turn are observed in assemblies. It was found that the sequence dependence of these conformations and the packing of resulting filaments are determined by multiple competing noncovalent forces, with hydrophobic interactions involving Phe being particularly important. The sequence pattern for each type of assembly conformation and packing has been identified. These results highlight the importance of the interplay between conformation, molecular packing, and sequences for determining detailed nanostructures of peptides and provide a detailed insight to support a more precise design of peptide-based nanomaterials.     

Effects of ethylene-octene copolymer (POE) on the brittle to ductile transition of high-density polyethylene/POE blends

Three kinds of ethylene-octene copolymers (POE) were melt-blended with high-density polyethylene (PE-HD) in different proportions. Detailed characterizations were conducted to analyze their structural differences of POE and its effects in toughening PE-HD. The higher molecular weight POE can improve the toughness of PE-HD. 60:40 PE-HD/POE is elongated to break up to 700% while impact strength is 84.7 kJ/m² at −30°C, which is 21-fold of PE-HD. In the brittle to ductile transition (BDT) during impact, the fracture mechanism changes from the crazing mode to the shear yield-plastic deformation mode. The BDT temperature decreases as the POE molecular weight and its content increase. The interface strength in tension is estimated to access their effects. The Boltzmann-type models were successfully extended to describe the typical S-shaped curves in BDT of notched impact strength vs POE content or temperature. The supplementary decay model is suggested for the attenuation in toughening. Transition map in impact is proposed to select the use range of composition (c ) and temperature (T ) for high toughness. The curves are converted into 3D graph of T -c -impact strength for illustrating their coupling-separate effects, and further into the contour map of impact strength in T -c space for finding their partial equivalence.