Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro,Molecular Docking,Molecular Dynamics,DFT, and SAR Studies

In this article, 34 anticoagulant drugs were screened in silico against the main protease (M^pro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 M^pro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC₅₀). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC₅₀ value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC₅₀ values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 M^pro enzyme was investigated by utilizing the SARS-CoV-2 M^pro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 M^pro inhibitory potential was attained for fondaparinux sodium with an IC₅₀ value of 2.36 µM, surpassing the reference tipranavir (IC₅₀ = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 M^pro inhibitory potential was attained for dabigatran with an IC₅₀ value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.     

Effects of ductility on seismic response of piping systems and their implication on design and qualification

This study is concerned with the inelastic seismic response of nuclear power plant piping systems. Two systems are examined. The first one is an idealized four-equal-span pipe run and the second one consists of two configurations modified from an existing pipe run. Detailed finite element seismic time history analyses are performed using the computer program. By varying the various geometrical and physical parameters, calculations are made for a total of 76 cases. The results show that ductility generally contributes to reducing the response of piping systems. An empirical relation between the support load reduction factor and support ductility demand is given and a chart and simple procedures are suggested for the design and qualification of piping supports taking ductility into consideration.     

Inactivation of Foodborne Pathogens by NiO/TiO2 Composite Nanofibers: A Novel Biomaterial System

This study presents the fabrication and characterization of novel NiO/TiO₂ composite nanofibers and their antibacterial activity. The utilized NiO/TiO₂ composite nanofibers were prepared by electrospinning of a sol–gel composed of nickel nitrate hexahydrate, titanium isopropoxide and poly(vinyl acetate). The obtained electrospun nanofiberous mat was vacuum dried at 80 °C and then calcined at 600 °C in air for 2 h. The physicochemical properties of the synthesized nanofibers were determined by X-ray diffraction pattern, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, electron probe microanalysis and transmission electron microscopy. The antibacterial activity was tested against four common foodborne pathogenic bacteria viz., Staphylococcus aureus, Escherichia coli, Salmonella typhimurium and Klebsiella pneumoniae by minimum inhibitory concentration (MIC) method taking five different concentrations (5–45 μg/ml). Our investigation reveals that the lowest concentration of NiO/TiO₂ composite solution inhibiting the growth of tested strains was found to be 5 μg/ml. TEM analysis demonstrated that the exposure of the selected microbial strains to the composite nanofibers led to disruption of cell membranes and depressed the activity of some membranous enzymes, which caused bacteria to die eventually. Furthermore, the results illustrate that the combination of NiO and TiO₂ can be synergistic and resulted in superior antimicrobial activity of NiO/TiO₂ composite nanofibers. To sum up, novel NiO/TiO₂ composite nanofibers that possess large surface-to-volume ratio with excellent antimicrobial activity were fabricated that can be used to inhibit the microbial growth associated with food stuff.     

Effect of mineralogical composition and kerogen content on oil shale natural floatability

Mineralogical composition is one of the important factors that affect the performance of separation processes. In the current study, two oil shale samples, from El-Nakhil and El-Bieda localities, differ in their mineralogical composition, were subjected to flotation tests. Chemical analysis, differential thermal analysis (DTA), thermo-gravimetric analysis (TGA), and microscopic examination are among the used characterization techniques. In addition, their responses for upgrading by flotation were conducted as a function of pH, solid-liquid ratio, stirring speed and different particle sizes. The characterization results indicated that the kerogen content in El-Nakhil sample was 30% while in El-Beida sample was 10%. On the other hand, the flotation results indicated that El-Bieda responses better than that of El-Nakhil in terms of the difference in kerogen % between the original sample and the concentrated ones. The difference in flotation results of two samples can be explained by the difference in kerogen morphology as well as its interaction with surrounding matrix. In El-Bieda the kerogen has a laminated structure but in El-Nakhil it appears as laminated liptinitic component, in addition to the higher carbonate content in El-Nakhil sample in comparison to higher clay content in El-Bieda sample.     

Vector Control Scheme of Five-Phase Induction Machines under Open-Circuit Phase Faults

Multiphase induction machine is normally controlled using rotor field oriented vector control. Under phase（s） loss, the machine currents can be optimally controlled to satisfy certain optimization criteria. In this paper, a vector control scheme to a five-phase induction machine is introduced to ensure equal phase currents and minimum torque ripples under a phase open circuit. The controller idea can be extended to any number of phases with any number of open phases. The fundamental dq components of the stator voltage are obtained using only two PI controllers for the fundamental sequence plane, as in conventional vector control of three-phase machines. Based on steady state model, a simple expression is derived to estimate the required dq voltage components of other sequence planes to ensure equal stator phase currents and minimum torque ripple. A five-phase machine is simulated using MATLAB/Simulink to ensure controller validity.     

Modeling and simulation of solar-powered liquid desiccant regenerator for open absorption cooling cycle

This paper presents the modeling and simulation of solar-powered desiccant regenerator used for open absorption cooling cycles. The input heat, which is the total radiation incident on an inclined surface, is evaluated via a solar radiation model in terms of the location, day of the year, and time of the day. Calcium Chloride (CaCl₂) is applied as the working desiccant in this investigation. The solar radiation model is integrated with the desiccant regenerator model to produce a more realistic simulation. A finite difference method is used to simulate the combined heat and mass transfer processes that occur in the liquid desiccant regenerator. The system of equations is solved using the Matlab-Simulink platform. The effect of the important parameters, namely the regenerator length, desiccant solution flow rate and concentration, and air flow rate, on the performance of the system is investigated. It has been found that the vapor pressure difference has a maximum value for a given regenerator length. It is also shown that for specified operating conditions, a maximum value of the coefficient of performance occurs at a given range of air and solution flow rates. Therefore, it is essential to select the design parameters for each ambient condition to maximize the coefficient of performance of the system.     

Analyzing cytogenetic chromosomal aberrations on fibrolamellar hepatocellular carcinoma detected by single-nucleotide polymorphs array

Fibrolamellar hepatocellular carcinoma is a unique malignant liver tumor type which arises in young adults and children. It is uncommon variation subtype of hepatocellular carcinoma which remains ineffectively recorded. Learning of cytogenetic changes in fibrolamellar hepatocellular carcinoma has lagged behind the information obtained from alternate entities of hepatocellular carcinoma lately. Gene expression profiling may prompt new biomarkers that may help develop diagnostic precision for distinguishing fibrolamellar hepatocellular carcinoma. The subatomic cytogenetic approach permits positional identification of gains, amplification, and deletion of DNA sequences of the whole tumor genome, to search for recurrent and particular cytogenetic changes in human fibrolamellar hepatocellular carcinoma. In this work, 13 cell lines of fibrolamellar carcinomas and 30 hepatocellular carcinoma samples examined by a single-nucleotide polymorphs array using two techniques to give more accuracy of the results. The majority of the abnormalities found in the fibrolamellar hepatocellular carcinoma positive cases seen as gain in 1q, 4q, 6q, 7p, 8q, 17q, 20q and loss in 1p, 4p-q, 8p, 11p, 13q, 17p, 18q, 19p, and 22q. The ultimate successive were central amplification at 1q (in 54% of 13 samples), 4q (in 54% of 13 samples), 7p (in 46% of 13 samples), and deletions at 19p13 (in 28% of 13 samples). The study revealed 3 distinct structural variations highlights-related genes MDM4, PRDM5, and WHSC1, and these genes are a novel target signature that can help to predict survival of patients with detecting fibrolamellar hepatocellular carcinoma.

     

OpenSim: open-source software to create and analyze dynamic simulations of movement

Dynamic simulations of movement allow one to study neuromuscular coordination, analyze athletic performance, and estimate internal loading of the musculoskeletal system. Simulations can also be used to identify the sources of pathological movement and establish a scientific basis for treatment planning. We have developed a freely available, open-source software system (OpenSim) that lets users develop models of musculoskeletal structures and create dynamic simulations of a wide variety of movements. We are using this system to simulate the dynamics of individuals with pathological gait and to explore the biomechanical effects of treatments. OpenSim provides a platform on which the biomechanics community can build a library of simulations that can be exchanged, tested, analyzed, and improved through a multi-institutional collaboration. Developing software that enables a concerted effort from many investigators poses technical and sociological challenges. Meeting those challenges will accelerate the discovery of principles that govern movement control and improve treatments for individuals with movement pathologies.     

Hepatic cholesterol metabolism in experimental nephrotic syndrome

Hypercholesterolemia is a consistent feature of the nephrotic syndrome. However, the mechanisms underlying this perturbation are unclear. In the present work, we have investigated different factors that influence hepatic cholesterol metabolism using the nephrotic rat as a model. The induction of nephrosis resulted in a severe and sustained hypercholesterolemia. However, no effect on the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase, could be detected. Further, plasma lathosterol/cholesterol ratio, a measure of cholesterol synthesis, was not altered. Also, plasma levels of mevalonate, both a substrate for cholesterogenesis beyond the rate-limiting step and a marker for cholesterol synthesis, did not differ between control rats and those with established hypercholesterolemia. There was no detectable change in the expression of low density lipoprotein (LDL) receptor between the two experimental groups. We conclude that the early increase in cholesterol synthesis reported after the induction of nephrosis is not necessary for the maintenance of hypercholeserolemia. Established hypercholesterolemia of the nephrotic syndrome seems to represent a steady state in which neither enhanced hepatic cholesterol synthesis nor retarded LDL cholesterol clearance is of major importance.