Dynamic Stability Behavior Research Articles

Discovery of Isojacareubin as a covalent inhibitor of SARS-CoV-2 main protease using structural and experimental approaches.

The ongoing pandemic with the emergence of immune evasion potential and, particularly, the current omicron subvariants intensified the situation further. Although vaccines are available, the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Hence, considering the necessity of the small molecule inhibitor, we target the main protease (3CLpro), which is an appealing target for the development of antiviral drugs against SARS-CoV-2. High-throughput molecular in silico screening of South African natural compounds database reported Isojacareubin and Glabranin as the potential inhibitors for the main protease. The calculated docking scores were reported to be -8.47 and -8.03 kcal/mol, respectively. Moreover, the structural dynamic assessment reported that Isojacareubin in complex with 3CLpro exhibit a more stable dynamic behavior than Glabranin. Inhibition assay indicated that Isojacareubin could inhibit SARS-CoV-2 3CLpro in a time- and dose-dependent manner, with half maximal inhibitory concentration values of 16.00 ± 1.35 μM (60 min incubation). Next, the covalent binding sites of Isojacareubin on SARS-CoV-2 3CLpro was identified by biomass spectrometry, which reported that Isojacareubin can covalently bind to thiols or Cysteine through Michael addition. To evaluate the inactivation potency of Isojacareubin, the inactivation kinetics was further investigated. The inactivation kinetic curves were plotted according to various concentrations with gradient-ascending incubation times. The KI value of Isojacareubin was determined as 30.71 μM, whereas the Kinact value was calculated as 0.054 min-1 . These results suggest that Isojacareubin is a covalent inhibitor of SARS-CoV-2 3CLpro .

Study of dynamic performance of heat-integrated distillation columns considering the effect of relative volatility of the mixtures

In this paper the dynamic performance of Heat-Integrated Distillation Columns (HIDiC) is presented. The dynamic performance was determined for the optimal HIDiC designs optimized previously using a constrained Boltzmann-based estimation of distribution algorithm. Eight close-boiling mixtures, covering a range of relative volatility (α) from 1.12 to 2.4, were used as case studies. The dynamic behavior was obtained under open and closed-loop process analysis. The results obtained showed that the HIDiC columns undergo worse dynamic performance than their equivalent traditional columns for all case studies. Furthermore, it was notorious that the difference in the dynamic behavior of both configurations kept a relatively uniform trend for most systems. However, a marked difference in the dynamic properties was determined for the mixture close to azeotropic behavior, which experienced a considerably larger control effort.Thus, the novel findings disclosed in this paper show that, although the HIDiC sequences experienced worse dynamics than the conventional columns, the HIDiC configurations reached a stable dynamic behavior for all the range of α of the mixtures under study. Nevertheless, high control difficulties were particularly determined for the HIDiC configuration used to separate the mixture with α close to unity (mixture of xylenes), which in fact is the HIDiC sequence with the best energetic and economic benefits.Hence, the energetic and economic potential of the HIDiC columns is not limited by the dynamic behavior for most case studies analyzed, at least in theoretical terms. However, such potential might be particularly reduced or unharnessed in the separation of the mixture with α near the azeotropic behavior due to the dynamics of the HIDiC column for this separation.So, the findings presented in this paper allow to infer that sequential or simultaneous dynamic studies must be achieved along with the optimization of the HIDiC columns to determine the integral performance (energetic, economic and dynamic) of these configurations.

SPONTANEOUS STABILIZATION AND LARGE-SCALE OSCILLATIONS OF AN ACTIVE MEDIUM WITH NEGATIVE DISSIPATION

A numerical model of an “active medium” is considered which invokes linear elasticity and a negative seed dissipative constant dynamically renormalized under deformation. It is shown that despite the expected instability of such a system, it spontaneously exhibits stable dynamic behavior in a wide range of geometric configurations and initial causes of deformations. In the stable dynamic modes, dissipation that changes its sign in time and space forms complex quasi-periodically repeating patterns and the entire volume (length, area) of the system undergoes large-scale oscillations. In addition to academic interest, the results obtained can be applied to mechanical and biological studies.

Nonlinear dynamic stability analysis of axial impact loaded structures via the nonlocal strain gradient theory

In engineering applications, there has been an overwhelming tendency towards portability, miniaturization, and integration in recent years. To link the intrinsic size dependency feature of the small-scale structure with its structural stability, the nonlocal strain gradient theory, which captures the size effect in a more general size-dependent continuum-based model, is introduced to explore the nonlinear dynamic stability behaviour of nanoplates. Four types of axial impact loading configurations, namely, sinusoidal, exponential, rectangular, and damping, are considered. Some practical factors, such as Winkler-Pasternak elastic foundation and damping, are taken into account in the analysis. The equations of motion for the size-dependent initially imperfect plate are derived in the framework of the first-order shear deformation plate theory in conjunction with the Von Kármán nonlinear terms. Then the Airy stress function corresponding to simply supported nanoplate is introduced; then, by applying the Galerkin method, the obtained differential equations are addressed by the fourth-order Runge-Kutta algorithm. Subsequently, the specific value of the critical dynamic buckling load is determined by the Volmir criterion. Organic solar cells (OSCs), a type of emerging solar-to-electrical energy conversion nanodevice, are used as an illustrative example within the existing framework. The effects of size dependency in conjunction with the pulse load configuration, the initial imperfection, the elastic foundation, as well as the damping ratio on the nonlinear dynamic buckling behaviour of the OSC are thoroughly investigated.

Analytic detection of chaos zones in response of a shape memory alloy beam under simultaneous external and parametric excitations

ABTRACT In this article, the dynamic stability and chaotic behavior of a shape memory alloy (SMA) beam with large deformation under simultaneous lateral and axial excitations is investigated through a fully analytic approach. First, the nonlinear governing equation of motion is derived. Second, Melnikov’s method, as an analytic approach, is employed to obtain the chaos zones. After that, by introducing non-dimensional parameters, border curves of chaotic areas were evaluated and plotted for some case studies which give a reader a precise and clear look at how the material and load properties can affect the chaos zones. Finally, the sufficient condition is approved via corresponding poincaré maps.

Nobiletin as a Neuroprotectant against NMDA Receptors: An In Silico Approach.

Excitotoxicity is a type of neurodegenerative disorder. It caused by excessive glutamate receptor activation, which leads to neuronal malfunction and fatality. The N-methyl-D-aspartate (NMDA) receptors are found in glutamatergic neurons, and their excessive activation is primarily responsible for excitotoxicity. They are activated by both glutamate binding and postsynaptic depolarization, facilitating Ca2+ entry upon activation. Therefore, they are now widely acknowledged as being essential targets for excitotoxicity issues. Molecular docking and molecular dynamics (MD) simulation analyses have demonstrated that nobiletin efficiently targets the binding pocket of the NMDA receptor protein and exhibits stable dynamic behavior at the binding site. In this study, five potential neuroprotectants, nobiletin, silibinin, ononin, ginkgolide B, and epigallocatechin gallate (EGCG), were screened against the glutamate NMDA receptors in humans via computational methods. An in silico ADMET study was also performed, to predict the pharmacokinetics and toxicity profile for the expression of good drug-like behavior and a non-toxic nature. It was revealed that nobiletin fulfills the criteria for all of the drug-likeness rules (Veber, Lipinski, Ghose, Muegge, and Egan) and has neither PAINS nor structural alerts (Brenks). In conclusion, nobiletin demonstrated a possible promising neuroprotectant activities compared to other selected phytochemicals. Further, it can be evaluated in the laboratory for promising therapeutic approaches for in vitro and in vivo studies.

Stability of Cracked Functionally Graded Graphene-Reinforced Beams under Magnetic Field

This paper studies linear dynamic stability of cracked functionally graded (FG) graphene platelet (GPL)-reinforced composite laminated beams subjected to the combined action of magnetic field and a periodic axial force. GPL weight fraction follows a layer-wise variation across the beam thickness. Effective material properties are estimated by micromechanics models, and the bending stiffness of the cracked section is evaluated by a rotational spring model. The governing equation is derived by Ritz method and Lagrange equation within the framework of the first-order shear deformation theory. The linear principle unstable regions of the cracked beams are determined by Bolotin method. Numerical results show that magnetic field intensity, GPL distribution pattern, boundary condition, crack depth and location have significant influence on the linear dynamic stability behaviors of the cracked beams.

Alternated Superior Chaotic Biogeography-Based Algorithm for Optimization Problems

In this study, we consider a switching strategy that yields a stable desirable dynamic behaviour when it is applied alternatively between two undesirable dynamical systems. From the last few years, dynamical systems employed “chaos1 + chaos2 = order” and “order1 + order2 = chaos” (vice-versa) to control and anti control of chaotic situations. To find parameter values for these kind of alternating situations, comparison is being made between bifurcation diagrams of a map and its alternate version, which, on their own, means independent of one another, yield chaotic orbits. However, the parameter values yield a stable periodic orbit, when alternating strategy is employed upon them. It is interesting to note that we look for stabilization of chaotic trajectories in nonlinear dynamics, with the assumption that such chaotic behaviour is not desirable for a particular situation. The method described in this paper is based on the Parrondo’s paradox, where two losing games can be alternated, yielding a winning game, in a superior orbit.

Computational studies to identify the common type-I and type-II inhibitors against the CDK8 enzyme.

In this study, multicomplex-based pharmacophore modeling was conducted on the structural proteome of the two states of CDK8 protein, that is, DMG-in and out. Three pharmacophores having six, five, and four features were selected as the representative models to conduct the virtual screening process using the prepared drug-like natural product database. The screened candidates were subjected to molecular docking studies on DMG-in (5XS2) and out (4F6U) conformation of the CDK8 protein. Subsequently, the common four docked candidates of 5XS2 and 4F6U were selected to perform the molecular dynamics simulation studies. Apart from one of the complexes of DMG-in (5XS2-UNPD163102), all other complexes displayed stable dynamic behavior. The interaction and stability studies of the docked complexes were compared with the references selected from the two conformations (DMG-in and out) of the protein. The current work leads to the identification of three common DMG-in and out hits with diverse scaffolds which can be employed as the initial leads for the design of the novel CDK8 inhibitors.

Dynamic stability analysis of porous functionally graded microplates using a refined isogeometric approach

This paper is devoted to analyzing dynamic stability behaviors of porous functionally graded (FG) microplates subjected to periodic uniaxial/biaxial in-plane compressions by utilizing a refined plate theory (RPT) in conjunction with modified couple stress theory (MCST) within isogeometric analysis (IGA) framework. In this setting, the displacement field of microplates is expressed based on four-variable RPT-based IGA, while the effects of microstructure could be thoroughly captured by employing MCST involving only one material length scale parameter. To define dynamic instability region boundaries, Bolotin’s method is adopted in the present work. Three different dispersions of internal porosities i.e. even, uneven, and logarithmic uneven through the thickness direction are investigated in detail. In addition, porosity-dependent material properties are estimated via a modified rule of mixture. A number of numerical investigations are carried out to study, for the first time, the influences of several key factors such as porosity coefficient and porosity distribution, material length scale, power law index, static and dynamic load factors on dynamic instability characteristics of FG microplates considering internal porosity.

Design parameters of a reluctance actuation system for stable operation conditions with applications of high‐precision motions in lithography machines

Recently, the reluctance actuator has attracted great attention to replace the Lorentz actuator in the next generation of wafer scanners in semi-conductor lithography machines. The reluctance actuator has a non-linear position-force characteristic, which may cause high oscillations and unstable operation. This study presents a linearisation technique by optimising the main parameters of the reluctance actuator to operate away from the saturation point. Also, in this study, the critical current is formulated for the stable dynamic behaviour of the reluctance actuator. Optimisation based on the Grey Wolf Optimiser is performed considering the high-precision motion requirements and physical constraints. The high-precision motion requirements include the desired work-space displacement, natural frequency, and maximum force. The electromechanical dynamic model of the reluctance actuator motion system is formulated to characterise the interaction among electrical, magnetic, and mechanical parts. The simulation results show that the optimal design of the reluctance actuator works in the linear region, and for stable dynamic behaviour, the input current is limited by the critical current. Finally, a feedforward controller is designed based on the approximation of the force–current relationship to improve the tracking performances of the reluctance actuator motion system. The simulation results in time and frequency domains show an improvement in tracking performances using the feedforward controller.

Effect of unified power flow controller installation in dual feed induction generator (DFIG) wind turbines

Abstract In recent years, the use of wind energy to generate electricity in the world has been accelerating and growing. Wind farms are unstable when dynamic voltage fluctuations occur, especially sudden and sudden changes in load, and show oscillating performance at their output. In this paper, the Unified Power Flow Controller (UPFC) has been simulated and studied by Matlab software to improve the dynamic stability and transient behavior of the wind power plant in the event of sudden load changes. The simulation results show that by controlling the UPFC series inverter, voltage fluctuations in the PCC bus are prevented and the UPFC parallel inverter injects power after changing the load for faster recovery and stability of the PCC bus voltage and thus the stability of the wind farm. The UPFC can control the active and reactive power at the transmission line, and in fact, controls the output of the wind turbine with the generator from both sides to the fluctuations caused by sudden load changes that play a role such as sudden disturbances and oscillating errors. Also, the presence of UPFC in the system reduces power fluctuations.

An in silico molecular dynamics simulation study on the inhibitors of SARS-CoV-2 proteases (3CLpro and PLpro) to combat COVID-19

ABSTRACT The work attempts to recognise the possible inhibitors against Papain-like protease (PLpro) and 3-Chymotrypsin-like protease (3CLpro) of SARS-CoV-2 to combat infectious COVID-19 virus using in silico studies. These two proteases are predominantly involved in the virus replication cycle; hence they are considered as potential drug targets. The virtual dock screening was performed for 53 selected drugs. The drugs with higher binding energy and oriented in the vicinity of active binding sites were selected for finding thermal stability using molecular dynamics (MD) simulation. The docking result reflects that the drugs A17 (Dasabuvir) and A34 (Methisazone) bind with PLpro and the drugs A17 and A53 (Vaniprevir) bind with 3CLpro with higher binding affinities. The MD simulation and principal component analysis show that the drug A17 has stable dynamic behaviour with both proteins over the 300 ns time-scale. The binding free energy of complexes was predicted from the last 100 ns trajectories using MM/PBSA. The predicted binding free energy of PLPro-A17 (Dasabuvir) and PLpro-A34 complexes (Methisazone) were −16.1 kcal/mol and −12.3 kcal/mol, respectively and −41.3 kcal/mol and −11.9 kcal/mol for 3CLpro-A17 (Dasabuvir) and 3CLpro-A53 (Vaniprevir) complexes, respectively. However, further experimental validation is required to confirm their inhibitory activities against SARS-CoV-2 causing COVID-19.

Free vibration and dynamic stability of functionally graded composite microtubes reinforced with graphene platelets

This paper studies the free vibration and dynamic stability characteristics of functionally graded composite multilayer microtubes reinforced with graphene platelets under axial mechanical load. The graphene platelets are assumed to be uniformly or gradiently distributed across the radial direction of the microtube, and the corresponding effective material properties are estimated by the modified Halpin-Tsai model and the rule of mixture. Based on the modified couple stress theory and a refined higher-order beam theory, a size-dependent multilayer tube model for the dynamic analysis is developed. By employing Hamiltons principle, the governing equations and associated boundary conditions are derived. Galerkin technique is applied to convert the governing partial differential equations into ordinary ones, from which the analytical solutions of natural frequencies and dynamic instability regions under different boundary conditions can be obtained. After verifying the accuracy of the proposed model, the influences of graphene platelets distribution pattern and weight fraction, microstructure effect, axial load as well as geometrical parameters on the free vibration and dynamic stability behaviors of functionally graded composite multilayer microtubes are investigated. It is found that distributing more graphene platelets in the outer layers but fewer in the inner layers has the best reinforcing effect for the composite microtubes.

Dynamic stability analysis of delaminated composite beams in frequency domain using a unified beam theory with higher order displacement continuity

In this paper the dynamic stability behaviour of single delaminated composite beam is investigated using higher order shear deformable beam theories. The system is discretised by the finite element method and the mass, material stiffness and geometric stiffness matrices are formulated by means of higher order displacement continuity in the intact part. The natural frequencies and critical buckling forces are determined for various beam theory orders and delamination lengths and positions. Furthermore, using the multi frequency method the dynamic stability properties of the system are calculated in frequency domain. Based on the stability analysis the sufficient beam theory order and multi frequency method’s corresponding truncated matrix determinant order are determined in order to achieve the desired accuracy on the observed parameter plane. The results indicate that the dependence of the natural frequencies and buckling forces is negligible on the order of the applied beam theory. In contrast the former quantities are significantly influenced by the delamination length and position. Finally, it is shown that the dynamic stability diagrams and the boundary frequencies of parametric instability do not depend on the delamination length and position from the engineering point of view.

Evaluation of the Double Snap-Through Mechanism on the Wave Energy Converter\u2019s Performance

Lower efficiencies induce higher energy costs and pose a barrier to wave energy devices’ commercial applications. Therefore, the efficiency enhancement of wave energy converters has received much attention in recent decades. The reported research presents the double snap-through mechanism applied to a hemispheric point absorber type wave energy converter (WEC) to improve the energy absorption performance. The double snap-through mechanism comprises four oblique springs mounted in an X-configuration. This provides the WEC with different dynamic stability behaviors depending on the particular geometric and physical parameters employed. The efficiency of these different WEC behaviors (linear, bistable, and tristable) was initially evaluated under the action of regular waves. The results for bistable or tristable responses indicated significant improvements in the WEC’s energy capture efficiency. Furthermore, the WEC frequency bandwidth was shown to be significantly enlarged when the tristable mode was in operation. However, the corresponding tristable trajectory showed intra-well behavior in the middle potential well, which induced a more severe low-energy absorption when a small wave amplitude acted on the WEC compared to when the bistable WEC was employed. Nevertheless, positive effects were observed when appropriate initial conditions were imposed. The results also showed that for bistable or tristable responses, a suitable spring stiffness may cause the buoy to oscillate in high energy modes.

Dynamic Instability Response of Soft Core Sandwich Plates Based on Higher-Order Plate Theory

The dynamic stability of the foam-filled sandwich plates under arbitrary periodic loads is studied by using Lo’s high-order shear deformation theory. The periodic load is simulated as a combination of axial stress and bending stress. The governing equations are established based on a perturbation method. Through the derived Mathieu-type equation and using the Bolotin method, the dynamic instability regions are determined by solving the eigenvalue problem. The effects of core thickness, static and dynamic load, and bending stress on the dynamic stability behavior of composite sandwich plates with stiff face sheets and soft foam core are studied. The results reveal that the presented higher-order plate theory adopted gives a better estimate of the dynamic stability of the foam-filled sandwich plate than the first-order plate theory.

Dynamic instability of trapezoidal composite plates under non-uniform compression using moving kriging based meshfree method

Meshfree formulation based on the element free Galerkin method (EFGM) in conjunction with moving kriging (MK) shape function is employed to investigate buckling and parametric instability behaviour of shear deformable isotropic and laminated composite trapezoidal plates subjected to different types of non-uniform periodic edge compressive loads. Hamilton’s principle is used to derive the governing equations, which are transformed into the discretized form using the EFG method. The actual pre-buckling stresses are determined from static analysis to evaluate the accurate buckling loads of isotropic and laminated composite trapezoidal plates under non-uniform edge compression. The ordinary differential equations of Mathieu–Hill type are solved using Bolotin’s method to determine regions of dynamic instability. The accuracy of the present formulation is examined first by comparing results with those available in the literature. Thereafter, the influence of geometric parameters, lamination scheme, boundary conditions, static pre-load, and various types of non-uniform edge compression on the critical buckling loads and dynamic instability behaviour of both isotropic and laminated composite trapezoidal plate is investigated. The new results on dynamic stability behaviour of trapezoidal plates under non-uniform edge loads are presented for the first time, which may serve as benchmark results for future research. Furthermore, the time history response and corresponding phase plots are also presented for a better understanding of the dynamic behaviour of the trapezoidal plates.

Design of a Fuzzy Optimization Control Structure for Nonlinear Systems: A Disturbance-Rejection Method

This paper tackles the control problem of nonlinear disturbed polynomial systems using the formalism of output feedback linearization and a subsequent sliding mode control design. This aims to ensure the asymptotic stability of an unstable equilibrium point. The class of systems under investigation has an equivalent Byrnes–Isidori normal form, which reveals stable zero dynamics. For the case of modeling uncertainties and/or process dynamic disturbances, conventional feedback linearizing control strategies may fail to be efficient. To design a robust control strategy, meta-heuristic techniques are synthesized with feedback linearization and sliding mode control. The resulting control design guarantees the decoupling of the system output from disturbances and achieves the desired output trajectory tracking with asymptotically stable dynamic behavior. The effectiveness and efficiency of the designed technique were assessed based on a benchmark model of a continuous stirred tank reactor (CSTR) through numerical simulation analysis.

Influence of step-surface visual properties on confidence, anxiety, dynamic stability, and gaze behaviour in young and older adults.

Step-surface visual properties are often associated with stair falls. However, evidence for decorating stairs typically concerns the application of step-edge highlighters rather than the entire step-surface. Here we examine the influence of step-surface visual properties on stair descent safety, with a view to generating preliminary evidence for safe stair décor. Fourteen young (YA: 23.1±3.7years), 13 higher (HAOA: 67±3.5) and 14 lower (LAOA: 73.4±5.7) ability older adults descended a seven-step staircase. Older adults were stratified based on physiological/cognitive function. Step-surface décor patterns assessed were: Black and white (Busy); fine grey (Plain); and striped multicolour (Striped); each implemented with/without black edge-highlighters (5.5cm width) totalling six conditions. Participants descended three times per condition. Confidence was assessed prior to, and anxiety following, the first descent in each condition. 3D kinematics (Vicon) quantified descent speed, margin of stability, and foot clearances with respect to step-edges. Eye tracking (Pupil-labs) recorded gaze. Data from three phases of descent (entry, middle, exit) were analysed. Linear mixed-effects models assessed within-subject effects of décor (×3) and edge highlighters (×2), between-subject effects of age (×3), and interactions between terms (α= p<.05). Décor: Plain décor reduced anxiety in all ages and abilities (p=.032, effect size: gav=0.3), and increased foot clearances in YA and HAOA in the middle phase (p<.001, gav=0.53), thus improving safety. In contrast, LAOA exhibited no change in foot clearance with Plain décor. Patterned décor slowed descent (Busy: p<.001, gav=0.2), increased margins of stability (Busy: p<.001, gav=0.41; Striped: p <.001, gav =0.25) and reduced steps looked ahead (Busy: p =.053, gav =0.25; Striped: p =.039, gav =0.28) in all ages and abilities. This reflects cautious descent, likely due to more challenging conditions for visually extracting information about the spatial characteristics of the steps useful to guide descent. Edge highlighters: Step-edge highlighters increased confidence (p <.001, gav=0.53) and reduced anxiety (p <.001, gav=0.45) in all ages and abilities and for all décor, whilst removing them slowed descent in HAOA (p =.01, gav=0.26) and LAOA (p=.003, gav=0.25). Step-edge highlighters also increased foot clearance in YA and HAOA (p =.003, gav=0.14), whilst LAOA older adults showed no adaptation. No change in foot clearances with décor or step-edge highlighters in LAOA suggests an inability to adapt to step-surface visual properties. Patterned step surfaces can lead to more cautious and demanding stair negotiation from the perspective of visually extracting spatial information about the steps. In contrast, plain décor with step edge highlighters improves safety. We therefore suggest plain décor with edge highlighters is preferable for use on stairs.