There is a misconception about using the terms photon and electron. When the electron of the outer ring in the silicon atom executes interstate dynamics for only one cycle, it generates force and energy for the unit photon. The unit photon has a shape similar to a Gaussian distribution with turned ends. When a photon of suitable length interacts with the side of the laterally orientated electron of a semisolid or solid atom, it converts into heat. At an approximate angle of 90°, when a photon interacts with the tip of a laterally orientated electron, it divides into bits of energy with shapes similar to integral symbols. Solid or semisolid element atoms can reveal the phenomenon of heat energy if their electrons address the interactions of photons. In the neutral state silicon atom, the center acts as the reference point for electrons executing interstate dynamics, and the north-south tips of the electrons remain along the north-south poles. The energy shapes around the force tracing along the trajectory of electron dynamics. Two forces are exerted on the electron at one time. In interstate dynamics, the electron of the outer ring first reaches the maximum limit point, where the one-bit energy is shaped. In the remaining half cycle, that electron also generates energy of one bit. When there is an uninterrupted supply of heat energy to the silicon atom, electron dynamics generate photons with a shape-like wave. Path-independent but interstate-dependent forces assume the control of an electron. This electron executes dynamics nearly at the speed of light. In dynamics, conservative forces are exerted on position-acquiring electrons. A photon can be unending in length if the electron dynamics remain uninterrupted. The changing aspect of the electron reflects the auxiliary moment of inertia at each turning point. Atoms of suitable elements generate differently shaped photons when executing dynamics for the outer ring electrons. Thus, they can also reveal the phenomenon of photon energy.

The optimization methods are increasingly used to solve challenging problems of aeronautical engineering. Typically, the optimization methods are utilized in design of aircraft airframe or its structure. The presented study is focused on an improvement of aircraft-flight-control procedures through the numerical optimization approach. The optimization problems concern selected phases of flight of light gyroplane - a rotorcraft using an unpowered rotor in autorotation to develop lift and an engine-powered propeller to provide thrust. An original methodology of computational simulation of rotorcraft flight was developed and implemented. In this approach the aircraft-motion equations are solved step-by-step, simultaneously with the solution of the Unsteady Reynolds-Averaged Navier-Stokes equations, which is conducted to assess aerodynamic forces acting on the aircraft. As a numerical optimization method, the BFGS algorithm was adapted. The developed methodology was applied to optimize the flight-control procedures in selected stages of gyroplane flight in direct proximity of the ground, where properly conducted control of the aircraft is critical to ensure flight safety and performance. The results of conducted computational optimizations proved qualitative correctness of the developed methodology. The research results can be helpful in design of easy-to-control gyroplanes and also in the training of pilots of this type of rotorcraft.

Principal component analysis (PCA) is used to reduce the dimensionalities of high dimensional datasets in a variety of research areas. For example, biological macromolecules, such as proteins, exhibit many degrees of freedom, allowing them to adopt intricate structures and exhibit complex functions by undergoing large conformational changes. Therefore, molecular simulations of and experiments on proteins generate a large number of structure variations in high dimensional space. PCA and many PCA-related methods have been developed to extract key features from such structural data, and these approaches have been widely applied for over 30 years to elucidate macromolecular dynamics. This review mainly focuses on the methodological aspects of PCA and related methods, and their applications for investigating protein dynamics.

Fluctuations of protein three-dimensional structures and large-scale conformational transitions are crucial for the biological function of proteins and their complexes. Experimental studies of such phenomena remain very challenging and therefore molecular modeling can be a good alternative or a valuable supporting tool for the investigation of large molecular systems and long-time events. In this mini-review, we present two alternative approaches to the coarse-grained (CG) modeling of dynamic properties of protein systems. We discuss two CG representations of polypeptide chains used for Monte Carlo dynamics simulations of protein local dynamics and conformational transitions and, on other hand, highly simplified structure-based Elastic Network Models of protein flexibility. In contrast to classical Molecular Dynamics the modeling strategies discussed here allow quite accurate modeling of much larger systems and longer time dynamic phenomena. We briefly describe the main features of these models and outline some of their applications, including modeling of near-native structure fluctuations, sampling of large regions of the protein conformational space, or possible support for the structure prediction of large proteins and their complexes.

Transport of hydrophobic drugs in the human body exhibits complications due to the low solubility of these compounds. With the purpose of enhancing the bioavailability and biodistribution of such drugs, recent studies have reported the use of amphiphilic molecules, such as phospholipids, for synthesis of nanoparticles or nanocapsules. Given that phospholipids can self–assemble in liposomes or micellar structures, they are ideal candidates to function as vehicles of hydrophobic molecules. In this work, we report mesoscopic simulations of nanoliposomes, constituted by lecithin and coated with a shell of chitosan. The stability of such structure and the efficiency of encapsulation of capsaicin, as well as the internal and superficial distribution of capsaicin and chitosan inside the nanoliposome were analyzed. The characterization of the system was carried out through density maps and the potentials of mean force for the lecithin–capsaicin, lecithin–chitosan and capsaicin–chitosan interactions. The results of these simulations show that chitosan is deposited on the surface of the nanoliposome, as has been reported in some experimental works. It was also observed that a nanoliposome of approximately 18 nm in diameter is stable during the simulation. The deposition behavior was found to be influenced by pattern of N-acetylation of chitosan.

Li₂MnO₃ is critical component in the well-studied Li-excess cathode materials xLi₂MnO₃•(1- x)LiMO₂ for achieving high lithium storage capacity. In this article, the diffusion of Li ions in Li₂MnO₃ is studied using molecular dynamics (MD) simulation with well-behaved empirical force fields obtained by fitting against the crystal structure from experiment and phonons calculated using Density Function Theory (DFT). We have found two possible tetrahedral hopping channels, 0-TM and 1-TM(Mn⁴⁺) channel, which are differentiated by the face sharing octahedral cations. Simulation results show that the 0-TM channel is active for Li hopping, while 1-TM(Mn4+) channel is inactive. During the delithiation process, the Li ions in the TM layered are firstly removed, then those in the Li layer. However, the Li ions will be trapped in the tetrahedral 0-TM channels as long as the four face sharing octahedral sites are cleared. Up to x=1.0 for Li₂-xMnO₃, almost all the Li ions are located at the tetrahedral sites, forming a regular array along a axis. The de-intercalation of tetrahedral Li ions requires a high voltage (>5.2 V vs. Li/Li+), limiting the practical capacities measured in lab. The diffusion of Mn ions into the Li layers is observed in a deeper delithiated structure (x=1.2 for Li₂-xMnO₃), indicating an initial phase transformation to a spinel-like structure. However, the Mn ions are mainly trapped in the tetrahedral sites in the Li layer, instead of the octahedral sites fin spinel-like structure. A few of Mn ions diffusing into the octahedral sites in Li layers have no face sharing tetrahedral Li ions, revealing a further Li de-intercalation is imperative for the complete phase transformation. Our model is not stable for x≥1.4 in Li₂-xMnO₃. Other charge compensation mechanism should be considered in this high delithiation stage, eg. oxygen release.

G protein-coupled receptors (GPCRs) play a key role in many cellular signaling mechanisms, and must select among multiple coupling possibilities in a ligand-specific manner in order to carry out a myriad of functions in diverse cellular contexts. Much has been learned about the molecular mechanisms of ligand-GPCR complexes from Molecular Dynamics (MD) simulations. However, to explore ligand-specific differences in the response of a GPCR to diverse ligands, as is required to understand ligand bias and functional selectivity, necessitates creating very large amounts of data from the needed large-scale simulations. This becomes a Big Data problem for the high dimensionality analysis of the accumulated trajectories. Here we describe a new machine learning (ML) approach to the problem that is based on transforming the analysis of GPCR function-related, ligand-specific differences encoded in the MD simulation trajectories into a representation recognizable by state-of-the-art deep learning object recognition technology. We illustrate this method by applying it to recognize the pharmacological classification of ligands bound to the 5-HT2A and D2 subtypes of class A GPCRs from the serotonin and dopamine families. The ML-based approach is shown to perform the classification task with high accuracy, and we identify the molecular determinants of the classifications in the context of GPCR structure and function. This study builds a framework for the efficient computational analysis of MD Big Data collected for the purpose of understanding ligand-specific GPCR activity.

The tsscds method, recently developed in our group, discovers chemical reaction mechanisms with minimal human intervention. It employs accelerated molecular dynamics, spectral graph theory, statistical rate theory and stochastic simulations to uncover chemical reaction paths and to solve the kinetics at the experimental conditions. In the present review, its application to solve mechanistic/kinetics problems in different research areas will be presented. Examples will be given of reactions involved in photodissociation dynamics, mass spectrometry, combustion chemistry and organometallic catalysis. Some planned improvements will also be described.

Molecular dynamics simulation is currently the theoretical technique eligible to simulate a wide range of systems from soft condensed matter to biological systems. However, of the excellent results that the technique has arrogated, this approach remains computationally expensive, but with the emergence of the new supercomputing technologies bases on graphics processing units graphical processing units-based systems GPUs, the perspective has changed. The GPUs allow performing large and complex simulations at a significantly reduced time. In this work, we present recent innovations in the acceleration of molecular dynamics in GPUs to simulate non-Hamiltonian systems. In particular, we show the performance of measure-preserving geometric integrator in the canonical ensemble, that is, at constant temperature. We provide a validation and performance evaluation of the code by calculating the thermodynamic properties of a Lennard-Jones fluid. Our results are in excellent agreement with reported data reported from literature, which were calculated with CPUs. The scope and limitations for performing simulations of high-throughput MD under rigorous statistical thermodynamics in the canonical ensemble are discussed and analyzed.

Tree-killing bark beetles are the most economically important insects in conifer forests worldwide. Yet despite >200 years of research, the drivers of population eruptions or crashes are still not fully understood, precluding reliable predictions of the effects of global change on beetle population dynamics and impacts on ecosystems and humans. We critically analyze potential biotic and abiotic drivers of population dynamics of the European spruce bark beetle (Ips typographus) and present a novel ecological framework that integrates the multiple drivers governing this bark beetle system. We call for large-scale collaborative research efforts to improve our understanding of the population dynamics of this important pest; an approach that might serve as a blueprint for other eruptive forest insects.

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists either in blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-Epigallocatechin-3-gallate, Quercetin, and Rosmarinic acid) with the amyloid-β(1-40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulate the double-layered structure stability.

Salmonella, especially invasive non-typhoidal Salmonella (iNTS) are responsible for developing various invasive diseases, and possess higher mortality rate, due to their higher antibiotic resistance profile than the other bacteria. Therefore, the present study was concerned to develop epitope based peptide vaccine against iNTS species as a successive and substitute protective measures. The study considered comprehensive Immunoinformatic approaches, followed by molecular docking and molecular dynamics simulation to predict the efficient vaccine candidate T cell and B cell epitopes, based on the outer membrane proteins. The study identified two best epitopes YGIFAITAL and KVLYGIFAI from total iNTS outer membrane proteins, which showed higher immunity, non-allergenicity, non-toxicity and also showed higher conservancy and population coverage values. Both epitopes showed higher binding affinity and stability towards HLA-C* 03:03. The MM-PBSA binding free energy showed the YGIFAITAL epitope binds more tightly with both MHC-I and MHC-II molecules. The total contact, H-bond analysis and RMSF results also validate the efficiency of these epitopes as vaccine candidate. The projected B cell epitopes AAPVQVGEAAGS, TGGGDGSNT and TGGGDGSNTGTTTT showed higher antigenicity. Overall, the study concluded that these epitopes can be considered as the potential vaccine candidate to make a successive vaccine against iNTS species. However, this result further needs to be validate by wet lab research to make successive vaccine with these projected epitopes.

The details of antigen-antibody interactions and the identification of epitopes are critical for the development of monoclonal antibody drugs. Ab42 is a native human-derived anti-CFH monoclonal antibody. In this study, the interaction between antigen pCFH and antibody (Ab42) was theoretically demonstrated by molecular docking and MD simulation, combined with free energy calculation and computational alanine scanning (CAS), and key amino acids and epitopes were identified. Experimental alanine scanning (EAS) was then carried out to verify the results of the calculation, and our results indicated that Ab42 antibody forms hydrogen bonds and interacts hydrophobically with pCFH through the Tyr315, Ser100, Gly33, and Tyr53 residues on its CDR, while the main pCFH epitopes are located at the six sites of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448. In conclusion, this study has explored the mechanism of antigen-antibody interaction from both theoretical and experimental aspects, and our results have important theoretical significance for the design and development of relevant antibody drugs.

We performed for the first time to our knowledge fully ab initio molecular dynamics simulations of additive tribochemistry in boundary lubrication conditions. We consider an organophosphourus additive that has been experimentally shown to reduce friction in steel-on-steel sliding contacts thanks to the tribologically-induced formation of an iron phosphide tribofilm. The simulations allow us to observe in real time the molecular dissociation at the sliding iron interface under pressure and to understand the mechanism of iron phosphide formation. We discuss the role played by the mechanical stress by comparing the activation times for molecular dissociation observed in the tribological simulations at different applied loads with that expected on the basis of the dissociation barrier.

In this effort we propose a data-driven learning framework for reduced order modeling of fluid dynamics. Designing accurate and efficient reduced order models for nonlinear fluid dynamic problems is challenging for many practical engineering applications. Classical projection-based model reduction methods generate reduced systems by projecting full-order differential operators into low-dimensional subspaces. However, these techniques usually lead to severe instabilities in the presence of highly nonlinear dynamics, which dramatically deteriorates the accuracy of the reduced-order models. In contrast, our new framework exploits linear multistep networks, based on implicit Adams-Moulton schemes, to construct the reduced system. The advantage is that the method optimally approximates the full order model in the low-dimensional space with a given supervised learning task. Moreover, our approach is non-intrusive, such that it can be applied to other complex nonlinear dynamical systems with sophisticated legacy codes. We demonstrate the performance of our method through the numerical simulation of a two-dimensional flow past a circular cylinder with Reynolds number Re = 100. The results reveal that the new data-driven model is significantly more accurate than standard projection-based approaches

Wave energy converter (WEC) arrays deployed in coastal regions may create physical disturbances potentially resulting in environmental stresses. Presently, limited information is available on the nature of these physical disturbance or the resultant effects. A quantitative Spatial Environmental Assessment Tool (SEAT) for evaluating potential effects of wave energy converter (WEC) arrays on nearshore hydrodynamics and sediment transport is presented for the central Oregon coast (USA) through coupled numerical model simulations of an array of WECs. Derived climatological wave conditions were used as inputs to the model to allow for the calculation of risk metrics associated with various hydrodynamic and sediment transport variables such as maximum shear stress, bottom velocity, and change in bed elevation. The risk maps provided simple, quantitative, and spatially-resolved means of evaluating physical changes in the vicinity of a hypothetical WEC array in response to varying wave conditions. Near-field risk of sediment mobility was determined to be moderate in the lee of the densely spaced array, where the potential for increased sediment deposition could result in benthic habitat alteration. Modifications to the nearshore sediment deposition and erosion patterns were observed near headlands and topographic features, which could have implications for littoral sediment transport. The results illustrate the benefits of a risk evaluation tool for facilitating coastal resource management at early market marine renewable energy sites.

In this paper, an attempt has been made to analyze the effect of spool port/ groove geometry on the pressure drop and chamber pressures which effect the performance parameters of the flow distributor valve. The work mainly involves formulation of detailed mathematical model of the valve and compare them on the same platform. For mathematical modelling, Matlab has been used. The size of the orifices is considered same throughout the model for better comparison. Initially the construction and functioning of flow distributor valve along with working principles of hydrostatic motor (Rotary Piston) is shown. Next shown the analytical analysis of area change and pressure drops due to different geometry of the spool valve ports. After that the computational fluid dynamics (CFD) analysis has been shown. A complete mathematical model to describe such flow distributor valve is developed after having a comprehensive knowledge of orifice characteristics, flow interactions based on valve geometry. Equations of flow through different orifices (fixed and variable area) of the valve have been developed based on the relationships obtained earlier.

Time recordings of impulse-type oscillation responses are short and highly transient. These characteristics may complicate the usage of classical spectral signal processing techniques for a) describing the dynamics and b) deriving discriminative features from the data. However, common model identification and validation techniques mostly rely on steady-state recordings, characteristic spectral properties and non-transient behavior. In this work, a recent method, which allows reconstructing differential equations from time series data, is extended for higher degrees of automation. With special focus on short and strongly damped oscillations, an optimization procedure is proposed that fine-tunes the reconstructed dynamical models with respect to model simplicity and error reduction. This framework is analyzed with particular focus on the amount of information available to the reconstruction, noise contamination and non-linearities contained in the time series input. Using the example of a mechanical oscillator, we illustrate how the optimized reconstruction method can be used to identify a suitable model and to extract features from uni-variate and multivariate time series recordings in an engineering-compliant environment. Moreover, the determined minimal models allow for identifying the qualitative nature of the underlying dynamical systems as well as testing for the degree and strength of non-linearity. The reconstructed differential equations would then be potentially available for classical numerical studies, such as bifurcation analysis. These results represent a physically interpretable enhancement of data-driven modeling approaches in structural dynamics.

Quantum Computation, in the gate array version, uses logical gates adopting convenient forms for computational algorithms based on those of classical computation. There, two-level quantum systems are the basic elements connecting the binary nature of classical computation with the settlement of quantum processing. Despite, their design depends on specific quantum systems and physical interactions involved, exacerbating the dynamics analysis. Predictable and controllable manipulation should be addressed to control the quantum states, but resources are restricted to limitations imposed by the physical settlement. This work presents a formalism to decompose the quantum information dynamics in SU(2^2d) for 2d-partite two-level systems into 2^2d-1 SU(2) quantum subsystems. Decomposition lets to set control procedures, to generate large entangled states and to design specialized dedicated quantum gates. There, easy and traditional operations proposed by quantum computation are recovered for more complex and large systems. Alternating the parameters of local and non-local interactions, the procedure states a universal exchange semantics on the generalized Bell states basis. It could be understood as a momentary splitting of the 2d information channels into 2^2d-1 pairs of 2 level quantum information subsystems and a settlement of the quantum information manipulation free of the imposed restrictions by the underlying physical system.

By manipulating the various physico-chemical properties of amino acids, design of peptides with specific self-assembling properties has been emerging since more than a decade. In this context, short peptides possessing detergent properties (so-called “peptergents”) have been developed to self-assemble into well-ordered nanostructures that can stabilize membrane proteins for crystallization. In this study, the peptide with “peptergency” properties, called ADA8 extensively described by Zhang et al., is studied by molecular dynamics for its self-assembling properties in different conditions. In water, it spontaneously forms beta sheets with a β barrel-like structure. We next simulated the interaction of this peptide with a membrane protein, the bacteriorhodopsin, in the presence or absence of a micelle of dodecylphosphocholine. According to the literature, the peptergent ADA8 is thought to generate a belt of β structures around the hydrophobic helical domain that could help stabilize purified membrane proteins. Molecular dynamics is here used to challenge this view and to provide further molecular details for the replacement of detergent molecules around the protein. To our best knowledge, this is the first molecular mechanism proposed for ''peptergency''. In addition, our calculation approach should serve as a predicting tool for the design of beta peptergent with diverse amphipathic properties.

In this research, atomistic molecular dynamics simulations are combined with mesoscopic phase-field computational methods in order to investigate phase-transformation in polycrystalline Aluminum microstructure. In fact, microstructural computational modeling of engineering materials could help to optimize their mechanical properties for industrial applications (e.g. directional solidification for turbine blades). As a result, a multiscale modeling approach is developed to find a relation between manufacturing variables (e.g. temperature) and microstructural properties of crystalline materials (e.g. grain size), which could be used to develop an advanced manufacturing process for sensitive applications. The results show that atomistic modeling of grain growth could be used as a first-principle approach in order to study phase transformation's kinetics, which could capture morphology of polycrystalline materials more accurately. On the other hand, phase-field mesoscopic approach needs less computational efforts, but still it relies on semi-empirical data to capture accurate phase transformation regimes, which makes this approach suitable for rapid examining of new manufacturing conditions as well as its effects on microstructural properties of polycrystalline materials.

Studies performed at single-cell resolution have demonstrated the physiological significance of cell-to-cell variability. Various types of mathematical models and systems analyses of biological networks have further been used to gain a better understanding of the sources and regulatory mechanisms of such variability. In this work, we present a novel sensitivity analysis method, called molecular density function perturbation (MDFP), for the dynamical analysis of cellular heterogeneity. The proposed analysis is based on introducing perturbations to the density or distribution function of the cellular state variables at specific time points, and quantifying how such perturbations affect the state distribution at later time points. We applied the MDFP analysis to a model of signal transduction pathway involved in TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis in HeLa cells. The MDFP analysis showed that caspase-8 activation regulates the timing of the switch-like increase of cPARP (cleaved poly(ADP-ribose) polymerase), an indicator of apoptosis. Meanwhile, the cell-to-cell variability in the commitment to apoptosis depended on mitochondrial outer membrane permeabilization (MOMP) and events following MOMP, including the release of Smac (second mitochondria-derived activator of caspases) and cytochrome-C from mitochondria, the inhibition of XIAP (X-linked inhibitor of apoptosis) by Smac and the formation of apoptosome.

In this work it is acknowledged that important attempts to devise an emergent quantum (gravity) theory require space-time to be discretized at the Planck scale. It is therefore conjectured that reality is identical to a sub-quantum dynamics of ontological micro-constituents that are connected by a single interaction law. To arrive at a complex system-based toy-model identification of these micro-constituents, two strategies are combined. First, by seeing gravity as an entropic phenomenon and generalizing the dimensional reduction of the associated holographic principle, the universal constants of free space are related to assumed attributes of the micro-constituents. Second, as the effective field dynamics of the micro-constituents must eventually obey Einstein’s field equations, a sub-quantum interaction law is derived from a solution of these equations. A Planck-scale origin for thermodynamic black hole characteristics and novel views on entropic gravity theory result from this approach, which eventually provides a different view on quantum gravity and its unification with the fundamental forces.

Mitochondrial functions are essential for life, critical for development, maintenance of stem cells, adaptation to physiological changes, responses to stress and aging. The complexity of mitochondrial biogenesis requires coordinated nuclear and mitochondrial gene expression, owing to the need of stoichiometrically assemble the OXPHOS system for ATP production. It requires, in addition, the import of thousands of proteins from the cytosol to keep optimal mitochondrial function and metabolism. Moreover, mitochondria require lipid supply for membrane biogenesis, while it is itself essential for the synthesis of membrane lipids. To achieve mitochondrial homeostasis, multiple mechanisms of quality control have evolved to ensure that mitochondrial function meets cell, tissue and organismal demands. Herein, we give an overview of mitochondrial mechanisms that are activated in response to stress, including mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response (UPR^mt). We then discuss the role of these stress responses in aging, with particular focus on Caenorhabditis elegans. Finally, we review observations that point to the mitochondrial PHB (prohibitin) complex as a key player in mitochondrial homeostasis, being essential for mitochondrial biogenesis and degradation, and responding to mitochondrial stress. Understanding how mitochondria responds to stress and how such responses are regulated is pivotal to combat aging and disease.

Current progress in the prediction of mechanical behavior of solids requires understanding of spatiotemporal complexity of plastic flow caused by self-organization of crystal defects. It may be particularly important in hexagonal materials because of their strong anisotropy and combination of different mechanisms of plasticity, such as dislocation glide and twinning. These materials often display complex behavior even on the macroscopic scale of deformation curves, e.g., a peculiar three-stage elastoplastic transition, the origin of which is a matter of debates. The present work is devoted to a multiscale study of plastic flow in α-Ti, based on simultaneous recording of deformation curves, 1D local strain field, and acoustic emission (AE). It is found that the average AE activity also reveals three-stage behavior, but in a qualitatively different way depending on the crystallographic orientation of the sample axis. On the finer scale, the statistical analysis of AE events and local strain rates testifies to an avalanche-like character of dislocation processes, reflected in power-law probability distribution functions. The results are discussed from the viewpoint of collective dislocation dynamics and are confronted to predictions of a recent micromechanical model of Ti strain hardening.

In this paper, we introduce the evolve-then-filter (EF) regularization method for reduced order modeling of convection-dominated stochastic systems. The standard Galerkin projection reduced order model (G-ROM) yield numerical oscillations in a convection-dominated regime. The evolve-then-filter reduced order model (EF-ROM) aims at the numerical stabilization of the standard G-ROM, which uses explicit ROM spatial filter to regularize various terms in the reduced order model (ROM). Our numerical results based on a stochastic Burgers equation with linear multiplicative noise. It shows that the EF-ROM is significantly better results than G-ROM.

To understand functions of biomolecules such as proteins, not only structures but their conformational change and kinetics are important to be characterized but its atomistic details are hard to obtain both experimentally and computationally. We review our recent computational studies using novel enhanced sampling techniques for conformational sampling of biomolecules and calculations of their kinetics. For efficiently characterizing the free energy landscape of a biomolecule, we introduce the multiscale enhanced sampling method, which uses a combined system of atomistic and coarse-grained models. Based on the idea of Hamiltonian replica exchange, we can recover the statistical properties of the atomistic model without any biases. We next introduce the string method as a path search method to calculate the minimum free energy pathways along a multidimensional curve in high dimensional space. Finally we introduce novel methods to calculate kinetics of biomolecules based on the ideas of path sampling: One is the Onsager-Machlup action method, and the other is the weighted ensemble method. Some applications of above methods to biomolecular systems are also discussed and illustrated.

Heavy metal contamination of drinking water is a public health concern that requires the development of more efficient bioremediation techniques. Absorption technologies, including biosorption, provide opportunities for improvements to increase the diversity of metal ions removed and overall binding capacity. Microorganisms are a key component in wastewater treatment plants and they naturally bind metal ions through surface macromolecules but with limited capacity. The long-term goal of this work is to engineer capsule polymerases to synthesize molecules with novel functionalities. In previously published work, we showed that the Neisseria meningitidis serogroup W (NmW) galactose-sialic acid (Gal—NeuNAc) heteropolysaccharide binds lead effectively, thereby demonstrating the potential for using this capsular polysaccharide in environmental decontamination applications. In this study, computational analysis of the NmW capsule polymerase galactosyltransferase (GT) domain was used to gain insight into how the enzyme could be modified to enable the synthesis N-acetylgalactosamine-sialic acid (GalNAc—NeuNAc) heteropolysaccharide. Various computational approaches, including molecular modeling with I-TASSER and molecular dynamics simulations (MD) with NAMD, were utilized to identify key amino acid residues in the substrate binding pocket of the GT domain that may be key to conferring UDP-GalNAc specificity. Through these combined strategies and using BshA, a UDP-GlcNAc transferase, as a structural template, several NmW active site residues were identified as mutational targets to accommodate the proposed N-acetyl group in UDP-GalNAc. Thus, a rational approach for potentially conferring new properties to bacterial capsular polysaccharides is demonstrated.

In this study, an optimization of the first blade in new test rig presented. Blade tuning is conducted using 3D geometrical parameters. Sweep and dihedral play an essential role in this study. Compressor characteristics and blades vibrational behavior are the main objective of the evaluation. Here, the attachments are designed to isolate blade dynamics from Disk. So, the Vibrational behaviors of the one's blade are tuned based on the self-excited and forced vibration phenomenon. Using a semi analytical MATLAB code instability conditions are satisfied. The code takes advantages of whitehead and force response theory to predict classically and stall flutter speeds. Beside, Forced vibrations instability is controlled using a theory presented by Campbell. Aerodynamics of new blade geometry determined using multistage simulations Computational fluid dynamics (CFD) software. Numerical results show increasing performance near the surge line and working interval along with increasing mass flow.

ND1 subunit possesses the majority of the inhibitor binding domain of the human MRC-I. This is an attractive target for the search for new inhibitors that seek mitochondrial dysfunction. It is known, from in vitro experiments, some metabolites from Annona muricata called acetogenins have important biological activities such as anticancer, antiparasitic, and insecticide. Previous studies propose an inhibitory activity of bovine MRC-I by bis-THF acetogenins such as annocatacin B, however, there are few studies on its inhibitory effect on human MRC-I. In this work, we evaluate the molecular and energetic affinity of the annocatacin B molecule with the human ND1 subunit in order to elucidate its potential capacity to be a good inhibitor of this subunit. For this purpose, QM optimizations, MD simulations and MM/PBSA analysis were performed. As a control to compare our outcomes, the molecule rotenone, which is a known MRC-I inhibitor, was chosen. Our results show that annocatacin B has a greater affinity for the ND1 structure, its size and folding were probably the main characteristics that contributed to stabilize the molecular complex. Furthermore, the MM/PBSA calculations showed a 35% stronger BFE compared to the rotenone complex. Detailed analysis of the BFE shows that the aliphatic chains of annocatacin B play a key role in molecular coupling by distributing favorable interactions throughout the major part of the ND1 structure. These results are consistent with experimental studies that mention that acetogenins may be good inhibitors of MRC-I.

The past two decades have witnessed the introduction of and then a steady increase in the use of computational techniques in the study and development of molecularly imprinted polymers (MIPs). Molecular dynamics (MD) based studies have had a significant role in this development as they can provide insights concerning the mechanisms governing the molecular level events underlying MIP synthesis and MIP-ligand interactions and can be used for the identification of preferred monomer compositions and for the prediction of MIP properties. We here review the role that MD has played in the development of molecular imprinting and examine the different types of MD strategies that have been used, including their advantages and challenges. Recent trends in the application of MD to the study of MIPs are presented, along with a perspective on the future importance of MD-based studies for the development of molecular imprinting science and technology.

Few data are available on the health impact of tobacco heating products (THPs) at the population level. We used systems dynamics modelling to estimate effects in the established THP market in Japan. We projected effects of THP use in overall mortality up to 2100 and compare those projections against a baseline scenario based on smoking rates pre-THP launch, i.e., smoking only. The model was informed using data from publicly available sources and the literature, including population size, yearly deaths and smoking prevalence with initialisation year (2004) and, births and migration from 2004 to 2065. Transitions between products were estimated from cross-sectional population surveys in Japan. Potential life-years saved with the introduction of THPs was 13 million by 2100 compared with smoking only. In worst-case scenario, population health gains would be seen with THPs risk 10–50% lower risk than smoking. Assuming equal risk for dual use and smoking, THP risk would need to be at least 10% lower than smoking to achieve a population health benefit by 2100. In credible scenarios, substantial population health gains will follow the introduction of THPs in Japan in a relatively short time frame.

Complex systems can be described as the network of interactions between their components. In directed networks, information, energy and matter flow in dominant directions. Undirected networks, on the other hand, cannot easily capture these asymmetries. The local flow of information depends on the node spin, which is a function of the number of incoming and outgoing links attached to it. And yet, how the heterogeneous association between in-degree and out-degree constraints global dynamics remains poorly understood. Here, we develop a new theoretical model to study the relationship between node directionality and global flow dynamics. Our computational analysis of random and scale-free directed networks indicates that structural diversity constrains the dimensionality of reachable dynamical space. These results suggest how local directionality might be an universal driver of global dynamics in many systems, from social networks, to technological systems to the connectome.

The outbreak of COVID-19, the disease caused by SARS-CoV-2, continues to affect millions of people around the world. The absence of a globally distributed effective treatment makes the exploration of new mechanisms of action a key step to address this situation. Stabilization of non-native Protein-Protein Interactions (PPIs) of the nucleocapsid protein of MERS-CoV has been reported as a valid strategy to inhibit viral replication. In this study, the applicability of this unexplored mechanism of action against SARS-CoV-2 is analyzed. During our research, we were able to find three inducible interfaces of SARS-CoV-2 N protein NTD, compare them to the previously reported MERS-CoV stabilized dimers, and identify those residues that are responsible for their formation. A drug discovery protocol implemented consisting of docking, molecular dynamics and MM-GBSA enabled us to find several compounds that might be able to exploit this mechanism of action. In addition, a common catechin skeleton was found among many of these molecules, which might be useful for further drug design. We consider that our findings could motivate future research in the fields of drug discovery and design towards the exploitation of this previously unexplored mechanism of action against COVID-19.

In this contribution, we aim to show that opinion dynamics and population balance modeling can benefit from an exchange of problems and methods. To support this claim, the Deffuant-Weisbuch model, a classical approach in opinion dynamics, is formulated as a population balance model. This new formulation is subsequently analyzed in terms of moment equations, and conservation of the first and second order moment is shown. Exemplary results obtained by our formulation are presented and agreement with the original model is found. Also the influence of the initial distribution is studied. Additionally, the Deffuant-Weisbuch model is transferred to engineering and interpreted as mass transfer between liquid droplets which results in a more flexible formulation compared to alternatives from the literature. On the one hand, it is concluded that the transfer of opinion-dynamics problems to the domain of population balance modeling offers some interesting insights as well as stimulating challenges for the population-balance community. On the other hand, it is inferred that population-balance methods can contribute to the solution of problems in opinion dynamics. In a broad outlook, some further possibilities of how the two fields can possibly benefit from a close interaction are outlined.

With the diversified development of media forms, livestreaming e-commerce has become a new sales model. Unlike the traditional sales model, this paper constructs a three-party game model composed of manufacturers, social media influencers and consumers based on the livestreaming model. It explores the equilibrium strategy selections of each participant in the supply chain system. In analyzing the evolutionary game stability of each participant, this paper obtains the equilibrium strategy and stability factors by analysis of the income and expenditure matrix. It uses the simulation model to analyze reasons for strategy selections of different game participants in the livestreaming e-commerce model. The results show that the strategies of manufacturers, social media influencers and consumers' selections have different impacts on their decision-making mechanism, and man-ufacturers are more sensitive to consumers' active participation in livestreaming e-commerce.

To solve a series of major problems, such as the singularity before the Big Bang, the inflation of the early universe and the accelerating expansion of the present universe, this series of studies start with super gravity, dark energy and dark matter, go beyond the surface of a lot of observation data, and systematically reveal the arche-internal mechanism of all things, to establish the arche-unity of physics, and give a natural and reasonable explanation. At present, there are at least three basic pathways that are leading our research field to repulsion against gravitation, quantum repulsion against quantum gravitation and high-dimensional superrepulsion against high-dimensional supergravity, that is, the research on the accelerating expansion mechanism of the current universe, the research on the dynamic mechanism of the early cosmic inflation, and the research on the rebound mechanism near the singularity before the Big Bang. In this series of studies, the arche problem of everything is always placed under the extreme environmental conditions of the initial universe, the starting point of scientific logic is closely combined with the starting point of the universe history, the pseudo vacuum energy considered by the inflationary universe model, the Higgs field predicted by the standard physical model and the dark energy speculated by the observational cosmology are reduced to the positive energy system with strong negative pressure, and they are reduced to the repulsion (all the resistance to gravity) that forms a conjugate relation with gravity. In our opinion, dark energy and dark matter are essentially at the level of quantum gravity and quantum repulsion. Therefore, we not only consider the conventional quantum effect and non commutative quantum effect, but also further consider the arche-conjugate effect and the cluster resonance-at-cofrenquence effect. For noncommutative space-time, we put forth the ultimate supersymmetry, the arche-conjugation and the cluster resonance-at-cofrenquence. A relatively complete natural mechanism forms such an important inference: the closer they get to Planck scale, the stronger the conventional quantum effect, non commutative quantum effect, arche-conjugate effect and co-frequency resonance effect are. In the high-dimensional space-time (the 11 dimensional hyperspace compactly reduced to M 4 × N r ), corresponding to the introduction of supergravity with the supersymmetry between the graviton and the gravitino, we put forth the superrepulsion with the supersymmetry between the repulsion and the repulsitino, and establish the arche-conjugate relationship between the high-dimensional supergravity and the high-dimensional superrepulsion. Therefrom, we propose a basic inference that can be promoted to the principle of hyperholography of high-dimensional universe (or multiuniverse): in a parallel universe formed by mutual coupling and holographic correspondence between the P universe dominated by negative pressure (high-dimensional superrepulsion and quantum repulsion of accumulating positive energy, mainly composed of dark energy) and the N universe dominated by positive pressure (high-dimensional supergravity and quantum gravity of accumulating negative energy, mainly composed of dark matter), there is a correspondence between the small-scale physics (ultraviolet cutoff) of the P universe and the large-scale physics (infrared cutoff) of the N universe, while there is a correspondence between the large-scale physics (ultraviolet cutoff) of the P universe and the small-scale physics (infrared cutoff) of the N universe. In the new research paradigms set in this series, the arche-conjugation between the high-dimensional supergravity and the high-dimensional super repulsion, as well as between the quantum gravity and the quantum repulsion, is higher than the supersymmetry, so it becomes the core concept of the new theory. The arhce-unity of physics is a super unity that transcends the grand unification of four basic interaction, which is formed between high-dimensional supergravity (related to dark matter) and high-dimensional superrepulsion (related to dark energy), between quantum gravity (related to dark matter) and quantum repulsion (related to dark energy). From the basic component point of view, before or after the big bang, the gravitons and repulsons are coupled together, the negative energy contraction dominated by the positive pressure and the positive energy expansion dominated by the negative pressure work alternately, forming the arche-conjugate pulsaton of neither the point particle nor the linear superstring. Under the big unified framework of quantum gravitational field and quantum repulsive field, this series of work comprehensively expands the general relativity and loop quantum ring gravitation theory, sets up the quantum repulsive field equation corresponding to the quantum gravitational field equation, and then establishes the quantum hedge-unified field equation describing the interaction of quantum gravitational field and quantum repulsive field; On this basis, the quantum repulsive universe equation corresponding to the quantum gravitational universe equation is established, thus a set of new equations describing the expansive universe with quantum hedge-unified field are established. On the one hand, scalar disturbance is considered as the exhibition of repulsive effect, on the other hand, tensor disturbance is considered as the exhibition of gravitational effect. In the initial stage of the big ripping, due to the mutual restraint of quantum repulsion and quantum gravity, the scalar and tensor perturbations are not obvious. However, at the end of the big ripping, the scalar and tensor perturbations are very significant, and there is a large power spectral exponential run. Between particle physics and cosmology, we improve and expand the path integral of quantum gravity, create the path integral of quantum hedge-unified field, and set up the basic equation of quantum cosmic-synergetic dynamics, and then establish the basic equation of quantum-cosmic paradigm dynamics. Thus we put up the operator distribution function and its dynamic equation of the quantum arche- pulsaton, and finally use the Wigner-Ville distribution as a non-linear time-frequency distribution to establish the Wigner joint-distribution of quantum-conjuagted pulsation function, so as to analyze the arche of all things with three evolutionary forms: quantum chaotic-pulsaton, quantum quasi-spherical pulsaton and quantum spherical-pulsaton. In this series of work, the mechanism to avoid the singularity of the universe is put forward fundamentally, and the dark energy and dark matter are explained through new mechanisms and effects at the level of quantum gravity. Between particle physics and cosmology, we improve and expand the path integral of quantum gravity, establish the path integral of quantum hedge-unified field, thus establish the basic equation of quantum cosmic-synergy dynamics, and then establish the basic equation of quantum cosmic-paradigm dynamics. Thus the covariant gravitational mass and the covariant inertial mass formed by the ultra-synergy between particles and the universe are presented, and the equivalence hypothesis on the covariant non-inertial system which can be elevated to the basic principle, is presented. Based on this hypothesis, a systematic calculation and analysis of binary stars composed of neutron stars and black holes are made. The master equation, variance and Fokker-Planck equation for the birth-death and migration of a large number of particles are established between binary stars composed of neutron stars and black holes.

Change orders have received considerable attention from researchers thus far, but none have considered pricing strategies of change orders through the interaction between general contractors and subcontractors. Previous studies found that contractors’ opportunistic bidding considering beyond-contractual reward (BCR) in the execution stage can be reduced by improving the construction management system and strengthening the supervision of contractors’ performance. However, the BCR remains in ecology of construction engineering. This study proposes an integrated evolutionary game theory-system dynamics model (ET-SD model) and simulates the pricing strategy of change orders between general contractors and subcontractors to explore the root cause of BCR phenomenon. Sensitivity analysis on the evolutionary dynamics of payoff is explored. Results reveal that change orders with BCR maintain Nash equilibrium and evolutionary stable strategy (ESS) unless changing the payoff structure between general and subcontractors’ pricing strategies. This study presents important managerial insights from the evolutionary game perspectives, nature of change orders, and payoff of the alternative.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.

A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.

The study is based on the results of long-term field studies, satellite and aerial data analysis. In the maximum of the Little Ice Age (LIA) 243 glaciers with a total area of 353.4 km2 were reconstructed. By the results of interpretation of Corona images by 1968 the number of glaciers increased (236), the total area reduced to 242 km2. In 2010 glaciation was represented by 237 glaciers with a total area of 201 km2. Thus, from the maximum of the LIA, the glaciation of the Tavan-Bogd mountains decreased by 43%, which is somewhat less than the neighboring glacial centers (Ikh-Turgen, Tsambagarav, Tsengel-Khayrkhan and Mongun-Taiga mountains). The probable cause is the predominance of larger glaciers relatively resistant to warming and higher altitudes. The effect of glacier size on their stability is supported by differences in the relative shrinkage of glaciers in different parts of the Tavan-Bogdo-Ola massif: the smallest decline occurred in the basins of the Tsagan-Gol (31.7%) and Sangadir (36.4%) rivers where the largest glaciers are located. On the contrary, on the lower periphery of the massif, where small glaciers predominate, the relative reduction was large (74-79%). On the background of the general retreat trend large valleys glaciers retreated faster in 1968-1977 and after 2010. In 1990-s the retreat was slow. After 2010 the glacial retreat was extremely fast. The retreat of glaciers in the last 50-60 years was caused by a trend towards a decrease in the amount of precipitation until the mid-1970s and a sharp warming in the 1990s and early 2000s.

In recent years, applying deep learning to solve physics problems has attracted much attention. Data-driven deep learning methods produce operators that can learn solutions to the whole system of partial differential equations. However, the existing methods are only evaluated on simple flow equations (e.g., Burger's equation), and only consider the generalization ability on different initial conditions. In this paper, we construct CFDBench, a benchmark with four classic problems in computational fluid dynamics (CFD): lid-driven cavity flow, laminar boundary layer flow in circular tubes, dam flows through the steps, and periodic Karman vortex street. Each flow problem includes data with various boundary conditions, fluid physical properties, and domain geometries. Compared to existing datasets, the advantages of CFDBench are (1) comprehensive. It contains common physical parameters such as velocity, pressure, and cavity fraction. (2) realistic. It is very suitable for deep learning solutions of fluid mechanics equations. (3) challenging. It has a certain learning difficulty, prompting to find models with strong learning ability. (4) standardized. CFDBench facilitates a comprehensive and fair comparison of different deep learning methods for CFD. We make appropriate modifications to popular deep neural networks to apply them to CFDBench and enable the accommodation of more changing inputs. The evaluation on CFDBench reveals some new shortcomings of existing works and we propose possible directions for solving such problems.

There must exist a reformulation of quantum field theory which does not refer to classical time. We propose a pre-quantum, pre-spacetime theory, which is a matrix-valued Lagrangian dynamics for gravity, Yang-Mills fields, and fermions. The definition of spin in this theory leads us to an eight dimensional octonionic space-time. The algebra of the octonions reveals the standard model; model parameters are determined by roots of the cubic characteristic equation of the exceptional Jordan algebra. We derive the asymptotic low energy value 1/137 of the fine structure constant, and predict the existence of universally interacting spin one Lorentz bosons, which replace the hypothesised graviton. Gravity is not to be quantized, but is an emergent four-dimensional classical phenomenon, precipitated by the spontaneous localisation of highly entangled fermions.

Micro-plasma is generated in ultra-high-pure hydrogen gas filled inside a cell at a pressure of (1.08 ± 0.033) × 10⁵ Pa (810 ± 25 Torr) by using a Q-switched Nd:YAG laser device operated at 1064 nm wavelength and 14 ns pulse duration. Micro-plasma emission spectra of the hydrogen Balmer alpha line, H_α, are recorded with a Czerny-Turner type spectrometer and an intensified charge-coupled device. The spectra are calibrated for wavelength and corrected for detector sensitivity. During the first few tens of nanoseconds after initiating optical breakdown, significantly Stark-broadened and Stark-shifted H_α lines mark the well-above hypersonic outward expansion. The vertical diameters of the spectrally resolved plasma images are measured for time delays of 10 ns to 35 ns to determine expansion speeds of the order of 100 km/s to 10 km/s. For time delays of the order of 0.5 µs to 1 µs, the expansion decreases to the speed of sound of 1.3 km/s in the near ambient temperature and pressure hydrogen gas.

Climate projections show that southern Indonesia such as West Nusa Tenggara is projected to experience a lower precipitation and higher temperatures. To date, research on climate change impact on Indonesian rice production yield is limited. As climate change is projected to decrease rainfall and to increase temperatures, this paper offers a qualitative analysis using system archetypes to understand the impacts of climate change on rice production. Two system archetypes are identified including Limits to Growth and Success to Successful. Both archetypes explain that rice production is hampered by high minimum temperature as photosynthesis output is decreased by increasing respiration. This paper shows that using a simple tool, system archetypes, we can describe the impacts of climate change on rice production. The outputs of this study such as a causal loop diagram and system archetypes can be a basis to develop a simulation model in understanding the impacts of climate change on main crops.

The second law of thermodynamics states the increase of entropy, ΔS > 0, for real processes from state A to state B at constant energy from chemistry over biological life and engines to cosmic events. The connection of entropy to information, phase-space and heat is helpful, but does not immediately convince observers of the validity and basis of the second law. This gave grounds for finding a rigorous, but more easily acceptable reformulation. Here we show using statistical mechanics that this principle is equivalent to a force law ⟨⟨f⟩⟩> 0 in systems where mass centres and forces can be identified. The sign of this net force - the average mean force along a path from A to B - determines the direction of the process. The force law applies to a wide range of processes from machines to chemical reactions. The explanation of irreversibility by a driving force appears more plausible than the traditional formulation as it emphasizes the cause instead of the effect of motions.

The main regulatory factors during the adaptation of cancer cells to hypoxic stress are the hypoxia-inducible factors (HIFs), which are being increasingly recognized as an interesting and challenging target for the design of new chemotherapeutic molecules. HIF2A was found to have an large internal hydrophilic cavity within its PAS-B domain, unique to this sub-unit and is suggested to be a possible ligand-binding site. Regulation of HIF2A by cellular molecules is still greatly unknown. In This paper we have employed in-silico techniques, such as molecular docking and dynamic simulation, to design new direct inhibitors against HIF-2A subunit via targeting one of its critical domains and the final top screened molecules have been tested on hypoxic cancer cells for further validation of their inhibitory potential. we targeted the hydrophilic cavity inside the PAS-B domain of the HIF2A to identify novel molecules with a high binding capacity. Virtual Screening methodology was used for molecular docking of NSC library against the target domain inside the HIF2A PAS-B domain with the top 5% compounds with significant MolDock and Re-rank scores were selected for further analysis. The NSC 106416, NSC 217021, NSC 217026, and NSC 215639 compounds were selected based on their docking scores. NSC 215639 had the minimum polar solvation energy and also had a relative strong binding energy. NSC 217026 had the strongest binding energy among other compounds.

Most mature companies have started some kind of “transformation”, either digital, or agile transformations, to cope with changes in the environment, yet most fail, ending up delivering nothing or just one more reorganization. We postulate that considering the Organization as a self-aware Complex Adaptative System (CAS) is paramount, as the common conception (Industrial: mechanistic and predictive) results in bringing the systems in a frozen or defensive mode. Stimulating the system enables us to use its adaptative power to develop new capabilities, and all layers should be tackled simultaneously, to prevent the system from collapsing back into its original state. To ensure this, it is necessary to create a seed per level, and a mechanism to propagate the transformation, with a focus on development instead of growth, that is qualitative change rather than quantitative. A common vocabulary should also be provided, so conversations can occur at every level. Finally, changing mindsets is key, and both concepts and techniques should be provided as enablers to the adequate mindset level. We detail one such transformation that resulted in distributed leadership and more intrinsic motivation, providing both an account of the transformation itself and a model to read it.

Evaporation studies of water using classical molecular dynamics simulations are largely limited due to its high computational expense. We aim at addressing the computational issues by developing a coarse grain model for evaporation of water on solid surfaces by combining four water molecules into a single bead. Most commonly used mono atomic pair potentials like Lennard Jones, Morse, Mie and three body potential like Stillinger-Weber are optimized using a combination of Genetic algorithm and Nelder-Mead algorithm. Among them, Stillinger-Weber based model shows excellent agreement of density and Enthalpy of vaporization with experimental results for a wide range of temperatures. Further, the new water model is used to simulate contact angle of water and thin film evaporation from surfaces with different wettabilities.

Matrix Metaloproteinase-2 (MMP-2) is an extracellular Zn²⁺ protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal ions were characterized using a 1.0 µs molecular dynamics simulation. Dihedral principle component analysis revealed 10 families of conformations with the greatest degree of variability occurring in the link region connecting the catalytic and hemopexin domains. Dynamics cross correlation analysis indicated domain movements corresponding to opening and closing of the hemopexin domain in relation to the fibronectin and catalytic domains facilitated by the link region. Interaction energies were calculated using the MMPBSA-interaction entropy analysis method and revealed strong binding energies for the catalytic Zn²⁺ ion 1, Ca²⁺ ion 1, and Ca²⁺ ion 3 with significant conformational stability at the binding sites of Zn²⁺ ion 1 and Ca²⁺ ion 1. Ca²⁺ ion 2 diffuses freely away from its crystallographically defined binding site. Zn²⁺ ion 2 plays a minor role in conformational stability of the catalytic domain while Ca²⁺ ion 3 is strongly attracted to the highly electronegative sidechains of the Asp residues around the central β-sheet core of the hemopexin domain.

Modelling errors, robust stabilization/tracking problems under parameter and model uncertainties complicate the control of the flexible underactuated systems. Chattering-free sliding-mode based input-output control law realizes robustness against the structured and unstructured uncertainties in the system dynamics and avoids excitation of unmodeled dynamics. The main purpose is to propose a robust adaptive solution for stabilizing and tracking direct-drive (DD) flexible robot arms under parameter and model uncertainties, as well as external disturbances. A lightweight robot arm subject to external and internal dynamic effects was taken into consideration. The challenges are compensating actuator dynamics with the inverter switching effects and torque ripples, stabilizing the zero dynamics under parameter/model uncertainties and disturbances while precisely track the predefined reference position. The precise control of this kind of system demands an accurate system model and knowledge of all sources that excite unmodeled dynamics. For this purpose, equations of motion for a flexible robot arm were derived and formulated for the large motion via Lagrange’s method. The goals were determined to achieve high-speed, precise position control, and satisfied accuracy by compensating the unwanted torque ripple and friction that degrades performance through an adaptive robust control approach. The actuator dynamics and their effect on the torque output were investigated due to the transmitted torque to the load side. The high-performance goals, precision&robustness issues, and stability concerns were satisfied by using robust-adaptive input-output linearization-based control law combining chattering-free sliding mode control (SMC) while avoiding the excitation of unmodeled dynamics.

Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and a thereby be trafficked to specific locations. The description of curvature-sensing is another fundamental challenge. Curved lipid membranes and their interplay with membrane-associated proteins can be investigated with molecular dynamics (MD) simulations, given the right tools. Various methods for simulating curved membranes with MD are discussed here, including tools for setting up simulation of vesicles, and methods for sustaining membrane curvature. The latter are divided into methods that exploit scaffolding virtual beads, methods that use curvature-inducing molecules, and methods applying virtual forces. The variety of simulation tools allow the researcher to closely match the conditions of experimental studies of membrane curvatures.

Remanufacturing is a viable option to extend the useful life of an end-of-use product or its parts, ensuring sustainable competitive advantages under the current global economic climate. Challenges typical to remanufacturing still persist, despite its many benefits. According to the European Remanufacturing Network a key challenge is lack of accurate, timely and consistent product knowledge as highlighted in a 2015 survey of 188 European remanufacturers. With more data being produced by electric and hybrid vehicles, this adds to the information complexity challenge already experienced in remanufacturing. Therefore, it is difficult to implement real-time and accurate remanufacturing for the shop floor; there are no papers that focus on this within an electric and hybrid vehicle environment. To address this problem this paper attempts to (1) identify the required parameters/ variables needed for fuel cell remanufacturing by means of interviews (2) rank the variables by Pareto analysis (3) develop a casual loop diagram for the identified parameters/ variables to visualise its impact on remanufacturing (4) model a simple stock and flow diagram to simulate and understand data and information-driven schemes in remanufacturing.

Statistical mechanics investigates how emergent properties of macroscopic systems (such as temperature and pressure) relate to microscopic state fluctuations. The underlying idea is that global statistical descriptors of order and variability can monitor the relevant dynamics of the whole system at hand. Here we test the possibility of extending such an approach to psychotherapy research investigating the possibility of predicting the outcome of psychotherapy on the sole basis of coarse-grained empirical macro-parameters. Four good-outcome and four poor-outcome brief psychotherapies were recorded, and their transcripts coded in terms of standard psychological categories (abstract, positive emotional and negative emotional language pertaining to patient and therapist). Each patient-therapist interaction is considered as a discrete multivariate time series made of subsequent word-blocks of 150-word length, defined in terms of the above categories. Static analysis (Principal Component Analysis) highlighted a substantial difference between good-outcome and poor-outcome cases in terms of mutual correlations among those descriptors. In the former, the patient’s use of abstract language correlated with therapist’s emotional negative language, while in the latter it co-varied with therapist’s emotional positive language, thus showing the different judgment of the therapists regarding the same variable (abstract language) in poor and good outcome cases. On the other hand, the dynamic analysis, based on five coarse-grained descriptors related to variability, degree of order and complexity of the series, demonstrated a relevant case-specific effect, pointing to the possibility of deriving a consistent picture of any single psychotherapeutic process. Overall, the results showed that the systemic approach to psychotherapy (an old tenet of psychology) is mature to shift from a metaphorical to a fully quantitative status.

For condensed systems, the incorporation of quantum chemical solvent effects into molecular dynamics simulations has been a major concern. To this end, quantum mechanical/molecular mechanical (QM/MM) techniques are popular and powerful options to treat gigantic systems. However, they cannot be directly applied because of temporal and spatial discontinuity problems. To overcome these problems, in a previous study, we proposed a corrective QM/MM method, size-consistent multipartitioning (SCMP) QM/MM, and successfully demonstrated that, using SCMP, it is possible to perform stable molecular dynamics simulations by effectively taking into account solvent quantum chemical effects. The SCMP method is characterized by two original features: size-consistency of a QM region among all QM/MM partitioning and partitioning update. However, in our previous study, the performance was not fully elicited compared to the theoretical upper bound, and the optimal partitioning update protocol and parameters were not fully verified. To elicit the potential performance, in the present study, we simplified the theoretical framework and modified the partitioning protocol.

Modeling brain dynamics to better understand and control complex behaviors underlying various cognitive brain functions are of interests to engineers, mathematicians, and physicists from the last several decades. With a motivation of developing computationally efficient models of brain dynamics to use in designing control-theoretic neurostimulation strategies, we have developed a novel data-driven approach in a long short-term memory (LSTM) neural network architecture to predict the temporal dynamics of complex systems over an extended long time-horizon in future. In contrast to recent LSTM-based dynamical modeling approaches that make use of multi-layer perceptrons or linear combination layers as output layers, our architecture uses a single fully connected output layer and reversed-order sequence-to-sequence mapping to improve short time-horizon prediction accuracy and to make multi-timestep predictions of dynamical behaviors. We demonstrate the efficacy of our approach in reconstructing the regular spiking to bursting dynamics exhibited by an experimentally-validated 9-dimensional Hodgkin-Huxley model of hippocampal CA1 pyramidal neurons. Through simulations, we show that our LSTM neural network can predict the multi-time scale temporal dynamics underlying various spiking patterns with reasonable accuracy. Moreover, our results show that the predictions improve with increasing predictive time-horizon in the multi-timestep deep LSTM neural network.

The present study explores the effect of using two porous deflectors on the performance of the Savonius wind turbine compared to only one porous deflector. The numerical simulation is performed to solve the unsteady Navier-Stokes equations using the SST k-

The most cited evidence for (nonbaryonic) dark matter has been an apparent lack of visible mass to gravitationally support the observed orbital velocity of matters in rotating disk galaxies. Yet measurement of the mass of celestial objects cannot be straightforward, requiring theories derived from the known physical laws along with some empirically established semi-quantitative relationship. The most reliable means for determining the mass distribution in rotating disk galaxies is to solve a force balance equation according to Newton’s laws from measured rotation curves, similar to calculating the Sun’s mass from the Earth’s orbital velocity. Another common method to estimate galactic mass distribution is to convert measured brightness from surface photometry based on empirically established mass-to-light ratio. For convenience, most astronomers commonly assumed a constant mass-to-light ratio for estimation of the so-called “luminous” or “visible” mass, which should not be expected accurate. The mass determined from rotation curve typically exhibit an exponential-like decline with galactrocentric distance, qualitatively consistent with observed surface brightness. This fact scientifically suggests variable mass-to-light ratio of baryonic matter in galaxies without the need for dark matter.

This paper deals with the characteristics of the cyclone separator from the Lagrangian perspective to design important dependent variables, develops a neural network model for predicting the separation performance parameter, and compares the predictive performance between the traditional surrogate model and the neural network model. In order to design the important parameters of the cyclone separator based on the particle separation theory, the force acting until the particles are separated was calculated using the Lagrangian-based CFD methodology. As a result, it was proved that the centrifugal force and drag acting on the critical diameter having a separation efficiency of 50% were similar, and the particle separation phenomenon in the cyclone occurred from the critical diameter, and it was set as an important dependent variable. For developing a critical diameter prediction model based on machine learning and multiple regression methods, Unsteady-RANS analyzes according to shape dimensions were performed. The input design variables for predicting the critical diameter were selected as four geometry parameters that affect the turbulent flow inside the cyclone. As a result of comparing the model prediction performances, the ML model showed the 32.5 % of improvement rate of R2 compared to the traditional MLR considering the nonlinear relationship between the cyclone design variable and the critical diameter. The proposed techniques have proven to be fast and practical tools for cyclone design.

Abstract: Changes in forest landscapes have been connected with human activity for centuries, which can be considered as one of the main driving forces of change in the global perspective. The spatial distribution of forests changes along with the geopolitical situation, demographic changes, intensification of agriculture, urbanization or changes in the land use policy. However, due to the limited availability of historical data, the driving forces of changes in forest landscapes are most often considered in relation to recent decades, without taking into account long-term analyzes. The aim of this paper is to determine the impact of natural and socio-economic factors on changes in forest landscapes within the protected area – Ślęża Landscape Park and its buffer zone in the aspect of long-term analyzes covering the period of 140 years (1883-2013). The comparison of historical and current maps, demographic data on 4 different periods as well as natural and location factors by using the ArcGIS software allowed analyzing selected driving forces of forest landscape transformations. We took into account natural factors like altitude, slope, exposure of the hillside and socio-economic drivers like population changes, distances to centers of municipalities, main roads and built-up areas.

Soil-transmitted helminthiasis (STH), a neglected tropical disease (NTD) remains a major health problem all over the world including Ghana, which has STH prevalence of 25.4%. To control the disease, the government of Ghana currently concentrates on implementing mass drug administration (MDA) efforts focusing only among school-aged children. However, various studies have suggested that focusing on only a specific group for MDA may not be cost-effective. Moreover, some adults such as teachers and school-workers spend large fraction of their time with children, who shed more parasite in environment due to unhygienic behavior, and thus have a higher risk of getting infected as compared to other adults. In this study we use a mathematical model to evaluate age-structured and risk-based policies for implementing MDA while capturing transmission dynamics of STH in Ghana. A cost model was developed that included various costs related to MDA to study cost-effectiveness of current policies of MDA in Ghana against novel policies to control STH in Ghana. We carry out analysis for five different scenarios— I: no MDA (baseline), II: current MDA policy (focusing children) in Ghana, III: MDA for different age groups (adults and children groups) for unlimited budget, IV: MDA for different age groups with limitations of number of individuals treated, and, V: MDA for different groups based on their risk of getting infected (adults school workers (high-risk group), adults non-school workers and children groups). Our results suggest that it might be more cost-effective to allocate treatment through MDA to at least some proportion of adults along with children. In case of unlimited budget, the best strategy in Scenario IV would be to treat approximately 22% of adults and approximately 45% of children. The most cost-effective among the 5 scenarios is suggested through scenario V, where high-risk adults group and children are provided MDA at higher level than low-risk adults. In conclusion, age-structured and risk-based allocation of treatment and resources is crucial to reducing STH load in developing countries.

Utility perceived by individuals is believed to be different from the utility experienced by that individual. System dynamicists implicitly categorize this phenomenon as a form of bounded rationality and traditionally employ a simple smoothing function to capture it. We challenge this generalization by testing it against an alternative formulation of utility perception that is suggested by modern theories of behavioral economics. In particular, the traditional smoothing formulation is compared with the peak-end rule in a simple theoretical model as well as in a medium-size model of electronic health record implementation. Experimentation with the models reveals that the way utility perception is formulated is important and might affect behavior and policy implications of system dynamics models.

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL^-1 s^-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

It has been more than a year since the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found. This coronavirus has infected more than 110 million people worldwide by the end of February, 2021, and several virulent as well as more spreadable mutant forms of SARS-CoV-2 have emerged subsequently. In the latter group, three variants B.1.1.7, B.1.351, and P1 lineages, have been reported. Using computer simulation, the present paper investigates the structural differences between the wild type SARS-CoV-2 spike protein and its Asn501Tyr (N501Y) mutant variant. Time-based structural changes between the receptor binding domains of these two species are also examined. The N501Y mutation is common to all the three aforesaid mutant variants.

Recently, the properties of bouncing oil droplets, also known as `walkers', have attracted much attention because they are thought to offer a gateway to a better understanding of quantum behaviour. They indeed constitute a macroscopic realization of wave-particle duality, in the sense that their trajectories are guided by a self-generated surrounding wave. The aim of this paper is to try to describe walker phenomenology in terms of de Broglie-Bohm dynamics and of a stochastic version thereof. In particular, we first study how a stochastic modification of the de Broglie pilot-wave theory, à la Nelson, affects the process of relaxation to quantum equilibrium, and we prove an H-theorem for the relaxation to quantum equilibrium under Nelson-type dynamics. We then compare the onset of equilibrium in the stochastic and the de Broglie-Bohm approaches and we propose some simple experiments by which one can test the applicability of our theory to the context of bouncing oil droplets. Finally, we compare our theory to actual observations of walker behavior in a 2D harmonic potential well.

Land degradation a serious and nationwide environmental concern in Ethiopia. The problem is its iterative relationship between land degradation, climate change, and agriculture, exacerbating one another via negative and positive feedback loops. Due to the need for an efficient response to land degradation in the country, different sustainable land management practices have been implemented since the late 1980s. The objective of this study was to analyze land degradation neutrality status using remote sensing data in the study area. We have studied the land degradation neutrality conditions of the North Wello Zone by using indicators data, namely land cover change, land productivity dynamics, and soil organic carbon stock. The result shows that the settlement areas consistently expanded at the fifth speed (2010-2018) from 1995 to 2010. Between 1995 and 2010, forestland declined by 18 percent, while an increasing trend of 26.8 percent from 2010 to 2018. The assessment results also indicate that 52.8 percent of the total area is stable and characterized by less stressed land productivity. The soil organic carbon is comparatively abundant in the high and midland vegetation areas but very thin in lowland areas. Most of the highland and midland parts of the study areas are in the conditions of stable and increasing land productivity with high biomass and soil organic content. However, most lowland areas showed a decline in land productivity conditions.

Deformation flows are flows incorporating shear, strain and rotational components. These flows are ubiquitous in the geophysical flows, such as the ocean and atmosphere. They appear near almost any salience, such as isolated coherent structures (vortices and jets), various fixed obstacles (submerged obstacles, continental boundaries). Fluid structures subject to such deformation flows may exhibit drastic changes in motion. In this review paper, we focus on the motion of a small number of coherent vortices embedded in deformation flows. Problems involving isolated one and two vortices are addressed. When considering a single-vortex problem, the main focus is on the evolution of the vortex boundary and its influence on the passive scalar motion. Two vortex problems are addressed with the use of point vortex models, and the resulting stirring patterns of neighbouring scalars are studied by a combination of numerical and analytical methods from the dynamical system theory. Many dynamical effects are reviewed with emphasis on the emergence of chaotic motion of the vortex phase trajectories and the scalars in their immediate vicinity.

A general procedure is described, to generate material parameter sets to simulate fire propagation in horizontal cable tray installations. Cone Calorimeter test data is processed in an inverse modelling approach. Here, parameter sets are generated procedurally and serve as input for simulations conducted with the Fire Dynamics Simulator (FDS). The simulation responses are compared with the experimental data and ranked based on their fitness. The best fitness was found for a test condition of \SI{50}{\kilo\watt\per\meter^2}. Low flux conditions \SI{25}{\kilo\watt\per\meter^2} and less exhibited difficulties to be simulated accurately. As a validation step, the best parameter sets are then utilised to simulate fire propagation within a horizontal cable tray installation and are compared with experimental data. It is important to note, the inverse modelling process is focused on the Cone Calorimeter and not aware of the actual validation step. Despite this handicap, the general features in the fire development can be reproduced, however not exact. The fire in the tray simulation extinguishes earlier and the total energy release is slightly higher as compared to the experiment. The responses of the material parameter sets are briefly compared with a selection of state of the art procedures.

This contribution addresses dry sliding friction of a “Non-Asbestos Organic” friction material (pad) rubbed against a pearlitic grey cast iron disc. This configuration is commonly used in brakes in US, Europe and Asia. The initial stage of friction is of particular interest when addressing “creep-groan” phenomena occurring in passenger and sport utility vehicles with automatic transmissions. The custom built Universal Friction Tester allowing the variation of sliding speed, test temperature, normal load, stiffness and humidity of the system was used in this experiment in combination with surface analysis by polarized light microscopy, scanning electron microscopy and stylus profilometry. The obtained results indicate that the “stick” phase in the so-called “stick-slip” phenomenon does not really exist. The surfaces of pad and disc are in continuous relative movement. The complexity of surfaces does not allow for a definitive description of exact mechanisms responsible for the detected changes of friction forces. The observed friction process can be rather described as a stretching with possible localized relaxations causing the jerky behavior in the stretching phase, followed by slip between two materials in contact. Understanding of factors contributing to the stretching at different scale levels of friction system is necessary for development of proper models. An accurate friction model should also incorporate the vibrational element introduced by phenomena occurring at the friction surfaces. The absence of heterogeneous regions on the friction surface and “evenly distributed friction level” can help when mitigating creep-groan in the investigated brake system. Understanding of factors on different scales of friction is also required when developing the improved brakes.

Background: Selectively targeting dopamine receptors has been a persistent challenge in the last years for the development of new treatments to combat the large variety of diseases evolving these receptors. Although, several drugs have been successfully brought to market, the subtype-specific binding mode on a molecular basis has not been fully elucidated. Methods: Homology modeling and molecular dynamics were applied to construct robust conformational models of all dopamine receptor subtypes (D1-like and D2-like receptors). Fifteen structurally diverse ligands were docked to these models. Contacts at the binding pocket were fully described in order to reveal new structural findings responsible for DR sub-type specificity. Results: We showed that the number of conformations for a receptor:ligand complex was associated to unspecific interactions > 2.5 Å and hydrophobic contacts, while the decoys binding energy was influenced by specific electrostatic interactions. Known residues such as 3.32Asp, the serine microdomain and the aromatic microdomain were found interacting in a variety of modes (HB, SB, π-stacking). Purposed TM2-TM3-TM7 microdomain was found to form a hydrophobic network involving Orthosteric Binding Pocket (OBP) and Secondary Binding Pocket (SBP). T-stacking interactions revealed as especially relevant for some large ligands such as apomorphine, risperidone or aripiprazole. Conclusions: This in silico approach was successful in showing known receptor-ligand interactions as well as in determining unique combinations of interactions, key for the design of more specific ligands.

The novel coronavirus disease 19 (COVID-19) has resulted in an estimated 20 million excess deaths and the recent resurgence of COVID-19 in China is predicted to result in up to 1 million deaths over the next few months. With vaccines unable to halt transmission it is important to continue our quest for safe, effective, affordable drugs that will be available to all countries. Drug repurposing is one of the strategies being explored in this context. Recently, out of 7,817 approved drugs, 214 candidates were systematically down-selected using a combination of 11 filters including approval status, assay data against SARS-CoV-2, pharmacokinetic, pharmacodynamic and toxicity profiles. These drugs were subjected in this study to virtual screening against various targets of SARS-CoV-2 followed by molecular dynamic studies of the best scoring ligands against each target. The chosen molecular targets were Spike receptor binding domain, Nucleocapsid protein RNA binding domain, and key non-structural proteins 3, 5, 12, 13 and 14. Four drugs approved for other indications — alendronate, cromolyn, natamycin and treprostinil — look sufficiently promising from our in silicostudies to warrant further in vitro and in vivo investigations as appropriate to ascertain their extent of anti-viral activities.

Due to failure of the continuum hypothesis for higher Knudsen numbers, rarefied gases and microflows of gases are particularly difficult to model. Macroscopic transport equations compete with particle methods, such as DSMC to find accurate solutions in the rarefied gas regime. Due to growing interest in micro flow applications, such as micro fuel cells, it is important to model and understand evaporation in this flow regime. Here, evaporation boundary conditions for the R13 equations, which are macroscopic transport equations with applicability in the rarefied gas regime, are derived. The new equations utilize Onsager relations, linear relations between thermodynamic fluxes and forces, with constant coefficients, that need to be determined. For this, the boundary conditions are fitted to DSMC data and compared to other R13 boundary conditions from kinetic theory and Navier-Stokes-Fourier (NSF) solutions for two one-dimensional steady-state problems. Overall, the suggested fittings of the new phenomenological boundary conditions show better agreement to DSMC than the alternative kinetic theory evaporation boundary conditions for R13. Furthermore, the new evaporation boundary conditions for R13 are implemented in a code for the numerical solution of complex, two-dimensional geometries and compared to NSF solutions. Different flow patterns between R13 and NSF for higher Knudsen numbers are observed.

The work is devoted to the study of a MEMS resonator dynamics under the action of phase-locked and automatic gain control loops. Particular attention is directed to the study of the nonlinearity factor of the resonator elastic restoring force. It was found that the determination of control system parameters based on the stability analysis of the operating resonant mode, in the general case, does not provide the required phase adjustment and stabilization of the oscillation amplitude. Stable multifrequency modes of oscillations are found, an analytical study of the mechanisms of their appearance and evolution is carried out under variation of the key parameters of the system. The real regions of the control system stable operation are determined (which do not coincide, as was found, with the regions of stability of the operating resonant mode, due to the presence of hidden attractors in the phase space of the system). A methodology has been developed for identifying such areas of stable operation. A significant complication of the structure of possible motions in the system with an increase in the Q-factor of the resonator is revealed.

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

The natural products and conventional chemotherapeutic drugs are believed to increase the cure rates of anti-cancer treatment while reducing their toxicity. The current study investigates the cytotoxic and apoptogenic effects of bioactive compounds from Monotheca buxifolia on Hep G2 cell lines. The effect on the viability of Hep G2 cells was evaluated by MTT assay; Morphological changes were studied, the apoptotic activity was demonstrated through Annexin-V-FITC/ PI, a molecular dynamics simulation study was conducted to explore the binding pattern of the compounds in the active site of the PPRAδ protein. The isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells, as determined by MTT assay and annexin V-FITC/PI. The IC50 value for lauric acid was 56.4584 ± 1.20 µg/ml, that for oleanolic acid was 31.9421 ± 1.03 µg/ml, and that for bis(2-ethylhexyl) phthalate was 83.8019 ± 2.18 µg/ml. After 24 h of treatment, 29.5% of Hep G2 cells treated with lauric acid, 52.1% of those treated with oleanolic acid, and 22.4% of those treated with bis(2-ethylhexyl) phthalate were apoptotic. Morphological assay and Hoechst staining microscopy revealed the morphological alterations of cell membrane accompanied by nuclear condensation after treatment. The high fluctuation indicates the high potency and adopting various interactions, and vice versa, the oleanolic acid showed highly residues fluctuation, which remains stable in the active site of PPARδ protein and involved in various interactions while remaining locally fluctuated in the binding site the other two compounds. In conclusion, a significant apoptogenic effect was exhibited by lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate against HepG2 cells in inducing apoptosis. Our findings indicate that these bioactive compounds hold promise as potential therapeutic for hepatocellular carcinoma.

A bacterial strain that could effectively degrade DEHP was isolated from the activated sludge and identified as Bacillus sp. by DNA sequencing. The biochemical degradation pathway of DEHP was further analyzed by GC-MS, and the results showed that DEHP was first decomposed into phthalates (DBP). Diuretic sylycol (DEP) was then generated, and phthalates (PA) were generated by a continuous de-ehelateization reaction. Phthalic acid (PA) was oxidized, dehydrogenated, and decarboxylated into protocatechins. Protocatechins enter the TCA cycle through orthotopic ring opening.　To enhance DEHP degradation, sodium alginate and calcium chloride were used as embedding and cross-linking materials, and the strain was immobilized. The immobilization conditions were optimized via an orthogonal experiment, and the results showed that the optimal immobilization conditions were SA mass fraction of 4%, CaCl2 mass fraction of 5%, ratio of bacteria to SA of 1:1, and the crosslinking time of 6 hours. The immobilized bacteria agent was further applied to MBR systems. The results showed that the removal rate of DEHP (5mg/L) in the system by immobilized bacteria was 91.9%, which is significantly higher than that of free bacteria. The 3, 4-dioxygenase gene and microbial community dynamics were analyzed by q-PCR and Illumina Miseq sequencing. The q-PCR results showed that the number of copies of 3, 4-dioxygenase gene in the immobilized system was significantly higher than that of free bacteria. Illumina Miseq sequencing results showed that Micromonospora, Rhodococcus, Bacteroides and Pseudomonas were the dominant generas in the MBR system. The analysis of bacterial community structure indicated that immobilization technology had a positive impact on the system stability. The results implied that this immobilized technique had potential applications in DEHP wastewater treatment.

Culture exploits the acquisition of meaningful content by crafting regimes of shared attention, determining what is relevant, valuable, and salient. Culture changes the field of relevant social affordances worthy of being acted upon in a context-sensitive manner. When relevant affordances are highly weighted, their attentional capture and their salience increase the probability of them being enacted due to the associated expectation for minimizing prediction error. This process is known as active inference. In the digital era, individuals need to infer the action-related attributes of digital cues, here characterized as digital affordances. The digital affordances of digital social platforms are of particular interest here. Digital social affordances are defined as online possibilities of social interactions. By their own nature, these are salient because they are related to social interactions and relevant social cues. However, the problem of digital social platforms is that they are not equivalent to situated social interactions because their structure is built, mediated, and defined by third-parties with diverse interests. The third-parties behind the digital social platforms are using the same mechanism exploited by culture to manipulate the shared patterns of attention. Moreover, digital social platforms are deliberately designed to be hyper-stimulating, making digital social affordances highly rewarding and increasingly salient. This appropriation, for economic purposes, is an issue of great importance, especially as the COVID-19 pandemic brought deep global changes, pushing societies to an online digital way of life. Here, we examined different types of digital social affordances under an active inference view, placing them into two categories, those for self-identity formation, and those for belief-updating. This paper aims to analyze digital social affordances in light of the prediction error dynamics they might elicit to their users. Although each of the analyzed digital social affordances allows different epistemic and instrumental digital actions, they all share the characteristic of having an "easy" and a fast expected rate of error reduction. Here, we aim to provide a new hypothesis about how the design behind digital social affordances is built on our natural attractiveness to minimize prediction error and the resulting positive embodied feelings when doing so. Finally, it is suggested that because digital social affordances are becoming highly weighted in the field of affordances, this might be putting at risk our context-sensitive grip on a rich, dynamic and varied field of relevant affordances.

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

Most fully developed galaxies have vivid spiral structure, but the formation and evolution of spiral structure is still a mystery that is not fully understood in astrophysics. We find that the currently used equations of galactic dynamics contain some unreasonable components. In this paper, the following three working assumptions are introduced to simplify the galactic structural equations. 1. In the research of large-scale structure, the retarded potential of the gravitational field should be taken into account. The propagating time of the gravitational field from center to border is longer than the revolution periods of the stars near the center of galaxy. Newton's gravitational potential is unreasonable for such case, and the weak field and low velocity approximation of Einstein's field equation should be adopted. 2. The stars in a fully developed galaxy should be zero-pressure and inviscid fluid, and the equation of motion is different from that of ordinary continuum mechanics. Stars move along geodesics. 3. The structure of the galaxy is only related to the total mass density distribution. The equation of state of dark halo is different from that of ordinary luminous interstellar matter, so their trajectories are also very different. Dark halo and ordinary matter in galaxy are automatically separated. The total mass density distribution can be presupposed according to the observation data, and then it can be determined by comparing the solution of the equations with the observed data. These assumptions and treatments are supported by theory and observation. The variables of the equations of simplified galactic dynamics are separated from each other, and the equations are well-posed and can be solved according to a definite procedure. Therefore, this simplified dynamic equation system provides a more reasonable and practical framework for the further study of galactic structure, and can solve many practical problems. Besides, it is closely related to the study of dark energy and dark matter.

Persistent, non-explosive passive degassing is a common characteristic of active volcanoes. Distinct periodic components in measurable parameters of gas release have been widely identified over timescales ranging from seconds to months. The development and implementation of high temporal resolution gas measurement techniques now enables the robust quantification of high frequency processes operating on timescales comparable to those detectable in geophysical datasets. This review presents an overview of the current state of understanding regarding periodic volcanic degassing, and evaluates the methods available for detecting periodicity, e.g., autocorrelation, variations of the Fast Fourier Transform (FFT), and the continuous wavelet transform (CWT). Periodicities in volcanic degassing from published studies are summarised and statistically analysed, together with analyses of literature-derived datasets where periodicity had not previously been investigated. Finally, an overview of current knowledge on drivers of periodicity is presented and discussed in the framework of four main generating categories, including: (1) non-volcanic (e.g., atmospheric or tidally generated); (2) gas-driven, shallow conduit processes; (3) magma movement, intermediate to shallow storage zone; and (4) deep magmatic processes.

Background: Previous papers have developed a statistical mechanics of neocortical interactions (SMNI) fit to short-term memory and EEG data. Adaptive Simulated Annealing (ASA) has been developed to perform fits to such nonlinear stochastic systems. An N-dimensional path-integral algorithm for quantum systems, qPATHINT, has been developed from classical PATHINT. Both fold short-time propagators (distributions or wave functions) over long times. Previous papers applied qPATHINT to two systems, in neocortical interactions and financial options. Objective: In this paper the quantum path-integral for Calcium ions is used to derive a closed-form analytic solution at arbitrary time that is used to calculate interactions with classical-physics SMNI interactions among scales. Using fits of this SMNI model to EEG data, including these effects, will help determine if this is a reasonable approach. Method: Methods of mathematical-physics for optimization and for path integrals in classical and quantum spaces are used for this project. Studies using supercomputer resources tested various dimensions for their scaling limits. In this paper the quantum path-integral is used to derive a closed-form analytic solution at arbitrary time that is used to calculate interactions with classical-physics SMNI interactions among scales. Results: The mathematical-physics and computer parts of the study are successful, in that there is modest improvement of cost/objective functions used to fit EEG data using these models. Conclusions: This project points to directions for more detailed calculations using more EEG data and qPATHINT at each time slice to propagate quantum calcium waves, synchronized with PATHINT propagation of classical SMNI.

COVID-19 appeared as an infectious disease of global health emergency and the highest public health concern of 21st century for this world due to its high-speed of spread across the globe. The disease started as one single case to a cluster of cases in Wuhan, China (Dec 2019) and within few months with its continuous upsurge of cases spreading globally which has created enormous threat and tension across the global Public health care field. Most significantly to share the fact that, this disease caused high level of Risk Group mortality, high morbidity, health care services burden, panic anxiety, mental trauma and tension, social and economic insecurity, which also collectively surfaced by diverse range of social reaction and political pressure across the world. Also with the appearance of new and unknown pathogenesis of the disease has created the most and significant attention and concern for the scientific community and political leaders as well. The disease also varies much with its pattern of virus, sign, symptoms, characteristics including its epidemiological and public health response (like prevention strategy, diagnoses, case management, treatment pattern) across the countries. However, this variance is comparatively less rather even more in commonality while it comes to basic public health prevention interventions like frequent hand washing, wearing face mask, maintaining social/physical distancing (2 - 6 meter in between), individual isolation and community quarantine for suspected exposure and lockdown in community areas where cases are identified. These are with the most commonly practiced public health interventions to deal with this disease in majority of the epicenters across countries. Also with the progress of the disease with its diverse categorical appearance of sign symptoms which are uniquely portraying this disease is more of a kind of COVID-19 syndrome than as COVID-19. Moreover, various factors including socio economic status, health status, population dynamics, health system and infrastructure, health behavioral pattern, nutrition and food habit and access to information and knowledge made this viral disease one of the historically counted on expensive disease of the modern world to fight for. Specially to mention here, the case fatality rate distinctively vary with the population dynamics and the health system infrastructure and ability factors which have already created clear evidence as explained in this paper how these factors are uniquely distinguished and different from country to country. Apart from the contextual differences, the various kind of ongoing preventive measures (like prevention, diagnosis and treatment) learnt every day from the emerging characteristics and pattern of this viral disease which are most commonly practiced across countries with a variance. According to the Public health prevention practice and interventions, the total world is connected and learning from each other’s public health experiences to fight for the virus. However, the world communities are eagerly waiting to see the result and outcome of the ongoing therapeutics and vaccine trial initiated in several countries, the people of the world are quite optimistic and hopeful that, global scientific community will be able to invent some miraculous and magic solution in upcoming months which ultimately will free the world from this most terrifying COVID-19 pandemic of 21st century.

Tissue engineering has the potential for repairing large bone defects, which impose a heavy financial burden on the public health. However, difficulties with O₂ delivery to the cells residing in the interior of tissue engineering scaffolds make it challenging to grow artificial tissues of clinically-relevant sizes. This study uses image-based simulation in order to provide insight into how to better optimize the scaffold manufacturing parameters, and the culturing conditions, in order to resolve the O₂ bottleneck. To do this, high resolution 3D X-ray images of two common scaffold types (salt leached foam and non-woven fiber mesh) are fed into a Lattice Boltzmann Method fluid dynamics and reactive Lagrangian Scalar Tracking mass transfer solvers. The obtained findings indicate that the scaffolds should have maximal surface area-to-solid volume ratios, for higher chances of the molecular collisions with the cells. Furthermore, the cell culture media should be flown through the scaffold pores as fast as practically possible (without detaching or killing the cells). Finally, we have provided a parametric sweep that maps how the molecular transport within the scaffolds is affected by variations in rates of O₂ consumption by the cells. Ultimately, the results of this study are expected to benefit the computer-assisted design of tissue engineering scaffolds and culturing experiments.

In this review we summarize the recent development in understanding the role of PIP2 in cellular function and signaling. We first discuss the effect of PIP2 on actin binding proteins addressing the mechanism of the actin cytoskeletal dynamics such as polymerization or depolymerization of the filamentous network or the coupling to membrane to generate forces. Next, we outline the role of PIP2 in membrane dynamics. We summarized how the membrane organization depends upon PIP2 in the presence of ions or transmembrane proteins that are sensitive to membrane curvature. We discuss how clathrin coated pits interact with adaptor proteins during the endocytosis process, which is facilitated by PIP2. Finally, we discuss the role of PIP2 in cell signaling and diseases.

This study delves into the dynamic intersection of artificial intelligence (AI) and English Language Teaching (ELT) within the post-pandemic educational landscape. Grounded in Constructivism, Connectivism, and Technological Pedagogical Content Knowledge (TPACK), this research explores how AI integration impacts language instruction efficiency, benefits and challenges perceived by St. Michael's College students, differences in learning outcomes, and its potential to address the digital divide. Employing a qualitative approach, the study employs a rigorous method that includes intensive in-depth reviews of literature, maximum purposeful sampling, informal interviews, observation, and thematic analysis. Through these methods, data was collected from 30 participants, leading to the identification of five key themes. Findings suggest that AI enhances instructional efficiency, offers personalized learning experiences, and bridges gaps in remote settings. However, challenges and the importance of pedagogical balance emerged. The study underscores the need for adaptive pedagogical strategies to fully harness AI's potential. Future directions and limitations are discussed, emphasizing the study's implications for shaping the future of ELT.

Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.

There must exist a reformulation of quantum field theory, even at low energies, which does not depend on classical time. The octonionic theory proposes such a reformulation, leading to a pre-quantum pre-spacetime theory. The ingredients for constructing such a theory, which is also a unification of the standard model with gravitation, are : (i) the pre-quantum theory of trace dynamics – a matrix-valued Lagrangian dynamics, (ii) the spectral action principle of non-commutative geometry, (iii) the number system known as the octonions, for constructing a non-commutative manifold and for defining elementary particles via Clifford algebras, (iv) a Lagrangian with $E_8 \times E_8$ symmetry. The split bioctonions define a sixteen dimensional space (with left-right symmetry) whose geometry (evolving in Connes time) relates to the four known fundamental forces, while predicting two new forces, $SU(3)_{grav}$ and $U(1)_{grav}$. This latter interaction is possibly the theoretical origin of MOND. Coupling constants of the standard model result from left-right symmetry breaking, and their values are theoretically determined by the characteristic equation of the exceptional Jordan algebra of the octonions. The quantum-to-classical transition, precipitated by the entanglement of a critical number of fermions, is responsible for the emergence of classical spacetime, and also for the familiar formulation of quantum theory on a spacetime background.

The creation of computer models is often driven by the need to make predictions in regions where there is no data (i.e. extrapolations). This makes validation challenging as it is difficult to ensure that a model will be suitable when it is applied in a region where there are no observations of the system of interest. The current paper proposes a method that can reveal flaws in a model which may be difficult to identify using traditional approaches for model calibration and validation. The method specifically targets the situation where one is attempting to model a dynamical system that is believed to possess time-invariant calibration parameters. The proposed approach allows these parameters to vary with time, even though it is believed that they are time-invariant. The of such an analysis is to identify key discrepancies - indications that a model has inherent flaws and, as a result, should not be used to influence decisions in regions where there is no data. The proposed method isn't necessarily a predictor of extrapolation performance, rather, it is a stringent test that, the authors believe, should be applied before extrapolation is attempted. The approach could therefore form a useful part of wider validation frameworks in the future.

The fundamental question in the field of sensor research is new directions of scientific fields, which play a vital role in the progress of science and technology. This study confronts this question here by developing a bibliometric analysis, which endeavors to explain the evolution of sensor research and new technologies that are critical to science and society. The database of Scopus concerning scientific documents and patents is used for statistical and computational analyses in these topics. Results suggest that emerging technological trajectories in sensors are wireless sensor networks, wearable sensors and biosensors. Main characteristics of these growing research fields and technologies in sensors are described for fruitful implications of research and innovation policy directed to science advances and technological change in society.

In a thin-volume photobioreactor where a concentrated suspension of microalgae is circulated throughout the established spatial irradiance gradient, microalgal cells experience a time-variable irradiance. Deploying this feature is the most convenient way of obtaining the so-called “flashing light” effect, improving biomass production in high irradiance. This work investigates the light flashing features of sloping wavy photobioreactors, a recently proposed type, by introducing and validating a Computational Fluid Dynamics model. Two characteristic flow zones (straight top-bottom stream and local recirculation stream), both effective toward light flashing, have been found and characterised: a recirculation-induced frequency of 3.7 Hz and straight flow-induced frequency of 5.6 Hz were estimated. If the channel slope is increased, the recirculation area becomes less stable while the recirculation frequency is nearly constant with flow rate. The validated CFD model is a mighty tool that could be reliably used to further increase the flashing frequency by optimising the design, the dimensions, the installation and the operational parameters of the sloping wavy photobioreactor.

A new formulation for a proposed solution to the 3D Navier-Stokes Equations in cylindrical co-ordinates coupled to the continuity and level set convection equation is presented in terms of an additive solution of the three principle directions in the radial, azimuthal and z directions of flow and a connection between the level set function and composite velocity vector for the additive solution is shown. For the case of a vertical tube configuration with small inclination angle, results are obtained for the level set function defining the interface in both the radial and azimuthal directions. It is found that the curvature dependent part of the problem alone induces sinusoidal azimuthal interfacial waves wheras when the curvature together with the equation for the composite velocity is considered oscillating radial interfacial waves occur. The implications of two extremes indicate the importance of looking at the full equations including curvature.

In this research, the computational fluid dynamic (CFD) approach that has been used in wind power generation field was applied for the solution of the problems of local strong wind areas in railway fields, and the mechanism of wind generation was discussed. At the same time, the affectivity of the application of computational fluid dynamic approach to railway field was discussed. The problem of local wind that occurs on the railway line in winter was taken up in this research. A computational simulation for the prediction of wind conditions by LES was implemented and it was clarified that the local strong wind area is mainly caused by separated flows originating from the small‐scale terrain positioned at its upstream (at approximately 180.0 m above sea level). Meanwhile, the effects of the size of calculation area and spatial grid resolution on the result of calculation and the effect of atmospheric stability were also discussed. It was clarified that when the air flow characteristic of the separated flow originating from the small‐scale terrain (at altitude of approximately 180.0 m) targeted in this research is reproduced at high accuracy by computational simulation of wind conditions, approximately 10.0 m of spatial resolution of computational grid in horizontal direction is required. As a result of the computational simulation of wind conditions of stably stratified flow (Fr = 1.0), lee waves were excited at the downstream of the terrain over time. As a result, the reverse‐flow region lying behind the terrain that had been observed at a neutral time was inhibited. Consequently, local strong wind area was generated at the downstream of the terrain and the strong wind area passing through the observation mast was observed. By investigating the speed increasing rate of local strong wind area induced at the time of stable stratification, it was found that the wind was approximately 1.2 times stronger than what was generated at a neutral time.

The aim of this paper is to expose the main involved physical phenomena underlying the alteration of convective heat transfer in a heat exchanger subjected to imposed vibrations. This technique seems to have interesting features and industrial applications, such as efficiency increase, heat transfer rate control and cleanliness action. However, a clear description and comprehension of how vibrations may alter the convective heat transfer coefficient in a heat exchanger is no still reached due to the complexity of the involved physical mechanisms. For this reason, after a presentation and a schematisation of the analyzed thermodynamic system, the fundamental alterations of the thermo-fluid dynamics fields are described. Then, the main involved physical phenomena are exposed for the three cases of gaseous, monophasic liquid and boiling liquid mediums. Finally, on the basis of the characteristics of these described phenomena, some considerations and indications of general validity are presented.

The combination of artificial intelligence algorithms and numerical methods has recently become popular in the prediction of macroscopic and microscopic hydrodynamics parameters of bubble column reactors. The multi inputs and outputs machine learning can cover small phase interactions or large fluid behavior in industrial domains. This numerical combination can develop the smart multiphase bubble column reactor with the ability of low-cost computational time. It can also decrease case studies for the optimization process when big data is appropriately used during learning. There are still many model parameters that need to be optimized for a very accurate artificial algorithm, including data processing and initialization, the combination of inputs and outputs, number of inputs and model tuning parameters. For this study, we aim to train four inputs big data during learning process by an adaptive neuro-fuzzy inference system or adaptive-network-based fuzzy inference system (ANFIS) method, and we consider the superficial gas velocity as one of the input variables, while for the first time, one of the computational fluid dynamics (CFD) outputs named gas velocity is used as an output of the artificial algorithm. The results show that the increasing number of input variables improves the intelligence of the ANFIS method up to , and the number of rules during learning process has a significant effect on the accuracy of this type of modeling. The results also show that propper selection of model parameters results in more accuracy in prediction of the flow characteristics in the column structure.

Arterial hypertension is a health problem that affects millions of people around the world. Particularly in Chile, according to the last health survey in 2019, 28.7% of the population had this condition, and arterial hypertension complications cause one in three deaths per year. In this work, we have used molecular simulation tools to evaluate new compounds designed in silico by our group as possible anti-hypertensive agents, taking Neutral Endopeptidase (NEP) as a target, a key enzyme in the arterial hypertension regulation at the level kidney. We use docking experiments, molecular dynamics simulation, free energy decomposition calculations (by MM-PBSA method), and ligand efficiency analysis to identify the best anti-hypertensive agent pharmacokinetic and toxicological predictions (ADME-Tox). The energetic components that contribute to the complexes stability are the electrostatic and Van der Waals components; however, when the ADME-Tox properties were analyzed, we conclude that the best anti-hypertensive candidate agents are Lig783 and Lig3444, taking Neutra Endopeptidase as a target.

2-Hydroxypropyl-β-cyclodextrin (HPβCD) has unique properties to enhance the stability and the solubility of low water-soluble compounds by inclusion complexation. Understanding of the structural properties of HPβCD and its derivatives based on the number of 2-hydroxypropyl (HP) substituents at the a-D-glucopyranose subunits is rather important. In this work, replica exchange molecular dynamics simulations were performed to investigate the conformational changes of single- and double-sided HP-substitution called as 6-HPβCDs and 2,6-HPβCDs, respectively. The results show that glucose subunits in both 6-HPβCDs and 2,6-HPβCDs have lower chance to flip than in βCD. Also, HP groups are occasionally blocking the hydrophobic cavity of HPβCDs, thus hindering the drug inclusion. We found that HPβCDs with high number of HP-substitutions are more likely to be blocked, while HPβCDs with double-sided HP-substitution are even more probable to be blocked. Overall, 6-HPβCDs with three and four HP-substitutions are highlighted as the most suitable structures for guest encapsulation based on our conformational analyses such as structural distortion, radius of gyration, circularity and cavity self-closure of the HPβCDs.

We quantitatively investigated the statistical behaviors of semiflexible polymer chains, which are simultaneously subjected to force stretching and rectangular tube confinement. Based on the wormlike chain model and Odijk deflection theory, we derived a new deflection length, by which new compact formulas are obtained for the confinement free energy and force-confinement-extension relation. These newly derived formulas have been justified by numerical solutions of an eigenvalue problem associated with the Fokker-Planck governing equation and extensive Brownian dynamics simulations based on the so-called Generalized Bead-Rod (GBR) model. We found that, comparing to the classical deflection theory, these new formulas are valid for a much extended range of the confinement-size /persistence-length ratio, and have no adjustable fitting parameters for sufficient long semiflexible chains in the whole deflection regime.

This study examines the geopolitical dynamics of water conflicts in Central Asia, with a specific focus on Uzbekistan and its neighbors. Drawing upon a mixed methods approach within the framework of political geography, the research investigates the interactions among regional nations and the implications of population growth, agricultural industrialization, and economic competition, which heavily rely on shared irrigation systems and watersheds. The study establishes clear research objectives aimed at evaluating the water crisis in the region, addressing challenges in water management, and analyzing contentious issues. By uncovering historical and contemporary factors influencing water conflicts, regional power dynamics, and the complexities of water governance, the study highlights the potential for conflict, regional instability, and disruptions to peace resulting from population growth and economic competition within shared watersheds. The study concludes by providing recommendations to enhance regional cooperation, promote sustainable water management, and foster peacebuilding efforts. These recommendations draw on “soft power theory” and advocate for collaborative approaches. The findings of this research offer valuable insights for policymakers, researchers, and stakeholders involved in water management and regional cooperation amid evolving geopolitical challenges. By contributing to informed decision-making and promoting strategies for sustainable development in the region, this study aims to support efforts toward effective water resource management and long-term stability in Central Asia. The implications of this research extend beyond the immediate region, serving as a reference for other areas facing similar water-related conflicts and providing a foundation for future studies in the field of geography.

Complex colloidal fluids, depending on particulates’ shapes and packing fractions, may have a wide range of shear thinning and thickening behaviors. A particular interesting way to transition between different types of such behavior is by infusing functional complex particles that can be manufactured using modern techicques such as 3D printing. In this paper, we display 2D molecular dynamics simulations of such fluids with infused star-shaped functional particles, with variable leg length and number of legs, as they are infused in a non-interacting, coarse-grained fluid. We vary the packing fraction (ϕ) of the system, and for each different system we apply shear with various strain rate that turns the fluid into a jammed state and rise the apparent viscosity of fluid. We demonstrate the dependence of viscosity with the particles’ packing fraction. We show the role of shape and design dependence of the functional particles towards the transition to a shear thickening fluid .

Mitochondria are highly dynamic organelles that continuously change their shape. Their main function is ATP production; however, they are additionally involved in a variety of cellular phenomena, such as apoptosis, cell cycle, proliferation, differentiation, reprogramming, and aging. The change in mitochondrial morphology is closely related to the functionality of mitochondria. Normal mitochondrial dynamics are critical for cellular function, embryonic development, and tissue formation. Thus, defect in proteins involved in mitochondrial dynamics that control mitochondrial fusion and fission can affect cellular differentiation, proliferation, cellular reprogramming, and aging. Here we review the processes and proteins involved in mitochondrial dynamics and its various associated cellular phenomena.