Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. 5 to 10% of recovered patients in Wuhan test positive again; this suggest that for controlling COVID-19, vaccines may be better option than drugs. A clinical trial to evaluate an anti-COVID-19 vaccine has started recently. However, its efficacy and potency have to be evaluated and validated. As an alternative, we are presenting a first-of-its-kind, designed multi-peptide subunit based epitope vaccine against COVID-19. The vaccine construct comprise an adjuvant, CTL, HTL, and B-cell epitopes joined by linkers. The vaccine is non-toxic, non-allergenic, thermostable and immunogenic with the capability to elicit a humoral and cell-mediated immune response. The findings are validated with high-end computation-based methods. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as public health priority.

The use of unmanned aerial vehicle (UAV) during emergency response of a disaster has been widespread in recent years and the terrain images captured by the cameras on board these vehicles are significant sources of information for such disaster monitoring operations. Thus, analyzing such images are important for assessing the terrain of interest during such emergency response operations. Further, these UAVs are mainly used in disaster monitoring systems for the automated deployment of sensor nodes in real time. Therefore, deploying and localizing the wireless sensor nodes optimally, only in the regions of interest that are identified by segmenting the images captured by UAVs, hold paramount significance thereby effecting their performance. In this paper, the highly effective nature-inspired Plant Growth Simulation Algorithm (PGSA) has been applied for the segmentation of such terrestrial images and also for the localization of the deployed sensor nodes. The problem is formulated as a multi-dimensional optimization problem and PGSA has been used to solve it. Furthermore, the proposed method has been compared to other existing evolutionary methods and simulation results show that PGSA gives better performance with respect to both speed and accuracy unlike other techniques in literature.

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic affecting approximately 490,000 people and accounting for more than 22,000 deaths and has no generally acceptable cure. Here, the recently resolved 3D structure of SARS-CoV-2 receptor binding domain (RBD) in complex with its receptor-the angiotensin converting enzyme-2 (ACE-2) have provided the basis for screening chemical database for novel entry inhibitors. Methods: Molecular docking protocols have been used to rapidly screen FDA database for high affinity interaction at the SARS-CoV-2-RBD/ACE-2 interface. One of the top candidates, ubrogepant has been selected and further studied using atomistic molecular dynamics simulation method. Results: Molecular docking result showed that ubrogepant (UBR) and darunavir have binding energies of -10.4 kcal/mol. MMPBSA free energy analyses of UBR bound to RBD, ACE-2 and RBD/ACE-2 revealed RBD/ACE-2 > ACE-2 > RBD preference. Network analysis showed that interaction captured in the crystal structure were disrupted in UBR-bound state, hydration of the interface and increased atomic fluctuation within the RBD oligomerization interface and ACE-2 zinc binding site. Conclusions: The ability of ubrogepant to rupture the interaction at the RBD/ACE-2 interface residues of SARS-CoV-2 RBD/ACE-2 complex may result in loss of protein function with direct implication on oligomerization formation in RBD and loss of function in ACE-2 thus, making binding, cellular receptor recognition impossible. General Significance: Ubrogepant represents a new therapeutic candidate in the fight against COVID-19, as it binds with relatively high affinity with free RBD, ACE-2 receptor and SARS-CoV-2 RBD/ACE-2 complex based on binding affinity calculations.

Process simulation represents an important tool for plant design and optimisation, either applied to well established or to newly developed processes. Suitable thermodynamic packages should be selected in order to properly describe the behaviour of reactors and unit operations and to precisely define phase equilibria. Moreover, a detailed and representative kinetic scheme should be available to predict correctly the dependence of the process on its main variables. This review points out some models and methods for kinetic analysis specifically applied to the simulation of catalytic processes, as a basis for process design and optimisation. Attention is paid also to microkinetic modelling and to the methods based on first principles, to elucidate mechanisms and calculate thermodynamic and kinetic parameters. Different case histories support the discussion. At first, we have selected two basic examples from the industrial chemistry practice, e.g. ammonia and methanol synthesis, which may be described through a relatively simple reaction pathway. Then, a more complex reaction network is deeply discussed to define the conversion of bioethanol into syngas/hydrogen or into building blocks, such as ethylene.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

Gas and power networks are tightly coupled and interact with each other due to physically interconnected facilities. In an integrated gas and power network, a contingency observed in one system may cause iterative cascading failures, resulting in network wide disruptions. Therefore, understanding the impacts of the interactions in both systems is crucial for governments, system operators, regulators and operational planners, particularly, to ensure security of supply for the overall energy system. Although simulation has been widely used in the assessment of gas systems as well as power systems, there is a significant gap in simulation models that are able to address the coupling of both systems. In this paper, a simulation framework that models and simulates the gas and power network in an integrated manner is proposed. The framework consist of a transient model for the gas system and a steady state model for the power system based on AC-Optimal Power Flow. The gas and power system model are coupled through an interface which uses the coupling equations to establish the data exchange and coordination between the individual models. The bidirectional interlink between both systems considered in this studies are the fuel gas offtake of gas fired power plants for power generation and the power supply to LNG terminals and electric drivers installed in gas compressor stations and underground gas storage facilities. The simulation framework is implemented into an innovative simulation tool named SAInt (Scenario Analysis Interface for Energy Systems) and the capabilities of the tool are demonstrated by performing a contingency analysis for a real world example. Results indicate how a disruption triggered in one system propagates to the other system and affects the operation of critical facilities. In addition, the studies show the importance of using transient gas models for security of supply studies instead of successions of steady state models, where the time evolution of the line pack is not captured correctly.

In this work, we'll present the power spectra density, auto-correlation function, dentrended fluctuation analysis and multifractal spectrum are performed to the daily light curves of Blazars monitored by Fermi LAT. Some signs of power law are found.

Blazars show rapid and high amplitude variability. In this work , Fermi daily light curve of 130 sources are analyzed, distribution of daily variability are compared with each other by using Kolmogorov-Smirnov (K-S) test. results show: 1)Some pairs of the distributions are similar; 2) In most cases, the distributions are not Gaussian.

Urban rail transit hub platform is the most important area for passenger flow distribution. In order to calculate passenger flow volume in platform and evaluate platform service level during rush hours, this paper presents a method for modeling and simulation of passenger flow distribution in platform. Passenger flow distribution model (PFDM) is proposed based on the basic analysis and the superposition principle of passenger flow. Simulation design for PFDM is proposed by Anylogic, which contains simulation process and simulation model. Experiment results show that PFDM and simulation design are effective and accordant with the reality scenario, and the simulation precision is comparatively ideal. This research could provide a beneficial reference for train scheduling and operation management under the viewpoint of traffic safety and service level.

Industries, which are mainly responsible for high energy consumptions, need to invest in research projects in order to develop new managing systems for rational energy use and to tackle the devastating effects of climate change caused by human behavior. The study reported in this paper concerns the forging industry, where the production processes generally start with the heating of the steel in furnaces and continue with other processes, such as heat treatments and mechanical machining. One of the most critical operations, in terms of energy loss, is the opening of the furnace doors for the insertion and extraction operations. During this time, the temperature of the furnaces decreases by hundreds of degrees in a few minutes. Because the dispersed heat needs to be supplied again through the combustion of fuel, increasing the consumption of energy and the pollutant emissions, the evaluation of the amount of the lost energy is crucial for the development of operating or mechanical systems able to contain this dispersion. To perform this study, CFD simulation software was used. Results show that at the door opening, because of temperature and pressure differences between the furnace and the ambient, turbulences are generated. Results also show that the amount of energy lost for an opening of 10 minutes for radiation, convection and conduction is equal to 5606 MJ where convection is the main contributor with 5020 MJ. The model created, after being validated, has been applied to perform other simulations in order to improve the energy performance of the furnace. Results show that a reduction of the opening time of the door allows energy savings and limits pollutant emissions.

In this paper we report a new development on the numerical model for aluminum-steam combustion. This model is based on diffusion flame of continuum regime and the thermal equilibrium between the particle and the flow field, which can be used to calculate the aluminum particle combustion model for two phase calculation conditions. The model prediction is in good agreement with the experimental data. A new type of vortex combustor was proposed for the combustion of aluminum and steam, and the mathematical model of the two phase reacting flow with in this combustor was established. The turbulence effects are modeled using the Reynolds Stress Model (RSM) with Linear Pressure-Strain approach, and the Eddy-Dissipation model is used to simulate the gas phase combustion. Aluminum particles are injected into the vortex combustor and form a swirling flow around the chamber and their trajectories are traced using the Discrete Phase Model (DPM). The simulation results show that the vortex combustor can achieve high efficient combustion of aluminum and steam. The influencing factors, such as the eccentric distance of the inlet of aluminum particles, particle size and steam inlet diameter, etc., are studied. The work described in this paper represents an attempt to the design of a vortex combustor in order to increase aluminum combustion efficiency.

In the present paper, laminar forced convection nanofluid flows in a uniformly heated horizontal tube were revisited by direct numerical simulations. Single and two-phase models were employed with constant and temperature-dependent properties. Comparisons with experimental data showed that the mixture model performs better than the single-phase model in the all cases studied. Temperature-dependent fluid properties also resulted in a better prediction of the thermal field. A particular attention was paid to the grid arrangement. The two-phase model was used then confidently to investigate the influence of the nanoparticle size on the heat and fluid flow with a particular emphasis on the sedimentation process. Four nanoparticle diameters were considered: 10, 42, 100 and 200 nm for both copper-water and alumina/water nanofluids. For the largest diameter dnp = 200 nm, the Cu nanoparticles were more sedimented by around 80 %, while the Al₂O₃ nanoparticles sedimented only by 2.5 %. Besides, it was found that increasing the Reynolds number improved the heat transfer rate, while it decreased the friction factor allowing the nanoparticles to stay more dispersed in the base fluid. The effect of nanoparticle type on the heat transfer coefficient was also investigated for six different water-based nanofluids. Results showed that the Cu-water nanofluid achieved the highest heat transfer coefficient, followed by C, Al₂O₃, CuO, TiO₂, and SiO₂, respectively. All results were presented and discussed for four different values of the concentration in nanoparticles, namely φ = 0, 0.6, 1 and 1.6%. Empirical correlations for the friction coefficient and the average Nusselt number were also provided summarizing all the presented results.

The total enthalpies of the 16 different spin configurations that can be realized in the unit cell of the archetype spin crossover complex [Fe(phen)₂(NCS)₂] (phen=1,2-phenanthroline) were calculated applying periodic density functional theory combined with the Hubbard model and the Grimme-D2 dispersion correction (DFT+U/D2). The obtained enthalpy differences between the individual spin configurations were used to determine spin couplings of an Ising-like model and subsequent Monte Carlo simulations for this model allowed to estimate the phenomenological interaction parameter Г of the Slichter-Drickamer model, which is commonly used to describe the cooperativity of the spin transition. The calculational procedure described here, which led to an estimate of about 3 kJ/mol⁻¹ for Г, in good agreement with experiment, may be used to predict from first principles how modifications of spin crossover complexes can change the character of the spin transition from gradual to abrupt and vice versa.

We present observations from evaluation of internal environmental quality of industrial halls with priority on daylighting in combination with the integral lighting. The physical parameters related to indoor lighting in large industrial halls in winter and summer periods were analyzed using in situ measurements and computational methods. These are part of a comprehensive research on indoor environmental quality of industrial halls with the aims of saving energy and providing a comfortable environment for the workers while improving the productivity. The results showed that the procedures used for evaluation of residential or office buildings may not be used for industrial buildings. We also observed that the criteria of occupants’ comforts for indoor industrial buildings may differ from those of other kinds of buildings. Based on these results, an adequate attention is required for designing the industrial buildings. For this reason, appropriate evaluation methods and criteria should be created. We found the measured values of daylight factor very close to the skylight component of the total illumination. The skylight component was observed on average 30% that of the measured daylight factor values. Although the daylight is not emphasized when designing the industrial buildings and its contribution is small, but it is very important for the workers psychology and physiology. The workers must feel a connection with the exterior environment; otherwise, their productivity decreases.

In this paper we introduce a computational model for the simulation of hypervelocity impact (HVI) phenomena which is based on the Discrete Element Method (DEM). Our paper constitutes the first application of DEM to the modeling and simulating of impact events for velocities beyond 5 kms⁻¹. We present here the results of a systematic numerical study on HVI of solids. For modeling the solids, we use discrete spherical particles that interact with each other via potentials. In our numerical investigations we are particularly interested in the dynamics of material fragmentation upon impact. We model a typical HVI experiment configuration where a sphere strikes a thin plate and investigate the properties of the resulting debris cloud. We provide a quantitative computational analysis of the resulting debris cloud caused by impact and a comprehensive parameter study by varying key parameters of our model. We compare our findings from the simulations with recent HVI experiments performed at our institute. Our findings are that the DEM method leads to very stable, energy–conserving simulations of HVI scenarios that map the experimental setup where a sphere strikes a thin plate at hypervelocity speed. Our chosen interaction model works particularly well in the velocity range where the local stresses caused by impact shock waves markedly exceed the ultimate material strength.

Considering the need to reduce greenhouse gas emissions, onshore wind energy is certain to play a major role in future energy systems. This topic has received significant attention from the research community, producing many estimations of Europe's onshore wind potential for capacity and generation. Despite this focus, previous estimates have relied on distribution assumptions and simulation schemes that summarily under predict both the amount of available future wind capacity as well as its performance. Foremost in this regard is the common use of contemporary, or at least near-future, turbine designs which are not fitting for a far-future context. To fulfill this role, an improved, transparent, and fully reproducible work flow is presented for determining European onshore wind potential. Within a scenario of turbine cost and design in 2050, 13.5 TWof capacity is found to be available, allowing for 34.4 PWh of generation. By sorting the explicitly-placed potential generation locations by their expected generation cost, national relations between turbine cost and performance versus a desired capacity are exposed. In this way, it is shown that all countries possess some potential for onshore wind energy generation below 4 €_ct kWh^-1. and, furthermore, that it is unlikely for these costs to exceed 6 €_ct kWh^-1.

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.

The difficult current environmental situation, caused by construction industry residues containing ceramic materials could be improved by using these materials as recycled aggregates in mortars, with their processing causing a reduction in their use in landfill, contributing to recycling and also minimizing the consumption of virgin materials. Although some research is currently being carried out into recycled mortars, little is known about their stress-strain (σ-ε); therefore this work will provide the experimental results obtained from recycled mortars with recycled ceramic aggregates (with contents of 0, 10, 20, 30, 50 and 100%), such as: the density, the compression strength, as well as the σ-ε curves representative of their behavior. The values obtained from the analysis process of the results are those of: σ (elastic ranges and failure maximum), ε (elastic ranges and failure maximum), and Resilience and Toughness; in order to finally obtain, through numerical analysis, the equations to predict their behavior (related to their recycled content). At the end of the investigation it is established that mortars with recycled ceramic aggregate contents of up to 20% could be assimilated just like mortars with the usual aggregates, and the prediction equations produced could be used in cases of similar applications.

The expansion of renewable energies is progressing strongly. The influence on the power supply networks by the volatility of the infeed must be met with new concepts. In this paper we investigate the possibilities of integrating microgrids as a cooperating unit in the power supply network to support further expansion of RES power plants. In this paper a differentiation of microgrids from similar network structures is established, a classification of proposed groups is made. Then, after the description of simulation of components in a microgrid, with practical advice, an example model is shown, which aids the dimensioning of the components within a microgrid to achieve a specified goal.

The paper presents the design and the implementation of different advanced control strategies that are applied to a nonlinear model of a thermal unit. A data–driven grey–box identification approach provided the physically meaningful nonlinear continuous–time model, which represents the benchmark exploited in this work. The control problem of this thermal unit is important since it constitutes the key element of passive air conditioning systems. The advanced control schemes analysed in this paper are used to regulate the outflow air temperature of the thermal unit by exploiting the inflow air speed, whilst the inflow air temperature is considered as an external disturbance. The reliability and robustness issues of the suggested control methodologies are verified with a Monte–Carlo analysis for simulating modelling uncertainty, disturbance and measurement errors. The achieved results serve to demonstrate the effectiveness and the viable application the suggested control solutions to air conditioning systems. The benchmark model represents one of the key issues of this study, which is exploited for benchmarking different model–based and data–driven advanced control methodologies through extensive simulations. Moreover, this work highlights the main features of the proposed control schemes, while providing practitioners and heating, ventilating and air conditioning engineers with tools to design robust control strategies for air conditioning systems.

Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multi-function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography. Optimization was started with central composite design based experiments to characterize the importance of different decision variables. The three variables used in the optimization were flow rate, length of gradient and final salt concentration in the linear elution gradient step. The obtained empiric functional model represented the effect of the significant factors on the yield as the objective function. Afterwards, the calibrated mechanistic model was employed to predict accurate optimal set of variables. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results while keeping purity, a product quality characteristic, equal or above to a predefined value.

Utilization of wasted heat instead of fuel combustion is effective to reduce primary energy consumption for mitigating global warming problem. Because wasted heat sources are not necessarily located close to areas of heat demand, one of the difficulties is that wasted heat has to be transferred from heat source side to heat demand side, which may require heat transportation over long distance. From this point we proposed and have examined new idea of heat transportation using ammonia-water as the working fluid which system is named Solution Transportation Absorption chiller, in short STA. Our previous studies of STA were mainly the experimental investigation with STA facility which cooling power was 25RT (90kW). As a result, the COP of STA was found almost same value 0.65 with the conventional absorption chiller without depending on the transportation distances. The simulation using AspenHYSYS also examined with same experimental condition. The experimental data showed good agreement with the simulation calculation. In this study, we examined the large-scale cooling power STA on simulation. The examination cooling powers were from 90 kW(25RT) to 3517 kW(1000RT). All cooling power achieved around COP 0.64 including pump power consumptions. In addition, we performed the dynamic simulation. As the results, there was no effect of pipeline size on the cooling capacities and mass flow rates. Furthermore, the stability time of the cooling capacities and mass flow rates were almost same regardless of the pipeline size and cooling capacity. In other words, STA may be achieved the same COP even though having various complex conditions compared with the conventional absorption chiller.

The application of the sensors optical fiber in the areas of scientific instrumentation and industrial instrumentation is very attractive due to its numerous advantages. In the industry of civil engineering for example, quasi-distributed sensors made with optical fiber are used for reliable strain and temperature measurements. Here, a quasi-distributed sensor in the frequency domain is discussed. The sensor consists of a series of low-finesse Fabry-Perot interferometers where each Fabry-Perot interferometer acts as a local sensor. Fabry-Perot interferometers are formed by pairs of identical low reflective Bragg gratings imprinted in a single mode fiber. All interferometer sensors have different cavity length, provoking the frequency-domain multiplexing. The optical signal represents the superposition of all interference patterns which can be decomposed using the Fourier transform. The frequency spectrum is analyzed and sensor´s properties were defined. Following, a quasi-distributed sensor was numerically simulated. Our sensor simulation considers sensor properties, signal processing, noise system and instrumentation. The numerical results show the behavior of resolution vs. signal-to-noise ratio. From our results, the Fabry-Perot sensor has high resolution and low resolutions. Both resolutions are conceivable because the FDPA algorithm elaborates two evaluations of Bragg wavelength shift

Arylamine N-acetyltransferases (NATs) are cytosolic enzymes, highly polymorphic, present in both eukaryotes and prokaryotes. These enzymes play an important role in the detoxification and activation of xenobiotics as well as in the synthesis of endogenous compounds. Specific NATs have been pointed out in the literature as possible therapeutic targets. In particular, the human NAT1, for the treatment of certain cancers, and the NAT from M. tuberculosis (TBNAT), for the treatment of tuberculosis. This paper describes an in silico approach to prospect and select potentially inhibitors of NAT1 and TBNAT from the Traditional Chinese Medicine (TCM) using free available tools. A library with ligands from TCM was previously screened in order to select only compounds with optimal pharmacological properties. The affinity of the selected ligands with respect to NAT enzymes was then evaluated by virtual screening (VS). Subsequently, the complexes with the best ligands were submitted to molecular dynamics (MD) simulations aiming to obtain better quality information on affinity and selectivity. The results for one specific ligand, ZINC14690579, indicated its potential for affinity and selectivity. ZINC14690579 structure may represent the discovery of a new scaffold for future development of NAT inhibitors.

Recently, there has been a growing interest in the production of electricity from renewable energy sources (RES). The RES investment is characterized by uncertainty, which is long-term, costly, depend on feed-in-tariff and support schemes. In this paper, we address the real option valuation (ROV) of a solar power plant investment. The real option framework is investigated. This framework considers the renewable certificate price, furthermore the cost of delay between establishing and operating the solar power plant. The optimal time of launching the project and assess the value of deferred option are discussed. The new three stage numerical methods are constructed, the Lobatto3C-Milstein (L3CM) methods. The numerical methods are integrated with concept of Black-Scholes option pricing theory, and applied in option valuation for solar energy investment with uncertainty. The numerical results of L3CM, finite difference and Monte Carlo methods are compared to show the efficiency of our methods. Our data set refers to the Arab Republic of Egypt.

The future of machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved in labs for the most common machining operations by using models based on equations describing the physical laws of the machining processes; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep-knowledge and models” that aid machine designers, production engineers or machinists to get the best of the machine-tools. This article proposes a methodology to reduce problems in machining by means of a simulation utility, which uses the main variables of the system&process as input data, and generates results that help in the proper decision-making and machining planification. Direct benefits can be found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter-free optimum cutting conditions and d) the right programming of cutting toolpaths at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies and are explained in the paper.

In networked driving simulation, two or more human drivers participate interactively within a shared virtual environment. Thereby, typical applications of driving simulation can be extended to consider multi-driver scenarios, where a much closer approximation of reality with its unpredictability is achieved. However, the utilized network is typically prone to a considerable amount of message traffic. In addition to restricted system scalability, the resulting degradation of network performance leads to invalid simulation outcomes or unacceptable system behavior. High-level architecture (HLA) is an IEEE standard for networked simulation. Data distribution management (DDM) is one of the service groups provided by HLA standard. The aim of the DDM service is to reduce network traffic and to save effort required to process unnecessary received data. However, different approaches for current DDM implementations show major drawbacks in terms of utilization complexity, inefficiency, and yet added network overhead. This paper presents a concept of an interest manager that takes over the DDM functionality and avoids these drawbacks. Simulation data is exchanged between the participating driving simulators only when it is necessary according to the driving situations. The concept is validated by analyzing the network load of two driving maneuvers with and without the interest manager.

In this study, we repositioned thiopurine drugs used for the treatment of acute leukaemia as new tyrosinase inhibitors. Tyrosinase catalyses two distinct and successive oxidations in melanin biosynthesis: the conversions of tyrosine to dihydroxyphenylalanine (DOPA) and DOPA to dopaquinone. Continuous efforts are underway to discover small molecule inhibitors of tyrosinase for therapeutic, cosmetic, and agricultural purposes. Structure-based virtual screening has predicted inhibitor candidates for mushroom tyrosinase from drugs approved by the US Food and Drug Administration (FDA). Enzyme assays have confirmed the thiopurine leukaemia drug, thioguanine, as a tyrosinase inhibitor. Two other thiopurine drugs, mercaptopurine and azathioprine, were also evaluated for their tyrosinase inhibitory activity; mercaptopurine caused stronger inhibition than thioguanine did, whereas azathioprine was a poor inhibitor. The inhibitory constants of thioguanine and mercaptopurine were calculated as 52 and 16 µM, respectively, and the value of mercaptopurine was comparable to that of the well-known inhibitor kojic acid (13 µM). The cell lysate and melanin content assay in B16F10 melanoma cells confirmed that the compounds inhibited mammalian tyrosinase. In particular, 50 µM thioguanine reduced the melanin content by 57% without cytotoxicity. Furthermore, the thiopurine drugs shared little chemical similarity with the known tyrosinase inhibitors.

The next future using machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved for the most common cases by sing models based on equations describing the physical laws dominating the machining process; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep knowledge and models” that aid the machine designer, the production engineer, or machinists to get the best of their machines. This article proposes a systematic methodology to reduce problems in machining by means of a simulation utility, which recognizes, collects and uses the main variables of the system/process as input data, and generates objective results that help in the proper decision-making. Direct benefits by such an application are found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter free optimum cutting conditions and the right programming of cutting tool path at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies.

Collision avoidance is an important feature in advanced driver-assistance systems, aiming at providing correct, timely and reliable warnings before an imminent collision (objects, vehicles, pedestrians, etc.). A co-simulation framework is proposed in this paper to address the design and evaluation of collision avoidances in a cyber-physical system. The co-simulation framework is supported on the interaction between SCANeR and Matlab/Simulink. From the best of authors’ knowledge, two main contributions are reported in this paper. Firstly, the modelling and simulation of virtual on-chip LIDAR sensors in a cyber-physical system (CPS) considering traffic scenarios is presented. The CPS is designed and implemented in SCANeR. Secondly, an obstacle recognition library with three specific Artificial Intelligence-based methods is also designed based on sensory information database provided by SCANeR. Three methods for collision avoidance detection are considered, i.e.; a multi-layer perceptron neural network, a self-organization map and a support vector machine. Finally, a comparison among these methods for detecting obstacles before different weather conditions is done with very promising results in terms of accuracy. The best results are achieved using the multi-layer perceptron in sunny and fog conditions, the support vector machine in rainy and self-organized map in snowy conditions.

Recent advances in sensor and platform technologies such as satellite systems, unmanned aerial vehicles (UAV), manned aerial platforms, and ground-based sensor networks have resulted in massive volumes of data is produced and collected about the earth. Processing, managing, and analyzing these data is one of the main challenges in 3D synthetic representation used in modeling and simulation (M&S) of the natural environment. M&S devices, such as flight simulators, traditionally require a variety of different databases to provide a synthetic representation of the world. M&S often requires integration of data from a variety of sources stored in different formats. Thus, for simulation of a complex synthetic environment, such as a 3D terrain model, tackling interoperability among its components (geospatial data, natural and man-made objects, dynamic and static models) is a critical challenge. Conventional approaches used local proprietary data models and formats. These approaches often lacked interoperability and created silos of content within the simulation community. Therefore, open geospatial standards are increasingly perceived as a means to promote interoperability and reusability for 3D M&S. In this paper, the Open Geospatial Consortium (OGC) CDB Standard is introduced. “CDB” originally refers to Common DataBase which is currently considered as a name with no abbreviation in the OGC community. The OGC CDB is an international standard for structuring, modeling, and storing geospatial information required in high performance modeling and simulation applications. CDB defines the core conceptual models, use cases, requirements, and specifications for employing geospatial data in 3D M&S. The main features of the OGC CDB Standard are described as run-time performance, full plug-and-play interoperable geospatial data store, usefulness in 3D and dynamic simulation environment, ability to integrate proprietary and open-source data formats. Furthermore, compatibility with the OGC standards baseline reduces the complexity of discovering, transforming, and streaming geospatial data into the synthetic environment and makes them more widely acceptable to major geospatial data/software producers. This paper includes an overview of OGC CDB version 1.0 which defines a conceptual model and file structure for the storage, access, and modification of a multi-resolution 3D synthetic environment data store. Finally, this paper presents a perspective of future versions of the OGC CDB and what the steps are for humanizing the OGC CDB standard with the other OGC/ISO standards baseline.

This article argues that despite a citation review is a rarely used research tool, this can be very useful to assess the impact of new research topics, both from the future research direction and the bibliometric perspectives. An explorative study is presented around the research area marked as Industry 4.0 with the conference paper mentioned in the title of this citation review. Even though the given reference paper is relatively recent, there are already twenty-seven citations listed among three different scholar databases. These are Google Scholar, ResearchGate and Semantic Scholar. In light of this, the article provides a bibliometric confirmation and analysis for the progression of the line of research adopted by de Giorgio et al. in the exploration of non-traditional methods using virtual reality technology and human-robot collaboration for adaptive applications in Industry 4.0. Furthermore, it represents a model for the authors’ self-development and an example of an unconventional approach to scientific work that may help improve related bibliometric research and scholar database strategies to index new articles and topics in the future.

Summary: Studying biological systems generally relies on computational modeling and simulation, e.g., for model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED-ML), or the Open Modeling EXchange format (OMEX). Conducting simulation experiments based on these formats requires efficient and reusable implementations to make them accessible to the broader scientific community and to ensure the reproducibility of the results. The Systems Biology Simulation Core Library (SBSCL) provides interpreters and solvers for these standards as a versatile open-source API in Java™. The library simulates even complex bio-models and supports deterministic Ordinary Differential Equations (ODEs); Stochastic Differential Equations (SDEs); constraint-based analyses; recent SBML and SED-ML versions; exchange of results, and visualization of in silico experiments; open modeling exchange formats (COMBINE archives); hierarchically structured models; and compatibility with standard testing systems, including the Systems Biology Test Suite and published models from the BioModels and BiGG databases. Availability and implementation: SBSCL is freely available at https://draeger-lab.github.io/SBSCL/.

The processing of woody biomass waste piles for use as fuel instead of burning them was investigated. At each landing slash pile location, a 132 kW grapple excavator was used to transfer the waste piles into a 522 kW horizontal grinder. Economies of scale could be expected when grinding a larger pile, although the efficiency of the loading operation might be diminished. Here, three piles were ground and the operations were time-studied: Small (20 m long × 15 m wide × 4 m high), Medium (30 × 24 × 4 m), and Large (35 × 30 × 4 m) piles. Grinding the Medium pile was found to be the most productive at 30.65 bone dry tons per productive machine hour without delay (BDT/PMH₀), thereby suggesting that there might be an optimum size of slash pile for a grinding operation. We also examined modeling of the excavator and grinder operations, and we observed that the constructed simulation model well-replicated the actual operations. Based on the modeling, we estimated that the productivity of grinding at a landing area of 710 m² of slash pile location was 31.24 BDT/PMH₀, which was the most productive rate.

Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N_CTL=8 and N_HTL=6) and B-cell (N_LBL=4) epitopes from each LASV-derived protein with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor (TLR2) showed binding efficiency followed by dynamic simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.

This paper is focused on understanding multiscale modelling to obtain a bridge among different time and length scales of simulation techniques. These techniques are vital as it holds the potential to understand and predict the capabilities of polymer nanocomposites (PNCs). However, an appropriate approach in controlling the interfacial interaction between nanoparticle and polymer in nanocomposites structure is still needed to develop. In this review, an initial brief introduction to various trending simulation techniques has been discussed at all three levels of scale (nm, μm, mm). Later, descriptive study on fundamental issues such as thermodynamics, kinetics, mechanical properties, and morphology has been studied deeply. The multiscale modeling bridges the gaps of simulation between the different scales of models from molecular to mesoscale levels working over the broad range of length and timescale. Through the sequential, adaptive, and concurrent approaches, we can develop a system that may comprehend multiscale mode modeling adaptive resolution approach has recently added approach the molecule of the subject can shift their position freely in the domain and through this approach and studied the Brownian motion. Co-The co-current coach is also termed as handshaking path and it is linked aiming at different scale models. Covering the rigid techniques smoothly and linking them at different scales helps in normalizing the statistical behaviour.

Confidence interval of is an interval corresponding to a specified confidence and including the true value. It can be used to describe the precision of a statistical quantity and quantify its uncertainty. Although the principle of maximum entropy (POME) has been used for a variety of applications in hydrology, the confidence intervals of the POME quantile estimators have not been available. In this study, the calculation formulas of asymptotic variances and confidence intervals of quantiles based on POME for Gamma, Pearson type 3 (P3) and Extreme value type 1 (EV1) distributions were derived. Monte Carlo Simulation experiments were performed to evaluate the performance of derived formulas for finite samples. Using four data sets for annual precipitation at the Weihe River basin in China, the derived formulas were applied for calculating the variances and confidence intervals of precipitation quantiles for different return periods and the results were compared with those of the methods of moments (MOM) and of maximum likelihood (ML) method. It is shown that POME yields the smallest standard errors and the narrowest confidence intervals of quantile estimators among the three methods, and can reduce the uncertainty of quantile estimators

Automotive aerodynamics comprises of the study of aerodynamics of road vehicles. Its main goals are reducing drag, minimizing noise emission, improving fuel economy, preventing undesired lift forces and minimizing other causes of aerodynamic instability at high speeds. The Ahmed body has the form of a highly simplified car, consisting of a blunt nose with rounded edges fixed onto a box-like middle section and a rear end that has an upper slanted surface, the angle of which can be varied. It retains vital features of real vehicles in order to study the flow fields around it and the related turbulence models which characterizes the actual flow at elevated Reynolds number. In the present study, the aerodynamic behavior of this body is investigated numerically by the aid of commercial CFD tool: Ansys Fluent. The results of the simulation are validated with available experimental data and results of the simulations from other literatures. The numerical data were obtained for a fixed free stream velocity of 25 m/s at the inlet. The simulations were performed at a fixed slant angle of 25 degree and zero yaw angle. The present study focuses on how local refinement of mesh inside the concerned body and the outside, helps affect the results and for which grid dependency test is the primary objective of this paper. The present study also helps demonstrate how the drag of the body behaves, which is mainly the effect of pressure drag force generated at the rear portion of the body. The study also focuses on important properties like the velocity magnitude at different locations for different meshing cases, and to capture the flow pattern in the front or near the wake region. The study can be further helpful to future researchers in determining resistance, fuel efficiency etc. helping designers to optimize in specialized areas for better efficiency.

X-ray fluorescence is largely employed in the measurement of the thickness of coatings. Despite of its diffusion, the task is not straightforward because of the complex physics involved that results in high dependence on matrix effects. Thickness quantification is in practice accomplished using the Fundamental Parameters approach, adjusted with empirical measurements of standards with known composition and thickness. This approach has two major drawbacks: i) there are no standards for any possible coating and coating architecture and ii) even relying on standards, the quantification of unknown samples requires the precise knowledge of the matrix nature (e.g., in case of multilayer coatings the thickness and the composition of each underlayer). In this work, we describe a semiquantitative approach to coatings thickness measurement based on the construction of calibration curves through simulated XRF spectra built with Monte Carlo simulations. Simulations have been performed with the freeware software XMI-MSIM. We have assessed the accuracy of the methods by comparing the results with those obtained by i) XRF thickness determination with standards and ii) FIB-SEM cross-sectioning. Then we evaluated which parameters are critical in this kind of indirect thickness measurements.

Most of the structures in flowing water are a challenge to their stability and sustainable with different flow conditions. Recent, renewable energy research and development covers ocean and river energy platform in which flow of water drag considered in various conversion devices towards the offshore and onshore establishment. Various energy platforms have been suggested for offshore development. However, the stability of these platforms in water is a serious concern. To study the water interaction over circular and square cross-section cascade system under the water has been carried out. Water flow around the pillars or column of the energy platform are analyzed through simulation software. Very low velocity 0.5 m/s has been considered to analyze the system. Total fifteen numbers of cascade pillars having circular and square cross-section area were considered. K-ε turbulence model is adopted to calculate the flow interaction to the column. A velocity, pressure, and energy fields are found around the column.

Energy dissipation is one of the most important factors in choosing stepped spillways. However, few studies are about energy dissipation with different horizontal face angles. In this paper, the realizable k-ε turbulence model was used to study the flow field and energy dissipation rates of different stepped spillways with five horizontal face angles in the skimming flow regions. It shows that the free water surfaces and energy dissipation rates change with horizontal face angles and the energy dissipation rates initially decrease and then increase as the horizontal face angle increases. And the horizontal face angles cause the great changes of flow field.

During speciation-with-gene-flow, a transition from single-locus to multi-locus processes can occur, as strong coupling of multiple loci creates a barrier to gene flow. Testing predictions about such transitions with empirical data requires building upon past theoretical work and the continued development of quantitative approaches. We simulated genomes under different evolutionary scenarios of gene flow and divergent selection, extending previous work with the additions of neutral sites and coupling statistics, allowing us to investigate if and how selected and neutral sites differ in the conditions they require for transitions during speciation. As the per-locus strength of selection grew and/or migration decreased, it became easier for selected sites to show divergence – and thus to rise in linkage disequilibrium (LD) with each other as a statistical consequence – farther in advance of the conditions under which neutral sites could diverge. Indeed, even very low rates of gene flow were sufficient to prevent differentiation at neutral sites. However, once strong enough, coupling among selected sites eventually reduced gene flow at neutral sites as well. To explore whether similar transitions might be detectable in empirical data, we used published genome resequencing data from three taxa of Heliconius butterflies. We found that allele-frequency outliers and F ST outliers exhibited stronger patterns of LD than the genomic background, as expected. The statistical characteristics of LD – likely indicative of the strength of coupling of barrier loci – varied between chromosomes and taxonomic comparisons. Broad qualitative agreement between the patterns we observed in the empirical data and our simulations suggests that selection drives rapid genome-wide transitions to multi-locus coupling, illustrating how divergence and gene flow interact along the speciation continuum.

We have proposed a data-driven approach for designing mesoscale porous structures of Li-ion battery electrode with three-dimensional virtual structures and machine learning techniques. Over 2,000 artificial 3D structures assuming positive electrode composed of random packed spheres as active material particles are generated, and charge/discharge resistance has been evaluated using simplified Physico-chemical model. In this model, resistance from Li diffusion in active material particles (diffusion resistance), transfer resistance of Li+ in electrolyte (electrolyte resistance) and reaction resistance on the interface between active material and electrolyte are simulated based on mass balance of Li, Ohm’s law in and linearized Butler-Volmer equation, respectively. Using these simulation results, regression models via Artificial Neural Network (ANN) have been created in order to predict charge/discharge resistance from porous structure features. In this study, porosity, active material particle size and volume fraction, pressure in the compaction process, electrolyte conductivity, and binder volume fraction are adopted as features, associated with controllable process parameters for manufacturing battery electrode. As results, the predicted electrode resistance by ANN regression model is good agreement with the simulated values. Furthermore, sensitivity analysis and optimization of the process parameters have been carried out. The proposed data-driven approach could be a solution as a guiding principle for manufacturing battery electrode.

GNSS have been widely used in navigation, positioning and timing. Nowadays, the multipath errors previously considered detrimental may be re-utilized for the remote sensing of geophysical parameters (soil moisture, vegetation and snow depth), e.g. GPS- Multipath Reflectometry (GPS-MR). In this paper, a new element describing bistatic scattering properties of vegetation is incorporated into the traditional GPS-MR model. This new element is the first-order radiative transfer equation model. The new forward GPS multipath simulator is able to explicitly link the vegetation parameters with GPS multipath observables (signal-to-noise-ratio (SNR), code pseudorange and carrier phase observables). The trunk layer and its corresponding scattering mechanisms are ignored since GPS-MR is not suitable for high forest monitoring due to the coherence of direct and reflected signals. Based on this new model linking the GPS observables (SNR, phase and pseudorange) with detailed vegetation parameters, the developed simulator can present how the GPS signals (L1 and L2 carrier frequencies, C/A, P(Y) and L2C modulations) are transmitted (scattered and absorbed) through vegetation medium and received by GPS receivers. Simulation results show that wheat will decrease the amplitudes of GPS multipath observables, if we increase the vegetation moisture contents or the scatters sizes (stem or leaf), the amplitudes of GPS multipath observables (SNR, phase and code) decrease. Although the Specular-Ground component dominates the total specular scattering, vegetation covered ground soil moisture has almost no effects on the final multipath signatures. Our simulated results are consistent with published results for environmental parameter detections with GPS-MR.

To enable purposeful design and implementation of automated concrete technologies, precise assessment and prediction of the complex material flow at various stages of the process chain are necessary. This paper investigates the intermediate stage of the extrusion and deposition processes in extrusion-based 3D-concrete-printing, using a numerical model based on the Particle Finite Element Method (PFEM). In PFEM, due to the Lagrangian description of motion, remeshing algorithms and the alpha shape method are used to track the free surface during large deformation scenarios. The Bingham constitutive model was used for describing the rheological behaviour of fresh concrete. This model is validated by comparing the numerically predicted layer geometries with those obtained from laboratory 3D printing experiments. Extensive parametric studies were then conducted using the numerical simulation, delineating the influence of process and material parameters on the layer geometries, the dynamic surface forces generated under the extrusion nozzle and the inter-layer interactions.

An empirical model is presented for estimating discharge on the Ubombo Sugar Limited (USL) main gravity canal to enhance bulk water management and water use efficiency. It uses stage readings obtained from measuring flumes A, B, C, and UPS to simulate discharge. The rationale for the development of the mathematical flow simulation model is the significance of the UPS flume as it measures readings that influence the daily operations of the farm, and the experiences with the ultrasonic flow meter installed in the flume. The model also provides a first for the simulation of accurate flow rates for flumes A, B, and C. A spreadsheet program that enables express prediction of canal flow rates was developed to influence timely implementation of these water management decisions. Calibrations demonstrated that the model is capable of predicting discharge at high accuracy (p>95%), and can be reliably used as a decision support tool for bulk water management. It can also be expanded to include other water measuring structures along Canal 1 and Canal 2, as well as the development of a stand-alone water management application for desktop and mobile computers.

Nuclear export of viral mRNAs, is an essential step in the HIV replication cycle. This role is played by a small regulatory protein of HIV-1 called Rev.The N-terminal region of Rev contains an arginine-rich sequence. The arginine-rich motif (ARM) is located between amino acids 38-50 and forms an alpha-helical secondary structure. Expression of the structural proteins of human immunodeficiency virus type 1 requires the direct interaction of multiple copies of the viral Rev protein with its highly structured RNA target sequence, the Rev Response element (RRE). The major viral proteins are not produced if this transport of RNA is stopped. Therefore, knowledge of Rev structure is essential for understanding of its cooperative binding to the RRE, for understanding the mechanism of HIV infection and for the development of antiviral drugs that interfere with Rev’s essential functions and for acknowledgment of good candidate drugs for treatment of AIDS. To understand how REV interact with RRE element of HIV-RNA and its formation of oligomeric complex it is better to characterize the domain wise structure of REV with regard in function of each domain. Due to lack of structural data on Rev no single compound is reported as inhibitor of REV expect antiviral drugs. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev Protein is much more important. The ARM is a highly specific sequence which allows for the multimerization of Rev and also binding of REV with RNA. Here we are first time exploring the structural characteristics of REV protein both in free form and in complex with RNA at domain function level especially explore the role of ARM motif in REV HIV-1 protein as RNA binding sites by molecular dynamics (MD) simulation and homology modeling studies. Results indicate that the arginine-rich motif (ARM) is crucial in stability of this complex. The residues ARG38, 39, 41, 43, 44, 48, 50, and ASN40 are most interacting with nucleobases of RRE in Crystal structure of Rev and Rev-response-element RNA complex. Our study plays a major role in elaboration of binding of RNA with REV and pave the way for further investigation for therapeutically agent for HIV.

Aurora kinase A (AURKA) is a normal cell proliferation-inducing enzyme encoded by AURKA gene, with over-expression observed in different types of malignancies. Hence, the goal is to find potential inhibitors against AURKA. In this study, molecular docking, Standard Precision and Extra Precision methods were employed. After the docking study, the ligands showed an extremely low binding score which suggested very high binding affinity of the ligands. Furthermore, Quantum polarized ligand docking (QPLD) was performed to predict the binding status of the molecules. Based on the binding affinity, the top four compounds were chosen for further analysis. The docked complexes were further analyzed in explicit water conditions using 100 ns molecular dynamics simulations and binding free energy calculation. Then, density functional theory (DFT) calculation was used to calculate the molecular properties of the molecules. Finally, systems biology experiments validated the molecular docking and molecular dynamics simulation studies and indicated that quercetin, kaempferol, luteolin and rutin could inhibit the AURKA. The results show that, these four molecules have high binding affinity to the AURKA and significant interactions (LEU139, GLU211and ALA213) were also identified with the hinge region of Aurora kinase A. Thus, LEU139, GLU211, and ALA213 were identified as the crucial protein mechanisms.

The powder bed fusion (PBF) metal additive manufacturing (AM) method uses an energy source like a laser to melt the metal powders. The laser can locally melt the metal powders and creates a solid structure as it moves. The complexity of the heat distribution in laser PBF metal AM is one of the main features that need to be accurately addressed and understood to design and manage an optimized printing process. In this research, the dependency of local thermal rates and gradients on print after solidification (in the heat-affected zone) was numerically simulated and studied to provide information for designing the print process. The simulation results were validated by independent experimental results. The simulation shows that the local thermal rates are higher at higher laser power and scan speed. Also, the local thermal gradients increase if the laser power increases. The effect of scan speed on the thermal gradients is opposite during heating versus cooling times. Increasing the scan speed increases the local thermal gradients in the cooling times and decreases the local thermal gradients during the heating. In addition, these simulation results could be used in artificial intelligence (AI) and machine learning for developing digital additive manufacturing.

In this work, we examined the effect of tropospheric emissions on tropospheric ozone (O₃) by conducting three-dimensional (3D) chemistry transport model (CTM) simulations. For the control run, the CTM model simulates tropospheric O₃ levels with a complete set of anthropogenic, biomass burning, and vegetation emissions [8]. For the no-emission simulation, all anthropogenic, biomass burning, and vegetation emissions were turned off. Comparisons of results from these two simulations exhibit the emission impacts on the tropospheric O₃. In the no-emission simulation, distinctive low surface O₃ with concentrations less than 5 ppbv prevail over the Amazon basin, tropical South America, tropical South Africa, Southeast Asia. Transport of air from these land areas downwind contributes to the low O₃ over the remote marine boundary layer. In contrast, elevated O₃ levels over the extra-tropical remote marine boundary layer are less supported by the anthropogenic and biomass burning emissions but more sustained by the downward transport of O₃ from the stratosphere. These results demonstrate that the northern hemisphere continental areas (north of 30^◦N ), polar regions, and tropical continental regions are more sensitive to the tropospheric emissions. The northern hemisphere winter is mostly dominated by the stratospheric processes, while the tropospheric emissions dominate over the southern hemisphere tropical continental areas from tropics to 30^◦S latitudinal bands. The northern hemisphere continental regions are increasingly dominated by tropospheric emissions from spring, to reach maxima in summer, and started to reduce in autumn months.

The link between language processing and motor systems has been the focus of increasing interest to Cognitive Neuroscience. Some classical papers studying Event Related Potentials (ERPs) induced by linguistic stimuli have found differences in electrophysiological activity when comparing action and non-action words; more specifically, a bigger p200 for action words. On the other hand, a series of studies have validated the use of a grip force sensor (GFS) to measure language-induced motor activity during both isolated words and sentence listening, finding that action words induce an augmentation in the grip force around 250-300 ms after the onset of the stimulus. The purpose of the present study is to combine both techniques to assess if the p200 is related to the augmentation of the grip force measured by a GFS. We measured ERP and GFS changes elicited by listening to action and non-action words while maintaining an active grasping task in 10 healthy subjects. Our results show that the amplitude of the p200 in central electrodes is correlated to the augmentation in the GFS around 300 ms induced by linguistic stimuli. To our knowledge, this is the first study where the electrophysiological activity and the changes in the grip force induced by auditory language processing are put together, opening new venues of interpretation for the sensorimotor interaction in language processing.

The purpose of this paper is to simulate a two-dimensional Rayleigh-Taylor instability problem using the classical method of Finite Element analysis of a multiphase model using ANSYS FLUENT 19.2. The governing equations consist of a system of coupled nonlinear partial differential equations for conservation of mass, momentum and phase transport equations. The study focuses on the transient state simulation of Rayleigh Taylor waves and subsequent turbulent mixing in the two phases incorporated in the model. The Rayleigh Taylor instability is an instability of an interface between two fluids of different densities which occurs when the lighter fluid is pushing the heavier fluid in a gravitational field. The problem was governed by the Navier-Stokes and Cahn-Hilliard equations in a primitive variable formulation. The Cahn- Hilliard equations were used to capture the interface between two fluids systems. The objective of this article is to perform grid dependency test on Rayleigh Taylor Instability for 2 different mesh size and compare the results for the variation in Atwood Number. The results were validated with the observations from previous published literatures.

We review and assess the classic SIR and SEIR epidemiological models regarding possible applications to the COVID-19 pandemic. In spite of numerous more complicated models, we show how the qualitative features of the solution to the SIR and SEIR models continue to provide valuable public health insights in some scenarios. Using estimated COVID-19 data as of this date, the SEIR model shows that if it were possible to reduce R₀ from 2.5 to 1.25 through social distancing and other measures, the maximum fraction of the population that would become infected at any particular time would drop from 17% to 4%, provided that all of the model assumptions are satisfied. Finally, we compare the classic SIR model with a recent stochastic model with favorable results. Since this comparison underscores the importance of underlying connectivity assumptions, we conclude with Monte-Carlo simulations with specific connectivity that reproduce the classical SIR model with standard incidence.

Physical-law based models are widely utilized in the aerospace industry. One such use is to provide flight dynamics models for use in flight simulators. For human-in-the-loop use, such simulators must run in real-time. Due to the complex physics of rotorcraft flight, to meet this real-time requirement, simplifications to the underlying physics sometimes have to be applied to the model, leading to model response errors in the predictions compared to the real vehicle. This study investigated whether a machine-learning technique could be employed to provide rotorcraft dynamic response predictions, with the ultimate aim of this model taking over when the physics-based model's accuracy degrades. In the current work, a machine-learning technique was employed to train a model to predict the dynamic response of a rotorcraft. Machine learning was facilitated using a Gaussian Process (GP) non-linear autoregressive model, which predicted the on-axis pitch rate, roll rate, yaw rate and heave responses of a Bo105 rotorcraft. A variational sparse GP model was then developed to reduce the computational cost of implementing the approach on large data sets. It was found that both of the GP models were able to provide accurate on-axis response predictions, particularly when the input contained all four control inceptors and one lagged on-axis response term. The predictions made showed improvement compared to a corresponding physics-based model. The reduction of training data to one-third (rotational axes) or one-half (heave axis) resulted in only minor degradation of the GP model predictions.

For evaluating probabilities of arbitrary random events with respect to a given multivariate probability distribution, specific techniques are of great interest. An important two-dimensional high risk limit law is the Gauss-exponential distribution whose probabilities can be dealt with based upon the Gauss-Laplace law. The latter will be considered here as an element of the newly introduced family of (p,q)-spherical distributions. Based upon a suitably defined non-Euclidean arc-length measure on (p,q)-circles we prove geometric and stochastic representations of these distributions and correspondingly distributed random vectors, respectively. These representations allow dealing with the new probability measures similarly like with elliptically contoured distributions and more general homogeneous star-shaped ones. This is demonstrated at hand of a generalization of the Box-Muller simulation method. En passant, we prove an extension of the sector and circle number functions.

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.

The study aims to analyze the performance criteria of the GR4J model to reproduce high water flows in the Ouémé watershed at Bonou's outlet which has been vulnerable to climate change in recent decades. The methodology focused on the use of daily climatological and hydrometric data extracted from files of National Directorate of Meteorology, and General Directorate of Water; they were supplemented by those of SIEREM/HSM dataset over the period 1961-2015. The rainfall was regionalized using Thiessen method. The performance of the GR4J model was assessed with NSE, RMSE and KGE criteria. The results indicate that the study area is marked by rainfall variabilities and detection of two breakpoints (1968 and 1987) which divide the series into three sub-periods; these discontinuities have repercussions on the streamflow. It's found that GR4J model overestimates the streamflow during the low water period and underestimates them in high water. However, the efficiency and performance criteria NSE, RMSE and KGE calculated on high water flow rates are better in calibration than in validation. The KGE values are range between 83-85% in calibration and 56-68% during validation, which gives to GR4J model the efficiency and performance to reproduce high flow rates in the study area

This paper highlights the problems associated with daylight use in industrial facilities. In a case study of a multi-story textile factory, we report how to evaluate daylight (as part of integral light) in the production halls marked F and G. This study follows the article in the Buildings journal, where Hall E was evaluated (unilateral daylight). These two additional halls have large areas that are 54 × 54 meters and are more than 5 meters high. The daylight is only on the side through the attached windows in envelope structures in the vertical position. In this paper, we want to present two case studies of these two production halls in a textile factory in the eastern part of Slovakia. These are halls that are illuminated by daylight from two sides through exterior peripheral walls that are against or next to each other. The results of the case studies can be applied in similar production halls illuminated by a ‘double-sided’ (bilateral) daylight system. This means that they are illuminated by natural illumination through windows on two sides in a vertical position. Such a situation is typical for multi-storied industrial buildings. The proposed approximate calculation method for the daylight factor can be used to predict the daylight in similar spaces in other similar buildings.

Curcumin is one of the bioactive metabolites of turmeric (Curcuma longa), known for its pleiotropic pharmacological actions, including antioxidant and anti-inflammation, anticholinesterase, immunomodulation, and neuroprotection. Substantial evidence suggests the therapeutic benefits of curcumin against neurodegenerative disorders, including Alzheimer’s disease (AD), acting on a diverse array of brain targets that make the molecular mechanisms complicated. System biology level-investigation could potentially present a comprehensive molecular mechanism to delineate the neuropharmacological action of curcumin. In this study, we used integrated system pharmacology and molecular simulation analysis to gain insights into the underlying mechanism of curcumin action against AD. Network pharmacology study identified curcumin-targeted potential cellular pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, neurotrophin signaling, toll-like receptor (TLR) signaling, and autophagy, and proteins such as tropomyosin receptor kinase B (TrkB), liver X-receptor-beta (LXR-β), estrogen receptor-β (ER-β), mammalian target of rapamycin (mTOR), TLR-2, N-methyl-D-acetate receptor subunit 2B (GluN2B), β-secretase and glycogen synthase kinase-3β (GSK-3β), which are intimately associated with neuronal growth and survival, immune response, and inflammation. Moreover, the molecular modeling further verified that curcumin showed a significant binding affinity to mTOR, TrkB, LXR-β, TLR-2, ER-β, GluN2B, β-secretase, and GSK-3β, which are the crucial regulators of molecular and cellular processes associated with AD. Together, the present system pharmacology and in silico findings demonstrate that curcumin might play a significant role in modulating AD-pathobiology, supporting its therapeutic application for the prevention and treatment of AD.

Vertical-channel organic dual-gate/base transistors would be highly interesting since vertical organic transistors are the fastest organic transistors demonstrated today. However, incorporating a dual gate/base structure into an ultra-short channel vertical architecture represents a substantial challenge. Here, we successfully realize a new device concept of vertical organic permeable dual-base transistors (OPDBTs), where either of both base electrodes can be used to change the on-currents and tune the threshold voltages. The optimized devices yield a high on-current density of 1.54 A cm^-2 and a large current gain of 9.2×10⁵, corresponding to a high transmission value of 99.998%. The detailed operation mechanisms are investigated by calibrated TCAD simulations with the Poole-Frenkel mobility model, Gaussian density of states and tunneling model. Finally, high-performance logic circuits, e.g. inverter, NAND/AND computation functions are demonstrated with one single OPDBT operating at supply voltages of < 2.0 V. We believe that OPDBTs offer a compact and technologically simple hardware platform with excellent application potential for vertical-channel organic transistors in complex logic circuits.

The water cushion depth of stilling basin with shallow-water cushion is a key factor that affects the flow regime of hydraulic jump in the basin. However, the specific depth at which the water cushion is considered as “shallow” has not be stated clearly for now, and only conceptual description is provided. This paper attempts to specify the best water cushion depth based on the flow regime of hydraulic jump and underflow speed; namely, in case of critical hydraulic jump in the basin, the best water cushion depth is located where the minimum distance to the bottom plate of the stilling basin is 1/5~1/4 of the water cushion depth. The theoretical analysis indicates, at different inclinations of discharge chute (θ) and depth ratios of inlet (m), instead of monotonic change, the Froude number (Fr) at inlet of the stilling basin with shallow-water cushion firstly reduces and then increases as the flow velocity at discharge chute inlet (V) increases; the parameters of inflection point (critical flow velocity and critical Fr) increase as the inclinations of discharge chute (θ) and depth ratios of inlet (m) increase. Such regularity is the theoretical basis for selecting representative study cases. The reliability of the large eddy simulation calculation results are verified by a model test; in the paper, 30 cases including five different Froude numbers and six shallow-water cushion depths are selected, for calculating the hydraulic factors such as flow profile, flow regime and flow velocity in the stilling basin with shallow-water cushion; and the varying pattern between the best depth of stilling basin with shallow-water cushion (depth-to-length ratio) and the inflow Froude number is obtained which indicates that the best depth of stilling basin with shallow-water cushion varies little as the change of the Froude number before reaching the critical Froude number; however, the best depth-to-length ratio of stilling basin with shallow-water cushion increases as the Froude number increases after the critical Froude number is reached. The study results in this paper are of reference significance to design and calculation of the stilling basin with shallow-water cushion.

This paper deals with the problem of real-time management of Smart Grids. For this sake, the energy management is integrated with the power system through a telecommunication system. The use of Multiagent Systems leads the proposed algorithm to find the best-integrated solution, taking into consideration the operating scenario and the system characteristics. The proposed technique is tested with the help of an academic microgrid, so the results may be replicated.

The United Arab Emirates (UAE) is significantly dependent on desalinated water and groundwater resource, which is expensive and highly energy intensive. Despite the scarce water resource, only 54% of the recycled water was reused in 2015. In this study, an “Oasis” complex comprised of Sustainable Farming Compartments (SFCs) was proposed for reusing treated wastewater to decrease the ambient temperature of the SFC via an evaporative cooling system. A prototype SFC with half the original scale (width = 1.8 m, depth = 1.5 m, front height = 1.2 m back height = 0.9 m) was designed, built, and tested in an environmentally controlled laboratory and field site to evaluate the feasibility and effectiveness of the SFC under the climatic conditions in Abu Dhabi. Based on the experimental results, the temperature drops obtained from the SFC in the laboratory and field site were 5 ̊C at initial relative humidity of 60% and 7- 15 ̊C at initial relative humidity of 50%, respectively. An energy simulation using dynamic numerical simulations was performed in comparison to the results of the experiment. The energy-based dynamic simulation shows good agreement with the experimental results. The total power consumption of the SFC system was approximately three and a half times lower than that of an electrical air conditioner.

Carrying out technological tests and research is indispensably connected with high costs and elongation of implementation time of new casting technologies and their modifications in industry. Hence, the application of specialised computer software, enabling the simulation and analysis of metallurgical and casting processes in modern foundry industry is of special interest. The present work presents an experimental application of MAGMASoft software in casting process of EV31A magnesium alloy structural element of helicopter engine. The results of computer simulation have been compared with industrial cast of the simulated element, fabricated in the same conditions. It has been revealed that the computer simulation provides a complex information on the analysed process, leading to reduction of costs and time, connected with technological tests in implementation of new casting technologies.

In this review we summarize existing trends of flow control used to improve the aerodynamic efficiency of wings. We first discuss active methods to control turbulence, starting with flat-plate geometries and building towards the more complicated flow around wings. Then, we discuss active approaches to control separation, a crucial aspect towards achieving high aerodynamic efficiency. Furthermore, we highlight methods relying on turbulence simulation, and discuss various levels of modelling. Finally, we thoroughly revise data-driven methods, their application to flow control, and focus on deep reinforcement learning (DRL). We conclude that this methodology has the potential to discover novel control strategies in complex turbulent flows of aerodynamic relevance.

The properties of rubber are strongly influenced by the distribution of filler within the polymer matrix. Here we introduce a Monte Carlo-based morphology generator. The basic elements of our model are cubic cells, which, in the current version, can be either silica filler particles or rubber volume elements in adjustable proportion. The model allows the assignment of surface free energies to the particles according to whether a surface represents, for instance, 'naked' silica or silanised silica. The amount of silanisation is variable. We use a nearest-neighbour site-exchange Monte Carlo algorithm to generate filler morphologies, mimicking flocculation. Transmission electron micrographs (TEM) as well as small angle scattering (SAS) intensities can be calculated along the Monte Carlo trajectory. In this work we demonstrate the application of our morphology generator in terms of selected examples. We illustrate its potential as a tool for screening studies, relating interface tensions between the components to filler network structure as characterized by TEM and SAS.

During mechanical ventilation, a disparity between flow, pressure or volume demands of the patient and the assistance delivered by the mechanical ventilator often occurs. Asynchrony effect and ventilator performance are frequently studied from ICU datasets or using commercially available lung simulators and test lungs. This paper introduces an alternative approach of simulating and evaluating patient-ventilator interactions with high fidelity using the electro-mechanical lung simulator xPULM™ under selected conditions. The xPULM™ approximates respiratory activities of a patient during alternating phases of spontaneous breathing and apnoea intervals while connected to a mechanical ventilator. Focusing on different triggering events, volume assist-controlled (V/A-C) and pressure support ventilation (PSV) modes were chosen to test patient-ventilator interactions. In V/A-C mode a double-triggering was detected every third breathing cycle leading to an asynchrony index of 16.67%, being classified as severe. This asynchrony causes a major increase of Peak Inspiratory Pressure PIP = 12.80 ± 1.39 cmH2O and Peak Expiratory Flow PEF = -18.33 ± 1.13 L/min when compared to synchronous phases of the breathing simulation. Additionally, events of premature cycling were observed during PSV mode. In this mode, the peak delivered volume during simulated spontaneous breathing phases almost doubles compared to apnoea phases. The presented approach demonstrates the possibility of simulating and evaluating disparities in fundamental ventilation characteristics caused by double-triggering and premature cycling under V/A-C and PSV ventilation modes. Various dynamic clinical situations can be approximated and could help to identify undesired patient-ventilation interactions in the future. Rapidly manufactured ventilator systems could also be tested using this approach.

In this paper, the computational fluid dynamics (CFD) method has been used to simulate the gas flow and the catalytic hydrogenation process of the C-2 hydrogenation adiabatic reactor in a practical ethylene production unit of a chemical plant. The laminar finite-rate model was used for the chemical reaction model. The standard two-equation model was used for the turbulence model. The exponent-function kinetic model was used for the reaction dynamics model. The simulation results were in good agreement with the actual industrial data obtained from the C-2 hydrogenation reactor, and the distributions of reaction parameters such as temperature and component concentrations in the reactor were further analyzed. Based on the validated CFD models, the structure and operating conditions of the reactor, as well as hydrogen load distribution ratios, are simulated for comparing the comprehensive performance metrics of ethylene selectivity and acetylene conversion rate; as a result, we can obtain the optimal temperature of 312 K, the optimal hydrogen/acetylene ratio of 0.10 as well as the optimal hydrogen load distribution ratio of 4:4:2, and the diameter/height ratio exerts a marginal effect on the selectivity, conversion rate and harmonic mean of the reactor.

The peri-urban and urban forests in Greece occupy a total area of 105.353 ha. In these vulnerable ecosystems, fire constitutes a natural disaster presenting particular challenges and specific difficulties. These include the high number of visitors as well as forests characteristics - such as the presence of particularly flammable tree species and high accumulation of combustible biomass – that make the on-start of fires more likely. The main purpose of the current research is to identify the optimum combination of silvicultural treatments to efficiently reduce potential forest fire severity and to facilitate their successful suppression by firefighting crews. In order to simulate the basic fire environment of urban forests, two main experimental plots were established and several tree and topographical characteristics were measured. Additionally, the NEXUS wildfire system was used to simulate forest fire potential behavior before and after the adoption of the silvicultural treatments that altered critical characteristics of the forest fire environment. The results clearly show that specific silvicultural prescriptions altered the type of forest fire spreading potential, revealing the overall efficiency of preventing actions during forest management.

In order to be able to face competition, thriving corporations have to be compelled to maintain an awfully smart relationship with their existing customers and additionally to be able to anticipate their future wants. Thus, corporations do not target customers as teams, however they’re attempting to focus on them as individuals. However, to be able to use this information, corporations have to be compelled to use promoting automation tools. Marketing Automation was an idea first introduced in 2001 by John D.C. Little in his presentation at the 5th Invitational Choice Symposium UC Berkeley 2001. This survey paper assesses prominent research on Marketing Automation and suggests how it can be modified to adapt to the current marketing scenario.

The multidrug resistance transporter NorM is an important drug resistance pump and plays a critical role in multidrug resistance in bacteria and mammals. In this study we carried out molecular dynamics simulation to study the mechanism of Na+ binding and dynamical structures of two long loops in the substrate-releasing process in substrate binding NorM. Our simulation study identified several key residues (D41, E261 D377) along the Na+ binding pathway and a multi-state ion-binding mechanism is proposed based on the simulation study. In this proposed model, the transport of Na+ is a multi-stage process with D41 being the first station for binding to Na+, followed by Na+ binding to the second station E262 and finally to the cation-binding site of E262 and D377. During the transport of Na+, the transmembrane components TM1, TM7 and TM2 are rearranged to facilitate the ion transport as well conformational changes of NorM to a closed state. Further, substrate-bound simulation revealed that Loop3-4 and Loop9-10 control the substrate-releasing process.

Micro-pollutants such as 17β-Estradiol (E2) have been detected in different water resources and their negative effects on the environment and organisms have been observed. Aptamers are established as a possible detection tool, but the underlying ligand binding is largely unexplored. In this study, a previously described 35-mer E2-specific aptamer was used to analyse the binding characteristics between E2 and the aptamer with a MD simulation in an aqueous medium. Because there is no 3D structure information available for this aptamer, it was modeled using coarse-grained modeling method. The E2 ligand was positioned inside a potential binding area of the predicted aptamer structure, the complex was used for an 25 ns MD simulation, and the interactions were examined for each time step. We identified E2-specific bases within the interior loop of the aptamer and also demonstrated the influence of frequently underestimated water-mediated hydrogen bonds. The study contributes to the understanding of the behavior of ligands binding with aptamer structure in an aqueous solution. The developed workflow allows generating and examining further appealing ligand-aptamer complexes.

Human factors are the most relevant issues contributing to adverse events in obstetrics. Specific training of Crisis Resource Management (CRM) skills (i.e., problem solving and team management, resource allocation, awareness of environment, and dynamic decision-making) are now widespread and are often based on High Fidelity Simulation. In order to be used as a guideline in simulated scenarios, they need to be translated into specific and observable behavioral markers. To this purpose, we developed a set of observable behaviors related to the main elements of CRM in the delivery room. The observational tool was then adopted in a two-days seminar on obstetric hemorrhage where teams working in obstetric wards of six Italian hospitals took part to simulations. The tool was used as guide for the Io and as a peer-to-peer feedback. It was then rated for its usefulness in facilitating the reflection upon one’s own behavior, its ease of use, and its usefulness for the peer-to-peer feedback. The ratings were highly positive, around 4 in a 5-point scale. The CRM observational tool is therefore a useful, quick and easy solution to facilitate the debriefing, the peer-to-peer feedback and, most of all, the transfer of safe behavior from simulation to everyday practice.

Based on the geologic conditions of natural gas hydrate (NGH) accumulations in the Shenhu area, northern slope of the South China Sea, this paper used a method of combining reservoir stimulation technique (RST) with depressurization to investigate the conversion efficiency of marine NGH reservoirs in different intrinsic permeability and initial NGH saturation conditions, and analyze the influence of variably-stimulation effect on marine NGH conversion efficiency in different accumulation conditions, provided a reference scheme for improving the NGH conversion efficiency in the Shenhu area. In this work, we performed calculations for the variations in CH4 production rate and cumulative volume of CH4 in different initial NGH saturation, intrinsic permeability and stimulation effect conditions, variance analysis and range analysis methods were used to analyze the significance of these key factors and their interaction, and investigated the sensitivity of stimulation effect on NGH conversion efficiency, respectively. The simulation results showed that stimulation effect have a significant influence on NGH conversion efficiency, and the influence of interaction between these three factors were not obvious. Possibly most important, we clarified an optimum stimulation effect for higher NGH conversion efficiency under different accumulation conditions, especially in low-permeability and high-saturation, which corresponding stimulation effect were different.

Binder jet printed components typically have low overall density in the green state and high shrinkage and deformation after heat treatment. It has previously been demonstrated that, by including nanoparticles of the same material in the binder, these properties can be improved as the nanoparticles can fill the interstices and pore throats between the bed particles. The beneficial effects from using these additive binder particles can be improved by maximising the binder particle size, enabling the space within the powder bed to be filled with a higher packing efficiency. The selection of maximum particle size for a binder requires detailed knowledge of the pores and pore throats between the powder bed particles. In this paper, a raindrop model is developed to determine the critical radius at which binder particles can pass between pores and penetrate the bed. The model is validated against helium pycnometry measurements and binder particle drop tests. It is found that the critical radius can be predicted, with acceptable accuracy, using a linear function of the mean and standard deviation of the particle radii. Percolation theory concepts have been employed in order to generalise the results for powder beds that have different mean particle sizes and size distributions. The results of this work can be employed to inform the selection of particle sizes required for binder formulations, to optimise density and reduce shrinkage in printed binder jet components.

Whether evaluating gridded population dataset estimates (e.g. WorldPop, LandScan) or household survey sample designs, a population census linked to residential locations are needed. Geolocated census microdata data, however, are almost never available and are thus best simulated. In this paper, we simulate a close-to-reality population of individuals nested in households geolocated to realistic building locations. Using the R simPop package and ArcGIS, multiple realizations of a geolocated synthetic population are derived from the Namibia 2011 census 20% microdata sample, Namibia census enumeration area boundaries, Namibia 2013 Demographic and Health Survey (DHS), and dozens of publicly available spatial datasets. Realistic household latitude-longitude coordinates are manually generated based on public satellite imagery. Simulated households are linked to latitude-longitude coordinates by identifying distinct household types with multivariate kmeans analysis, and modelling a probability surface for each household type using Random Forest machine learning methods. We simulate five realizations of a synthetic population in Namibia's Oshikoto region, including demographic, socioeconomic and outcome characteristics at the level of household, woman, and child. Comparison of variables in the synthetic population were made with 2011 census 20% sample and 2013 DHS data by primary sampling unit/enumeration area. We found that synthetic population variable distributions matched observed observations and followed expected spatial patterns. We outline a novel process to simulate a close-to-reality microdata census geolocated to realistic building locations in a low- or middle-income country setting to support spatial demographic research and survey methodological development while avoiding disclosure risk of individuals.

This paper describes a case study for applying of hybrid-electric propulsion system for a general aviation aircraft. The work was performed by a joint team of CIRA and the Department of Industrial Engineering of the University of Naples “Federico II”. Electric and hybrid electric propulsion for aircraft has gained widespread and significant attention over the past decade. The driver for industry interest has principally been the need to reduce emissions of combustion engine exhaust products and noise, but increasingly studies revealed potential for overall improvement in energy efficiency and mission flexibility of new aircraft types. The project goal was to demonstrate feasibility of aeronautic parallel hybrid-electric propulsion for a Light aircraft varying the mission profiles and the electric configuration. Through a creation, and application, of a global model, with software AMESim^®, in which it can be represented everything about the components chosen by the industrial partners, some interesting considerations are carried out. In particular, it was confirmed that with the only integration of state of the art technologies, for some particular missions, the advantages of aircraft hybrid-electric propulsion, for light aircraft, are notable.

Many scientific and technological problems are studied with the help of computer codes that simulate the phenomena of interest rather than via traditional laboratory experiments. Such models play an important role in neuroscience where they are used to mimic brain function from the sub-cellular to the macroscopic level. Exploration with computer models carries with it a number of statistical challenges: where to sample the input space for the simulator, how to make sense of the data that is generated, how to estimate unknown parameters in the model, how to validate a model. The simulator setting also has some unique problems and possibilities. This review paper describes statistical research on these issues and how that work might be applied to neural simulations.

This paper shows that by applying the Nyquist-Shannon sampling theorem, the spatial and temporal resolution of a simulation can be no more than half the resolution of the simulating reality. This has significant implications for not only the values of the observables in the simulation but also its physical laws. This progressive halving of nested simulations coupled with the minimum resolution compatible with the production of a simulation also sets a limit to the nestedness of a lineage of simulations (it is by no means infinite). The limit of nestedness is then used to calculate the probability that we are living in a simulation assuming a single base reality. This will be shown to be significantly lower than popular expectation. A Kardashev-like scale, with three variants, is also developed to gauge the technological advancement of a civilization in relation to the extent to which it can extract information from space and time.

Lightning strike can cause a considerable damage in aircraft parts made from semiconducting materials such as Carbon Fiber Reinforced Plastics (CFRPs). Therefore, in recent years, the lightning strike phenomenon has attracted the interest of the academic community and the aircraft industry. Until now, the problem has been addressed mainly experimentally, while the reported numerical works are very limited. In the present work, a coupled electro-thermal FE model has been developed using the ANSYS commercial FE code to simulate the lightning strike damage in unidirectional CFRP laminates due to the Joule heat flux phenomenon. The model is based on the SOLID69 thermoelectric element and applies a non-linear, time-transient analysis. The main input to the model is the thermal-electrical properties of the composite material which vary with temperature. Using the model, a parametric study on the effect of mesh density and peak intensity on the thermal damage has been performed. Three electrical lightning strikes of low (10 kA), medium (30 kA) and high peak intensity (40 kA) have been applied according to the SAE ARP 5412 standard. The electro-thermal model has been validated against a numerical model from the literature. The numerical results reveal that the increase of peak intensity leads to the increase of the area and penetration depth of matrix thermal damage (pyrolysis) as well as to the increase of the area of fiber damage (deterioration and ablation). Through progressive damage modeling, the residual tensile strength of the CFRP plate after being subjected to lightning strike of different peak intensity has been predicted. Lightning strike initial damage has been simulated by translating the thermal field into degradation of elastic properties of the lamina. The results show an increase in the accumulated matrix damage and a decrease of tensile strength due to the initial lightning strike damage. For the maximum peak intensity of 40 kA, a decrease in tensile strength of 4.8% has been predicted

The effect of configuration of an asymmetric bulky initiator 2,2’-[1,1’-binaphtyl-2,2’-diyl- bis-(nitrylomethilidyne)]diphenoxy aluminum isopropoxide (Ini) on structure of copolymer of asymmetric monomer L,L-lactide (Lac) with symmetric comonomer trimethylene carbonate (Tmc) was studied using polarimetry, dilatometry, SEC and ¹³C NMR. When the S-enantiomer of Ini was used the distribution in copolymer chains at the beginning of polymerization is statistical, with alternacy tendency, changing next through a gradient region to homoblocks of Tmc. When, however, R-Ini was used, the product formed was a gradient oligoblock one, with Tmc blocks prevailing at the beginning, changing to Lac blocks dominating at end part of chains. Initiation of copolymerization with the mixture of both initiator enantiomers (S:R = 6:94) gave multiblock copolymer, of similar features but shorter blocks. Analysis of copolymerization progress required complex analysis of dilatometric data, assuming different molar volume contraction coefficients for units located in different triads. Comonomer reactivity ratios of studied copolymerizations were determined.

Project logistics is one of the specific logistics operations. Compared to other logistics operations, it needs more efficient planning and engineering applications in each operational process. On the other hand, each project logistics operation can be defined as tailor-made operations, since it has no similarity with other operations. Consequently, each project logistics operation should be planned and carried out according to its own conditions and parameters. This study focuses on the simulation of project logistics operations under the light of computerized applications from start to finish of the logistics operation. In this study, transportation operations of 600 tons of autoclave from the Petkim port to the Gördes building site were selected as a case study.

Subsurface temperature is the key parameter in geothermal exploration. An accurate estimation of the reservoir temperature is of high importance and usually done either by interpolation of borehole temperature measurement data or numerical modeling. However, temperature measurements at depths which are of interest for deep geothermal applications (usually deeper than 2 km) are generally sparse. A pure interpolation of such sparse data always involves large uncertainties and usually neglects knowledge of the 3D reservoir geometry or the rock and reservoir properties governing the heat transport. Classical numerical modeling approaches at regional scale usually only include conductive heat transport and do not reflect thermal anomalies along faults created by convective transport. These thermal anomalies however are usually the target of geothermal exploitation. Kriging with trend does allow including secondary data to improve the interpolation of the primary one. Using this approach temperature measurements of depths larger than 1,000 m of the federal state of Hessen/Germany have been interpolated in 3D. A 3D numerical conductive temperature model was used as secondary information. This way the interpolation result reflects thermal anomalies detected by direct temperature measurements as well as the geological structure. This results in a considerable quality increase of the subsurface temperature estimation.

Energy system modelling is an essential practice to assist a set of heterogeneous stakeholders in the process of defining an effective and efficient energy transition. From the analysis of a set of open source energy system models, it has emerged that most models employ an approach directed at finding the optimal solution for a given set of constraints. On the contrary, a simulation model is a representation of a system that is used to reproduce and understand its behaviour under given conditions, without seeking an optimal solution. Given the lack of simulation models that are also fully open source, in this paper a new open source energy system model is presented. The developed tool, called Multi Energy Systems Simulator (MESS), is a modular, multi-node model that allows to investigate non optimal solutions by simulating the energy system. The model has been built having in mind urban level analyses. However, each node can represent larger regions allowing wider spatial scales to be be represented as well. MESS is capable of performing analysis on systems composed by multiple energy carriers (e.g. electricity, heat, fuels). In this work, the tool’s features will be presented by a comparison between MESS itself and an optimization model, in order to analyze and highlight the differences between the two approaches, the potentialities of a simulation tool and possible areas for further development.

The beautiful and stable posture is essential for ballet. Especially the pirouette which dancers balance themselves on their one leg is one of the most impressive postures. During the pirouette motion, loads from the rotation and the body weight are concentrated to the one leg. Proper ballet shoes can reduce the muscle burden and improve the stability. Four types of shoes; bare feet, running shoes, pointe shoes, and dance sneakers are analyzed. The motion capture system and SIMM are used for the analysis of muscle burden and stability during pirouette. The major 6 muscles in the leg (beceps femoris long head, beceps femoris short head, soleus, rectus femoris, gastrocnemius medialis, and gastrocnemius lateralis) are analyzed, and the effect of rotating velocity is considered. Dance sneakers are outstanding for improving the stability and lessening the muscle burdens in all conditions for beginners. That comes from the design feature of the divided shoe soles and protecting the ankle of the axis leg. With the results and analysis, the direction for design optimization of ballet shoes is suggested. Consequently, this research is about the verification of sports equipment using computer simulation with the musculoskeletal model from a scientific viewpoint of biomechanics.

This paper proposes a novel model for a PV cell with parameters variance dependency on temperature and irradiance included. The model relies on commercial available data, calculates the cell parameters for standard conditions and then extrapolates them for the whole operating range. An up-to-date review of the PV modeling is also included with series and parallel parasitic resistance values and dependencies discussed. The parameters variance is analyzed and included in the proposed PV model, where the self-heating phenomenon is also considered. Each parameter variance is compared to the results from different authors. The model includes only standard components and can be run on any SPICE-based simulator. Unlike other approaches that consider the internal temperature as a parameter, our proposal relies on air temperature as an input and computes the actual internal temperature accordingly. Finally, the model is validated via experiments and comparisons to similar approaches are provided.

The increasing complexity of the design and operation evaluation process of multi-energy grids (MEGs) requires tools for the coupled simulation of power, gas and district heating grids. Most tools analyzed in this paper either do not allow coupling of infrastructures, simplify the grid model or are not publicly available. We introduce the open source piping grid simulation tool pandapipes that – in interaction with pandapower - fulfills three crucial criteria: clear data structure, adaptable MEG model setup and performance. In an introduction to pandapipes we illustrate how it fulfills these criteria through its internal structure and demonstrate how it performs in comparison to STANET®. Then we show two case studies that have been performed with pandapipes already. The first case study demonstrates a peak shaving strategy as interaction of a local electricity and district heating grid in a small settlement. The second case study analyzes the potential of a power-to-gas device to serve as flexibility in a power grid under consideration of gas grid constraints. They both show the importance of a clear database, a simple simulation setup and good performance to set up different large and complex studies on grid infrastructure design and operation.

Previous research has shown that the effectiveness of selecting filter set from a large set of commercial broadband filters by vector analyzing method based on maximum linear independence (MLI). However, the traditional MLI is suboptimal due to predefining the first filter of the selected filter set being the maximum ℓ2 norm among all those of the filters. An exhaustive imaging simulation is conducted to investigate the features of the most competent filter set. In the simulation, every filter in a subset of all the filters is selected serving as the first filter in turn. From the results of the simulation, we found there are remarkable characteristics for the most competent filter set. Besides smaller condition number, the geometric features of the best-performed filter set comprise the distinct peak of the transmittance of the first filter, the generally uniform distributing of the peaks of the transmittance curve of the filters, the substantial overlapping of the transmittance curves with those of the adjacent filer sets. Therefore, the best-performed filter sets can be decided intuitively by simple vector analyzing and just a few experimental verifications. This work would be useful for optimizing spectral sensitivity of broadband multispectral imaging sensors or SFA sensors.

First of all the paper presents a solid solution of piezoelectric ceramic that was synthesized according to the general formula Pb(1-x)Srx(Ti0.48Zr0.52)(1-y)NbyO3 with x = 0.05 and y = 0.02, using wet ceramic processing technology and using an oxide mix as prime material. The effects of dopants (Sr2+ and Nb5+) on phase constitution, on microstructure and on the dielectric and piezoelectric properties were determinate. The Zr/Ti ratio was chosen near the morphotropic phase boundary of the PZT system in studied composition. The XRD data revealed that the PZT doped composition had tetragonal perovskite structure. Secondly the paper presents the design of the novel piezo-motor based on a surface wave which translates the linear extension of different piezoelectric segments of a piezoelectric cylinder into a rotational bending movement. This rotational bending of the piezoelectric cylinder is then transformed into a continuous rotation of the rotor through a calculated contact. The design of the motor takes advantage of the high piezoelectric constants of the developed material in an optimal way in order to increase the energetic efficiency. A brief mathematical model of electromechanical answer of piezoelectric materials is presented as it was used in the modeling of the material during the numerical simulations.

A numerical approach for generating a limited number of water demand scenarios and estimating their occurrence probabilities in a Water Distribution Network (WDN) is proposed. This approach makes use of the demand scaling laws in order to consider the natural variability and spatial correlation of nodal consumptions. The scaling laws are employed to determine the statistics of nodal consumption as a function of the number of users and the main statistical features of the unitary user's demand. Besides, consumption at each node is considered to follow a Gamma probability distribution. A high number of groups of cross-correlated demands, i.e., scenarios, for the entire network were generated using Latin Hypercube Sampling (LHS) and the numerical procedure proposed by Iman and Conover. The Kantorovich distance is used to reduce the number of scenarios and estimate their corresponding probabilities, while keeping the statistical information on nodal consumptions. By hydraulic simulation, the whole number of generated demand scenarios was used to obtain a corresponding number of pressure scenarios on which the same reduction procedure was applied. The probabilities of the reduced scenarios of pressure were compared with the corresponding probabilities of demand.

Bimetallic nanoparticles are of interest since they lead to many interesting electrical, chemical, catalytic, and optical properties. They are particularly important in the field of catalysis since they show superior catalytic properties than their monometallic counterparts. The structures of bimetallic nanoparticles depend mainly on the synthesis conditions and the miscibility of the two components. In this work, PdPt alloyed-bimetallic nanoparticles (NPs) were synthesized through the polyol method, and characterized using spherical aberration (Cs) corrected scanning transmission electron microscopy (STEM). High-angle annular dark-field (HAADF)-STEM images of bimetallic nanoparticles were obtained. The contrast of images shows that nanoparticles have an alloy structure with an average size of 8.2 nm. Together with the characterization of nanoparticles, a systematic molecular dynamics simulations study, focused on the structural stability and atomic surface segregation trends in 923-atom PdPt alloyed-bimetallic NPs was carried out.

Background: Simulations have historically aided training programs by providing a realistic and holistic replication of professional scenarios and procedures. Simulations have developed over the past 40 years to include varying fidelities and modalities of simulation. Learning in a simulation-centered environment has benefits, ranging from improved patient care to specific skills acquisition while catering to students’ numerous and varied learning approaches. Simulation is a multifaceted field that benefits all parties, the teachers, the learners, and the patients. The application of simulation to medical education and its amalgamation with other modes and substitutes allows for a more integrated learning and testing curriculum that advances the current trajectory of medical education. Such developments, however, are limited to resource rich areas, leaving behind low-middle income countries to use traditional, less evolved methodologies and practices. This review aimed to explore different aspects of simulation and focus specifically on low-cost task trainers and their accessibility. Method: The purpose of the study was to assess the accessibility of low-cost task trainers in terms of cost-effectiveness, distribution, validation, and frequency within specific specialties. To do so, 84 PubMed publications have been screened, and 39 filtered research studies have collected the necessary data. After analyzing the papers, we classified the following information – process, specialization, validation (y/n), costs, development location, and year of publication. Results: After carefully analyzing the accumulated data from the selected 39 publications, we found that most studies (i.e., 6 out of 39) were published in 2020. Emergency Medicine was the most common specialty for which low-cost trainers were developed (9 out of 39 procedural simulators); Otolaryngology followed this with 8 out of 39 trainers and general surgery with 7/39 of the task-trainers. The price ranges fluctuated and fell within the price bracket of USD 0 to USD 400 collectively. Our review also uncovered the concentration of development of such innovations solely in high income countries (HICs). Conclusion: Simulation is an invaluable tool applicable to a diverse range of phases of medical education. Future conjunction of simulation with low-cost substitutes along with increased encouragement and enthusiasm towards developing cost effective simulation-based learning environments (SBLEs) with the reserves and requirements of these areas in mind may prove to be a reliable option for low and middle resource settings

The heavy demand of water resources from the Zarqa River Basin (ZRB) has resulted in a base-flow reduction of the River from 5m³/s to less than 1m³/s. This paper aims at predicting Curve Numbers (CN) as a baseline scenario and proposing restoration scenarios for ZRB. The method includes classifying the soil type and land use, predicting CNs, and proposing CN restoration scenarios. Prediction of existing CNs will be in parallel with the runoff prediction using the US Army Corps of Engineers HEC-1 Model, and Rainfall-Runoff Model (RRM). The models have been set up at the land use distribution of 0.3% water body, 9.3% forest and orchard, 71% mixture of grass, weeds, and desert shrubs, 7.0% crops, 4.0% urban areas, and 8.4% bare soil. The results show that CN under dry condition are 59, 78 under a normal condition and 89 under a wet condition. During vegetation period, CN are 52, 72 and 86 for the dry, normal and wet condition respectively. The restoration scenarios; CN decreases runoff, and increases soil moisture when using the contours, terraces and crop residues. Analyzing results of CN scenarios will be a fundamental tool to support end-users related to their targets to achieve watershed restoration.

Microfluidic devices which integrate both rapid mixing and liquid jetting for sample delivery are an emerging solution for studying molecular dynamics via X-ray diffraction. Here we use finite element modelling to investigate the efficiency and time-resolution achievable using microfluidic mixers within the parameter range required for producing stable liquid jets. Three-dimensional simulations, validated by experimental data, are used to determine the velocity and concentration distribution within these devices. The results show that by adopting a serpentine geometry, it is possible to induce chaotic mixing, which effectively reduces the time required to achieve a homogeneous mixture for sample delivery. Further, we investigate the effect of flow rate and the mixer microchannel size on the mixing efficiency and minimum time required for complete mixing of the two solutions whilst maintaining a stable jet. In general, we find that the smaller the cross-sectional area of the mixer microchannel, the shorter the time needed to achieve homogeneous mixing for a given flow rate. The results of these simulations will form the basis for optimised designs enabling the study of molecular dynamics occurring on millisecond timescales using integrated mix-and-inject microfluidic devices.

Natural calamities observation, study and simulation has always been a prime concern for disaster management agencies. Billions of dollars are spent annually to explore geo-seismic movements especially earthquakes but it has always been a unique accident. The real-time study of seismic waves, ground motions, and earthquakes always needed a programmable mechanical structure capable of physically producing the identical geo-seismic motions with seismology domain definitions. A programmable multi-parametric five degrees of freedom electromechanical seismic wave events simulation platform to study and experiment seismic waves and earthquakes realization in the form of geo-mechanic ground motions is exhibited in this work. The proposed platform was programmed and interfaced through an IoT cloud-based Web application. The geo-mechanics was tested in the range of i) frequencies of extreme seismic waves from 0.1Hz to 178Hz; ii) terrestrial inclinations from -10.000° to 10.000°; iii) velocities of 1km/s to 25km/s iv) variable arrival times 1us to 3000ms; v) magnitudes M1.0 to M10.0 earthquake; vi) epi-central and hypo-central distances of 290+ and 350+ kilometers. Wadati and triangulation methods have been used for entire platform dynamics design and implementation as one of key contributions in this work. This platform is as an enabler for a variety of applications such as training self-balancing and calibrating seismic-resistant designs and structures in addition to studying and testing seismic detection devices as well as motion detection sensors. Nevertheless, it serves as an adequate training colossus for machine learning algorithms and event management expert systems.

Computational neuroscience combines mathematics, computer science models, and neurosciences for theorizing, investigating, and simulating neural systems involved in the development, structure, physiology, and cognitive abilities of the brain. Computational models constitute a major stake in translational neuroscience: the analytical understanding of these models seems fundamental to consider a translation towards clinical applications. Method: We propose a minimal typology of computational models, which allows distinguishing between more realistic models (e.g., mechanistic models) and pragmatic models (e.g., phenomenological models). Result: Understanding the translational aspects of computational models goes far beyond the intrinsic characteristics of models. First, we assume that a computational model is rarely uniquely mechanistic or phenomenological. Idealization seems necessary because of i) the researcher’s perspectives on the phenomena and the purposes of the study (i.e., by the relativity of the model); ii) The complexity of reality across different levels and therefore the nature and number of dimensions required to consider a phenomenon. Especially, the use of models goes far beyond their function, and requires considering external characteristics rooted in path dependence, interdisciplinarity, and pluralism in neurosciences. Conclusion: The unreasonable use of computational models, which are highly complex and subject to a shift in their initial function, could be limited by bringing to light such factors.

During the last decades, the production systems have developed different strategies to increase their competitiveness in the global market. In a manufacturing and services systems, Lean Manufacturing has been consolidated through the correct implementation of its tools. The present paper presents a case study developed in a Food Packer company where a Simulation Model was considered as an alternative to reduce the waste time generated by the poor distribution of operations and transportation areas for a product within the factory. As a matter of fact, the company has detected problems on the layout distribution that prevents to fulfill the market demand. In addition, the principal aim was to create a simulation model to test different hypothetical scenarios and alternative designs for the layout distribution without modifying its facilities. Moreover, the implemented methodology was based on classical models of simulation projects and a compendium of the manufacturing systems optimization by simulation process used during the last ten years. Also, a mathematic model supported by the Promodel ® simulation software was developed considering the company characteristics; along with the model development, it was possible to compare the production system performance from the percentage of used locations, the percentage of resources utilization, the number of finished products, and the level of Work in Process (WIP). Finally, the verification and validation stages were performed before running the scenarios in the real production area. The results generated by the implementation of the project represent an increase of 68% in the production capacity and a reduction of 5% in the WIP. In addition, both outcomes are associated with the resources management, which were reassigned to other production areas.

The operation of electricity and natural gas transmission networks in the U.S. are increasingly interdependent, due to the growing number of installations of gas fired generators and the penetration of renewable energy sources. This development suggests the need for closer communication and coordination between gas and power transmission system operators in order to improve the efficiency and reliability of the combined energy system. In this paper, we present a co-simulation platform for examining the interdependence between natural gas and electricity transmission networks based on a direct current unit-commitment and economic dispatch model for the power system and a transient hydraulic gas model for the gas system. We analyze the value of day-ahead coordination of power and natural gas network operations and show the importance of considering gas system constraints when analyzing power systems operation with high penetration of gas generators and renewable energy sources. Results show that day-ahead coordination contributes to a reduction in curtailed gas during high stress periods (e.g., large gas offtake ramps) and a reduction in energy consumption of gas compressor stations.

Background: Simulation plays a crucial role in health studies, as it helps medical students apply their theoretical knowledge in real-life situations. Moulage is one of the techniques that helps in making simulation more realistic or high-fidelity. It uses special effects to emulate wounds for a better understanding of what the wound is like visually. Still, moulage is expensive, time-consuming, resource-intensive, and requires the training of staff, which is why we need to find low-cost substitutes for moulage materials. Method: When searching the database “PubMed” for the terms “Low-cost and Medical moulage”, we retrieved 222 studies, out of which when excluding results not related to low-cost, we obtained 62 studies, from which when removing studies that do not contain information regarding moulage, we found two papers, after referring to citations and cited articles of those papers, we ended up with six studies. Based on the selected articles and additional articles sourced from their reference list, a total of 11 studies were included in the review. Results: We understand that moulage is a technique that helps make simulations come alive, but the resources required to use it are at times, expensive, which is why we need to find methods to do low-cost moulage, and many studies address that it can be as simple as using homemade ingredients. Students from a previous study have talked about their opinions regarding the realistic component of moulage and whether if it is any different from other moulages. Most of the students agreed that the moulage ranked well in face and content validity. However, further innovations must be introduced in the field to be widely spread and lead to newer opportunities. Conclusion: Although the research done under moulage is limited, it is accepted that moulage is helpful for simulation-based studies and that low-cost moulage can help make medical studies a better experience for students studying it. Students have a favorable opinion on the realistic aspect of the low-cost moulage applied to them. Newer methods can be introduced to moulage, and it can be implemented in low-income countries.

The models used to estimate disease transmission, susceptibility and severity determine what epidemiology can (and cannot tell) us about COVID-19. These include: ‘model organisms’ chosen for their phylogenetic/aetiological similarities; multivariable statistical models to estimate the strength/direction of (potentially causal) relationships between variables (through ‘causal inference’), and the (past/future) value of unmeasured variables (through ‘classification/prediction’); and a range of modelling techniques to predict beyond the available data (through ‘extrapolation’), compare different hypothetical scenarios (through ‘simulation’), and estimate key features of dynamic processes (through ‘projection’). Each of these models: address different questions using different techniques; involve assumptions that require careful assessment; and are vulnerable to generic and specific biases that can undermine the validity and interpretation of their findings. It is therefore necessary that the models used: can actually address the questions posed; and have been competently applied. In this regard, it is important to stress that extrapolation, simulation and projection cannot offer accurate predictions of future events when the underlying mechanisms (and the contexts involved) are poorly understood and subject to change. Given the importance of understanding such mechanisms/contexts, and the limited opportunity for experimentation during outbreaks of novel diseases, the use of multivariable statistical models to estimate the strength/direction of potentially causal relationships between two variables (and the biases incurred through their misapplication/misinterpretation) warrant particular attention. Such models must be carefully designed to address: ‘selection-collider bias’, ‘unadjusted confounding bias’ and ‘inferential mediator adjustment bias’ – all of which can introduce effects capable of enhancing, masking or reversing the estimated (true) causal relationship between the two variables examined. Selection-collider bias occurs when these two variables independently cause a third (the ‘collider’), and when this collider determines/reflects the basis for selection in the analysis. It is likely to affect all incompletely representative samples, although its effects will be most pronounced wherever selection is constrained (e.g. analyses focusing on infected/hospitalised individuals). Unadjusted confounding bias disrupts the estimated (true) causal relationship between two variables when: these share one (or more) common cause(s); and when the effects of these causes have not been adjusted for in the analyses (e.g. whenever confounders are unknown/unmeasured). Inferentially similar biases can occur when: one (or more) variable(s) (or ‘mediators’) fall on the causal path between the two variables examined (i.e. when such mediators are caused by one of the variables and are causes of the other); and when these mediators are adjusted for in the analysis. Such adjustment is commonplace when: mediators are mistaken for confounders; prediction models are mistakenly repurposed for causal inference; or mediator adjustment is used to estimate direct and indirect causal relationships (in a mistaken attempt at ‘mediation analysis’). These three biases are central to ongoing and unresolved epistemological tensions within epidemiology. All have substantive implications for our understanding of COVID-19, and the future application of artificial intelligence to ‘data-driven’ modelling of similar phenomena. Nonetheless, competently applied and carefully interpreted, multivariable statistical models may yet provide sufficient insight into mechanisms and contexts to permit more accurate projections of future disease outbreaks.