Integrated Computer Simulation Research Articles

Kinetic pathway of HIV-1 TAR cotranscriptional folding.

The Trans-Activator Receptor (TAR) RNA, located at the 5'-end untranslated region (5' UTR) of the human immunodeficiency virus type 1 (HIV-1), is pivotal in the virus's life cycle. As the initial functional domain, it folds during the transcription of viral mRNA. Although TAR's role in recruiting the Tat protein for trans-activation is established, the detailed kinetic mechanisms at play during early transcription, especially at points of temporary transcriptional pausing, remain elusive. Moreover, the precise physical processes of transcriptional pause and subsequent escape are not fully elucidated. This study focuses on the folding kinetics of TAR and the biological implications by integrating computer simulations of RNA folding during transcription with nuclear magnetic resonance (NMR) spectroscopy data. The findings reveal insights into the folding mechanism of a non-native intermediate that triggers transcriptional pause, along with different folding pathways leading to transcriptional pause and readthrough. The profiling of the cotranscriptional folding pathway and identification of kinetic structural intermediates reveal a novel mechanism for viral transcriptional regulation, which could pave the way for new antiviral drug designs targeting kinetic cotranscriptional folding pathways in viral RNAs.

Development of the Integrated Computer Simulation Model of the Intracellular, Transmembrane, and Extracellular Domain of Platelet Integrin α IIb β 3 (Platelet Membrane Glycoprotein: GPIIb-IIIa).

Background The structure and functions of the extracellular domain of platelet integrin α IIb β 3 (platelet membrane glycoprotein: GPIIb-IIIa) change substantially upon platelet activation. However, the stability of the integrated model of extracellular/transmembrane/intracellular domains of integrin α IIb β 3 with the inactive state of the extracellular domain has not been clarified. Methods The integrated model of integrin α IIb β 3 was developed by combining the extracellular domain adopted from the crystal structure and the transmembrane and intracellular domain obtained by Nuclear Magnetic Resonace (NMR). The transmembrane domain was settled into the phosphatidylcholine (2-oleoyl-1-palmitoyl-sn-glycerol-3-phosphocholine (POPC)) lipid bilayer model. The position coordinates and velocity vectors of all atoms and water molecules around them were calculated by molecular dynamic (MD) simulation with the use of Chemistry at Harvard Macromolecular Mechanics force field in every 2 × 10 -15 seconds. Results The root-mean-square deviations (RMSDs) of atoms constructing the integrated α IIb β 3 model apparently stabilized at approximately 23 Å after 200 ns of calculation. However, minor fluctuation persisted during the entire calculation period of 650 ns. The RMSDs of both α IIb and β 3 showed similar trends before 200 ns. The RMSD of β 3 apparently stabilized approximately at 15 Å at 400 ns with persisting minor fluctuation afterward, while the structural fluctuation in α IIb persisted throughout the 650 ns calculation period. Conclusion In conclusion, the integrated model of the intracellular, transmembrane, and extracellular domain of integrin α IIb β 3 suggested persisting fluctuation even after convergence of MD calculation.

CoSiReT: Innovation of ReT (Refutation Texts) to Reduce Students' Misconceptions Concerning Transverse Waves

The research goal was to develop innovative learning media on refutation texts (ReT), scilicet integrating Computer Simulations on Refutation Texts (CoSiReT). CoSiReT's role is to reduce students' misconceptions concerning the basic concept of transverse waves. This research design used 4D (Define, Design, Develop, and Disseminate). Participants include 64 students aged 16-18 years in the Tuban region, East Java, Indonesia (37 male were called Mas, and 27 female were called Mbak). The research instrument used a media validation sheet (15 assessment indicators). The pre-post test instrument used the Multi-representation of a Four-tier Instrument on Transverse Wave (MOFI-OTW). Analysis of data validation results was using a rater test assisted by Rasch's Mini-Facets software. According to the seven validators, the results of CoSiReT fulfill aspects of instructions for use, language, content presentation, and appearance. The percentage of students' misconception reduction was analyzed using the Reduction Misconceptions (RM) adapted from Hake's n-gain equation. Overall, the reduction of misconceptions is in the high category. Thus, it can be concluded that CoSiReT can be developed and used a role in reducing student misconceptions. Researchers or practitioners are expected to implement CoSiReT as a learning innovation that aims to reduce basic misconceptions of transverse waves.

Modeling of Resistance Spot Welding Using FEM

The resistance spot welding process is significant for joining materials in the automotive industry because it offers high speed and can be easily automated. Recently, there has been a demand in the automotive industry to reduce vehicle weight to improve fuel efficiency. Aluminium alloys are considered a viable alternative for auto-body materials to meet this requirement. It not only helps enhance fuel efficiency but also addresses the issue of vehicle corrosion. However, joining aluminium through resistance spot welding presents serious challenges compared to steel. One significant difficulty arises from the faster deterioration of electrodes. Aluminium alloys possess high electrical and thermal conductivity, significant shrinkage during solidification, and a natural oxide coating. These features make the spot welding process for aluminium alloys notably distinct. When exposed to high temperatures, aluminium undergoes a chemical reaction with the copper alloy found in the electrode material. This results in the unpredictable removal of material from the electrode surfaces, causing wear and significantly reducing the lifespan of the electrode during spot welding of aluminium alloys. This decrease in electrode tip longevity poses a significant drawback in weldability, as the durability of the electrode tip significantly affects its suitability for automotive applications. Due to the rapid nature of the process, obtaining crucial information, such as the transient distribution of current density and temperature through experimental methods, becomes challenging. Therefore, this study aims to develop an integrated computer simulation model using the finite element method to analyze the resistance spot welding process of aluminium alloys. Multiple calculations were performed considering different welding currents, weld times, electrode forces, and various surface conditions of the aluminium sheets. The simulation considers the nonlinear, temperature-dependent, thermo-physical properties of the materials. Interestingly, it was observed that in most cases, the nugget diameter is formed within a short time frame of 0.02 to 0.04 seconds, and further application of welding current primarily increases the heating of the electrode face. Moreover, the aluminium sheets’ initial surface condition significantly influences the nugget’s formation. Several other conclusions have been drawn as a result of this study.

A latent survival model integrated computer simulation-based evaluation for nursing home staffing

Nursing homes (NHs) are critical facilities for caring frail older adults with around-the-clock formal care and personal assistance. To ensure quality of care for NH residents, an adequate staffing level is of great importance. Current NH staffing practice is mainly based on experience and regulation. The objective of this paper is to investigate the viability of experience-based and regulation-based strategies, as well as alternative staffing strategies to meet the heterogeneous service demand of NH residents at reduced labor cost under various scenarios of census compositions. We propose a predictive analytics integrated computer simulation model to characterize the heterogeneous service demand of NH residents, and further evaluate and identify promising staffing strategies at the facility level. Specifically, we propose a predictive model based on latent survival analysis to characterize diverse length-of-stay (LOS) with multiple discharge dispositions among NH residents. Further, we develop a simulation model with the incorporation of predictive analytics and domain knowledge to characterize the heterogeneous service demand of NH residents on different types of caregivers over time. Based on the simulation model, we develop a graphical user interface for the simulator to evaluate different staffing strategies at the facility level and inform NH administrators about promising strategies. We use real NH data to validate the proposed model and demonstrate its effectiveness. The proposed predictive LOS model considering multiple discharge dispositions exhibits superior prediction performance and offers better staffing decisions at reduced costs than those without the consideration. With the improved modeling fidelity via integrating predictive analytics with computer simulation, the proposed model is flexible to evaluate various staffing strategies using total labor cost as a performance metric, and can identify promising staffing strategies to meet the service demand of NH residents. Promising staffing strategies with the suggested staff-to-resident (SR) ratio can significantly reduce the total labor cost of multiple types of caregivers, as compared to the benchmark strategies, such as the SR ratios based on industrial practice or minimum requirement of state regulation. Moreover, we construct multiple scenarios of different census compositions of NH residents to demonstrate the capability of the proposed model. Our proposed model can facilitate NH staffing decision making to meet the heterogeneous service demand of NH residents at reduced labor costs.

Integrative Strategy for Investigating the Interactions between STING and Small-Molecule Ligands.

Although small-molecule agonists of stimulator of interferon genes (STING) show significance in activating the immune system, the dynamic process involved in ligands activating STING remains unclear. Herein, we developed a biochemical strategy, integrating computer simulation and a biochemical engineering approach, to reveal the interaction mechanism between STING and 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an agonist that activates the TANK binding kinase 1-interferon regulatory factor 3 signaling pathway. Specifically, inspired by an analysis of the STING-DMXAA crystal structure, we designed and synthesized DMXAA derivatives to investigate the STING-DMXAA binding model. We identified that the carboxyl moiety of DMXAA was a major pharmacophore responsive to STING activation. In particular, the loss of hydrogen bond interaction between the carboxylic acid of DMXAA and the side chain Thr262 of STING led to STING inhibition. DMXAA N-methyl amide derivative (DNHM) exhibited good inhibitor activity, inhibited STING-mediated interferon production in vitro and in vivo, and effectively attenuated STING-associated inflammatory diseases. Therefore, we provide a new insight into STING-ligand interactions, which may improve the understanding of STING biology.

Integrating computer simulation and the normalized normal constraint method to plan a temporary hospital for COVID-19 patients

Although Temporary Hospitals (THs) usually present improvised structures, they are considered necessary solutions in extreme situations, such as critical moments of the COVID-19 pandemic. Timely planning of hospital resources is a challenging task for public health decision-makers and essential to caring for patients to ensure the healthcare system's sustainability. For this reason, we propose the integration of Discrete Event Simulation (DES), Response Surface Methodology (RSM), and Normalized Normal Constraint (NNC) for planning a TH in Brazil amid the COVID-19 pandemic. While DES is an outstanding process modelling approach, RSM and NNC are methods for planning and analysing experiments and generating a representative set of optimal solutions for decision-makers. This study defined the number of beds in the Short Stay Unit (SSU) that maximizes the number of patients attended and the patient conformity rate while minimizing the SSU daily cost. Moreover, two uncontrollable input factors are also considered: the number of patients arriving at the TH and the percentage of these patients who have COVID-19. We developed complete and evenly distributed Pareto frontiers considering controllable and uncontrollable factors, which decision-makers can use according to the metrics prioritization and the pandemic status.

Multiscale Modeling of the Mitochondrial Origin of Cardiac Reentrant and Fibrillatory Arrhythmias.

While mitochondrial dysfunction has been implicated in the pathogenesis of cardiac arrhythmias, how the abnormality occurring at the organelle level escalates to influence the rhythm of the heart remains incompletely understood. This is due, in part, to the complexity of the interactions formed by cardiac electrical, mechanical, and metabolic subsystems at various spatiotemporal scales that is difficult to fully comprehend solely with experiments. Computational models have emerged as a powerful tool to explore complicated and highly dynamic biological systems such as the heart, alone or in combination with experimental measurements. Here, we describe a strategy of integrating computer simulations with optical mapping of cardiomyocyte monolayers to examine how regional mitochondrial dysfunction elicits abnormal electrical activity, such as rebound and spiral waves, leading to reentry and fibrillation in cardiac tissue. We anticipate that this advanced modeling technology will enable new insights into the mechanisms by which changes in subcellular organelles can impact organ function.

Computer Simulation Integration in Secondary Physics

This paper explored the teaching experiences of physics teachers in integrating computer simulations in their pedagogy to promote a constructivist learning environment. Its objectives are to determine how physics teachers describe computer simulations based on how they are used, how these are embedded in the teaching-learning process, their impact on the teaching-learning process, and the challenges of integrating these into physics teaching. Using the phenomenological design, two themes emerged for the first objectives, which are process-based and system-based. First, the teacher-manipulated with sub-themes of engaging, demonstrating, elaborating, and evaluating, and student-manipulated emerged on how the simulations are used. Second, the impact to teaching generated knowledge-based, skill-based, and value-based learning-based primarily on the three learning domains. Also, respondents emphasized that the integrations of computer simulations are convenience, efficacy, and heterogeneity. Finally, the challenges in the integration process are classified as teacher and school-related. The results showed that teachers are integrating computer simulations differently depending on their resources and the TPACK knowledge.

Anisotropic protein organofibers for cellular mechanobiology applications

Anisotropic protein organofibers for cellular mechanobiology applications

On the role of integrated computer modelling in fusion technology

• We analyse critically current capabilities and maturity levels of existing simulation tools relevant to fusion blanket physics and design. • The progress in the development of computational tools in each particular is found to be significant. • The requirements that need to be addressed for code integration are common to all areas and tools. • The integration into one single computational tool is currently premature and looser coupling ways need to be considered. Computer modelling is expected to play an increasingly important role in fusion design and technology, where the complexity of the physical processes involved (plasma, materials, engineering), and the highly interconnected nature of systems and components (“system of systems” design), call for support from sophisticated and integrated computer simulation tools. In this paper, we review the contribution of coupled computer modelling to the design of the reactor, breeding blanket and integrated first wall in terms of neutronics, materials behaviour (including plasma-materials interaction, radiation effects and compatibility with fluids), magnetohydrodynamics thermofluid issues and thermo-hydraulic aspects, as well as simulations of plasma transport out of the confinement region to determine heat and particle loads on plasma facing components. The current capabilities and levels of maturity of existing simulation tools are critically analysed, having in mind the possibility of integrating several tools in a single computational suite in the future and highlighting the perspectives and difficulties of such an endeavour.

Students\u2019 problem-solving strategies in qualitative physics questions in a simulation-based formative assessment

Previous studies on quantitative physics problem solving have been concerned with students’ using equations simply as a numerical computational tool. The current study started from a research question: “How do students solve conceptual physics questions in simulation-based formative assessments?” In the study, three first-year college students’ interview data were analyzed to characterize their problem-solving strategies in qualitative physics questions. Prior to the interview, the participating students completed four formative assessment tasks in physics integrating computer simulations and questions. The formative assessment questions were either constructed-response or two-tiered questions related to the simulations. When interviewing students, they were given two or three questions from each task and asked to think aloud about the questions. The findings showed that students still used equations to answer the qualitative questions, but the ways of using equations differed between students. The study found that when students were able to connect variables to a physical process and to interpret relationships among variables in an equation, equations were used as explanatory or conceptual understanding tools, not just as computational tools.

The Impact of Integrating Computer Simulations and Videos on Senior Secondary School Learners’ Performance Achievement on Atomic Physics and Radioactivity Concepts

This study explored the impact of integrating computer simulations and videos in addition to lecture discussions on learner’s understanding of concepts on atomic physics and radioactivity. The study was a randomly assigned pre-test post-test counter balanced quasi-experimental design involving two grade 11 classes at a secondary school located in Kitwe on the Copperbelt Province of Zambia. One class was assigned to be the experimental group while the other was made the comparison group for six lessons. Post-test results were analysed following teaching using computer simulations, video and lecture method (experimental group) and using videos only and lecture method (comparison group). In the second half the groups were swapped for purposes of counterbalancing. Post-tests on achievement were analysed yielding a comparison of the groups under the different treatments. Results indicated that the mean of the experimental group (Epost-test = 66.60%) was significantly higher than the mean of the comparison group (C post-test = 45.68%) (t = 4.179; df, 37; p = .000; α = .05). The results indicated a substantial effect size by Cohen's d of 1.34. Overall, the results suggest that integrating computer simulations and videos into teaching atomic physics and radioactivity significantly enhances learners' performance.

Development of learning instrument of active learning strategy integrated with computer simulation in physics teaching and learning on makassar state university

One of the physics learning strategies in the university is active learning. Active learning strategy requires students to be able to learn independently. So that this can be realized learning should be integrated with computer simulation.This research aims to produce learning instrument of active learning strategy integrated computer simulation which are valid, and reliable on Physics Department, Makassar State University. The type of this research is a 4D Development model. The development procedure was referred to Four-D model consisted of definition phase, design phase, development phase and dissemination phase. The data analysis used Content Validity Ratio (CVR), Content Validity index and continued with reability analysis. Before used in the real class then first was conducted a limited trial test. a limited trial test aimed to avoid biased data by taking 5 students as a limited trial sample. The results obtained that physics learning instrument of active learning strategy integrated computer simulation were valid and reliabel.

Lesson Exemplars in Electricity and Students’ Epistemological Beliefs

The study evaluated the effects of a developed lesson exemplars in electricity integrating computer simulations and constructivist approach on students' Epistemological Beliefs. Specifically, it sought to determine how computer simulations, constructivist approach and Formative Assessment Classroom Technique (FACT) can be integrated with the lesson exemplars in electricity; and evaluate the effects of the developed lesson exemplars in the students’ Epistemological Beliefs. The investigation employed the pre-experimental single-group pretest and posttest study using the Epistemological Beliefs Assessment in Physical Sciences (EBAPS) questionnaire. The study was conducted among seventy-two (72) Grade 10 students of a laboratory high school from a state university in the Philippines. They were taught using Physics Educational Technology (PhET) and other web-based simulations, constructivist approach, and formative assessment classroom technique. The results revealed that the over-all Epistemological Beliefs of the students did not change significantly; only along Nature of Knowing and Learning and Real-Life Applicability. Generally, utilizing computer simulations and applying constructivist approach did not alter students' epistemological beliefs in its entirety. However, it can be engaging and effective in promoting students’ understanding of Physics.

Numerical simulation of ballistic electron dynamics and heat transport in metallic targets exposed to ultrashort laser pulse

The role of ballistic electrons generated during ultrashort pulse laser (USPL) absorption in metallic targets was investigated in a wide range of laser intensities using our developed simulation package FEMTO-2D. The simulation package is based on the numerical solution of the two-temperature model with the assumption of local thermal equilibrium for electron and lattice subsystems within the simulation cell at any time step. Electron thermodynamic parameters were calculated through the processes of material transition from the cold solid state into the dense plasma state during and after the pulse based on the collision theory. The appropriate model for temperature dependent thermodynamic parameters allows defining the heat transport during an early stage of the USPL-matter interaction directly, without relying on the effective absorption depth model. The study investigated, for the first time, using integrated computer simulation the role of ballistic electrons in energy transfer and heat conduction during USPL deposition. The simulation predictions of the electron heat transport dynamics during and shortly after the laser pulse were benchmarked for the gold target against available experimental data and were able to confirm the dominant role of the ballistic electrons in the initial heat propagation within 100–120 nm of the target at laser intensities below 1013 W/cm2.

Automating computer simulation and statistical analysis in production planning and control research

Computer simulation is commonly used to study production planning and control prior to actual shop floor implementation. The majority of simulations are discrete events and involve modeling of elements and interactions. A complete simulation analysis requires multiple runs to infer stochastic behaviors of the system under different combination of factors. The analysis takes in results obtained from all the runs and confirms a hypothesis statistically. The resources required greatly rely upon the number of simulation models, simulation run length, technical knowledge, and computer resource available. Although latest commercial production simulation software allows some forms of automation, the analysis functions included are considered rudimentary. Integrating computer simulation and advanced statistical methods can result in substantial time and resource savings. In this paper, computer simulation and statistical analysis have been integrated and automated to cater for a large combination of simulation runs. With the system named as ProSA (production simulation and analysis), the work has been completed in 2011 and was demonstrated in a recent case study. The evidence provides concrete proof of such a possibility and provides an invitation to others to explore application research into technical knowledge and tasks transfer to computer.

Entrainment of circadian rhythms to irregular light/dark cycles: a subterranean perspective.

Synchronization of biological rhythms to the 24-hour day/night has long been studied with model organisms, under artificial light/dark cycles in the laboratory. The commonly used rectangular light/dark cycles, comprising hours of continuous light and darkness, may not be representative of the natural light exposure for most species, including humans. Subterranean rodents live in dark underground tunnels and offer a unique opportunity to investigate extreme mechanisms of photic entrainment in the wild. Here, we show automated field recordings of the daily light exposure patterns in a South American subterranean rodent, the tuco-tuco (Ctenomys aff. knighti ). In the laboratory, we exposed tuco-tucos to a simplified version of this natural light exposure pattern, to determine the minimum light timing information that is necessary for synchronization. As predicted from our previous studies using mathematical modeling, the activity rhythm of tuco-tucos synchronized to this mostly simplified light/dark regimen consisting of a single light pulse per day, occurring at randomly scattered times within a day length interval. Our integrated semi-natural, lab and computer simulation findings indicate that photic entrainment of circadian oscillators is robust, even in face of artificially reduced exposure and increased phase instability of the synchronizing stimuli.

Integration of Computer Simulation, Design of Experiments and Particle Swarm Optimization to Optimize the Production Line Efficiency

The goal of this paper is to optimize the productivity of manufacturing system by integrating computer simulation, design of experiments (DOE) and particle swarm optimization (PSO) algorithm. Optimizing productivity of colour factory was considered as the case of this study. To evaluate and estimate the effect of main factors, 2n factorial design with higher and upper levels and centre points was considered. After obtaining the significant factors, the local optimum setting of the significant factors was determined using the steepest ascent method and response surface methodology (RSM) approach. Finally, the global optimum productivity was achieved by computer programing of PSO method. Base on the final result, maximum productivity occurs in the point of 87.23 that is relevant to number of labour (B) = 26 and failure time of lifter (C) = 78.04 min. In addition, other two factors A (Service rate of Delpak mixer) and D (Number of permil) should be located at low level to obtain maximum productivity.

Simulation optimisation of total cost in M/G/C retrial queuing systems with geometric loss, feedback and linear retrial policy

This paper presents an integrated computer simulation model for optimisation of total cost in an M/G/C retrial queue system with geometric loss, feedback and linear retrial policy. First, the computer simulation model is used to verify and validate an M/G/C retrial queue system. Second, certain important performance measures are obtained under steady–state condition. Finally, the simulation model is used to identify the preferred alternatives to optimise the current system. Significantly, it should be noted that there is no mathematical model to analyse an M/G/C retrial queue system. In this study, an integrated approach is used to develop the simulation model of the M/G/C retrial queue system. The objective of simulation model is to minimise the total cost and find the optimum solution. Also, a case study provided in which incoming calls of a clinic are modelled and analysed, because the most obvious retrial queue application lies in phone calls. This is the first study that utilises an integrated simulation approach for optimisation of total cost in an M/G/C queuing system with geometric loss and linear retrial policy.