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COVID-19, an airborne disease caused by a betacoronavirus named SARS-- CoV-2, was officially declared a pandemic in early 2020, resulting in more than 770 million confirmed cases and over 6.9 million deaths by September 2023. Although the introduction of vaccines in late 2020 helped reduce the number of deaths, the global effort to fight COVID-19 is far from over. While significant progress has been made in a short period, the fight against SARS-CoV-2/COVID-19 and other potential pandemic threats continues. Like AIDS and hepatitis C epidemics, controlling the spread of COVID-19 will require the development of multiple drugs to weaken the virus's resistance to different drug treatments. Therefore, it is essential to continue developing new drug candidates derived from natural or synthetic small molecules. Coumarins are a promising drug design and development scaffold due to their synthetic versatility and unique physicochemical properties. Numerous examples reported in scientific literature, mainly by in silico prospection, demonstrate their potential contribution to the rapid development of drugs against SARS-CoV-2/COVID-19 and other emergent and reemergent viruses.

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The daily proportion of light and dark hours (photoperiod) changes annually and plays an important role in the synchronization of seasonal biological phenomena, such as reproduction, hibernation, and migration. In mammals, the first step of photoperiod transduction occurs in the suprachiasmatic nuclei (SCN), the circadian pacemaker that also coordinates 24-h activity rhythms. Thus, in parallel with its role in annual synchronization, photoperiod variation acutely shapes day/night activity patterns, which vary throughout the year. Systematic studies of this behavioral modulation help understand the mechanisms behind its transduction at the SCN level. To explain how entrainment mechanisms could account for daily activity patterns under different photoperiods, Colin Pittendrigh and Serge Daan proposed a conceptual model in which the pacemaker would be composed of 2 coupled, evening (E) and morning (M), oscillators. Although the E-M model has existed for more than 40 years now, its physiological bases are still not fully resolved, and it has not been tested quantitatively under different photoperiods. To better explore the implications of the E-M model, we performed computer simulations of 2 coupled limit-cycle oscillators. Four model configurations were exposed to systematic variation of skeleton photoperiods, and the resulting daily activity patterns were assessed. The criterion for evaluating different model configurations was the successful reproduction of 2 key behavioral phenomena observed experimentally: activity psi-jumps and photoperiod-induced changes in activity phase duration. We compared configurations with either separate light inputs to E and M or the same light inputs to both oscillators. The former replicated experimental results closely, indicating that the configuration with separate E and M light inputs is the mechanism that best reproduces the effects of different skeleton photoperiods on day/night activity patterns. We hope this model can contribute to the search for E and M and their light input organization in the SCN.

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This work aims to compare the ultrasonic inspection of 9%Ni steel joints welded with the Gas Metal Arc Welding (GMAW) process and Shielded Metal Arc Welding (SMAW) process. These are the two most widely used processes used to weld pipes for CO2 injection units for floating production storage and offloading (FPSO) in the Brazilian oil and gas industry. The SMAW equipment is simple and portable, which is convenient for the FPSO; however, the GMAW process has the advantage of welding with high productivity. In this study we performed a numerical simulation using the software CIVA, 11th version, to analyze the behavior of ultrasonic longitudinal wave beams through GMAW and SMAW dissimilar weld joints. Ultrasonic tests were performed on calibration blocks drawn from both welded joints to evaluate the simulation results. The results are discussed with regard to the microstructure of the weld metal via electron backscatter diffraction (EBSD) analyses. The SMAW process presented better inspection performance than the GMAW process in terms of attenuation and dispersion effects. Although the SMAW had a better outcome, for both processes the configuration of 16 active elements and a scanning angle of 48° resulted in an optimized inspection of the entire joint.

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Artificial lab manipulation of LD cycles has enabled simulations of the disruptive conditions found in modern human societies, such as jet-lag, night-work and light at night. New techniques using animal models have been developed, and these can greatly improve our understanding of circadian disruption. Some of these techniques, such as in vivo bioluminescence assays, require minimum external light. This requirement is challenging because the usual lighting protocols applied in circadian desynchronization experiments rely on considerable light input. Here, we present a novel LD regimen that can disrupt circadian rhythms with little light per day, based on computer simulations of a model limit-cycle oscillator. The model predicts that a single light pulse per day has the potential to disturb rhythmicity when pulse times are randomly distributed within an interval. Counterintuitively, the rhythm still preserves an underlying 24-h periodicity when this interval is as large as 14 h, indicating that day/night cues are still detectable. Only when pulses are spread throughout the whole 24-h day does the rhythm lose any day-to-day period correlation. In addition, the model also reveals that stronger pulses of brighter light should exacerbate the disrupting effects. We propose the use of this LD schedule-which would be compatible with the requirements of in vivo bioluminescence assays-to help understand circadian disruption and associated illnesses.

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Cellular automatons and computer simulation games are widely used as heuristic devices in biology, to explore implications and consequences of specific theories. Conway's Game of Life has been widely used for this purpose. This game was designed to explore the evolution of ecological communities. We apply it to other biological processes, including symbiopoiesis. We show that Conway's organization of rules reflects the epigenetic principle, that genetic action and developmental processes are inseparable dimensions of a single biological system, analogous to the integration processes in symbiopoiesis. We look for similarities and differences between two epigenetic models, by Turing and Edelman, as they are realized in Game of Life objects. We show the value of computer simulations to experiment with and propose generalizations of broader scope with novel testable predictions. We use the game to explore issues in symbiopoiesis and evo-devo, where we explore a fractal hypothesis: that self-similarity exists at different levels (cells, organisms, ecological communities) as a result of homologous interactions of two as processes modeled in the Game of Life.

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Adsorption studies of phenol molecules on a sodium dodecyl sulfate (SDS) micelle were investigated by molecular dynamics simulations. Simulations were carried out in bulk and on three distinct solid surfaces, silicon dioxide, titanium dioxide and graphite. It was observed that different surfactant micellar shapes were formed on the surfaces. For the silicon dioxide and titanium dioxide surfaces the surfactants were adsorbed by their headgroups whereas for the graphite surface they were adsorbed mainly by their tail groups. It was found that the amount of phenol adsorbed on the SDS micelle was altered by the surfactant shape deposited on the solid surface. However, the best phenol adsorption was obtained by the surfactant modified silicon dioxide surface. Moreover, in all cases, from structural investigations, it was determined that the phenol molecules were located inside the surfactant micelle with their hydroxyl groups close to the SDS headgroups.

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AIMS: This computational modelling work illustrates the influence of hyperkalaemia and electrical uncoupling induced by defined ischaemia on action potential (AP) propagation and the incidence of reentry at the Purkinje-ventricle interface in mammalian hearts. METHODS AND RESULTS: Unidimensional and bidimensional models of the Purkinje-ventricle subsystem, including ischaemic conditions (defined as phase 1B) in the ventricle and an ischaemic border zone, were developed by altering several important electrophysiological parameters of the Luo-Rudy AP model of the ventricular myocyte. Purkinje electrical activity was modelled using the equations of DiFrancesco and Noble. Our study suggests that an extracellular potassium concentration [K(+)]o >14 mM and a slight decrease in intercellular coupling induced by ischaemia in ventricle can cause conduction block from Purkinje to ventricle. Under these conditions, propagation from ventricle to Purkinje is possible. Thus, unidirectional block (UDB) and reentry can result. When conditions of UDB are met, retrograde propagation with a long delay (320 ms) may re-excite Purkinje cells, and give rise to a reentrant pathway. This induced reentry may be the origin of arrhythmias observed in phase 1B ischaemia. CONCLUSION: In a defined setting of ischaemia (phase 1B), a small amount of uncoupling between ventricular cells, as well as between Purkinje and ventricular tissue, may induce UDBs and reentry. Hyperkalaemia is also confirmed to be an important factor in the genesis of reentrant rhythms, since it regulates the range of coupling in which UDBs may be induced.

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Thiol redox chemical reactions play a key role in a variety of physiological processes, mainly due to the presence of low-molecular-weight thiols and cysteine residues in proteins involved in catalysis and regulation. Specifically, the subtle sensitivity of thiol reactivity to the environment makes the use of simulation techniques extremely valuable for obtaining microscopic insights. In this work we review the application of classical and quantum-mechanical atomistic simulation tools to the investigation of selected relevant issues in thiol redox biochemistry, such as investigations on (1) the protonation state of cysteine in protein, (2) two-electron oxidation of thiols by hydroperoxides, chloramines, and hypochlorous acid, (3) mechanistic and kinetics aspects of the de novo formation of disulfide bonds and thiol-disulfide exchange, (4) formation of sulfenamides, (5) formation of nitrosothiols and transnitrosation reactions, and (6) one-electron oxidation pathways.

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Se revisan los modelos de remodelación ósea empleados en simulaciones computacionales. Se describen sus principales variables y relaciones matemáticas mostrando resultados de la aplicación de cada uno de los modelos en aplicaciones clínicas

The bone remodeling models used in computer simulations are reviewed. The main variables and mathematical relations are described as well as the results of application of each of models in the clinical practice