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Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.

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While the clinical gold standard for pressure difference measurements is invasive catheterization, 4D Flow MRI is a promising tool for enabling a non-invasive quantification, by linking highly spatially resolved velocity measurements with pressure differences via the incompressible Navier-Stokes equations. In this work we provide a validation and comparison with phantom and clinical patient data of pressure difference maps estimators. We compare the classical Pressure Poisson Estimator (PPE) and the new Stokes Estimator (STE) against catheter pressure measurements under a variety of stenosis severities and flow intensities. Specifically, we use several 4D Flow data sets of realistic aortic phantoms with different anatomic and hemodynamic severities and two patients with aortic coarctation. The phantom data sets are enriched by subsampling to lower resolutions, modification of the segmentation and addition of synthetic noise, in order to study the sensitivity of the pressure difference estimators to these factors. Overall, the STE method yields more accurate results than the PPE method compared to catheterization data. The superiority of the STE becomes more evident at increasing Reynolds numbers with a better capacity of capturing pressure gradients in strongly convective flow regimes. The results indicate an improved robustness of the STE method with respect to variation in lumen segmentation. However, with heuristic removal of the wall-voxels, the PPE can reach a comparable accuracy for lower Reynolds' numbers.

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Viability of a fractional-order proportional-integral-derivative (PID) approximation to regulate voltage in buck-boost converters is investigated. The converter applications range not only to high-power ones but also in micro/nano-scale systems from biomedicine for energy management/harvesting. Using a classic closed-loop control diagram the controller effectiveness is determined. Fractional calculus is considered due to its ability at modeling different types of systems accurately. The non-integer approach is integrated into the control strategy through a Laplacian operator biquadratic approximation to generate a flat phase curve in the system closed-loop frequency response. The controller synthesis considers both robustness and closed-loop performance to ensure a fast and stable regulation characteristic. A simple tuning method provides the appropriate gains to meet design requirements. The superiority of proposed approach, determined by comparing the obtained time constants with those from typical PID controllers, confirms it as alternative to controller non-minimum phases systems. Experimental realization of the resulting controller, implemented through resistor-capacitor (RC) circuits and operational amplifiers (OPAMPs) in adder configuration, confirms its effectiveness and viability.

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Protein immobilization by electrostatic adsorption to a support could represent a good option. On the other hand, lysozyme (EC 3.2.1.17) is a little and basic protein. The objective of this work was to test the functionality of the strategy of Rational Design of Immobilized Derivatives for the immobilization by electrostatic adsorption of egg white lysozyme on SP-Sepharose FastFlow support. The RDID1.0 software was used to predict the superficial lysozyme clusters, the electrostatic configuration probability for each cluster, and the theoretical and estimated maximum quantity of protein to be immobilized. In addition, immobilization was performed and the experimental parameter practical maximum quantity of protein to be immobilized and the enzymatic activity of the immobilized derivative were assessed. The estimated maximum quantity of protein to be immobilized (9.49 protein mg/support g) was close to the experimental practical maximum quantity of protein to be immobilized (14.73 ± 0.09 protein mg/support g). The enzymatic activity assay with the chitosan substrate showed the catalytic functionality of the lysozyme-SP-Sepharose immobilized derivative (35.85 ± 3.07 U/support g), which preserved 78% functional activity. The used algorithm to calculate the estimated maximum quantity of protein to be immobilized works for other proteins, porous solid supports and immobilization methods, and this parameter has a high predictive value, useful for obtaining optimum immobilized derivatives. The applied methodology is valid to predict the most probable protein-support configurations and their catalytic competences, which concur with the experimental results. The produced biocatalyst had a high retention of functional activity. This indicates its functionality in enzymatic bioconversion processes.

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With about 400,000 annual deaths worldwide, malaria remains a public health burden in tropical and subtropical areas, especially in low-income countries. Selection of drug-resistant Plasmodium strains has driven the need to explore novel antimalarial compounds with diverse modes of action. In this context, biodiversity has been widely exploited as a resourceful channel of biologically active compounds, as exemplified by antimalarial drugs such as quinine and artemisinin, derived from natural products. Thus, combining a natural product library and quantitative structure-activity relationship (QSAR)-based virtual screening, we have prioritized genuine and derivative natural compounds with potential antimalarial activity prior to in vitro testing. Experimental validation against cultured chloroquine-sensitive and multi-drug-resistant P. falciparum strains confirmed the potent and selective activity of two sesquiterpene lactones (LDT-597 and LDT-598) identified in silico. Quantitative structure-property relationship (QSPR) models predicted absorption, distribution, metabolism, and excretion (ADME) and physiologically based pharmacokinetic (PBPK) parameters for the most promising compound, showing that it presents good physiologically based pharmacokinetic properties both in rats and humans. Altogether, the in vitro parasite growth inhibition results obtained from in silico screened compounds encourage the use of virtual screening campaigns for identification of promising natural compound-based antimalarial molecules.

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BACKGROUND: Organocalcogens are a class of organic compounds obtained by the synthesis experiments to include S, Se, or Te. Among the elements that comprise this class, Se is characterized as an essential mineral and nutrient for humans. Se has been widely studied in many aspects. Organic synthesis of organoselenides is used for obtaining new potential drug candidates and may be highly beneficial from the use of computational approaches to reduce time and cost of the experiments. Thus, the goal of our study is to evaluate the computational approaches used in the organoselenides research from 1999 to 2019. METHODS: A literature review was performed by searching the database "Web of Sciences". RESULTS: Most of the theoretical studies included structural elucidation or structure-property analysis. We also found research regarding molecular docking approaches and Quantitative Structure-Activity Relationship (QSAR) studies. CONCLUSIONS: Computational studies have been widely applied to organoselenides. They demonstrated promising results and resulted in reduced the cost of research, increased efficacy, and, ultimately, novel organoselenides with desired properties.

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BACKGROUND: Past studies reported a low correlation between rhinomanometry and computational fluid dynamics (CFD), but the source of the discrepancy was unclear. Low correlation or lack of correlation has also been reported between subjective and objective measures of nasal patency. OBJECTIVE: This study investigates (1) the correlation and agreement between nasal resistance derived from CFD (RCFD) and rhinomanometry (RRMN), and (2) the correlation between objective and subjective measures of nasal patency. METHODS: Twenty-five patients with nasal obstruction underwent anterior rhinomanometry before and after mucosal decongestion with oxymetazoline. Subjective nasal patency was assessed with a 0-10 visual analog scale (VAS). CFD simulations were performed based on computed tomography scans obtained after mucosal decongestion. To validate the CFD methods, nasal resistance was measured in vitro (REXPERIMENT) by performing pressure-flow experiments in anatomically accurate plastic nasal replicas from 6 individuals. RESULTS: Mucosal decongestion was associated with a reduction in bilateral nasal resistance (0.34 ± 0.23 Pa.s/ml to 0.19 ± 0.24 Pa.s/ml, p = 0.003) and improved sensation of nasal airflow (bilateral VAS decreased from 5.2 ± 1.9 to 2.6 ± 1.9, p < 0.001). A statistically significant correlation was found between VAS in the most obstructed cavity and unilateral airflow before and after mucosal decongestion (r = -0.42, p = 0.003). Excellent correlation was found between RCFD and REXPERIMENT (r = 0.96, p < 0.001) with good agreement between the numerical and in vitro values (RCFD/REXPERIMENT = 0.93 ± 0.08). A weak correlation was found between RCFD and RRMN (r = 0.41, p = 0.003) with CFD underpredicting nasal resistance derived from rhinomanometry (RCFD/RRMN = 0.65 ± 0.63). A stronger correlation was found when unilateral airflow at a pressure drop of 75 Pa was used to compare CFD with rhinomanometry (r = 0.76, p < 0.001). CONCLUSION: CFD and rhinomanometry are moderately correlated, but CFD underpredicts nasal resistance measured in vivo due in part to the assumption of rigid nasal walls. Our results confirm previous reports that subjective nasal patency correlates better with unilateral than with bilateral measurements and in the context of an intervention.

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Aim: Computer-aided drug design approaches were applied to identify chalcones with antiplasmodial activity. Methodology: The virtual screening was performed as follows: structural standardization of in-house database of chalcones; identification of potential Plasmodium falciparum protein targets for the chalcones; homology modeling of the predicted P. falciparum targets; molecular docking studies; and in vitro experimental validation. Results: Using these models, we prioritized 16 chalcones with potential antiplasmodial activity, for further experimental evaluation. Among them, LabMol-86 and LabMol-87 showed potent in vitro antiplasmodial activity against P. falciparum, while LabMol-63 and LabMol-73 were potent inhibitors of Plasmodium berghei progression into mosquito stages. Conclusion: Our results encourage the exploration of chalcones in hit-to-lead optimization studies for tackling malaria.

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This work presents numerical simulations and an experimental validation of sheet laser forming processes using general scanning paths with different laser beam operating parameters (i.e., power, diameter, and scanning speed) in two specific graphite coated stainless steel blanks (i.e., with thicknesses of 0.3 mm and 0.6 mm for the AISI 302 and 304 alloys, respectively). To this end, three specific laser forming tests involving single S-shaped, multiple circular, and single piecewise linear scanning paths are carried out. On the other hand, the numerical simulation of these tests is performed via a coupled thermomechanical finite element formulation, accounting for large viscoplastic strains, temperature-dependent material properties, and convection-radiation phenomena. The final bending angles provided by this model are found to be in good agreement with the experimental measurements for all of the cases studied. Therefore, this modeling framework can be established as a reliable approach to predict the material thermomechanical response during sheet laser forming using general scanning paths.

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El Instrumento de Temor a la Evaluación Social Negativa (ITESN) ha mostrado evidencias de validez y confiabilidad al utilizarse en muestras culturalmente distintas y al traducirse a diferentes idiomas (Duke et al., 2006; Gallego, 2010; Gallego et al., 2007; Weeks et al., 2005; Tavoli et al., 2009). Dada la relevancia del estudio de la ansiedad y fobia social, y con la intención de aportar herramientas para estudiar estas variables en muestras mexicanas, este proyecto presenta evidencias de validez y confiabilidad de una traducción al castellano del ITESN (Leary, 1983) en una muestra de estudiantes universitarios de Ciudad de México. Se realizaron análisis de discriminación de reactivos, factoriales exploratorios y factoriales confirmatorios mediante modelamiento de ecuaciones estructurales. Los resultados muestran una estructura unifactorial que agrupa ocho de los doce reactivos del instrumento original, explica el 53.8 % de la varianza total y muestra consistencia interna adecuada (α = 0.88). Se obtienen evidencias de validez de criterio del ITESN, así: a) se asocia positivamente con el Instrumento de Ansiedad Rasgo y b) mediante un procedimiento experimental, se observan asociaciones positivas entre el ITESN y mediciones de ansiedad estado y motivación de autopresentación ante la expectativa de conocer a otra persona. Se discute el funcionamiento de los cuatro reactivos redactados de forma negativa y la interpretación teórica de las relaciones que respaldan la validez de criterio.

The Brief fear of Negative Evaluation Scale (BFNE) has shown good validity and reliability properties in different cultural samples, as well as when it has been translated to other languages (Duke et al., 2006; Gallego, 2010; Gallego et al., 2007; Weeks et al., 2005; Tavoli et al., 2009). Given the relevance of the study of anxiety and social phobia and the need for research tools for Mexican samples, this study presents validity and reliability evidences for a translation to Spanish language of the BFNE (Leary, 1983) in a sample of undergraduate students from Mexico City. Psychometric tests included discrimination analysis for each item, principal component factorial analysis, and confirmatory factor analysis through structural equation modeling. Results show a one factor structure with just eight of the 12 original items. It explains 53.8% of total variance and has good reliability ( α = 0.88). In addition, evidence was found concerning criterion validity for the BFNE: a) It correlates positively with a Trait Anxiety Scale; and b) through an experimental procedure, positive correlations for the BFNE with a State Anxiety Scale and a Self-Presentation Motivation Scale when participants had the expectation of being introduced to another person. The discussion verses in relation to the performance of score reversed items and the theoretical meaning of items and to the observed relationships that support the criterion validity of this translation to Spanish language of the BFNE scale.

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