Computational Estimation of the Acidities of Pyrimidines and Related Compounds

Pyrimidines are key components in the genetic code of living organisms and the pyrimidine scaffold is also found in many bioactive and medicinal compounds. The acidities of these compounds, as represented by their pKas, are of special interest since they determine the species that will prevail under different pH conditions. Here, a quantum chemical quantitative structure–activity relationship (QSAR) approach was employed to estimate these acidities. Density-functional theory calculations at the B3LYP/6-31+G(d,p) level and the SM8 aqueous solvent model were employed, and the energy difference ∆EH2O between the parent compound and its dissociation product was used as a variation parameter. Excellent estimates for both the cation → neutral (pKa1, R2 = 0.965) and neutral → anion (pKa2, R2 = 0.962) dissociations were obtained. A commercial package from Advanced Chemical Design also yielded excellent results for these acidities.

Calculated assessment of the impact of geometric deviations from the design on the parameters of mechanical safety of building metal structures within the framework of scientific and technical support for construction

An important part of scientific and technical support of civil engineering facilities at a construction stage - evaluation of influence of fluctuations from a designed geometry onto mechanical safety parameters of load-bearing metal structures - is considered. A multi-tier structure (industrial frame tower) is employed to demonstrate main features of such an assessment. Given is an approach to an analysis of as-built documentation and to a choice of most significant fluctuations of structural metal elements from a designed geometry. Effect of erection sequence being taken into consideration, the so-called genetic non-linearity, during computational estimation of a stress-strain state of metal structures mounted with deviations from their design positions is investigated. Results of static and dynamic analyses of designed and as-built (with geometry fluctuations taken into consideration) models of the multi-level industrial frame tower are obtained and compared with each other. Basing on these results, guidelines for computational assessment of effects of fluctuations from a designed geometry onto mechanical safety parameters of similar frame systems are formulated.

Numerical evaluation of the effectiveness of coronary revascularization

In the present paper we construct the model of coronary flow which utilizes the patient’s CT data on both large CA and perfusion. We reconstruct large coronary vessels based on the CT data and extrude possibly invisible vessels from the branches of the left coronary artery so that every terminal point supply every of standardized zone of myocardium. We apply a previously developed and validated 1D model of haemodynamics. Utilizing the patient-specific CTP data for modifying outflow terminal resistance at rest and under stress conditions is the major novelty of the present work. From our results it follows that acceptable values of fractional flow reserve (FFR) after the stenotic treatment may produce false negative output. Therefore healthy FFR values may be observed after ineffective revascularization. We also conclude that microvascular perfusion impairment plays significant role in correct computational estimation of haemodynamic indices before stenotic treatment. The advantage of the presented approach is the availability of transmural perfusion ratio assessment in everyday practice.

EXPRESS: Effects of Presentation Modality and Duration on Children’s Strategy Use: A Study in Computational Estimation

Two experiments were run to determine how presentation modality and duration influence children’s arithmetic performance and strategy selection. Third and fourth graders were asked to find estimates for two-digit addition problems (e.g., 52 + 39). Children were tested in three conditions: (1) time-unlimited visual, (2) time-limited visual, or (3) time-limited auditory conditions. Moreover, we assessed children’s working-memory updating and arithmetic fluency. Children were told which strategy to use on each problem to assess arithmetic performance while executing strategies, in Experiment 1, and were asked to choose the best strategy of three available strategies to assess strategy selection, in Experiment 2. Presentation modality influenced strategy execution (i.e., children were faster and more accurate in problems under visual than auditory conditions) but only in children with low updating abilities. In contrast, presentation modality had no effect on children’s strategy selection. Presentation duration had an effect on both strategy execution and strategy selection with time-limited presentation leading to a decline in children’s performance. Interestingly, specifically in children with low updating abilities, time-limited presentation led to poorer performance. Hence, efficient updating seemed to compensate for detrimental effects of auditory in comparison to visual and time-limited in comparison to time-unlimited presentation. These findings have important implications for determining conditions under which children execute strategies most efficiently and select the best strategy on each problem most often, as well as for understanding mechanisms underlying strategic behaviour.

Nexus of E-government, cybersecurity and corruption on public service (PSS) sustainability in Asian economies using fixed-effect and random forest algorithm

PurposeE-government development (EGD) is vital in enhancing the institutional quality and sustainable public service (SPS) delivery by eradicating corruption and cybersecurity crimes.Design/methodology/approachThe present study applied econometric fixed-effect (FE) regression analysis and random forest (RF) algorithm through machine learning for comprehensive estimations in achieving SPS. This study gauges the nexus between the EGD as an independent variable and public service sustainability (PSS) as a proxy of public health services as a dependent variable in the presence of two moderators, corruption and cybersecurity indices from 47 Asian countries economies from 2015 to 2019.FindingsThe computational estimation and econometric findings show that EGD quality has improved with time in Asia and substantially promoted PSS. It further explores that exercising corruption control measures and introducing sound cybersecurity initiatives enhance PSS's quality and support the EDG effect much better.Practical implicationsThe study concludes that E-Government has positively impacted PSS (healthcare) in Asia while controlling cybersecurity and institutional malfunctioning made an E-Government system healthier and SPS development in Asia.Originality/valueThis study added a novel contribution to existing E-Government and public services literature by comprehensively applied FE regression and RF algorithm analysis. Moreover, E-Government and cybersecurity improvement also has taken under consideration for PSS in Asian economies.

3-hydroxykynurenine as a Potential Ligand for Hsp70 Proteins and its Effects on Drosophila Memory After Heat Shock

Kynurenine products of tryptophan metabolism are modifiers of the nervous activity and oxidative processes in mammals and invertebrates. 3-hydroxykynurenine (3HOK) in moderate concentrations is a lipid peroxidation inhibitor. However, its accumulation and oxidative auto dimerization lead to oxidative stress development manifested in age-related neurodegenerative diseases (NDDs) and neurologic disorders provoked by acute stress. Different forms of stress, the mostly studied being heat shock response, rely on functioning of heat shock proteins of Hsp70 superfamily. Since kynurenines are called “kids of stress”, we performed computational estimation of affinity of 3HOK and other kynurenines binding to predicted ATP site of Drosophila Hsp70 cognate 71 protein (Dhsp71) using Autodock Vina. The binding energy of 3HOK dimer is -9.4 kcal/mol, its orientation within the active site is close to that of ATP. This might be a new mechanism of producing a competitive inhibitor of Hsp70 chaperones that decreases organism ability to adapt to heat shock. We also showed that the Drosophila melanogaster cardinal (cd1) mutant with 3HOK excess, serving as a model for Huntington's disease (HD), manifests severe defects of short-term memory after heat shock applied either in adults, or at the prepupal stage.