Drugs,Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19

Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.     

CFD‐Modellierung von Nasselektroabscheidern mit koaxial angeordneten Draht‐und Rohrelektroden

The design of electrostatic precipitators is very complex, especially if the intended operational conditions are characterized by the presence of a very high load of particles or droplets. In this case the high amount of particle bounded charge leads to a significant disturbance of the corona development causing a deterioration of precipitation efficiency. This effect is known as corona quenching. The objective of this work is the development of a numerical model based on computational fluid dynamics and capable to cover this working range.     

Effect of Scandium on Microstructure and Mechanical Properties of Cast Al-Si-Mg Alloy

Microstructural modification and grain refinement due to addition of scandium in Al-6Si-0.3Mg alloy has been studied in this article. It is seen from the microstructure that the dendrites of the cast Al-6Si-0.3Mg alloy have been refined significantly because of addition of scandium. Increasing amount of scandium leads to a greater dendrite refinement. The age hardening effect has been studied by subjecting the alloys containing varying amounts of scandium ranging from 0.2 to 0.6?wt.% to isochronal and isothermal aging at various temperatures for different times. It is observed that addition of scandium is the most effective in suppressing the softening effect during prolonged aging treatment.     

Vibrating Orifice Droplet Generator for Studying Fast Processes Associated with Microdroplets

ABSTRACT

A light scattering technique, based on resonances, has been applied to a linear stream of highly monodisperse droplets generated by a modified vibrating orifice aerosol generator to study evaporation of ethanol droplets. The residence time of droplets was varied by altering the distance between the orifice and a laser beam. Frequencies at which intensity peaks (i.e., resonances) appear in elastic and Raman scattered light were determined by varying the frequency of droplet generation. The absolute droplet size and refractive index were determined by matching the observed resonances with theoretical resonances that minimize the difference between the observed and calculated resonance frequencies. The size and refractive index changes between two successive residence time observations were determined from the frequency shifts of the resonances. These procedures permit determination of size and refractive index with a precision of 2 parts in 10⁴, and their changes within 1 part in 10⁴ of the absolute values. For the examined residence time of 650 μs the evaporation process was unsteady. The evaporation rate as well as droplet temperature estimated from the refractive index was found to decrease with time. The experimental technique can be applied to study any fast process associated with microdroplets where observable changes occur over microsecond level time scales.     

Densification and grain growth during sintering of porous Ce0.9Gd0.1O1.95 tape cast layers: A comprehensive study on heuristic methods

The sintering behavior of porous Ce_0.9Gd_0.1O_1.95 (CGO10) tape cast layers was systematically investigated to establish fundamental kinetic parameters associated to densification and grain growth. Densification and grain growth were characterized by a set of different methods to determine the dominant sintering mechanisms and kinetics, both in isothermal and at constant heating rate (iso-rate) conditions. Densification of porous CGO10 tape is thermally activated with typical activation energy which was estimated around 440–470 kJ mol^?1. Grain growth showed similar thermal activation energy of ～427 ± 22 kJ mol^?1 in the temperature range of 1100–1250 °C. Grain-boundary diffusion was identified to be the dominant mechanism in porous CGO10 tapes. Grain growth and densification mechanism were found strictly related in the investigated temperature range. Porosity acts as a grain growth inhibitor and grain boundary mobility in the porous body was estimated around 10^?18–10^?16 m³ N^?1 s^?1 at the investigated temperature range.     

Assessment of Different Measurement Methods Using <Superscript>1</Superscript>H-NMR Data for the Analysis of the Transesterification of Vegetable Oils

In the present work we make assessments of the correlation of equations based on ¹H-NMR data for the analysis of FAME in 45 transesterification products with methanol from several vegetable oils (soybean, corn, sunflower, canola, linseed, cottonseed and jatropha). The products employed in this study were of high and low yield. A comprehensive approach to the applicability, advantages and limitations of employing NMR expressions is described. A new expression to determine the degree of unsaturation of combined and free fatty acids was found to be satisfactory when compared with the classic expression. Estimates of uncertainties for classic equations, which have been used to determine yield and degree of unsaturation, were proposed in the present work. The results show that either one or both of the expressions for estimating yields could not be satisfactorily used for products from linseed oil, and also indicate the possibility that products from cottonseed oil may also be exceptions. Both the equations were found to be satisfactory for the products obtained from the other oils (soybean, corn, sunflower, canola and jatropha), considering the uncertainties proposed in the present work.     

Peptidyl Succinimidyl Peptides as Taspase 1 Inhibitors

Taspase 1 is an N‐terminal threonine protease implicated in leukemia and other cancers. Despite intensive efforts in recent years, only a limited number of Taspase 1 inhibitors are currently available, and they lack general applicability. Here we present a novel class of Taspase 1 inhibitors based on a peptidyl succinimidyl peptide motif. These inhibitors were obtained from the substrate cleavage sequence and mechanistic considerations involving the previously proposed asparaginase‐type cleavage mechanism. We anticipate that this class of Taspase 1 inhibitor will find wide application in further biochemical and structural studies, for example for better investigating the molecular details of the unusual enzymatic cleavage mechanism of Taspase 1.     

Electrical and mechanical behaviour of metal thin films with deformation-induced cracks predicted by computational homogenisation

International Journal of Fracture - Motivated by advances in flexible electronic technologies and by the endeavour to develop non-destructive testing methods, this article analyses the capability...     

Deposition of hydroxyapatite and tricalcium phosphate coatings by suspension plasma spraying: Effects of torch speed

This research focuses on the deposition of hydroxyapatite (HA) and tricalcium phosphate (TCP) coatings produced by suspension plasma spraying (SPS) using in-house liquid feedstock suspensions. The work studied the effects of torch speed on the thickness, microstructure, and crystalline composition of the coatings. SPS allowed the deposition of HA and TCP coatings with thickness between 28 and 90?μm. The coatings presented lamellar microstructure with complex porosity between the splats. Micropores ranging from 0.2 to 6?μm and close mesopores, from 8 to 45?μm, had a spherical morphology and were homogenously distributed within the coatings. Water evaporation during SPS allowed the retention of pure and crystalline HA coatings. In contrast, the presence of water molecules led to the formation of HA as a secondary phase in the TCP coatings, which formed α-TCP as the major component due to the high temperature reached by the powder during deposition.     

Densification and grain growth during early-stage sintering of Ce0.9Gd0.1O1.95−δ in a reducing atmosphere

The present work investigates the processes of densification and grain growth of Ce_0.9Gd_0.1O_1.95?δ (CGO10) during sintering under reduced oxygen partial pressure. Sintering variables were experimentally characterized and analyzed using defect chemistry and sintering constitutive laws. Based on the results achieved, the grain size–relative density relationship, the densification rate and the grain-growth rate were determined. The activation energies for densification and grain growth were evaluated, and the dominant densification mechanism was indicated. For comparison, the densification behavior of CGO10 sintered in air was also studied. Accelerated densification was observed in early-stage sintering of CGO10 in a reducing atmosphere. This might be attributed to the oxygen vacancies generated by the reduction of Ce⁴⁺ to Ce³⁺ in the reducing atmosphere, which facilitate the diffusion of ions through the lattice. The densification activation energy of CGO10 in the reducing atmosphere was evaluated to be 290 ± 20 kJ mol^?1 in the relative density range of 0.64–0.82, which was much smaller than that of CGO10 sintered in air (770 ± 40 kJ mol^?1). The grain-growth activation energy of CGO10 sintered in the reducing atmosphere was evaluated to be 280 ± 20 kJ mol^?1 in the grain size range of 0.34–0.70 μm. The present work describes a systematic investigation of sintering behavior of CGO10 under reduced oxygen partial pressure, which contributes to the first known determination of the fundamental parameters associated with densification and grain growth during early-stage sintering of CGO10 in a reducing atmosphere.