Critical Negatively Charged Residues Are Important for the Activity of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides

Coronaviruses are a major infectious disease threat, and include the human pathogens of zoonotic origin SARS-CoV (“SARS-1”), SARS-CoV-2 (“SARS-2”) and MERS-CoV (“MERS”). Entry of coronaviruses into host cells is mediated by the viral spike (S) protein. Previously, we identified that the domain immediately downstream of the S2’ cleavage site is the bona fide FP (amino acids 798-835) for SARS-1 using ESR spectroscopy technology. We also found that the SARS-1 FP induces membrane ordering in a Ca2+ dependent fashion. In this study, we want to know which residues are involved in this Ca2+ binding, to build a topological model and to understand the role of the Ca2+. We performed a systematic mutation study on the negatively charged residues on the SARS-1 FP. While all six negatively charged residues contributes to the membrane ordering activity of the FP to some extent, D812 is the most important residue. We provided a topological model of how the FP binds Ca2+ ions: both FP1 and FP2 bind one Ca2+ ion, and there are two binding sites in FP1 and three in FP2. We also found that the corresponding residue D830 in the SARS-2 FP plays a similar critical role. ITC experiments show that the binding energies between the FP and Ca2+ as well as between the FP and membranes also decreases for all mutants. The binding of Ca2+, the folding of FP and the ordering activity correlated very well across the mutants, suggesting that the function of the Ca2+ is to help to folding of FP in membranes to enhance its activity. Using a novel pseudotyped virus particle (PP)-liposome methodology, we monitored the membrane ordering induced by the FPs in the whole S proteins in its trimer form in real time. We found that the SARS-1 and SARS-2 PPs also induce membrane ordering as the separate FPs do, and the mutations of the negatively charged residues also greatly reduce the membrane ordering activity. However, the difference in kinetic between the PP and FP indicates a possible role of FP trimerization. This finding could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel to combat the ongoing COVID-19 pandemic.

On the topological compatibility of parallel tasks and computing systems

The aspects of topological compatibility of parallel computing systems and tasks are investigated in the present contribution. Based on the original topological model of parallel computations and on the unconventional graph description by its projections, the introduction of appropriate indexes is proposed and elucidated. On the example of hypercubic computing system (CS) and tasks with ring and star information topologies, we demonstrate the determination of indexes and their use in a comparative analysis of the applicability of interconnect with a given topology to solve the tasks with the same and different types of information topologies.

In Silico Study of the Electrically Conductive and Electrochemical Properties of Hybrid Films Formed by Bilayer Graphene and Single-Wall Nanotubes under Axial Stretching

Using the self-consistent-charge density-functional tight-binding (SCC-DFTB) method, we studied the effect of axial stretching on the electrical conductivity and quantum capacitance of hybrid films formed by AB-stacked bilayer graphene and horizontally oriented single-walled carbon nanotubes (SWCNTs) with indices chirality (12,6). The paper discusses several topological models of hybrid graphene/SWCNT(12, 6) films, which differ in the width of the graphene layer in the supercell and in the value of the shift between the graphene layers. It is shown that axial stretching has a different effect on the electrical conductivity and quantum capacity of the hybrid graphene/SWCNT (12, 6) film depending on the width of the graphene layer. For a topological model with a minimum width of the graphene layer (2 hexagons) under a 10% stretching strain, the transformation of bilayer graphene from planar to wave-like structures is characteristic. This transformation is accompanied by the appearance of the effect of anisotropy of electrical conductivity and a sharp decrease in the maximum of quantum capacitance. For a topological model with a graphene layer width of 4 hexagons, axial stretching, on the contrary, leads to a decrease in the effect of anisotropy of electrical conductivity and insignificant changes in the quantum capacitance. Based on the obtained results, the prospects for using hybrid graphene/SWCNT(12, 6) films as a material for creating flexible electrodes of supercapacitors are predicted.

Selection of the optimal hydraulic drive for the press

The research presented in the article is devoted to the selection of the electric motor of the hydraulic press drive with a nominal force of 5MN. The article presents the main characteristics and the description of the press operation using the means of mechanization of the technological process of pressure treatment. Using the Deform-3D software package, the process of stamping the crosspiece of the ZIL-130 cardan shaft was simulated. Based on the presented hydraulic scheme of the press, its topological model was formed in the PA-9 software package. The deformation force obtained in the course of modeling the technological process of stamping was used in the topological model of the press. Using a tabular cyclogram, the sequence of actuation of the end switches and hydraulic distributors during the stamping process is shown. In the article, two variants of engine operation were analyzed. Based on the results of the conducted research, it is necessary to focus on the second version of the 55 kW engine, the operation of which will provide the required characteristics of the hydraulic drive of the press, which in turn will allow for technological stamping operations. The simulation tools allow providing estimated information when selecting the necessary tools to ensure the optimal characteristics of hydraulic press drives. The article considered the variation of electric motors that differ from each other in nominal characteristics, with constant characteristics of the pump. For more accurate estimates of energy savings during the operation of the hydraulic drive, it is necessary to vary the characteristics of the pump in the simulation, and the best option is to form an experiment planning matrix when combining the characteristics of the electric motor and the hydraulic pump. This approach ultimately allows forming a function for which one can select a hydraulic drive from existing brands of electric motors and hydraulic pumps for presses of the corresponding range of nominal force.

USE OF GRAPHS IN THE DIGITAL MODEL OF A BUILDING

Currently, the digitalization of construction projects is becoming a reality. The energy model of a build-ing (BEM) is being introduced into the design practice, which does not allow directly solving the prob-lems of designing engineering systems of a building. There is a gap in approaches to building a digital building information model. On the one hand, there is the maximum use of information from the digital model during design calculations. On the other hand, there is a simplification of mathematical models for solving problems related to the design of engineering systems. Many important tasks of design and op-eration of engineering systems are not solved in conjunction with the premises of the building. It is pro-posed to use the representation of the building as a graph, which will allow you to solve the problems of design and operation of engineering systems correctly. Most of the necessary information is already pre-sent in the building information model and can be extracted from it automatically. As an example of con-verting information from a digital model, the problem of determining the heat loss of premises was cho-sen. This task is a mandatory part of any project. Existing software products do not allow you to automat-ically determine the dimensions of the enclosing structures of the room that are necessary for solving the problem, and do not take into account the relative location of the premises. These reasons determine the need to develop the application. Materials and methods: To solve the problems of design and operation of engineering systems of a building, it is proposed to use a topological model of a building, which is a connected graph, the compo-nents of which are a base subgraph describing the connections between the premises of the building and subgraphs of engineering systems. The data structure and algorithm for forming a basic building sub-graph based on a digital building model are presented Results: The software application that implements the proposed algorithm was tested on the calculation of heat loss in the premises of a building. A 3D model of a 10-storey residential building was used as the object of the experiment. As a result of the experiment, a reduction in the time required for the prepara-tion of the initial information and for the calculation was revealed from 8 hours to 20 minutes.. Conclusions: Taking into account the relative location of building premises and life support systems in the topological model of the building allows solving problems of environmental and fire safety, optimiz-ing design solutions for supply, exhaust, smoke ventilation systems and other tasks. The developed soft-ware module designed for calculating the heat loss of premises is the first step in the development of software products that use a digital model of a building as the initial information for building a topologi-cal model.