eXNVerify: coverage analysis for long and short-read sequencing data in clinical context

Accurate identification of genetic variants to a large extent is based on type of experimental technology, quality of the material and coverage of obtained sequencing data. Our motivation was to create a tool that will evaluate genome coverage and accelerate the introduction of long-read sequencing to medical diagnostics and clinical practice. Here we present eXNVerify: a tool for inspection of clinical data in the context of pathogenic variants. The tool calculates Clinical Depth Coverage – a measure of coverage which we introduce to evaluate loci with pathogenic germline and somatic variants reported in ClinVar. The tool additionally provides visualization options for user-defined genes of interest. Finally, we present an examples of BRCA1, TP53, CFTR application and results of a test conducted in the Extensive Sequence Dataset of Gold-Standard Samples for Benchmarking and Development.

Development and analysis of entropy stable no-slip wall boundary conditions for the Eulerian model for viscous and heat conducting compressible flows

Nonlinear entropy stability analysis is used to derive entropy stable no-slip wall boundary conditions for the Eulerian model proposed by Svärd (Phys A Stat Mech Appl 506:350–375, 2018). The spatial discretization is based on entropy stable collocated discontinuous Galerkin operators with the summation-by-parts property for unstructured grids. A set of viscous test cases of increasing complexity are simulated using both the Eulerian and the classic compressible Navier–Stokes models. The numerical results obtained with the two models are compared, and similarities and differences are then highlighted. However, the differences are very small and probably smaller than what the current experimental technology allows to measure.

Increasing the service life of pellet car grate bars made of 40Х24Н12СЛ steel

Intercrystallite corrosion (ICC) is the main reason to decrease service life of pellet car grate bars made of steel 40Х24Н12СЛ. In the process of the study of microstructure of pellet car grate bars manufactured according to GOST 977–88, the structure defects were established that increase the tendency to ICC. To prevent the ICC of the bars, a mode of heat treatment was elaborated, consisting of two basic operations: air hardening with preliminary exposure within 80 minutes at the temperature 1100 °С, followed by tempering within 150 minutes at the temperature 900 °С. The study of the structure of the pilot grate bar showed that the selected mode of the hardening enables to dissolve the carbide network in the structure of the detail and crash large carbides, and the subsequent tempering contributes to the growth of the carbide phase in the entire volume of metal, partially remaining in the structure after hardening. It was shown that the proposed mode of the heat treatment contributes to bringing the structure of the metal to a more “equilibrium” state, which will allow to exclude the formation of large carbides and carbide network, growth and coagulation along the grain boundary. Results of tests of a pilot batch of grate bars installed at an industrial induration machine with a working area of 768 m2 and operating temperature of 20–1310°С presented. It was established that the elaborated technology ensures absence of casting defects in the grate bars – cracks and warping, inclination of the grate bars to ICC, increased by 23.13% heat resistance compared to the reference grate bars of foreign supply due to the globular form of carbide secretions with a minimum length of borders along which the metal matrix is depleted by chrome. Industrial testing of the grate bars manufactured under the experimental technology has proved the practical significance and applicability of the performed research.

OF FUNCTIONAL AND TECHNOLOGICAL PROPERTIES OF SEMI-FINISHED LEATHER PROPERTIES WITH DIMETHYL SULFOXIDE USE

The work is devoted to the study of the possibility of using dimethylsulfoxide (DMSO) in the technology of obtaining a semi-finished leather product to improve its functional and technological properties and to intensify the process of leather production. The semi-finished leather product was prepared according to the traditional (control) and experimental technologies by dipping method. The experimental technology involved the introduction of DMSO into ash, pickle and tannin solutions in various concentrations: 2.0; 2.5; 3.0 % of the weight of the minnow for each operation, as well as in the proportion of 3.0 % in the ash solution and 1.5% in the pickle and tannin. The best results on the welding temperature and deformation properties of the semi-finished leather product were obtained when using DMSO in concentrations of 2.0:2.0:2.0 % and 3.0:1.5:1.5 % of the minnow weight. In addition, the advantage of the proposed technical solution is the ability to optimise the process of ashing and pickling.

Physical Simulation Experimental Technology and Mechanism of Water Invasion in Fractured-Porous Gas Reservoir: A Review

In the development process for a fractured-porous gas reservoir with developed fracture and active water, edge water or bottom water easily bursts rapidly along the fracture to the production well, and the reservoir matrix will absorb water, reducing the gas percolation channel and increasing the gas phase percolation resistance of the reservoir matrix, therefor reducing the stable production capacity and recovery efficiency of the gas reservoir. For this reason, this paper investigates physical simulation experimental technology and mechanisms as reported by both domestic and foreign scholars regarding water invasion in fractured-porous gas reservoirs. In this paper, it is considered that the future trend and focus of water invasion experiments will be to establish a more realistic three-dimensional physical model on the basis of fine geological description, combined with gas reservoir well pattern deployment and production characteristics, and to fully consider the difference between horizontal and vertical water invasion along the reservoir side; at the same time, dynamic parameters such as model pressure field and water saturation field can be obtained in real time. Based on this understanding of the water invasion mechanism of fractured-porous gas reservoirs, we propose the next research direction and the development countermeasures such as water controls, drainage, and dissolved water seals and water locks to combat water invasion in reservoirs, along with the injection of gas to replenish formation energy, etc., so as to slow down and control the influence of water invasion.

Function Characterization of Endogenous Plasmids in Cronobacter sakazakii and Identification of p-Coumaric Acid as Plasmid-Curing Agent

Virulence traits and antibiotic resistance are frequently provided by genes located on plasmids. However, experimental verification of the functions of these genes is often lacking due to a lack of related experimental technology. In the present study, an integrated suicide vector was used to efficiently and specifically delete a bacterial endogenous plasmid in Cronobacter sakazakii. The pESA3 plasmid was removed from C. sakazakii BAA-894, and we confirmed that this plasmid contributes to the invasion and virulence of this strain. In addition, the pGW1 plasmid was expunged from C. sakazakii GZcsf-1, and we confirmed that this plasmid confers multidrug resistance. We further screened plasmid-curing agents and found that p-coumaric acid had a remarkable effect on the curing of pESA3 and pGW1 at sub-inhibitory concentrations. Our study investigated the contribution of endogenous plasmids pESA3 and pGW1 by constructing plasmid-cured strains using suicide vectors and suggested that p-coumaric acid can be a safe and effective plasmid-curing agent for C. sakazakii.

Optimization of production technologyof continuous cast rail steel for increasing its purity by non-metallic inclusions

The purpose of the work was to examine the reasons for formation of non-deformable non-metallic inclusions in rail steel and ways to reduce the rejection of finished rails due to the defects revealed during ultrasonic testing. The study was conducted at the steelmaking plant of JSC “Ural Steel”. In the central laboratory of the combine, a chemical analysis of non-metallic inclusions was carried out in the samples of finished rails produced from blanks manufactured by JSC “Ural Steel” and rejected at the ultrasonic test unit during the rail production at the “Aktobe Rail and Section Works” LLP. Non-metallic inclusions by their composition are represented by aluminium oxides. The most probable reasons for their formation have been determined as following: the use of aluminium containing ferroalloys and interaction of the melt components with refractory materials and casting powder. The authors made analysis of the ferroalloys used in production of rail steel. Industrial trials of the manufacturing process of continuously cast blanks from rail steel were carried out, where FS65 ferrosilicon, which contains aluminium, was replaced with silicon carbide. An increasing degree of silicon and carbon recovery in trial heats was noted. Evaluation of contamination with non-metallic inclusions and mechanical properties of the rail steel manufactured using the experimental technology showed that the service characteristics of the rail steel meet requirements of the state standard GOST R 51685 – 2013. The full-scale experiment has confirmed that the technology of alloying E76F rail steel with silicon carbide at JSC “Ural Steel” is technically feasible. The yield of 100-meter rails was increased by 17 % on a trial batch produced from JSC “Ural Steel” continuously cast blanks.

The Newtonian Gravitational Constant G Interpreted as the Gravitational Inertia of Vacuum - G0. How to Arrange Twelve Precise Experimental Determinations of GZ in their Spread 500 ppm?

We have newly interpreted the Newtonian gravitational constant G as the gravitational inertia of vacuum G0. The source mass inserted into vacuum decreases this value G0 to GZ on the dependence of the atomic number Z of atoms in the source mass. This is the mechanism for the attraction of test masses through vacuum – the test mass follows the decrease of the gravitational inertia of vacuum towards the source mass. We have extracted the relationship GZ = G0 (1 – k Z) where k is the experimental constant from ten actual precise experimental determinations of GZ. This model was tested on two precise experimental values of GZ determined for GEARTH, and GBRASS. This model enables to predict values GZ for atoms, molecules and compositions of the studied source masses and to realize experimental verification with the existing experimental technology. The experimental GZ values are thus arranged into a system and the spread in these data is explained as the influence of atoms of the source masses on their surrounding via the decrease of the gravitational inertia of vacuum. We might achieve the accuracy of experimental values GZ with six significant figures for all configurations of source and test masses.