Reproduction and apoptosis of EBV- latent infected cells under influence a TRIZ-created antiviral drugs

Introduction. We had worked persistently and in 1997, the first model of such a structure based on oligopeptides of horse albumin was revealed. We named this project and called Albuvir (combined from the word Albumin and the word virus) and applied in veterinary medicine, where viral infections represent more than 95% of all pathologies. In 2000 an application was filed for the first modification of this drug. Subsequently, for the production and sale of this product, registration certificates of the State Committees in Veterinary Medicine of Eastern European countries were obtained.  In 2010, we signed a license agreement to transfer of limited rights in the field of veterinary medicine for the production and sale of Albuvir in Eastern Europe. The drug was produced commercially and was successfully used to cure hundreds of thousands of chickens, rabbits, sheeps, cows, pigs, pigeons, fish (industrial - sturgeon), cats, dogs, geese, ducks, and other types of farm birds and animals. Thus, the task of this work was to study the ability of Albuvir to inhibit EBV reproduction and induce apoptosis of latently infected cells in the culture. Materials and methods. Cell culture. The inhibitory effect of Albuvir on EBV was studied in the following cell cultures: Raji - cell culture of the B-phenotype of Burkitt's lymphoma. Namalwa is a B-phenotype cell culture from Burkitt's lymphoma that lacks the EBV genome. B95-8 is a marmoset monkey B-lymphocyte cell line containing the complete EBV genome, producing complete viral particles. To control cell viability, a 0.4% trypan blue dye (Sigma, United States) was used. EBV was isolated from a lymphoblastoid culture of B95-8 cells (B-lymphocytes of monkeys-marmazetka), which produces this virus, according to the method of Walls, Crawford. Investigated substances. Albuvir (N. 1) - dynamic acylated acidic peptides - antagonists of signal peptides of nuclear (nucleolar) localization and polyribosomes. Lysine tris-succinamide (N. 2). Acyclovir was used as a reference drug (references data)  MTT test. The cytotoxic concentration was determined in the Raji lymphoblastoid cell system using the colorimetric MTT method. This method is widely used to determine the CC50 of potential drugs in the study of the cytopathic action of viruses in vitro. Raji cells were plated into 96 well culture plates, 100 μl per well, 25 μl MTT (final concentration 5 μg / ml) was added and incubated for 3 h at 37 ° C in an atmosphere of 5% CO2. After incubation, cells were washed with PBS and resuspended in 96% ethanol to dissolve formazan. The results were analyzed spectrophotometrically on a Dynatech reader (Sweden) at a wavelength of 540 nm. Polymerase chain reaction. The degree of influence of drugs on EBV reproduction was determined using PCR test systems "AmpliSens-100-R". A fragment encoding the VCA protein of the virus with a size of 290 nucleotide sequences was the chosen genome region of the Epstein-Barr virus. The control was cells that, after infection with the virus, were incubated in the growth medium without the addition of the substances that were studied. We determined the percentage of inhibition of the level of accumulation of viral DNA in the samples treated with the test substances in relation to the control sample, the value of which was taken as 100%. Results and discussion. Effect of the dynamic antiviral drug Albuvir on reproduction and apoptosis latently infected with the Epstein-Barr virus cells in vitro. Modern approaches to the treatment of herpes infection, in particular the Epstein-Barr virus (EBV), include the use of ethyotropic drugs, as well as sensitizing therapy. The range of drugs active against EBV remains very limited to ganciclovir and acyclovir. The search for new compounds active against EBV remains relevant. The aim of this study was to find out the anti-EBV activity of the drug Albuvir in Raji, B95-8, Namalwa lymphoblastoid cells. The cytotoxicity index (CC50) was determined, which was 3000 ug/mL, and the concentration of the drug that inhibits the reproduction of the virus (EC50) was 0.1 ug/mL. The ability of the drug Albuvir to inhibit the reproduction of the Epstein-Barr virus in all studied cell cultures was revealed. When the economic efficiency of creating static drugs in accordance with the S-shaped curve decreases, the need arises for a transition to a supersystem, namely, the creation of dynamic drugs systems. It has been proven that the drug Albuvir is able to inhibit the reproduction of the Epstein-Barr virus in Raji, B95-8 and Namalwa cell cultures. It is determined that the drug has a high activity in the culture of Raji cells (SI 8400), respectively, the drug is promising enough to develop as a treatment for EBV-associated diseases.DOI: 10.5281/zenodo.403892

Metasurface design for determination of protein concentration in enzymatic reaction mixture

In the paper a standard multiwell plate structure was utilized to determine the concentration of human serum albumin in water solutions and enzymatic reaction mixtures. This study marks the first application of the multiwell plate structure as a resonant metasurface unit cell through numerical simulation using the COMSOL Multiphysics software. By adjusting the operating parameters of the proposed multiwell plate (MWP) metasurface, resonance phenomena within the microwave range could be observed. The complex permittivity (CP) values of the tested solutions, obtained experimentally using the microwave dielectrometry method, were employed for the MWP metasurface modelling. The correspondence between the resonance frequency shifts of the MWP metasurface and the changes in CP values of the tested solutions was demonstrated. For the convenience of the protein concentration determination, the concentration calibration graph was proposed. Our approach enables the detection of protein concentration in the reaction mixture after 60 minutes duration of the enzymatic reaction course. The study demonstrated the customization of metasurface dimensions to enable interaction with electromagnetic waves at specific frequencies. The availability of standard multiwell plates in different sizes allows for testing solutions across various frequency ranges

Deformation Behavior of Wrought and EBAM Ti-6Al-4V under Scratch Testing

The microstructure, mechanical properties, and deformation behavior of wrought and electron beam additive manufactured (EBAM) Ti-6Al-4V samples under scratching were studied. As-received wrought Ti-6Al-4V was subjected to thermal treatment to obtain the samples with microstructure and mechanical characteristics similar to those of the EBAM samples. As a result, both alloys consisted of colonies of [alpha] phase laths within prior [beta] phase grains and were characterized by close values of hardness. At the same time, the Young's modulus of the EBAM samples determined by nanoindentation was lower compared with the wrought samples. It was found that despite the same hardness, the scratch depth of the EBAM samples under loading was substantially smaller than that of the wrought alloy. A mechanism was proposed, which associated the smaller scratch depth of EBAM Ti-6Al-4V with [alpha]′→[alpha]″ phase transformations that occurred in the contact area during scratching. Ab initio calculations of the atomic structure of V-doped Ti crystallites containing [alpha] or [alpha]″ phases of titanium were carried out to support the proposed mechanism

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Study of forward Z + jet production in pp collisions at √s=7 TeV

A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction.A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction

Elliptic flow of muons from heavy-flavour hadron decays at forward rapidity in Pb-Pb collisions at root s(NN)=2.76TeV

The elliptic flow, v(2), of muons from heavy-flavour hadron decays at forward rapidity (2.5 <y <4) is measured in Pb-Pb collisions at root s(NN)= 2.76TeVwith the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee-Yang zeros methods are used. The dependence of the v(2) of muons from heavy-flavour hadron decays on the collision centrality, in the range 0-40%, and on transverse momentum, p(T), is studied in the interval 3 <p(T)<10 GeV/c. A positive v(2) is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10-20% and 20-40% centrality classes) for the p(T) interval from 3 to about 5GeV/c with a significance larger than 3 sigma, based on the combination of statistical and systematic uncertainties. The v(2) magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6 <p(T)<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe