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

Realization of electrical signal monitoring of metal surface modification by means of low-temperature plasma treatment

The paper shows good prospects of modifying the working surfaces of metal products by low-temperature plasma treatment. We suggest a treatment monitoring method based on the recording of signals that arise in the electrical circuit of the processing unit and present the results of this approach realization. The study substantiates the expediency, assesses possibility, and shows the efficiency of controlling the low-temperature plasma modification based on the correction of its operating parameters according to monitoring data

Effect of triphosphate modifications in 2′-deoxynucleoside 5′-triphosphates on their specificity towards various DNA polymerases

AbstractSome natural and glycon-modified dNTPs with β,γ-pyrophosphate substitution at the triphosphate residue were synthesized and studied to evaluate the effect of these modifications on substrate properties of dNTPs in DNA synthesis catalyzed by human placental DNA polymerases α and β, avian myeloblastosis virus reverse transcriptase, and calf thymus terminal deoxynucleotidyl transferase. Reverse transcriptase proved to be the enzyme least specific to such modifications; the substrate activity of β,γ-methylenediphosphonate substituted dTTP and 3′-azido-3′-deoxy-dTTP decreased in the following order: CF2=CHF>CBr2>CFMe≫CH2. This order is individual for each DNA polymerase. It is interesting to mention that β,γ-CBr2 substituted dTTP is neither a substrate nor an inhibitor of DNA polymerase β. This specificity distinguishes DNA polymerase β from other DNA polymerases studied

Экологическая безопасность транспортно-технологических средств

Abstract. Intensified production, an increased fleet of vehicles with internal combustion engines, as well as increased operational mass of transport and technological vehicles continuously aggravate the environmental situation in the world every year. (Research purpose) To identify the main impacts made by the transport and technological vehicles on the environment and the problems associated with their disposal, as well as with the disposal of automobile and tractor tires. (Materials and methods) The authors have generalized the materials published in periodicals, as well as the results of bench, field and operational tests of the transport and technological vehicles. (Results and discussion) The authors have identified the problem of the destructive impact of the wheeled movers on the supporting road surface, the soil and the soil cover. Measurements have been taken under the contact area of several mover types and the values of the stress-strained state of the soil affected by these movers have been determined in the form of the distribution of normal stress diagrams. The authors have also studied the influence of the design features of transport and technological vehicles performing curvilinear motion on the track size and soil destruction and identified characteristic patterns of the track. Conclusion has been made that in winter the level of environmental pollution depends on the road surface condition and the use of chemical reagents for deicing. The authors have considered a possibility of using electrical-and-hydraulic technology for the disposal of transport and technological vehicles and stressed the need to form regulatory documents for the designing, operation and disposal of transport and technological vehicles, taking into account foreign experience in organizing the environmental management system, as well as environmental auditing and labeling, the procedure for assessing the environmental performance of production systems and products at all life cycle stages. (Conclusions) The paper presents the main impact factors of the transport and technological vehicles on the environment during their life cycle up to full disposal. The authors have proved the need for a safe and energy-saving electro-hydraulic technology for the disposal of electronic components and batteries of transport and technological vehicles based on selective destruction of plastic casings and the separation of pure noble, rare-earth and other metals and their alloys.Реферат. Интенсификация производства, рост парка машин с двигателями внутреннего сгорания, а также увеличение эксплуатационной массы транспортно-технологических средств с каждым годом все больше обостряют экологическую ситуацию в мире. (Цель исследования) Выявить основные факторы воздействия транспортно-технологических средств на окружающую среду и проблемы, связанные с их утилизацией, а также с утилизацией автомобильных и тракторных шин. (Материалы и методы) Обобщили материалы, опубликованные в периодической печати, а также результаты испытаний транспортно-технологических средств – стендовых, полигонных и эксплуатационных. (Результаты и обсуждение) Выявили проблему разрушающего воздействия колесного движителя на опорную поверхность дороги, почвы и почвенный покров. Провели замеры под пятном контакта нескольких типов движителей. Определили величины напряженно-деформированного состояния почвы от воздействия этих движителей в виде распределения эпюр нормальных напряжений. Изучили влияние конструктивных особенностей транспортно-технологических средств при их криволинейном движении на размер колеи и разрушение почвы. Выделили характерные зоны следа. Заключили, что зимой уровень экологического загрязнения зависит от состояния дорожного покрытия и использования химических реагентов для борьбы с гололедом. Рассмотрели возможность использования электрогидравлической технологии при утилизации транспортно-технологических средств. Отметили необходимость формирования нормативно-правовых документов при создании, эксплуатации и утилизации транспортно-технологических средств с учетом зарубежного опыта по организации системы экологического управления, а также экологического аудита и маркировки, порядка оценки экологичности производственных систем и продукции на всех стадиях жизненного цикла. (Выводы) Представили основные факторы воздействия транспортно-технологических средства на окружающую среду в период жизненного цикла, вплоть до полной утилизации. Доказали необходимость безопасной и энергосберегающей электрогидравлической технологии утилизации электронных компонент и аккумуляторных батарей транспортно-технологических средств, базирующейся на избирательном разрушении пластиковых корпусов и выделении чистых благородных, редкоземельных и других металлов и их сплавов

At last, a Pennsylvanian stem-stonefly (Plecoptera) discovered

<p>Abstract</p> <p>Background</p> <p>Stem-relatives of many winged insect orders have been identified among Pennsylvanian fossils (Carboniferous Period). Owing to their presumed 'basal' position in insect phylogeny, stoneflies were expected to occur at this period. However, no relative has ever been designated convincingly.</p> <p>Results</p> <p>In this paper, we report specimens belonging to a new fossil insect species collected from the Tupo Formation (Pennsylvanian; China). The wing venation of <it>Gulou carpenteri </it><b>gen. et sp. nov</b>. exhibits character states diagnostic of the order Plecoptera, but lack character states shared by unequivocal representatives of the order. Derived from this identification, the delimitation of the fossil species is ascertained based on comparison of several extant stonefly species. This comparative analysis allowed a trait present in <it>G. carpenteri </it><b>gen. et sp. nov</b>., but rarely occurring in extant species, to be documented and highlighted as atavistic. Affinities of taxa formerly proposed as putative stem-stoneflies are reconsidered in the light of the new discovery.</p> <p>Conclusions</p> <p><it>Gulou carpenteri </it><b>gen. et sp. nov</b>. is considered the only genuine Plecoptera reported from the Pennsylvanian. Continuing efforts on the systematics of Pennsylvanian winged insects indicate a fauna more diverse than previously appreciated. It suggests that insects already had a long, yet undocumented, history by this time.</p

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