Ulyanovsk Automobile Plant during Great Patriotic War: Problem of Personnel and Its Solution

The process of the labor collective formation of the Ulyanovsk Automobile Plant during the Great Patriotic War is studied. The relevance of the study is due to the need for a detailed study of the mechanisms of the automotive industry functioning in the extreme conditions of the Great Patriotic War. Documents on the history of the enterprise evacuation, materials of the primary party organization of the automobile plant, office work documentation of the party and state authorities, factory and departmental reports, and eye-witness accounts of the events were used as sources. The process of creating the Ulyanovsk Automobile Plant, constructed on the basis of the evacuated equipment and labor resources of the Moscow Automobile Plant named after I.V. Stalin (ZIS), is considered. Changes in the number and composition of the enterprise's employees during 1941—1945 are analyzed. Particular attention is paid to the interdependence of the change in the number of employees of the plant on the volume of industrial output. It is concluded that thanks to the evacuation of experienced engineers, production managers and highly skilled workers, it was possible to maintain and recreate hightech production in the rear areas of the country. It was noted that the enterprises created during the evacuation laid the foundation for the development of automotive production in the Volga region and the Urals

Increasing protectivity of the smallpox vaccine

At the present time, vast majority of human population lacks immunity against orthopoxvirus infections caused by variola (smallpox), monkeypox, cowpox, or buffalopox viruses. More and more mass outbreaks of orthopoxvirus infections are yearly registered among humans on different continents. To prevent transition of these outbreaks to widespread epidemics, we should develop appropriate immunoprophylaxis strategies. Currently, massive usage of the classic live vaccine based on vaccinia virus is not acceptable, due to its high reactogenicity. Therefore, it is necessary to develop the variants of vaccinia virus with reduced virulence and increased immunogenicity/protectivity. The aim of this work was to study protective effects against a lethal orthopoxvirus infection occuring after low-dose immunization of mice with vaccinia virus variants, i.e., carrying mutant A34R gene causing increased production of extracellular virions, or a A35R gene deletion encoding protein product inhibiting antigen presentation by the major histocompatibility complex class II. The LIVP viral strain used in Russia as a smallpox vaccine, and its recombinant variants (LIVP-A34R*, LIVP-dA35R and LIVP-A34R*-dA35R) were compared with intranasal or intradermal immunization of BALB/c mice at the doses of 105 or 103 PFU. 28 days following administration of viral preparations (experimental groups) or saline (control groups), the mice underwent intravital blood sampling from retroorbital venous sinus. The levels of virion-specific antibodies were determined in individual serum samples by enzyme immunoassay. On the day 30 of experiment, the mice were infected with cowpox virus at a dose of 32 LD50, which caused total death of control mice on days 6-10. In the groups immunized with the studied viruses at a dose of 105 PFU, all the animals survived, regardless of strain, or immunization method. Upon intradermal immunization (103 PFU) of mice immunized with the original LIVP virus, 83% of the animals survived, whereas all mutant strains of the vaccinia virus provided 100% protection of the mice from subsequent cowpox virus infection. Intranasal immunization of mice at a dose of 103 PFU with LIVP strain protected only 33% of animals from lethal infection with cowpox virus, while the mutant strains LIVP-A34R* and LIVP-A34R*-dA35R provided 67% protection, and the LIVP-dA35R strain has resqued 75% of the mice. The studied mutant vaccinia viruses can be considered not only new candidate vaccines against smallpox and other human orthopoxvirus infections, but also as vector platforms for creating live multivalent vaccines against other infectious diseases

Mutations in the <i>A34R</i> gene increase the immunogenicity of vaccinia virus

Vaccination is the most simple and reliable approach of protection to virus infections. The most effective agents are live vaccines, usually low-virulence organisms for humans and closely related to pathogenic viruses or attenuated as a result of mutations/deletions in the genome of pathogenic virus. Smallpox vaccination with live vaccinia virus (VACV) closely related to smallpox virus played a key role in the success of the global smallpox eradication program carried out under the World Health Organization auspices. As a result of the WHO decision as of 1980 to stop smallpox vaccination, humankind has lost immunity not only to smallpox, but also to other zoonotic, orthopoxviruscaused human infections. This new situation allows orthopoxviruses to circulate in the human population and, as a consequence, to alter several established concepts of the ecology and range of sensitive hosts for various orthopoxvirus species. Classic VACV-based live vaccine for vaccination against orthopoxvirus infections is out of the question, because it can cause severe side effects. Therefore, the development of new safe vaccines against orthopoxviral infections of humans and animals is an important problem. VACV attenuation by modern approaches carried out by targeted inactivation of certain virus genes and usually leads to a decrease in the effectiveness of VACV in vivo propagation. As a result, it can cause a diminishing of the immune response after administration of attenuated virus to patients at standard doses. The gene for thymidine kinase is frequently used for insertion/inactivation of foreign genes and it causes virus attenuation. In this research, the effect of the introduction of two point mutations into the A34R gene of attenuated strain LIVP-GFP (ТК–), which increase the yield of extracellular enveloped virions (EEV), on the pathogenicity and immunogenicity of VACV LIVP-GFP-A34R administered intranasally to laboratory mice were studied. It was shown that increase in EEV production by recombinant strain VACV LIVP-GFP-A34R does not change the attenuated phenotype characteristic of the parental strain LIVP-GFP, but causes a significantly larger production of VACV-specific antibodies

STUDY OF CESIUM SORPTION BY IRON AND NICKEL FERROCYANIDES

Sorption of cesium on four commercially available iron and nickel ferrocyanides was studied in this work.It was shown that these ferrocyanides adsorb cesium at a wide pH range (0.5 – 12) with distribution coefficient of approximately 105 L kg-1

Route-coupled pathogenicity and immunogenicity of vaccinia virus variant inoculated mice

Vaccinia virus had played a key role in the global smallpox eradication. However, in case of mass vaccination with various Vaccinia virus strains severe side effects were revealed sometimes ending up with lethal outcomes, especially in immunocompromised humans. Hence, in 1980 the World Health Organization recommended to cancel smallpox vaccination after declaring about smallpox eradication. Over the last 40 years, human population virtually lost immunity not only against smallpox, but also against other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camelpox. All of them pose a represent increasing threat to human health and heighten a risk of emerging highly contagious viruses due to natural evolution of previous zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, efforts should be applied to develop safe new generation live vaccines based on Vaccinia virus with target virulence genes inactivation. These strains should be examined in laboratory animal models inoculated via different routes. Currently, Vaccinia virus often becomes attenuated to create live recombinant vaccines due to inserting target DNA sequences into the virus virulence genes resulting in their inactivation. Vaccinia virus strain LIVP used in the Russian Federation as smallpox vaccine as well as derivative attenuated variant LIVP-GFP created by using genetic engineering methods with inactivating its thymidine kinase gene were examined. Such viruses were intracerebrally inoculated into suckling mice at doses of 101 or 102 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally at doses of 107 or 108 PFU/animal and clinical manifestations were analyzed for 14 days. On the 28th day after the onset, blood serum samples were collected from individual mice to measure virus specific antibody level by using ELISA. It was shown that recombinant Vaccinia virus strain LIVP-GFP displayed markedly lowered neurovirulence and pathogenicity for mice as compared to parental LIVP. Finally, intradermal route turned out to demonstrate the most safe and effective profile for immunization with both examined Vaccinia virus strains

RNA sequencing of single cells obtained from immunolabeled tumor sections: the first experience

We performed laser microdissection-assisted RNA sequencing of single cells of breast tumo

Изучение физико-химических и сорбционных свойств гексацианоферратов никеля и железа по отношению к цезию

The decontamination of liquid media contaminated by anthropogenic radionuclides provides a serious technological challenge. Sorption methods are often used to perform this task. The paper studies the physico-chemical and sorption characteristics of pure samples of iron (samples 1 and 2) and nickel (samples 3 and 4) hexacyanoferrates with respect to caesium radionuclides. It is shown that iron hexacyanoferrates have better granulometric composition than nickel hexacyanoferrates due to a smaller quantity of fine fraction (0.5-10 µm), thus providing for easier sedimentation and filtration. The results of thermal gravimetric and differential thermal analysis have shown that the lower limit of thermal stability of all hexacyanoferrates was at least 200°С. This means that spent sorbents can be dried at 100–150°С. Nickel hexacyanoferrates demonstrated a slightly higher thermal stability as compared with iron hexacyanoferrates. The experiment performed with simulated solutions demonstrated that pH does not affect the sorption of caesium by hexacyanoferrates with the рН range of 0.5 to 11.5. The distribution coefficients of caesium varied from 3·104 to 3·105 cm3/g. The effect of sodium and potassium on the sorption of cesium by iron and nickel hexacyanoferrates was studied at the concentrations of Na+ and K+ of up to 5 mol/dm3. The study demonstrates that the sorption of caesium by iron hexacyanoferrates does not depend on sodium and potassium concentration; whereas in case of nickel hexacyanoferrates distribution coefficients of caesium slightly decrease with concentrations of sodium and potassium of 1 mol/dm3and higher. However, distribution coefficients of caesium remained at least 104 cm3/g under any of the conditions studied. Ammonium ions showed significantly stronger suppressing effect on caesium sorption at the concentration of 0.5 mol/dm3, which can be explained by similar ionic radii of hydrated Cs+ and NH4+. Thus, the iron and nickel hexacyanoferrates can be recommended for caesium separation from a wide spectrum of acidic, neutral, slightly alkaline and salty intermediate-level liquid radioactive wastes. © 2021 MEDICC Review. All rights reserved

SNP-Based Chromosomal Microarray Analysis for Detecting DNA Copy Number Variations in Fetuses with a Thickened Nuchal Fold

The aim of the study was to assess the diagnostic potential of SNP-based chromosomal microarray analysis for detecting pathogenic copies number variations (CNVs) in fetuses with a normal karyotype, in which an increase in the nuchal translucence of >2.5 mm was detected by ultrasound at a gestational age of 11 weeks to 13 weeks 6 days. MATERIALS AND METHODS: The study included 225 pregnant women who underwent invasive prenatal diagnostic procedures following the detection of an isolated thickening of the fetal nuchal fold. The fetal material obtained was examined using a cytogenetic test; if a normal karyotype was confirmed, chromosomal microarray analysis was performed as a second-line test. RESULTS: Pathogenic CNVs were detected in 22 of 225 fetuses (9.8%) with a normal karyotype. Of these 22 fetuses, pathogenic CNVs not classified as syndromes were detected in 14 cases (63.6%), and those previously described as syndromes — in 8 cases (36.4%). In 9 fetuses (41%), CNVs in two non-homologous chromosomes were determined; these findings indicated a high likelihood of carrying balanced translocations in the parents. Indeed, when analyzing the parent’s karyotype, in 8 out of 9 couples, balanced translocations were found in one of the parents. CONCLUSION: Using chromosomal microarray analysis in fetuses with a thickened nuchal fold makes it possible to increase the ability to detect chromosomal imbalances, including those caused by pathological meiotic segregation of parental reciprocal translocation

Моделирование снегонакопления и снеготаяния в бассейне р. Кама с применением данных глобальных моделей прогноза погоды

Currently, the improvement of numerical models of weather forecasting allows using them for hydrological problems, including calculations of snow water equivalent  (SWE) or snow storage. In this paper, we discuss the applicability of daily precipitation forecasts for three global atmospheric models: GFS (USA), GEM (Canada) and PL-AV (Russia) for calculating snow storage (SWE) in the Kama river basin for the cold season of 2017–2018. As the main components of the balance of snow storages the following parameters were taken into account: precipitation (with regard for the phase); snow melting during thaws; evaporation from the surface of the snow cover; interception of solid precipitation by forest vegetation. The calculation of snow accumulation and melting was based on empirical methods and performed with the GIS technologies. The degree-day factor was used to calculate snowmelt intensity, and snow sublimation was estimated by P.P. Kuz’min formula. The accuracy of numerical precipitation forecasts was estimated by comparing the results with the data of 101 weather stations. Materials of 40 field and 27 forest snow-measuring routes were taken into account to assess the reliability of the calculation of snow storages (SWE). During the snowmelt period, the part of the snow-covered area of the basin was also calculated using satellite images of Terra/Aqua MODIS on the basis of the NDFSI index. The most important result is that under conditions of 2017/18 the mean square error of calculating the maximum snow storage by the GFS, GEM and PL-AB models was less than 25% of its measured values. It is difficult to determine which model provides the maximum accuracy of the snow storage calculation since each one has individual limitations. According to the PL-AV model, the mean square error of snow storage calculation was minimal, but there was a significant underestimation of snow accumulation in the mountainous part of the basin. According to the GEM model, snow storages were overestimated by 10–25%. When calculating with use of the GFS model data, a lot of local maximums and minimums are detected in the field of snow storages, which are not confirmed by the data of weather stations. The main sources of uncertainty in the calculation are possible systematic errors in the numerical forecasts of precipitation, as well as the empirical coefficients used in the calculation of the intensity of snowmelt and evaporation from the snow cover surface.На примере холодного периода 2017/18  г. выполнено моделирование формирования и таяния снежного покрова в бассейне р.  Кама с применением выходных данных глобальных моделей прогноза погоды GFS (США), GEM (Канада) и ПЛ-АВ (Россия). Валидация результатов проведена по данным 40 полевых и 27 лесных снегомерных маршрутов, а в весенний период – и по спутниковым снимкам MODIS. Ошибка расчёта снегозапасов по данным всех трёх моделей не превысила 25% фактических значений

A single blind, placebo-controlled randomized study of the safety, reactogenicity and immunogenicity of the “EpiVacCorona” Vaccine for the prevention of COVID-19, in volunteers aged 18–60 years (phase I–II)

Vaccination of the population is one of the most effective countermeasures in responding to the pandemic caused by novel coronavirus infection. Therefore, scientists all over the world have been working to develop effective and safe vaccines. We have developed a synthetic peptide vaccine, EpiVacCorona, against novel SARS-CoV-2 coronavirus, which is a suspension for intramuscular administration containing a composition of chemically synthesized peptide immunogens of the S protein of SARS-CoV-2 coronavirus conjugated to a carrier protein and adsorbed on aluminum hydroxide. Phase I–II clinical trials of the vaccine have started that consist of two stages: Stage 1 is an open study of the safety, reactogenicity, and immunological activity of the vaccine with the involvement of 14 volunteers aged 18–30 years; Stage 2 is a single blind, comparative, randomized placebo-controlled study with the involvement of 86 volunteers. The study involved volunteers aged 18–60 years; the vaccine was injected intramuscularly twice, spaced 21 days apart between injections. All local reactions in response to vaccine administration were mild, such as a short-term pain at the injection site. There were no signs of development of local or systemic adverse reactions. The two-dose vaccination scheme induced the production of antibodies, specific to the antigens that make up the vaccine, in 100% of the volunteers. Seroconversion with a neutralizing antibody titer ≥ 1:20 was reported in 100% of the volunteers 21 days following the second immunization dose. No seroconversion was reported in the groups of volunteers vaccinated with a placebo. The peptide-based EpiVacCorona Vaccine has low reactogenicity and is a safe, immunogenic product. Clinical Trials Identifier: NCT04527575