Russian Science Foundation Grant Research Articles

Therapeutic Vaccines for Follicular Lymphoma: A Systematic Review.

(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary outcome. We searched databases (PubMed, Embase, Scopus, Web of Science Core, medRxiv) and registries (PROSPERO, CENTRAL, ClinicalTrials.gov, EuCTR, WHO ICTRP) and conducted online, citation, and manual searches. We assessed risks of bias across outcomes using RoB 2.0 and across studies using ROB-ME and a contour-enhanced funnel plot. (3) Results: Three RCTs were included (813 patients, both previously treated and untreated). Patients with a complete or partial response after chemotherapy were randomized to either a patient-specific recombinant idiotype keyhole limpet hemocyanin (Id-KLH) vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo immunotherapy (KLH + GM-CSF). Meta-analyses showed that PFS was worse with the vaccine, but not significantly: hazard ratio, 1.09 (95% CI 0.91-1.30). The GRADE certainty of evidence was moderate. Adverse event data were mixed. (4) Conclusions: We are moderately certain that Id-KLH results in little to no difference in PFS in FL. (5) Funding: Russian Science Foundation grant #22-25-00516. (6) Registration: PROSPERO CRD42023457528.

Transplastomic plants — new approaches to solving “old” problems

Transplastomic plants are capable to accumulate the significant amounts (up to 70% of TSP) of target recombinant proteins in tissues. However, the production of such forms is severely limited by the low yield of initial transformants. This problem requires the development and optimization of new approaches to the delivery of transgenes into chloroplasts and an increase in the frequency of their integration into the plastome. Transplastomic tobacco plants expressing thegfpreporter gene and theaadAselectable marker under the control of thePrrnG10Lpromoter and theTpsbAterminator were obtained in the laboratory of plant bioengineering. It is known that the selected promoter and insertion region (between the tRNA genes of isoleucine and alanine) are capable to provide a high yield of recombinant proteins in the leaves of transplastomic plants [1]. However, the content of recombinant GFP in the leaves of the obtained transplastomic plants was determined at the level of 0.12%, and the variability for this trait was minimal and ranged from 0.09 to 0.16% of TSP. Insufficient accumulation of the target protein in transformants is not associated with transcription disorders or the presence of non-transgenic copies of the plastome. Probably, the low frequency of transformation and the lack of variability between the transformants are the reasons that make it difficult to select highly productive forms. It is proposed to increase the efficiency of targeted delivery of genetic constructs to plastids using single-walled carbon nanotubes loaded with recombinant DNA. This process can also be facilitated by our proposed approach to increase the frequency of DNA double-strand breaks in target regions of the plastome through the use of the CRISPR-Cas9 genome editing system.
 This work was supported by the Russian Science Foundation grant No. 23-24-00545.

A set of Saccharomyces cerevisiae strains possessing [PSI+] prion formed by Sup35 protein with various deletions in prionogenic domain

Amyloid aggregation is a key factor for the development of a series of lethal and incurable diseases, commonly named amyloidoses. The development of various pathologies might be caused by the aggregation of the same protein. This can be due to the ability of any particular protein to adopt several amyloid conformations, specific for the exact disease (Pick’s and Alzheimer’s disease-specific forms of tau protein). How the specific amyloid conformation is formed in each case is not fully understood.
 In yeast, translation termination factor Sup35 is one of the most extensively studied amyloidogenic proteins. Sup35 aggregation (induction of [PSI+] prion) inactivates the protein and leads to the suppression of nonsense-mutation as the result of read-through.
 Prionogenic domain of Sup35 protein (Sup35N) has several specific regions: N-terminal QN-rich region (QN), oligopeptide repeats (NR) and C-terminal region (CTN). Sup35 can form various strains of [PSI+] with predominant involvement of different regions of Sup35N into amyloid core thus mimicking disease-specific strains of amyloids described for human amyloidogenic proteins.
 We implemented the deletions of fragments encoding 1-39 a.a. (QN region) or 75-123/98-123 a.a. (CTN region) intoSUP35gene of yeastSaccharomyces cerevisiae. Then, we induced aggregation of Sup35 protein in the strains carrying mutatedSUP35gene and got the strains possessing [PSIΔ39+], [PSIΔ75–123+], or [PSIΔ98–123+] prion. A set of strains possessing [PSI+] formed by Sup35 protein with various deletions in Sup35N may be convenient model to study disease-specific strains of amyloids formed by human proteins.
 This research was funded by Russian Science Foundation (grant 20-14-00148-П) and by the St. Petersburg State University (project 94031363).

Controlled germination of grain crops is an effective way to processing low-quality raw materials

Relevance. The development of technologies of cereal crops germination and obtaining of raw ingredients with increased antioxidant properties, containing in their composition biologically active substances of natural origin, will allow to form a modern domestic market of useful food products to maintain the health of the country in the long term. One such approach could be controlled germination of grain crops by ultrasonic treatment during the soaking stage. This technology will maximise the yield of finished products per unit of processed raw material, process low-quality raw materials and create products with increased nutritional value.Methods. The objects of the study were three samples of grain crops: wheat, barley, oats. At the initial stage, incoming quality control of raw materials and their disinfection by physical method of exposure were carried out. For experimental samples of cereal crops at the stage of soaking the impact of ultrasound (22 ± 1.25 kHz) 245 W/l for 5 min, then the grain was soaked for 8 hours (wheat grain) and 12 hours (barley and oats grain), the process of germination was carried out until reaching the sprout size 1.5–2 mm in more than 90% of grains. All operations with control samples were performed in the same sequence, excluding the process of ultrasound exposure. The total content of flavonoids and polyphenolic compounds was determined in all tested samples using spectrophotometric method, total antioxidant activity using DPPH-method, and γ-aminobutyric acid content using automated liquid chromatography system.Results. The studies showed that all germinated samples of cereal crops are characterized by sufficiently high values of flavonoid and polyphenolic compounds. At the same time, the samples obtained by ultrasound exposure showed an increase in the content of flavonoids by an average of 7.3–8.9 times, polyphenols by 2–5.6 times. In the process of intensified controlled germination, the total antioxidant activity increased by 31.6–40.0%, relative to the control samples of grain crops. The increase in GABA content in samples after ultrasound exposure averaged 360–490%. The results confirmed the possibility and feasibility of using the proposed technology of controlled germination in obtaining raw ingredients from germinated cereal crops. The study was carried out with the financial support of the Russian Science Foundation Grant 23-26-00290.

Medical Antennas for Microwave Radiothermometry of Biological Objects.

The results of an analytical review of various antennas used in medicine are presented. Issues of modern microwave radiothermometry related to the development of new antennas are discussed, as well as possible ways to solve them. The tasks of further research aimed at creating new designs for conformal antennas and antenna arrays providing a significant expansion of the functionality and improvements in the characteristics of medical radiothermographs are formulated. The study was supported by the Russian Science Foundation (Grant No. 22-19-00113), https://rscf.ru/project/22-19-00113/.

Wooden buildings of Chita in the work of the first architects of the city

The article presents the results of a study conducted by the authors with the support of the Russian Science Foundation grant "Architects and engineers of the eastern outskirts of Russia (second half of the 19th - early 20th centuries)". The features of a significant layer of regional wooden architecture, preserved in the capital of the Trans-Baikal Territory - the city of Chita, are considered. Based on the materials of field surveys and the State Archives of the Trans-Baikal Territory, the preserved objects and original designs of a number of buildings and structures for various purposes were studied. The wooden architecture of the city is viewed through the prism of the activities of the first city architects and engineers, as well as other masters of the building art who received professional education in the leading architectural and engineering schools of central Russia, as well as specialists who did not have a specialized education, but received the right to carry out architectural and construction work after passing exams at the Ministry of Construction Affairs in St. Petersburg. As a result, a complete systematized picture of the historical evolution of the wooden architecture of Chita was compiled, which was formed under the influence of all-Russian architectural traditions, but at the same time had its own distinctive features associated with the specifics of the development of the region and the personal ideas of the masters of architectural and construction art, as well as customers of architecture of this type.

Promoters of genes encoding β-amylase, albumin and globulin in food plants have weaker affinity for TATA-binding protein as compared to non-food plants: in silico analysis.

It is generally accepted that during the domestication of food plants, selection was focused on their productivity, the ease of their technological processing into food, and resistance to pathogens and environmental stressors. Besides, the palatability of plant foods and their health benefits could also be subjected to selection by humans in the past. Nonetheless, it is unclear whether in antiquity, aside from positive selection for beneficial properties of plants, humans simultaneously selected against such detrimental properties as allergenicity. This topic is becoming increasingly relevant as the allergization of the population grows, being a major challenge for modern medicine. That is why intensive research by breeders is already underway for creating hypoallergenic forms of food plants. Accordingly, in this paper, albumin, globulin, and β-amylase of common wheat Triticum aestivum L. (1753) are analyzed, which have been identified earlier as targets for attacks by human class E immunoglobulins. At the genomic level, we wanted to find signs of past negative selection against the allergenicity of these three proteins (albumin, globulin, and β-amylase) during the domestication of ancestral forms of modern food plants. We focused the search on the TATA-binding protein (TBP)-binding site because it is located within a narrow region (between positions -70 and -20 relative to the corresponding transcription start sites), is the most conserved, necessary for primary transcription initiation, and is the best-studied regulatory genomic signal in eukaryotes. Our previous studies presented our publicly available Web service Plant_SNP_TATA_Z-tester, which makes it possible to estimate the equilibrium dissociation constant (KD) of TBP complexes with plant proximal promoters (as output data) using 90 bp of their DNA sequences (as input data). In this work, by means of this bioinformatics tool, 363 gene promoter DNA sequences representing 43 plant species were analyzed. It was found that compared with non-food plants, food plants are characterized by significantly weaker affinity of TBP for proximal promoters of their genes homologous to the genes of common-wheat globulin, albumin, and β-amylase (food allergens) (p < 0.01, Fisher's Z-test). This evidence suggests that in the past humans carried out selective breeding to reduce the expression of food plant genes encoding these allergenic proteins.

Analysis of the use of vector autoregressions in economic forecasting

Using vector autoregressions is a promising direction in short-term economic forecasting. They do not simply model the relationship between different factors, but also model the time-distributed relationship of these factors. Vector autoregressions are suitable for modeling complex dynamic economic multifactor processes. The complexity of the problem of estimating coefficients, which increases with the dimensionality of vectors, prevents the widespread use of autoregressions in practice. Vector autoregressions in complex-valued form with the same dimensionality as the modeled vector contain a much smaller number of coefficients. This facilitates the estimation of the coefficients of vector autoregressions. Some problems requiring further investigation arise when using vector autoregressions in complex form. Among them is the problem of selecting the best model. The information criteria used for this purpose limit the variety of vector autoregressions, reducing them to elementary models. The study was supported by the Russian Science Foundation grant No. 23-28-01213, https://rscf.ru/project/23-28-01213.

Diepoxy-treated bovine jugular vein conduit for pulmonary artery replacement

Objective: To evaluate the performance and short-term capacity of the diepoxy-treated bovine jugular vein conduit in large animals during 6-month follow-up.Methods: Thirteen diepoxy-treated bovine jugular vein conduits were implanted into the pulmonary artery of young mini-pigs. During the follow-up, graft function was tested using transesophageal echocardiography. The animals were withdrawn at 6 months, and the explanted conduits were assessed histologically.Results: All the conduits were successfully implanted without any surgical complications. All the animals survived throughout the follow-up. By the end of the follow-up period, the pressure gradient increased on five animals’ conduits including one case of mismatch between the conduit and the native pulmonary artery, two cases of distal stenosis, and two case of endocarditis. No significant increase in valve regurgitation or conduit thrombosis was observed during the follow-up. In conduits without dysfunction, the structure of the walls and leaflets was intact. A thin fibrous tissue covered the conduit inner wall with complete surface endothelialization. Neither signs of degeneration or calcification nor inflammatory cells were found in the conduit wall or leaflets. Neointima proliferation without calcium deposits was observed in two distally stenosed conduits. Inflammatory cells consisting of multinucleated macrophages, lymphocytes, and histiocytes were found in the adventitia. There were no inflammatory cells in the media or intima, and the leaflets showed no changes.Conclusion: Diepoxy-treated bovine jugular vein demonstrated acceptable performance, good endothelialization, and low tendency to thrombosis and calcium accumulation in the wall and leaflets. Received 31 October 2022. Revised 25 November 2022. Accepted 28 November 2022. Funding: The study was supported by Russian Science Foundation (grant No. 22-25-20102). Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: N.R. Nichay, I.Yu. Zhuravleva, A.V. Bogachev-ProkophievData collection and analysis: N.R. Nichay, Yu.Yu. Kulyabin, I.S. Zykov, E.V. Boyarkin, O.Yu. Malakhova, E.V. Kuznetsova, T.P. Timchenko, Ya.L. Rusakova, I.S. Murashov, A.A. DokuchaevaStatistical analysis: N.R. Nichay, I.Yu. ZhuravlevaDrafting the article: N.R. Nichay, I.Yu. Zhuravleva, Yu.Yu. Kulyabin, I.S. Zykov, E.V. Boyarkin, O.Yu. Malakhova, T.P. Timchenko, Ya.L. Rusakova, I.S. Murashov, A.A. DokuchaevaCritical revision of the article: N.R. Nichay, I.Yu. Zhuravleva, Yu.Yu. Kulyabin, A.A. Dokuchaeva, A.V. Bogachev-ProkophievFinal approval of the version to be published: N.R. Nichay, I.Yu. Zhuravleva, Yu.Yu. Kulyabin, I.S. Zykov, E.V. Boyarkin, O.Yu. Malakhova, E.V. Kuznetsova, T.P. Timchenko, Ya.L. Rusakova, I.S. Murashov, A.A. Dokuchaeva, A.V. Bogachev-Prokophiev

Prospects for the use of natural transgenic cultivated peanut (&lt;i&gt;Arachis hypogaea&lt;/i&gt; L.) in breeding

Common peanut (Arachis hypogaea L.), or peanut, is an annual herbaceous plant from the legume family (Fabaceae). Russia is one of the largest buyers of peanuts, and at the same time, in the south of the country, a number of zones meet the requirements for the cultivation of this crop. However, at present there are no commercial peanut crops in Russia, and selection work is almost not carried out. It is necessary to identify a new source material for breeding and breeding new high-yielding varieties. In the genomes of species of the genus Arachis, homologues of agrobacterial opine synthase genes, cucumopine synthase (cus) and deoxyfructosylglutamine synthase (mas2`), have been identified. The expression of these genes can affect the economically valuable traits of the plant, since the synthesis of various opines affects the composition of the microbiome in the rhizosphere. We have analyzed the expression of the cus gene in various organs of 9 peanut lines from the VIR collection, which have different geographical origin, belong to different cultivar types, and differ in morphological characters. As a result of the analysis, the organ-specific expression was shown; samples were identified that were contrasting in terms of the level of cus gene expression, including those with a high level of expression in the roots (kk-168, 416, 751). For the first time, data were obtained on the work of the cus gene at different stages of plant development on accessions k-168 and k-1157. An increase in the level of expression in the roots during flowering was revealed; during seed germination, the expression is lower. Further analysis and search for a correlation between the expression level of the cus gene and the manifestation of economically valuable traits in peanuts can provide new material for creating promising varieties.&#x0D; The studies were carried out using the equipment of the resource center of the Science Park of Saint Petersburg State University Development of molecular and cellular technologies.&#x0D; This work was supported by the Russian Science Foundation grant No. 21-14-00050.

Holographic signal processing for estimation of sound source direction by a vector receiver in shallow water

A holographic signal processing method for estimation of sound source direction of broadband moving sound source is proposed in the paper. The holographic estimation of sound source direction is based on signal processing of single vector receiver (VR) channels: x-th and y-th components of the oscillatory velocity. The sound field of a moving sound source creates a stable interference pattern of the intensity distribution (interferogram) in the frequency-time domain on VR channels. The two-dimensional Fourier transformation (2D-FT) is applied to analyze the channels interferograms. The result of the 2D-FT are holograms of the x-th and y-th oscillatory velocity components. The angle distributions of channels holograms are calculated. The offered holographic method is based on the ratio of the absolute values of the holograms angle distributions maxima. The expressions for VR channels holograms are derived. The results of the numerical experiment for source direction reconstruction are presented. A significant advantage of the proposed holographic method that there is no need for information about noise signal source, the additive noise obstacle and waveguide transfer function. [This study was supported by Russian Science Foundation grant no. 22-79-10233. Tkachenko’s numerical experiment was supported by grant no. МК-4846.2022.4.]

Modes selection based on holographic interferometry in presence of intense internal waves in shallow water

A holographic method is proposed for sound field modes selection and estimating their parameters (amplitude, horizontal wavenumber, group velocity, absorption coefficient) in shallow water by single scalar receiver in presence of intense internal waves (IIW). It is taken into account that IIW leads to horizontal refraction and modes coupling. The offered holographic method is based on the two-dimensional Fourier transform (2D-FT) of the real part of the moving-source sound field in time–frequency domain. It is shown in the paper that different sound field modes create different focal spots in the hologram domain in presence of IIW. The relationship of the mode phases and group velocities with the coordinates of focal-spot peaks is derived. The hologram domain allows to reconstruct the selected mode field and mode parameters in presence of IIW. The results of modes selection within framework of the numerical experiments are presented in the paper. The modal parameters are estimated. Analysis of influence of IIW on mode selection and mode parameters estimations is performed. It is shown that the effects of horizontal refraction and modes coupling do not lead to loss of the identity of mode parameters of the received signal. [This study was supported by Russian Science Foundation grant no. 22-79-10233. E.S. Kaznacheeva’s numerical experiment was supported grant no. МК-6144.2021.4]

Structure and properties of aluminized alloys of the Fe–Cr–Al system

The formation features of the aluminide coating structure on Cr15Al5 and Cr23Al5 alloys after aluminizing by immersing in aluminum and silumin melt are studied. The influence of Si on the transformation of the structure and phase composition of the aluminide coating under high-temperature heating conditions are studied. It is shown that aluminizing of the Fe&ndash;Cr&ndash;Al system alloys by immersion in an aluminum melt ensures the formation of a defect-free continuous coating on their surface, which is a crystallized eutectic mixture of Al + FeAl3 and a layered diffusion zone at the boundary with the substrate. Replacing the aluminum melt with silumin with 12 % Si leads to the appearance of the Al7Fe2Si ternary intermetallic compound in the coating composition, which almost completely replaces FeAl3. In the process of hightemperature transformation of the coating structure, the presence of Cr and Si at the initial stage leads to the appearance in the coating composition intermetallic compounds (Cr,Fe)5Al8, Cr3Si, Al7Fe2Si, Fe3(Si,Al)5 and Cr5Si3 along with Fe&ndash;Al binary, and at the final stage &ndash; does not affect the phase composition, forming solid solutions based on iron aluminides. It is shown that the oxidation of aluminide coating on the Fe&ndash;Cr&ndash;Al system alloys at its early stages is accompanied by the formation of a stable modification of &alpha;-Al2O3 aluminum oxide and (Fe,Cr)2O3 ternary oxide, and with long-term oxidation leads to the appearance of &delta;-Al2O3 metastable modification and FeAl2O4. It has been established that the Si-alloyed aluminide coating on the Cr15Al5 alloy has a lower corrosion penetration depth at 1100 &deg;C. At the same time, the retention time of heatresistant properties for the aluminide coating on the Cr23Al5 alloy is ~20000 h, and on the Cr15Al5 alloy it is ~5000 h for the aluminide and 6000 h for aluminosilicide coatings.The study was supported by the Russian Science Foundation grant No. 21-79-10246, https://rscf.ru/project/21-79-10246/.

Genome-wide association study of depression symptoms using online self-questionnaires in the Russian population cohort: preliminary results

IntroductionDepression is a chronic, recurrent mental disorder with a moderate level of genetic impact. Modern GWAS of depression require extra-large sample sizes and new effective, clinically sensitive, objective and simple to fill online phenotyping tools for population studies are necessary today.ObjectivesAim: to test online phenotyping tools based on clinical and psychometric instruments to evaluate depressive symptoms in population cohort for using in GWASMethodsParticipants: 2610 Russian-speaking respondents- clients of Genotek Ltd., provider of genetic testing services in Russian Federation. The online survey included HADS-D (Hospital Anxiety and Depression Scale - depression subscale), original questionnaire adapted for self-report from major depression DSM-5 criteria, questions about sex and age. Three research phenotypes were defined: quantitative “HADS-D score” and two categorical “HADS-D depression” (cut-off 8 points) - 20.63 %, “DSM depression” 16.73 %. DNA samples obtained from saliva were genotyped on Illumina Infinium GSA v1.0/v2.0/v3.0 microarrays. GWAS analysis was performed independently for each of the research phenotypes.ResultsNone of the signals reached genome-wide significance (p value 10-8), but some signals with subthreshold significance were identified including four signals in the genes encoding proteins: “DSM_Depression”: rs2131596 in GRIP1 (p=3.682e-06,β=0.6965), rs11158021 in SAMD4A (p=2.841e-06, β=0.6762), “HADS-D Depression”: rs2425793 in CDH22 (p=4.408e-07, β=1.539), rs36006890 in PDIA6 (p = 6.529e-07, β=1.549).ConclusionsPreliminary results of the first GWAS of depression symptoms in the Russian population are acceptable and confirm the accuracy of the research strategy using online phenotyping tools based on clinical and psychometric instruments and provide basis for further studies.DisclosureThe study was supported by Russian Science Foundation Grant # 20-15-00132

Association of Eating Disorders with Recurrent Pain in Adolescent Girls

IntroductionEating disorders (ED) are associated with other mental illnesses, but the association of ED with pain is less well understood.ObjectivesTo study the association of ED with headache and abdominal pain in adolescent girls.MethodsIn 2015-2018, 917 girls aged 12-17 were examined using the Body Image and Eating Distress scale (Koskelainen et al., 2001) and questions about frequency of recurrent headache and abdominal pain over the past six months. Adolescents were divided into three groups: girls with eating disorders (ED, n = 20); subthreshold eating disorders (SED, n = 88); and a control group (CG, n = 809).ResultsHeadaches of varying frequency are were reported by 80% of girls with ED, 70.4% of girls with SED and 52.2% of CG girls. Frequent headaches (every week) were reported by 60% of girls with ED, 40.9% of girls with SED, and 29.9% of CG girls (χ2 = 20.21, p = 0.003). Recurrent abdominal pain was reported by 65% of girls with ED, 56.8% of girls with SED, and by 46.6% of CG girls. Weekly abdominal pain affected 30% of girls with ED, 20.4% of girls with SED and 12.9% of CG girls. Combined weekly pain were commoner in girls with eating distress (in 20% of girls with ED and in 12.5% with SED) than in CG (7.7%, χ2 = 3.92, p = 0.04).ConclusionsEating disorders in adolescents are often associated with pain, which can lead to late recognition of the disease, worsening its course and prognosis.DisclosureThe study was supported by the Russian Science Foundation grant # 21-15-00033

Suicidal Behavior in Adolescent Girls with Eating Disorders

IntroductionEating disorders are associated with suicidal behavior in adolescents. But the relationship between subthreshold eating disorders and suicidality is not well understood.ObjectivesTo examine suicidal behavior in adolescent girls with eating disorders (ED) and subthreshold eating disorders (SED).MethodsThe study of 917 girls aged 12–17 used the Body Image and Eating Distress scale (Koskelainen et al., 2001) and questions about intentional self-harm (burns or cuts), suicidal thoughts and suicidal attempts. Adolescents were divided into three groups: girls with ED (n = 20); girls with SED (n = 88); and control group (CG, n = 809).ResultsSelf-harm was reported by 55% of girls with ED, 35.2% of girls with SED and 20.2% of CG girls (χ2 = 15.82, p &lt;0.001). Suicidal ideation was reported by 65% of girls with ED, 51.1% of girls with SED and 27.2% of CG girls (χ2 = 21.86, p &lt;0.001). Suicidal attempts were reported by 45% of girls with ED, 17.1% of girls with SED and 7.5% of the CG. There were no differences in the prevalence of self-harm and suicidal ideation between the ED and SED groups, rates of suicide attempts were 2.6 times higher in the ED group.ConclusionsGirls with both ED and SED have a high risk of suicidal behavior: 2.7-4.5 times higher rates of self-harm, 1.9-2.4 times higher rates of suicidal ideation, and 2.3-6 times higher rates of suicidal attempts. Management of such adolescents should include assessment of the risk of suicide.DisclosureThe study was supported by the Russian Science Foundation grant # 21-15-00033.

Structure and mechanical properties of hot rolled sheets of Al – 2% Cu – 2% Mn – 0.4% Si – 0.2% Zr alloy subjected to friction stir welding

On the example of a hot-rolled sheet of aluminum alloy Al &ndash; 2Cu &ndash; 2Mn &ndash; 0.4Si &ndash; 0.2Zr% (wt.), the possibility of obtaining joints providing high mechanical properties and thermal stability by friction stir welding (FSW) is considered. From a non-homogenized ingot with a thickness of 40 mm from this alloy a sheet with a thickness of 4 mm was obtained on a laboratory rolling mill at a temperature of 350 оC (reduction degree 90 %). After rolling, cards were cut out of the sheet, which were joined by the double-sided STP method in two modes. For mode 1, the pressing force of the tool was 7551.12 N at a speed of longitudinal movement of the tool of 0.3 m/min, and for mode 2 &mdash; 7256.92 N and 0.125 m/min. The tool rotation frequency for the two modes was the same &mdash; 800 rpm. The structure and properties of the joints were studied before and after annealing at a temperature of 400 оC for 3 hours. It was found that the experimental alloy has high thermal stability, due to which, after FSW in the weld and heat-affected zones, the decrease in hardness does not exceed 10 % and remains practically unchanged. after annealing. It is shown that the FSW method makes it possible to obtain a high quality of welded joints, retaining almost the original strength (&sigma;w = 280&ndash;290 MPa) with a significant increase in relative elongation (&delta; from 3 to 12&ndash;16%). The increase in plasticity is due to the formation of an ultrafine-grained structure in the weld zone (grain size less than 5 &mu;m), which can be explained by the occurrence of dynamic recrystallization during the FSW. The totality of the results obtained allows to consider the use of the FSW method to be promising for obtaining equal-strength and thermally stable joints of rolled sheets of experimental alloys of the Al &ndash; Cu &ndash; Mn (Si, Zr) system, the structure of which differs from the grade alloys of the 2xxx series by a higher content of Mn-containing dispersoids. This work was supported by the Russian Science Foundation grant No. 20-19-00249.

SARS-CoV-2 epitope-specific CD8+ clonotypes persist 8 month post-infection despite reduced clonality.

Abstract Memory T cells play a crucial role in acceleration of immune response during reinfection with the same pathogen. Since the beginning of the COVID-19 pandemic, attention has been focused on determining the epitopes of SARS-CoV-2 that give rise to long-lived memory T cells. We examined the immune response to 12 immunogenic CD8+ epitopes in 26 COVID-19 convalescent patients. Paired blood samples were collected shortly after infection and approximately 8 months after. Using ex vivo T cell expansions with a subsequent MHC-tetramer+ cell-sorting and T cell receptor beta-chain (TCRβ) sequencing we studied the epitope-specific CD8+ response on the clonal level. In total in both time points we identified 756 epitope-specific TCRβ sequences. Nine epitopes were immunodominant while five immunogenic epitopes (YLQ, KCY, LLY, KTF and ALW) yielded response in 100% of tested individuals. This coincided with a high number of clones per individual specific to these epitopes (median = 16.5). Despite the very low frequency of specific cells in the total repertoire most (75.4%) of responses were retained at 8-month post-infection. The median number of clones for the top five most immunogenic epitopes dropped to 6. The TCRβ repertoires of T cells specific to the studied epitopes were characterized by different degrees of CDR3 homology. LLY and YLQ-specific TCRβ had the highest degree of mutual similarity while KCY and KTF-specific TCRβ were the most diverse. Our data demonstrates that despite the overall decrease of T cell reactivity and clonality most epitopes are still recognized due to the ability of memory SARS-CoV-2-specific CD8+ cells to survive over prolonged periods of time. The work was supported by the Russian Science Foundation grant 20-15-00395.

Clonal structure and epitope specificity of Ad5-nCoV vaccine-induced T cell response to SARS-CoV-2

Abstract As a part of phase 3 clinical trial of a single-dose adenoviral COVID-19 vaccine, we evaluated the dynamics and clonal structure of T cell response to the SARS-CoV-2 Spike protein. T cell response measured in 50 donors by IFNg ELISpot after Spike stimulation peaked on the 14th day (d14) after vaccination. Flow cytometry demonstrated that the response was skewed to CD4+ cells. To isolate Spike-specific T cells we performed short-term T cell expansion of d14 samples (n=17 donors) with the recombinant Spike, restimulated and FACS sorted IFNg+ cells. T cell receptor (TCR) beta chain sequencing identified from 36 to 629 Spike-specific clones (median 186) per individual. CD4+ response was more clonal than CD8+ (median 116 and 17 respectively) but CD8+ occupied a larger share of the total TCR repertoire (median 0.25% for CD4+ and 0.52% for CD8+) as a result of the larger average clone size at d14 (3.4×10−5 for CD8+ vs. 6.6×10−6 for CD4+). Both the number and total share of Spike-specific clones in the TCR repertoire decreased at day 28 and further at day 180. At 6 months a median of 1 (0 to 18) of the initial Spike-specific clones were detectable in the peripheral blood. This number increased to 39 (9 to 105) as a result of T cell expansion. For 14 donors we also performed rapid expansion of T cells sampled at d14 with 11 Spike-epitopes (9 MHC I and 2 MHC II) followed by sorting of activated cells and TCR sequencing. We identified on average 41 unique epitope-specific clones (2 to 141). They were mostly undetectable in the peripheral blood at 6 months (0 to 8 clones), but their numbers increased to the median of 7 clones (0 to 35) after cultivation with Spike. Overall this demonstrates the induction of polyclonal and stable T cell response by a single injection of adenoviral vaccine. The work was supported by the Russian Science Foundation grant 20-15-00395.

Effects of low-temperature treatment on the coals mechanical properties microscale and airborne dust formation

The effect of freezing-thawing on the mechanical properties of coals at the microscale, the character of their destruction during cyclic nanoindentation, and the release of airborne dust have been studied. For these purposes, three hard coals from the Apsatsky deposit, two hard coals from the Pechora coal basin, and two lignites from the Kangalassky deposit were studied. It has been established that low-temperature impacts lead to a decrease in the content of airborne dust for all the coals. It was revealed that after freezingthawing of coals, their strength decreases, however, the character of destruction under mechanical impacts do not change. The exception is the coal of the middle stage of metamorphism of the Pechora basin, selected from a pack potentially prone to coal and gas outbursts. For this coal, low-temperature effects lead to a change in the character of its destruction during cyclic nanoindentation. Namely, there was a switch from the local (in the zone of contact with the indenter) character of destruction of the initial coal to the bulk one (outside the zone of contact with the indenter) for coal after low-temperature treatment. To assess the coals propensity to form fine dust particles, an index characterizing the degree of compaction of coal matter during cyclic nanoindentation with increasing load was introduced. It has been established that this index is proportionally connected with the content of airborne dust in coals (with sizes of less than 10 microns). It is shown that the coals proneness to form airborne dust under low-temperature impacts does not depend on the stage of coal metamorphism. For bituminous coals of the Apsatsky deposit with similar metamorphism degree the propensity to form dust is different. Variations in the propensity to form dust in coals of the Pechora basin, which also have a similar metamorphism degree, are apparently due to the peculiarities of the vitrinite structure of these coals.This work was carried out with the financial support of the Russian Science Foundation (Grant No. 18-77-10052).