Some aspects of joint-stock companies functioning in Russia today

The author attempts to identify the peculiarities of joint stock companies in Russia at the present stage. In the beginning of this article, the author shows the importance of joint-stock companies for economic relations. There are historical examples, such as Muscovy Company (1555), the Chicago City Railway Company (1859)yesBelgorod State National Research Universit

Marketing express research of a condition of modern wheat export on the global market

The author of the article attempts to assess the possibilities of different countries in terms of wheat exports based on the study of a certain list of scientific primary sources. Information on world grain prices ($/t) for the period 2014-2015 of the Committee on the General Organization of Agricultural Markets was the starting point of the study. The main wheat exporters at the present stage are described. The obtained data are summarized and the information is systematized. The prospects for the development of export opportunities of some countries are substantiate

Immune Fingerprinting through Repertoire Similarity

Immune repertoires provide a unique fingerprint reflecting the immune history of individuals, with potential applications in precision medicine. However, the question of how personal that information is and how it can be used to identify individuals has not been explored. Here, we show that individuals can be uniquely identified from repertoires of just a few thousands lymphocytes. We present "Immprint," a classifier using an information-theoretic measure of repertoire similarity to distinguish pairs of repertoire samples coming from the same versus different individuals. Using published T-cell receptor repertoires and statistical modeling, we tested its ability to identify individuals with great accuracy, including identical twins, by computing false positive and false negative rates $< 10^{-6}$ from samples composed of 10,000 T-cells. We verified through longitudinal datasets and simulations that the method is robust to acute infections and the passage of time. These results emphasize the private and personal nature of repertoire data

The modular structure of the adaptive machine learning system

Machine learning system based on the modular structure can tune to particular subject area flexibly and form the optimal individual educational trajector

Exploring the pre-immune landscape of antigen-specific T cells

Abstract Background Adaptive immune responses to newly encountered pathogens depend on the mobilization of antigen-specific clonotypes from a vastly diverse pool of naive T cells. Using recent advances in immune repertoire sequencing technologies, models of the immune receptor rearrangement process, and a database of annotated T cell receptor (TCR) sequences with known specificities, we explored the baseline frequencies of T cells specific for defined human leukocyte antigen (HLA) class I-restricted epitopes in healthy individuals. Methods We used a database of TCR sequences with known antigen specificities and a probabilistic TCR rearrangement model to estimate the baseline frequencies of TCRs specific to distinct antigens epitopespecificT-cells. We verified our estimates using a publicly available collection of TCR repertoires from healthy individuals. We also interrogated a database of immunogenic and non-immunogenic peptides is used to link baseline T-cell frequencies with epitope immunogenicity. Results Our findings revealed a high degree of variability in the prevalence of T cells specific for different antigens that could be explained by the physicochemical properties of the corresponding HLA class I-bound peptides. The occurrence of certain rearrangements was influenced by ancestry and HLA class I restriction, and umbilical cord blood samples contained higher frequencies of common pathogen-specific TCRs. We also identified a quantitative link between specific T cell frequencies and the immunogenicity of cognate epitopes presented by defined HLA class I molecules. Conclusions Our results suggest that the population frequencies of specific T cells are strikingly non-uniform across epitopes that are known to elicit immune responses. This inference leads to a new definition of epitope immunogenicity based on specific TCR frequencies, which can be estimated with a high degree of accuracy in silico, thereby providing a novel framework to integrate computational and experimental genomics with basic and translational research efforts in the field of T cell immunology

Precise tracking of vaccine-responding T-cell clones reveals convergent and personalized response in identical twins

T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 500-1500 responding TCRs in each donor and validated them using three independent assays. While the responding TCRs were mostly private, albeit with higher overlap between twins, they could be well predicted using a classifier based on sequence similarity. Our method can also be applied to samples obtained post-infection, making it suitable for systematic discovery of new infection-specific TCRs in the clinic

Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones

The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Previous studies show that secondary responses to the yellow fever vaccine - the model for acute infection in humans - are weaker than primary ones, but only quantitative measurements can describe the concentration changes and lineage fates for distinct T-cell clones in vivo over time. Using TCR alpha and beta repertoire sequencing for T-cell subsets, as well as single-cell RNAseq and TCRseq, we track the concentrations and phenotypes of individual T-cell clones in response to primary and secondary yellow fever immunization showing their large diversity. We confirm the secondary response is an order of magnitude weaker, albeit $\sim10$ days faster than the primary one. Estimating the fraction of the T-cell response directed against the single immunodominant epitope, we identify the sequence features of TCRs that define the high precursor frequency of the two major TCR motifs specific for this particular epitope. We also show the consistency of clonal expansion dynamics between bulk alpha and beta repertoires, using a new methodology to reconstruct alpha-beta pairings from clonal trajectories

Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities.

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4⁺ and CD8⁺ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.Wuji Zhang, Lukasz Kedzierski, Brendon Y. Chua, Mark Mayo, Claire Lonzi, Vanessa Rigas, Bianca F. Middleton, Hayley A. McQuilten, Louise C. Rowntree, Lilith F. Allen, Ruth A. Purcell, Hyon-Xhi Tan, Jan Petersen, Priyanka Chaurasia, Francesca Mordant, Mikhail V. Pogorelyy, Anastasia A. Minervina, Jeremy Chase Crawford, Griffith B. Perkins, Eva Zhang, Stephanie Gras, E. Bridie Clemens, Jennifer A. Juno, Jennifer Audsley, David S. Khoury, Natasha E. Holmes, Irani Thevarajan, Kanta Subbarao, Florian Krammer, Allen C. Cheng, Miles P. Davenport, Branka Grubor-Bauk, P. Toby Coates, Britt Christensen, Paul G. Thomas, Adam K. Wheatley, Stephen J. Kent, Jamie Rossjohn, Amy W. Chung, John Boffa, Adrian Miller, Sarah Lynar, Jane Nelson, Thi H. O. Nguyen, Jane Davies, Katherine Kedziersk