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

One-Dimensional Models in Turbine Blades Dynamics

Turbine blades are considered as straight naturally twisted rods. Two models are discussed: BernoulliEuler beam and Cosserat rod. Linear theories with small displacements, rotations and loads are used. The equations of dynamics taking into account bending, twisting, axial and shear deformations and cross links between them are derived. The stiffness coefficients in elasticity relations are defined. In the case of harmonic oscillations, we have for amplitudes the ordinary differential equations solved by means of computer mathematics (Mathcad). As a result the normal modes, the natural frequencies and also the amplitudes of forced oscillations are obtained. For the BernoulliEuler beam the LagrangeRitzKantorovich variational approach with approximations of deflections is proposed. The unknown coefficients of approximation depending on time are found by the numerical integration of the Lagrange system of equations. Proposed methods are applied to calculation of the real turbine blade.(VLID)484893

Mass Transport through Defects in Graphene Layers

The paper reports an experimental study of ZnTe and CuI transport through graphene wall of SWNTs by high resolution transmission electron microscopy. It is shown that encapsulated material evacuates the tube through the defects in the nanotube walls, while in-tube diffusion appears high enough to provide matter intake from the nanotube volume. Diffusion kinetics was studied by “atoms count” resulting in ZnTe and CuI diffusivities of 7.67 × 10^–21 and 1.99 × 10^–20 m²/s through single defects in SWNT wall. Semiempirical and DFT modeling of potential energy profiles for different types of defects was utilized to propose minimal structural disturbances in a graphene layer to make possible cross-plane transport of matter. The comparison of experimentally observed diffusivities with calculated activation barrier heights was carried out taking into account an effective temperature of substance under electron beam. Neither of the defects including framework disturbance with 5–7 defects or sp³-bound carbon atomic pairs give rise to valuable mass-transport efficiencies through graphene layer. Reasonable conformity of the results is only achieved with carbon vacancy pairs in sp²-carbon layer, thus, indicating effective transport of matter occurring through the “holes” in graphene

Glass-Ceramic Synthesis of Cr-Substituted Strontium Hexaferrite Nanoparticles with Enhanced Coercivity

Magnetically hard ferrites attract considerable interest due to their ability to maintain a high coercivity of nanosized particles and therefore show promising applications as nanomagnets ranging from magnetic recording to biomedicine. Herein, we report an approach to prepare nonsintered single-domain nanoparticles of chromium-substituted hexaferrite via crystallization of glass in the system SrO–Fe2O3–Cr2O3–B2O3. We have observed a formation of plate-like hexaferrite nanoparticles with diameters changing from 20 to 190 nm depending on the annealing temperature. We demonstrated that chromium substitution led to a significant improvement of the coercivity, which varied from 334 to 732 kA m−1 for the smallest and the largest particles, respectively. The results provide a new strategy for producing high-coercivity ferrite nanomagnets

Spray-Deposited Anisotropic Ferromagnetic Hybrid Polymer Films of PS- b -PMMA and Strontium Hexaferrite Magnetic Nanoplatelets

Spray deposition is a scalable and cost-effective technique for the fabrication of magnetic hybrid films containing diblock copolymers (DBCs) and magnetic nanoparticles. However, it is challenging to obtain spray-deposited anisotropic magnetic hybrid films without using external magnetic fields. In the present work, spray deposition is applied to prepare perpendicular anisotropic magnetic hybrid films by controlling the orientation of strontium hexaferrite nanoplatelets inside ultra-high-molecular-weight DBC polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) films. During spray deposition, the evolution of DBC morphology and the orientation of magnetic nanoplatelets are monitored with in situ grazing-incidence small-angle X-ray scattering (GISAXS). For reference, a pure DBC film without nanoplatelets is deposited with the same conditions. Solvent-controlled magnetic properties of the hybrid film are proven with solvent vapor annealing (SVA) applied to the final deposited magnetic films. Obvious changes in the DBC morphology and nanoplatelet localization are observed during SVA. The superconducting quantum interference device data show that ferromagnetic hybrid polymer films with high coercivity can be achieved via spray deposition. The hybrid films show a perpendicular magnetic anisotropy before SVA, which is strongly weakened after SVA. The spray-deposited hybrid films appear highly promising for potential applications in magnetic data storage and sensors