Corrector estimates in homogenization of a nonlinear transmission problem for diffusion equations in connected domains

This paper is devoted to the homogenization of a nonlinear transmission problem stated in a two-phase domain. We consider a system of linear diffusion equations defined in a periodic domain consisting of two disjoint phases that are both connected sets separated by a thin interface. Depending on the field variables, at the interface, nonlinear conditions are imposed to describe interface reactions. In the variational setting of the problem, we prove the homogenization theorem and a bidomain averaged model. The periodic unfolding technique is used to obtain the residual error estimate with a first-order corrector. © 2019 The Authors. Mathematical Methods in the Applied Sciences published by John Wiley & Sons Ltd

On feasibility of rate-independent stress paths under proportional deformations within hypoplastic constitutive model for granular materials

We study stress paths that are obtained under proportional deformations within the rate-independent hypoplasticity theory of Kolymbas type describing granular materials like soil and broken rock. For a particular simplified hypoplastic constitutive model by Bauer, a closed-form solution of the corresponding system of non-linear ordinary differential equations is available. Since only negative principal stresses are relevant for the granular body, the feasibility of the solution consistent with physics is investigated in dependence of the direction of a proportional strain path and constitutive parameters of the model

Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost “Sputnik V” vaccine administered at 1/10 and 1/5 doses to adolescents aged 12–17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants.;Clinical Trial RegistrationClinicalTrials.gov, NCT04954092, LP-007632

Опыт вакцинации 13-валентной конъюгированной пневмококковой вакциной пациентки с ювенильным идиопатическим артритом с частыми респираторными инфекциями на фоне терапии метотрексатом

The article presents the experience of vaccination with a pneumococcal 13-valent conjugate vaccine (PCV13) of a patient aged 5 years with oligoarticular juvenile idiopathic arthritis (JIA) receiving methotrexate at a dose of 15 mg/m2 per week subcutaneously. Treatment with methotrexate provided a remission of JIA, but was accompanied by frequent respiratory infections — up to 8 times a year. During infection progression, methotrexate injections were omitted. Gaps in the treatment with methotrexate were accompanied by an exacerbation of the underlying condition. Vaccination of the patient with PCV13 reduced the frequency of respiratory infections to 2 times a year, which was accompanied by the development of persistent remission of the disease. Adverse events and exacerbation of JIA in a child after vaccination with PCV13 were not registered.Представлен опыт вакцинации 13-валентной конъюгированной пневмококковой вакциной (13ПКВ) пациентки в возрасте 5 лет с олигоартикулярным ювенильным идиопатическим артритом (ЮИА), получавшей метотрексат в дозе 15 мг/м2 в неделю подкожно. Лечение метотрексатом обеспечило ремиссию ЮИА, но сопровождалось частыми респираторными инфекциями — до 8 раз в год. При развитии инфекций инъекции метотрексата пропускались. Перерывы в лечении метотрексатом сопровождались обострением основного заболевания. Вакцинация пациентки 13ПКВ обеспечила снижение частоты респираторных инфекций до 2 раз в год, что сопровождалось развитием стойкой ремиссии заболевания. Нежелательных явлений и обострения ЮИА у ребенка на фоне вакцинации 13ПКВ не зарегистрировано

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

On Lyapunov stability in hypoplasticity

summary:We investigate the Lyapunov stability implying asymptotic behavior of a nonlinear ODE system describing stress paths for a particular hypoplastic constitutive model of the Kolymbas type under proportional, arbitrarily large monotonic coaxial deformations. The attractive stress path is found analytically, and the asymptotic convergence to the attractor depending on the direction of proportional strain paths and material parameters of the model is proved rigorously with the help of a Lyapunov function

Monogenic diabetes associated with PAX4 gene mutations (MODY9): first description in Russia

Maturity-onset diabetes of the young (MODY) is a heterogeneous group of disorders characterised by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic beta-cells. To date, at least 13 subtypes of MODY have been described in the literature, the most frequent of which are MODY types 13. MODY2 and MODY3 are the most prevalent subtypes, and were previously described in our country, Russia. Several cases of rare MODY subtypes were subsequently described in the Russian literature. The current report is the first in the Russian literature to present clinical and molecular genetic characteristics of two cases of another rare MODY subtypeMODY9. This type of MODY is associated with mutations in the PAX4 gene, which encodes transcription factor PAX4, one of the factors essential for pancreatic beta-cell differentiation. Molecular genetic analysis was performed using next-generation sequencing, a new method recently applied to verify monogenic diseases and, in particular, MODY. This study reports a novel mutation in the PAX4 gene in MODY patients

Topographic Distribution of miRNAs (miR-30a, miR-223, miR-let-7a, miR-let-7f, miR-451, and miR-486) in the Plasma Extracellular Vesicles

There are many articles on the quantitative analysis of miRNAs contained in a population of EVs of different sizes under various physiological and pathological conditions. For such analysis, it is important to correctly quantify the miRNA contents of EVs. It should be considered that quantification is skewed depending on the isolation protocol, and different miRNAs are degraded by nucleases with different efficiencies. In addition, it is important to consider the contribution of miRNAs coprecipitating with the EVs population, because the amount of miRNAs in the EVs population under study is skewed without appropriate enzymatic treatment. By studying a population of EVs from the blood plasma of healthy donors, we found that the absolute amount of miRNA inside the vesicles is commensurate with the amount of the same type of miRNA adhered to the outside of the EVs. The inside/outside ratio ranged from 1.02 to 2.64 for different investigated miRNAs. According to our results, we propose the hypothesis that high occupancy of miRNAs on the outer surface of EVs influence on the transporting RNA repertoire no less than the inner cargo received from the host cell