Safe Imitation Learning of Nonlinear Model Predictive Control for Flexible Robots

Flexible robots may overcome some of the industry's major challenges, such as enabling intrinsically safe human-robot collaboration and achieving a higher load-to-mass ratio. However, controlling flexible robots is complicated due to their complex dynamics, which include oscillatory behavior and a high-dimensional state space. NMPC offers an effective means to control such robots, but its extensive computational demands often limit its application in real-time scenarios. To enable fast control of flexible robots, we propose a framework for a safe approximation of NMPC using imitation learning and a predictive safety filter. Our framework significantly reduces computation time while incurring a slight loss in performance. Compared to NMPC, our framework shows more than a eightfold improvement in computation time when controlling a three-dimensional flexible robot arm in simulation, all while guaranteeing safety constraints. Notably, our approach outperforms conventional reinforcement learning methods. The development of fast and safe approximate NMPC holds the potential to accelerate the adoption of flexible robots in industry.Comment: Submitted to ICRA 202

Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides.

Risk of the development of multiple sclerosis (MS) is known to be increased in individuals bearing distinct class II human leukocyte antigen (HLA) variants, whereas some of them may have a protective effect. Here we analyzed distribution of a highly polymorphous HLA-DRB1 locus in more than one thousand relapsing-remitting MS patients and healthy individuals of Russian ethnicity. Carriage of HLA-DRB1*15 and HLA-DRB1*03 alleles was associated with MS risk, whereas carriage of HLA-DRB1*01 and HLA-DRB1*11 was found to be protective. Analysis of genotypes revealed the compensatory effect of risk and resistance alleles in trans. We have identified previously unknown MBP153−161 peptide located at the C-terminus of MBP protein and MBP90−98 peptide that bound to recombinant HLA-DRB1*01:01 protein with affinity comparable to that of classical antigenic peptide 306-318 from the hemagglutinin (HA) of the influenza virus demonstrating the ability of HLA-DRB1*01:01 to present newly identified MBP153−161 and MBP90−98 peptides. Measurements of kinetic parameters of MBP and HA peptides binding to HLA-DRB1*01:01 catalyzed by HLA-DM revealed a significantly lower rate of CLIP exchange for MBP153−161 and MBP90−98 peptides as opposed to HA peptide. Analysis of the binding of chimeric MBP-HA peptides demonstrated that the observed difference between MBP153−161, MBP90−98, and HA peptide epitopes is caused by the lack of anchor residues in the C-terminal part of the MBP peptides resulting in a moderate occupation of P6/7 and P9 pockets of HLA-DRB1*01:01 by MBP153−161 and MBP90−98 peptides in contrast to HA308−316 peptide. This leads to the P1 and P4 docking failure and rapid peptide dissociation and release of empty HLA-DM–HLA-DR complex. We would like to propose that protective properties of the HLA-DRB1*01 allele could be directly linked to the ability of HLA-DRB1*01:01 to kinetically discriminate between antigenic exogenous peptides and endogenous MBP derived peptides

Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement

The identification of low-frequency antigen-specific CD4+ T cells is crucial for effective immunomonitoring across various diseases. However, this task still encounters experimental challenges necessitating the implementation of enrichment procedures. While existing antigen-specific expansion technologies predominantly concentrate on the enrichment of CD8+ T cells, advancements in methods targeting CD4+ T cells have been limited. In this study, we report a technique that harnesses antigen-presenting extracellular vesicles (EVs) for stimulation and expansion of antigen-specific CD4+ T cells. EVs are derived from a genetically modified HeLa cell line designed to emulate professional antigen-presenting cells (APCs) by expressing key costimulatory molecules CD80 and specific peptide–MHC-II complexes (pMHCs). Our results demonstrate the beneficial potent stimulatory capacity of EVs in activating both immortalized and isolated human CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Our technique successfully expands low-frequency influenza-specific CD4+ T cells from healthy individuals. In summary, the elaborated methodology represents a streamlined and efficient approach for the detection and expansion of antigen-specific CD4+ T cells, presenting a valuable alternative to existing antigen-specific T-cell expansion protocols

ЗАСТОСУВАННЯ ЕКСПЕРТНОГО ОЦІНЮВАННЯ ПРИ ОБРОБЦІ РОЗВІДУВАЛЬНИХ ДАНИХ

In the paper there have been considered a methodology of expert selection uppon the personal characteristics, the survey and processing of expert evaluation results for application of expert evaluation in processing of reconnaissance data. The selection of reconnaissance expert has been offered to carry out taking into account of personal characteristics of experts in this area and to use for evaluation of gotten reconnaissance data during data processing. The method of quantitative processing and calculation of entropy of the results of expert evaluation has been offered. The method of determination of the competence level of reconnaissance groups. The selection of reconnaissance experts taking into account a number of personal characteristics of experts has been offered to carry out upon determination of the factor of quantitative personal characteristics. The characteristics of expert group have been determined based on personal characteristics of separate experts: competence, creativeness and attitude to expert examination, conformism, thinking constructiveness, team spirit and self-criticism. The expert evaluation, which must considered when processing of reconnaissance data, will influence on the level of trustworthiness of these data and, thereby, will provided increasing of effectiveness of the results of reconnaissance data processing. The working model of application of the method of selection of reconnaissance experts based on offered quantitative personal characteristics has been considered. The offered methodology can provide better grounded, objective and qualitative selection of reconnaissance experts.В статье расмотрены вопросы и методология подбора экспертов по индивидуальным характеристикам, проведении опроса и обработки результатов экспертной оценки для применения экспертного оценивания при обработке разведывательных данных. Чтобы применить метод экспертной оценки в процессе принятия решений по разведывательной информации, рассмотрены и проанализированы вопросы отбора экспертов по разведке по индивидуальным характеристикам, а также экспертный опрос и обработки результатов экспертной оценки разведывательных данных. Предлагается осуществлять подбор экспертов по разведке с учетом индивидуальных характеристик специалистов в этой области определенных количественно и привлекать их для оценивания пол ученных разведданных при их обработке. Предлагается количественное оценивание индивидуальных характеристик специалистов разведки и на основании этих результатов подбор экспертной группы, способ количественной обработки и расчета энтропии результатов экспертной оценки. Предложен метод, по которому можно определить уровень компетентности разведывательных групп. Подбор экспертов по разведке с учетом ряда количественных показателей индивидуальных характеристик специалистов предлагается проводить определением коэффициента индивидуальных характеристик. Экспертная оценка, которая должна учитываться при обработке полученных разведывательных данных, будет влиять на степень их достоверности и тем самым будет способствовать повышению эффективности результата обработки разведданных.У статті розглянута методологія підбору експертів за індивідуальними характеристиками, проведення опитування і обробки результатів експертної оцінки для застосування експертного оцінювання при обробці розвідувальних даних. Підбір експертів з розвідки пропонується здійснювати з урахуванням індивідуальних кількісних характеристик фахівців в цій області, і використовувати їх для оцінювання отриманих розвідданих при їх обробці. Пропонується спосіб кількісної обробки і розрахунку ентропії результатів експертної оцінки. Розроблено метод, за яким можна визначити рівень компетентності розвідувальних груп. Підбір експертів з розвідки з урахуванням ряду індивідуальних характеристик фахівців пропонується проводити визначенням коефіцієнта кількісних індивідуальних характеристик. Характеристики групи експертів визначаються на основі індивідуальних характеристик окремих експертів: компетентності, креативності, відносини до експертизи, конформізму, конструктивності мислення, колективізму, самокритичності. Експертна оцінка, яка повинна враховуватися при обробці отриманих розвідувальних даних, буде впливати на ступінь їх достовірності, і тим самим, сприятиме підвищенню ефективності результатів обробки розвідданих. Розглянуто практичний приклад застосування методу підбору фахівців з розвідки на основі запропонованих кількісних індивідуальних характеристик. Запропонована методологія може забезпечити більш обґрунтований, об'єктивний і якісний підбір фахівців з розвідки

MHC Class II Presentation in Autoimmunity

Antigen presentation by major histocompatibility complex class II (MHC-II) molecules is crucial for eliciting an efficient immune response by CD4+ T cells and maintaining self-antigen tolerance. Some MHC-II alleles are known to be positively or negatively associated with the risk of the development of different autoimmune diseases (ADs), including those characterized by the emergence of autoreactive T cells. Apparently, the MHC-II presentation of self-antigens contributes to the autoimmune T cell response, initiated through a breakdown of central tolerance to self-antigens in the thymus. The appearance of autoreactive T cell might be the result of (i) the unusual interaction between T cell receptors (TCRs) and self-antigens presented on MHC-II; (ii) the posttranslational modifications (PTMs) of self-antigens; (iii) direct loading of the self-antigen to classical MHC-II without additional nonclassical MHC assistance; (iv) the proinflammatory environment effect on MHC-II expression and antigen presentation; and (v) molecular mimicry between foreign and self-antigens. The peculiarities of the processes involved in the MHC-II-mediated presentation may have crucial importance in the elucidation of the mechanisms of triggering and developing ADs as well as for clarification on the protective effect of MHC-II alleles that are negatively associated with ADs

Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules

The T-cell immune response is a major determinant of effective SARS-CoV-2 clearance. Here, using the recently developed T-CoV bioinformatics pipeline (https://t-cov.hse.ru) we analyzed the peculiarities of the viral peptide presentation for the Omicron, Delta and Wuhan variants of SARS-CoV-2. First, we showed the absence of significant differences in the presentation of SARS-CoV-2-derived peptides by the most frequent HLA class I/II alleles and the corresponding HLA haplotypes. Then, the analysis was limited to the set of peptides originating from the Spike proteins of the considered SARS-CoV-2 variants. The major finding was the destructive effect of the Omicron mutations on PINLVRDLPQGFSAL peptide, which was the only tight binder from the Spike protein for HLA-DRB1*03:01 allele and some associated haplotypes. Specifically, we predicted a dramatical decline in binding affinity of HLA-DRB1*03:01 and this peptide both because of the Omicron BA.1 mutations (N211 deletion, L212I substitution and EPE 212-214 insertion) and the Omicron BA.2 mutations (V213G substitution). The computational prediction was experimentally validated by ELISA with the use of corresponding thioredoxin-fused peptides and recombinant HLA-DR molecules. Another finding was the significant reduction in the number of tightly binding Spike peptides for HLA-B*07:02 HLA class I allele (both for Omicron and Delta variants). Overall, the majority of HLA alleles and haplotypes was not significantly affected by the mutations, suggesting the maintenance of effective T-cell immunity against the Omicron and Delta variants. Finally, we introduced the Omicron variant to T-CoV portal and added the functionality of haplotype-level analysis to it

Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody

The engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant κ light chain by the λ chain (A17λ), and the X-ray structure of A17λ has been determined at 1.95 Å resolution. It was found that compared with A17κ the active centre of A17λ is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the VL and VH domains. These VL/VH domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126° compared with 138° in A17κ. These structural differences account for the subtle changes in catalytic efficiency and thermodynamic parameters determined with two organophosphate ligands, as well as in the affinity for peptide substrates selected from a combinatorial cyclic peptide library, between the A17κ and A17λ variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions