Разработка и исследование асинхронного электропривода с наблюдателем состояния

Выпускная квалификационная работа 109 с., 35 рис., 18 табл., 47 источников, 5 прил. Объектом исследования является дискретная математическая модель наблюдателя состояния полного порядка асинхронного двигателя. Цель работы – Разработка и исследование асинхронного электропривода с наблюдателем состояния В процессе исследования проводилось имитационное моделирование разработанной дискретной математической модели асинхронного двигателя и разработанной дискретной математической модели наблюдателя состояния полного порядкаFinal qualifying work 109 p., 35 fig., 18 tab., 47 sources, 5 adj. The object of research is a discrete mathematical model of the observer status of full order of the induction motor. Objective - Development and research of the asynchronous electric drive with observer status The study was conducted simulations developed discrete mathematical model of the induction motor and the developed mathematical model of discrete observer of full order stat

IL-26 inhibits hepatitis C virus replication in hepatocytes

Publisher Copyright: © 2021 European Association for the Study of the LiverBackground & Aims: Interleukin-26 (IL-26) is a proinflammatory cytokine that has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. We previously observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic HCV infection and showed that infiltrating CD3+ lymphocytes were the principal source of IL-26. Surprisingly, IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV. Based on this observation and possible interactions between IL-26 and nucleic acids, we investigated the possibility that IL-26 controlled HCV infection independently of the immune system. Methods: We evaluated the ability of IL-26 to interfere with HCV replication in hepatocytes and investigated the mechanisms by which IL-26 exerts its antiviral activity. Results: We showed that IL-26 penetrated HCV-infected hepatocytes, where it interacted directly with HCV double-stranded RNA replication intermediates, thereby inhibiting viral replication. IL-26 interfered with viral RNA-dependent RNA polymerase activity, preventing the de novo synthesis of viral genomic single-stranded RNA. Conclusions: These findings reveal a new role for IL-26 in direct protection against HCV infection, independently of the immune system, and increase our understanding of the antiviral defense mechanisms controlling HCV infection. Future studies should evaluate the possible use of IL-26 for treating other chronic disorders caused by RNA viruses, for which few treatments are currently available, or emerging RNA viruses. Lay summary: This study sheds new light on the body's arsenal for controlling hepatitis C virus (HCV) infection and identifies interleukin-26 (IL-26) as an antiviral molecule capable of blocking HCV replication. IL-26, which has unique biochemical and structural characteristics, penetrates infected hepatocytes and interacts directly with viral RNA, thereby blocking viral replication. IL-26 is, therefore, a new player in antiviral defenses, operating independently of the immune system. It is of considerable potential interest for treating HCV infection and other chronic disorders caused by RNA viruses for which few treatments are currently available, and for combating emerging RNA viruses.Peer reviewe

Role of Gas6 Receptors in Platelet Signaling during Thrombus Stabilization and Implications for Antithrombotic Therapy

Mechanisms regulating thrombus stabilization remain largely unknown. Here, we report that loss of any 1 of the Gas6 receptors (Gas6-Rs), i.e., Tyro3, Axl, or Mer, or delivery of a soluble extracellular domain of Axl that traps Gas6 protects mice against life-threatening thrombosis. Loss of a Gas6-R does not prevent initial platelet aggregation but impairs subsequent stabilization of platelet aggregates, at least in part by reducing “outside-in” signaling and platelet granule secretion. Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the β3 integrin, thereby amplifying outside-in signaling via αIIbβ3. Blocking the Gas6-R–αIIbβ3 integrin cross-talk might be a novel approach to the reduction of thrombosis

Variability of protein level and phosphorylation status caused by biopsy protocol design in human skeletal muscle analyses

<p>Abstract</p> <p>Background</p> <p>Bergström needle biopsy is widely used to sample skeletal muscle in order to study cell signaling directly in human tissue. Consequences of the biopsy protocol design on muscle protein quantity and quality remain unclear. The aim of the present study was to assess the impact of different events surrounding biopsy protocol on the stability of the Western blot signal of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, glycogen synthase kinase-3β (GSK-3β), muscle RING finger protein 1 (MuRF1) and p70 S6 kinase (p70 S6K). Six healthy subjects underwent four biopsies of the <it>vastus lateralis</it>, distributed into two distinct visits spaced by 48 hrs. At visit 1, a basal biopsy in the right leg was performed in the morning (R1) followed by a second in the left leg in the afternoon (AF). At visit 2, a second basal biopsy (R2) was collected from the right leg. Low intensity mobilization (3 × 20 right leg extensions) was performed and a final biopsy (Mob) was collected using the same incision site as R2.</p> <p>Results</p> <p>Akt and p70 S6K phosphorylation levels were increased by 83% when AF biopsy was compared to R1. Mob condition induced important phosphorylation of p70 S6K when compared to R2. Comparison of R1 and R2 biopsies revealed a relative stability of the signal for both total and phosphorylated proteins.</p> <p>Conclusions</p> <p>This study highlights the importance to standardize muscle biopsy protocols in order to minimize the method-induced variation when analyzing Western blot signals.</p

Neutralising Antibodies against Ricin Toxin

The Centers for Disease Control and Prevention have listed the potential bioweapon ricin as a Category B Agent. Ricin is a so-called A/B toxin produced by plants and is one of the deadliest molecules known. It is easy to prepare and no curative treatment is available. An immunotherapeutic approach could be of interest to attenuate or neutralise the effects of the toxin. We sought to characterise neutralising monoclonal antibodies against ricin and to develop an effective therapy. For this purpose, mouse monoclonal antibodies (mAbs) were produced against the two chains of ricin toxin (RTA and RTB). Seven mAbs were selected for their capacity to neutralise the cytotoxic effects of ricin in vitro. Three of these, two anti-RTB (RB34 and RB37) and one anti-RTA (RA36), when used in combination improved neutralising capacity in vitro with an IC50 of 31 ng/ml. Passive administration of association of these three mixed mAbs (4.7 µg) protected mice from intranasal challenges with ricin (5 LD50). Among those three antibodies, anti-RTB antibodies protected mice more efficiently than the anti-RTA antibody. The combination of the three antibodies protected mice up to 7.5 hours after ricin challenge. The strong in vivo neutralising capacity of this three mAbs combination makes it potentially useful for immunotherapeutic purposes in the case of ricin poisoning or possibly for prevention

Cellular Response to Surface Wettability Gradient on Microtextured Surfaces

Objective: Topography, chemistry, and energy of titanium (Ti) implants alter cell response through variations in protein adsorption, integrin expression, and downstream cell signaling. However, the contribution of surface energy on cell response is difficult to isolate because altered hydrophilicity can result from changes in surface chemistry or microstructure. Our aim was to examine a unique system of wettability gradients created on microstructured Ti on osteoblast maturation and phenotype. Method: A surface energy gradient was created on sand-blasted/acid-etched (SLA) Ti surfaces. Surfaces were treated with oxygen plasma for 2 minutes, and then allowed to age for 1, 12, 80, or 116 hours to generate a wettability gradient. Surfaces were characterized by contact angle and SEM. MG63 cells were cultured on SLA or experimental SLA surfaces to confluence on TCPS. Osteoblast differentiation (IBSP, RUNX2, ALP, OCN, OPG) and integrin subunits (ITG2, ITGA5, ITGAV, ITGB1) measured by real-time PCR (n=6 surfaces per variable analyzed by ANOVA/Bonferroni’s modified Student’s t-test). Result: After plasma treatment, SLA surface topography was retained. A gradient of wettability was obtained, with contact angles of 32.0° (SLA116), 23.3° (SLA80), 12.5° (SLA12), 7.9° (SLA1). All surfaces were significantly more hydrophilic than the original SLA surface (126.8°). Integrin expression was affected by wettability. ITGA2 was higher on wettable surfaces than on SLA, but was highest on SLA1. ITGAV and ITGB1 were decreased on hydrophilic surfaces, but ITGA5 was not affected. IBSP, RUNX2, and ALP increased and OPG decreased with increasing wettability. OCN decreased with increasing wettability, but levels on the most wettable surface were similar to SLA. Conclusion: Here we elucidated the role of surface energy on cell response using surfaces with the same topography and chemistry. The results show that osteoblastic maturation was regulated in a wettability-dependent manner and suggest that the effects are mediated by integrins.Undergraduat

Role of T3SS-1 SipD protein in protecting mice against non-typhoidal Salmonella Typhimurium

Background : Salmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5 years and immunocompromised adults. Vaccines targeting typhoidal diseases are already marketed, but none protect against non-typhoidal Salmonella. The existence of multiple non-typhoidal Salmonella serotypes as well as emerging antibiotic resistance highlight the need for development of a broad-spectrum protective vaccine. All Salmonella spp. utilize two type III Secretion Systems (T3SS 1 and 2) to initiate infection, allow replication in phagocytic cells and induce systemic disease. T3SS-1, which is essential to invade epithelial cells and cross the barrier, forms an extracellular needle and syringe necessary to inject effector proteins into the host cell. PrgI and SipD form, respectively, the T3SS-1 needle and the tip complex at the top of the needle. Because they are common and highly conserved in all virulent Salmonella spp., they might be ideal candidate antigens for a subunit-based, broad-spectrum vaccine. Principal Findings : We investigated the immunogenicity and protective efficacy of PrgI and SipD administered by subcutaneous, intranasal and oral routes, alone or combined, in a mouse model of Salmonella intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins, particularly SipD. Mice orally immunized with SipD alone or SipD combined with PrgI were protected against lethal intestinal challenge with Salmonella Typhimurium (100 Lethal Dose 50%) depending on antigen, route and adjuvant. Conclusions and Significance : Salmonella T3SS SipD is a promising antigen for the development of a protective Salmonella vaccine, and could be developed for vaccination in tropical endemic areas to control infant mortality

Fast and Simple Detection of Yersinia pestis Applicable to Field Investigation of Plague Foci

International audienceYersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. There is now a convenient and effective test (F1-dipstick) for the rapid identification of Y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the F1 capsule is mostly produced at 37uC. The plasminogen activator (PLA), a key virulence factor encoded by a Y. pestis-specific plasmid, is synthesized both at 20uC and 37uC, making it a good candidate antigen for environmental detection of Y. pestis by immunological methods. A recombinant PLA protein from Y. pestis synthesized by an Escherichia coli strain was used to produce monoclonal antibodies (mAbs). PLA-specific mAbs devoid of cross-reactions with other homologous proteins were further cloned. A pair of mAbs was selected based on its specificity, sensitivity, comprehensiveness, and ability to react with Y. pestis strains grown at different temperatures. These antibodies were used to develop a highly sensitive one-step PLA-enzyme immunoassay (PLA-EIA) and an immunostrip (PLA-dipstick), usable as a rapid test under field conditions. These two PLA-immunometric tests could be valuable, in addition to the F1-disptick, to confirm human plague diagnosis in non-endemic areas (WHO standard case definition). They have the supplementary advantage of allowing a rapid and easy detection of Y. pestis in environmental and flea samples, and would therefore be of great value for surveillance and epidemiological investigations of plague foci. Finally, they will be able to detect natural or genetically engineered F1-negative Y. pestis strains in human patients and environmental samples. Citation: Simon S, Demeure C, Lamourette P, Filali S, Plaisance M, et al. (2013) Fast and Simple Detection of Yersinia pestis Applicable to Field Investigation of Plague Foci

An antibody targeting type III secretion system induces broad protection against Salmonella and Shigella infections

International audienceSalmonella and Shigella bacteria are food- and waterborne pathogens that are responsible for enteric infections in humans and are still the major cause of morbidity and mortality in the emerging countries. The existence of multiple Salmonella and Shigella serotypes as well as the emergence of strains resistant to antibiotics requires the development of broadly protective therapies. Recently, the needle tip proteins of the type III secretion system of these bacteria were successfully utilized (SipD for Salmonella and IpaD for Shigella ) as vaccine immunogens to provide good prophylactic cross-protection in murine models of infections. From these experiments, we have isolated a cross-protective monoclonal antibody directed against a conserved region of both proteins. Its conformational epitope determined by Deep Mutational Scanning is conserved among needle tip proteins of all pathogenic Shigella species and Salmonella serovars, and are well recognized by this antibody. Our study provides the first in vivo experimental evidence of the importance of this common region in the mechanism of virulence of Salmonella and Shigella and opens the way to the development of cross-protective therapeutic agents

Duplex lateral flow immunoassay (LFIA) for detection of Yersinia pestis in environmental samples and suspicious substances

International audienceYersinia pestis (Y. pestis), the causative agent of the plague disease, has long been considered as a potent weapon of biological warfare. The rapid detection of the bioterrorist agent in environment or suspicious substances is essential to protect the civil population in case of malicious act. In this context, several dipsticks for rapid detection of Y. pestis have been developed and are now available on the market. These tests target almost exclusively the fraction capsular antigen 1 (F1) expressed mostly at 37°C (in course of infection or in-vitro culture), and are thus not always adapted for detection of Y. pestis from environmental source.For this reason, we developed a duplex lateral flow immunoassay (LFIA) combining the detection of F1 and an antigen expressed independently of the temperature. An industrial pre-batch was produced and its analytical sensitivity was assessed using bacteria grown at temperature in the range of 20°C to 37°C. The specificity was checked using various Y. pestis strains, strains of closely related species and more distantly related species. All ten Y. pestis strains grown at 30°C or 37°C were detected positive, as well as some Y. pseudotuberculosis strains but with a lower signal intensity. Other species were tested negative. Moreover, we investigated the impact of various environmental matrices and suspicious substances on the field. Most of them had no effect on the observed results