Long-term persistence and effects of fetal microchimerisms on disease onset and status in a cohort of women with rheumatoid arthritis and systemic lupus erythematosus

BACKGROUND: The discovery of a fetal cells transfer to the mother is a phenomenon with multiple implications for autoimmunity and tolerance. The prevalence and meaning of the feto-maternal microchimerism (MC) in rheumatic diseases has not been thoroughly investigated. The aim of this study was to analyze the prevalence of fetal MC in patients with inflammatory rheumatic diseases and to investigate the association of MC with disease onset and current status. METHODS: A total of 142 women who gave birth to at least one male offspring were recruited: 72 women with rheumatoid arthritis (RA), 16 women with systemic lupus erythematosus (SLE), and 54 healthy women. For the detection of fetal microchimerism a nested PCR method was used to amplify a Y chromosome specific sequence (TSPY1). For characterization of disease activity we analyzed autoantibody profiles and X-rays in RA, and in addition complement levels in SLE respectively. RESULTS: A significant higher prevalence of fetal MC was found in RA (18%) and SLE (31%) compared to controls (3.7%) (p = 0.02 and p = 0.006, resp.). The mean age at disease onset was comparable in MC + and MC- RA patients. Disease onset occurred 18.7 (MC +) and 19.8 (MC-) years post partum of the first son, respectively. The presence of anti-CCP and RF did not differ significantly, anti-CCP were found in 75% of MC + and 87% of MC- patients, RF in 75% of both MC + and MC- patients. A slightly higher mean Steinbrocker score in MC + patients was associated with longer disease duration in MC + compared to MC- RA. In SLE patients the mean age at disease onset was 42.6 years in MC + and 49.1 years in MC- patients. Disease onset occurred 24.0 and 26.4 years post partum of the first son for MC + and MC- patients, respectively. The presence of ANA and anti-dsDNA antibodies, C3, C4 and CH50 did not differ significantly. CONCLUSION: Our results indicate a higher frequency of long-term male MC in RA and SLE patients compared with controls without impact on disease onset and status in RA and SLE

Исследование алгоритмов функционирования СМО с использованием библиотеки SimEvents

Выпускная квалификационная работа 80 с., 18 рис., 6 табл., 21 источник. Объект исследования — модель управления графитовыми стержнями в ядерном реакторе. Цель работы — разработка модели управления замедляющими стержнями в реакторе с использованием библиотеки SimEvents. Изучены принципы имитационного моделирования с помощью библиотек SimEvents, Simulink. Разработана модель управления графитовыми стержнями в реакторе, получены параметры системы, проведен их анализ. Модель может использоваться как имитатор физического процесса в атомном производстве. Имитационная модель дает подтверждение расчетов, прогноз работы системы, позволяет исследовать работу в критических режимах. Планируется изучение новых характеристик системы, разработка более сложной модели, параметров, влияющих на новую модельGraduation qualification project consist of 80 p., 18 fig., 6 tab., 21 sources. The object of this study is graphite rods’s control model in nuclear reactors. The purpose of work – graphite rods’s control model development using SimEvents in nuclear reactors. Is studied the simulation principles using libraries SimEvents, Simulink. Are obtained the model of the control rods in the reactor graphite, the system parameters , their analysis was carried out. The model can be used as a simulator of a physical process in nuclear industry. A simulation model provides evidence calculations, the forecast of the system, allows you to explore the critical operation. It is planned to study the characteristics of the new system, the development of a more complex model, the parameters affecting a mode

Технология и техника сооружения поисково-оценочных скважин на Майском месторождении алмазов (Республика Саха (Якутия))

Объектом исследования является кимберлитовая руда на объекте "Майское". Цель работы: составление проекта на бурение поисково-оценочных скважин; геологическое изучение объекта; разработка технологии проведе-ния поисковых работ на участке; разработка управления и организации работ на объекте. В процессе проектирования проводились: выбор бурового оборудования; поверочный расчет выбранного оборудования; расчет режимных параметров; анализ вредных и опасных факторов при проведении геологоразведочных работ и меры по их предупреждению; выбор вспомогательного оборудования и организации работ; сметно-финансовый расчет.The object of the study is kimberlite ore at the Mayskoye facility. The purpose of the work: preparation of the project for the drilling of exploration and evaluation wells; geological study of the object; development of technology for prospecting works on the site; development of management and organization of works on the site. In the process of design were carried out: selection of drilling equipment; calibration calculation of the selected equipment; calculation of operating parameters; analysis of harmful and dangerous factors during exploration and measures to prevent them; selection of auxiliary equipment and organization of wo

Mutations of the Ephrin-B1 Gene Cause Craniofrontonasal Syndrome

Craniofrontonasal syndrome (CFNS) is an X-linked craniofacial disorder with an unusual manifestation pattern, in which affected females show multiple skeletal malformations, whereas the genetic defect causes no or only mild abnormalities in male carriers. Recently, we have mapped a gene for CFNS in the pericentromeric region of the X chromosome that contains the EFNB1 gene, which encodes the ephrin-B1 ligand for Eph receptors. Since Efnb1 mutant mice display a spectrum of malformations and an unusual inheritance reminiscent of CFNS, we analyzed the EFNB1 gene in three families with CFNS. In one family, a deletion of exons 2–5 was identified in an obligate carrier male, his mildly affected brother, and in the affected females. In the two other families, missense mutations in EFNB1 were detected that lead to amino acid exchanges P54L and T111I. Both mutations are located in multimerization and receptor-interaction motifs found within the ephrin-B1 extracellular domain. In all cases, mutations were found consistently in obligate male carriers, clinically affected males, and affected heterozygous females. We conclude that mutations in EFNB1 cause CFNS

Mice Lacking the Nuclear Pore Complex Protein ALADIN Show Female Infertility but Fail To Develop a Phenotype Resembling Human Triple A Syndrome

Triple A syndrome is a human autosomal recessive disorder characterized by adrenal insufficiency, achalasia, alacrima, and neurological abnormalities affecting the central, peripheral, and autonomic nervous systems. In humans, this disease is caused by mutations in the AAAS gene, which encodes ALADIN, a protein that belongs to the family of WD-repeat proteins and localizes to nuclear pore complexes. To analyze the function of the gene in the context of the whole organism and in an attempt to obtain an animal model for human triple A syndrome, we generated mice lacking a functional Aaas gene. The Aaas(−/−) animals were found to be externally indistinguishable from their wild-type littermates, although their body weight was on the average lower than that of wild-type mice. Histological analysis of various tissues failed to reveal any differences between Aaas(−/−) and wild-type mice. Aaas(−/−) mice exhibit unexpectedly mild abnormal behavior and only minor neurological deficits. Our data show that the lack of ALADIN in mice does not lead to a triple A syndrome-like disease. Thus, in mice either the function of ALADIN differs from that in humans, its loss can be readily compensated for, or additional factors, such as environmental conditions or genetic modifiers, contribute to the disease