Промышленный унифицированный рекуператор на базе модульных элементов «Силал» М-I 115x460x860-05 и «Силал» М-II 230x460x860-1,0 (типоряд М-I и М-II)

The paper proposes a fundamentally new modification of cast iron recuperative heat exchanger assembled on the basis of the following modules: «Silal» M-I 115x460x860-05 and «Silal» M-II 230x460x860-1.0.It is shown that such recuperative heat exchanger does not have the disadvantages which are inherent to presently applied recuperators.Предлагается принципиально новая модификация чугунного рекуператора, собранного из модулей («Силал» М-I 115x460x860-05 и «Силал» М-II 230x460x860-1,0).Показано, что такой рекуператор лишен недостатков, которые присущи используемым в настоящее время

Характеристики системы «газогорелочное устройство - технологическая зона» как объекта автоматического регулирования и уравнение общей тепловой нагрузки нагревательной (термической) печи

An equation pertaining to dynamics of automatic control of «gas-burning device - high-temperature zone» object has been formulated in the paper. The equation may serve as a basis for development of automatic control scheme. Записано уравнение динамики автоматического регулирования объекта «газогорелочное устройство - высокотемпературная зона», которое может служить основой для разработки схемы автоматического регулирования

ГИДРОДИНАМИЧЕСКОЕ СОПРОТИВЛЕНИЕ УНИФИЦИРОВАННОГО МОДУЛЬНОГО РЕКУПЕРАТОРА НАГРЕВАТЕЛЬНЫХ И ТЕРМИЧЕСКИХ ПЕЧЕЙ ЗАГОТОВИТЕЛЬНОГО И МЕХАНОСБОРОЧНОГО КОМПЛЕКСОВ МАШИНОСТРОИТЕЛЬНЫХ И АВТОТРАКТОРНЫХ ЗАВОДОВ

Analysis of hydrodynamic resistance of gas and air paths of a recuperator assembled with the help of unified module elements M-I and M-II has been carried out. The paper shows the possibility to change path resistance within a wide range of values. Выполнен анализ гидродинамического сопротивления газового и воздушного трактов рекуператора, собранного из унифицированных модульных элементов М-I и М-II. Показана возможность изменения сопротивления трактов в широком диапазоне значений

К расчету унифицированного модульного рекуператора (модули М-I и М-II) для нагревательных и термических печей заготовительного и механосборочного производств машиностроительных и автотракторных заводов Республики Беларусь

The paper shows an influence of outside ribbing of heat-exchange surface of unified modules M-I and M-II on heat transfer factor of the proposed recuperator and its hydro-dynamic resistance.Показано влияние наружного оребрения поверхности теплообмена унифицированных модулей М-I и М-II на коэффициент теплопередачи предлагаемого рекуператора и его гидродинамическое сопротивление

Peculiarities of the influenza viruses circulation and their properties during 2018-2019 epidemic season in Russia and countries of the Northern Hemisphere

Objective. To identify the drift variability of influenza viruses during the period of epidemic rise in the incidence of acute respiratory viral infections in the period 2018-2019. The biological and molecular-genetic properties of epidemic strains isolated in certain territories of the Russian Federation were studied and compared with data from the countries of the Northern Hemisphere. Materials and methods. A range of laboratory diagnostic methods has been applied, including immune fluorescence, RT-PCR, sequencing, methods for determining sensitivity to influenza drugs and receptor specificity. Results and discussion. The proportion of influenza viruses was as follows: A (H1N1) pdm09 - 53 %, A (H3N2) - 46 %, B - about 1 %. Cases of severe acute respiratory infections have most often been associated with influenza A(H1N1) pdm09 virus. According to antigenic properties, isolated strains corresponded to the properties of vaccine viruses (A/Michigan/45/2015 - by 99.6 % and A/Singapore INFIMH-16-0019/2016 - by 86 %). The heterogeneity of influenza A virus strains population was revealed as regards individual mutations in hemaglutinin. The influenza B virus population was equally represented by both evolutionary lines (B/Victoria and B/Yamagata-like). Receptor specificity was favorable for the course and outcome of the disease. Among 70 studied epidemic strains, no strains resistant to anti-neuraminidase drugs, oseltamivir and zanamivir, were detected. The article presents WHO recommendations on the composition of influenza vaccines for the countries of the Northern Hemisphere for 2019-2020, provides data on cases of human infection with avian influenza viruses A(H5N1), A(H5N6), A(H7N9) and A(H9N2)

The Phospholipid Scramblases 1 and 4 Are Cellular Receptors for the Secretory Leukocyte Protease Inhibitor and Interact with CD4 at the Plasma Membrane

Secretory leukocyte protease inhibitor (SLPI) is secreted by epithelial cells in all the mucosal fluids such as saliva, cervical mucus, as well in the seminal liquid. At the physiological concentrations found in saliva, SLPI has a specific antiviral activity against HIV-1 that is related to the perturbation of the virus entry process at a stage posterior to the interaction of the viral surface glycoprotein with the CD4 receptor. Here, we confirm that recombinant SLPI is able to inhibit HIV-1 infection of primary T lymphocytes, and show that SLPI can also inhibit the transfer of HIV-1 virions from primary monocyte-derived dendritic cells to autologous T lymphocytes. At the molecular level, we show that SLPI is a ligand for the phospholipid scramblase 1 (PLSCR1) and PLSCR4, membrane proteins that are involved in the regulation of the movements of phospholipids between the inner and outer leaflets of the plasma membrane. Interestingly, we reveal that PLSCR1 and PLSCR4 also interact directly with the CD4 receptor at the cell surface of T lymphocytes. We find that the same region of the cytoplasmic domain of PLSCR1 is involved in the binding to CD4 and SLPI. Since SLPI was able to disrupt the association between PLSCR1 and CD4, our data suggest that SLPI inhibits HIV-1 infection by modulating the interaction of the CD4 receptor with PLSCRs. These interactions may constitute new targets for antiviral intervention

Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition

SummarySmoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant

Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy1,2,3. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations2. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes1,3. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1)1,3,4. Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.This work was supported by an Alex's Lemonade Stand Young Investigator Award (S.C.M.), The CIHR Banting Fellowship (S.C.M.), The Cancer Prevention Research Institute of Texas (S.C.M., RR170023), Sibylle Assmus Award for Neurooncology (K.W.P.), the DKFZ-MOST (Ministry of Science, Technology & Space, Israel) program in cancer research (H.W.), James S. McDonnell Foundation (J.N.R.) and NIH grants: CA154130 (J.N.R.), R01 CA169117 (J.N.R.), R01 CA171652 (J.N.R.), R01 NS087913 (J.N.R.) and R01 NS089272 (J.N.R.). R.C.G. is supported by NIH grants T32GM00725 and F30CA217065. M.D.T. is supported by The Garron Family Chair in Childhood Cancer Research, and grants from the Pediatric Brain Tumour Foundation, Grand Challenge Award from CureSearch for Children’s Cancer, the National Institutes of Health (R01CA148699, R01CA159859), The Terry Fox Research Institute and Brainchild. M.D.T. is also supported by a Stand Up To Cancer St. Baldrick’s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113)

Разнообразие и опасность Achromobacter spp., поражающих дыхательные пути больных муковисцидозом

Background and aims. Achromobacter spp., as causative agent of the nosocomial infections, has caught the eye last Decades. The growth of the infecting of the respiratory tract of the cystic fibrosis patients by this microorganism is formidable. The aim of this investigation was the Achromobacter spp. identification in expanded cohort of the Russian CF patients, genotyping of the microorganism according to the international standards and molecular epidemiological analysis of the situation with this opportunistic microorganism. Methods. Clinical samples from about 300 patients: sputum, tracheal aspirate, throat swabs and strains, isolated from the samples, were the material for the investigation. Method of the multilocus sequence typing (MLST), extended by the additional targets, was the base for the research. Results. 25 percents of the patients routinely hospitalized because of the severity of the disease, were infected by Achromobacter spp. of five species: A. xylosoxidans, A. ruhlandii, A. marplatensis, A. dolens, A. pulmonis, and one genogroup. The species A. ruhlandii has dominated (58.5%). One of the drug resistance indicator – oxacillinase gene blaOXA – helps in the differentiation of the genera Achromobacter and Burkholderia, and also some species in the genus Achromobacter. From 26 identified Achromobacter spp. genotypes (sequence type, ST) 16 STs relate to the species A. xylosoxidans, five – to A. ruhlandii. ST263 is specific to the patients from the Far Eastern Federal District. ST261 and 36 are the most numerous: the patients of all Federal Districts are infected by this ST. The chronological analysis allows suggesting the replacement of the genotype 261 by the genotype 36 in the end of the 1990s years and the A. ruhlandii ST36 nosocomial outbreak. At present 39% of the patients with Achromobacter spp. are infected by A. ruhlandii ST36, transmissivity of which is proved the coinfection cases of the siblings and simultaneously hospitalized patients. The influence on the respiratory function of the CF patients was the most expressed for the A. ruhlandii ST261strains. For the younger age group (1997 year of birth and younger), infected by A. ruhlandii ST36, the median of the FEV1 was slightly lower than in older age group, infected by those strain, that can indicate the accumulation of the pathogenic properties by the A. ruhlandii ST36 during the circulation between the patients. Conclusions. A. ruhlandii ST36 strain by the combination of the identified properties may be considered as the Russian epidemic strain.Achromobacter spp. как возбудитель внутрибольничных инфекций обратил на себя внимание в последние десятилетия. Особые опасения вызывает рост инфицирования этим микроорганизмом дыхательных путей больных муковисцидозом (МВ). Цель данного исследования заключалась в идентификации Achromobacter spp. в расширенной выборке российских больных МВ, генотипировании микроорганизмов в соответствии с международными стандартами и в проведении молекулярно эпидемиологического анализа ситуации по данному условно патогенному микроорганизму. Материалами для исследования послужили биологические образцы около 300 больных МВ: мокрота, трахеальный аспират, мазки из зева и штаммы, выделенные из образцов. Метод мультилокусного секвенирования, расширенный дополнительными мишенями, стал основой исследования. Результаты. 25 % пациентов, регулярно госпитализируемых в стационары в силу тяжести течения заболевания, инфицированы Achromobacter spp. 5 видов: A. xylosoxidans, A. ruhlandii, A. marplatensis, A. dolens, A. pulmonis, и 1 геномной группы. Преобладающим является вид A. ruhlandii (58,5 %). Один из индикаторов лекарственной устойчивости – ген оксациллиназы blaOXA – помогает в дифференциации рода Achromobacter и Burkholderia, а также ряда видов внутри рода Achromobacter. Из 26 выявленных генотипов (sequence type, ST) Achromobacter spp. 16 относятся к виду A. xylosoxidans, 5 – к A. ruhlandii. ST263 специфичен для пациентов Дальневосточного федерального округа. ST261 и 36 – самые многочисленные, ими инфицированы пациенты всех федеральных округов. Хронологический анализ позволил предположить смену генотипа 261 генотипом 36 в конце 1990 х гг. и внутрибольничную вспышку A. ruhlandii ST36. В настоящее время 39 % пациентов с Achromobacter spp. инфицированы A. ruhlandii ST36, трансмиссивность которого оказывают случаи заражения сиблингов и одновременно госпитализированных пациентов. Влияние на функцию дыхания больных МВ наиболее выражено у штаммов A. ruhlandii ST261. Для младшей возрастной группы пациентов (1997 г. р. и моложе), инфицированных A. ruhlandii ST36, медиана объема форсированного выдоха в 1 ю секунду несколько ниже, чем в старшей возрастной группе больных, зараженных тем же штаммом, что свидетельствует о накоплении A. ruhlandii ST36 патогенных свойств в процессе циркуляции в среде пациентов. Заключение. Штамм A. ruhlandii ST36 по совокупности выявленных свойств может быть признан российским эпидемическим штаммом

HIV-1 assembly in macrophages

The molecular mechanisms involved in the assembly of newly synthesized Human Immunodeficiency Virus (HIV) particles are poorly understood. Most of the work on HIV-1 assembly has been performed in T cells in which viral particle budding and assembly take place at the plasma membrane. In contrast, few studies have been performed on macrophages, the other major target of HIV-1. Infected macrophages represent a viral reservoir and probably play a key role in HIV-1 physiopathology. Indeed macrophages retain infectious particles for long periods of time, keeping them protected from anti-viral immune response or drug treatments. Here, we present an overview of what is known about HIV-1 assembly in macrophages as compared to T lymphocytes or cell lines