Composition of Initiated Cracking Products of High-sulfur Natural Bitumen

The analysis of the cracking products of bitumen Karmalskoye deposits (the content of fractions boiling up to 200 °C 6,7% wt.) has been performed. The influence of power plant coal ash microspheres on orientation of cracking bitumen components is stated. Bitumen cracking leads to significant yields of gas and coke for more than 20% wt. and destructions of all components. The initiated bitumen cracking in the presence of 10% microspheres at cracking temperature 450 °C leads to reduction of gas and coke yields and increase in fractions of ibp (initial boiling point) –360 °C at 10% wt. in comparison with products of the thermal bitumen cracking. The analysis of composition and amount of sulfur compounds in initial bitumen and the cracking products in the various conditions has shown that the thermal cracking leads to increased homologues benzothiophene contents due to partial destruction of resins, and to decrease in the content of homologues dibenzothiophene

Composition of Pre-ozonated High-Sulfur Natural Bitumen Cracking Products

The results analysis of fractional and material composition of the cracking products of Ashalchinskoye and Karmalskoye bitumen deposits was presented in this work. The effect of bitumen ozone-oxygen mixture pretreatment followed by cracking on thermolysis processes was investigated. It was shown that molecules of resins and asphaltenes containing large amounts of aliphatic fragments in its structure readily undergo thermal decomposition to form additional distillate fractions. Low content of aliphatic fragments leads to aromatization of the naphthenic cycles in the molecule of resins and asphaltenes, the thermal degradation reactions proceed in high yields of gas and coke

ANALYSIS OF STATISTICAL DATA FROM NETWORK INFRASTRUCTURE MONITORING TO DETECT ABNORMAL BEHAVIOR OF SYSTEM LOCAL SEGMENTS

We propose a method of information security monitoring for a wireless network segments of low-power devices, "smart house", "Internet of Things". We have carried out the analysis of characteristics of systems based on wireless technologies, resulting from passive surveillance and active polling of devices that make up the network infrastructure. We have considered a number of external signs of unauthorized access to a wireless network by the potential information security malefactor. The model for analysis of information security conditions is based on the identity, quantity, frequency, and time characteristics. Due to the main features of devices providing network infrastructure, estimation of information security state is directed to the analysis of the system normal operation, rather than the search for signatures and anomalies during performance of various kinds of information attacks. An experiment is disclosed that provides obtaining statistical information on the remote wireless devices, where the accumulation of data for decision-making is done by comparing the statistical information service messages from end nodes in passive and active modes. We present experiment results of the information influence on a typical system. The proposed approach to the analysis of network infrastructure statistical data based on naive Bayesian classifier can be used to determine the state of information security

Влияние нарушенной экспрессии HNF4α на чувствительность клеток гепатоцеллюлярной карциномы к действию ингибиторов проопухолевых сигнальных каскадов

Introduction. Hepatocellular carcinoma (HCC) is characterized by aggressive course, high lethality rate and resistance to current systemic treatment. Analysis of molecular aberrations associated with HCC pathogenesis that control biological properties of HCC allows to evaluate potential efficacy of inhibiting certain oncogenic cascades. The present study is focused on investigation of the impact of reduced expression of the key hepatocyte differentiation regulator, HNF4α, often downregulated in HCC, that influences sensitivity of HCC cells to inhibitors  of the major oncogenic pathways mTOR, CDK4/6-pRb and ROCK.Materials and methods. Changes in cells proliferation and migration caused by HNF4А gene stable knockdown were tested in human HCC cell cultures HepG2 and Huh7 followed by examination of these cellular properties under mTOR (rapamycin), CDK4/6 (PD0332991, palbociclib) and ROCK 1/2 (Y27632) inhibitors treatment. Gene expression levels were estimated by the real-time polymerase chain reaction method (Real-Time PCR).Results. HNF4А gene knockdown alters HepG2 and Huh7 cell migration associated with E-cadherin and N-cadherin expression changes. The HNF4α repression weakens Y27632-induced blockade of HCC cells migration potential. HNF4А gene knockdown causes resistance  of Huh7 cells and increase of HepG2 cells sensitivity to rapamycin and PD0332991 that block cells migration ability.Conclusions. Expression level of HNF4α renders influence on migration of HCC cells and contributes to their sensitivity to mTOR, CDK4/6 and ROCK1/2 inhibitors’ impact on cell migration activity.Введение. Гепатоцеллюлярная карцинома (ГК) характеризуется агрессивным течением, высокой частотой случаев летальности и устойчивостью к существующим схемам терапии. Исследование ассоциированных с патогенезом ГК молекулярных нарушений, которые влияют на биологические свойства клеток ГК, позволяет оценить потенциальную эффективность ингибирования конкретных проопухолевых сигнальных каскадов. Настоящая работа посвящена изучению действия снижения экспрессии ключевого регулятора гепатоцитарной дифференцировки HNF4α, которое часто происходит в ГК, на чувствительность клеток культур ГК к ингибиторам важных проопухолевых сигнальных путей mTOR, CDK4 / 6-pRb и ROCK.Материалы и методы. В культурах ГК человека HepG2 и Huh7 со стабильным нокдауном гена HNF4A определяли изменение пролиферативного и миграционного потенциалов клеток, а также изменение данных свойств при действии ингибиторов mTOR (рапамицина), CDK4 / 6 (PD0 332 991, палбоциклиба) и ROCK 1 / 2 (Y27 632). Уровни экспрессии генов определяли методом полимеразной цепной реакции в реальном времени.Результаты. Нокдаун гена HNF4А вызывает изменение миграционной способности клеток HepG2 и Huh7, ассоциированное с изменением экспрессии Е-кадгерина и N-кадгерина. Снижение экспрессии HNF4α ослабляет опосредованное Y27632-подавление миграционного потенциала в клетках ГК. Нокдаун гена HNF4А приводит к возникновению устойчивости клеток Huh7 и увеличению чувствительности клеток HepG2 к действию рапамицина и PD0 332 991, блокирующих миграционную способность клеток.Заключение. Уровень экспрессии HNF4α влияет на миграционную способность клеток ГК и их чувствительность к действию ингибиторов mTOR, CDK4 / 6 и ROCK1 / 2 на миграционную активность

Infective and nonbacterial thrombotic endocarditis in patients with post-COVID-19 viral-immune myocarditis

The possibility of heart inflammation (both myocardial and endocardial) months after a coronavirus disease 2019 (COVID-19) has not been practically studied, especially since approaches to the treatment of myocarditis in combination with various endocarditis forms have not been developed.Aim. To study the prevalence and mechanisms of SARS-CoV-2-associated endocardial injury in patients with morphologically verified post-COVID-19 myocarditis, as well as to develop approaches to comprehensive therapy.Material and methods. The study included 18 patients with severe morphologically verified post-COVID-19 myocarditis (men, 9; 51,1±9,4 years; 35 to 66 years). Patients with prior verified myocarditis/myocardial infarction, rheumatic heart disease, and systemic immune diseases were excluded. The average time after COVID-19 was 6,5 [3.5; 10] months The diagnosis of myocarditis was confirmed by endomyocardial biopsy (including immunohistochemical examination with antibodies to CD3, CD20, CD45, CD68, and to SARS-CoV-2 antigens; polymerase chain reaction for SARS-CoV-2 RNA, DNA of cardiotropic viruses). The blood level of anticardiac antibodies was determined by indirect immunofluorescence. In addition, echocardiography, magnetic resonance imaging (n=8), cardiac multislice tomography (n=1), and coronary angiography (n=14) were performed.Results. Biopsy revealed active (n=12) and borderline (n=3) lymphocytic myocarditis, eosinophilic (n=2) and giant cell (n=1) myocarditis. In 4 patients, nonbacterial thrombotic endocarditis (NBTE) with parietal and intravascular thrombosis was diagnosed, and in one patient — infective endocarditis (IE) of the bicuspid aortic valve. Myocardial persistence of SARS-CoV-2 was detected in 72% of cases (in 3 patients — with NBTE; in 1 — with IE; in 9 — without endocarditis). Titers of anticardiac antibodies increased by 3-4 times in 94% of patients. Patients with endocarditis were characterized by larger heart chambers, lower ejection fraction (27,5±6,6 vs 36,0±13,4%), more severe pulmonary hypertension, and valvular regurgitation. Intraventricular thrombosis according to echocardiography/magnetic resonance imaging and cardiac embolism was not observed. Treatment in all patients included methylprednisolone at an average dose of 24 mg a day. In 10 patients, the result was monitored for at least 3 months as follows: the ejection fraction was 46,0±12,7% and 44,3±7,3% in patients with and without endocarditis, respectively.Conclusion. Endocarditis in patients with post-COVID-19 myocarditis was detected in 28% (1 patient — IE; 4 — NBTE). The key mechanisms of post-COVID-19 myocarditis and NBTE are long-term (up to 18 months) myocardial persistence of SARS-Cov-2 and the development of an autoimmune reaction. Endocarditis was diagnosed in more severe patients, including those with giant cell and eosinophilic myocarditis. The effectiveness of steroid therapy in combination with anticoagulants in patients with NBTE requires further study. In case of IE, steroids can also be used in the treatment of myocarditis (in combination with antibiotics and immunoglobulin)

Методы детекции специфических для опухолевой ткани однонуклеотидных соматических мутаций в препаратах цДНК из плазмы крови

Introduction. Liquid biopsy is considered as a minimally invasive method of molecular genetic analysis that can be used for early diagnosis, prognosis of disease development, monitoring of residual disease or treatment outcomes, and selection of optimal drug therapy schemes for a patient. Along with the development of tests based on the study of panels of oncologically significant genes or their regions, for various forms of genetically heterogeneous tumors a promising approach could be the use as an object of liquid biopsy of an individual spectrum of somatic mutations of a particular patient that can be detected on the basis of high-throughput sequencing of tumor tissue.Aim. To determine the applicability of different methods for detecting single-nucleotide somatic mutations detected in tumor tissue of a particular patient in cDNA preparations from blood plasma obtained before surgical removal of the tumor and to evaluate the possibility of quantifying the proportion of the alternative variant in the total pool of cDNA. Materials and methods. We used normal and tumor tissue, as well as blood plasma samples from patients with hepatocellular carcinoma, and various methods for detecting single-nucleotide somatic mutations: real-time polymerase chain reaction (PCR) with intercalating dye or with TaqMan probes, droplet digital PCR and high-throughput sequencing of target amplicons.Results. Using the example of a somatic mutation in the TLN1 gene detected in tumor tissue of a patient with hepatocellular carcinoma, methods were developed and tested, each of which allows specific detection of the mutant variant in small amounts (2 ng) of cDNA from the blood plasma of the same patient. The use of droplet PCR and target amplicon sequencing methods allowed us to quantify the proportion of the mutant variant in the total cDNA pool, which was 19.7 and 23.5 %, respectively.Conclusion. Among the methods investigated, droplet digital PCR and targeted amplicon sequencing allow not only reliable detection of mutant variants in small amounts of cDNA, but also adequate quantification, which is particularly important for the development of ways to monitor tumor growth during treatment. The close values of the proportion of mutant variants in cDNA detected by these methods indicate the accuracy of quantitative analysis and the possibility of their use for cross-validation of the results obtained.Введение. Жидкостная биопсия рассматривается как малоинвазивный способ проведения молекулярно-генетического анализа, который может быть использован для ранней диагностики, прогноза течения заболевания, мониторинга остаточной болезни или результатов лечения, а также выбора оптимальных для пациента схем лекарственной терапии. Наряду с разработкой тестов, основанных на исследовании панелей онкологически значимых генов или их участков, для различных форм генетически гетерогенных опухолей перспективным подходом может стать использование в качестве объекта жидкостной биопсии индивидуального спектра соматических мутаций конкретного больного, которые могут быть выявлены с помощью высокопроизводительного секвенирования опухолевой ткани.Цель исследования - определить возможность использования различных методов детекции однонуклеотидных соматических мутаций, выявленных в опухолевой ткани конкретного пациента, в препаратах циркулирующей ДНК (цДНК) из плазмы крови, полученных до хирургического удаления опухоли, и выявить возможность количественной оценки доли альтернативного варианта в общем пуле цДНК.Материалы и методы. В работе использованы препараты нормальной и опухолевой тканей, плазмы крови пациентов с гепатоцеллюлярной карциномой, а также различные методы детекции однонуклеотидных соматических мутаций: полимеразная цепная реакция (ПЦР) в реальном времени с интеркалирующим красителем или с зондами TaqMan, капельная цифровая ПЦР и высокопроизводительное секвенирование таргетных ампликонов.Результаты. На примере соматической мутации в гене TLN1, выявленной в опухолевой ткани пациента с гепатоцеллюлярной карциномой, разработаны и апробированы методы, каждый из которых позволяет специфично детектировать мутантный вариант в малых количествах (2 нг) цДНК из плазмы крови того же пациента. использование капельной ПЦР и секвенирования таргетных ампликонов позволило провести количественную оценку долей мутантного варианта в общем пуле цДНК, которые составили 19,7 и 23,5 % соответственно.Заключение. Капельная цифровая ПЦР и таргетное секвенирование ампликонов позволяют не только надежно детектировать мутантные варианты в малых количествах цДНК, но и адекватно проводить их количественную оценку, что особенно важно для разработки способов мониторинга опухолевого роста в процессе лечения. Близкие значения доли мутантного варианта в цДНК, детектированной этими методами, свидетельствуют о точности количественного анализа и возможности их использования для кросс-валидации получаемых результатов

Impact of HNF4α disrupted expression on hepatocellular carcinoma cells sensitivity to oncogenic pathways inhibitors

Introduction. Hepatocellular carcinoma (HCC) is characterized by aggressive course, high lethality rate and resistance to current systemic treatment. Analysis of molecular aberrations associated with HCC pathogenesis that control biological properties of HCC allows to evaluate potential efficacy of inhibiting certain oncogenic cascades. The present study is focused on investigation of the impact of reduced expression of the key hepatocyte differentiation regulator, HNF4α, often downregulated in HCC, that influences sensitivity of HCC cells to inhibitors  of the major oncogenic pathways mTOR, CDK4/6-pRb and ROCK.Materials and methods. Changes in cells proliferation and migration caused by HNF4А gene stable knockdown were tested in human HCC cell cultures HepG2 and Huh7 followed by examination of these cellular properties under mTOR (rapamycin), CDK4/6 (PD0332991, palbociclib) and ROCK 1/2 (Y27632) inhibitors treatment. Gene expression levels were estimated by the real-time polymerase chain reaction method (Real-Time PCR).Results. HNF4А gene knockdown alters HepG2 and Huh7 cell migration associated with E-cadherin and N-cadherin expression changes. The HNF4α repression weakens Y27632-induced blockade of HCC cells migration potential. HNF4А gene knockdown causes resistance  of Huh7 cells and increase of HepG2 cells sensitivity to rapamycin and PD0332991 that block cells migration ability.Conclusions. Expression level of HNF4α renders influence on migration of HCC cells and contributes to their sensitivity to mTOR, CDK4/6 and ROCK1/2 inhibitors’ impact on cell migration activity

AVAILABILITY RESEARCH OF REMOTE DEVICES FOR WIRELESS NETWORKS

We consider the wireless network under attack, aimed at "broadcast storm" initiation, in order to determine the availability of stand-alone units and the ability to carry out their functional tasks under information exposure. We determine a set of conditions for such type of attacks on the part of potential information interloper. The functional analysis of the systems based on wireless technology is made. We examine the remote device of a self-organizing wireless network as a queuing system M/M/1/n. Model dependencies are shown for normal system performance and at information exposure on the part of potential information interloper. Analytical simulation of wireless network functioning is carried out in the normal mode and under the attack aimed at "broadcast storm" initiation. An experiment is described which provides statistical information on operation of network remote devices. We present experiment results on carrying out attack at typical system transferring data by broabcast net scanning package at different noise intensities on the part of information interloper. The proposed model can be used to determine the technical characteristics of wireless ad-hoc network, develop recommendations for node configuration, aimed at countering "broadcast storm"