The lithological-petrography characteristics of chalk, paleogen-miocene deposits of Yalama-Khudat areas and Siyazan monocline anticline in connection with their oil and gas content (south-east immersions of megaanticlinoric of Greater Caucasus)

In recent years, geological prospecting and geophysical works in Azerbaijan were carried out in considerable volume in order to study an oil and gas potential of Meso-Cenozoic deposits. Based on the results of these studies the criteria were developed as the basis for further research. It is known that the sedimentation basin mainly dipped in the Meso-Cenozoic time. As a result, the researchers have no doubt about the potential of these deposits in the central part of the studied area and at greater depths, but there have been no precise calculations yet. In order to solve this problem, we have studied the reservoir rocks properties of considered ages of Khudat, Yalama oil and gas bearing structures and Siyazan monocline formed in Gusar-Davachi superimposed mulde in various geological conditions and at different depths. For an easier analysis, all the actual data are given in tables showing the physical parameters of the different rock types, involved in geological structure of oil and gas bearing areas. In order to clarify the obtained results and the changes nature study of the considered physical properties the various petrophysical methods were applied. As a result the regularity in changing of rocks density, carbonate contents, porosity, permeability and the propagation velocity of ultrasonic waves in them were established. However, in tectonically complex structures of the Siyazan monocline the applied methods have not given expected results of studies because of their severe dislocation and outlet to the surface. Taking this into account the reservoir characteristics studies of rock samples of considered ages from fields being developed in the north-eastern slope of the south-east Greater Caucasus dipping were conducted. The main objective is to study the petrophysical parameters and reservoir rocks properties of the Cretaceous, Paleogene-Miocene age in tectonically complex uplifts of Yalama, Khudat and Siyazan monocline placed at southeast Greater Caucasus dipping due to its petroleum potential

Performance of a plastic scintillator developed using styrene monomer polymerization

This paper presents a newly developed plastic scintillator produced in collaboration with Turkiye Energy, Nuclear and Mineral Research Agency (TENMAK). The scintillator is manufactured using thermal polymerization of commercially available styrene monomer. The absorption spectrum of the scintillator exhibited two absorption bands at 225 nm and 340 nm, with an absorption edge observed at 410 nm. The wavelength of the emitted light was measured in the range of 400-800 nm, with a maximum intensity at 427 nm. Monoenergetic electrons from the 137Cs source were used to evaluate the characteristics of the new scintillator, particularly its light yield. As the light readout the MAPD-3NM type silicon photomultiplier array (4 x 4) with an active area of 15 x 15 mm2, assembled using single MAPDs with an active area of 3.7 x 3.7 mm2, was used. The light yield of the scintillator was determined to be 6134 photons/MeV. In addition, the efficiency of the scintillator for gamma rays with an energy of 662 keV was found to be approximately 1.8 %. A CmBe neutron source was employed to evaluate its fast neutron detection performance. However, neutron/gamma discrimination using pulse shape discrimination (charge integration) method was not observed. The results demonstrate the potential of a newly produced plastic scintillator for various applications, particularly in radiation monitoring and detection systems.Comment: 7 pages, 7 figure

Интернализация рекомбинантной имиглюцеразы в перитонеальные макрофаги мыши и фибробласты мыши линии L929

Enzyme replacement therapy (ERT) is one of the most efficient treatments for lysosomal storage diseases. Type 1 Gaucher disease is caused by β-glucocerebrosidase enzyme deficiency, which may be compensated for by intravenous infusions of imiglucerase—a recombinant enzyme. Imiglucerase targets macrophages and enters these cells via interaction with mannose receptors on the cell membrane. Characterisation of internalization of enzymes by target cells is important in the context of the development of new medicines and production of existing ERT medicines. The peritoneal and alveolar macrophages, as well as macrophages of the spleen of small laboratory animals (rats and mice) are widely used in such studies. However, isolation of cells from animal sources raises ethical issues, and therefore continuous mammalian cell lines may offer an attractive alternative. The aim of the study: to conduct comparative studies on the internalization of recombinant imiglucerase into mouse peritoneal macrophages and L929 mouse fibroblasts. Materials and methods: CerezymeR batches 7HV0913, C6214H05, 7HV0888 (Genzyme Ltd., UK); Glurazim batches 020416, 011117, 021117 (LLC “IBC “Generium”, Russia). We used peritoneal macrophages obtained from BALB/c mice and L929 mouse fibroblasts. The cells were cultured in DMEM/F12 complete growth medium with 10% fetal bovine serum. The activity of imiglucerase internalized into the cells was evaluated spectrophotometrically by hydrolysis of the artificial substrate—4-methylumbelliferyl-β-Dglucopyranoside. Results: the study compared internalization of recombinant imiglucerase (the active ingredient of CerezymeR and Glurazim) by mouse peritoneal macrophages and L929 mouse fibroblasts. It was demonstrated that the medicines activity in the lysates of peritoneal macrophages is comparable with that in the lysates of L929 mouse fibroblasts. Regardless of the model system, the activity of Glurazim stayed within the acceptable range (80–125%) established for biosimilar products. Conclusions: the experiments proved that L929 mouse fibroblasts could be recommended for assessment of internalization of recombinant imiglucerase.Фермент-заместительная терапия (ФЗТ) является одной из самых действенных при лечении болезней лизосомального накопления. Болезнь Гоше первого типа характеризуется недостатком нативного фермента β-глюкоцереброзидазы, который возмещают внутривенными инфузиями рекомбинантного фермента (имиглюцераза). Клетками-мишенями имиглюцеразы являются макрофаги, в которые фермент проникает посредством взаимодействия с рецепторами маннозы на клеточной мембране. Оценка интернализации ферментов клетками-мишенями представляет интерес при разработке новых и воспроизведении существующих препаратов для ФЗТ. Для этих исследований широко применяются перитонеальные и альвеолярные макрофаги, макрофаги селезенки мелких лабораторных животных (крыс и мышей). Однако получение таких клеток затрагивает этические вопросы использования лабораторных животных. Альтернативой являются перевиваемые клеточные линии млекопитающих. Цель работы: провести сравнительные исследования интернализации рекомбинантной имиглюцеразы в перитонеальные макрофаги мыши и фибробласты мыши линии L929. Материалы и методы: Церезим®, серии 7HV0913, C6214H05, 7HV0888 (Джензайм Лтд., Великобритания); Глуразим, серии 020416, 011117, 021117 (ООО «МБЦ «Генериум», Россия). В работе использовали перитонеальные макрофаги, полученные от мышей линии BALB/c, и фибробласты мыши линии L929. Клетки культивировали в полной ростовой среде ДМЕМ/Ф12 c добавлением 10% сыворотки плода крупного рогатого скота. Активность имиглюцеразы, проникшей в клетки, оценивали спектрофотометрически по гидролизу искусственного субстрата 4-метилумбеллиферил-β-D-глюкопиранозида. Результаты: представлены данные сравнительной оценки интернализации рекомбинантной имиглюцеразы, действующего вещества препаратов Церезим® и Глуразим, перитонеальными макрофагами мыши и клетками фибробластов мыши линии L929. Показано, что активность препаратов в лизатах перитонеальных макрофагов сопоставима с их активностью в лизатах клеток фибробластов мыши линии L929, при этом активность разработанного препарата Глуразим независимо от типа клеток, была в границах допустимого диапазона (80–125%), установленного для биоподобных препаратов. Выводы: экспериментально доказано, что фибробласты мыши линии L929 могут быть рекомендованы для оценки интернализации рекомбинантной имиглюцеразы

Теоретико-методологічні аспекти розвитку інноваційно-промислових кластерів в умовах цифровізації

Ця стаття узагальнює аргументи та контраргументи в рамках наукової дискусії з питань визначення основних теоретичних та практичних засад функціонування інноваційно-промислових кластерів у різних країнах світу, а також формалізації впливу цифровізації на їх діяльність. У статті узагальнено наукові підходи до визначення основних характеристик та особливостей функціонування інноваційно-промислових кластерів. З метою обґрунтування теоретичних закономірностей взаємозв’язку між діяльністю інноваційно-промислових кластерів та процесами цифровізації, у роботі здійснено бібілометричний аналіз основних публікацій Scopus за означеним напрямком з використанням інструментарію Vosviewer. У ході дослідження визначено головні змістовноконтекстуальні кластери наукових досліджень з релевантної тематики, охарактеризовано еволюційні закономірності їх зміни за досліджуваний період. З метою визначення емпіричних закономірностей впливу цифровізації на інноваційно-промисловий розвиток, авторами розроблено інтегральний показник інноваційнопромислового розвитку. Індекс враховує основні параметри та регіональні особливості промислового, підприємницького та інноваційного розвитку. Інтегрування індикаторів проведено з використанням методу головних компонент та адитивної згортки. У роботі здійснено моделювання впливу параметрів цифровізації економіки на інтегральний показник інноваційно-промислового розвитку з використанням інструментарію регресійного моделювання панельних даних у програмному продукті Stata 14.2/SE. У дослідженні застосовано однофакторні регресійні моделі для визначення детермінант цифрового розвитку держави, які найбільшою мірою залежать від волатильності інноваційно-промислового розвитку країни. Обʼєктом дослідження є 10 країн, серед яких Азербайджан, Естонія, Грузія, Казахстан, Киргизстан, Латвія, Литва, Польща, Румунія та Україна. Періодом дослідження обрано 2009-2021 рр. (чи останній доступний період). Результати проведеного дослідження можуть бути корисними науковцям, органам державної влади та місцевого самоврядування.This article summarizes the arguments and counterarguments within the scientific debate on the identification of the main theoretical and practical principles of the functioning of innovative-industrial clusters in different countries, as well as the formalization of the impact of digitalization on their activities. The article summarizes scientific approaches to determining the main characteristics and features of the functioning of innovation-industrial clusters. In order to substantiate the theoretical background of the relationship between innovation-industrial clusters’ performance and digitalization processes, a bibliometric analysis of the main Scopus publications in this direction is carried out using the VOSviewer toolkit. That made it possible to identify the main essential and contextual clusters of scientific research on relevant topics to characterize the evolutionary patterns of their changes during the analysis period. In order to determine the empirical causality of the impact of digitalization on innovative and industrial development, an integral indicator of innovative and industrial development is developed. The Index considers the measurement parameters and regional features of industrial, entrepreneurial, and innovative development. Indicators were integrated using the principal components analysis and additive convolution. The study modelled the influence proxies of the digital economy on the integrated indicator of innovative and industrial development using panel data regression modelling in the Stata 14.2/SE software. In the paper, it is also identified those determinants of the digital development of the state that depends to the greatest extent on the volatility of the innovative and industrial development of the country using one-factor regression models. The study is conducted for the country sample with 10 countries, including Azerbaijan, Estonia, Georgia, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Poland, Romania, and Ukraine. The time horizon of the study covers the period 2009-2021 (or the latest available period). The research results can be useful to scientists, state authorities, and local governments

Assessment of T-cell immunity to SARS-CoV-2 in COVID-19 convalescents and vaccinated subjects, using TigraTest^® SARS-CoV-2 ELISPOT kit

With the onset of the COVID-19 pandemic, a number of molecular-based tests have been developed to diagnose SARS-CoV-2 infection. However, numerous available serological tests lack sufficient sensitivity or specificity. They do not detect specific antibodies in a significant proportion of patients with PCR-confirmed COVID-19. There is evidence that some convalescents have a relatively short-lived humoral immunity. In contrast, a number of publications have shown that T-cell response to human coronaviruses, including SARS-CoV-1, MERS, and SARS-CoV-2, can be strong and long-term. Assessment of T-cell immunity to SARS-CoV-2 is important not only for stratification of risks and identification of potentially protected populations with immunity acquired as a result of previous infection, but also for determining immunogenicity and potential efficacy of vaccines under development. The existing methods of quantitative or semi-quantitative assessment of specific T-cell response are mainly used in scientific research and are not standardised. The aim of the study was to develop and verify experimentally a test kit to be used in a standardised procedure for in vitro determination of T-cells specific to SARS-CoV-2 antigens, in human peripheral blood. Materials and methods: the TigraTest® SARS-CoV-2 kit developed by GENERIUM, which determines the number of T-cells secreting interferon gamma in vitro, was tested in the study. Samples of venous blood of volunteers from three different groups were analysed in the study: presumably healthy volunteers; COVID-19 convalescents; individuals vaccinated against SARS-CoV-2. Results: the authors developed the TigraTest® SARS-CoV-2 kit for in vitro determination of T-cells specific to SARS-CoV-2 antigens in human peripheral blood, demonstrated its specificity and performed preliminary assessment of its sensitivity. The study analysed the range and magnitude of the T-cell response in convalescent and vaccinated individuals. A pronounced T-cell response was also shown in some individuals with no symptoms or with unconfirmed diagnosis. It was discovered that the mean T-cell response to peptides of the spike protein (S-protein) was higher in the vaccinated individuals than in the convalescent patients. A correlation was determined between the severity of the disease and the level of T-cell response. Specific contributions of various groups of antigens to the T-cell response after COVID-19 infection were also determined. Conclusions: the TigraTest® SARS-CoV-2 kit is a specific and sensitive tool for the assessment of T-cell immunity to the SARS-CoV-2 virus, which can also be used for vaccinated individuals. The kit may be used in clinical practice for comprehensive assessment of immunity to SARS-CoV-2

Internalization of Recombinant Imiglucerase into Mouse Peritoneal Macrophages and L929 Mouse Fibroblasts

Enzyme replacement therapy (ERT) is one of the most efficient treatments for lysosomal storage diseases. Type 1 Gaucher disease is caused by β-glucocerebrosidase enzyme deficiency, which may be compensated for by intravenous infusions of imiglucerase—a recombinant enzyme. Imiglucerase targets macrophages and enters these cells via interaction with mannose receptors on the cell membrane. Characterisation of internalization of enzymes by target cells is important in the context of the development of new medicines and production of existing ERT medicines. The peritoneal and alveolar macrophages, as well as macrophages of the spleen of small laboratory animals (rats and mice) are widely used in such studies. However, isolation of cells from animal sources raises ethical issues, and therefore continuous mammalian cell lines may offer an attractive alternative. The aim of the study: to conduct comparative studies on the internalization of recombinant imiglucerase into mouse peritoneal macrophages and L929 mouse fibroblasts. Materials and methods: CerezymeR batches 7HV0913, C6214H05, 7HV0888 (Genzyme Ltd., UK); Glurazim batches 020416, 011117, 021117 (LLC “IBC “Generium”, Russia). We used peritoneal macrophages obtained from BALB/c mice and L929 mouse fibroblasts. The cells were cultured in DMEM/F12 complete growth medium with 10% fetal bovine serum. The activity of imiglucerase internalized into the cells was evaluated spectrophotometrically by hydrolysis of the artificial substrate—4-methylumbelliferyl-β-Dglucopyranoside. Results: the study compared internalization of recombinant imiglucerase (the active ingredient of CerezymeR and Glurazim) by mouse peritoneal macrophages and L929 mouse fibroblasts. It was demonstrated that the medicines activity in the lysates of peritoneal macrophages is comparable with that in the lysates of L929 mouse fibroblasts. Regardless of the model system, the activity of Glurazim stayed within the acceptable range (80–125%) established for biosimilar products. Conclusions: the experiments proved that L929 mouse fibroblasts could be recommended for assessment of internalization of recombinant imiglucerase

Оценка Т-клеточного иммунитета к SARS-CoV-2 у переболевших и вакцинированных против COVID-19 лиц с помощью ELISPOT набора ТиграТест® SARS-CoV-2

With the onset of the COVID-19 pandemic, a number of molecular-based tests have been developed to diagnose SARS-CoV-2 infection. However, numerous available serological tests lack sufficient sensitivity or specificity. They do not detect specific antibodies in a significant proportion of patients with PCR-confirmed COVID-19. There is evidence that some convalescents have a relatively short-lived humoral immunity. In contrast, a number of publications have shown that T-cell response to human coronaviruses, including SARS-CoV-1, MERS, and SARS-CoV-2, can be strong and long-term. Assessment of T-cell immunity to SARS-CoV-2 is important not only for stratification of risks and identification of potentially protected populations with immunity acquired as a result of previous infection, but also for determining immunogenicity and potential efficacy of vaccines under development. The existing methods of quantitative or semi-quantitative assessment of specific T-cell response are mainly used in scientific research and are not standardised. The aim of the study was to develop and verify experimentally a test kit to be used in a standardised procedure for in vitro determination of T-cells specific to SARS-CoV-2 antigens, in human peripheral blood. Materials and methods: the TigraTest® SARS-CoV-2 kit developed by GENERIUM, which determines the number of T-cells secreting interferon gamma in vitro, was tested in the study. Samples of venous blood of volunteers from three different groups were analysed in the study: presumably healthy volunteers; COVID-19 convalescents; individuals vaccinated against SARS-CoV-2. Results: the authors developed the TigraTest® SARS-CoV-2 kit for in vitro determination of T-cells specific to SARS-CoV-2 antigens in human peripheral blood, demonstrated its specificity and performed preliminary assessment of its sensitivity. The study analysed the range and magnitude of the T-cell response in convalescent and vaccinated individuals. A pronounced T-cell response was also shown in some individuals with no symptoms or with unconfirmed diagnosis. It was discovered that the mean T-cell response to peptides of the spike protein (S-protein) was higher in the vaccinated individuals than in the convalescent patients. A correlation was determined between the severity of the disease and the level of T-cell response. Specific contributions of various groups of antigens to the T-cell response after COVID-19 infection were also determined. Conclusions: the TigraTest® SARS-CoV-2 kit is a specific and sensitive tool for the assessment of T-cell immunity to the SARS-CoV-2 virus, which can also be used for vaccinated individuals. The kit may be used in clinical practice for comprehensive assessment of immunity to SARS-CoV-2.С началом пандемии COVID-19 в мире и Российской Федерации был разработан ряд молекулярно-биологических тестов для диагностики инфекции, вызванной SARS-CoV-2. Однако результаты применения многочисленных серологических тестов свидетельствуют об их недостаточной чувствительности или специфичности. У существенной части пациентов с подтвержденным ПЦР-диагнозом COVID-19 специфические антитела не обнаруживаются. Существуют доказательства того, что у части выздоровевших гуморальный иммунный ответ является относительно кратковременным. В ряде публикаций показано, что Т-клеточный ответ на человеческие коронавирусы, включая SARS-CoV-1, MERS и SARS-CoV-2, может быть сильным и долговременным. Оценка Т-клеточного иммунитета к SARS-CoV-2 важна не только для стратификации рисков и определения потенциально защищенных групп населения с иммунитетом, приобретенным вследствие перенесенной инфекции, но и для определения иммуногенности и потенциальной эффективности разрабатываемых вакцин. Существующие методики количественной или полуколичественной оценки специфического Т-клеточного ответа применяются в основном в научных исследованиях и не стандартизованы. Цель работы: разработка и апробация тест-системы для выполнения стандартизованной методики определения специфических к антигенам SARS-CoV-2 Т-клеток в периферической крови человека in vitro. Материалы и методы: разработанный компанией «ГЕНЕРИУМ» набор ТиграТест® SARS-CoV-2, принцип работы которого заключается в определении количества Т-клеток, секретирующих гамма-интерферон in vitro. Исследования проводили на образцах венозной крови добровольцев трех групп: условно здоровых, переболевших COVID-19, прошедших вакцинацию против COVID-19. Результаты: разработана тест-система для определения специфических к антигенам SARS-CoV-2 Т-клеток в периферической крови человека in vitro. Показана специфичность и определена предварительная чувствительность теста ТиграТест® SARS-CoV-2. Исследован диапазон и величина Т-клеточного ответа у переболевших и вакцинированных. Показан выраженный Т-клеточный ответ и у части лиц с отсутствующими симптомами или неподтвержденным диагнозом. Обнаружено, что среднее значение Т-клеточного ответа в отношении пептидов белка-шипа (S-белка) выше у вакцинированных, чем у переболевших. Найдена корреляция между тяжестью заболевания и уровнем Т-клеточного ответа. Определен удельный вклад различных групп антигенов в Т-клеточный ответ после перенесенного заболевания COVID-19. Выводы: набор ТиграТест® SARS-CoV-2 является специфичным и чувствительным инструментом в оценке Т-клеточного иммунитета к вирусу SARS-CoV-2, в том числе и для вакцинированных. Разработанный набор целесообразно использовать в клинической практике для комплексной оценки иммунитета к SARS-CoV-2