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The Epstein-Barr virus (EBV) is the first virus that has been classified as a human oncology virus. The ability of EBV to immortalize the cells of the human body is the highest among all known transforming viruses. Fluorine-containing nucleoside analogs represent a significant class of the chemotherapeutics widely used in the treatment for a lot of diseases. They have been playing a major role in treating tumor and virus either as selective inhibitors of enzymes for cancer or viral replication or as nucleic acid chain terminators which interrupt the replication of cancer cells or a virus.Aim. The purpose of this study was to analyze the potential antiviral and apoptosis modulating activity of fluorinated derivatives of uracil by using in silico and in vitro methods.Materials and methods. Two analogs (compound G26 and G27) on the base of 5-(p-tolilsulfonil)-6(polyfluoroalkyl)uracil were used in the study. The studies were conducted on cultures of Raji (latent infected EBV) and B95-8 (chronically producing virus) B-lymphoma cells. Trypan blue assay, MTT-method, neutral red uptake assay, PCR, flow cytometry, and web-servers PASS, PharmMapper were used.Results. According to PASS prediction, all compounds may possess the antiviral activity and anticancer activity. The in vitro study let to reveal the low level of cytotoxicity of these uracil derivatives. Anti-EBV activity was observed for all compounds and EC50 values were 75 and 65 µg/ml. Using PharmMapper, it has been shown that the targets are enzymes necessary for the replication of viral DNA (protease, kinase) and proteins that provide an apoptotic cascade (MAPK, cytochrome). For compound G27, several peaks on the histogram were observed, which may be evidence of changes in the cell cycle of lymphoblastoid cultures.Conclusions. In this way, the results of the present research shown an antiviral and apoptosis modulating activity of derivatives based on uracil. The data assumed by in silico methods can be used to mode, Першим вірусом класифікованим, як онкологічний був вірус Епштейна-Барр. Метою роботи було дослідити біологічні властивості фторованих похідних на основі урацилу. Згідно прогнозування PASS, сполуки G26 та G27 можуть мати противірусну активність. Анти-ВЕБ активність in vitro була показана для обох досліджуваних сполук. Таким чином, похідні урацилу є перспективними для створення нових антивірусних агентів

Background: The amount of data generated in large clinical and phenotyping studies that use single-cell cytometry is constantly growing. Recent technological advances allow the easy generation of data with hundreds of millions of single-cell data points with >40 parameters, originating from thousands of individual samples. The analysis of that amount of high-dimensional data becomes demanding in both hardware and software of high-performance computational resources. Current software tools often do not scale to the datasets of such size; users are thus forced to downsample the data to bearable sizes, in turn losing accuracy and ability to detect many underlying complex phenomena. Results: We present GigaSOM.jl, a fast and scalable implementation of clustering and dimensionality reduction for flow and mass cytometry data. The implementation of GigaSOM.jl in the high-level and high-performance programming language Julia makes it accessible to the scientific community and allows for efficient handling and processing of datasets with billions of data points using distributed computing infrastructures. We describe the design of GigaSOM.jl, measure its performance and horizontal scaling capability, and showcase the functionality on a large dataset from a recent study. Conclusions: GigaSOM.jl facilitates the use of commonly available high-performance computing resources to process the largest available datasets within minutes, while producing results of the same quality as the current state-of-art software. Measurements indicate that the performance scales to much larger datasets. The example use on the data from a massive mouse phenotyping effort confirms the applicability of GigaSOM.jl to huge-scale studies.

Background: The amount of data generated in large clinical and phenotyping studies that use single-cell cytometry is constantly growing. Recent technological advances allow the easy generation of data with hundreds of millions of single-cell data points with >40 parameters, originating from thousands of individual samples. The analysis of that amount of high-dimensional data becomes demanding in both hardware and software of high-performance computational resources. Current software tools often do not scale to the datasets of such size; users are thus forced to downsample the data to bearable sizes, in turn losing accuracy and ability to detect many underlying complex phenomena. Results: We present GigaSOM.jl, a fast and scalable implementation of clustering and dimensionality reduction for flow and mass cytometry data. The implementation of GigaSOM.jl in the high-level and high-performance programming language Julia makes it accessible to the scientific community and allows for efficient handling and processing of datasets with billions of data points using distributed computing infrastructures. We describe the design of GigaSOM.jl, measure its performance and horizontal scaling capability, and showcase the functionality on a large dataset from a recent study. Conclusions: GigaSOM.jl facilitates the use of commonly available high-performance computing resources to process the largest available datasets within minutes, while producing results of the same quality as the current state-of-art software. Measurements indicate that the performance scales to much larger datasets. The example use on the data from a massive mouse phenotyping effort confirms the applicability of GigaSOM.jl to huge-scale studies.

Background: The amount of data generated in large clinical and phenotyping studies that use single-cell cytometry is constantly growing. Recent technological advances allow the easy generation of data with hundreds of millions of single-cell data points with >40 parameters, originating from thousands of individual samples. The analysis of that amount of high-dimensional data becomes demanding in both hardware and software of high-performance computational resources. Current software tools often do not scale to the datasets of such size; users are thus forced to downsample the data to bearable sizes, in turn losing accuracy and ability to detect many underlying complex phenomena. Results: We present GigaSOM.jl, a fast and scalable implementation of clustering and dimensionality reduction for flow and mass cytometry data. The implementation of GigaSOM.jl in the high-level and high-performance programming language Julia makes it accessible to the scientific community and allows for efficient handling and processing of datasets with billions of data points using distributed computing infrastructures. We describe the design of GigaSOM.jl, measure its performance and horizontal scaling capability, and showcase the functionality on a large dataset from a recent study. Conclusions: GigaSOM.jl facilitates the use of commonly available high-performance computing resources to process the largest available datasets within minutes, while producing results of the same quality as the current state-of-art software. Measurements indicate that the performance scales to much larger datasets. The example use on the data from a massive mouse phenotyping effort confirms the applicability of GigaSOM.jl to huge-scale studies.

Background: The amount of data generated in large clinical and phenotyping studies that use single-cell cytometry is constantly growing. Recent technological advances allow the easy generation of data with hundreds of millions of single-cell data points with >40 parameters, originating from thousands of individual samples. The analysis of that amount of high-dimensional data becomes demanding in both hardware and software of high-performance computational resources. Current software tools often do not scale to the datasets of such size; users are thus forced to downsample the data to bearable sizes, in turn losing accuracy and ability to detect many underlying complex phenomena. Results: We present GigaSOM.jl, a fast and scalable implementation of clustering and dimensionality reduction for flow and mass cytometry data. The implementation of GigaSOM.jl in the high-level and high-performance programming language Julia makes it accessible to the scientific community and allows for efficient handling and processing of datasets with billions of data points using distributed computing infrastructures. We describe the design of GigaSOM.jl, measure its performance and horizontal scaling capability, and showcase the functionality on a large dataset from a recent study. Conclusions: GigaSOM.jl facilitates the use of commonly available high-performance computing resources to process the largest available datasets within minutes, while producing results of the same quality as the current state-of-art software. Measurements indicate that the performance scales to much larger datasets. The example use on the data from a massive mouse phenotyping effort confirms the applicability of GigaSOM.jl to huge-scale studies.

Відзначена роль структурної модифікації 1,4-бензодіазепінових систем діалкіламіногрупами, яка раніше була успішно використана для одержання низки важливих похідних із комплексом специфічних біологічних властивостей. В поданій статті значно розширений спектр гетероанельованих діазепінів шляхом розробки препаративно зручного варіанту синтезу нових амінозаміщених піразоло[3,4-e][1,4]діазепінів. З цією метою детально досліджена реакція 4-хлоро-1,6-дигідропіразоло[3,4-e][1,4]діазепінів із первинними алкіл(арил)амінами та вторинними циклоалкіламінами. Встановлено, що така взаємодія перебігає при 8-10-годинному кип’ятінні в етанолі і у випадку первинних та вторинних алкіламінів приводить до гідрохлоридів 4-аміно-1,6-дигідропіразоло[3,4-e][1,4]діазепінів, а в разі ариламінів – до відповідних вільних основ з високими виходами. З’ясовано, що реакція з вторинними амінами дуже чутлива до їх просторових параметрів, тому діетил- або діізопропіламіни не схильні до взаємодії з 4-хлоропохідними 1,6-дигідропіразоло[3,4-e][1,4]діазепінів. Структура синтезованих сполук не суперечить результатам елементного аналізу, хроматомас-, ІЧ- та ЯМР-спектрів. Для надійного віднесення сигналів циклоалкіламінозамісників у відповідних 1,6-дигідропіразоло[3,4-e][1,4]діазепінах використані методики COSY та EXSY. Спектральні зміни в процесі протонування 5-циклоалкіламінопіразолодіазепінів узгоджуються з результатами квантово-хімічного моделювання, згідно із яким найвигіднішою є структура з протонованим атомом азоту в положенні 5 піразолодіазепінової системи., The role of the structural modification of 1,4-benzodiazepine systems with dialkylamino groups previously used successfully for a number of important derivatives possessing a complex of specific biological properties has been noted. This paper significantly expands the variety of hetero-annelated diazepines by developing a preparatively convenient synthetic route of new amino substituted pyrazol[3,4-e][1,4]diazepines. For this purpose, the reaction of 4-chloro-1,6-dihydropyrazolo[3,4-e][1,4]diazepines with the primary alkyl (aryl) amines and the secon- dary cycloalkylamines has been studied in detail. It has been found that this interaction occurs under 8-10 hour reflux in ethanol and for the primary and secondary alkylamines it leads to 4-amino-1,6-dihydropyrazolo[3,4-e] [1,4]diazepine hydrochlorides, and in case of aryl amines – to their corresponding free bases with high yields. The reaction of the secondary amines has been shown to be very sensitive to their steric parameters: dietyl- or diisopropylamines do not interact with 4-chloro derivatives of 1,6-dihydropyrazolo[3,4-e][1,4]diazepines. The structure of the compounds synthesized is consistent with the results of elemental analysis, LS/MS-, IR- and NMR-spectra. The COSY and EXSY methods were used for reliable identification of signals of cycloalkylamino substituents of 1,6 dihydropyrazolo[3,4-e][1,4]diazepines. Changes in NMR-spectra during protonation of 5-cycloalkylaminopyrazolodiazepines correspond to the results of quantum chemical simulations, according to them the preferred structure is the one with the protonated nitrogen atom in position 5 of the pyrazolodiazepine system., Отмечена роль структурной модификации 1,4-бензодиазепиновых систем диалкиламиногруппами, которая ранее была успешно использована для получения ряда важных производных c комплексом специфических биологических свойств. В данной статье значительно расширен спектр гетероаннелированных диазепинов путём разработки препаративно удобного варианта синтеза новых аминозамещенных пиразол[3,4-e] [1,4] диазепинов. С этой целью подробно исследована реакция 4-хлор-1,6- дигидропиразоло[3,4-e][1,4] диазепинов с первичными алкил(арил)аминами и вторичными циклоалкиламинами. Установлено, что такое взаимодействие протекает при 8-10-часовом кипячении в этаноле и в случае первичных и вторичных алкиламинов приводит к гидрохлоридам 4-амино-1,6-дигидропиразоло[3,4-e][1,4]диазепинов, а в случае ариламинов – к соответствующим свободным основаниям с высокими выходами. Показано, что реакция со вторичными аминами чувствительна к их пространственным параметрам, и диэтил- или диизопропиламины не склонны к взаимодействию с 4-хлорпроизводными 1,6-дигидропиразоло[3,4-e][1,4] диазепинов. Структура синтезированных соединений не противоречит данным элементного анализа, хроматомасс-, ИК- и ЯМР-спектров. Для надежного отнесения сигналов циклоалкиламинозаместителей в соответствующих 1,6-дигидропиразоло[3,4-e][1,4]диазепинах использованы методики COSY и EXSY. Спектральные изменения в процессе протонирования 5-циклоалкиламинопиразолодиазепинов согласуются с результатами квантово-химического моделирования, согласно которым наиболее выгодной является структура с протонированным атомом азота в положении 5 пиразолодиазепиновой системы.

The extract of the aerial parts of S. johnstonii afforded five known prenylated p-hydroxyacetophenone derivatives, scopoletin and 5-pentadecyl resorcinol together with the tridecyl derivative. The chemotaxonomic situation is discussed briefly.

The synthesis and characterization are described of linear polymers, having a carbon chain regularly interrupted by the Group IV elements silicon, germanium, tin, or lead. Such polymers were obtained by means of: (1) poly- addition reactions involving an organotin dihydride and either a dienic, a diynic, or a monoynic compound; (2) Wurtz-type poly-condensations involving appropriate combinations of p-chlorophyenyl and chloro derivatives of the Group IV elements. The synthesis and polymerization of vinyl-type Group IV organometallic monomers is dealt with briefly. Furthermore, interesting Group IV metal-containing heterocycles were prepared and also a few polymers containing, in addition to Group IV atoms, other, other heteroelements in their backbone. All polymer-forming reactions were studied by carrying out model reactions on a low-molecular weight level.

The results of a synthetic program directed towards the preparation of IVth main group organometallic polymers are presented. The main body of the report is concerned with the synthesis of linear polymers having a carbon chain regularly interrupted by tin (and in some cases other IVth group) atoms Such polymers have been obtained by means of true poly-addition reactions (hydrogen transfer polymerization) involving an organotin dihydride and either a dienic or a diynic or a monoyni C coumpound The synthesis of lVth group organometal-substituted polystyrenes carbon chain polymers containing the organometallic moiety as a substituent group as well as of a series of poly-p-phenylenesilanes-polymers consisting of chains of p-phenylene groups connected by dialkyl(aryl) silane groups are dealt with briefly.

The synthesis and characterization are described of linear polymers, having a carbon chain regularly interrupted by the Group IV elements silicon, germanium, tin or lead. Such polymers were obtained by means of: (1) poly-addition reactions involving an organotin dihydride and either a dienic, a diynic or a monoynic compound; (2) Wurtz-type poly-condensations involving appropriate combinations of p-chlorophenyl and chloro derivatives of the Group IV elements. The synthesis and polymerization of vinyl-type IVth group organometallic monomers is dealt with briefly. Furthermore, interesting IVth group metal-containing heterocyoles were prepared and also a few polymers, containing in addition to Group IV atoms other hetero-elements in their backbone. All polymer-forming reactions have been studied by carrying out model reactions on a low-molecular weight level. (Author)