Static and dynamic management models production at the entity

Static and dynamic economic-mathematical models for the solution of tasks of information support and optimization of integrated management of engineering procedures at the entity are described. Within these models algorithms of the solution of static and dynamic tasks of information support and complex optimization of management of engineering procedures at the entity are proposed

Lynx: A knowledge-based AI service platform for content processing, enrichment and analysis for the legal domain

The EU-funded project Lynx focuses on the creation of a knowledge graph for the legal domain (Legal Knowledge Graph, LKG) and its use for the semantic processing, analysis and enrichment of documents from the legal domain. This article describes the use cases covered in the project, the entire developed platform and the semantic analysis services that operate on the documents. © 202

A simple method for the preparation of 3,5-dinitrimino-1,2,4-triazole and its salts

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The reaction of 2-methyl-1-nitrоisothiourea with hydrazine in the presence of alkali metal bicarbonates (carbonates) resulted in the formation of 3,5-dinitrimino-1,2,4-triazole salts. The same salts were also formed by a reaction of 2-methyl-1-nitrоisothiourea with alkali metal salts of 4-nitrоsemicarbazide. This represents the first synthesis and characterization of the high-energy 3,5-dinitrimino-1,2,4-triazole, which can be readily isolated by treatment of its disodium salt with HCl

A simple method for the preparation of 3,5-dinitrimino-1,2,4-triazole and its salts

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The reaction of 2-methyl-1-nitrоisothiourea with hydrazine in the presence of alkali metal bicarbonates (carbonates) resulted in the formation of 3,5-dinitrimino-1,2,4-triazole salts. The same salts were also formed by a reaction of 2-methyl-1-nitrоisothiourea with alkali metal salts of 4-nitrоsemicarbazide. This represents the first synthesis and characterization of the high-energy 3,5-dinitrimino-1,2,4-triazole, which can be readily isolated by treatment of its disodium salt with HCl

The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells

The long noncoding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), also known as MALAT-1 or NEAT2 (nuclear-enriched abundant transcript 2), is a highly conserved nuclear noncoding RNA (ncRNA) and a predictive marker for metastasis development in lung cancer. To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements using zinc finger nucleases. The achieved 1,000-fold MALAT1 silencing provides a unique loss-of-function model. Proposed mechanisms of action include regulation of splicing or gene expression. In lung cancer, MALAT1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes. Consequently, MALAT1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft. Antisense oligonucleotides (ASO) blocking MALAT1 prevent metastasis formation after tumor implantation. Thus, targeting MALAT1 with ASOs provides a potential therapeutic approach to prevent lung cancer metastasis with this ncRNA serving as both predictive marker and therapeutic target. Finally, regulating gene expression, but not alternative splicing, is the critical function of MALAT1 in lung cancer metastasis. In summary, 10 years after the discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis, our loss-of-function model unravels the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis. © 2012 American Association for Cancer Research

The long non-coding RNA MALAT1 is an essential gene regulator for lung cancer metastasis in a novel human knockout model

The long non-coding RNA MALAT1 was one of the first lncRNAs associated with cancer: it is a highly conserved nuclear ncRNA and a predictive marker for metastasis development in lung cancer. However, its high abundance and nuclear localization have greatly hampered its functional analysis since it is only inefficiently knocked down by RNA interference (RNAi). To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements site-specifically into the MALAT1 locus using Zinc Finger Nucleases (ZFN).This approach yielded a more than 1000-fold silencing of MALAT1 providing a unique loss-of-function model. Proposed mechanisms of action of MALAT1 include regulation of splicing or gene expression. In lung cancer, MALAT1 does not alter alternative splicing but actively regulates gene expression inducing a signature of metastasis-associated genes. Consequently, MALAT1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft model. Encouraged by this discovery of the essential function of MALAT1 in lung cancer metastasis, we wanted to analyze whether MALAT1 could also be therapeutically targeted: We developed Antisense oligonucleotides (ASOs) effectively blocking MALAT1 expression in the cell culture and in the animal. Notably, MALAT1-ASO treatment prevents metastasis formation after tumor implantation. Thus, targeting MALAT1 with antisense oligonucleotides provides a potential therapeutic approach to prevent lung cancer metastasis with MALAT1 serving as both, predictive marker and therapeutic target. Lastly, regulating gene expression, but not alternative splicing is the critical function of MALAT1 in lung cancer metastasis. In summary, ten years after the discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis, our loss-of-function model unravels the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis