ИНФОРМАЦИОННО-АЛГОРИТМИЧЕСКАЯ ПОДДЕРЖКА РАЗРАБОТКИ ТВЕРДЫХ ЛЕКАРСТВЕННЫХ ФОРМ

The article deals with the application of the system approach for constructing informationalgorithmic support for the pharmaceutical development of solid dosage forms. Information modeling of the life cycle of pharmaceutical drug development has been carried out starting from the stage of studying the active pharmaceutical substance and ending with the utilization of the drug. These models are built in the IDEF0 nomination. A generalized block diagram is presented that reflects, in its most general form, the iterative process of developing a ready-made dosage form as applied to the further transfer of technology. The basis of the system approach is QbD - "Quality planned in the development". To implement the QbD principle on the basis of the system approach, systemic set-theoretic models of information support of pharmaceutical development in the nomenclature of Melentiev have been constructed. A model for controlling the pressing process is also provided, which takes into account all the technological stages in the development of a solid dosage form. Functional models in the IDEF0 nomenclature of the technological process are constructed from the preparation of premises, personnel and components of the dosage form to the stage of packing and packaging of the finished dosage form. The construction of an informational intellectual control system for pharmaceutical development has been considered in detail with particular attention paid to the construction of a database of medicinal and auxiliary substances using the example of solid dosage forms. In Melentiev's bracket notation, the database of auxiliary substances necessary for the design of a solid dosage form is filled. The "Entity-relationship" model and the relational model for the database of medicinal and auxiliary substances have been constructeВ статье рассматривается применение системного подхода для построения информационно-алгоритмической поддержки фармацевтической разработки твердых лекарственных форм. Проведено информационное моделирование жизненного цикла фармацевтической разработки лекарственного препарата, начиная c этапа изучения активной фармацевтической субстанции и заканчивая утилизацией препарата. Данные модели построены в нотации IDEF0. Приводится обобщенная блок-схема, отражающая в самом общем виде итерационный процесс разработки готовой лекарственной формы применительно к дальнейшему трансферу технологии. В основу применения системного подхода положен принцип QbD - «Качество, запланированное при разработке». Для реализации принципа QbD проведено построение системных теоретико-множественных моделей информационной поддержки фармацевтической разработки в скобочной нотации Мелентьева. Также приведена модель для управления процессом прессования, где учитываются все технологические стадии при разработке твердой лекарственной формы. В статье построены функциональные модели в нотации IDEF0 технологического процесса: от подготовки помещений, персонала и компонентов лекарственной формы до стадии фасовки и упаковки готовой лекарственной формы. Подробно рассмотрено построение информационной интеллектуальной системы управления фармацевтической разработкой, при этом особенное внимание уделено построению базы данных лекарственных и вспомогательных веществ на примере твердых лекарственных форм. В скобочной нотации Мелентьева приведено наполнение базы данных вспомогательных веществ, необходимых для дизайна твердой лекарственной формы. Построены модель «Сущность-связь» и реляционная модель для базы данных лекарственных и вспомогательных веществ

СИСТЕМНЫЙ ПОДХОД К ИНФОРМАЦИОННОЙ ПОДДЕРЖКЕ ФАРМАЦЕВТИЧЕСКОЙ РАЗРАБОТКИ ГОТОВЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВ

The article considers the application of the system approach for constructing informational support for the life cycle of the production of medicinal products. The principal difficulties of creating a single informational system of the entire life cycle are considered in this article. A brief analysis of the information and computer support of individual links in the life cycle is given. Particular attention is paid to the use of a systematic approach to the creation of information support for the pharmaceutical development of medicines. The principle of QbD - “Quality planned for development” - was taken as a basis. For the implementation the QbD principle on the basis of the system approach, it is proposed to use the Shewhart-Deming iteration cycle to create an information support for a sustainable search for the optimal version (the program) of the conducted studies. The possibility of combining the PDCA cycle and the methodology of the system approach is shown. On its basis, system-theoretic multiple models of nformation support for pharmaceutical development in the graphic-analytical nomination were constructed. The method of applying the criterial approach for the formation of global and local criteria for managing research and the construction of system management models in the Melentiev’s brackets nomination are presented. The information modeling of the stage of pharmaceutical development has been carried out. Functional models have been constructed in the IDEF0 nomination.В статье рассматривается применение системного подхода для построения информационной поддержи жизненного цикла производства лекарственных препаратов. Рассмотрены принципиальные трудности создания единой информационной системы всего жизненного цикла. Дается краткий анализ информационной и компьютерной поддержки отдельных звеньев жизненного цикла. Особое внимание уделено применению системного подхода к созданию информационной поддержки звена фармацевтической разработки лекарственных средств. За основу взят принцип QbD - «Качество, запланированное при разработке». Для реализации принципа QbD на основе системного подхода при создании информационной поддержки устойчивого поиска оптимального варианта (программы) проводимых исследований предложено использовать итерационный цикл Шухарта-Деминга. Показана возможность совмещения цикла PDCA и методики системного подхода. На его основе проведено построение системных теоретико-множественных моделей информационной поддержки фармацевтической разработки в графо-аналитической номинации. Приводится методика применения критериального подхода для формирования глобального и локальных критериев управления исследованиями и построение системных моделей управления в скобочной номинации Мелентьева. Проведено информационное моделирование этапа фармацевтической разработки, построены функциональные модели в номинации IDEF0

The genetic history of admixture across inner Eurasia

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Data Availability. Genome-wide sequence data of two Botai individuals (BAM format) are available at the European Nucleotide Archive under the accession number PRJEB31152 (ERP113669). Eigenstrat format array genotype data of 763 present-day individuals and 1240K pulldown genotype data of two ancient Botai individuals are available at the Edmond data repository of the Max Planck Society (https://edmond.mpdl.mpg.de/imeji/collection/Aoh9c69DscnxSNjm?q=).The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report additional damage-reduced genome-wide data of two previously published individuals from the Eneolithic Botai culture in Kazakhstan (~5,400 BP). We find that present-day inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries, mirroring geography. The Botai and more recent ancient genomes from Siberia show a decrease in contribution from so-called “ancient North Eurasian” ancestry over time, detectable only in the northern-most “forest-tundra” cline. The intermediate “steppe-forest” cline descends from the Late Bronze Age steppe ancestries, while the “southern steppe” cline further to the South shows a strong West/South Asian influence. Ancient genomes suggest a northward spread of the southern steppe cline in Central Asia during the first millennium BC. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.Max Planck SocietyEuropean Research Council (ERC)Russian Foundation for Basic Research (RFBR)Russian Scientific FundNational Science FoundationU.S. National Institutes of HealthAllen Discovery CenterUniversity of OstravaCzech Ministry of EducationXiamen UniversityFundamental Research Funds for the Central UniversitiesMES R

INFORMATION-ALGORITHMIC SUPPORT FOR DEVELOPMENT OF SOLID PHARMACEUTICAL FORM

The article deals with the application of the system approach for constructing informationalgorithmic support for the pharmaceutical development of solid dosage forms. Information modeling of the life cycle of pharmaceutical drug development has been carried out starting from the stage of studying the active pharmaceutical substance and ending with the utilization of the drug. These models are built in the IDEF0 nomination. A generalized block diagram is presented that reflects, in its most general form, the iterative process of developing a ready-made dosage form as applied to the further transfer of technology. The basis of the system approach is QbD - "Quality planned in the development". To implement the QbD principle on the basis of the system approach, systemic set-theoretic models of information support of pharmaceutical development in the nomenclature of Melentiev have been constructed. A model for controlling the pressing process is also provided, which takes into account all the technological stages in the development of a solid dosage form. Functional models in the IDEF0 nomenclature of the technological process are constructed from the preparation of premises, personnel and components of the dosage form to the stage of packing and packaging of the finished dosage form. The construction of an informational intellectual control system for pharmaceutical development has been considered in detail with particular attention paid to the construction of a database of medicinal and auxiliary substances using the example of solid dosage forms. In Melentiev's bracket notation, the database of auxiliary substances necessary for the design of a solid dosage form is filled. The "Entity-relationship" model and the relational model for the database of medicinal and auxiliary substances have been construct

SYSTEM APPROACH TO INFORMATIONAL SUPPORT OF PHARMACEUTICAL DEVELOPMENT OF FINISHED MEDICINAL PRODUCTS

The article considers the application of the system approach for constructing informational support for the life cycle of the production of medicinal products. The principal difficulties of creating a single informational system of the entire life cycle are considered in this article. A brief analysis of the information and computer support of individual links in the life cycle is given. Particular attention is paid to the use of a systematic approach to the creation of information support for the pharmaceutical development of medicines. The principle of QbD - “Quality planned for development” - was taken as a basis. For the implementation the QbD principle on the basis of the system approach, it is proposed to use the Shewhart-Deming iteration cycle to create an information support for a sustainable search for the optimal version (the program) of the conducted studies. The possibility of combining the PDCA cycle and the methodology of the system approach is shown. On its basis, system-theoretic multiple models of nformation support for pharmaceutical development in the graphic-analytical nomination were constructed. The method of applying the criterial approach for the formation of global and local criteria for managing research and the construction of system management models in the Melentiev’s brackets nomination are presented. The information modeling of the stage of pharmaceutical development has been carried out. Functional models have been constructed in the IDEF0 nomination

The possible role of social selection in the distribution of major haplotypes of Y-chromosome haplogroup C3 in Central Asian populations

There is a strong connection between social selection and birth rate of the descendants, whose fathers had achieved high social status during the expansion of the Mongol Empire and associated historical events. We suppose this major ancestral haplotype to be the “proto-Mongolian haplotype”, inherited by Genghis Khan and his descendants. It can be assumed that the four common haplotypes also spread as a result of positive social selection, because some clans were endowed with a number of privileges and high status during the Mongol expansion

The possible role of social selection in the distribution of major haplotypes of Y-chromosome haplogroup C3 in Central Asian populations

There is a strong connection between social selection and birth rate of the descendants, whose fathers had achieved high social status during the expansion of the Mongol Empire and associated historical events. We suppose this major ancestral haplotype to be the “proto-Mongolian haplotype”, inherited by Genghis Khan and his descendants. It can be assumed that the four common haplotypes also spread as a result of positive social selection, because some clans were endowed with a number of privileges and high status during the Mongol expansion

Characterizing the genetic history of admixture across inner Eurasia

The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report genome-wide data of two Eneolithic individuals (~5,400 years before present) associated with the Botai culture in northern Kazakhstan. We find that inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries. This genetic separation is well mirrored by geography. The ancient Botai genomes suggest yet another layer of admixture in inner Eurasia that involves Mesolithic hunter-gatherers in Europe, the Upper Paleolithic southern Siberians and East Asians. Admixture modeling of ancient and modern populations suggests an overwriting of this ancient structure in the Altai-Sayan region by migrations of western steppe herders, but partial retaining of this ancient North Eurasian-related cline further to the North. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe