Site-specific quantification of lysine acetylation in the N-terminal tail of histone H4 using a double-labelling, targeted UHPLC MS/MS approach

We developed a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the site-specific quantification of lysine acetylation in the N-terminal region of histone H4 by combining chemical derivatization at the protein and peptide levels with digestion using chymotrypsin and trypsin. Unmodified epsilon-amino groups were first modified with propionic acid anhydride and the derivatized protein digested with trypsin and chymotrypsin. The newly formed peptide N-termini were subjected to a second derivatization step with d(6)- (heavy) or d(0)- (light) acetic acid anhydride. Samples were mixed at different ratios and peptides monitored by multiple reaction monitoring (MRM) LC-MS/MS. The method was validated in terms of linearity (R (2) a parts per thousand yenaEuro parts per thousand 0.94), precision (RSD a parts per thousand currency signaEuro parts per thousand 10 %), and accuracy (a parts per thousand currency sign27 %) and used to assess the effect of the histone deacetylase (HDAC) inhibitors SAHA and MS-275 in the murine macrophage-like cell line RAW 264.7. SAHA and MS-275 showed site-specific effects on the acetylation levels of K5 and K8 with the K5(Ac)-K8 and K5-K8(Ac) peptides increasing 2.5-fold and 5-fold upon treatment with SAHA and MS-275, respectively. Assessing lysine acetylation in a site-specific manner is important for gaining a better understanding of the effects of HDAC inhibitors and for clarifying disease mechanisms where lysine acetylation plays a role

МЕТРИКИ ДЛЯ ДИНАМИЧЕСКОГО МАСШТАБИРОВАНИЯ БАЗ ДАННЫХ В ОБЛАЧНЫХ СРЕДАХ

This article analyzes the main methods of scaling databases (replication, sharding) and their support at the popular relational databases and NoSQL solutions with different data models: a document-oriented, key-value, column-oriented, graph. The article provides an assessment of the capabilities of modern cloud-based solution and gives a model for the organization of dynamic scaling in the cloud infrastructure. In the article are analyzed different types of metrics and are included the basic metrics that characterize the functioning parameters and database technology, as well as sets the goals of the integral metrics, necessary for the implementation of adaptive algorithms for dynamic scaling databases in the cloud infrastructure. This article was prepared with the support of RFBR grant № 13-07-00749.В статье проводится анализ основных методов масштабирования баз данных (репликация, шардинг) и их поддержки на уровне популярных реляционных СУБД и NoSQL решений с различными моделями данных: документо-ориентированной, ключ-значение, поколоночной, графовой. Приводится оценка возможности современных облачных решений и модель для организации динамического масштабирования в облачной инфраструктуре. Выделяются группы базовых метрик, характеризующих параметры функционирования СУБД и технических средств, а также определяются цели и группы интегральных метрик, необходимых для реализации адаптивных алгоритмов динамического масштабирования баз данных в облачной инфраструктуре

АЛГОРИТМ ДИНАМИЧЕСКОГО МАСШТАБИРОВАНИЯ РЕЛЯЦИОННЫХ БАЗ ДАННЫХ В ОБЛАЧНЫХ СРЕДАХ

This article analyzes the main methods of scalingdatabases (replication, sharding) and their supportat the popular relational databases and NoSQLsolutions with different data models: document-oriented, key-value, column-oriented and graph.The article presents an algorithm for the dynamicscaling of a relational database (DB), that takesinto account the specifics of the different types of logic database model. This article was prepared with the support of RFBR (grant № 13-07-00749).В статье анализируются основные методы масштабирования баз данных (репликация, шардинг) и их поддержки на уровне популярных реляционных СУБД и NoSQL решений с различнымимоделямиданных: документо-ориентированной, ключ-значение, поколоночной, графовой; приводитсяалгоритмдинамического масштабирования реляционной базы данных (БД), учитывающий специфику различных типов даталогической модели БД

Comparison of Targeted Mass Spectrometry Techniques With an Immunoassay:A Case Study For HSP90α

PURPOSE: The objective of this study was to better understand factors governing the variability and sensitivity in SRM and PRM, compared to immunoassay. EXPERIMENTAL DESIGN: A 2D-LC-MS/MS-based SRM and PRM assay was developed for quantitative measurements of HSP90α in serum. Forty-three control sera were compared by SRM, PRM and ELISA following the manufacturer's instructions. Serum samples were trypsin-digested and fractionated by SCX chromatography prior to SRM and PRM measurements. Analytical parameters such as linearity, LOD, LOQ, repeatability and reproducibility of the SRM, PRM and ELISA were determined. RESULTS: PRM data obtained by high-resolution mass spectrometry correlated better with ELISA measurements than SRM data measured on a triple quadrupole mass spectrometer. While all three methods (SRM, PRM, ELISA) were able to quantify HSP90α in serum at the ng/mL level, the use of PRM on a high-resolution mass spectrometer reduced variation and showed comparable sensitivity to immunoassay. CONCLUSIONS AND CLINICAL RELEVANCE: Using fractionation, it is possible to measure ng/mL levels of HSP90α in a reproducible, selective and sensitive way using PRM in serum. This opens up the possibility to use PRM in a multiplexed way as an attractive alternative for immunoassays without the use of antibodies or comparable binders. This article is protected by copyright. All rights reserved

Сучасні тренди підготовки фахівців з управління проектами та програмами

У збірнику матеріалів конференції висвітлено роботи фіналістів Усеукраїнського конкурсу студентських наукових робіт 2018–2019 навчального року з «Управління проектами та програмами» й сучасні тренди підготовки фахівців з управління проектами та програмами, які були обговорені на науково-практичній конференції в м. Луцьку 5 квітня 2019 р. Збірник розрахований на широке коло фахівців з управління проектами та програмами, спеціалістів, що працюють у структурних підрозділах органів державної влади й управління, економістів, викладачів, аспірантів, здобувачів і студентів, а також усіх, хто цікавиться сучасними трендами підготовки фахівців з управління проектами та програмами

A Spectral Method of the Analysis of Linear Control Systems

A spectral method of the analysis of linear control systems is considered. Within the framework of this approach the σ-entropy of input signals and the σ-entropy norm of systems are introduced. The invariance of the introduced norm makes it possible to get invariant results of σ-entropy analysis

A Spectral Method of the Analysis of Linear Control Systems

A spectral method of the analysis of linear control systems is considered. Within the framework of this approach the σ-entropy of input signals and the σ-entropy norm of systems are introduced. The invariance of the introduced norm makes it possible to get invariant results of σ-entropy analysis

METRICS FOR DYNAMIC SCALING OF DATABASE IN CLOUDS

This article analyzes the main methods of scaling databases (replication, sharding) and their support at the popular relational databases and NoSQL solutions with different data models: a document-oriented, key-value, column-oriented, graph. The article provides an assessment of the capabilities of modern cloud-based solution and gives a model for the organization of dynamic scaling in the cloud infrastructure. In the article are analyzed different types of metrics and are included the basic metrics that characterize the functioning parameters and database technology, as well as sets the goals of the integral metrics, necessary for the implementation of adaptive algorithms for dynamic scaling databases in the cloud infrastructure. This article was prepared with the support of RFBR grant № 13-07-00749

LINEAR SOLVATION ENERGY RELATIONSHIPS FOR CHARACTERIZATION OF MLC SYSTEMS WITH SODIUM DODECYL SULPHATE MOBILE PHASES MODIFIED BY ALIPHATIC ALCOHOLS OR CARBOXYLIC ACIDS

The Linear Solvation Energy Relationships (LSER) have been successfully used for the modeling of partition and retention of the set of test compounds in different systems. The properties of micellar chromatographic systems with the mobile phases on the basis of sodium dodecylsulphate modified (ODS) by additives of aliphatic alcohols (1-butanol, 1-pentanol) or aliphatic carboxylic acids (butanoic, pentanoic) were characterized on the basis of comparison of calculated LSER coefficients. Principal component analysis (PCA) was used for the classification of studied systems