How to track cellular aging of mesenchymal stromal cells?

Mesenchymal stromal cells (MSC) are currently tested in a large number of clinical trials and raise high hope in regenerative medicine. These cells have to be expanded in vitro before transplantation and several studies demonstrated that long-term culture evokes continuous changes in MSC: proliferation rate decays, the cell size increases, differentiation potential is affected, chromosomal instabilities may arise and molecular changes are acquired. Long-term culture of cell preparations might also have therapeutic consequences, although this has hardly been addressed in ongoing trials so far. Reliable therapeutic regimens necessitate quality control of cellular products. This research perspective summarizes available methods to track cellular aging of MSC. We have demonstrated that gene expression changes and epigenetic modifications are continuously acquired during replicative senescence. Molecular analysis of a suitable panel of genes might provide a robust tool to assess efficiency and safety of long-term expansion

The applying of three-dimensional reconstruction for planning and supporting surgical operations

Аппаратно-программный комплекс для помощи хирургу во время проведения операции,представляет собой систему отображения набора анатомических компьютерных 3D моделей зоны интереса на дисплее в хирургической операционной. Данные анатомические модели получаются в результате предварительной реконструкции на основе сегментации медицинских изображений, таких модальностей как КТ, МРТ, ПЭТ и др. Аппаратно-программный комплекс поддержки проведения хирургического вмешательства включает в себя также систему захвата движения, предназначенную длябесконтактного управления, за сч?т жестов оператора набором анатомических 3D моделей на дисплее. Система позволяет управлять положением набора 3D моделей, их масштабом и прозрачностью отдельных моделей, а также перемещаться между наборами 3D моделей, построенных для различных стадий проведения хирургической операции.Hardware and software system to assist the surgeon during surgery. This is a system for displaying a set ofanatomical 3D computer models of regions of interest on display in the surgery. These anatomical models areobtained by a preliminary reconstruction based segmentation of medical images of such modalities as CT, MRI,PET, etc. Hardware and software system support surgery also includes motion-capture system designed for contactmanagement, through gestures of the operator, a set of 3D anatomical models on display. The system allows tocontrol the position of the set of 3D models, their scale and transparency of individual models and to navigatebetween sets of 3D models for various stages of the surgery

Donor Age of Human Platelet Lysate Affects Proliferation and Differentiation of Mesenchymal Stem Cells

The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1), but it was significantly higher with HPLs from younger donors (<35 years) as compared to older donors (>45 years). Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal). HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1) or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation

Обоснование выбора электродвигателя и схемы его включения для системы точного поддержания скорости

Рассматривается применение в системах точного поддержания скорости различных синхронных электродвигателей. В результате сравнения рекомендовано применение в таких системах конденсаторного синхронного реактивного двигателя с трехфазными обмотками статора. Это позволяет упростить и удешевить систему точного электропривода и повысить ее надежность

Specific Age-Associated DNA Methylation Changes in Human Dermal Fibroblasts

Epigenetic modifications of cytosine residues in the DNA play a critical role for cellular differentiation and potentially also for aging. In mesenchymal stromal cells (MSC) from human bone marrow we have previously demonstrated age-associated methylation changes at specific CpG-sites of developmental genes. In continuation of this work, we have now isolated human dermal fibroblasts from young (<23 years) and elderly donors (>60 years) for comparison of their DNA methylation profiles using the Infinium HumanMethylation27 assay. In contrast to MSC, fibroblasts could not be induced towards adipogenic, osteogenic and chondrogenic lineage and this is reflected by highly significant differences between the two cell types: 766 CpG sites were hyper-methylated and 752 CpG sites were hypo-methylated in fibroblasts in comparison to MSC. Strikingly, global DNA methylation profiles of fibroblasts from the same dermal region clustered closely together indicating that fibroblasts maintain positional memory even after in vitro culture. 75 CpG sites were more than 15% differentially methylated in fibroblasts upon aging. Very high hyper-methylation was observed in the aged group within the INK4A/ARF/INK4b locus and this was validated by pyrosequencing. Age-associated DNA methylation changes were related in fibroblasts and MSC but they were often regulated in opposite directions between the two cell types. In contrast, long-term culture associated changes were very consistent in fibroblasts and MSC. Epigenetic modifications at specific CpG sites support the notion that aging represents a coordinated developmental mechanism that seems to be regulated in a cell type specific manner

Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks

Cells in culture undergo replicative senescence. In this study, we analyzed functional, genetic and epigenetic sequels of long-term culture in human mesenchymal stem cells (MSC). Already within early passages the fibroblastoid colonyforming unit (CFU-f) frequency and the differentiation potential of MSC declined significantly. Relevant chromosomal aberrations were not detected by karyotyping and SNP-microarrays. Subsequently, we have compared DNA-methylation profiles with the Infinium HumanMethylation27 Bead Array and the profiles differed markedly in MSC derived from adipose tissue and bone marrow. Notably, all MSC revealed highly consistent senescence-associated modifications at specific CpG sites. These DNA-methylation changes correlated with histone marks of previously published data sets, such as trimethylation of H3K9, H3K27 and EZH2 targets. Taken together, culture expansion of MSC has profound functional implications - these are hardly reflected by genomic instability but they are associated with highly reproducible DNA-methylation changes which correlate with repressive histone marks. Therefore replicative senescence seems to be epigenetically controlled

On the physical nature of photon and the modeling of its wave function of free propagation in space and time

In the framework of quantum mechanics the physical nature of the photon is discussed. It is substantiated that a photon is a quantum quasiparticle, the free propagation of which must be considered taking into account the processes in a physical vacuum at Planck distances. For practical purposes on a macroscopic scale, the photon propagation can be modeled using the wave function (wave packet) normalized to the unit probability in the coordinate representation

Совершенствование управленческого учета на предприятии

Объектом исследования является группа компаний, производящая Эко-продукты. Цель работы – совершенствование системы управленческого учета группы компаний в части формирования финансовой отчетности. В процессе исследования были изучены теоретические аспекты управленческого учета, а также методы и инструменты, используемые в нем. Рассмотрена роль управленческого учета в информационном обеспечении руководства предприятия. Проводилась организационно-экономическая характеристика предприятия, в рамках которой была рассмотрена действующая организационная структура и проведен финансовый анализ. Проанализирована действующая система управленческого учета группы компаний. Проведен финансовый анализ по двум формам отчетности.The object of research is a group of companies that produce eco-products. The purpose of the work is to improve the management accounting system of a group of companies in terms of the formation of financial statements. During the study, the theoretical aspects of management accounting were studied, as well as the methods and tools used in it. The role of management accounting in the information support of enterprise management is considered. The organizational and economic characteristics of the enterprise were carried out, in the framework of which the current organizational structure was reviewed and a financial analysis was carried out. The current management accounting system of a group of companies is analyzed. Conducted financial analysis in two reporting forms

Повышение эффективности противопожарной защиты магазина «Fix Price»

Целью работы является усовершенствование системы противопожарной защиты магазина "Fix Price". В выпускной квалификационной работе проведен обзор литературных источников по вопросам состояния проблем обеспечения пожарной безопасности на предприятиях торговли, дан анализ автоматических систем пожаротушения, обоснован выбор автоматической установки пожаротушения тонкораспылённой водой для объекта исследования, произведены расчёты индивидуального пожарного риска.The aim of the work is to improve the fire protection system of the "Fix Price" store. In the final qualifying work, a review of literature sources on the state of problems of fire safety in commercial enterprises is conducted, an analysis of automatic fire extinguishing systems is given, the choice of an automatic fire extinguishing system with thin-sprayed water for the object of research is justified, and calculations of individual fire risk are made