The research of the pulsed electron beam effect on polylactic acid scaffolds

The effect of nanosecond pulsed electron beam irradiation on properties of polylactic acid (PLLA)scaffolds was investigated. Modification of scaffolds was performed in electron beam accelerator with absorbeddose from 30 to200 kGy. Properties of the scaffolds were examined by means of XRD analysis and scanningelectron microscopy. It was shown that pulsed electron beam exposure leads to the recrystallization and changesin surface morphology

Постановка задачи для разработки ИС учета игровых подходов в обучении

Рассмотрены положительные и отрицательные аспекты обучения через онлайн-среды с применением игровых методов обучения, поставлена задача разработки

Разработка налоговой политики МУП «КРУ г.Юрги»

Объектом исследования является муниципальное унитарное предприятие "Комбинат ритуальных услуг г. Юрги". Цель работы – формирования налоговой политики муниципального унитарного предприятия "Комбинат ритуальных услуг г. Юрги". Актуальность работы определяется критическим влиянием налоговой политики на финансово-хозяйственную деятельность предприятия и повышение эффективности управления его налоговыми потоками. Для достижения поставленной цели решены следующие задачи: 1.Рассмотреть теоретическую базу проведения налогового анализа на микроуровне. 2.Выполнить анализ финансово-хозяйственной деятельности МУП КРУ г. Юрги. 3.Оценить влияние налоговых платежей на финансовый результат деятельности МУП КРУ г. Юрги. 4.Предложить рекомендации по оптимизации налоговых выплат.The purpose of the work is the formation of the tax policy of the municipal unitary enterprise "Combine of funeral services of Yurga". The relevance of the work is determined by the critical impact of tax policy on the financial and economic activities of the enterprise and improving the efficiency of managing its tax flows. To achieve this goal, the following tasks were solved: 1. Consider the theoretical basis for conducting tax analysis at the micro level. 2. To analyze the financial and economic activities of the municipal unitary enterprise of the switchgear of the city of Yurga. 3. To assess the impact of tax payments on the financial result of the activities of the municipal unitary enterprise of KRU of Yurga 4. To offer recommendations for optimizing tax payments

Влияние параметров пласта на процесс конусообразования в горизонтальных скважинах при разработке нефтегазовых месторождений

Анализ механизма проявления конусообразования и прорыва воды при разработке месторождения. Обоснование применения технологий предотвращения поступления нецелевого флюида. Комплексные решения для повышение эффективности разработки нефтегазовых залежей в условиях конусообразования.Analysis of the mechanism of manifestation of coning and water breakthrough during field development. Justification of the use of technologies to prevent the ingress of non-target fluid. Integrated solutions to improve the efficiency of oil and gas deposits development in coning conditions

Therapeutic application of dominant-negative PDGF beta-receptor in liver fibrosis

Upon liver injury hepatic stellate cells (HSC) undergo phenotype transformation with acquisition of myofibroblast-like features characterized by increased cell proliferation, motility, contractility and extra cellular matrix production. HSC activation is regulated by several cytokines and growth factors including platelet derived growth factor B-chain (PDGF-BB) which exerts cellular effects by binding to PDGF receptors (PDGFR) and further inducing receptor dimerization and tyrosine-autophosphorylation, thus initiating various signaling pathways, amongst which MAPK and PI3K as principals. These PDGF signaling pathways may provide a potential therapeutic target to modulate the fibrotic response in liver. We therefore generated a dominant-negative soluble PDGFR consisting of PDGFRBeta extracellular domains connected to the IgG-Fc part of human immoglobulin, and used adenovirus type 5 mediated gene transfer into Cos-7 cells and HSC. This Ad5-CMV-sPDGFRBeta construct produced a secreted chimeric protein with two cystein residues at the hinge region of the IgG-Fc part, culminating in predimerized soluble receptors. This PDGFRBeta secreted efficiently into the conditioned media of both Cos-7 cells and HSC and binds PDGF-BB. The secreted protein from Cos-7 cells was purified and applied to test its inhibitory effects on PDGF signaling in HSC. The soluble PDGFRBeta did inhibit autophosphorilation of endogenous membrane-bound receptors upon PDGF stimulation and completely blocked p44 and p42 (ERK1 and ERK2) phosphorylation. PDGF activation of ERK triggers proliferative responses in HSC, further underlining that our sPDGFRBeta inhibits HSC proliferation and DNA synthesis along with inhibition of PDGF-induced PI3K/Akt activation, thus leading to reduced collagen type I(Alphal) gene expression. Adenovirus-mediated sPDGFRBeta gene transfer in HSC in vitro proved highly effective. Infected HSC produced the soluble receptor to scavenge available PDGF-BB and inhibit HSC proliferation. Ad5-CMV-sPDGFRBeta infected HSC did inhibit also autocrine looping on PDGF mRNA production resulting in decreased expression of thrombospondin-1, a latent TGF-Beta activator, leading to decreased fibrogenesis as proven by reduced levels of collagen type I(Alphal) mRNA compared to the control cultures.We then used a bile duct ligation (BDL) rat model to examine the effects of sPDGFRBeta on hepatic fibrogenesis. It is known that expression of PDGFRBeta-subunit does increase during experimental liver injury. In our model both approaches, adenovirus mediated sPDGFRBeta gene transfer and direct application of sPDGFRBeta as purified protein, significantly attenuated ongoing fibrosis in BDL rats as evidenced by reduced expression of Alpha-SMA and collagen type I(AlphaI). In conclusion, our experiments did demonstrate the potent antifibrogenetic effects of sPDGFRBeta, a PDGF antagonist, in experimentally induced liver fibrosis

Therapeutic application of dominant-negative PDGF beta-receptor in liver fibrosis

Upon liver injury hepatic stellate cells (HSC) undergo phenotype transformation with acquisition of myofibroblast-like features characterized by increased cell proliferation, motility, contractility and extra cellular matrix production. HSC activation is regulated by several cytokines and growth factors including platelet derived growth factor B-chain (PDGF-BB) which exerts cellular effects by binding to PDGF receptors (PDGFR) and further inducing receptor dimerization and tyrosine-autophosphorylation, thus initiating various signaling pathways, amongst which MAPK and PI3K as principals. These PDGF signaling pathways may provide a potential therapeutic target to modulate the fibrotic response in liver. We therefore generated a dominant-negative soluble PDGFR consisting of PDGFRBeta extracellular domains connected to the IgG-Fc part of human immoglobulin, and used adenovirus type 5 mediated gene transfer into Cos-7 cells and HSC. This Ad5-CMV-sPDGFRBeta construct produced a secreted chimeric protein with two cystein residues at the hinge region of the IgG-Fc part, culminating in predimerized soluble receptors. This PDGFRBeta secreted efficiently into the conditioned media of both Cos-7 cells and HSC and binds PDGF-BB. The secreted protein from Cos-7 cells was purified and applied to test its inhibitory effects on PDGF signaling in HSC. The soluble PDGFRBeta did inhibit autophosphorilation of endogenous membrane-bound receptors upon PDGF stimulation and completely blocked p44 and p42 (ERK1 and ERK2) phosphorylation. PDGF activation of ERK triggers proliferative responses in HSC, further underlining that our sPDGFRBeta inhibits HSC proliferation and DNA synthesis along with inhibition of PDGF-induced PI3K/Akt activation, thus leading to reduced collagen type I(Alphal) gene expression. Adenovirus-mediated sPDGFRBeta gene transfer in HSC in vitro proved highly effective. Infected HSC produced the soluble receptor to scavenge available PDGF-BB and inhibit HSC proliferation. Ad5-CMV-sPDGFRBeta infected HSC did inhibit also autocrine looping on PDGF mRNA production resulting in decreased expression of thrombospondin-1, a latent TGF-Beta activator, leading to decreased fibrogenesis as proven by reduced levels of collagen type I(Alphal) mRNA compared to the control cultures.We then used a bile duct ligation (BDL) rat model to examine the effects of sPDGFRBeta on hepatic fibrogenesis. It is known that expression of PDGFRBeta-subunit does increase during experimental liver injury. In our model both approaches, adenovirus mediated sPDGFRBeta gene transfer and direct application of sPDGFRBeta as purified protein, significantly attenuated ongoing fibrosis in BDL rats as evidenced by reduced expression of Alpha-SMA and collagen type I(AlphaI). In conclusion, our experiments did demonstrate the potent antifibrogenetic effects of sPDGFRBeta, a PDGF antagonist, in experimentally induced liver fibrosis