Assessment of the reforms and programs results of Ukraine’s economy sustainable development by means of neural networks

It is necessary to choose proper methodology and indicators for assessing sustainable economic development as the information becomes a tool for decision-making support of sustainable development policies and implementation of programs. In Ukraine, evaluating the results of implementation of different programs for development is essential as an analytical basis for making a strategy for the next period and a prerequisite for further progress. Certain shortcomings of linear models for evaluating the results appeared during the design and implementation of the strategy to manage sustainable economic development. The potential for establishing erroneous targets increases in the formation of strategic objectives for the next forecast period. There is a special need to choose adequate indicators to comprehensively approximate the factors of economic development and evaluation methods that allow more sensitively measuring the results of management decisions in the implementation of the strategy. The article evaluates the results of the Sustainable Development Strategy “Ukraine – 2020”, employing the potential of the neural network method for a flexible combination of a large number of factors in constructing nonlinear models of impact on the resulting indicator. As a result of applying the neural network model with one hidden layer for evaluation, based on 16 indicators identifying economic, social, and institutional aspects of sustainable development of Ukraine, it was found that institutional transformations contribute most to achieving sustainable development. Reforms in terms of deregulation and support of entrepreneurship, property rights protection, and competitive environment have the most significant positive impact. On the other hand, low efficiency of capital market reforms, implementation of the energy efficiency program, and reform in the field of public procurement determine the need to revise the program of their fulfilment

Business angels as an alternative to financial support at the early stages of small businesses’ life cycle

In the process of small business establishment and development, it is very important to understand both the financial needs of entrepreneurs and the main obstacles and difficulties arising in the way of financing. Alternative sources of financial support, along with traditional ones, create opportunities to increase funds, but the solution to the issue of their attraction should be based on modern effective methods and decision- making technologies. The article uses the decision tree method to determine the optimal alternative to financial support of small business at the early stages of the life cycle. The results highlight the importance of alternative source of resources for small business entities, namely business angels’ means. The empirical and statistical analysis confirms that access to alternative sources of financing for small businesses in EU countries is improving, while in Ukraine, informal financing is a rather new and underdeveloped area. Based on the analysis of the advantages of using the business angels’ funds, it was concluded that they need to implement their potential in small business of Ukraine. The results show that the decision tree method is an effective tool for deciding on the prioritization of a financial alternative to the small business, and is characterized by ease of use, forecast precision and problems solution novelty

Численый анализ двумерной задачи сверхзвуковых взаимодействий скачка уплотнения с пограничным слоем

Наведено результати числового моделювання характеру взаємодій надзвукових турбулентних течій в області нахиленої з навітряної грані сходинки для кута нахилу відносно горизонту β = 8, 25, 90° та чисел Маха M∞ = 2,9, 2,94. В якості математичної моделі використані осереднені за Рейнольдсом рівняння Нав’є-Стокса з використанням моделі турбулентності k-ω SST для в’язкого стисливого середовища. Проведено порівняльний аналіз розподілу тиску та поверхневого тертя з наявними експериментальними даними.The results of numeric modeling of the nature of supersonic turbulent flows interaction in the field of inclined from the windward side plane of the step for the canting angle β = 8, 25, 90° and Mach numbers M∞ = 2,9, 2,94. The Navier-Stokes equations averaged by Reynolds with the usage of turbulent model were used as a mathematical model k-ω SST for viscous compressed environment. Comparative analysis of the pressure distribution and surface friction with gained experimental data was held.Приведены результаты численного моделирования характера взаимодействий сверхзвуковых турбулентных течений на наклоном участке с наветренной грани ступеньки для угла наклона относительно горизонта β = 8, 25, 90° та чисел Маха M∞ = 2,9, 2,94. В качестве математической модели использованы усредненные за Рейнольдсом уравнения Навье-Стокса с использованием модели турбулентности k-ω SST для вязкой сжимаемого среды. Проведен сравнительный анализ распределения давления и поверхностного трения с имеющимися экспериментальными данными

Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk

PPARδ Activation Acts Cooperatively with 3-Phosphoinositide-Dependent Protein Kinase-1 to Enhance Mammary Tumorigenesis

Peroxisome proliferator-activated receptorδ (PPARδ) is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1). PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling

Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes. However, Tat by itself or HHV8-genes alone cannot induce angiogenesis <it>in vivo </it>unless specific proteins/enzymes are produced synchronously by different cell-types. We therefore tested a hypothesis that <it>chronic </it>HIV-<it>replication in non-endothelial cells </it>may produce novel factors that provoke angiogenic pathways.</p> <p>Methods</p> <p>Genome-wide proteins from HIV-infected and uninfected T-lymphocytes were tested by subtractive proteomics analyses at various stages of virus and cell growth <it>in vitro </it>over a period of two years. Several thousand differentially regulated proteins were identified by mass spectrometry (MS) and >200 proteins were confirmed in multiple gels. Each protein was scrutinized extensively by protein-interaction-pathways, bioinformatics, and statistical analyses.</p> <p>Results</p> <p>By functional categorization, 31 proteins were identified to be associated with various signaling events involved in angiogenesis. 88% proteins were located in the plasma membrane or extracellular matrix and >90% were found to be essential for regeneration, neovascularization and angiogenic processes during embryonic development.</p> <p>Conclusion</p> <p>Chronic HIV-infection of T-cells produces membrane receptor-PTKs, serine-threonine kinases, growth factors, adhesion molecules and many diffusible signaling proteins that have not been previously reported in HIV-infected cells. Each protein has been associated with endothelial cell-growth, morphogenesis, sprouting, microvessel-formation and other biological processes involved in angiogenesis (p = 10^-4to 10^-12). Bioinformatics analyses suggest that overproduction of PTKs and other kinases in HIV-infected cells has <it>suppressed </it>VEGF/VEGFR-PTK expression and promoted <it>VEGFR-independent </it>pathways. This unique mechanism is similar to that observed in neovascularization and angiogenesis during embryogenesis. Validation of clinically relevant proteins by gene-silencing and translational studies <it>in vivo </it>would identify specific targets that can be used for early diagnosis of angiogenic disorders and future development of inhibitors of angiopathies. This is the first comprehensive study to demonstrate that HIV-infection alone, without any co-infection or treatment, can induce numerous "embryonic" proteins and kinases capable of generating novel <it>VEGF-independent </it>angiogenic pathways.</p