1,901 research outputs found

    Evaluation of innovation activities of small and medium-sized businesses in Slovak Republic

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    The aim of the presented paper is to contribute to the discussion on innovation activities of small and medium-sized businesses of the Slovak Republic and the European Union. It is based on the results of research carried out by the National Agency for the Development of Small and Medium Enterprises (NADSME), where the focus was on the innovation capacity of small and medium firms in Slovakia. And it was complemented by the results of an analysis of firms’ innovation activities in the Banská Bystrica region carried out within the project “Regional Innovation Strategy of the Banska Bystrica Regionâ€.Innovation, innovation activities, small and medium-sized businesses., Research and Development/Tech Change/Emerging Technologies, O31, O32,

    Characterization of dental tissue derived stem cells

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    Stem cells (SCs) are undifferentiated cells that are capable to differentiate into more specialized cells with specific functions. Oral tissues, which are easily accessible for dentists are a rich source of stem cells. The isolation of stem cells from these location may still not be convenient, because most of them requires surgical procedures, tooth or pulp extraction. Furthermore, these SCs are present in small quantities and can therefore be difficult to isolate, purify and homogenously expand them

    Homocystene and human astrocytes

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    Astrocytes are multipotent and serve surprisingly large and diverse variety of functions, providing for the overall brain homeostasis, assisting in neurogenesis, determining the microarchitecture of the grey matter, and defending the brain through evolutionary conserved astrogliosis programs. Astrocytes are specifically involved in various neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, and various forms of dementia. Homocysteine is a nonessential sulphur-containing amino acid that had been linked with neurodegenerative diseases and aging

    A Three-Site Mechanism for Agonist/Antagonist Selective Binding to Vasopressin Receptors

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    Molecular-dynamics simulations with metadynamics enhanced sampling reveal three distinct binding sites for arginine vasopressin (AVP) within its V2 -receptor (V2 R). Two of these, the vestibule and intermediate sites, block (antagonize) the receptor, and the third is the orthosteric activation (agonist) site. The contacts found for the orthosteric site satisfy all the requirements deduced from mutagenesis experiments. Metadynamics simulations for V2 R and its V1a R-analog give an excellent correlation with experimental binding free energies by assuming that the most stable binding site in the simulations corresponds to the experimental binding free energy in each case. The resulting three-site mechanism separates agonists from antagonists and explains subtype selectivity

    The Perception of Governmental Support in The Context of Competitiveness of SMEs in the Czech Republic

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    Whether or not an entrepreneur develops the enterprise successfully and increases competitiveness depends on many factors. All businesses, however, are inherently connected with the business environment which significantly influences their performance. In this regard, the state is among the most important factors. It also performs many other roles through which it may be either helpful or harmful in the eyes of a business owner, e.g. it determines the legislative framework of entrepreneurship, sets conditions for starting a business and regulates competition. The way the role of the state is perceived by small and medium-sized enterprises was researched in 2015 as a part of a project at Tomas Bata University in Zlín. The research analysed data from 1,141 respondents from all regions of the Czech Republic and included, among others, the question of the state’s role in the business environment. The presented paper covers three selected areas of the state’s influence on the business environment: creating favourable conditions for the business environment, governmental financial support of entrepreneurs, and administrative burden on entrepreneurs. These areas were also examined with the emphasis on the analysis of differences between the perception of entrepreneurs from different industries and entrepreneurs with different sizes of their businesses. It was revealed that entrepreneurs were very critical to the state’s role in the business environment; in particular, 60% of respondents disagree with the fact that the state creates favourable conditions for business in the Czech Republic. It was proved that the line of business of enterprises correlates with perception of the state’s role within the business environment. The research into perception of a governmental financial support was proved to be dependent on a company size which may signal the support of certain company sizes and influencing their competitiveness

    Annexin A5 D226K structure and dynamics: identification of a molecular switch for the large-scale conformational change of domain III

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    AbstractThe domain III of annexin 5 undergoes a Ca2+- and a pH-dependent conformational transition of large amplitude. Modeling of the transition pathway by computer simulations suggested that the interactions between D226 and T229 in the IIID–IIIE loop on the one hand and the H-bond interactions between W187 and T224 on the other hand, are important in this process [Sopkova et al. (2000) Biochemistry 39, 14065–14074]. In agreement with the modeling, we demonstrate in this work that the D226K mutation behaves as a molecular switch of the pH- and Ca2+-mediated conformational transition. In contrast, the hydrogen bonds between W187 and T224 seem marginal

    First Synthesis of Racemic Trans Propargylamino-Donepezil, a Pleiotrope Agent Able to Both Inhibit AChE and MAO-B, with Potential Interest against Alzheimer’s Disease

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    Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease towards which pleiotropic approach using Multi-Target Directed Ligands is nowadays recognized as probably convenient. Among the numerous targets which are today validated against AD, acetylcholinesterase (ACh) and Monoamine Oxidase-B (MAO-B) appear as particularly convincing, especially if displayed by a sole agent such as ladostigil, currently in clinical trial in AD. Considering these results, we wanted to take benefit of the structural analogy lying in donepezil (DPZ) and rasagiline, two indane derivatives marketed as AChE and MAO-B inhibitors, respectively, and to propose the synthesis and the preliminary in vitro biological characterization of a structural compromise between these two compounds, we called propargylaminodonepezil (PADPZ). The synthesis of racemic trans PADPZ was achieved and its biological evaluation established its inhibitory activities towards both (h)AChE (IC50 = 0.4 uM) and (h)MAO-B (IC50 = 6.4 uM)

    Characterization of dental tissue derived stem cells

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    Stem cells (SCs) are undifferentiated cells that are capable to differentiate into more specialized cells with specific functions. Oral tissues, which are easily accessible for dentists are a rich source of stem cells. The isolation of stem cells from these location may still not be convenient, because most of them requires surgical procedures, tooth or pulp extraction. Furthermore, these SCs are present in small quantities and can therefore be difficult to isolate, purify and homogenously expand them

    Conformation and dynamics of human urotensin II and urotensin related peptide in aqueous solution

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    Conformation and dynamics of the vasoconstrictive peptides human urotensin II (UII) and urotensin related peptide (URP) have been investigated by both unrestrained and enhanced-sampling molecular-dynamics (MD) simulations and NMR spectroscopy. These peptides are natural ligands of the G-protein coupled urotensin II receptor (UTR) and have been linked to mammalian pathophysiology. UII and URP cannot be characterized by a single structure but exist as an equilibrium of two main classes of ring conformations, <i>open</i> and <i>folded</i>, with rapidly interchanging subtypes. The <i>open</i> states are characterized by turns of various types centered at K<sup>8</sup>Y<sup>9</sup> or F<sup>6</sup>W<sup>7</sup> predominantly with no or only sparsely populated transannular hydrogen bonds. The <i>folded</i> conformations show multiple turns stabilized by highly populated transannular hydrogen bonds comprising centers F<sup>6</sup>W<sup>7</sup>K<sup>8</sup> or W<sup>7</sup>K<sup>8</sup>Y<sup>9</sup>. Some of these conformations have not been characterized previously. The equilibrium populations that are experimentally difficult to access were estimated by replica-exchange MD simulations and validated by comparison of experimental NMR data with chemical shifts calculated with density-functional theory. UII exhibits approximately 72% <i>open</i>:28% <i>folded</i> conformations in aqueous solution. URP shows very similar ring conformations as UII but differs in an <i>open:folded</i> equilibrium shifted further toward <i>open</i> conformations (86:14) possibly arising from the absence of folded N-terminal tail-ring interaction. The results suggest that the different biological effects of UII and URP are not caused by differences in ring conformations but rather by different interactions with UTR
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