Comparison of Antiplatelet Effects of Phenol Derivatives in Humans

Flavonoids are associated with positive cardiovascular effects. However, due to their low bioavailability, metabolites are likely responsible for these properties. Recently, one of these metabolites, 4-methylcatechol, was described to be a very potent antiplatelet compound. This study aimed to compare its activity with its 22 close derivatives both of natural or synthetic origin in order to elucidate a potential structure–antiplatelet activity relationship. Blood from human volunteers was induced to aggregate by arachidonic acid (AA), collagen or thrombin, and plasma coagulation was also studied. Potential toxicity was tested on human erythrocytes as well as on a cancer cell line. Our results indicated that 17 out of the 22 compounds were very active at a concentration of 40 μM and, importantly, seven of them had an IC50 on AA-triggered aggregation below 3 μM. The effects of the most active compounds were confirmed on collagen-triggered aggregation too. None of the tested compounds was toxic toward erythrocytes at 50 μM and four compounds partly inhibited proliferation of breast cancer cell line at 100 μM but not at 10 μM. Additionally, none of the compounds had a significant effect on blood coagulation or thrombin-triggered aggregation. This study hence reports four phenol derivatives (4-ethylcatechol, 4-fluorocatechol, 2-methoxy-4-ethylphenol and 3-methylcatechol) suitable for future in vivo testing.

Assessing Genotoxicity of Ten Different Engineered Nanomaterials by the Novel Semi-Automated FADU Assay and the Alkaline Comet Assay

Increased engineered nanomaterial (ENM) production and incorporation in consumer and biomedical products has raised concerns about the potential adverse effects. The DNA damaging capacity is of particular importance since damaged genetic material can lead to carcinogenesis. Consequently, reliable and robust in vitro studies assessing ENM genotoxicity are of great value. We utilized two complementary assays based on different measurement principles: (1) comet assay and (2) FADU (fluorimetric detection of alkaline DNA unwinding) assay. Assessing cell viability ruled out false-positive results due to DNA fragmentation during cell death. Potential structure–activity relationships of 10 ENMs were investigated: three silica nanoparticles (SiO2-NP) with varying degrees of porosity, titanium dioxide (TiO2-NP), polystyrene (PS-NP), zinc oxide (ZnO-NP), gold (Au-NP), graphene oxide (GO) and two multi-walled carbon nanotubes (MWNT). SiO2-NPs, TiO2-NP and GO were neither cytotoxic nor genotoxic to Jurkat E6-I cells. Quantitative interference corrections derived from GO results can make the FADU assay a promising screening tool for a variety of ENMs. MWNT merely induced cytotoxicity, while dose- and time-dependent cytotoxicity of PS-NP was accompanied by DNA fragmentation. Hence, PS-NP served to benchmark threshold levels of cytotoxicity at which DNA fragmentation was expected. Considering all controls revealed the true genotoxicity for Au-NP and ZnO-NP at early time points.

Peculiarities of formation of potential of telecommunications enterprises

The purpose of the article – to analyze the peculiarities of forming the potential of a telecommunication enterprise and to suggest ways to increase the efficiency of its use. Research methodology. In the process of preparation of the article the methods of analytical, statistical and financial analysis were used. A scientific novelty is the proposal to use effective indicators of economic efficiency of the enterprise, such as profitability, profitability, cost, return on resources, investment, etc. to assess the effectiveness of the formation and use of the potential of the telecommunications enterprise. Conclusions. 1. The study of trends in the formation of the potential of telecommunications enterprises in Ukraine has determined that the pace of its development corresponds to the basic principles and principles of the concept of economic development and strategy of information society development adopted in Ukraine. The development of the economy of telecommunications enterprises is facilitated at the state level by developing new legislation in the information and telecommunications technologies sector in Ukraine, discussing and adopting new strategies for digital transformation aimed at using big data, blockchain, cloud technologies, robotics and the Internet of Things. 2. It is determined that the potential of a telecommunications enterprise is a unity of organizational, technical and information capabilities that contribute to the preparation and adoption of management decisions and influence its development. Features of capacity building determine the following components that ensure its functioning: software and hardware; personnel; information (databases); organizational, marketing, technical, technological, etc. 3. The system of financial indicators for definition of efficiency of functioning of the formed potential of the telecommunication enterprise is offered. 4. To ensure the formation of a strong potential of the telecommunications company in the work identified a number of key measures, including the creation of information systems, ensuring its operation by special staff, information security, creating new digital products and services, e-commerce and digital marketing. business analytics and big data management, etc. Key words: telecommunication enterprises, capacity building, potential structure of telecommunication enterprise, evaluation indicators, state support.

Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish

Germline loss or mutation of one copy of the transcription factor GATA2 in humans leads to a range of clinical phenotypes affecting hematopoietic, lymphatic and vascular systems. GATA2 heterozygous mice show only a limited repertoire of the features observed in humans. Zebrafish have two copies of the Gata2 gene as a result of an additional round of ancestral whole genome duplication. These genes, Gata2a and Gata2b, show distinct but overlapping expression patterns, and between them, highlight a significantly broader range of the phenotypes observed in GATA2 deficient syndromes, than each one alone. In this manuscript, we use mutants for Gata2a and Gata2b to interrogate the effects on hematopoiesis of these two ohnologs, alone and in combination, during development in order to further define the role of GATA2 in developmental hematopoiesis. We define unique roles for each ohnolog at different stages of developmental myelopoiesis and for the emergence of hematopoietic stem and progenitor cells. These effects are not additive in the haploinsufficient state suggesting a redundancy between these two genes in hematopoietic stem and progenitor cells. Rescue studies additionally support that Gata2b can compensate for the effects of Gata2a loss. Finally we show that adults with loss of combined heterozygosity show defects in the myeloid compartment consistent with GATA2 loss in humans. These results build on existing knowledge from other models of GATA2 deficiency and refine our understanding of the early developmental effects of GATA2. In addition, these studies shed light on the complexity and potential structure-function relationships as well as sub-functionalization of Gata2 genes in the zebrafish model.

Magnetic Field Aligned Potentials as an Acceleration Mechanism at Jupiter

<p>Since arriving at Jupiter, Juno has observed instances of field-aligned proton and electron beams, in both the upward and downward current regions. These field-aligned beams are identified by inverted-V structures in plasma data, which indicate the presence of potential structures aligned with the magnetic field. The direction, magnitude and location of these potential structures is important, as it affects the characteristics of any resultant field-aligned current. At high latitudes, Juno has observed potentials of 100’s of kV occurring in both directions. Charged particles that are accelerated into Jupiter’s atmosphere and precipitate can excite aurora; likewise, particles accelerated away from the planet can contribute to the population of the magnetosphere.</p> <p>Using a time-varying 1-D spatial, 2-D velocity space Vlasov code, we examine magnetic field lines which extend from Jupiter into the middle magnetosphere. By applying and varying a potential difference at the ionosphere, we can gain insight into the effect these have on the plasma population, the potential structure, and plasma densities along the field line. Utilising a non-uniform mesh, additional resolution is applied in regions where particle acceleration occurs, allowing the spatial and temporal evolution of the plasma to be examined. Here, we present new results from our model, constrained, and compared with recent Juno observations, and examining both the upward and downward current regions.</p>

SELLING-AND-BUYING TRANSACTION PATTERNS IN A TRADITIONAL MARKET: A GENERIC STRUCTURE POTENTIAL APPROACH

This research aimed to investigate the patterns of selLing-and-buying transactions in a traditional market. The data sources of this research were the the sellers and the buyersin beef, chicken, fruit, grocery, and vegetable shopsof Pasar Waru, a traditional market, in Sidoarjo, Indonesia. The data were in the form of transactional conversations between the sellers and the buyers. Qualitative method was applied in this research by using the formula of generic structure potential theory proposed by Halliday Hasan (1985) to describe the patterns of buying-and-selling transaction in the market. The result shows that generic structure elements in some shops at Pasar Waru comprises: greeting (G), sale initiation (SI), sale enquiry (SE), sale request (SR), sale compliance (SC), sale (S), purchase (P), purchase closure (PC), and finish (F). The grocery, beef, and chicken shop had a similar structure of G^SR^SC^S^P^PC, whereas the fruit shop showed its actual structure G^SI^SE^SR^SC^S^P^PC. Meanwhile, the vegetable shop had G^SI^SR^SC^S^P^PC structure. As a whole, the five shops produced generic potential structure [(G).^] [{ SR^ SC }^S^] P^PC.

Model reduction by mean-field homogenization in viscoelastic composites. III. Dual theory

The mean-field homogenization scheme for viscoelastic composites proposed by Lahellec & Suquet (2013 Int. J. Plasticity 42, 1–13 ( doi:10.1016/j.ijplas.2012.09.005 )) is revisited from the standpoint recently adopted in a companion paper (Idiart MI et al. 2020 Proc. R. Soc. A 20200407 ( doi:10.1098/rspa.2020.0407 )). It is shown that the scheme generates a reduced-order approximation wherein the microscopic kinetics of the composite are described in terms of a finite set of macroscopic forces identified with the phase averages and intraphase covariances of the various microscopic force fields, which can be evaluated by mean-field homogenization techniques. The approximation exhibits a two-potential structure with a convex complementary energy density but a non-convex force potential. The consequential properties of the approximation are exposed and their implications are discussed. The exposition is supplemented by proofs of equivalence between the present scheme and other candidate schemes proposed in the literature for composites with elementary local rheologies of Maxwellian type.