403 research outputs found

    Comparative Assessment of the Factors and Conditions of the Formation of the Neoindustrial Social State in Russia and Germany

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    Russia and Germany are traditionally reputed as countries with socially oriented economies. Namely, these countries are also close by the index of the share of real sector of economy at GDP. And however, Germany is a founder of social market household largely defined its leadership in world economy, in current conditions of crisis of “the state of general welfare” the search of a new model of development for Germany is also important as for Russia stood on the way of modernization and neo-industrialization. In the article, the hypothesis about forming of the new model of development uniting the social orientation of economy, processes of neoindustrialization, and globalization is made. At the same time, the social orientation is the main aim of socio-economic development, neo-industrialization is a way to achieve it, and globalization is a criterion presupposing more effective use of resources. Theoretical backgrounds of development of “social state” are generalized in the works of German and Russian classics put the backgrounds of economic humanism, it has allowed to prove the fatality of modernization process without considering of deep mental backgrounds and civilization codes of the nation development. The methodological approaches to development of a new model of neo-industrial social state with emphasizing different levels: global, national, local, individual are worked out; and the technique for estimation of factors and conditions of its development is proposed. The technique is tested on the example of Russia and Germany. The comparative analysis conducted has allowed to make the conclusion about similarity of target guidelines, initial conditions, problems and ways of their solving in these countries, that is to be considered both in a strategy and a policy of socio-economic development of these countries and by their international partnership

    Fractal scaling of apparent soil moisture estimated from vertical planes of Vertisol pit images

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    Image analysis could be a useful tool for investigating the spatial patterns of apparent soil moisture at multiple resolutions. The objectives of the present work were (i) to define apparent soil moisture patterns from vertical planes of Vertisol pit images and (ii) to describe the scaling of apparent soil moisture distribution using fractal parameters. Twelve soil pits (0.70 m long × 0.60 m width × 0.30 m depth) were excavated on a bare Mazic Pellic Vertisol. Six of them were excavated in April/2011 and six pits were established in May/2011 after 3 days of a moderate rainfall event. Digital photographs were taken from each Vertisol pit using a Kodak™ digital camera. The mean image size was 1600 × 945 pixels with one physical pixel ≈373 μm of the photographed soil pit. Each soil image was analyzed using two fractal scaling exponents, box counting (capacity) dimension (DBC) and interface fractal dimension (Di), and three prefractal scaling coefficients, the total number of boxes intercepting the foreground pattern at a unit scale (A), fractal lacunarity at the unit scale (Λ1) and Shannon entropy at the unit scale (S1). All the scaling parameters identified significant differences between both sets of spatial patterns. Fractal lacunarity was the best discriminator between apparent soil moisture patterns. Soil image interpretation with fractal exponents and prefractal coefficients can be incorporated within a site-specific agriculture toolbox. While fractal exponents convey information on space filling characteristics of the pattern, prefractal coefficients represent the investigated soil property as seen through a higher resolution microscope. In spite of some computational and practical limitations, image analysis of apparent soil moisture patterns could be used in connection with traditional soil moisture sampling, which always renders punctual estimate

    Molecular analysis of two novel missense mutations in the GDF5 proregion that reduce protein activity and are associated with brachydactyly type C

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    Growth and differentiation factor 5 (GDF5) plays a central role in bone and cartilage development by regulating the proliferation and differentiation of chondrogenic tissue. GDF5 is synthesized as a preproprotein. The biological function of the proregion comprising 354 residues is undefined. We identified two families with a heterozygosity for the novel missense mutations p.T201P or p.L263P located in the proregion of GDF5. The patients presented with dominant brachydactyly type C characterized by the shortening of skeletal elements in the distal extremities. Both mutations gave rise to decreased biological activity in in vitro analyses. The variants reduced the GDF5-induced activation of SMAD signaling by the GDF5 receptors BMPR1A and BMPR1B. Ectopic expression in micromass cultures yielded relatively low protein levels of the variants and showed diminished chondrogenic activity as compared to wild-type GDF5. Interestingly, stimulation of micromass cells with recombinant human proGDF5(T201P) and proGDF5(L263P) revealed their reduced chondrogenic potential compared to the wild-type protein. Limited proteolysis of the mutant recombinant proproteins resulted in a fragment pattern profoundly different from wild-type proGDF5. Modeling of a part of the GDF5 proregion into the known three-dimensional structure of TGFbeta1 latency-associated peptide revealed that the homologous positions of both mutations are conserved regions that may be important for the folding of the mature protein or the assembly of dimeric protein complexes. We hypothesize that the missense mutations p.T201P and p.L263P interfere with the protein structure and thereby reduce the amount of fully processed, biologically active GDF5, finally causing the clinical loss of function phenotype

    Visualizing brain inflammation with a shingled-leg radio-frequency head probe for (19)F/(1)H MRI

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    Magnetic resonance imaging (MRI) provides the opportunity of tracking cells in vivo. Major challenges in dissecting cells from the recipient tissue and signal sensitivity constraints albeit exist. In this study, we aimed to tackle these limitations in order to study inflammation in autoimmune encephalomyelitis. We constructed a very small dual-tunable radio frequency (RF) birdcage probe tailored for (19)F (fluorine) and (1)H (proton) MR mouse neuroimaging. The novel design eliminated the need for extra electrical components on the probe structure and afforded a uniform -field as well as good SNR. We employed fluorescently-tagged (19)F nanoparticles and could study the dynamics of inflammatory cells between CNS and lymphatic system during development of encephalomyelitis, even within regions of the brain that are otherwise not easily visualized by conventional probes. (19)F/(1)H MR Neuroimaging will allow us to study the nature of immune cell infiltration during brain inflammation over an extensive period of time

    Small Changes in the Primary Structure of Transportan 10 Alter the Thermodynamics and Kinetics of its Interaction with Phospholipid Vesicles

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    ABSTRACT: The kinetics and thermodynamics of binding of transportan 10 (tp10) and four of its variants to phospholipid vesicles, and the kinetics of peptide-induced dye efflux, were compared. Tp10 is a 21-residue, amphipathic, cationic, cell-penetrating peptide similar to helical antimicrobial peptides. The tp10 variants examined include amidated and free peptides, and replacements of tyrosine by tryptophan. Carboxy-terminal amidation or substitution of tryptophan for tyrosine enhance binding and activity. The Gibbs energies of peptide binding to membranes determined experimentally and calculated from the interfacial hydrophobicity scale are in good agreement. The Gibbs energy for insertion into the bilayer core was calculated using hydrophobicity scales of residue transfer from water to octanol and to the membrane/ water interface. Peptide-induced efflux becomes faster as the Gibbs energies for binding and insertion of the tp10 variants decrease. If anionic lipids are included, binding and efflux rate increase, as expected because all tp10 variants are cationic and an electrostatic component is added. Whether the most important effect of peptide amidation is the change in charge or an enhancement of helical structure, however, still needs to be established. Nevertheless, it is clear that the changes in efflux rate reflect the differences in the thermodynamics of binding and insertion of the free and amidated peptide groups. We have recently reported a detailed investigation (1) o

    Effects of maternal modafinil treatment on fetal development and neonatal growth parameters — a multicenter case series of the European Network of Teratology Information Services (ENITS)

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    \ua9 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.Objective: In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. Method: Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. Results: One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%–84.8%), 9.3% (95% CI, 5.0%–16.9%), and 13.9% (95% CI, 8.1%–23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%–6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of −0.28 SDS (95% CI, −0.45 to −0.10) for BW and of −0.28 SDS (95% CI, −0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. Conclusion: The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy

    Side Chain Hydrophobicity Modulates Therapeutic Activity and Membrane Selectivity of Antimicrobial Peptide Mastoparan-X

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    The discovery of new anti-infective compounds is stagnating and multi-resistant bacteria continue to emerge, threatening to end the "antibiotic era". Antimicrobial peptides (AMPs) and lipo-peptides such as daptomycin offer themselves as a new potential class of antibiotics; however, further optimization is needed if AMPs are to find broad use as antibiotics. In the present work, eight analogues of mastoparan-X (MPX) were investigated, having side chain modifications in position 1, 8 and 14 to modulate peptide hydrophobicity. The self-association properties of the peptides were characterized, and the peptide-membrane interactions in model membranes were compared with the bactericidal and haemolytic properties. Alanine substitution at position 1 and 14 resulted in higher target selectivity (red blood cells versus bacteria), but also decreased bactericidal potency. For these analogues, the gain in target selectivity correlated to biophysical parameters showing an increased effective charge and reduction in the partitioning coefficient for membrane insertion. Introduction of an unnatural amino acid, with an octyl side chain by amino acid substitution, at positions 1, 8 and 14 resulted in increased bactericidal potency at the expense of radically reduced membrane target selectivity. Overall, optimized membrane selectivity or bactericidal potency was achieved by changes in side chain hydrophobicity of MPX. However, enhanced potency was achieved at the expense of selectivity and vice versa in all cases

    Dynamic Surface Activity by Folding and Unfolding an Amphiphilic α-Helix

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    We describe a rationally designed peptide with tunable surface activity, where the dynamics of surface activity are an outcome of helical folding. Our rationally designed model peptide is surface-active only as an α-helix. We apply circular dichroism to show that the folded population can be controlled with changes in electrolyte concentration, and we apply pendant bubble tensiometry to explore dynamic surfactant activity. This study shows a peptide that responds to environmental stimuli with dynamic folding and surface activity. Extending this concept to selective binding peptides will lead to new tools, where dynamic surface activity is coupled to targeted binding
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