45 research outputs found

    Requirement for a Uroplakin 3a-like protein in the development of zebrafish pronephric tubule epithelial cell function, morphogenesis, and polarity

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    Uroplakin (UP)3a is critical for urinary tract development and function; however, its role in these processes is unknown. We examined the function of the UP3a-like protein Upk3l, which was expressed at the apical surfaces of the epithelial cells that line the pronephric tubules (PTs) of the zebrafish pronephros. Embryos treated with upk3l-targeted morpholinos showed decreased pronephros function, which was attributed to defects in PT epithelial cell morphogenesis and polarization including: loss of an apical brush border and associated phospho-ERM proteins, apical redistribution of the basolateral Na+/K+-ATPase, and altered or diminished expression of the apical polarity complex proteins Prkcz (atypical protein kinase C zeta) and Pard3 (Par3). Upk3l missing its C-terminal cytoplasmic domain or containing mutations in conserved tyrosine or proline residues did not rescue, or only partially rescued the effects of Upk3l depletion. Our studies indicate that Upk3l promotes epithelial polarization and morphogenesis, likely by forming or stimulating interactions with cytoplasmic signaling or polarity proteins, and that defects in this process may underlie the pathology observed in UP3a knockout mice or patients with renal abnormalities that result from altered UP3a expression. © 2012 Mitra et al

    Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents

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    Activitat antibiòtica; Ribosoma bacterià; Simulacions de dinàmica molecularActividad antibiótica; Ribosoma bacteriano; Simulaciones de dinámica molecularAntibiotic activity; Bacterial ribosome; Molecular dynamics simulationsIn the current work, in continuation of our recent research, we synthesized and studied new chimeric compounds, including the ribosome-targeting antibiotic chloramphenicol (CHL) and the membrane-penetrating cation triphenylphosphonium (TPP), which are linked by alkyl groups of different lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compounds bind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar to that of the parent CHL, and significantly reduce membrane potential. Similar to CAM-C4-TPP, the mode of action of CAM-C10-TPP and CAM-C14-TPP in bacterial ribosomes differs from that of CHL. By simulating the dynamics of CAM-Cn-TPP complexes with bacterial ribosomes, we proposed a possible explanation for the specificity of the action of these analogs in the translation process. CAM-C10-TPP and CAM-C14-TPP more strongly inhibit the growth of the Gram-positive bacteria, as compared to CHL, and suppress some CHL-resistant bacterial strains. Thus, we have shown that TPP derivatives of CHL are dual-acting compounds targeting both the ribosomes and cellular membranes of bacteria. The TPP fragment of CAM-Cn-TPP compounds has an inhibitory effect on bacteria. Moreover, since the mitochondria of eukaryotic cells possess qualities similar to those of their prokaryotic ancestors, we demonstrate the possibility of targeting chemoresistant cancer cells with these compounds.This research was funded by RFBR [grants 20-04-00873 to N.V.S. (synthesis of analogs, binding assays, in vitro translation), 20-015-00537 to P.A.N. (potential measurement, screening of TolC-containing transporters), and 20-54-76002 to I.A.O. (toeprinting and in vitro translation)], President grant MD 2626.2021.1.4 to I.A.O. (bacteria inhibition assays), grants from the Instituto de Salud Carlos III: PI17/02087 to A.L. (cancer cell proliferation assays) by the Ministry of Science and Higher Education of the Russian Federation [grant FENU-2020-0019 to G.I.M. (molecular dynamics simulations)] and by the Government of the Russian Federation [No. AAAA-A17-117120570004-6 to A.A.B.]

    О ПРОМЫШЛЕННОЙ БЕЗОПАСНОСТИ В МОСТОСТРОЕНИИ

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    Industrial safety system evolved on the railways for decades. In new economic conditions, many of its basic principles remain, but also those factors have arisen that require scientific analysis, experimental verification, modern technical and technological means. At the example of construction and maintenance of bridgeworks, the authors examine and evaluate the situation with safety, injury rate, fire hazard in railway transport.Система промышленной безопасности складывалась на железных дорогах десятилетиями. В новых экономических условиях многие ее базовые принципы сохранились, но появились и те факторы, которые требуют научного анализа, экспериментальной проверки, современных технико-технологических средств. На примере строительства и обслуживания мостовых сооружений авторы исследуют и оценивают ситуацию с безопасностью труда, травматизмом, пожароопасностью на объектах железнодорожного транспорта

    Investigation of the Deformation Activation Volume of an Ultrafinegrained Ti50Ni50 Alloy

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    © 2015 Springer Science+Business Media New York The mechanical properties, strain rate sensitivity (m) and deformation activation volume (ΔV) are investigated at the experimental temperatures from 20 to 400°С in a Ti50Ni50alloy in a coarse-grained (CG) state with the austenite grain size D = 200 μm and in an ultrafine-grained (UFG) state with D = 700 μm following an ECAP treatment. It is observed that this treatment improves the yield strength of the alloy compared to its CG-state. The strain rate sensitivity, m, is found to be by a factor of 1.5–2 higher than that of CG-specimens; it increases with the temperature in both states of the material. As the temperature of the material in tension increases up to Т = 150–250°С, parameter ΔV increases to its maximum and with a further growth of the experimental temperature to 400°С, parameter ΔV decreases. The deformation activation volume of the alloy in the UFG-state is by a factor of 2–4 larger than that in the CG-state for the same experimental temperatures

    О ПОЖАРООПАСНОСТИ ДРЕВЕСИНЫ ПРИ ВОЗВЕДЕНИИ МОСТОВ

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    Successful construction and operation of bridges both depend on many factors. One of them is fire protection of bridgeworks and structures , that requires proper use of timber and other inflammable materials.Успешность строительства  и эксплуатации мостов зависит  от многих факторов. Один из них –  пожарная защита конструкции  и элементов сооружения, которая  связана в том числе и с грамотным  использованием строительной  древесины и других горючих  материалов

    EXCESSIVE MORTALITY IN WINTER IN MOSCOW AND ITS ECONOMIC VALUE DURING THE YEARS 2007-2014

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    Aim. To study the excessive mortality during the winter (EMW) from all causes and CVD, monthly values of mortality; to evaluate social and economic harm due to EMW in Moscow.Material and methods. The calculation of EMW (%) was done for Moscow by the mortality from all causes and from CVD by a special equation. For monthly values of mortality we estimated the average range per month by absolute number of the deaths — absolute parameters of mortality by every analyzed year were ranged from 1 to 12, and mean value of the range was calculated.Results. Mean EMW per 8 years was 5,1%, for CVD higher — 8,8%. In Moscow there is an influence of the anomaly heat of 2010 — EMW was 4,5% from all causes, from CVD — 6,0%. Maximum number of deaths was registered in January and march. Gross EH by 2007-2013 from EMW was 7,9 billion rubles in Moscow.Conclusion. A significant part of EMW are the deaths from CVD. The amount of EH from EMW has confirmed the shown previously relation from two factors — number of deaths and size of GRP in region. For Moscow — the capital of Russia, having the highest values of economic development, the harm, that is quite significant, grounds the necessity of investments into excessive mortality and search for effective by decrease of mortality in winter time

    Experimental Tests of Neutron Shielding for the ATLAS Forward Region

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    Experimental tests devoted to the optimization of the neutron shielding for the ATLAS forward region were performed at the CERN-PS with a 4 GeV/c proton beam. Spectra of fast neutrons, slow neutrons and gamma rays escaping a block of iron (40×\times40×\times80 cm3^3) shielded with different types of neutron and gamma shields (pure polyethylene - PE, borated polyethylene - BPE, lithium filled polyethylene - LiPE, lead, iron) were measured by means of plastic scintillators, a Bonner spectrometer, a HPGe detector and a slow neutron detector. Effectiveness of different types of shielding agaisnt neutrons and γ\gamma-rays were compared. The idea of a segmented outer layer shielding (iron, BPE, iron, LiPE) for the ATLAS Forward Region was also tested

    Investigation of the Deformation Activation Volume of an Ultrafinegrained Ti50Ni50 Alloy

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    © 2015 Springer Science+Business Media New York The mechanical properties, strain rate sensitivity (m) and deformation activation volume (ΔV) are investigated at the experimental temperatures from 20 to 400°С in a Ti50Ni50alloy in a coarse-grained (CG) state with the austenite grain size D = 200 μm and in an ultrafine-grained (UFG) state with D = 700 μm following an ECAP treatment. It is observed that this treatment improves the yield strength of the alloy compared to its CG-state. The strain rate sensitivity, m, is found to be by a factor of 1.5–2 higher than that of CG-specimens; it increases with the temperature in both states of the material. As the temperature of the material in tension increases up to Т = 150–250°С, parameter ΔV increases to its maximum and with a further growth of the experimental temperature to 400°С, parameter ΔV decreases. The deformation activation volume of the alloy in the UFG-state is by a factor of 2–4 larger than that in the CG-state for the same experimental temperatures

    Investigation of the Deformation Activation Volume of an Ultrafinegrained Ti50Ni50 Alloy

    No full text
    © 2015 Springer Science+Business Media New York The mechanical properties, strain rate sensitivity (m) and deformation activation volume (ΔV) are investigated at the experimental temperatures from 20 to 400°С in a Ti50Ni50alloy in a coarse-grained (CG) state with the austenite grain size D = 200 μm and in an ultrafine-grained (UFG) state with D = 700 μm following an ECAP treatment. It is observed that this treatment improves the yield strength of the alloy compared to its CG-state. The strain rate sensitivity, m, is found to be by a factor of 1.5–2 higher than that of CG-specimens; it increases with the temperature in both states of the material. As the temperature of the material in tension increases up to Т = 150–250°С, parameter ΔV increases to its maximum and with a further growth of the experimental temperature to 400°С, parameter ΔV decreases. The deformation activation volume of the alloy in the UFG-state is by a factor of 2–4 larger than that in the CG-state for the same experimental temperatures

    Investigation of the Deformation Activation Volume of an Ultrafinegrained Ti50Ni50 Alloy

    Get PDF
    © 2015 Springer Science+Business Media New York The mechanical properties, strain rate sensitivity (m) and deformation activation volume (ΔV) are investigated at the experimental temperatures from 20 to 400°С in a Ti50Ni50alloy in a coarse-grained (CG) state with the austenite grain size D = 200 μm and in an ultrafine-grained (UFG) state with D = 700 μm following an ECAP treatment. It is observed that this treatment improves the yield strength of the alloy compared to its CG-state. The strain rate sensitivity, m, is found to be by a factor of 1.5–2 higher than that of CG-specimens; it increases with the temperature in both states of the material. As the temperature of the material in tension increases up to Т = 150–250°С, parameter ΔV increases to its maximum and with a further growth of the experimental temperature to 400°С, parameter ΔV decreases. The deformation activation volume of the alloy in the UFG-state is by a factor of 2–4 larger than that in the CG-state for the same experimental temperatures
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