213 research outputs found

    The location of U.S. sugarbeet production

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    Cover title.Includes bibliographical references (pages 193-207)

    "Антропологизация" как фактор проблематизации в познании

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    Рассматривается процесс антропологизации познания через способы проблематизации знания. Делается вывод, что онтологический плюрализм требует соответствующего способа совмещения разных начал, проблематизация которых осуществляется на основе способностей человека познавать мир. Принцип дополнительности и антропный принцип выражают указанные особенности проблематизации знаний человека

    Endothelin-1 enhances β2-adrenoceptor gene transcription in human lung fibroblasts

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    AbstractAimsThe present study aimed to explore possible effects of endothelin-1 (ET-1) on ß2-adrenoceptor gene transcription in human lung fibroblasts.Main methodsMRC-5 human lung fibroblasts were cultured in absence or presence of test substances, followed by ß2-adrenoceptor mRNA determination by quantitative real time PCR.Key findingsET-1 caused a marked and rapid in onset (1hr) increase in β2-adrenoceptor mRNA, an effect additive to that of short time (1hr) exposure to the β2-adrenoceptor agonist olodaterol. The stimulatory effect of ET-1 on β2-adrenoceptor mRNA was prevented by the non-selective ET-A/ET-B receptor antagonist bosentan, indicating that it was mediated via specific ET receptors. In the presence of actinomycin D the effect of ET-1 was prevented indicating that ET-1 acts via increased transcription of the β2-adrenoceptor gene. ET-1-induced up-regulation of β2-adrenoceptor mRNA was also seen in the presence of cycloheximide excluding indirect effects via up-regulation of other regulatory proteins.ConclusionsET-1 can up-regulate β-adrenoceptor gene transcription in human lung fibroblasts

    Shifting new media: from content to consultancy, from heterarchy to hierarchy

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    This is a detailed case history of one of London’s iconic new media companies, AMX Studios. Some of the changes in this firm, we assume, are not untypical for other firms in this sector. Particularly we want to draw attention to two transformations. The first change in AMX and in London’s new media industry more generally refers to the field of industrial relations. What can be observed is a shift from a rather heterarchical towards a more hierarchical organized new media industry, a shift from short-term project networks to long-term client dependency. The second change refers to new media products and services. We want to argue for a shift from cool content production towards consultancy and interactive communications solutions

    Relationship between solidification microstructure and hot cracking susceptibility for continuous casting of low-carbon and high-strength low-alloyed steels: A phase-field study

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    © The Minerals, Metals & Materials Society and ASM International 2013Hot cracking is one of the major defects in continuous casting of steels, frequently limiting the productivity. To understand the factors leading to this defect, microstructure formation is simulated for a low-carbon and two high-strength low-alloyed steels. 2D simulation of the initial stage of solidification is performed in a moving slice of the slab using proprietary multiphase-field software and taking into account all elements which are expected to have a relevant effect on the mechanical properties and structure formation during solidification. To account for the correct thermodynamic and kinetic properties of the multicomponent alloy grades, the simulation software is online coupled to commercial thermodynamic and mobility databases. A moving-frame boundary condition allows traveling through the entire solidification history starting from the slab surface, and tracking the morphology changes during growth of the shell. From the simulation results, significant microstructure differences between the steel grades are quantitatively evaluated and correlated with their hot cracking behavior according to the Rappaz-Drezet-Gremaud (RDG) hot cracking criterion. The possible role of the microalloying elements in hot cracking, in particular of traces of Ti, is analyzed. With the assumption that TiN precipitates trigger coalescence of the primary dendrites, quantitative evaluation of the critical strain rates leads to a full agreement with the observed hot cracking behavior. © 2013 The Minerals, Metals & Materials Society and ASM International

    (Phospho)proteomic profiling of microsatellite unstable CRC cells reveals alterations in nuclear signaling and cholesterol metabolism caused by frameshift mutation of NMD regulator UPF3A

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    DNA mismatch repair-deficient colorectal cancers (CRCs) accumulate numerous frameshift mutations at repetitive sequences recognized as microsatellite instability (MSI). When coding mononucleotide repeats (cMNRs) are affected, tumors accumulate frameshift mutations and premature termination codons (PTC) potentially leading to truncated proteins. Nonsense-mediated RNA decay (NMD) can degrade PTC-containing transcripts and protect from such faulty proteins. As it also regulates normal transcripts and cellular physiology, we tested whether NMD genes themselves are targets of MSI frameshift mutations. A high frequency of cMNR frameshift mutations in the UPF3A gene was found in MSI CRC cell lines (67.7%), MSI colorectal adenomas (55%) and carcinomas (63%). In normal colonic crypts, UPF3A expression was restricted to single chromogranin A-positive cells. SILAC-based proteomic analysis of KM12 CRC cells revealed UPF3A-dependent down-regulation of several enzymes involved in cholesterol biosynthesis. Furthermore, reconstituted UPF3A expression caused alterations of 85 phosphosites in 52 phosphoproteins. Most of them (38/52, 73%) reside in nuclear phosphoproteins involved in regulation of gene expression and RNA splicing. Since UPF3A mutations can modulate the (phospho)proteomic signature and expression of enzymes involved in cholesterol metabolism in CRC cells, UPF3A may influence other processes than NMD and loss of UPF3A expression might provide a growth advantage to MSI CRC cells
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