318 research outputs found

    Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis through MafB

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    Disequilibrium between bone-forming osteoblasts and bone-resorbing osteoclasts is central to many bone diseases. Here, we show that dysregulated expression of translationally controlled isoforms of CCAAT/enhancer-binding protein beta (C/EBPbeta) differentially affect bone mass. Alternative translation initiation that is controlled by the mammalian target of rapamycin (mTOR) pathway generates long transactivating (LAP(*), LAP) and a short repressive (LIP) isoforms from a single C/EBPbeta transcript. Rapamycin, an inhibitor of mTOR signalling increases the ratio of LAP over LIP and inhibits osteoclastogenesis in wild type (WT) but not in C/EBPbeta null (c/ebpbeta(-/-)) or in LIP knock-in (L/L) osteoclast precursors. C/EBPbeta mutant mouse strains exhibit increased bone resorption and attenuated expression of MafB, a negative regulator of osteoclastogenesis. Ectopic expression of LAP and LIP in monocytes differentially affect the MafB promoter activity, MafB gene expression and dramatically affect osteoclastogenesis. These data show that mTOR regulates osteoclast formation by modulating the C/EBPbeta isoform ratio, which in turn affects osteoclastogenesis by regulating MafB expression

    Quantum Transport in a Nanosize Silicon-on-Insulator Metal-Oxide-Semiconductor

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    An approach is developed for the determination of the current flowing through a nanosize silicon-on-insulator (SOI) metal-oxide-semiconductor field-effect transistors (MOSFET). The quantum mechanical features of the electron transport are extracted from the numerical solution of the quantum Liouville equation in the Wigner function representation. Accounting for electron scattering due to ionized impurities, acoustic phonons and surface roughness at the Si/SiO2 interface, device characteristics are obtained as a function of a channel length. From the Wigner function distributions, the coexistence of the diffusive and the ballistic transport naturally emerges. It is shown that the scattering mechanisms tend to reduce the ballistic component of the transport. The ballistic component increases with decreasing the channel length.Comment: 21 pages, 8 figures, E-mail addresses: [email protected]

    Banking union in historical perspective: the initiative of the European Commission in the 1960s-1970s

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    This article shows that planning for the organization of EU banking regulation and supervision did not just appear on the agenda in recent years with discussions over the creation of the eurozone banking union. It unveils a hitherto neglected initiative of the European Commission in the 1960s and early 1970s. Drawing on extensive archival work, this article explains that this initiative, however, rested on a number of different assumptions, and emerged in a much different context. It first explains that the Commission's initial project was not crisis-driven; that it articulated the link between monetary integration and banking regulation; and finally that it did not set out to move the supervisory framework to the supranational level, unlike present-day developments
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