Modulation of the acetylation state of histones plays a pivotal role in the regulation of gene expression. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysines near the N termini of histones. This reaction promotes the condensation of chromatin, leading to repression of transcription. HDAC deregulation has been linked to several types of cancer, suggesting a potential use for HDAC inhibitors in oncology. Here we describe the first crystal structures of a human HDAC: the structures of human HDAC8 complexed with four structurally diverse hydroxamate inhibitors. This work sheds light on the catalytic mechanism of the HDACs, and on differences in substrate specificity across the HDAC family. The structure also suggests how phosphorylation of Ser39 affects HDAC8 activity.
We describe and review the current state of the art in atomic fountain clocks. These clocks provide the best realization of the SI second possible today, with relative uncertainties of a few parts in 10 16. Magnetic shields C-field coil Vacuum tank Ramsey cavity State-selection cavity Caesium reservoir to pump and window Detection zone
The uncertainty evaluation of CSF2, the second caesium fountain primary frequency standard at PTB, is presented. The fountain uses optical molasses to cool atoms down to 0.6 μK. The atoms are launched vertically in a moving optical molasses, and state-selected in the |F = 3, m F = 0 hyperfine ground state. During their ballistic flight, the atoms interact twice with a microwave field, thus completing the Ramsey interaction. With a launch height of 36.5 cm above the cavity center, the central Ramsey fringe has a width of 0.9 Hz. About 3 × 10 4 atoms, 30% of the initial number in the |F = 3, m F = 0 state, are detected after their second interaction with the microwave field. Stabilizing the microwave frequency to the center of the central Ramsey fringe, a typical relative frequency instability of 2.5 × 10 −13 (τ /s) −1/2 is obtained. The CSF2 systematic uncertainty for realizing the SI second is estimated as 0.80 × 10 −15. First comparisons with the fountain CSF1 at the Physikalisch-Technische Bundesanstalt and other fountain frequency standards worldwide demonstrate agreement within the stated uncertainties.
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