The ionospheric storm studies: further development of the mapping technique

The technique of using instantaneous maps for ionospheric storm studies is further developed. Integral parameters are introduced characterizing the main features of each map. These parameters are the net volumes of ?f0F2, ?M(3000)F2and their gradients. The magnetic storm 1-2 March, 1982 was considered and it was found that before the storm commencement and in recovery phase the Net Gradient (NG) is directed steadily to the East, while in the main phase it turns southward. NG shows where the changes of the F-layer come from. The net volume of ?f0F2 (NF) correlates well with Dst and AE indices

The ionospheric storm studies: further development of the mapping technique

The technique of using instantaneous maps for ionospheric storm studies is further developed. Integral parameters are introduced characterizing the main features of each map. These parameters are the net volumes of Δf0F2, ΔM(3000)F2and their gradients. The magnetic storm 1-2 March, 1982 was considered and it was found that before the storm commencement and in recovery phase the Net Gradient (NG) is directed steadily to the East, while in the main phase it turns southward. NG shows where the changes of the F-layer come from. The net volume of Δf0F2 (NF) correlates well with Dst and AE indices

Identification of a chemical probe for family VIII bromodomains through optimization of a fragment hit

The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date. The medicinal chemistry program that led to PFI-3 from an initial fragment screening hit is described in detail, and additional analogues with differing family VIII bromodomain selectivity profiles are also reported. We also describe the full pharmacological characterization of PFI-3 as a chemical probe, along with phenotypic data on adipocyte and myoblast cell differentiation assays

Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit

The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date. The medicinal chemistry program that led to PFI-3 from an initial fragment screening hit is described in detail, and additional analogues with differing family VIII bromodomain selectivity profiles are also reported. We also describe the full pharmacological characterization of PFI-3 as a chemical probe, along with phenotypic data on adipocyte and myoblast cell differentiation assays