Jet disc coupling in black hole binaries

In the last decade multi-wavelength observations have demonstrated the importance of jets in the energy output of accreting black hole binaries. The observed correlations between the presence of a jet and the state of the accretion flow provide important information on the coupling between accretion and ejection processes. After a brief review of the properties of black hole binaries, I illustrate the connection between accretion and ejection through two particularly interesting examples. First, an INTEGRAL observation of Cygnus X-1 during a 'mini-' state transition reveals disc jet coupling on time scales of orders of hours. Second, the black hole XTEJ1118+480 shows complex correlations between the X-ray and optical emission. Those correlations are interpreted in terms of coupling between disc and jet on time scales of seconds or less. Those observations are discussed in the framework of current models.Comment: Invited talk at the Fifth Stromlo Symposium: Disks, Winds & Jets - from Planets to Quasars. Accepted for publication in Astrophysics & Space Scienc

von Willebrand factor antigen compared with other factors in vasculitic syndromes.

In order to analyse their role as a specific marker of vascular damage and their value in monitoring disease activity the plasma concentrations of von Willebrand factor antigen (vWFAg) and the ristocetin cofactor (RiCoF) activities were determined in 43 children with vasculitis and 20 controls. These patients were sub-divided into three groups according to diagnosis: Henoch-Schönlein purpura (n = 18), polyarteritis nodosa (n = 16), and systemic lupus erythematosus (n = 9). High concentrations of vWFAg and activities of RiCoF were found in all the patient groups. vWFAg and RiCoF returned to normal as the patients became symptom free and remained above normal in those with continuing symptoms. The amount of vWFAg did not correlate with the acute phase reactants. vWFAg acted as a specific marker of vascular damage and was useful for the monitoring of disease activity both in small vessel vasculitis and systemic necrotising arteritis

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission

To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P. falciparum SCID mouse model. The series targets both merozoite egress and erythrocyte invasion, but crucially, also blocks transmission of mature P. falciparum gametocytes to Anopheles stephensi mosquitoes. A co-crystal structure of PvPKG bound to ML10, reveals intimate molecular contacts that explain the high levels of potency and selectivity we have measured. The properties of this series warrant consideration for further development to produce an antimalarial drug.Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes