Physical Properties of Wolf-Rayet Stars

The striking broad emission line spectroscopic appearance of Wolf-Rayet (WR) stars has long defied analysis, due to the extreme physical conditions within their line and continuum forming regions. Recently, model atmosphere studies have advanced sufficiently to enable the determination of stellar temperatures, luminosities, abundances, ionizing fluxes and wind properties. The observed distributions of nitrogen (WN) and carbon (WC) sequence WR stars in the Milky Way and in nearby star forming galaxies are discussed; these imply lower limits to progenitor masses of ~25, 40, 75 Msun for hydrogen-depleted (He-burning) WN, WC, and H-rich (H-burning) WN stars, respectively. WR stars in massive star binaries permit studies of wind-wind interactions and dust formation in WC systems. They also show that WR stars have typical masses of 10-25 Msun, extending up to 80 Msun for H-rich WN stars. Theoretical and observational evidence that WR winds depend on metallicity is presented, with implications for evolutionary models, ionizing fluxes, and the role of WR stars within the context of core-collapse supernovae and long-duration gamma ray bursts.Comment: 76 pages, 8 figures. Minor revision to "Annual Review of Astronomy & Astrophysics" review article Volume 45 (2007) following editors comments. Version with full resolution figures is available from ftp://astro1.shef.ac.uk/pub/pac/AnnRev_revised.pd

A Variant of TNFR2-Fc Fusion Protein Exhibits Improved Efficacy in Treating Experimental Rheumatoid Arthritis

Etanercept, a TNF receptor 2-Fc fusion protein, is currently being used for the treatment of rheumatoid arthritis (RA). However, 25% to 38% of patients show no response which is suspected to be partially due to insufficient affinity of this protein to TNFα. By using computational protein design, we found that residue W89 and E92 of TNFR2 were critical for ligand binding. Among several mutants tested, W89Y/E92N displayed 1.49-fold higher neutralizing activity to TNFα, as compared to that of Etanercept. Surface plasmon resonance (SPR) based binding assay revealed that the equilibrium dissociation constant of W89Y/E92N to TNFα was 3.65-fold higher than that of Etanercept. In a rat model of collagen-induced arthritis (CIA), W89Y/E92N showed a significantly better ability than Etanercept in reducing paw swelling and improvement of arthritic joint histopathologically. These data demonstrate that W89Y/E92N is potentially a better candidate with improved efficacy in treating RA and other autoimmune diseases