The T cell antigen receptor consists of the Ti alpha/beta heterodimer which recognizes antigen, and the associated CD3 chains, thought to be involved in signal transduction. To understand the nature of the interaction between Ti and CD3, chimeric molecules which included the COOH-terminal segments of Ti alpha or beta linked to the extracellular segment of CD8, were transfected into a mutant T cell deficient in Ti beta chain expression and cell surface CD3. Both chimeric chains were required to express the chimeric Ti and to restore CD3 surface expression. CD8/Ti and CD3 cointernalized and coimmunoprecipitated. Stimulation of the chimeric receptor induced transmembrane signaling events and cell activation. These results demonstrate that the Ti alpha and beta COOH termini containing the transmembrane domains are sufficient for structural and functional coupling of Ti to CD3.

© 2014 Mason et al.; licensee BioMed Central Ltd.Emergency Department demand continues to rise in almost all high-income countries, including those with universal coverage and a strong primary care network. Many of these countries have been experimenting w

Satellite radar interferometry data from 1995 to 2004, and airborne ice thickness data from 2002, reveal that the glaciers flowing into former Wordie Ice Shelf, West Antarctic Peninsula, discharge 6.8 ± 0.3 km3/yr of ice, which is 84 ± 30 percent larger than a snow accumulation of 3.7 ± 0.8 km3/yr over a 6,300 km2 drainage basin. Airborne and ICESat laser altimetry elevation data reveal glacier thinning at rates up to 2 m/yr. Fifty km from its ice front, Fleming Glacier flows 50 percent faster than it did in 1974 prior to the main collapse of Wordie Ice Shelf. We conclude that the glaciers accelerated following ice shelf removal, and have been thinning and losing mass to the ocean over the last decade. This and other observations suggest that the mass loss from the northern part of the Peninsula is not negligible at present. Copyright 2005 by the American Geophysical Union.

This White Paper provides a summary of presentations and discussions at a Cardiovascular Safety Outcome Trials Think Tank cosponsored by the Cardiac Safety Research Consortium, the US Food and Drug Administration, and the American College of Cardiology, held at American College of Cardiology's Heart House, Washington, DC, on February 19, 2014. Studies to assess cardiovascular (CV) risk of a new drug are sometimes requested by regulators to resolve ambiguous safety signals seen during its development or among other members of its class. Think Tank participants thought that important considerations in undertaking such studies were as follows: (1) plausibility-how likely it is that a possible signal indicating risk is real, based on strength of evidence, and/or whether a plausible mechanism of action for potential CV harm has been identified; (2) relevance-what relative and absolute CV risk would need to be excluded to determine that the drug had an acceptable benefit-to-risk balance for its use in the intended patient population; and (3) how plausibility and relevance influence the timing and approach to further safety assessment.