SphK1 regulates proinflammatory responses associated with endotoxin and polymicrobial sepsis

During sepsis, activation of phagocytes leads to the overproduction of proinflammatory cytokines, causing systemic inflammation. Despite substantial information regarding the underlying molecular mechanisms that lead to sepsis, several elements in the pathway remain to be elucidated. We found that the enzyme sphingosine kinase 1 (SphK1) is up-regulated in stimulated human phagocytes and in peritoneal phagocytes of patients with severe sepsis. Blockade of SphK1 inhibited phagocyte production of endotoxin-induced proinflammatory cytokines. We observed protection against sepsis in mice treated with a specific SphK1 inhibitor that was enhanced by treatment with a broad-spectrum antibiotic. These results demonstrated a critical role for SphK1 in endotoxin signaling and sepsis-induced inflammatory responses and suggest that inhibition of SphK1 is a potential therapy for septic shock.

Phase I trial of combretastatin A4 phosphate (CA4P) in combination with bevacizumab in patients with advanced cancer

The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity.

CODE repro2 product series for the IGS

CODE, the Center for Orbit Determination in Europe, is a joint venture of the following four institutions: • Astronomical Institute, University of Bern (AIUB), Bern, Switzerland • Federal Office of Topography swisstopo, Wabern, Switzerland • Federal Agency of Cartography and Geodesy (BKG), Frankfurt a. M., Germany • Institut für Astronomische und Physikalische Geodäsie, Technische Universität München (IAPG, TUM), Munich, Germany It acts as a global analysis center of the International GNSS Service (IGS, Dow et al, 2009). The operational computations are performed at AIUB using the latest development version of the Bernese GNSS Software (Dach et al., 2015). In this context the contribution to the IGS repro02 effort is generated considering only the GPS satellites between 1994 and 2001 as well as the GPS and GLONASS satellites from 2002 to the end of 2013.