Some Consequences of Thermosolutal Convection: The Grain Structure of Castings

The essential principles of thermosolutal convection are outlined, and how convection provides a transport mechanism between the mushy region of a casting and the open bulk liquid is illustrated. The convective flow patterns which develop assist in heat exchange and macroscopic solute segregation during solidification; they also provide a mechanism for the transport of dendritic fragments from the mushy region into the bulk liquid. Surviving fragments become nuclei for equiaxed grains and so lead to blocking of the parental columnar, dendritic growth front from which they originated. The physical steps in such a sequence are considered and some experimental data are provided to support the argument

L-Selectin/CD62L is a Key Driver of Non-Alcoholic Steatohepatitis in Mice and Men

CD62L (L-Selectin) dependent lymphocyte infiltration is known to induce inflammatory bowel disease (IBD), while its function in the liver, especially in non-alcoholic steatohepatitis (NASH), remains unclear. We here investigated the functional role of CD62L in NASH in humans as well as in two mouse models of steatohepatitis. Hepatic expression of a soluble form of CD62L (sCD62L) was measured in patients with steatosis and NASH. Furthermore, CD62L-/- mice were fed with a methionine and choline deficient (MCD) diet for 4 weeks or with a high fat diet (HFD) for 24 weeks. Patients with NASH displayed increased serum levels of sCD62L. Hepatic CD62L expression was higher in patients with steatosis and increased dramatically in NASH patients. Interestingly, compared to wild type (WT) mice, MCD and HFD-treated CD62L-/- mice were protected from diet-induced steatohepatitis. This was reflected by less fat accumulation in hepatocytes and a dampened manifestation of the metabolic syndrome with an improved insulin resistance and decreased cholesterol and triglyceride levels. Consistent with ameliorated disease, CD62L-/- animals exhibited an enhanced hepatic infiltration of Treg cells and a strong activation of an anti-oxidative stress response. Those changes finally resulted in less fibrosis in CD62L-/- mice. Additionally, this effect could be reproduced in a therapeutic setting by administrating an anti-CD62L blocking antibody. CD62L expression in humans and mice correlates with disease activity of steatohepatitis. CD62L knockout and anti-CD62L-treated mice are protected from diet-induced steatohepatitis suggesting that CD62L is a promising target for therapeutic interventions in NASH