Decreased β cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human β cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented β cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of β cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic β cell mass.

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Leukocyte rolling on the vascular endothelium requires initial contact between leukocytes circulating in the blood and the vessel wall. Although specific adhesion mechanisms are involved in leukocyte-endothelium interactions, adhesion patterns in vivo suggest other rheological mechanisms also play a role. Previous studies have proposed that the abundance of leukocyte rolling in postcapillary venules is due to interactions between red blood cells (RBCs) and leukocytes as they enter postcapillary expansions, but the details of the fluid dynamics have not been elucidated. We have analyzed the interactions of red and white blood cells as they flow from a capillary into a postcapillary venule using a lattice Boltzmann approach. This technique provides the complete solution of the flow field and quantification of the particle-particle forces in a relevant geometry. Our results show that capillary-postcapillary venule diameter ratio, RBC configuration, and RBC shape are critical determinants of the initiation of cell rolling in postcapillary venules. The model predicts that an optimal configuration of the trailing red blood cells is required to drive the white blood cell to the wall.

Operating conditions for the separation of a binary mixture using a nonadsorbable eluent through simulated moving-bed technology were designed. The results obtained using equilibrium theory for adsorption described by Langmuir models lead to the definition of explicit constraints on the operating parameters to operate the unit in the desired regime of separation. A more general approach was able to product the same result for a larger class of isotherms. The physical and mathematical conditions defining this larger class of isotherms are discussed, as well as the algorithms necessary to calculate the region of complete separation. Applications to the bi-Langmuir isotherm and the ideal adsorbed solution model, which are more flexible than the Langmuir model and can describe systems where selectivity changes with composition, are discussed. A shortcut method to get an explicit, though approximate, solution is proposed and its accuracy is discussed

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