The surface structure of SrTiOaGOO) was analyzed at r -120 K by means of low-energy-electron diffraction. The best theory-experiment fit results for a surface containing domains of two different layer terminations. Both of them show a first-layer puckering, with oxygen ions being pulled out of the surface by .s(Ti) =0.08 A and s(Sr) =0.16 A, combined with a relaxation of the first two layer distances. This proves the surface to be ferroelectric, different from the bulk property in agreement with theoretical predictions.

Sphingosine-1-phosphate (S1P) is a widespread lysophospholipid which displays a wealth of biological effects. Extracellular S1P conveys its activity through five specific G-protein coupled receptors numbered S1P(1) through S1P(5). Agonists of the S1P(1) receptor block the egress of T-lymphocytes from thymus and lymphoid organs and hold promise for the oral treatment of autoimmune disorders. Here, we report on the discovery and detailed structure-activity relationships of a novel class of S1P(1) receptor agonists based on the 2-imino-thiazolidin-4-one scaffold. Compound 8bo (ACT-128800) emerged from this series and is a potent, selective, and orally active S1P(1) receptor agonist selected for clinical development. In the rat, maximal reduction of circulating lymphocytes was reached at a dose of 3 mg/kg. The duration of lymphocyte sequestration was dose dependent. At a dose of 100 mg/kg, the effect on lymphocyte counts was fully reversible within less than 36 h. Pharmacokinetic investigation of 8bo in beagle dogs suggests that the compound is suitable for once daily dosing in humans.

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We prove an optimal regularity result for elliptic operators −∇ • µ∇ : W 1,q 0 → W −1,q for a q > 3 in the case when the coefficient function µ has a jump across a C 1 interface and is continuous elsewhere. A counterexample shows that the C 1 condition cannot be relaxed in general. Finally, we draw some conclusions for corresponding parabolic operators.