Separation of early afterdepolarizations from arrhythmogenic substrate in the isolated perfused hypokalaemic murine heart through modifiers of calcium homeostasis

In human type 1 diabetes (T1D) and in its murine model, the major histocompatibility complex (MHC) class II molecules, human leukocyte antigens (HLA)-DQ and -DR and their murine orthologues, IA and IE, are the major genetic determinants. In this report, we have ranked HLA class II molecule-associated T1D risk in a two-sided gradient from very high to very low. Very low risk corresponded to dominant protection from T1D. We predicted the protein structure of DQ by using the published crystal structures of different allotypes of the murine orthologue of DQ, IA. We discovered marked similarities both within, and cross species between T1D protective class II molecules. Likewise, the T1D predisposing molecules showed conserved similarities that contrasted with the shared patterns observed between the protective molecules. We also found striking inter-isotypic conservation between protective DQ, IA allotypes and protective DR4 subtypes. The data provide evidence for a joint action of the class II peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance with a main role for P9 in DQ/IA and for P1 and P4 in DR/IE. Overall, these results suggest shared epitope(s) in the target autoantigen(s), and common pathways in human and murine T1D

Advances in Additive Manufacturing Processes

Additive Manufacturing (AM) which is also referred as Three Dimensional Printing (3DP), Solid Freeform Fabrication (SFF) or Rapid Prototyping (RP) is a layer-by-layer technique of producing a three-dimensional (3D) objects directly from a digital model. The technique is used in engineering for prototyping, tooling, direct part manufacturing, maintenance and repair. Additive Manufacturing accounted for £1.2b ($2b) across all industries in worldwide sales of materials, equipment, and services in 2012, and is expected to reach £2.4b ($4b) by 2015. Additive Manufacturing is considered to be the breakthrough disruptive technology which permits end-products to be grown from materials such as inks, dielectrics and powders in a layer-wise manner. Even though the technique has had remarkable improvements since its emergence over 25 years ago, still faces several technical challenges related to material characterization and availability compared with other conventional techniques. This paper reviews the current commercially available Additive Manufacturing processes by describing generics and specifics as well as the build material characteristics. It also presents the “State of the Art” of Additive Manufacturing Technology and outlines the strengths and weaknesses of the techniques. Finally, several case studies are discussed in addition to the real life application of these techniques which will enable readers to understand and potentially exploit these emerging technologies