This paper describes the design and application of a full-system simulation environment that has been widely used in the exploration of the IBM PowerPCt processor and system design. The IBM full-system simulator has been developed to meet the needs of hardware and software designers for fast, accurate, execution-driven simulation of complete systems, incorporating parameterized architectural models. This environment enables the development and tuning of production-level operating systems, compilers, and critical software support well in advance of hardware availability, which can significantly shorten the critical path of system development. The ability to develop early versions of software can benefit hardware development by identifying design issues that may affect functionality and performance far earlier in the development cycle, when they are much less costly to correct. In this paper, we describe features of the simulation environment and present examples of its application in the context of the Sony-Toshiba-IBM Cell Broadband Enginee and IBM PERCS development projects.

SummaryEpidermolysis bullosa acquisita is an autoimmune blistering disease characterized by circulating and skin basement membrane-bound IgG autoantibodies to type VII collagen, a major structural protein of the dermal-epidermal junction. Regulatory T cells (T reg ) suppress self antigen-mediated autoimmune responses. To investigate the role of T reg in the the autoimmune response to type VII collagen in a mouse model, a monoclonal antibody against mouse CD25 was used to deplete T reg . A recombinant mouse type VII collagen NC1 domain protein and mouse albumin were used as antigens. SKH1 mice were used as a testing host. Group 1 mice received NC1 immunization and were functionally depleted of T reg ; group 2 mice received NC1 immunization and rat isotype control; and group 3 mice received albumin immunization and were functionally depleted of T reg . Results demonstrated that anti-NC1 IgG autoantibodies with high titres, as determined by enzymelinked immunosorbent assay and Western blotting, developed in all mice immunized with NC1 (groups 1 and 2), but were undetected in group 3 mice. The predominant subclasses of anti-NC1 autoantibodies were IgG1, IgG2a and IgG2b; furthermore, these antibodies carried only the kappa light chain. IgG autoantibodies in the sera of NC1-immunized mice reacted with mouse skin basement membrane in vitro and deposited in skin basement membrane in vivo as detected by indirect and direct immunofluorescence microscopy, respectively. Our data suggest that the development of autoimmunity against type VII collagen in mice is independent of T reg function and the autoimmune response is mediated by both Th1 and Th2 cells. We speculate that the basement membrane deposition of IgG may eventually lead to blister development.

Purpose Hepatitis E virus infection mainly presents with liver-related symptoms, and multiple studies have shown that hepatitis E virus infection can also induce extrahepatic-related symptoms. Thrombotic thrombocytopenic purpura is an uncommon and fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ damage, and microangiopathic haemolytic anaemia. We report the first case in which acute hepatitis E induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Patients and Methods A 53-year-old male was admitted to our emergency department with fever, thrombocytopenia, and abnormal liver function. Laboratory tests revealed significant bilirubin, AST, and ALT elevations, renal impairment, positive anti-HEV IgM and IgG antibody results, schistocytes on the blood smear, 0% ADAMTS-13 activity, and positive ADAMTS13 inhibitor results. He was diagnosed with acute hepatitis E, which induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Results After receiving treatment with plasmapheresis, glucocorticoid medication, rituximab, and other supportive medicines, the patient’s physiological circumstances and laboratory indicators improved, and a 4-month follow-up revealed no abnormalities. Conclusion This is a unique case report of an acute hepatitis E-induced immune-mediated thrombotic thrombocytopenic purpura initial episode. This case report offers evidence that hepatitis E virus infection can cause thrombotic thrombocytopenic purpura. In patients with abnormal liver function and thrombocytopenia, we advise screening for hepatitis E or thrombotic thrombocytopenic purpura.