The Recursive Record Semantics of Objects Revisited

In a call-by-value language, representing objects as recursive records requires using an unsafe fixpoint. We design, for a core language including extensible records, a type system which rules out unsafe recursion and still supports the reconstruction of a principal type. We illustrate the expressive power of this language with respect to object-oriented programming by introducing a sub-language for «mixin-based» programming

Update of the Inhibitor-Immunology-Study

Abstract We are presenting an update of our study in which risk factors for the development of inhibitors in patients with hemophilia are to be explored. The ultimate goal is to find out why some children suffering from severe or moderate hemophilia develop inhibitory antibodies during replacement therapy and others do not, and to define genetic and immunological risk factors. The development of inhibitors is one of the most important complications of the replacement therapy in hemophilia affecting mortality and morbidity. The development of inhibitory antigens is based on complex immunological factors, and to date, too little is known about the basic mechanisms of inhibitor development. Risk factors are presumably derived from the immune system. Inhibitory antibodies are mostly IgG-type immunoglobulins, especially subclass 4, rarely subclass 1. During inhibitor formation, CD4+ T cells are directed in a cytokine-dependent manner to the Th1 or Th2 pathway. The development of inhibitors is very likely to be a Th-2 mediated event where cytokines and their receptors, T-cell receptors, and the Major Histocompatibility Complex may also play important roles. One examples of the cytokine connection is a mouse model, in which the development of inhibitors is prevented by the blockade of the co-stimulating factor B7/CD28. Within the scope of our study we want to compare genetic polymorphisms in immune-response associated genes between patients with and without inhibitors and between patients and the normal population: The characterization of genetic polymorphisms including for instance TLR, TNF-a, CD40, IL-10 and IL-1b are emphasized. The correlation between some genotypes or polymorphisms in cytokines and the development of inhibitory antigens is to be studied. Up to now 15 centers agreed to take place in our study. 5 of these already sent samples, amounting to 46 samples of hemophiliacs. We evaluated 10 polymorphisms in different genes in the first 40 patients with Taq-Man-PCR, restriction fragment length polymorphisms (RFLP), ARMS and direct sequence analyzing. Promising results were seen in some polymorphisms, but in most of them so far the number of samples is too small to get significant results