V2:Performance of the solid deuterium ultra-cold neutron source at the pulsed reactor TRIGA Mainz

The performance of the solid deuterium ultra-cold neutron source at the pulsed reactor TRIGA Mainz with a maximum peak energy of 10 MJ is described. The solid deuterium converter with a volume of V=160 cm3 (8 mol), which is exposed to a thermal neutron fluence of 4.5x10^13 n/cm2, delivers up to 550 000 UCN per pulse outside of the biological shield at the experimental area. UCN densities of ~ 10/cm3 are obtained in stainless steel bottles of V ~ 10 L resulting in a storage efficiency of ~20%. The measured UCN yields compare well with the predictions from a Monte Carlo simulation developed to model the source and to optimize its performance for the upcoming upgrade of the TRIGA Mainz into a user facility for UCN physics.Comment: 23 pages, 8 figure

Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

Allogeneic stem cell transplantation in X-linked lymphoproliferative disease: two cases in one family and review of the literature

Summary:X-linked lymphoproliferative disease (XLP) is a rare immunodeficiency caused by mutations in the signaling lymphocyte activating molecule-associated protein/SH2D1A gene and characterized by a dysregulated immune response to Epstein-Barr virus and other pathogens. The clinical presentation is heterogeneous and includes fulminant infectious mononucleosis, lymphoma, hypogammaglobulinemia and aplastic anemia. XLP is associated with a high morbidity and overall outcome is poor. At present, allogeneic stem cell transplantation (alloSCT) is the only curative treatment. XLP patients may be recognized in various stages of disease and even when symptoms are not yet evident. We here present two related XLP patients in different stages of disease that were both treated successfully with alloSCT using a matched unrelated donor. In addition, we have reviewed all reported cases of alloSCTs in XLP patients. Based on these results and in order to improve the final outcome, we conclude that alloSCT should be recommended in both symptomatic and asymptomatic XLP patients.Bone Marrow Transplantation advance online publication, 23 May 2005; doi:10.1038/sj.bmt.170501