Two distinct intracytoplasmic regions of the T-cell adhesion molecule CD28 participate in phosphatidylinositol 3-kinase association

Through the interaction with its ligands, CD80/B7-1 and CD86/B7-2 or B70, the human CD28 molecule plays a major functional role as a costimulator of T cells along with the CD3-TcR complex. We and others have previously reported that phosphatidylinositol 3-kinase inducibly associates with CD28. This association is mediated by the SH2 domains of the p85 adaptor subunit interacting with a cytoplasmic YMNM consensus motif present in CD28 at position 173-176. Disruption of this binding site by site-directed mutagenesis abolishes CD28-induced activation events in a murine T-cell hybridoma transfected with human CD28 gene. Here we show that the last 10 residues of the intracytoplasmic domain of CD28 (residues 193-202) are required for its costimulatory function. These residues are involved in interleukin-2 secretion, p85 binding, and CD28-associated phosphatidylinositol 3-kinase activity. In contrast, the CD28/CD8O interaction is unaffected by this deletion, as is the induction of other second messengers such as the rise in intracellular calcium and tyrosine phosphorylation of CD28-specific substrates. Furthermore, we also demonstrate that, within these residues, the tyrosine at position 200 is involved in p85 binding, probably together with the short proline-rich motif present between residues 190 and 194 (PYAPP).     

A reproducing kernel hilbert space approach for q-ball imaging

Diffusion magnetic resonance (MR) imaging has enabled us to reveal the white matter geometry in the living human brain. The Q-ball technique is widely used nowadays to recover the orientational heterogeneity of the intra-voxel fiber architecture. This article proposes to employ the Funk-Radon transform in a Hilbert space with a reproducing kernel derived from the spherical Laplace-Beltrami operator, thus generalizing previous approaches that assume a bandlimited diffusion signal. The function estimation problem is solved within a Tikhonov regularization framework, while a Gaussian process model allows for the selection of the smoothing parameter and the specification of confidence bands. Shortcomings of Q-ball imaging are discussed.     

Breitung beim Warmwalzen auf geneigter Bahn

Zur Erweiterung der Grundlagen des Warmwalzens wurde das Walzen auf geneigter Bahn experimentell und theoretisch analysiert. Den Schwerpunkt der Arbeit stellt eine Untersuchung des Breitungsverhaltens dar. Basierend auf den Versuchsdaten wird eine Breitungsformel angegeben, die für Walzbahnneigungswinkel bis 60° anwendbar ist und als Sonderfall auch das Flachwalzen beinhaltet. Ausgehend vom Satz der ?Oberen Schranke“ wurde ein Rechenmodell entwickelt, das die Berechnung der Breitung für beliebige Walzbahnneigungswinkel kleiner als 60° ermöglicht. Während die Anwendung der Breitungsformel aufgrund ihrer einfachen Handhabung eher für den praktischen Einsatz im Walzbetrieb sinnvoll erscheint, ist die mit wesentlich größerem Rechenaufwand verbundene Modellrechnung in rechnergestützten Systemen zur Stichplanoptimierung einsetzbar oder als Ansatz für die Entwicklung weiterer mathematischer Modelle zu werten.     

Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features

OBJECTIVE: To determine whether the 2 periodic febrile syndromes familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS) are distinct diseases. METHODS: Clinical manifestations of the diseases were analyzed by physicians experienced with FMF and HIDS. Serum immunoglobulin (Ig) levels were studied in 70 patients with FMF using nephelometry or ELISA and compared with Ig levels in 50 patients with HIDS. Genetic linkage of HIDS with the chromosome 16 polymorphic locus RT70, currently used for refined localization of the FMF susceptibility gene (MEFV), was studied in 9 HIDS families (18 patients) using polymerase chain reaction amplification and gel electrophoresis. RESULTS: The main clinical features distinguishing FMF from HIDS were lymphadenectomy, skin eruption, and symmetrical oligoarthritis in HIDS, and monoarthritis, peritonitis, and pleuritis in FMF. Increased IgG levels were found in 12 patients with FMF (17%), IgA in 16 (23%), IgM in 9 (13%), and IgD in 9 (13%), significantly lower than the prevalence reported for HIDS. We found no evidence for genetic linkage between HIDS and the chromosome 16 marker RT70. CONCLUSION: HIDS and FMF are different entities, clinically, immunologically, and genetically.     

Computional cost of nonrigid registration algorithms based on fluid dynamics

Though fluid dynamics offer a good approach to nonrigid registration and give accurate results, even with large-scale deformations, its application is still very time consuming. We introduce and discuss different approaches to solve the core problem of nonrigid registration, the partial differential equation of fluid dynamics. We focus on the solvers, their computional costs and the accuracy of registration. Numerical experiments show that relaxation is currently the best approach, especially when reducing the cost/iteration by focusing the updates on deformation spots.