Updates on the antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by venous or arterial thrombosis, and/or pregnancy loss or complications in the presence of persistently positive antiphospholipid antibodies. Organ involvement, referred to as non-criteria manifestations, includes livedo reticularis, thrombocytopenia and nephropathy. Non-thrombotic inflammatory mechanisms are increasingly identified in the pathogenesis of APS, alongside a recognition that obstetric APS might be a specific subset of APS. Treatment remains focused on life-long anticoagulation and prevention of further thrombosis or obstetric complications. Identification of novel mechanisms is, however, leading the development of diagnostic tests and more targeted therapies to improve disease management

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

Objective: Previous studies have shown the importance of somatic mutations and arginine residues in the complementarity-determining regions (CDRs) of pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies in human and murine lupus, and in studies of murine antibodies, a role of mutations at position 53 in VH CDR2 has been demonstrated. We previously demonstrated in vitro expression and mutagenesis of the human IgG1 monoclonal antibody B3. The present study was undertaken to investigate, using this expression system, the importance of the arginine residue at position 53 (R53) in B3 VH. Methods: R53 was altered, by site-directed mutagenesis, to serine, asparagine, or lysine, to create 3 expressed variants of VH. In addition, the germline sequence of the VH3-23 gene (from which B3 VH is derived) was expressed either with or without arginine at position 53. These 5 new heavy chains, as well as wild-type B3 VH, were expressed with 4 different light chains, and the resulting antibodies were assessed for their ability to bind to nucleosomes, -actinin, cardiolipin, ovalbumin, 2-glycoprotein I (2GPI), and the N-terminal domain of 2GPI (domain I), using direct binding assays. Results: The presence of R53 was essential but not sufficient for binding to dsDNA and nucleosomes. Conversely, the presence of R53 reduced binding to -actinin, ovalbumin, 2GPI, and domain I of 2GPI. The combination B3 (R53S) VH/B3 VL bound human, but not bovine, 2GPI. Conclusion: The fact that the R53S substitution significantly alters binding of B3 to different clinically relevant antigens, but that the alteration is in opposite directions depending on the antigen, implies that this arginine residue plays a critical role in the affinity maturation of antibody B3

Implicit time accurate solutions on unstructured dynamic grids

In this paper an unstructured multigrid algorithm is used as an iterative solution procedure for the discrete equations arising from an implicit time discretisation of the unsteady Euler equations on tetrahedral grids. To calculate unsteady flows due to oscillating boundaries, a novel grid movement algorithm is introduced, in which an elliptic equation with a nonlinear diffusion coefficient is used to define the displacement of interior grid nodes. This allows large grid displacements to be calculated in a single step. The multigrid technique uses a edge--collapsing algorithm to generate a sequence of grids, and a pseudo--timestepping smoother. On the coarser grids, no grid motion is used. Instead, surface normals are rotated consistently and transfer/interpolation weights are based on the time-averaged grid coordinates. A 2D NACA0012 test case is used to validate the program. 3D results are presented for the M6 wing and a full aircraft configuration

Universality and Clustering in 1+1 Dimensional Superstring-Bit Models

We construct a 1+1 dimensional superstring-bit model for D=3 Type IIB superstring. This low dimension model escapes the problems encountered in higher dimension models: (1) It possesses full Galilean supersymmetry; (2) For noninteracting polymers of bits, the exactly soluble linear superpotential describing bit interactions is in a large universality class of superpotentials which includes ones bounded at spatial infinity; (3) The latter are used to construct a superstring-bit model with the clustering properties needed to define an $S$-matrix for closed polymers of superstring-bits.Comment: 11 pages, Latex documen

All fiber components for multimode SDM systems

Fiber based mode converters and mode splitters are important elements in the FMF mux./demux. Long Period Gratings (LPGs) have been investigated and results presented together with a potential technique for real time mode monitoring during manufacture