Three isoparametric solid elements for NASTRAN

Linear, quadratic, and cubic isoparametric hexahedral solid elements have been added to the element library of NASTRAN. These elements are available for static, dynamic, buckling, and heat-transfer analyses. Because the isoparametric element matrices are generated by direct numerical integration over the volume of the element, variations in material properties, temperatures, and stresses within the elements are represented in the computations. In order to compare the accuracy of the new elements, three similar models of a slender cantilever were developed, one for each element. All elements performed well. As expected, however, the linear element model yielded excellent results only when shear behavior predominated. In contrast, the results obtained from the quadratic and cubic element models were excellent in both shear and bending

Addition of three-dimensional isoparametric elements to NASA structural analysis program (NASTRAN)

Implementation is made of the three-dimensional family of linear, quadratic and cubic isoparametric solid elements into the NASA Structural Analysis program, NASTRAN. This work included program development, installation, testing, and documentation. The addition of these elements to NASTRAN provides a significant increase in modeling capability particularly for structures requiring specification of temperatures, material properties, displacements, and stresses which vary throughout each individual element. Complete program documentation is presented in the form of new sections and updates for direct insertion to the three NASTRAN manuals. The results of demonstration test problems are summarized. Excellent results are obtained with the isoparametric elements for static, normal mode, and buckling analyses

The automated multi-stage substructuring system for NASTRAN

The substructuring capability developed for eventual installation in Level 16 is now operational in a test version of NASTRAN. Its features are summarized. These include the user-oriented, Case Control type control language, the automated multi-stage matrix processing, the independent direct access data storage facilities, and the static and normal modes solution capabilities. A complete problem analysis sequence is presented with card-by-card description of the user input

The V_H repertoire and clonal diversification of B cells in inflammatory myopathies

The contribution of antigen-driven B-cell adaptive immune responses within the inflamed muscle of inflammatory myopathies (IMs) is largely unknown. In this study, we investigated the immunoglobulin VH gene repertoire, somatic hypermutation, clonal diversification, and selection of infiltrating B cells in muscle biopsies from IM patients (dermatomyositis and polymyositis), to determine whether B cells and/or plasma cells contribute to the associated pathologies of these diseases. The data reveal that Ig V<sub>H</sub> gene repertoires of muscle-infiltrating B cells deviate from the normal VH gene repertoire in individual patients, and differ between different types of IMs. Analysis of somatic mutations revealed clonal diversification of muscle-infiltrating B cells and evidence for a chronic B-cell response within the inflamed muscle. We conclude that muscle-infiltrating B cells undergo selection, somatic hypermutation and clonal diversification in situ during antigen-driven immune responses in patients with IMs, providing insight into the contribution of B cells to the pathological mechanisms of these disorders

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Resonance bifurcations from robust homoclinic cycles

We present two calculations for a class of robust homoclinic cycles with symmetry Z_n x Z_2^n, for which the sufficient conditions for asymptotic stability given by Krupa and Melbourne are not optimal. Firstly, we compute optimal conditions for asymptotic stability using transition matrix techniques which make explicit use of the geometry of the group action. Secondly, through an explicit computation of the global parts of the Poincare map near the cycle we show that, generically, the resonance bifurcations from the cycles are supercritical: a unique branch of asymptotically stable period orbits emerges from the resonance bifurcation and exists for coefficient values where the cycle has lost stability. This calculation is the first to explicitly compute the criticality of a resonance bifurcation, and answers a conjecture of Field and Swift in a particular limiting case. Moreover, we are able to obtain an asymptotically-correct analytic expression for the period of the bifurcating orbit, with no adjustable parameters, which has not proved possible previously. We show that the asymptotic analysis compares very favourably with numerical results.Comment: 24 pages, 3 figures, submitted to Nonlinearit

VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy- Terminal NRP1 Fragments That Regulate Angiogenic Signaling

OBJECTIVE: NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. To characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function. APPROACH AND RESULTS: NRP1 species comprising the carboxy (C)-terminal and transmembrane NRP1 domains but lacking the ligand-binding A and B regions are constitutively expressed in endothelial cells. Generation of these C-terminal domain NRP1 proteins is upregulated by phorbol ester and Ca2+ ionophore, and reduced by pharmacological inhibition of metalloproteinases, by small interfering RNA-mediated knockdown of 2 members of ADAM (a disintegrin and metalloproteinase) family, ADAMs 9 and 10, and by a specific ADAM10 inhibitor. Furthermore, VEGF upregulates expression of these NRP1 species in an ADAM9/10-dependent manner. Transduction of endothelial cells with adenoviral constructs expressing NRP1 C-terminal domain fragments inhibited VEGF-induced phosphorylation of VEGFR2 (VEGF receptor tyrosine kinase)/KDR and decreased VEGF-stimulated endothelial cell motility and angiogenesis in coculture and aortic ring sprouting assays. CONCLUSIONS: These findings identify novel NRP1 species in endothelial cells and demonstrate that regulation of NRP1 proteolysis via ADAMs 9 and 10 is a new regulatory pathway able to modulate VEGF angiogenic signaling