Inertia controlled instability and small scale structures of sheet and cloud cavitation

The present investigation focuses on the numerical simulation of inertia driven dynamics of 3-D sheet and cloud cavitation on a 2-D NACA 0015 hydrofoil. Special emphasis is put on the numerical analysis of the re-entrant flow, the break-up of the sheet cavity and the formation of clouds. We demonstrate that our CFD-Tool CATUM (CAvitation Technische Universität Mu?nchen) is able to predict even delicate 3-D flow features such as irregular break-up patterns, cavitating hairpin and horseshoe vortices, 3-D instabilities in spanwise direction and the formation and propagation of shocks due to collapsing clouds close to the trailing edge of the hydrofoil. The numerically predicted flow features agree well with the experimental observations of Kawanami et al [1].http://deepblue.lib.umich.edu/bitstream/2027.42/84219/1/CAV2009-final17.pd

Journal of Immunology Research / Prophylactic mRNA vaccination against allergy confers long-term memory responses and persistent protection in mice

Recently, mRNA vaccines have been introduced as a safety-optimized alternative to plasmid DNA-based vaccines for protection against allergy. However, it remained unclear whether the short persistence of this vaccine type would limit memory responses and whether the protective immune response type would be maintained during recurrent exposure to allergen. We tested the duration of protective memory responses in mice vaccinated with mRNA encoding the grass pollen allergen Phl p 5 by challenging them with recombinant allergen, 3.5, 6, and 9 months after vaccination. In a second experiment, vaccinated mice were repeatedly challenged monthly with aerosolized allergen over a period of 7 months. Antibody and cytokine responses as well as lung inflammation and airway hyperresponsiveness were assessed. mRNA vaccination induced robust TH1 memory responses for at least 9 months. Vaccination efficiently suppressed TH2 cytokines, IgE responses, and lung eosinophilia. Protection was maintained after repeated exposure to aerosolized allergen and no TH1 associated pathology was observed. Lung function remained improved compared to nonvaccinated controls. Our data clearly indicate that mRNA vaccination against Phl p 5 induces robust, long-lived memory responses, which can be recalled by allergen exposure without side effects. mRNA vaccines fulfill the requirements for safe prophylactic vaccination without the need for booster immunizations.(VLID)179427

Molecular and immunological characterization of profilin from mugwort pollen

In late summer in Europe, pollen of mugwort is one of the major sources of atopic allergens. No information about the complete molecular structure of any mugwort allergen has been published so far. Here we report the isolation and characterization of mugwort pollen cDNA clones coding for two isoforms of the panallergen profilin. Thirtysix percent of the mugwort allergic patients tested displayed IgE antibodies against natural and recombinant profilin, and no significant differences were observed in the IgEbinding properties of the isoforms. One profilin isoform was purified to homogeneity and detailed structural analysis indicated that the protein exists in solution as dimers and tetramers stabilized by sulfydryl and/or ionic interactions. Profilin monomers were detectable only after exposure of multimers to harsh denaturing conditions. Dimers and tetramers did not significantly differ in their ability to bind serum IgE from mugwort pollenallergic patients. However, oligomeric forms might have a higher allergenic potential than monomers because larger molecules would have additional epitopes for IgEmediated histamine release. Profilin isolated from mugwort pollen also formed multimers. Thus, oligomerization is not an artifact resulting from the recombinant production of the allergen. Inhibition experiments showed extensive IgE crossreactivity of recombinant mugwort profilin and profilin from various pollen and food extracts

Autoantibodies to BRAF, a new family of autoantibodies associated with rheumatoid arthritis

International audienceBRAF (v raf murine sarcoma viral oncogene homologue B1) is a serine-threonine kinase involved in the mitogen-activated protein kinase (MAPK) signalling pathway, known to be implicated in the production of pro-inflammatory cytokines.We have observed that sera from rheumatoid arthritis (RA) patients recognize the BRAF's catalytic domain, which encompasses amino acids 416 to 766. Here, we identify peptide targets of anti-BRAF autoantibodies and test whether anti-BRAF autoantibodies may interfere with BRAF kinase activity.METHODS:Anti-BRAF autoantibodies were detected by ELISA (enzyme-linked immunosorbent assay) in the serum of RA patients and controls, using 40 overlapping 20mer peptides encompassing the catalytic domain of BRAF as immunosorbents. To test whether autoantibodies to BRAF influence BRAF kinase activity, we developed an in vitro phosphorylation assay of MEK1 (mitogen extracellular regulated kinase), a major BRAF substrate. MEK1 phosphorylation by BRAF was tested in the presence of purified anti-BRAF autoantibodies from RA patients or control antibody.RESULTS:We found that one BRAF peptide, P25 (656 to 675), is specifically recognized by autoantibodies from RA patients. Of interest, anti-P25 autoantibodies are detected in 21% of anti-CCP (cyclic citrullinated peptides) negative RA patients. Anti-BRAF autoantibodies activate the in vitro phosphorylation of MEK1 mediated by BRAF.CONCLUSIONS:Anti-BRAF autoantibodies from RA patients preferentially recognize one BRAF peptide: P25. Autoantibody responses to P25 are detected in 21% of anti-CCP negative RA patients. Most anti-BRAF autoantibodies activate BRAF kinase activity

Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways

Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through -3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts

Numerical prediction of erosive collapse events in unsteady compressible cavitating flows

The objective of the present investigation is the numerical prediction of the potential of a flow to inflict surface damage by cavitation. For this purpose, physical criteria are derived that detect and quantify relevant flow phenomena. In particular, we present a numerical approach for tracing isolated collapses of vapor clouds during the numerical simulation of the flow. The suggested “collapse detector” provides the frequency of collapses, their positions and resulting maximum pressures as well as the maximum condensation rate of each event. These data, together with the maximum wall pressure, allow for an automatic indication of erosion-sensitive areas. The employed flow solver CATUM (CAvitation Technische Universität München) is a density-based 3-D finite volume method equipped with a Low-Mach-number consistent flux function. All fluid components (liquid, vapor, saturated mixture) are modeled by closed form equations of state. To assess the novel approach we simulate an experimentally investigated nozzle-target flow. A comparison of numerically predicted collapse events with the experimentally observed areas of cavitation erosion substantiates the proposed methodology. The obtained data represent a time-history of collapse events together with their position and strength and may be used to estimate erosion rates