Reduced basis method for the shape optimization of racing car components

In this work we apply reduced basis methods to parametrized airfoils configurations to study inviscid potential, thermal and viscous flows. Parametrization includes geometry, ground effect and airfoils interaction

Caspase-8 controls the gut response to microbial challenges by Tnf-alpha-dependent and independent pathways

Objectives: Intestinal epithelial cells (IEC) express toll-like receptors (TLR) that facilitate microbial recognition. Stimulation of TLR ligands induces a transient increase in epithelial cell shedding, a mechanism that serves the antibacterial and antiviral host defence of the epithelium and promotes elimination of intracellular pathogens. Although activation of the extrinsic apoptosis pathway has been described during inflammatory shedding, its functional involvement is currently unclear. Design: We investigated the functional involvement of caspase-8 signalling in microbial-induced intestinal cell shedding by injecting Lipopolysaccharide (LPS) to mimic bacterial pathogens and poly(I:C) as a probe for RNA viruses in vivo. Results: TLR stimulation of IEC was associated with a rapid activation of caspase-8 and increased epithelial cell shedding. In mice with an epithelial cell-specific deletion of caspase-8 TLR stimulation caused Rip3-dependent epithelial necroptosis instead of apoptosis. Mortality and tissue damage were more severe in mice in which IECs died by necroptosis than apoptosis. Inhibition of receptor-interacting protein (Rip) kinases rescued the epithelium from TLR-induced gut damage. TLR3-induced necroptosis was directly mediated via TRIF-dependent pathways, independent of Tnf-α and type III interferons, whereas TLR4-induced tissue damage was critically dependent on Tnf-α. Conclusions: Together, our data demonstrate an essential role for caspase-8 in maintaining the gut barrier in response to mucosal pathogens by permitting inflammatory shedding and preventing necroptosis of infected cells. These data suggest that therapeutic strategies targeting the cell death machinery represent a promising new option for the treatment of inflammatory and infective enteropathies

The use of a retrograde fixed-angle intramedullary nail for tibiocalcaneal arthrodesis after severe loss of the talus

Tibiocalcaneal arthrodesis may be the only means of obtaining a painless and stable limb when there is loss of the talus. We present the early results of a prospective study on tibiocalcaneal arthrodesis using a latest-generation retrograde intramedullary nail. In the period 2006–2007, nine patients underwent tibiocalcaneal arthrodesis with retrograde intramedullary nailing. Five of these patients had infection-related loss of the talus. SF-36, AOFAS ankle-hindfoot, and Mazur Ankle Arthrodesis scores were obtained pre-fusion, and at 6 weeks, 6 months and 1 year post-fusion. The patients were also followed up clinically and radiologically. Previous surgical procedures, chronic musculoskeletal problems and other comorbidities, and complications were recorded and analyzed. All patients were available for initial follow-up and were subjectively satisfied with their outcomes. Solid fusion was achieved and fully confirmed in nine cases. One subject died 8 weeks postoperatively of a pulmonary embolism. One patient had recurrent infection. At 1 year, only one patient still needed NSAIDs regularly for pain relief. The AOFAS score improved significantly (P = 0.012) from 32.1 pre-fusion to 71.5 points at 1 year as did the Mazur score, which rose by 31.2 to 72.5 points at 1 year (P = 0.012). The SF-36 score improved significantly in the domains physical functioning, role limitations due to physical problems, bodily pain, vitality, social functioning and mental health, as did the Physical Component Summary Score. Retrograde intramedullary nailing for tibiocalcaneal arthrodesis can produce a good outcome. However, in the presence of infection, patient selection for intramedullary procedures must be carefully considered on a case-by-case basis

EP4 receptor stimulation down-regulates human eosinophil function

Accumulation of eosinophils in tissue is a hallmark of allergic inflammation. Here we observed that a selective agonist of the PGE2 receptor EP4, ONO AE1-329, potently attenuated the chemotaxis of human peripheral blood eosinophils, upregulation of the adhesion molecule CD11b and the production of reactive oxygen species. These effects were accompanied by the inhibition of cytoskeletal rearrangement and Ca2+ mobilization. The involvement of the EP4 receptor was substantiated by a selective EP4 antagonist, which reversed the inhibitory effects of PGE2 and the EP4 agonist. Selective kinase inhibitors revealed that the inhibitory effect of EP4 stimulation on eosinophil migration depended upon activation of PI 3-kinase and PKC, but not cAMP. Finally, we found that EP4 receptors are expressed by human eosinophils, and are also present on infiltrating leukocytes in inflamed human nasal mucosa. These data indicate that EP4 agonists might be a novel therapeutic option in eosinophilic diseases

Progrediente Dyspnoe eines Hufschmieds — EAA und rezidivierende Rauchgasinhalation als seltene Ursache

Arbeitsplatzbezogene Atembeschwerden eines Hufschmiedes können auf chemisch-irritative oder allergisierende Effekte zurückgeführt werden. In der Diagnostik spielen neben einer subtilen allgemeinen und Berufs-Anamnese eine longitudinale und tätigkeitsparallele Lungenfunktionsanalytik und eine gezielte Allergiediagnostik eine entscheidende Rolle, in deren Verlauf sich - wie in der folgenden Kasuistik - auch die Diagnose einer seltenen Differentialdiagnose - einer EAA - stellen kann

Structure of \u3ci\u3eClostridium difficile\u3c/i\u3e PilJ Exhibits Unprecedented Divergence from Known Type IV Pilins

Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, cellular adhesion, and colonization. Recently, there has been an increased appreciation of the ability of Gram-positive species, including Clostridium difficile, to produce Type IV pili. Here we report the first three-dimensional structure of a Grampositive Type IV pilin, PilJ, demonstrate its incorporation into Type IV pili, and offer insights into how the Type IV pili of C. difficile may assemble and function. PilJ has several unique structural features, including a dual-pilin fold and the incorporation of a structural zinc ion. We show that PilJ is incorporated into Type IV pili in C. difficile and present a model in which the incorporation of PilJ into pili exposes the C-terminal domain of PilJ to create a novel interaction surface

System size and centrality dependence of the balance function in A+A collisions at sqrt[sNN]=17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at sqrt[sNN]=17.2 GeV with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions