A numerical study of two different specimen fixtures for the modified compact tension test – their influence on concrete fracture parameters

The modified compact tension test (MCT) may represent a new test configuration for the performance of static and other kinds of fatigue tests on concrete-like materials. Core drilling can be employed to obtain specimens which are cylindrical in shape and have a standard diameter of 150 mm, this being appropriate for the determination of the residual life of structures. This contribution focuses on the evaluation of MCT specimen fracture behavior during static tests. Cracks evolution are simulated numerically using ATENA finite element (FE) software, while the results are represented as L-COD diagrams, i.e. load vs. crack opening displacement measured on the loading axis. After numerical calculations, the results for two different fixtures are compared and the advantages or drawbacks for each solution are discussed

Multiple activation mechanisms of p38 alpha mitogen-activated protein kinase

The p38 alpha MAPK participates in a variety of biological processes. Activation of p38 alpha is mediated by phosphorylation on specific regulatory tyrosine and threonine sites, and the three dual kinases, MAPK kinase 3 (MKK3), MKK4, and MKK6, are known to be the upstream activators of p38 alpha. In addition to activation by upstream kinases, p38 alpha can autoactivate when interacting with transforming growth factor-beta-activated protein kinase 1-binding protein 1 (TAB1). Here we used MKK3 and MKK6 double knock-out (MKK3/6 DKO) and MKK4/7 DKO mouse embryonic fibroblast (MEF) cells to examine activation mechanisms of p38 alpha. We confirmed that the MKK3/6 pathway is a primary mechanism for p38 alpha phosphorylation in MEF cells, and we also showed the presence of other p38 alpha activation pathways. We show that TAB1-mediated p38 alpha phosphorylation in MEF cells did not need MKK3/4/6, and it accounted for a small portion of the total p38 alpha phosphorylation that was induced by hyperosmolarity and anisomycin. We observed that a portion of peroxynitrite-induced phospho-p38 alpha is associated with an similar to 85-kDa disulfide complex in wild-type MEF cells. Peroxynitrite-induced phosphorylation of p38 alpha in the similar to 85-kDa complex is independent from MKK3/6 because only phospho-p38 alpha not associated with the disulfide complex was diminished in MKK3/6DKO cells. In addition, our data suggest interference among different pathways because TAB1 had an inhibitory effect on p38 alpha phosphorylation in the peroxynitrite-induced similar to 85-kDa complex. Mutagenesis analysis of the cysteines in p38 alpha revealed that no disulfide bond forms between p38 alpha and other proteins in the similar to 85-kDa complex, suggesting it is a p38 alpha binding partner(s) that forms disulfide bonds, which enable it to bind to p38 alpha. Therefore, multiple mechanisms of p38 alpha activation exist that can influence each other, be simultaneously activated by a given stimulus, and/or be selectively used by different stimuli in a cell type-specific manner

Cell surface 4-1BBL mediates sequential signaling pathways 'downstream' of TLR and is required for sustained TNF production in macrophages

The stimulation of Toll-like receptors (TLRs) on macrophages triggers production of the cytokine tumor necrosis factor (TNF). TNF production occurs within 1 h of TLR stimulation and is sustained for 1 d. Here we document a function for the TNF family member 4-1BB ligand (4-1BBL) in sustaining TLR-induced TNF production. TLR signaling induced 4-1BBL, and 4-1BBL interacted with TLRs on the macrophage surface. The influence of 4-1BBL on TNF production was independent of its receptor (4-1BB) and did not require the adaptors MyD88 or TRIF. It did not influence TLR4-induced activation of transcription factor NF-kappa B (an early response) but was required for TLR4-induced activation of transcription factors CREB and C/EBP ( a late event). Transient TLR4-MyD88 complexes appeared during the first hour after lipopolysaccharide stimulation, and TLR4-4-1BBL interactions were detected between 2 h and 8 h after lipopolysaccharide stimulation. Our results indicate that two different TLR4 complexes sequentially form and selectively control early and late TNF production