Damage simulation of brittle heterogeneous materials at the grain size level

Microstructure models at the grain size level open new potentials for the numerical investigation of micromechanical damage and fracturing. This paper presents a strategy to model heterogeneous brittle structures composed of binder and aggregate using the Discrete Element Method (DEM). A discretisation concept for both components was developed and implemented using spherical particles as discrete elements. The aggregate grains were modelled by clusters of these particles. Special routines were developed to generate specimens, to simulate laboratory tests and to analyse these simulations. Methods were developed to calibrate homogeneous and heterogeneous material by the determination of appropriate constitutive laws and their corresponding parameters. The simulation strategy allows to distinguish in detail between inter- and intra-granular microfracturing, between shear- and tensile-cracking and between microcracks within or between the different components of the heterogeneous material. Exemplarily, selected simulation results are presented for MgO-concrete.     

Crystal structure and hydrogen bonding study of (10E)-2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione 10-oxime derived from α-lapachone

The compound (10E)-2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione-10-oxime (1) was synthesized from a-lapachone and hydroxylamine chloride in alkaline medium. Single-crystals suitable for X-ray diffraction measurements were grown from an ethanol solution, and the crystal structure of the title molecule is reported for the first time. The title molecule was also characterized by 1H- and 13C-NMR in CDCl? solution, FTIR and MS. The crystal structure of 1 shows an E stereochemistry and dimers formed through classical hydrogen bonds.     

Structural insights into calmodulin/adenylyl cyclase 8 interaction

Calmodulin (CaM) is a highly conserved intracellular Ca²⁺-binding protein that exerts important functions in many cellular processes. Prominent examples of CaM-regulated proteins are adenylyl cyclases (ACs), which synthesize cAMP as a central second messenger. The interaction of ACs with CaM represents the link between Ca²⁺-signaling and cAMP-signaling pathways. Thereby, different AC isoforms stimulated by CaM, comprise diverse mechanisms of regulation by the Ca²⁺ sensor. To extend the structural information about the detailed mechanisms underlying the regulation of AC8 by CaM, we employed an integrated approach combining chemical cross-linking and mass spectrometry with two peptides representing the CaM-binding regions of AC8. These experiments reveal that the structures of CaM/AC8 peptide complexes are similar to that of the CaM/skeletal muscle myosin light chain kinase peptide complex where CaM is collapsed around the target peptide that binds to CaM in an antiparallel orientation. Cross-linking experiments were complemented by investigating the binding of AC8 peptides to CaM thermodynamically with isothermal titration calorimetry. There were no hints on a complex, in which both AC8 peptides bind simultaneously to CaM, refining our current understanding of the interaction between CaM and AC8.

Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver

Background

The induction of sterile immunity and long lasting protection against malaria has been effectively achieved by immunization with sporozoites attenuated by gamma-irradiation or through deletion of genes. For mice immunized with radiation attenuated sporozoites (RAS) it has been shown that intrahepatic effector memory CD8⁺ T cells are critical for protection. Recent studies have shown that immunization with genetically attenuated parasites (GAP) in mice is also conferred by liver effector memory CD8⁺ T cells.

Findings

In this study we analysed effector memory cell responses after immunization of GAP that lack the P52 protein. We demonstrate that immunization with p52 ^-GAP sporozoites also results in a strong increase of effector memory CD8⁺ T cells, even 6 months after immunization, whereas no specific CD4⁺ effector T cells response could be detected. In addition, we show that the increase of effector memory CD8⁺ T cells is specific for the liver and not for the spleen or lymph nodes.

Conclusions

These results indicate that immunization of mice with P. berghei p52 ^-GAP results in immune responses that are comparable to those induced by RAS or GAP lacking expression of UIS3 or UIS4, with an important role implicated for intrahepatic effector memory CD8⁺ T cells. The knowledge of the mediators of protective immunity after immunization with different GAP is important for the further development of vaccines consisting of genetically attenuated sporozoites.