5-Acetyl-4-(4-methoxy­phen­yl)-6-methyl-3,4-dihydro­pyrimidin-2(1H)-one

In the title mol­ecule, C14H16N2O3, the heterocyclic ring adopts a flattened boat conformation, and the plane through its four coplanar atoms makes a dihedral angle of 89.65 (7)° with the benzene ring. The non-H atoms of the carbonyl, acetyl and methyl groups are nearly coplanar with the attached heterocyclic ring. Inter­molecular N—H⋯O and C—H⋯O hydrogen bonds are present in the crystal structure

5-Acetyl-4-(2-chloro­phen­yl)-6-methyl-3,4-dihydro­pyrimidin-2(1H)-one

In the title mol­ecule, C13H13ClN2O2, the heterocyclic ring adopts a flattened boat conformation with the plane through the four coplanar atoms making a dihedral angle of 89.16 (5)° with the benzene ring, which adopts an axial orientation. The carbonyl, acetyl and methyl groups each have an equatorial orientation. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds lead to a tape motif. The H atoms of the methyl group at position 6 are disordered over two positions of opposite orientation

Conserved Protective Mechanisms in Radiation and Genetically Attenuated uis3(-) and uis4(-) Plasmodium Sporozoites

Immunization with radiation attenuated Plasmodium sporozoites (RAS) elicits sterile protective immunity against sporozoite challenge in murine models and in humans. Similarly to RAS, the genetically attenuated sporozoites (GAPs) named uis3(-), uis4(-) and P36p(-) have arrested growth during the liver stage development, and generate a powerful protective immune response in mice. We compared the protective mechanisms in P. yoelii RAS, uis3(-) and uis4(-) in BALB/c mice. In RAS and GAPs, sterile immunity is only achieved after one or more booster injections. There were no differences in the immune responses to the circumsporozoite protein (CSP) generated by RAS and GAPs. To evaluate the role of non-CSP T-cell antigens we immunized antibody deficient, CSP-transgenic BALB/c mice, that are T cell tolerant to CSP, with P. yoelii RAS or with uis3(-) or uis4(-) GAPs, and challenged them with wild type sporozoites. In every instance the parasite liver stage burden was approximately 3 logs higher in antibody deficient CSP transgenic mice as compared to antibody deficient mice alone. We conclude that CSP is a powerful protective antigen in both RAS and GAPs viz., uis3(-) and uis4(-) and that the protective mechanisms are similar independently of the method of sporozoite attenuation

Investigation of the influence of varying tumbling strategies on a tumbling self-piercing riveting process

Abstract The increasing demands for the reduction of carbon dioxide emission require intensified efforts to increase resource efficiency. Especially in the mobility sector with large moving masses, resource savings can contribute enormously to the reduction of emissions. One possibility is to reduce the weight of the vehicles by using lightweight technologies. A frequently used method is the implementation of multi-material systems. These consist of dissimilar materials such as steel, aluminium or plastics. In the production of these systems, the joining of the different materials and geometries is a central challenge. Due to the increasing demands on the joints, the challenges for the joining processes itself are also increasing. Since conventional joining processes are rather rigid and can only react to a limited extent to disturbance variables or changing process variables, new methods and technologies are required. A widely used conventional joining method with these properties is self-piercing riveting. Because of the rigid tool combination and the fact that the rivet geometry that can be used is related to the tools, the joining of multi-material systems requires tool and rivet changes during the process. In order to extend the process window of joining with self-piercing rivet elements, the process is enhanced with a tumbling kinematic of the punch. The integration of tumbling results in a significant increase in the adjustable process parameters. This enables a higher material flow control in the joining process through a specific tumbling strategy. The materials investigated are a steel and an aluminium alloy, which differ significantly in their mechanical properties and have many applications in automotive engineering, especially for structural car body components. The steel material is a galvanized HCT590X+Z dual-phase steel, which is characterised by a low yield strength, combined with high tensile strength and a good hardening behaviour. The aluminium alloy is an EN AW-6014. The precipitation-hardening alloy consists of aluminium, magnesium and silicon with a high strength and energy absorption capability. The objective of this work is to obtain a fundamental knowledge of the new tumbling self-piercing riveting process. With different mechanical properties and different sheet thicknesses of the joining partners, the influences of these parameters on the tumbling strategy of the riveting process are analysed. Such a tumbling strategy is based on the tumbling angle, the tumbling onset and the tumbling kinematics. These parameters are investigated in the context of the work for selected combinations of multi-material systems consisting of HCT590X+Z and EN AW-6014. With the variation of the parameters, the versatility of the process can be investigated and influences of the tumbling on the self-piercing riveting process can be identified. To illustrate the results, force–displacement curves from the joining process of the individual joints are compared and the geometry of the rivet undercut and rivet heads are geometrically measured. Furthermore, micrographs allow the analysis of the characteristic joint parameters interlock, residual sheet thickness and end position of the rivet head

Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium </it>sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step of malaria infection, the requirements of <it>Plasmodium </it>parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.</p> <p>Results</p> <p>To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of <it>P. berghei</it>-infected hepatoma cells. The data analysis shows differential expression patterns for 1064 host genes starting at 6 h and up to 24 h post infection, with the largest proportion correlating specifically with the early stages of the infection process. A considerable proportion of those genes were also found to be modulated in liver cells collected from <it>P. yoelii-</it>infected mice 24 and 40 h after infection, strengthening the data obtained with the <it>in vitro </it>model and highlighting genes and pathways involved in the host response to rodent <it>Plasmodium </it>parasites.</p> <p>Conclusion</p> <p>Our data reveal that host cell infection by <it>Plasmodium </it>sporozoites leads to a coordinated and sequential set of biological events, ranging from the initial stage of stress response up to the engagement of host metabolic processes and the maintenance of cell viability throughout infection.</p

Ethyl 4-(3-bromo­phen­yl)-6-methyl-2-oxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

In the title compound, C14H15BrN2O3, the dihydro­pyrimidin­one ring adopts a boat conformation. In the crystal, adjacent mol­ecules are linked through N—H⋯O hydrogen bonds forming an R22(8) ring motif and generating a zigzag chain extending in [010]

Ethyl 4-(2-bromo-5-fluoro­phen­yl)-6-methyl-1-phenyl-2-thioxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

In the title mol­ecule, C20H18BrFN2O2S, the pyrimidine ring adopts a flattened envelope conformation. The halogenated benzene ring is orthogonal to the planar part of the pyrimidine ring [dihedral angle = 89.05 (4)°], while the other phenyl ring is oriented at an angle of 85.14 (5)°. The ethoxy group is disordered over two orientations with site occpancies of ca 0.869 (4) and 0.131 (4). Intra­molecular C—H⋯Br and C—H⋯O hydrogen bonds generate S(5) and S(6) ring motifs. The crystal structure is stabilized by inter­molecular N—H⋯S, C—H⋯F, C—H⋯O and C—H⋯Br hydrogen bonds

Microwave Assisted Synthesis of Py-Im Polyamides

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps