Synthesis of enantiomerically pure 1-O-phosphocholine-2-O-acyl-octadecane and 1-O-phosphocholine-2-N-acyl-octadecane

This is the first report on the chemical synthesis of enantiomerically pure R- or S-1-O-phosphocholine-2-O-acyl-octadecanes and R- or S-1-O-phosphocholine-2-N-acyl-octadecanes. From a structural point of view these phospholipids are intermediates between phosphatidylcholine and sphingomyelin. The synthesis of these model compounds is based on R- or S-1.2-O-isopropylidene-glyceraldeyde for chain elongation in a Wittig reaction with pentadecane-triphenylphosphine bromide. The resulting 1.2-O-isopropylidene-octadec-3-en is converted to R- or S-1.2-octadecanediol by catalytic hydrogenation of the double bond and by acidic removal of the isopropylidene protecting group. Tritylation of R- or S-1.2-octadecanediol results in the general intermediates R- or S-1-O-trityl-2-hydroxy-octadecane. These are the key intermediates for the synthesis of the phosphatidylcholine- or sphingomyelin-like end products. R- or S-1-O-phosphocholine-2-O-acyl-octadecane is obtained from the tritylated intermediates via benzylation in position 2, acidic detritylation and conversion of the R- or S-1-hydroxy-2-benzyl-octadecanes to the respective phosphocholines via the phosphoethanolamines. Catalytic hydrogenolysis of the benzyl group results in R- or S-1-O-phosphocholine-2-hydroxy-octadecane, which is converted to the phosphatidylcholine-like end products by acylation. R- or S-1-O-phosphocholine-2-N-acyl-octadecane is obtained from the tritylated intermediate by conversion of the R- or S-2-hydroxy group into the N-phthalimido group, which is achieved by inversion of the configuration using the Mitsunobu reaction with phthalimid. After acidic detritylation, the product is converted to the respective S- or R-1-O-phosphocholine derivative in a similar sequence of reactions. The phthalimido group is converted to the 2-amino group, and acylation results in the sphingomyelin-like end products.     

Comparison of selective cytotoxicity of alkyl lysophospholipids

Alkyl lysophospholipids have been shown to be cytooxic to a number of neoplastic tissues. One, ET-18-OCH₃, has been used to selectively purge leukemic cells from mixtures with normal marrow progenitor cells,in vitro andin vivo. We have measured the 50% inhibitory (IC₅₀) effect of a series of ether, lipids (EL) on leukemic cells (HL60, K562, Daudi, KG-1, KG-1a) and normal marrow progenitor cells. Cells were incubated with varying concentrations of EL for 4 hr and assayed for viability, [³H]thymidine incorporation and clonogenicity in semi-solid media. The effect on protein kinase C (PKC) activity was assayed for each compound. Compounds tested included three glycerophosphocholine analogs-ET-18-OCH₃, ET-16-NHCOCH₃, and BM 41.440. In addition, a lipoidal amine, CP 46665, an ethyleneglycolphospholipid, AEPL, and four single chain alkylphosphocholine analogs, HePC₂, HePC₃, HePC₄ and HePC₆ were also tested. During the period of incubation, the cells remained viable (>70%) as judged by trypan blue dye exclusion. The glycerophosphocholines were the most active and showed the highest therapeutic index. The lipoidal amine was active, but toxic to normal marrow progenitor cells. The ethyleneglycolphospholipid was active against HL60, but not against the other cell lines. The single chain alkylphosphocholine analogs were less active. All of the compounds inhibited PKC activity; however, the glycerophosphocholines were the most inhibitory. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

Time-of-flight studies on catalytic model reactions

Time-of-flight spectroscopy (TOF) and REMPI-TOF (resonance enhanced multi-photon ionization-TOF) were applied to measure the angular and translational energy distribution, as well as the internal state resolved energy distribution of desorption and reaction products on some model systems. Desorption of hydrogen and deuterium from clean and modified Pd(111) surfaces was studied, where the palladium sample was part of a permeation source. Water formation by reaction of oxygen with hydrogen on palladium was investigated by using different types of hydrogen supply: molecular H₂ exposure and atomic H exposure from the gas phase, as well as H exposure by permeating hydrogen. Vanadium oxide nanostructures on Pd(111) were prepared and the influence on D₂ desorption and D₂O production was investigated with the permeation technique. Additionally, deuterium desorption from sulfur and oxygen covered V(111) and V(100) surfaces was studied by TOF and REMPI-TOF spectroscopy. From the TOF spectra information concerning the reaction and desorption dynamics (activation barriers) could be gained.     

添加碳纳米管对选区激光熔化AlSi10Mg合金缺陷的影响

利用选区激光熔化成形技术制备了纯AlSi10Mg合金及碳纳米管(carbon nanotubes,CNTs)-AlSi10Mg复合材料。当添加CNTs含量为0.05%(质量分数)时具有一定增强效果,但随着CNTs添加量增大,复合材料性能却因为缺陷的增加而明显下降。木实验利用纳米CT技术对纯合金及CNTs(0.5%)-AlSi10Mg复合材料进行缺陷的三维重构。结果表明,添加0.5%的CNTs后,成形缺陷体积所占比例由12%增加至46%;气孔型缺陷数量明显增加,并且等效直径相对较大。CNTs在粉体中的团聚及对气体的吸附作用是两种类型缺陷增加的根本原因。     

Rapid evaluation of long-term thermal degradation of carbon fibre epoxy composites

Two commercially available carbon fibre reinforced composites (8552/IM7 and M18-1/G939) were exposed to heat above maximum operational temperature at various durations. Mass loss and mechanical properties were measured over time. A chemical analysis was also performed on these composites. The two primary components of each matrix, the epoxy resin and the thermoplastic, were observed to degrade at different rates under various thermal loading conditions. The epoxy resins degrade predominantly as measured by IR spectroscopy and thermal desorption/gas chromatography mass spectrometry. By using mass loss, strength, and IR spectroscopic data, a correlation was made between strength characteristics of each composite and the relative amount of the two primary matrix components. The developed relationship can be used to estimate rapidly the mechanical properties from the intensity ratio of IR bands characteristic of the two components.     

Techniques for Numerical Simulations of Concrete Slabs for Demolishing by Blasting

The subject of this article is the numerical simulation of concrete under explosive loading using a meshbased and a meshfree discretization technique. The presented techniques are verified by experimental data. Experimental evidence suggests that the complete stress–strain history relation must be considered as a basis for constitutive modeling if concrete is subjected to high loading rates. These dynamic phenomena cause a retardation of damage activation which must be taken into account when constitutive modeling is pursued on mesolevel instead of microlevel. By including a dynamic relaxation formulation within the framework of a general three-dimensional coupled continuum damage-plasticity law, it is shown that the solution of the wave propagation problem in materials with strain-softening becomes independent of mesh size. As the simulation of concrete under contact detonation causes severe numerical problems because of the large deformations, special numerical spatial discretization techniques have to be used. In this article we compare the results of a concrete slab under contact detonation using the finite element method code LS-DYNA with an arbitrary Lagrangian Eulerian coupling and the results obtained by a MLSPH code developed at our institute with experimental data. The same constitutive model for concrete and the same equation of state for the explosive is implemented in the two codes. The results of the different numerical simulations and the experimental data agree with each other well.     

Strain-Rate-Sensitive Constitutive Law for Concrete

Concrete strength is highly sensitive to loading procedure, especially in the range of high strain rates. On the basis of experimental results, it is demonstrated that the full loading history must be included in a dynamic constitutive model, not just consideration of the current strain rate. The rate effect is mainly attributed to internal inertia forces during microdamage evolution. A strain-history-dependent constitutive model is proposed based on this retarded activation of microdamage. A simplified version allows identification of material parameters for practical application. It is shown how this dynamic approach fits into the general framework of continuum damage mechanics.     

Vaccination against tick-borne encephalitis virus, a flavivirus, prevents disease but not infection, although viremia is undetectable

By adoptive transfer of sera or immunoglobulin preparations, vaccine-induced protection against TBEV has been demonstrated to be mediated by antibodies to the surface protein of TBEV, glycoprotein E. Nevertheless, the mechanism of vaccine-induced protection against TBEV remains unclear. Protection by E antibodies without in vitro neutralization was shown by one group, whereas others found a correlation between protection in vivo and neutralization in vitro. Here, the authors confirm in a mouse model of tick-borne encephalitis (TBE) that immunization with the whole-killed virus vaccine protects mice against a subsequent challenge with a highly lethal dose of virus, i.e. 250 LD50 doses. Vaccine-induced immunity, however, is not completely neutralizing as demonstrated by the development of immune responses to a non-structural virus protein absent from the vaccine, yet expressed in the course of virus replication. Antibodies specific for the non-structural protein 1 (NS1) and cytotoxic T-cells could be detected after, but not prior to, virus challenge of vaccinated animals, establishing that protection by this highly effective vaccine is not equivalent with complete neutralization of the challenge virus.     

Prediction of proteasome cleavage motifs by neural networks

We present a predictive method that can simulate an essentialstep in the antigen presentation in higher vertebrates, namelythe step involving the proteasomal degradation of polypeptidesinto fragments which have the potential to bind to MHC ClassI molecules. Proteasomal cleavage prediction algorithms publishedso far were trained on data from in vitro digestion experimentswith constitutive proteasomes. As a result, they did not takeinto account the characteristics of the structurally modifiedproteasomes—often called immunoproteasomes—foundin cells stimulated by