Publications

Herein, the influence of carbon nanoparticle addition on the selective laser melting (SLM) behavior and the resultant properties of gas‐atomized CuCr0.3 powder are investigated. The carbon addition neither affects the powder flowability, nor its packing density, but it significantly enhances the optical absorption for infrared radiation. Despite the improved optical absorption of the powder bed after carbon addition, a comparable SLM behavior is observed for both virgin and carbon‐mixed CuCr0.3 powders. Furthermore, the addition of carbon nanoparticles facilitates in situ deoxidation of copper and chromium oxides present in the CuCr0.3 powder. Accordingly, a larger fraction of chromium is obtained in its metallic form in the as‐built carbon‐mixed CuCr0.3 part. The presence of metallic chromium allows tailoring of the mechanical and electrical properties by postheat treatments (HTs). The best combination of mechanical (tensile strength of 298 ± 19 MPa, yield strength of 208 ± 18 MPa, ductility of 21 ± 4%) and electrical (87 ± 1% international annealed copper standards [% IACS]) properties is realized for the carbon‐mixed CuCr0.3 alloy after a direct age hardening HT. The improvement in mechanical properties is attributed to the precipitation of nanometer‐sized, coherent, and metallic chromium precipitates in the copper matrix.

We have developed a flow cytometric method for demonstrating cell fusion between human immunodeficiency virus type 1 (HIV-1)- or HIV-2-infected HUT-78 cells and uninfected CD4-bearing MOLT-4 cells. Syncytium formation due to an interaction between the gp120 glycoprotein expressed on HIV-infected HUT-78 cells and the CD4 receptor present on MOLT-4 cells, resulted in an immediate decrease in the number of MOLT-4 cells; after a 24 h incubation period almost all MOLT-4 cells had disappeared from the culture. To show that the target MOLT-4 cells and not the aggressor HUT-78 cells were destroyed, specific monoclonal antibodies (MAbs) that reacted with antigens expressed on either MOLT-4 or HUT-78 cells were used. The formation of giant cells and the concomitant disappearance of MOLT-4 cells was blocked by MAbs specific for OKT4A and Leu3a, and, to a much lower level, by the MAbs specific of OKT4 and gp120. MAbs specific for OKT3, Leu2a, HLA-DR, Leu18 and LeuM3 did not prevent the disappearance of MOLT-4 cells. Sera from two AIDS patients containing antibodies to the HIV envelope glycoproteins did not protect MOLT-4 cells against the destructive effect of the HIV-infected HUT-78 cells. The fusion index, the percentage fusion inhibition and the 50% fusion inhibitory concentration of the MAbs can be accurately determined with the flow cytometric assay. The method can be readily implemented to evaluate any therapeutic treatment by examining its capacity to block cell-to-cell fusion, and hence destruction of the target bystander cells. Five anti-HIV compounds which have been previously shown to interfere with HIV binding to cells (namely pentosan polysulphate, heparin, suramin, aurintricarboxylic acid and Evans Blue) were further evaluated by this new method. With the exception of heparin, all of these compounds were found to inhibit cell-to-cell fusion and the concomitant destruction of the target bystander cells. Azidothymidine failed to inhibit fusion or bystander T cell destruction.

A kinetic analysis was performed for the novel 1-(8-phosphonooctyl)-6-amino-5-bromouracil and 1-(8-phosphonooctyl)-7-deazaxanthine inhibitors of Escherichia coli thymidine (dThd) phosphorylase (TPase). The structure of the compounds was rationally designed based on the available crystal structure coordinates of bacterial TPase. These inhibitors reversibly inhibited TPase. Kinetic analysis revealed that the compounds inhibited TPase in a purely competitive or mixed fashion not only when dThd, but also when inorganic phosphate (Pi), was used as the variable substrate. In contrast, the free bases 6-amino-5-bromouracil and 7-deazaxanthine behaved as non-competitive inhibitors of the enzyme in the presence of variable Pi concentrations while being competitive or mixed with respect to thymine as the natural substrate. Our kinetic data thus revealed that the novel 1-(8-phosphonooctyl)pyrimidine/purine derivatives are able to function as multisubstrate inhibitors of TPase, interfering at two different sites (dThd(Thy)- and phosphate-binding site) of the enzyme. To our knowledge, the described compounds represent the first type of such multisubstrate analogue inhibitors of TPase; they should be considered as lead compounds for the development of mechanistically novel type of TPase inhibitors.

The interaction between the HIV-1 transactivator protein Tat and RNA response element (TAR) plays a critical role in HIV-1 transcription. Based on the pharmacophore model of reported inhibitors, a series of novel substituted guanidine indole derivatives was designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 inhibitory activity using the IIIB strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity against HIV-1 IIIB. Quite unexpectedly, compound a-7 was also endowed with the moderate anti-HIV-2 potency (EC50 = 58.14 µM). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.

The synthesis and the antiviral activities of C-3 acyclic nucleoside analogues of imidazo[1,2-a]pyridine and pyrimidine are reported. From these compounds, 20, 21, 22, 23, 28, and 34 showed a specific activity against cytomegalovirus and/or varicella-zoster virus.