4,552 publications from this institution
Abstract An improved synthesis of 5′-cycloSal-FdUMP 3a-g and 3′,5′-bis-cycloSal-FdUMP 9a-g as potential prodrugs of FdU 1 is described. In hydrolysis studies, phosphotriesters 3 released FdUMP 2 selectively by a tandem reaction. The biological activity of cycloSal-phosphotriesters 3 and 9 was evaluated in different cell lines.
A series of 3,5-bis(arylidene)-4-piperidones 1 and related N-acryloyl analogues 2 were prepared as candidate cytotoxic agents with a view to discerning those structural features which contributed to bioactivity. A number of the compounds were markedly cytotoxic toward murine P388 and L1210 leukemic cells and also to human Molt 4/C8 and CEM neoplasms. Approximately 40% of the IC50 values generated were lower than the figures obtained for melphalan. In virtually all cases, the N-acyl compounds were significantly more bioactive than the analogues 1. In general, structure−activity relationships revealed that the cytotoxicity of series 1 was correlated positively with the size of the aryl substituents, while in series 2, a -σ relationship was established. In particular, various angles and interatomic distances were obtained by molecular modeling, and the presence of an acryloyl group on the piperidyl nitrogen atom in series 2 affected the relative locations of the two aryl rings. This observation, along with some differences in distances between various atoms in series 1 and 2, may have contributed to the disparity in cytotoxicity between 1 and 2. The results obtained by X-ray crystallography of representative compounds were mainly in accordance with the observations noted by molecular modeling. Selected compounds interfered with the biosynthesis of DNA, RNA, and protein in murine L1210 cells, while others were shown to cause apoptosis in the human Jurkat leukemic cell line. This study has revealed the potential of these molecules for development as cytotoxic and anticancer agents.
Abstract In product design, a CAD model often needs to be constructed from a physical part. This process is called reverse engineering and is performed through dimensional digitising and CAD modelling. The dimensional digitising results in a cloud of points, which are input for the CAD modelling of surfaces corresponding to the object's features. Consistent with these features, some of the modelled surfaces need to join with positional, tangential or curvature continuity. This paper reports on the incorporation of these geometric boundary conditions in the CAD modelling of free-form surfaces from a cloud of points with non-uniform rational B-splines (NURBS). The described methods are illustrated with some practical, industrial examples and some alternative solutions are briefly described.
Innovative powder preparation and post-processing techniques can be employed to obtain high density ceramic parts by means of indirect selective laser sintering. Thermally induced phase separation (TIPS) was used to produce polymer and polymer–ceramic composite particles. The effect of polymer concentration, cooling rate, stirring and alumina particles on polymer and polymer–ceramic composite particles was investigated. Homogeneous spherical alumina–polypropylene (PP) composite powder was synthesized by TIPS for selective laser sintering (SLS). Green Al2O3–PP component parts with a density of 34% could be produced by conventional SLS of the polymer under optimized laser power, scan speed, scan spacing and powder preheating temperature. Various post-processing techniques like pressure infiltration (PI), warm isostatic pressing (WIPing) or a combination of both were applied to increase the green density of the Al2O3–PP SLM parts. Infiltrating the open porosity green SLS parts with a 30vol% alumina-powder based ethanol suspension allowed to increase the sintered density, i.e. after polymer debinding and pressureless sintering in air at 1600°C, from 38 to 64% of the theoretical density (TD). WIPing of the SLS and SLS/infiltrated green parts at 135°C and 64MPa allowed raising the green density up to 93 and 83% TD and a sintered density up to 89 and 88% TD, respectively.
No abstract is provided for this article.
Abrasive waterjet cutting is a manufacturing process that allows cutting a wide range of materials which are often difficult to process by means of conventional cutting methods. Similar to other beam type cutting processes, the waterjet is traditionally applied in a direction perpendicular to the surface to be cut. For cutting contours in pre-formed parts, 5- or 6-axis control is required to orient the waterjet beam perpendicular to the part surface along the cutting profile. In this paper, the results of experiments, performed to test the applicability of 3-axis nozzle control for cutting 3D profile parts, are presented. In these experiments, water pressure, feed rate, stand-off distance and inclination angle were varied as the most crucial process parameters. A case study of 3D cutting demonstrates that, with 3-axis control, tolerances of the order of magnitude of the positioning accuracy of the test set-up can be obtained.
