High-resolution spectrum of xenon ions at 13.4 nm

The spectrum of xenon excited in a low-inductance vacuum spark was photographed at high resolution in the region of 9.5-15.5 nm. The observed transitions were identified as belonging to ions from Xe8+ to Xe13+. In the region of importance for extreme-ultraviolet lithography around 13.4 nm, the strongest lines were identified as 4d8-4d7 5p transitions in Xe10+. The identifications were made by use of energy parameters extrapolated along the isoelectronic sequence.     

The initiation,evaluation and selection of operational research projects

This paper discusses the problems involved in conducting successful Operational Research within a large organisation and suggests ways of overcoming them. It describes ways in which Operational Research projects arise, methods of assessing their relative merits, and methods used by the authors to obtain a suitable portfolio of projects. It is argued that an Operational Research Group should apply to its own project planning the scientific approach that it advocates for others.     

Regioselective synthesis of 4-(2-alkyl-5-methyl-2H-pyrazol-3-yl)-piperidines

The regioselective, scaleable synthesis of three 4-(2-alkyl-5-methyl-2H-pyrazol-3-yl)-piperidines is discussed.     

A statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophoric molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis

A statistical sampling protocol is described to assess the fidelity of libraries encoded with molecular tags. The methodology, termed library QA, is based on the combined application of tag decode analysis and single bead LC/MS. The physical existence of library compounds eluted from beads is established by comparing the molecular weight predicted by tag decode with empirical measurement. The goal of sampling is to provide information on overall library fidelity and an indication of the performance of individual library synthons. The minimal sampling size n for library QA is l0 x the largest synthon set. Data are reported as proportion (p) +/- lower and upper boundary (lb-ub) computed at the 95% confidence level (alpha = 0.05). As a practical demonstration, library QA was performed on a 25,200-member library of statine amides (size = 40 x 63 x 10). Sampling was conducted three times at n approximately 630 beads per run for a total of 1902 beads. The overall proportions found for the three runs were consistent with one another: p = 84.4%, lb-ub = 81.5-87.2%; p = 83.1%, lb-ub = 80.2-85.95; and p = 84.5%, lb-ub = 81.8-87.3%, suggesting the true value of p is close to 84% compound confirmation. The performance pi of individual synthons was also computed. Corroboration of QA data with biological screening results obtained from assaying the library against cathepsin D and plasmepsin II is discussed.     

Design, synthesis, and biological evaluation of a library of 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides

A library of 422 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides was prepared in five steps using solution-phase chemistry. The first step in the synthesis was the reaction of ethyl 2-ethoxymethylene-3-oxo-4,4,4-trifluorobutanoate with thiosemicarbazide, which is reported in the literature to afford a 1:1 mixture of ethyl 1-thiocarbamoyl-5-(trifluoromethyl)pyrazole-4-carboxylate and ethyl 1-thiocarbamoyl-3-(trifluoromethyl)pyrazole-4-carboxylate. We reassigned the structure of the product to be a single compound, ethyl 5-hydroxy-1-thiocarbamoyl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-4-carboxylate. This common intermediate was diversified by reaction with 17 alpha-bromoketones affording, in two steps, 17 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxylic acids. Scavenger resins were used to facilitate formation and purification of up to 27 amides from each of these acids in the last step. In addition, the Curtius reaction was applied to 12 of the acids followed by quenching with alcohols to afford a 108-member carbamate library. Certain compounds in the two libraries were toxic to C. elegans.     

Choosing the Operational Research Programme for B.I.S.R.A

This paper examines some important problems in the evaluation and selection of research projects, with particular reference to operational research projects in a central industry research organization. A method for project evaluation is suggested which provides data suitable for use in a powerful and flexible formal procedure for project selection. In evaluating a project, the assessment of resource requirements is based on a probabilistic network plan of the project, and the estimates of benefits are derived from the marginal effects on the industry of performing or not performing the project, using discounted cash flow techniques. The procedure for project selection chooses not only the projects to be undertaken, but also the team sizes that should be used. A wide variety of constraints can be imposed on the system to reflect different aspects of management policy or other special factors. The procedures described have been implemented, and have proved well worth while.     

(119)Sn MAS NMR and first-principles calculations for the investigation of disorder in stannate pyrochlores

The local structure and cation disorder in Y(2)Ti(2-x)Sn(x)O(7) pyrochlores, materials proposed for the encapsulation of lanthanide- and actinide-bearing radioactive waste, is studied using (119)Sn (I = 1/2) NMR spectroscopy. NMR provides an excellent probe of disorder, as it is sensitive to the atomic scale environment without the need for any long-range periodicity. However, the complex and overlapping spectral resonances that often result can be difficult to interpret. Here, we demonstrate how (119)Sn DFT calculations can be used to aid the spectral interpretation and assignment, confirming that Sn occupies only the six-coordinate pyrochlore B site, and that the Sn chemical shift is sensitive to the number of Sn/Ti on the neighbouring B sites. Although distinct resonances are resolved experimentally when the Ti content is low, there is significant spectral overlap for Ti-rich compositions. We establish that this is a result of two competing contributions to the Sn chemical shift; an upfield shift resulting from the incorporation of the more polarizing Ti(4+) cation onto the neighbouring B sites, and a concomitant downfield shift arising from the decrease in unit cell size. Despite the considerably easier spectral acquisition, the lower resolution in the (119)Sn spectra hinders the extraction of the detailed structural information previously obtained using (89)Y NMR. However, the spectra we obtain are consistent with a random distribution of Sn/Ti on the pyrochlore B sites. Finally, we consider whether an equilibrium structure has been achieved by investigating materials that have been annealed for different durations.