The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis

Antibiotic treatment options for Burkholderia cepacia infection are limited because of high intrinsic resistance. The problem is complicated by development of cross-resistance between antibiotics of different classes. We isolated antibiotic-resistant mutants by stepwise exposure to chloramphenicol (Chlor) and to trimethoprim/sulphamethoxazole (T/S) for four B. cepacia strains: ATCC13945, Per (clinical isolate), Cas and D4 (environmental isolates). Chlor(r) mutants did not produce chloramphenicol acetyl-transferase. Cross-resistance, defined as greater than four-fold increase in MIC by microtitre dilution method, was consistently seen in both types of mutants. For chloramphenicol-resistant (Chlor[r]) and trimethoprim/sulphamethoxazole-resistant (Tr/Sr) mutants of B. cepacia ATCC13945 and Cas, no MIC change was seen for piperacillin, ceftazidime, rifampicin, gentamicin, tobramycin, polymyxin B or azithromycin. B. cepacia-Per and -D4 mutants showed cross-resistance to ceftazidime and to piperacillin. Comparison of outer membrane protein (OMP) profiles of B. cepacia and their mutants by SDS-PAGE revealed Tr/Sr) mutants to be deficient in a major OMP (molecular weight 39-47 kDa). Tr/Sr mutants also expressed additional OMPs not found in wild type strains at 75-77 kDa for B. cepacia-ATCC13945 and -Cas, and 20-21 kDa in B. cepacia-D4 and -Per. No OMP changes occurred in Chlor(r) mutants. Lipopolysaccharide (LPS) profiles of each type of mutant showed new high and low molecular weight LPS bands. Cross-resistance seems to be mediated by alterations in porin and LPS for Tr/Sr mutants, but only by LPS in Chlor(r) mutants.     

Indicators for inspection and maintenance planning of concrete structures

Based on an idea introduced by Benjamin and Cornell (1970. Probability, statistics and decision for civil engineers. New York: McGaw Hill) and previous works by the authors it is demonstrated how condition indicators may be formulated for the general purpose of quality control and for assessment and inspection planning in particular. The formulation facilitates quality control based on sampling of indirect information about the condition of the considered components. This allows for a Bayesian formulation of the indicators whereby the experience and expertise of the inspection personnel may be fully utilized and consistently updated as frequentistic information is collected. The approach is illustrated on an example considering a concrete structure subject to corrosion. It is shown how half-cell potential measurements may be utilized to update the probability of excessive repair after 50 years. Furthermore in the same example it is shown how the concept of condition indicators might be applied to develop a cost optimal maintenance strategy composed of preventive and corrective repair measures.     

Substrate-induced conformational change in a trimeric ornithine transcarbamoylase

The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC 2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-L-ornithine (PALO) has been determined at 2.8-A resolution. This research on the structure of a transcarbamoylase catalytic trimer with a substrate analog bound provides new insights into the linkages between substrate binding, protein-protein interactions, and conformational change. The structure was solved by molecular replacement with the Pseudomonas aeruginosa catabolic OTCase catalytic trimer (Villeret, V., Tricot, C., Stalon, V. & Dideberg, O. (1995) Proc. Natl. Acad. Sci. USA 92, 10762-10766; Protein Data Bank reference pdb 1otc) as the model and refined to a crystallographic R value of 21.3%. Each polypeptide chain folds into two domains, a carbamoyl phosphate binding domain and an L-ornithine binding domain. The bound inhibitor interacts with the side chains and/or backbone atoms of Lys-53, Ser-55, Thr-56, Arg-57, Thr-58, Arg-106, His-133, Asn-167, Asp-231, Met-236, Leu-274, Arg-319 as well as Gln-82 and Lys-86 from an adjacent chain. Comparison with the unligated P. aeruginosa catabolic OTCase structure indicates that binding of the substrate analog results in closure of the two domains of each chain. As in E. coli aspartate transcarbamoylase, the 240s loop undergoes the largest conformational change upon substrate binding. The clinical implications for human OTCase deficiency are discussed.     

Energy-dependent phase-shift analysis of 2H+4He scattering in the energy range 0.87

VM Krasnopol''sky  VI Kukulin  EV Kuznetsova  J Horáek  NM Queen 《Canadian Metallurgical Quarterly》1991,43(2):822-834

Thermoreversible Gelcasting: A Novel Ceramic Processing Technique

A new ceramic processing method, thermoreversible gelcasting (TRG), has been developed. The method uses a gelation process that can be reversed multiple times. Two Al₂O₃ systems have been explored with the use of a specific triblock copolymer to form a binding gel network. The mixture becomes a free-flowing liquid on heating above 60°C. However, on cooling below 60°C, the slurry instantaneously transforms to a physical gel. This process can be reversed easily (essentially with an infinite processing time window) while the solvent is present in the system, which is advantageous when trying to produce high-quality dense pieces if initial casting irregularities occur. Near-theoretically dense specimens have been produced with properties consistent with reported values of high-density Al₂O₃.