On the basis of a simple theoretical model, the ease of penetration of f3-lactam antibiotics through the outer membrane ofEscherichia coli was measured. The cell envelope was found to act as a diffusion barrier to both penicillins and cephalosporins. The validity of the model and the cooperative action of cellbound f8-lactamase and outer membrane were further verified by comparing calculated and experimentally determined velocities of /8-lactam hydrolysis by intact cells and sonically treated cell suspensions. The results showed good correspondence at five different antibiotic concentrations. Similar conclusions could be drawn from a comparison of (3-lactam concentrations on both sides of the outer membrane, calculated from enzyme kinetic measurements and minimal inhibitory concentrations for both a (8-lactamase-producing E. coli and its enzyme-negative variant. in the case of benzylpenicillin and cephalothin, however, no correspondence was found. The joint action of several parameters determining the efficacy of penicillins and cephalosporins against 63-lactamaseproducing E. coli is discussed.Escherichia coli can carry extrachromosomal resistance determinants (R factors) mediating constitutive synthesis of 3-lactamase (EC 3.5.2.6). The production of this enzyme renders the organisms less susceptible to the lethal action of penicillins and cephalosporins and may even lead to complete resistance to these antibiotics (14, 15, 17).Whereas gram-positive 63-lactamase-producing organisms liberate their enzyme into the surrounding medium, the 3-lactamases of gram negative bacteria are compartmentalized (4,15). The fact that these enzymes can be totally released from E. coli by osmotic shock (8, 9) demonstrates that they are attached loosely to the cytoplasmic membrane or localized in the periplasm.Both f3-lactamases and the outer membrane are important factors in the resistance ofE. coli to penicillins and cephalosporins (1-3, 18). Conclusions regarding the ease of penetration of these antibiotics through the outer membrane, however, have mainly been drawn from comparisons of rates of hydrolysis by intact cells and sonically treated cell suspensions (6, 15). This determination alone is not sufficient to measure outer-membrane permeability.Given a periplasmic localization of 3-lactamase and assuming that both penicillins and

The effect of quindoxin on the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid, and protein in Escherichia coli KL 399 was examined under aerobic and anaerobic conditions. In the absence of oxygen the synthesis of DNA was completely inhibited by 10 ppm of quindoxin, whereas the syntheses of ribonucleic acid and protein were not affected. Quinoxalin-di-N-oxides (QdNO) induce degradation of DNA in both proliferating and non-proliferating cells.polA, recA, recB, recC, exrA, and uvrA mutants were more susceptible than the corresponding repair-proficient strains. All strains were more resistant in the presence of oxygen. The potent in vivo activity of various quinoxaline-1,4-di-N-oxides (QdNO) against diverse bacteria, Entamoeba histolytica, and Chlamydiae of the psittacosis-lymphogranuloma venereum group has been known for more than two decades (9,24,29,35,50). Like many antibiotics (e.g., penicillin or tetracyclines) and chemotherapeutics (e.g., nitrofuran or sulfonamide), QdNO increase the live weight gain in young chickens, pigs, and calves when added to the diet (5,12,16,37). At present two QdNO, carbadox and olaquindox, are on the market as growth promoters in various countries; a third, quindoxin, has been withdrawn.QdNO were first prepared as potential antagonists of vitamin K activity, but such antagonism has never been demonstrated (24,35). Only a few further reports on the mode of action have been published. Studies on the effect of 2,3-dihydroximethyl-quinoxaline-1,4-di-N-oxide on the incorporation of radioactive precursors into deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein in Escherichia coli revealed a specific inhibition of DNA synthesis (15). Morphological changes in cells of E. coli and Staphylococcus aureus treated with 2,3-dihydroxit Present address:

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Purpose: To quantify the reliability of fully automated image registration (IR) of planning CTs with 2D MV/kV projections or kV‐CBCTs in terms of its failure rate, and to investigate the influence of algorithmic and external parameters on registration quality. Methods: A gold standard registration is necessary to evaluate the failure rate. We develop a novel framework to obtain unique gold standards for MV imaging: we simulate setup images from 50 patient CTs (5 anatomic sites), using HU mapping, simple raytracing, a semi‐empirical scatter model and noise addition. Comparing simulated and acquired images yields excellent agreement. We introduce translations (≤2cm) and rotations (≤2°) with respect to the planned isocenter between planning CTs and setup images according to reported setup‐errors in the literature, followed by using the clinically available IR software from Varian Medical Systems (Palo Alto). Application of this simulation framework to 2D/3D kV imaging is work in progress. Results: We investigate the dependence of the registration failure rate on the field size of MV projection images (square, centered at planned isocenter, detected shift >2mm from known shift). The results suggest a minimum field size of 10×10 cm2 to achieve reasonably small failure rates (<10%). We define an optimized parameter set for 2D/3D MV IR, which outperforms the default one of the IR software with respect to the failure rate (<3%), while not significantly (<50%) increasing computation time. Conclusion: The developed framework demonstrates the possibility of systematic tests of automated IR for arbitrarily large patient datasets. To our current knowledge this is a novel strategy. We are able to define optimized default parameter sets for registration algorithms and to estimate the influence of parameters, such as imaging dose, on the quality of IR. The improvements made for MV IR in this work look promising. Similar studies for kV based IR are work in progress.