Uncertainty and Sensitivity Analysis in Aircraft Operating Costs in Structural Design Optimization

The paper focuses on the development of an aircraft design optimization methodology that models uncertainty and sensitivity analysis in the tradeoff between manufacturing cost, structural requirements, andaircraft direct operating cost.Specifically,ratherthanonlylooking atmanufacturingcost, direct operatingcost is also consideredintermsof the impact of weight on fuel burn, in addition to the acquisition cost to be borne by the operator. Ultimately, there is a tradeoff between driving design according to minimal weight and driving it according to reduced manufacturing cost. Theanalysis of cost is facilitated withagenetic-causal cost-modeling methodology,andthe structural analysis is driven by numerical expressions of appropriate failure modes that use ESDU International reference data. However, a key contribution of the paper is to investigate the modeling of uncertainty and to perform a sensitivity analysis to investigate the robustness of the optimization methodology. Stochastic distributions are used to characterize manufacturing cost distributions, andMonteCarlo analysis is performed in modeling the impact of uncertainty on the cost modeling. The results are then used in a sensitivity analysis that incorporates the optimization methodology. In addition to investigating manufacturing cost variance, the sensitivity of the optimization to fuel burn cost and structural loading are also investigated. It is found that the consideration of manufacturing cost does make an impact and results in a different optimal design configuration from that delivered by the minimal-weight method. However, it was shown that at lower applied loads there is a threshold fuel burn cost at which the optimization process needs to reduce weight, and this threshold decreases with increasing load. The new optimal solution results in lower direct operating cost with a predicted savings of 640=m2 of fuselage skin over the life, relating to a rough order-of-magnitude direct operating cost savings of $500,000 for the fuselage alone of a small regional jet. Moreover, it was found through the uncertainty analysis that the principle was not sensitive to cost variance, although the margins do change.

Comet sensitivity in assessing DNA damage and repair in different cell cycle stages

The comet assay is a sensitive tool for estimation of DNA damage and repair at the cellular level, requiring only a very small number of cells. In comparing the levels of damage or repair in different cell samples, it is possible that small experimental effects could be confounded by different cell cycle states in the samples examined, if sensitivity to DNA damage, and repair capacity, varies with the cell cycle. We assessed this by arresting HeLa cells in various cell cycle stages and then exposing them to ionizing radiation. Unirradiated cells demonstrated significant differences in strand break levels measured by the comet assay (predominantly single-strand breaks) at different cell cycle stages, increasing from G1 into S and falling again in G2. Over and above this variation in endogenous strand break levels, a significant difference in susceptibility to breaks induced by 3.5 Gy ionizing radiation was also evident in different cell cycle phases. Levels of induced DNA damage fluctuate throughout the cycle, with cells in G1 showing slightly lower levels of damage than an asynchronous population. Damage increases as cells progress through S phase before falling again towards the end of S phase and reaching lowest levels in M phase. The results from repair experiments (where cells were allowed to repair for 10 min after exposure to ionizing radiation) also showed differences throughout the cell cycle with G1-phase cells apparently being the most efficient at repair and M-phase cells the least efficient. We suggest, therefore, that in experiments where small differences in DNA damage and repair are to be investigated with the comet assay, it may be desirable to arrest cells in a specific stage of the cell cycle or to allow for differential cycle distribution.

Use of breakpoint combination sensitivity testing as a simple and convenient method to evaluate the combined effects of ceftazidime and tobramycin on Pseudomonas aeruginosa and Burkholderia cepacia complex isolates in vitro

An in vitro method of determining the activity of antibiotics in combination which is simple and convenient to perform and which could be used routinely in clinical microbiology laboratories is desirable. We investigated the activity, against Pseudomonas aeruginosa and Burkholderia cepacia complex clinical isolates, of ceftazidime and tobramycin in combination using a broth macrodilution sensitivity method based on breakpoint minimum inhibitory concentrations and compared the results obtained using this method with those obtained using the microtitre checkerboard method. There was good agreement in interpretation of results between the two methods for both P. aeruginosa (90%) and B. cepacia complex isolates (70%) with tobramycin and for P. aeruginosa isolates (70%) with ceftazidime. As the breakpoint combination sensitivity testing method employs only four tubes and does not require initial determination of individual antibiotic minimum inhibitory concentrations, it is simpler and more convenient for determining the activity of antibiotics in combination than the microtitre checkerboard method. The use of this method in routine microbiology laboratories to determine the activity of antibiotic combinations against clinical isolates should optimise treatment of infection by ensuring that appropriate antibiotic combinations are prescribed. (C) 2004 Elsevier B.V. All rights reserved.