Biologic Phenotyping of the Human Small Airway Epithelial Response to Cigarette Smoking

BACKGROUND: The first changes associated with smoking are in the small airway epithelium (SAE). Given that smoking alters SAE gene expression, but only a fraction of smokers develop chronic obstructive pulmonary disease (COPD), we hypothesized that assessment of SAE genome-wide gene expression would permit biologic phenotyping of the smoking response, and that a subset of healthy smokers would have a "COPD-like" SAE transcriptome. METHODOLOGY/PRINCIPAL FINDINGS: SAE (10th-12th generation) was obtained via bronchoscopy of healthy nonsmokers, healthy smokers and COPD smokers and microarray analysis was used to identify differentially expressed genes. Individual responsiveness to smoking was quantified with an index representing the % of smoking-responsive genes abnormally expressed (I(SAE)), with healthy smokers grouped into "high" and "low" responders based on the proportion of smoking-responsive genes up- or down-regulated in each smoker. Smokers demonstrated significant variability in SAE transcriptome with I(SAE) ranging from 2.9 to 51.5%. While the SAE transcriptome of "low" responder healthy smokers differed from both "high" responders and smokers with COPD, the transcriptome of the "high" responder healthy smokers was indistinguishable from COPD smokers. CONCLUSION/SIGNIFICANCE: The SAE transcriptome can be used to classify clinically healthy smokers into subgroups with lesser and greater responses to cigarette smoking, even though these subgroups are indistinguishable by clinical criteria. This identifies a group of smokers with a "COPD-like" SAE transcriptome

Developing an advanced PWM-switch model including semiconductor device non-linearities

The accurate simulation of power electronic systems is possible when including accurate models of the semiconductor devices, but practically not affordable. Classical ideal averaged models of the system are not suitable either. Hence, averaged models including the non-linear effects of the power semiconductor devices appear quite efficient. The proposed non-ideal PWM-switch model is a useful method for modeling pulse width modulated converters operating in the continuous conduction mode. The main advantages of the proposed averaged model are the takes into account of the non-linear effects of power devices and the possibility to estimate the dissipated power in the different circuit devices. The proposed electrical model can be applied to bi-directional converters and allows the coupling with thermal model in the power electronic system. A simple technique to evaluate the different static and dynamic parameters of the devices, from manufacturers data sheets or experimentally, is presented

Optimization of electronics component placement design on PCB using Self Organizing Genetic Algorithm (SOGA)

The optimal placement of electronic components on a printed circuit board (PCB) requires satisfying multiple conflicting design objectives as most of the components have different power dissipation, operating temperature, types of material and dimension. In addition, most electronic companies are currently emphasizing on designing a smaller package electronic system in order to increase the system performance. This paper presents a new self organizing genetic algorithm (SOGA) method for solving this multi-objective optimization problem. The SOGA can be viewed as a cascade of two GAs which consists of two steps fitness evaluation process to ensure that the fitness of selected chromosomes for each iteration process is optimally selected. The algorithm is developed based on weighted sum approach genetic algorithm (WSGA) where an inner loop GA is used to optimize the selection of weights of the WSGA. Experiments are conducted to evaluate the performance of SOGA. Four objective functions are formulated in the experiments which are temperature of components, area of PCB, high power component placement and high potential critical components distance. Comparisons of the performance of SOGA are made with two well known methods namely fixed weight GA (FWGA) and random weighted GA (RWGA). The results show that the SOGA gives a better optimal solution as compared to the other methods