Candidate lung tumor susceptibility genes identified through whole-genome association analyses in inbred mice

We performed a whole-genome association analysis of lung tumor susceptibility using dense SNP maps ( approximately 1 SNP per 20 kb) in inbred mice. We reproduced the pulmonary adenoma susceptibility 1 (Pas1) locus identified in previous linkage studies and further narrowed this quantitative trait locus (QTL) to a region of less than 0.5 Mb in which at least two genes, Kras2 (Kirsten rat sarcoma oncogene 2) and Casc1 (cancer susceptibility candidate 1; also known as Las1), are strong candidates. Casc1 knockout mouse tumor bioassays showed that Casc1-deficient mice were susceptible to chemical induction of lung tumors. We also found three more genetic loci for lung adenoma development. Analysis of one of these candidate loci identified a previously uncharacterized gene Lasc1, bearing a nonsynonymous substitution (D102E). We found that the Lasc1 Glu102 allele preferentially promotes lung tumor cell growth. Our findings demonstrate the prospects for using dense SNP maps in laboratory mice to refine previous QTL regions and identify genetic determinants of complex traits.     

Wildtype Kras2 can inhibit lung carcinogenesis in mice

Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.     

Fault-Tolerant Control for a Class of Uncertain Systems with Actuator Faults

The problem of fault-tolerant controller design for a class of polytopic uncertain systems with actuator faults is studied in this paper. The actuator faults are presented as a more general and practical continuous fault model. Based on the affine quadratic stability (AQS), the stability of the polytopic uncertain system is replaced by the stability at all corners of the polytope. For a wide range of problems including H∞ and mixed H 2 /H∞ controller design, sufficient conditions are derived to guarantee the robust stability and performance of the closed-loop system in both normal and fault cases. In the framework of the linear matrix inequality (LMI) method, an iterative algorithm is developed to reduce conservativeness of the design procedure. The effectiveness of the proposed design is shown through a flight control example.     

Extraction of affine invariant features for shape recognition based on ant colony optimization

A new approach to extraction of affine invariant features of contour image and matching strategy is proposed for shape recognition.Firstly,the centroid distance and azimuth angle of each boundary point are computed.Then,with a prior-defined angle interval,all the points in the neighbor region of the sample point are considered to calculate the average distance for eliminating noise.After that,the centroid distance ratios(CDRs) of any two opposite contour points to the barycenter are achieved as the representation of the shape,which will be invariant to affine transformation.Since the angles of contour points will change non-linearly among affine related images,the CDRs should be resampled and combined sequentially to build one-by-one matching pairs of the corresponding points.The core issue is how to determine the angle positions for sampling,which can be regarded as an optimization problem of path planning.An ant colony optimization(ACO)-based path planning model with some constraints is presented to address this problem.Finally,the Euclidean distance is adopted to evaluate the similarity of shape features in different images.The experimental results demonstrate the efficiency of the proposed method in shape recognition with translation,scaling,rotation and distortion.