We have combined genetic algorithm (GA) and all paired (AP) support vector machine (SVM) methods for multiclass cancer categorization. Predictive features can be automatically determined through iterative GA/SVM, leading to very compact sets of non-redundant cancer-relevant genes with the best classification performance reported to date. Interestingly, these different classifier sets harbor only modest overlapping gene features but have similar levels of accuracy in leave-one-out cross-validations (LOOCV). Further characterization of these optimal tumor discriminant features, including the use of nearest shrunken centroids (NSC), analysis of annotations and literature text mining, reveals previously unappreciated tumor subclasses and a series of genes that could be used as cancer biomarkers. With this approach, we believe that microarray-based multiclass molecular analysis can be an effective tool for cancer biomarker discovery and subsequent molecular cancer diagnosis.

P-glycoprotein (Pgp) mediated drug efflux affects the absorption, distribution, and clearance of a broad structural variety of drugs. Early assessment of the potential of compounds to interact with Pgp can aid in the selection and optimization of drug candidates. To differentiate nonsubstrates from substrates of Pgp, a robust predictive pharmacophore model was targeted in a supervised analysis of three-dimensional (3D) pharmacophores from 163 published compounds. A comprehensive set of pharmacophores has been generated from conformers of whole molecules of both substrates and nonsubstrates of P-glycoprotein. Four-point 3D pharmacophores were employed to increase the amount of shape information and resolution, including the ability to distinguish chirality. A novel algorithm of the pharmacophore-specific t-statistic was applied to the actual structure-activity data and 400 sets of artificial data (sampled by decorrelating the structure and Pgp efflux activity). The optimal size of the significant pharmacophore set was determined through this analysis. A simple classification tree using nine distinct pharmacophores was constructed to distinguish nonsubstrates from substrates of Pgp. An overall accuracy of 87.7% was achieved for the training set and 87.6% for the external independent test set. Furthermore, each of nine pharmacophores can be independently utilized as an accurate marker for potential Pgp substrates.

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In this paper, the production of a logarithmic spiral bevel gear prototype is illustrated by the manufacture of the gear pinion. Firstly, the conical gear body of a logarithmic spiral bevel gear pinion was shaped on a C6140A1 lathe. A kinematic model of a five-axis vertical machining centre DMG DMU40 monoBLOCK, with the position and orientation of each axis relative to the movement of the workpiece, was created. In addition, the processing coordinate transformation formula between the workpiece coordinate system and the cutter coordinate system was devised. The cutter location file was converted to the numerical control code of the DMG DMU40 monoBLOCK. Finally, the pinion of a logarithmic spiral bevel gear was machined on the DMG DMU40 monoBLOCK as a prototype to be used in further research of the logarithmic spiral bevel gear.

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Taking the frame-supported shear wall structure of a 102.1 m high metro depot as the test object, the structure has obvious vertical irregularity, and a quasi-static test was carried out on the structural model with the scale of 1/5. The damage development and strain of the structure were observed by applying displacement loads under different seismic actions, and the experimental phenomena and measured data were analyzed. The results show that the safety performance of the structure meets the seismic requirements of the MCE (Maximum considered earthquake) condition. Under the action of load, a reasonable damage mechanism is formed in which the components above the transfer story crack first and those below the transfer story crack later, which is in line with the design concept of “the performance objective of the bottom frame structure is higher than that of the upper shear wall structure”. The transfer plate is mainly subjected to shear deformation, the possible shear failure of the transfer plate should be avoided by reasonable design. Due to the large height difference between the first floor and the second floor, the structure may be adversely affected, so it is necessary to make the yielding floor appear in the bottom strengthening part above the transfer story. Under the SLE (Service level earthquake) and DBE (Design based earthquake) conditions, the bottom frame of the structure is mainly subjected to elastic deformation. Under the MCE (Maximum considered earthquake) condition, the bottom frame of the structure causes a lot of damage, increases energy consumption and decreases stiffness, which further proves that “the performance goal of the bottom frame structure is higher than that of the upper shear wall structure”.

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