Effects of dietary flavonoids on the transport of cimetidine via P-glycoprotein and cationic transporters in Caco-2 and LLC-PK1 cell models.

1. The hypotheses tested were to study cimetidine as a substrate of P-glycoprotein (P-gp) and organic cation transport systems and the modulatory effects of eight flavonoid aglycones and glycosides on these transport systems using Caco-2 and LLC-PK1 cells. 2. Transport and uptake experiments of (20 microM) (3)H-cimetidine were performed with and without co-exposure to quercetin, quercetrin, rutin, naringenin, naringin, genistein, genistin, and xanthohumol. Co-treatment decreased basolateral to apical (B to A) permeability (P(app)) of cimetidine from 2.02 to 1.24 (quercetin), 1.06 (naringenin), 1.24 (genistein), and 0.96 (xanthohumol) x 10(-6) cm s(-1) in Caco-2 cells and from 10.76 to 1.65 (quercetin), 2.05 (naringenin), 2.88 (genistein), and 1.95 (xanthohumol) x 10(-6) cm s(-1) in LLC-PK1 cells. Genistin significantly reduced B to A P(app) of cimetidine to 1.24 x 10(-6) cm s(-1) in Caco-2 cells. Basolateral intracellular uptake rate of cimetidine was enhanced 145-295% when co-treated with flavonoids. Co-treatment with P-glycoprotein and organic cation transporter inhibitors, verapamil and phenoxybenzamine, resulted in reduced B to A permeability and slower basolateral intracellular uptake rate of cimetidine. Intracellular uptake rate of (14)C-tetraethylammonium (TEA) was reduced in the presence of quercetin, naringenin and genistein in LLC-PK1 cells. 3. In conclusion, quercetin, naringenin, genistein, and xanthohumol reduced P-gp-mediated transport and increased the basolateral uptake rate of cimetidine. Quercetin, naringenin, genistein, but not xanthohumol, reduced intracellular uptake rate of TEA in LLC-PK1 cells. These results suggest that flavonoids may have potential to alter the disposition profile of cimetidine and possibly other therapeutics that are mediated by P-gp and/or cation transport systems.

Segmentation of psoriasis vulgaris images using multiresolution-based orthogonal subspace techniques.

In this paper, a method is proposed for the segmentation of color images using a multiresolution-based signature subspace classifier (MSSC) with application to psoriasis images. The essential techniques consist of feature extraction and image segmentation (classification) methods. In this approach, the fuzzy texture spectrum and the two-dimensional fuzzy color histogram in the hue-saturation space are first adopted as the feature vector to locate homogeneous regions in the image. Then these regions are used to compute the signature matrices for the orthogonal subspace classifier to obtain a more accurate segmentation. To reduce the computational requirement, the MSSC has been developed. In the experiments, the method is quantitatively evaluated by using a similarity function and compared with the well-known LS-SVM method. The results show that the proposed algorithm can effectively segment psoriasis images. The proposed approach can also be applied to general color texture segmentation applications.

Adaptive fuzzy terminal sliding mode controller for linear systems with mismatched time-varying uncertainties.

A new design approach of an adaptive fuzzy terminal sliding mode controller for linear systems with mismatched time-varying uncertainties is presented in this paper. A fuzzy terminal sliding mode controller is designed to retain the advantages of the terminal sliding mode controller and to reduce the chattering occurred with the terminal sliding mode controller. The sufficient condition is provided for the uncertain system to be invariant on the sliding surface. The parameters of the output fuzzy sets in the fuzzy mechanism are adapted on-line to improve the performance of the fuzzy sliding mode control system. The bounds of the uncertainties are not required to be known in advance for the presented adaptive fuzzy sliding mode controller. The stability of the fuzzy control system is also guaranteed. Moreover, the chattering around the sliding surface in the sliding mode control can be reduced by the proposed design approach. Simulation results are included to illustrate the effectiveness of the proposed adaptive fuzzy terminal sliding mode controller.

Internationalization of the animal science undergraduate curriculum: a survey of its current status, barriers to its implementation and its value.

The goal of this project was to identify the current level at which internationalization has been adopted as a theme in the North American animal science curriculum and to identify its value and the barriers to its implementation. We surveyed animal, dairy, and poultry science departments across Canada and the United States. One hundred twenty-four surveys were mailed and 60% were returned. Associations between aspects of internationalization and student outcomes (admission to veterinary and graduate schools and starting salaries) were examined. Although administrators strongly believed internationalization had value, implementation was limited. The most common practices included international content in core animal science classes, advising, international internships, and participation of faculty in international scholarly activities. Few departments have incorporated internationalization into their mission statements or developed a specific international-themed class, scholarships devoted to international activities, or roles for international students. Few departments reported participation of students in international programs. Barriers included finances and limited commitment from higher administration. Student outcomes were positively associated with faculty size, percentage of international faculty, the ratio of international students to the total student population, international content in core animal science classes, a specific international-themed class, availability of international internships, and exchange of class material internationally via the Internet. Departments that did not offer international opportunities had a negative association (r = -0.79) with starting salary, but these relationships may not be causal. Alternatively, progressive departments may attract and retain exceptional students. The analysis indicated an awareness of the value of international programs, positive impacts in student outcomes, and financial barriers to implementation.

Flexible complexity reduced PID-like fuzzy controllers.

In this paper, a flexible complexity reduced design approach for PID-like fuzzy controllers is proposed. With the linear combination of input variables as a new input variable, the complexity of the fuzzy mechanism of PID-like fuzzy controllers is significantly reduced. However, the performance of the complexity reduced fuzzy PID controller may be degraded since the degree of freedom is decreased by the combination of input variables. To alleviate the drawback and improve the performance of the complexity reduced PID-like fuzzy controller, a flexible complexity reduced design approach is introduced in which the functional scaling factors are heuristically generated. Since the functional scaling factors are heuristically created, they can be easily adjusted for the flexible complexity reduced PID-like fuzzy controller without a priori knowledge of the exact mathematical model of the plant. Moreover, heuristic scaling factors are implemented as functionals. Therefore, the complexity of the flexible PID-like fuzzy controller will not be increased. Further, the stability of the fuzzy control system with a flexible complexity reduced PID-like fuzzy controller is discussed. Finally, the simulation results are also included to show the effectiveness of the PID-like fuzzy controller designed with the flexible complexity reduced approach.

Design and analysis of region-wise linear fuzzy controllers.

In this paper, a methodology to reduce the complexity of a robust controller based on fuzzy if-then rules is proposed. The motivation and the design of this complexity-reduced fuzzy controller are presented. This fuzzy controller with the triangular membership functions and fuzzy partition methods used here leads to a region-wise linear fuzzy controller (RLFC). The properties of the region-wise linear fuzzy controllers are discussed and the reasons why they in general perform better than the PD controllers are also provided. And the simulation results based on a second order plant are included to show that the region-wise linear fuzzy controller outperforms the PD controller. We also show that the region-wise linear fuzzy controller and original fuzzy controller have similar performances.

Decision-based neural networks with signal/image classification applications.

Supervised learning networks based on a decision-based formulation are explored. More specifically, a decision-based neural network (DBNN) is proposed, which combines the perceptron-like learning rule and hierarchical nonlinear network structure. The decision-based mutual training can be applied to both static and temporal pattern recognition problems. For static pattern recognition, two hierarchical structures are proposed: hidden-node and subcluster structures. The relationships between DBNN's and other models (linear perceptron, piecewise-linear perceptron, LVQ, and PNN) are discussed. As to temporal DBNN's, model-based discriminant functions may be chosen to compensate possible temporal variations, such as waveform warping and alignments. Typical examples include DTW distance, prediction error, or likelihood functions. For classification applications, DBNN's are very effective in computation time and performance. This is confirmed by simulations conducted for several applications, including texture classification, OCR, and ECG analysis.