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Keywords
1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described.
2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created.
3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment.
4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.
Optical flow estimation is known from Computer Vision where it is used to determine obstacle movements through a sequence of images following an assumption of brightness conservation. This paper presents the first study on application of the optical flow method to aerated stepped spillway flows. For this purpose, the flow is captured with a high-speed camera and illuminated with a synchronized LED light source. The flow velocities, obtained using a basic Horn–Schunck method for estimation of the optical flow coupled with an image pyramid multi-resolution approach for image filtering, compare well with data from intrusive conductivity probe measurements. Application of the Horn–Schunck method yields densely populated flow field data sets with velocity information for every pixel. It is found that the image pyramid approach has the most significant effect on the accuracy compared to other image processing techniques. However, the final results show some dependency on the pixel intensity distribution, with better accuracy found for grey values between 100 and 150.
Autoradiography is a well-established method of nuclear imaging. When different radionuclides are present simultaneously, additional processing is needed to distinguish distributions of radionuclides. In this work, a method is presented where aluminium absorbers of different thickness are used to produce images with different cut-off energies. By subtracting images pixel-by-pixel one can generate images representing certain ranges of β-particle energies. The method is applied to the measurement of irradiated reactor graphite samples containing several radionuclides to determine the spatial distribution of these radionuclides within pre-defined energy windows. The process was repeated under fixed parameters after thermal treatment of the samples. The greyscale images of the distribution after treatment were subtracted from the corresponding pre-treatment images. Significant changes in the intensity and distribution of radionuclides could be observed in some samples. Due to the thermal treatment parameters the most significant differences were observed in the ³H and ¹⁴C inventory and distribution.