CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

DanNet: the challenge of compiling a wordnet for Danish by reusing a monolingual dictionary

This paper is a contribution to the discussion on compiling computational lexical resources from conventional dictionaries. It describes the theoretical as well as practical problems that are encountered when reusing a conventional dictionary for compiling a lexical-semantic resource in terms of a wordnet. More specifically, it describes the methodological issues of compiling a wordnet for Danish, DanNet, from a monolingual basis, and not—as is often seen—by applying the translational expansion method with Princeton WordNet as the English source. Thus, we apply as our basis a large, corpus-based printed dictionary of modern Danish. Using this approach, we discuss the issues of readjusting inconsistent and/or underspecified hyponymy hierarchies taken from the conventional dictionary, sense distinctions as opposed to the synonym sets of wordnets, generating semantic wordnet relations on the basis of sense definitions, and finally, supplementing missing or implicit information.     

Sensitivity of optimal shapes of artificial grafts with respect to flow parameters

The difficulties arising in the numerical solution of PDE-constrained shape optimization problems are manifold. Key ingredients are the optimization strategy and the shape deformation method. Furthermore, the robustness of the optimal shape with respect to simulation parameters is of great interest. In this paper, we consider fluid flows described by the incompressible Navier–Stokes equations. Previous studies on artificial bypass grafts indicated the need for specific constitutive models to account for the non-Newtonian nature of blood; in particular, the constitutive model was shown to affect the solution of the shape optimization problem. We employ a shape optimization framework that couples a finite element solver with quasi-Newton-type optimizers and a Bezier spline shape parametrization. To compute derivatives of the optimal shapes with respect to viscosity, we transform the entire optimization framework by combining the automatic differentiation tools Adifor2 and TAPENADE. We demonstrate the impact of the geometry parametrization and of geometric constraints on the optimization outcome. Finally, we employ the transformed framework to compute the sensitivity of the optimal shape of bypass grafts with respect to kinematic viscosity. The resulting sensitivities predict very accurately the influence of viscosity changes on the optimal shape. The proposed methodology provides a powerful tool to further investigate the necessity of intricate constitutive models by taking derivatives with respect to model parameters.     

Edge and line oriented contour detection: State of the art

We present an overview of various edge and line oriented approaches to contour detection that have been proposed in the last two decades. By edge and line oriented we mean methods that do not rely on segmentation. Distinction is made between edges and contours. Contour detectors are divided in local and global operators. The former are mainly based on differential analysis, statistical approaches, phase congruency, rank order filters, and combinations thereof. The latter include computation of contour saliency, perceptual grouping, relaxation labeling and active contours. Important aspects are covered, such as preprocessing aimed to suppress texture and noise, multiresolution techniques, connections between computational models and properties of the human visual system, and use of shape priors. An overview of procedures and metrics for quantitative performance evaluation is also presented. Our main conclusion is that contour detection has reached high degree of sophistication, taking into account multimodal contour definition (by luminance, color or texture changes), mechanisms for reducing the contour masking influence of noise and texture, perceptual grouping, multiscale aspects and high-level vision information.     

MICAST — The effect of magnetically controlled fluid flow on microstructure evolution in cast technical Al-alloys

The MICAST research program focuses on a systematic analysis of the effect of convection on the microstructure evolution in cast Al-alloys. The experiments within MICAST are carried out under well defined thermally and magnetically controlled, convective boundary conditions and analyzed using advanced diagnostics and theoretical modeling, involving phase field simulation, micro-modeling and global simulation of heat and mass transport. The MICAST team uses as a model material the Al-Si base alloys. This paper gives a brief overview on recent experimental results of the MICAST team on the effect of rotating magnetic fields on microstructure in AlSi alloys.     

Detecting infeasibility and generating cuts for mixed integer programming using constraint programming

We study a hybrid MIP/CP solution approach in which CP is used for detecting infeasibilities and generating cuts within a branch-and-cut algorithm for MIP. Our framework applies to MIP problems augmented by monotone constraints that can be handled by CP. We illustrate our approach on a generic multiple machine scheduling problem, and present a number of computational experiments.     

Artistic edge and corner enhancing smoothing.

Two important visual properties of paintings and painting-like images are the absence of texture details and the increased sharpness of edges as compared to photographic images. Painting-like artistic effects can be achieved from photographic images by filters that smooth out texture details, while preserving or enhancing edges and corners. However, not all edge preserving smoothers are suitable for this purpose. We present a simple nonlinear local operator that generalizes both the well known Kuwahara filter and the more general class of filters known in the literature as "criterion and value filter structure." This class of operators suffers from intrinsic theoretical limitations which give rise to a dramatic instability in presence of noise, especially on shadowed areas. Such limitations are discussed in the paper and overcome by the proposed operator. A large variety of experimental results shows that the output of the proposed operator is visually similar to a painting. Comparisons with existing techniques on a large set of natural images highlight conditions on which traditional edge preserving smoothers fail, whereas our approach produces good results. In particular, unlike many other well established approaches, the proposed operator is robust to degradations of the input image such as blurring and noise contamination.     

3D Virtual Pome Fruit Tissue Generation Based on Cell Growth Modeling

A 3D virtual fruit tissue generator is presented that can distinctly define the microstructural components of a fruit tissue and that can be used to model important physical processes such as gas transport during controlled atmosphere storage. The model is based on the biomechanics of plant cells in tissues. The main merit of this algorithm is that it can account for typical differences in intercellular air space networks and in cell size and shape found between different fruit species and tissues. The cell is considered as a closed thin walled structure, maintained in tension by turgor pressure. The cell walls of adjacent cells are modeled as parallel, linear elastic elements which obey Hooke's law. A 3D Voronoi tessellation is used to generate the initial topology of the cells. Intercellular air spaces of schizogenous origin are generated by separating the Voronoi cells along the edges where three Voronoi cells are in contact; while intercellular air spaces of lysigenous origin are generated by deleting (killing) some of the Voronoi cells randomly. Cell expansion then results from turgor pressure acting on the yielding cell wall material. To find the sequence of positions of each vertex and thus the shape of the tissue with time, a system of differential equations for the positions and velocities of each vertex is established and solved using a Matlab ordinary differential equation solver. Statistical comparison with synchrotron tomography images of fruit tissue is excellent. The virtual tissues can be used to study tissue mechanics and exchange processes of important metabolites.