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.     

Localized Synthesis of Iron Oxide Nanowires and Fabrication of High Performance Nanosensors Based on a Single Fe2O3 Nanowire

A composed morphology of iron oxide microstructures covered with very thin nanowires (NWs) with diameter of 15–50 nm has been presented. By oxidizing metallic Fe microparticles at 255 °C for 12 and 24 h, dense iron oxide NW networks bridging prepatterned Au/Cr pads are obtained. X‐ray photoelectron spectroscopy studies reveal formation of α‐Fe₂O₃ and Fe₃O₄ on the surface and it is confirmed by detailed high‐resolution transmission electron microscopy and selected area electron diffraction (SAED) investigations that NWs are single phase α‐Fe₂O₃ and some domains of single phase Fe₃O₄. Localized synthesis of such nano‐ and microparticles directly on sensor platform/structure at 255 °C for 24 h and reoxidation at 650 °C for 0.2–2 h, yield in highly performance and reliable detection of acetone vapor with fast response and recovery times. First nanosensors on a single α‐Fe₂O₃ nanowire are fabricated and studied showing excellent performances and an increase in acetone response by decrease of their diameter was developed. The facile technological approach enables this nanomaterial as candidate for a range of applications in the field of nanoelectronics such as nanosensors and biomedicine devices, especially for breath analysis in the treatment of diabetes patients.     

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.     

Development of the bus joint for the ITER Central Solenoid

The terminations of the Central Solenoid (CS) modules are connected to the bus extensions by joints located outside the CS in the gap between the CS and torodial field (TF) assemblies. These joints have very strict space limitations. Low resistance is a common requirement for all ITER joints. In addition, the CS bus joints will experience and must be designed to withstand significant variation in the magnetic field of several tenths of a Tesla per second during initiation of plasma. The joint resistance is specified to be less than 4 nΩ.The joints also have to be soldered in the field and designed with the possibility to be installed and dismantled in order to allow cold testing in the cold test facility. We have developed coaxial joints that meet these requirements and have demonstrated the feasibility to fabricate and assemble them in the vertical configuration. We introduced a coupling cylinder with superconducting strands soldered to the surface of the cable that can be installed in the ITER assembly hall and at the cold test facility. This cylinder serves as a transition area between the CS module and the bus extension.We made two racetrack samples and tested four bus joints in our Joint Test Apparatus. Resistance of the bus joints was measured by a decay method and by a microvoltmeter; the value of the current was measured by the Hall probes. This measurement method was verified in the previous tests. The resistance of the joints varied insignificantly from 1.5 to 2 nΩ.One of the challenges associated with a soldered joint is the inability to use corrosive chemicals that are difficult to clean. This paper describes our development work on cable preparation, chrome removal, compaction, soldering, and final assembly and presents the test results.