Chemically Synthesized 58‐mer LysM Domain Binds Lipochitin Oligosaccharide

Recognition of carbohydrates by proteins is a ubiquitous biochemical process. In legume–rhizobium symbiosis, lipochitin oligosaccharides, also referred to as nodulation (nod) factors, function as primary rhizobial signal molecules to trigger root nodule development. Perception of these signal molecules is receptor mediated, and nod factor receptor 5 (NFR5) from the model legume Lotus japonicus is predicted to contain three LysM domain binding sites. Here we studied the interactions between nod factor and each of the three NFR5 LysM domains, which were chemically synthesized. LysM domain variants (up to 58 amino acids) designed to optimize solubility were chemically assembled by solid‐phase peptide synthesis (SPPS) with microwave heating. Their interaction with nod factors and chitin oligosaccharides was studied by isothermal titration calorimetry and circular dichroism (CD) spectroscopy. LysM2 showed a change in folding upon nod factor binding, thus providing direct evidence that the LysM domain of NFR5 recognizes lipochitin oligosaccharides. These results clearly show that the L. japonicus LysM2 domain binds to the nod factor from Mesorhizobium loti, thereby causing a conformational change in the LysM2 domain. The preferential affinity for nod factors over chitin oligosaccharides was demonstrated by a newly developed glycan microarray. Besides the biological implications, our approach shows that carbohydrate binding to a small protein domain can be detected by CD spectroscopy.     

Design of a General‐Purpose European Compound Screening Library for EU‐OPENSCREEN

This work describes a collaborative effort to define and apply a protocol for the rational selection of a general‐purpose screening library, to be used by the screening platforms affiliated with the EU‐OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening‐compliant physicochemical properties, loose compliance to drug‐likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre‐filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in‐house methodology and expertise. An in‐depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics‐driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general‐purpose self‐organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU‐OPENSCREEN library could be directly compared with distributions of known bioactives of various classes. This mapping highlights the relevance of the selection and shows how the consensus reached by merging the five different 40K selections contributes to achieve this relevance. The approach also allows one to readily identify subsets of target‐ or target‐class‐oriented compounds from the EU‐OPENSCREEN library to suit the needs of the diverse range of potential users. The final EU‐OPENSCREEN library, assembled by merging five independent selections of 40K compounds from various expert groups, represents an excellent example of a Europe‐wide collaborative effort toward the common objective of building best‐in‐class European open screening platforms.     

A combinatorial intra-enterprise exchange for logistics services

The exchange of cargo capacities is a well established approach in logistics. However, only few logistics marketplaces are able to take into consideration synergies that can be generated by combining different transportation routes of different logistics carrierps. In order to exploit these synergies, we designed and implemented the combinatorial exchange mechanism ComEx for the intra-enterprise exchange of delivery orders in a logistics company organized in a profit center structure. Each profit center is able to release delivery orders to an adjacent profit center if the geographic locations of the customers allow for a reduced-cost delivery by the adjacent profit center. We demonstrate that by using the ComEx mechanism, the total cost of transportation of our logistics company can be reduced by up to 14%. Since our iterative auction mechanism is very complex and therefore resource-intensive, we reduce the complexity by applying a convex hull approach combined with a distance-based cost estimator.

Outsourcing der Informationsverarbeitung im Mittelstand: Test eines multitheoretischen Kausalmodells

In this paper determinants of information systems (IS) outsourcing are deduced from transaction cost economic theory, resource-based theory and power theory. They are summarized in a theoretical framework which is tested using a sample of small and medium sized enterprises (SMEs) in Germany. The results show that internal performance and know-how deficits vis-à-vis external service providers are key determinants that explain why different IS functions are outsourced to varying degrees in SMEs. Moreover, the determinants of IS functions were found to partially differ between IS functions. Revised reprint of an article from WIRTSCHAFTSINFORMATIK 43(4)2001:339–350.     

Megasonic agitation for enhanced electrodeposition of copper

In this paper we propose an agitation method based on megasonic acoustic streaming to overcome the limitations in plating rate and uniformity of the metal deposits during the electroplating process. Megasonic agitation at a frequency of 1 MHz allows the reduction of the thickness of the Nernst diffusion layer to less than 600 nm. Two applications that demonstrate the benefits of megasonic acoustic streaming are presented: the formation of uniform ultra-fine pitch flip-chip bumps and the metallisation of high aspect ratio microvias. For the latter application, a multi-physics based numerical simulation is implemented to describe the hydrodynamics introduced by the acoustic waves as they travel inside the deep microvias.     

Support vector classification of proteomic profile spectra based on feature extraction with the bi-orthogonal discrete wavelet transform

Automatic classification of high-resolution mass spectrometry data has increasing potential to support physicians in diagnosis of diseases like cancer. The proteomic data exhibit variations among different disease states. A precise and reliable classification of mass spectra is essential for a successful diagnosis and treatment. The underlying process to obtain such reliable classification results is a crucial point. In this paper such a method is explained and a corresponding semi automatic parameterization procedure is derived. Thereby a simple straightforward classification procedure to assign mass spectra to a particular disease state is derived. The method is based on an initial preprocessing stage of the whole set of spectra followed by the bi-orthogonal discrete wavelet transform (DWT) for feature extraction. The approximation coefficients calculated from the scaling function exhibit a high peak pattern matching property and feature a denoising of the spectrum. The discriminating coefficients, selected by the Kolmogorov–Smirnov test are finally used as features for training and testing a support vector machine with both a linear and a radial basis kernel. For comparison the peak areas obtained with the it ClinProt-System ¹ [33] were analyzed using the same support vector machines. The introduced approach was evaluated on clinical MALDI-MS data sets with two classes each originating from cancer studies. The cross validated error rates using the wavelet coefficients where better than those obtained from the peak areas².     

The analysis of embodied communicative feedback in multimodal corpora: a prerequisite for behavior simulation

Communicative feedback refers to unobtrusive (usually short) vocal or bodily expressions whereby a recipient of information can inform a contributor of information about whether he/she is able and willing to communicate, perceive the information, and understand the information. This paper provides a theory for embodied communicative feedback, describing the different dimensions and features involved. It also provides a corpus analysis part, describing a first data coding and analysis method geared to find the features postulated by the theory. The corpus analysis part describes different methods and statistical procedures and discusses their applicability and the possible insights gained with these methods.     

Heat-integrated reactor concepts for catalytic reforming and automotive exhaust purification

Optimal solutions in environmental catalysis require a well-coordinated development of catalysts and of process design. This contribution is devoted to energy integrated design concepts for fuel reforming and for automotive exhaust purification. The examples presented demonstrate the importance of an innovative process design for optimal utilization of existing catalysts and show the potential of future developments.

New concepts for steam reforming through the efficient coupling of the endothermic reforming reaction with an exothermic combustion reaction are discussed in the first part. These concepts have been implemented for methanol steam reforming in a counter-current reactor with distributed side feed of burner gas and for methane steam reforming in a modular reactor with a co-current reaction section for the endothermic and the combustion reaction and attached counter-current heat exchangers. Both applications employ the so-called folded sheet reactor design, which ensures an excellent heat transfer between the reforming and combustion channels and efficient heat recovery.

A similar design solution is introduced for the apparently different case of automotive exhaust purification. The proposed concept aims at decoupling exhaust after-treatment from engine control. Its main component is a counter-current heat exchanger with integrated purification stages for HC-oxidation, NO_X storage and reduction and soot filtering. A small catalytic burner at the hot end of the heat exchanger provides both heat and oxidizing or reducing agents on demand. A new soot filter design allows for safe soot filter regeneration.