Science and technology in the region: The output of regional science and technology, its strengths and its leading institutions

Summary We operationalize scientific output in a region by means of the number of articles (as in the SciSearch database) per year and technology output by means of the number of patent applications (as in the database of the European Patent Office) per priority year. All informetric analyses were done using the DIALOG online-system. The main research questions are the following: Which scientific and technological fields or topics are most influent within a region and which institutions or companies are mainly publishing articles or holding patents? Do the distributions of regional science and technology fields and of publishing institutions follow the well-known informetric function? Are there - as it is expected - only few fields and few institutions which dominate the region? Is there a connection between the economic power of a region and the regional publication and patent output? Examples studied in detail are seven German regions: Aachen, Düsseldorf, Hamburg, Köln (Cologne), Leipzig - Halle - Dessau, München (Munich), and Stuttgart. Three different indicators were used, science and technology attraction of a region (number of scientific articles and patents), science and technology intensity (articles and patents per 1,000 inhabitants), and science and technology density (articles and patents per 1 billion EURO gross value added). Top region concerning both attraction and intensity is Munich, concerning density it is Aachen.     

Biological evaluation and structural determinants of p38α mitogen-activated-protein kinase and c-Jun-N-terminal kinase 3 inhibition by flavonoids

A series of 42 naturally occurring flavonoids and one flavonoid glucuronide were tested for their ability to inhibit p38α mitogen-activated protein kinase (p38α) and c-Jun-N-terminal kinase 3 (JNK3). Potent inhibitors with IC(50) values in the low micromolar range were identified. Structure-activity relationships were evaluated and the most promising compounds were docked into the ATP binding site of these kinases. Among the different classes of flavonoids, the flavonol group showed better inhibition of p38α. Of this class, kaempferol-7,4'-dimethylether was a potent p38α inhibitor, displaying 13-fold selectivity for p38α over JNK3. The flavone compounds without a 6-methoxy group preferentially inhibited JNK3. The flavone glycoside, luteolin-7-O-glycoside, was identified as a potent inhibitor with the greatest selectivity toward JNK3. In contrast, the flavanol compounds displayed similar inhibitory activities toward both kinases.     

Synthesis and Biological Testing of N‐Aminoimidazole‐Based p38α MAP Kinase Inhibitors

The p38 mitogen‐activated protein (MAP) kinase α plays a central role in the regulation of cellular responses such as differentiation, proliferation, apoptosis, and inflammation. Inhibition of p38 results in decreased synthesis of pro‐inflammatory cytokines. To date, diverse p38α inhibitors are in phase II clinical trials for numerous cytokine‐dependent diseases. 2‐Sulfanylimidazole derivatives offer advantages over the prototype inhibitor SB 203580, including fewer cytochrome P450 interactions and better kinetic properties. The aim of this study was to develop novel 1,2,4,5‐tetrasubstituted pyridinylimidazoles with acyl residues at the imidazole N1 position that can interact with the kinase's hydrophobic region II (HR II) or sugar pocket (SP) to improve both selectivity and activity. The substitution pattern was optimized by variation of the acyl moiety at the N1 position of the N‐aminoimidazole core. Acylation of the amino function was used for optimization and led to potent p38α MAPK inhibitors.     

Wear Performance of Dental Materials: A Comparison of Substructure Ceramics,Veneering Ceramics,and Non‐Precious Alloys

The aim of this in vitro study was to compare the two‐body wear resistance of different dental ceramics and non‐precious alloys. Two‐body wear tests were performed in a chewing simulator with steatite antagonists. A pin‐on‐block design with a vertical load of 50 N for 1.2 × 10⁵ cycles (f = 1.6 Hz; lateral movement: 1 mm, mouth opening: 2 mm) was used for the wear test. Surface roughness R_a (SP6, Perthen‐Feinprüf, G) and wear depth were determined using a 3D‐Profilometer (Laserscan 3D, Willytec, G). Scanning electron microscopy (Quanta FEG 400, FEI, NL) was applied for evaluating wear performance of both, materials and antagonists. Statistics: one‐way ANOVA (α = 0.05). The in vitro wear test showed that the wear performance of dental materials is strongly influenced by the type of material (ceramic, zirconia, or alloy). Zirconia and alloy provided low wear in contrast to glass‐ceramic systems. In contradiction to common expectations, hard zirconia and alloy systems showed even lower antagonistic wear than glass‐ceramics.     

A proxy architecture for collaborative media streaming

Streaming media from the Internet is a successful application for end-users. With the upcoming success of mobile devices and home networking environments, cooperation among users will become more important in the future. To achieve such cooperation, explicit middleware standards have been defined. On the other hand, Internet conferencing applications do not handle collaborative streaming sessions with individual control for each user. We propose a new concept for cooperation exemplary for collaborative media streaming using IETF multimedia session control protocols together with a proxy architecture. This concept enables both synchronization among clients and flexible control to individual users.     

A digital library framework for heterogeneous music collections: from document acquisition to cross-modal interaction

In this paper, we present a digital library system for managing heterogeneous music collections. The heterogeneity refers to various document types and formats as well as to different modalities, e. g., CD-audio recordings, scanned sheet music, and lyrics. The system offers a full-fledged, widely automated document processing chain: digitization, indexing, annotation, access, and presentation. Our system is implemented as a generic and modular music repository based on a service-oriented software architecture. As a particular strength of our approach, the various documents representing aspects of a piece of music are jointly considered in all stages of the document processing chain. Our user interfaces allow for a multimodal and synchronized presentation of documents (WYSIWYH: what you see is what you hear), a score- or lyrics-based navigation in audio, as well as a cross- and multimodal retrieval. Hence, our music repository may be called a truly cross-modal library system. In our paper, we describe the system components, outline the techniques of the document processing chain, and illustrate the implemented functionalities for user interaction. We describe how the system is put into practice at the Bavarian State Library (BSB) Munich as a part of the German PROBADO Digital Library Initiative (PDLI).     

Scanning Protein Surfaces with DNA-Encoded Libraries

Understanding the ligandability of a target protein, defined as the capability of a protein to bind drug-like compounds on any site, can give important stimuli to drug-development projects. For instance, inhibition of protein–protein interactions usually depends on the identification of protein surface binders. DNA-encoded chemical libraries (DELs) allow scanning of protein surfaces with large chemical space. Encoded library selection screens uncovered several protein–protein interaction inhibitors and compounds binding to the surface of G protein-coupled receptors (GPCRs) and kinases. The protein surface-binding chemotypes from DELs are predominantly chemically modified and cyclized peptides, and functional small-molecule peptidomimetics. Peptoid libraries and structural peptidomimetics have been less studied in the DEL field, hinting at hitherto less populated chemical space and suggesting alternative library designs. Roughly a third of bioactive molecules evolved from smaller, target-focused libraries. They showcase the potential of encoded libraries to identify more potent molecules from weak, for example, fragment-like, starting points.     

Trans-Splicing Improvement by the Combined Application of Antisense Strategies

Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs) are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required.