Newly Isolated Animal Pathogen Corynebacterium silvaticum Is Cytotoxic to Human Epithelial Cells

Corynebacterium silvaticum is a newly identified animal pathogen of forest animals such as roe deer and wild boars. The species is closely related to the emerging human pathogen Corynebacterium ulcerans and the widely distributed animal pathogen Corynebacterium pseudotuberculosis. In this study, Corynebacterium silvaticum strain W25 was characterized with respect to its interaction with human cell lines. Microscopy, measurement of transepithelial electric resistance and cytotoxicity assays revealed detrimental effects of C. silvaticum to different human epithelial cell lines and to an invertebrate animal model, Galleria mellonella larvae, comparable to diphtheria toxin-secreting C. ulcerans. Furthermore, the results obtained may indicate a considerable zoonotic potential of this newly identified species.     

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

The Nexus of Corporate Entrepreneurship and Radical Innovation

This paper explores the linkage between the entrepreneurial orientation of established firms and the development of radical innovation. Through five case studies in firms involved in radical innovation, three propositions are developed, suggesting that proactiveness, risk‐taking and autonomy stimulate the development of radical innovation, whereas competitive aggressiveness does not necessarily do so, as radical innovations are directed towards the creation of entirely new arenas of business, where existing competitors are not present.     

The U.S. role in global internet governance

Who should control the Internet? A dozen years after the Internet became a mass medium, this issue has continued to grow in urgency, becoming white hot in fall 2005. At the September 2005 preparatory meeting for the UN World Summit on the Information Society (WSIS), a coalition of countries criticized the United States' unilateral control of the Internet's domain name system (DNS) and proposed the establishment of a multinational Council to supervise it. This proposal emerged from the Final Report of the UN Working Group on Internet Governance. Researchers from the Internet Governance Project, a university-based consortium for policy analysis, have concluded that the United States should internationalize governance of the Internet, but in a way that avoids intrusive, centralized control.     

PROBABILISTIC MODELLING OF LIGNIN LIQUEFACTION

The results of the thermal and catalytic reactions of lignin model compounds are used in the a priori prediction of its liquefaction. Lignin was defined probabilistically as an ensemble of single ring aromatics with substituents on each of their six ring positions. Elements in a substituent vector x¹, for each ring position i, were matched into all possible combinations to describe lignin. Initial number fractions, or probabilities, for each vector element were ascertained through inspection of lignin structural data. The reaction of lignins altered the probabilities within each substituent vector, and reaction products were also calculated by matching all combinations of vector elements for each ring position. Model compound results provided the identities and rates of change of vector elements.

This simulation of lignin liquefaction predicted the yields of permanent gases, aqueous liquids, single- and two-ring phenolic products, and a carbonaceous residue. The impact of the distribution of oligomeric sizes on catalyst effectiveness was probed.     

Numerical simulation model for exhaust gas transportation of dust in the BOF

During the BOF process for the production of crude steel, the specific amount of dust emitted is of the order of 2 % of the steel weight at turn down. The process gas conveys the dust through the boiler system into the primary and secondary dust catchers. The transportation of dust particles is influenced by blowing parameters; physical properties of process gas and of dust phases; and, type and layout of the converter and the filter system. In this work, a numerical simulation model is developed that simulates the pneumatic conveyance and sedimentation of primarily coarse dust particles in the BOF gas cleaning system. Comparison is then made of predicted coarse dust characteristics with values for dust sampled from an existing plant in order to verify the plausibility of the developed model.     

Die Anfänge der neuzeitlichen Chemie in der Pharmazie und Metallurgie. Zu E.F. Geoffroys tabelle stofflicher Beziehungen

E.F. Geoffroy's table of different relations (“rapports”) between different chemical substances is mainly based on empirical knowledge accumulated in 16th and 17th century metallurgy and pharmacy. The substances listed in the left half of the table were basic for the formation of salts which were produced for medical ends in the chemical-pharmaceutical practice of the 17th century. The right half of the table refers to substances and operations of metallurgy which had already been described in the metallurgical writings of the 16th century. Even Geoffroy's ordering of the substances within the columns of his table has its origin in metallurgical and pharmaceutical practice. The key concept of the conceptual framework underlying the table and its commentary is the concept of chemical compound which emerged at the end of the 17th century. Geoffroy extends the range of application of this concept, which was first limited to chemical artefacts, to include natural bodies. Eliminating the peripatetical distinction between natural bodies and chemical artefacts he formulates a new research program, consisting in the determination of the “laws” of the relations (“rapports”) between different chemical substances.