Exploring the Binding Site of Ubiquinone in Complex I by EPR/DEER

Größe: px
Ab Seite anzeigen:

Download "Exploring the Binding Site of Ubiquinone in Complex I by EPR/DEER"

Transkript

1 Exploring the Binding Site of Ubiquinone in Complex I by EPR/DEER Müge Aksoyoglu*, Udo Glessner**, Thomas Spatzal**, Erik Schleicher*, Stefan Weber* * Department of Physical Chemistry, Albert-Ludwigs-Universität Freiburg, Germany ** Department of Biochemistry, Albert-Ludwigs-Universität Freiburg, Germany The proton pumping NADH:ubiquinone oxidoreductase, the respiratory complex I, couples electron transfer from NADH to ubiquinone with the translocation of protons across the membrane [1]. Ubiquinone, which binds to complex I, is a key component of the electrontransport chain because it delivers electrons from complex I to complex III. Recently, the three-dimensional structure of the entire complex I from Thermus thermophilius was determined [2]. However, the structure does not show the presence of bound quinone but a large cavity at the end of the peripheral arm was proposed as binding site. In this study, sitedirected spin labelling (SDSL) in combination with EPR/DEER spectroscopy is used to localize the ubiquinone binding site in complex I on a molecular level. Various positions in the protein as well as decyl-ubiquinone (Q 10 ) were spin labelled with MTSL to measure distances between the two labels via cw-epr and DEER experiments. We present some of our results considering the binding site of ubiquinone. Moreover, we present preliminary data on the FeMo cofactor from nitrogenase, which reduces the dinitrogen triple bond under atmospheric pressure and temperature, thereby forming ammonia in a reaction coupled to the hydrolysis of ATP [3]. Various EPR and HYSCORE methods were used to investigate the FeMo cofactor, which is not yet fully understood in terms of its composition. [1] Pohl, T., Spatzal, T., Aksoyoglu, M., Schleicher, E., Rostas, A.M., Lay, H., Glessner, U., Boudon, C., Hellwig, P., Weber, S., Friedrich, T., Spin labelling of the Escherichia coli NADH ubiquinone oxidoreductase (complex I). Biochim. Biophys. Acta 2010, 1797, [2] Efremov, R.G., Baradaran, R., Sazanov, L.A., The architecture of respiratory complex I. Nature 2010, 465, [3] Lee, H., Benton, P., Laryukhin, M., Igarashi, R., Dean, D.R., Seefeldt, L.C., Hoffmann, B.M., The interstitial atom of the nitrogenase FeMo-cofactor: ENDOR and ESEEM show it is not exchangeable nitrogen. J. Am. Chem. Soc. 2003, 125,

2 PELDOR Study of Nitroxide-Labeled Proteins Florian Altvater, Stephan Rein, Stefan Weber and Sylwia Kacprzak Investigating biomacromolecules in solution with pulsed electron-electron double resonance (PELDOR) spectroscopy yields distance distributions, which provide information about structure and dynamics. The distances are measured between two paramagnetic centers, e. g. nitroxides, that are introduced into the desired positions via site-directed spin labeling. PELDOR is a method of choice especially when no crystal structure is available. Based on the results of distance measurements initial model structures can be refined or the conformational changes during enzymatic actions can be followed. We present the application of PELDOR method on the examples of two distinct proteins, Gyrase of Bacillus subtilis and Agp1 of Agrobacterium tumefaciens. Gyrase is a heterotetramer consisting of two A and two B subunits. Preliminary results of the distance distribution in the Gyrase A dimmer of the mutant N399C are shown. The second example present molecular dynamics (MD) simulation approach to refine the model structure of phytochrome Agp1 of Agrobacterium tumefaciens. 2

3 A Flexible Approach to Benzotropolones Deniz Arican and Reinhard Brückner Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstraße 21, Freiburg, Germany, Benzotropolones (1) are bicyclic aromatic compounds, which are found in plants and fungi. Besides they are interesting from an industrial point of view. Within the last six years patents have been granted regarding their use as anti-inflammatory agents, anti-obesity medication, UV-absorbers in sunscreens, antimicrobial agents, and for the stabilization of household, cosmetic, and nutritional products. Perceiving benzotropolone (1) not as a benz-annulated aromatic but rather as the enol tautomer of 1,2-diketone 5 gave rise to the idea of tracing back the latter to the monoketal 6. Being a substituted cycloheptenone of sorts 6 should be accessible by a ring-closing metathesis of diolefin 7. The latter could originate from the aldehyde 8 and the aromatic compound 9. Following this strategy benzotropolones with 1-3 substituents at various locations were synthesized in overall yields from 18% over 8 steps to 78% over 6 steps. 3

4 Enantiomerically Pure para-benzoquinone Spiroketals Novel Building-Blocks for Stereochemically Versatile Syntheses of Cyclohexitols and Carbasugars Johannes Aucktor, a Chiara Anselmi, a,b Reinhard Brückner,* a and Manfred Keller a a) Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstraße 21, Freiburg, Germany b) New address: Dipartimento di Chimica, Università degli Studi di Perugia, Via Elce di Sotto 8, Perugia, Italy Conduritols (1), quercitols (2), and inositols (3) are structurally diverse polyhydroxycyclohexanes ( cyclohexitols ) from nature. Carbapyranoses (4) are analogously structured unnatural compounds. The great stereochemical variety of these species makes them challenging synthetic targets. HO HO * * * * * 2 OH OH OH OH HO HO 3 * * * * OH * * OH OH HO 1 OH * * * * OH OH O 5 * O * O O * H/R * OH * * HO * * * 4 OH OH OH HO OH We recognized that (almost) all such compounds may stem from one common precursor 5. The latter was accessible from hydroquinone with 99% ee. 5 contains a rigid tricyclic scaffold. It allows to functionalize the cyclohexenone-moiety with a high degree of diastereocontrol. Well-working functionalizations include cis-vic-dihydroxylation, nucleophilic epoxidation, carbonyl group reduction, and enolate hydroxylation. Precursors of the above-mentioned polyhydroxycyclohexanes are accessible under a variety of conditions from such functionalized scaffolds. 4

5 Biaxial Liquid Crystalline Polymers F. Brömmel 1, D. Kramer 1, P. Benzie 2, G. Osterwinter 1, H. Finkelmann 1, S. Elston 2, A. Hoffmann 1 1.) Institut für Makromolekulare Chemie, Albert-Ludwigs-Universität Freiburg, Freiburg 2.) Department of Engineering Science, University of Oxford, Oxford, Parks Road, Oxford, OX1 3PJ, UK The recent experimental discovery of biaxial liquid crystal (LC) phases provides the opportunity to develop the technology for a new generation of faster biaxial LC displays. These expectations are based on the existence of a secondary director that can be controlled by external fields. It is estimated that the reorientation of the secondary director can be more than one order of magnitude faster than the reorientation of the uniaxial nematic director. However, fundamental questions concerning the biaxial nematic phase behaviour, its alignment with respect to external fields and its relation to the molecular architecture are still open. So far, a large number of nematic polymers and elastomers have been found to form biaxial nematic phases. We deuterated these systems in various positions. This allowed us to compare the obtained biaxiality parameters from 2 H NMR experiments on directly deutrated monomers and deuterated probe molecules, that are commonly used to determine biaxiality in order to overcome the synthetical effort of deuteration. Also, it is possible to vary the molecular geometry of the mesogens while preserving the biaxiality. This way the influence of the molecular geometry on biaxiality was studied. The temperature dependence of the biaxiality for all polymers investigated so far suggests that the formation of the biaxial phase is connected to the glass transition. Accordingly, the dynamic of the polymer chains plays a decisive role in the formation of the biaxial phase. For potential applications, the manipulation of the minor director by external fields without affecting the orientation of the principal axis is crucial. X-ray scattering experiments and conoscopy measurements performed under mechanical deformation reveal that the reorientation of the secondary director occurs before the reorientation of the primary nematic director sets in. This proves the selective addressability of the biaxial director by mechanical fields. 5

6 International Bunsen Discussion Meeting FRET in Life Sciences 27th - 30th March 2011 Single molecule spectroscopy of membrane bound H + -ATPsynthases from E. coli Markus Burger *, Peter Gräber* * Institut für Physikalische Chemie, Albert-Ludwigs Universität Freiburg, Germany Subunit movements within the H + -ATPsynthase from E. coli (EF 0 F 1 ) are investigated by single molecule FRET spectroscopy. The enzyme is covalently labeled at cysteines within the γ-subunit (γc106) and the ε-subunit (εc114). The labeling procedure is carried out with a mixture of both fluorescent dyes. Therefore, the binding at the two positions with the donorfluorophor (ATTO532) and the acceptor-fluorophor (ATTO610) occurs statistically. The donor and acceptor labeled EF 0 F 1 is integrated into liposomes and single-pair fluorescence resonance energy transfer is measured in freely diffusing proteoliposomes with a confocal two channel microscope. Addition of AMPPNP (a non-hydrolysable analogue of ATP) leads to a conformational change of the ε-subunit from an extended to a folded form. Analysis of ensemble-fret and single-pair-fret indicates distance changes in the range of 4 nm. The fluorescence time traces obtained with single-pair-fret reveal a time-dependent switching of the ε-subunit in the presence of nucleotides. ε114 UP γ106c ε114 DOWN Fig. 1. The γ (blue) and ε subunits from E.coli. The ε subunit is shown in up (cyan-green) and down (cyan-red) conformation. Labeled positions are marked with spheres. 6

7 Jan Caspar Arbeitskreis Prof. Dr. P. Spiteller Institut für Organische Chemie und Biochemie Titel: Verwundungsaktivierte Verteidigung in Marasmius oreades durch Cyanwasserstoff Pilze entwickelten wie auch Pflanzen eine Reihe von Abwehrmechanismen, um sich gegen Fraßfeinde und Schädlinge schützen zu können. Bei der verwundungsaktivierten Verteidigung liegen inaktive Vorläuferverbindungen der eigentlichen Wirkstoffe vor, welche durch enzymatische Umwandlung im Verteidigungsfall in ihre bioaktive Form überführt werden. Neben komplexeren, biologisch aktiven Verbindungen werden auch einfachere Toxine zur Verteidigung eingesetzt. So konnte aus Fruchtkörpern der Art Aleurodiscus amorphus ein Cyanhydrin isoliert werden, welches durch einen oxidativen Mechanismus zu HCN und Aleurodiscoester umgesetzt wird. In Fruchtkörpern der Art Marasmius oreades konnte nach Beschädigung ebenfalls eine Cyanidfreisetzung festgestellt werden. Die zugehörige Ausgangsverbindung ist jedoch nicht bekannt. Erste Experimente legen nahe, dass es sich hierbei um ein hochpolares, geschütztes Cyanhydrin handelt. Die Substanz soll mittels HPLC- Techniken isoliert und NMR-spektroskopisch und massenspektrometrisch vollständig charakterisiert werden. Da die Substanz kein Chromophor enthält, muss die Detektion durch eine Abbaureaktion zur Freisetzung von Cyanid sowie anschließendem Cyanidnachweis durchgeführt werden. 7

8 Crater morphologies in impact experiments into sandstone targets A.Dufresne, M.H.Poelchau, T.Kenkmann, and the MEMIN-Team Department of Geological Sciences Geology, Albert-Ludwigs Universität Freiburg, Germany Understanding the dynamics of a hypervelocity body impacting onto a planetary surface can give numerous insights into the processes that formed the solar system. During an impact process, the impacting projectile initially excavates a roughly hemispherical cavity in the target, known as the transient crater, which is usually modified by late stage processes. Constraining the dimensions of the transient crater and late stage modification features like spallation lead to a better understanding of the physical parameters that affect crater formation. Therefore, impact experiments into sandstone cubes were performed at the twostage light gas acceleration facilities of the EMI Freiburg. Spherical projectiles of steel, meteoritic iron and aluminium were accelerated to velocities of km/s and impact energies from 0.7 to 58 kj. In a detailed study, the processes influencing crater volume, morphology and spall behaviour were investigated through visual mapping, 3D digital modelling and 2D profile analyses. All experimental impact craters in dry sandstone targets share four characteristic morphological features: (1) a light-coloured, fragile, highly fragmented central part, (2) areas of arrested spallation where the target is fractured but the outlined spall fragments remains within the crater context, (3) typically two inner depressions, and (4) an outer, shallow (10-20 ) dipping area. Constraining the percentage of spallation within a crater and determining the shape and volume of the transient crater are vital for comparison with non-brittle materials like metals, with numerical modelling results, and with natural impact craters. Transient crater morphologies are derived from (i) parabolas fitted to the central depressions of crater profiles, (ii) reconstructed spallation dimensions, (iii) ejecta imprint diameters on catcher systems, (iv) ejecta cone angle and dynamic crater diameter from high-speed videos, and (i) the distribution of ejecta weight fractions. Results show that spallation, as a late-stage cratering process, increases the volume of the transient crater by a factor of The refined transient crater model will be applied to other experimental and to real-size impact craters in due course. 8

9 in-vivo localization of the OXPHOS complexes in E. coli Erhardt H. and Friedrich T. Institute for Organic Chemistry and Biochemistry, Albert-Ludwigs-University Freiburg, Germany Biological membranes show a high level of organization of their compounds. Lipids and membrane proteins are not randomly distributed within these membranes, but organized in distinct and dynamic clusters and show a huge variety in localization patterns. It has been proposed that protein complexes connected by a common substrate chain form supercomplexes, which are located in specific areas within the membrane. Such an organization provides advantages such as stabilization of the individual complexes or catalytic enhancement. The aerobic OXPHOS system of E. coli consists of several multi-subunit enzyme complexes. To address the question whether these complexes are localized in distinct lipid areas and if they show any dynamic behavior, we decorated the membrane protein complexes with different fluorescent proteins and visualized their distribution in the membrane by in-vivo fluorescence microscopy. FP-decorated variants of the NADH:ubiquinone oxidoreductase, the succinate dehydrogenase, the cytochrome-bd complex and the F 0 F 1 -ATP-synthase, were created by means of λ- RED mediated mutagenesis. The labeled complexes were catalytically active and fully assembled. By fluorescence microscopy we observed an uneven distribution of the OXPHOS complexes in the cytoplasmatic membrane of living E. coli cells. From these data we conclude that they reside in distinct and dynamic membrane domains, which might be of functional importance. References: Pohl, T., Uhlmann, M., Kaufenstein, M. & Friedrich, T., Biochemistry 2007, 46, Lenn, T., Leake, M. C., Mullineaux C. W., Mol Microbiol. 2008,70, Mileykovskaya, E. & Dowhan, W., J. Bacteriol. 2000, 182, Johnson, A. S., van Horck, S. & Lewis P. J., Microbiology 2004, 150,

10 Factors controlling stress perturbations in faulted reservoirs - insights from numerical parameter studies Fischer, K. & Henk, A. Institut für Geowissenschaften Geologie, Albert-Ludwigs-Universität Freiburg, Germany Das tektonische Spannungsfeld beeinflusst die optimale Erschließung einer Lagerstätte in vielfältiger Weise. So hängen u.a. Bohrlochstabilität, Orientierung von hydraulisch induzierten Fracs und insbesondere in geklüfteten Reservoiren Permeabilitätsanisotropien von den rezenten in situ Spannungen ab. Allerdings kann das regionale Spannungsfeld durch Störungen und Lithologiewechsel lokal in Magnitude und Orientierung variieren. Insbesondere bei störungskontrollierten Lagerstätten können solche Perturbationen dazu führen, dass das Spannungsfeld innerhalb einzelner Störungsblöcke deutlich vom regionalen Trend abweicht. Eine belastbare pre-drilling Prognose von tektonischen Spannungen zur Minderung des Erschließungsrisikos und zur Optimierung der Bohrungen erfordert daher die Einbeziehung der spezifischen Lagerstättengeometrie sowie der mechanischen Eigenschaften der beteiligten Lithologien und Störungen. Als Prognosewerkzeug bieten sich geomechanische Lagerstättenmodellierungen auf Basis der Finite Elemente (FE) Methode an. Im Rahmen des DGMK Forschungsprojekts 721 wird das Potential von solchen geomechanischen Lagerstättenmodellen für die Prognose von Spannungsfeldern und Kluftnetzwerken am Beispiel des Erdgasfeldes Nord Hannover untersucht. In der ersten Projektphase wurden im Rahmen von Parameterstudien die wesentlichen Kontrollfaktoren für Spannungsfeldperturbationen an Störungen bearbeitet. Ausgehend von einem Standardmodell, das sich hinsichtlich der idealisierten Geometrie eines Störungsblocks, der Materialeigenschaften und Randbedingungen bereits an die Fallstudie Nord Hannover anlehnt, wurden systematisch die Magnitude und die Orientierung der maximalen regionalen Hauptnormalspannung (σ Hmax ), die Reibungskoeffizienten der Störungen sowie die mechanischen Eigenschaften der Gesteine variiert. Darüber hinaus wurden Modellszenarien mit mehreren Störungsblöcken bzw. unterschiedlichen Größen der Störungsblöcke untersucht und zwei- und dreidimensionale numerische Simulationen miteinander verglichen. Für alle Szenarien wurden die Ergebnisse in Form von Isolinien- und Vektorplots für unterschiedliche Ausgabegrößen von Spannung und Deformation (Magnituden und Orientierungen der Hauptnormalspannungen, von Mises Vergleichsspannung, mittlere Spannnung, Differentialspannung, elastische und plastische Deformationsanteile, fault slip and dilation tendencies ) dokumentiert. Die Parameterstudien zeigen, dass die Reibungskoeffizienten der Störungen, der Winkel zwischen Störung und σ Hmax sowie die mechanischen Eigenschaften der aneinandergrenzenden Gesteine den relativ größten Einfluss auf Spannungsfeldperturbationen haben. Während das Standardmodell an den Störungen lediglich kleinräumige Veränderungen in der Magnitude der Normalspannungen zeigt, haben z.b. deutlich herabgesetzte Reibungseigenschaften ausgeprägte Veränderungen in Magnitude und Orientierung des Spannungsfeldes zur Folge. Die Ergebnisse dieser Parameterstudien werden in der nächsten Projektphase zur Validierung eines detaillierten Lagerstättenmodells von Nord Hannover genutzt, das die spezifische Störungsgeometrie und mechanische Gesteinseigenschaften berücksichtigt. 10

11 Cloning, Expression, Purification and Crystallization of the First Archaeal 4-Hydroxyphenylpyruvate Dioxygenase Eduard Frick, 1 Thomas Spatzal, 2 Oliver Einsle, 2 Michael Müller, 1 and Wolfgang Hüttel 1 1 Institut für Pharmazeutische Wissenschaftten der Albert-Ludwigs-Universität Freiburg, Lehrstuhl für Pharmazeutische und Medizinische Chemie, Albertstr. 25, D Freiburg, 2 Institut für Organische und Biochemie der Albert-Ludwigs-Universität Freiburg, Lehrstuhl für Biochemie, Albertstr. 21, D Freiburg, 4-Hydroxyphenylpyruvate dioxygenase (Hpd) catalyzes the conversion of 4-hydroxyphenylpyruvate (4-HPP) into 2,5-dihydroxyphenylacetate (homogentisate). This reaction is part of the aerobic tyrosine catabolism in nearly all forms of life. Hpd is a valuable target for agrichemical (development of herbicides) and therapeutical (treatment of hereditary tyrosinaemia) research. [1] Enzymes of extremophilic organisms offer a promising access to biocatalysts with increased stability. We focussed on the Hpd from the acidophilic and mesothermophilic archaeon Picrophilus torridus. [2] We managed to clone, express, purify, characterize and crystallize the protein. The structure of P. torridus Hpd was determined at 2.3 Å resolution and will provide further insights into the reasons for acid stability of certain proteins. References: [1] G. R. Moran, Arch. Biochem. Biophys. 2005, 433, [2] C. Schleper, et al., J. Bacteriol. 1995, 177,

12 Tag der Forschung 2011 Laurdan labeled liposomes a new approach to quantify drug partitioning Gesche Först, Rolf Schubert Dept. of Pharmaceutical Technology and Biopharmacy, University of Freiburg The knowledge of the partition behaviour of a drug between buffer and biological membranes is important to predict its distribution and accumulation in the human organism. Liposomes are common membrane models and ideal systems for the characterization of drug-membrane interactions [1]. The aim of this project is to establish an indirect screening method to investigate the liposome/buffer partition coefficient of drugs using the easily available fluorescence dye 6-Lauryl-2-dimethylaminonaphtalene (Laurdan) [2]. After investigating the partitioning behaviour of bile salts as amphiphilic model drugs in previous studies [3] the Laurdan method has also been applied to the ß-blockers as additional substance class and the attained results are comparable to literature [4]. Plemper v. Balen G, Marca Martinet C, Caron G, Bouchard G, Reist M, Carrupt PA, Fruttero R, Gasco A, Testa B. Liposome/water lipophilicity: methods, information content, and pharmaceutical applications. Med Res Review. 2004; 24(3): doi: /med [2] Paternostre M, Meyer O, Grabielle-Madelmont C, Lesieur S, Ghanam M, Ollivon M. Partition coefficient of a surfactant between aggregates and solution: application to the micelle-vesicle transition of Egg-phosphatidylcholine and Octyl- -Dglucopyranosid. Biophys J 1995; 69: [3] Theobald A, Thesis, Laurdan als Fluoreszenzsonde zur Quantifizierung der Wechselwirkung von Gallensalzen mit Liposomenmembranen 2009; University of Freiburg [4] Liu X., Hefesha H., Scriba G., Fahr A. Retention Behavior of Neutral and Positively and Negatively Charged Solutes on an Immobilized-Artificial-Membrane Stationary Phase Helv. Chim. Acta 2008; 91:

13 Mechanistical studies of the Rhodium catalyzed Hydroformylation with Self-Assembling Ligands Urs Gellrich, Bernhard Breit* Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, Freiburg Selectivity control in homogeneous metal complex catalysis is most frequently achieved by crafting the microenvironment of the catalytically active metal center upon binding of appropriate ligand architectures to the metal center. Among the many ligands used, bidentate ligands occupy an important position. During the last years our group was able to apply self-assembling ligands, interacting via hydrogen bonds,[1] successfully in many catalytic reactions, for example hydroformylation, hydrogenation and others.[2,3,4] In order to improve catalytic reactions and ligands it is by all means necessary to completely understand the nature of the catalytically active species. Hence, online monitoring of progressing catalytic transformations, supported by quantum mechanical calculations can deliver valuable informations on the intermediates involved in catalysis. We herein report on our first insights into hydroformylation reactions with the 6-DPPon ligand using online TM ReactIR -spectroscopy together with DFT calculations. Figure 1: Direct observation of the formation of an intermediat of the catalytic cycle and the corresponding DFT calculated structure (B3P86/def2-SVP). [1] W. Seiche, B. Breit Angew. Chem., Int. Ed. 2005, 44, [2] C. Waloch, J. Wieland, M. Keller, B. Breit, Angew. Chem. 2007, 119, 309, Angew. Chem. Int. Ed. 2007, 46, [3] J. Wieland, B. Breit Nature Chemistry 2010, 2, 832. [4] M. degreef, B. Breit Angew. Chem., Int. Ed. 2009, 48,

14 Streptomyces calvus from bald to beautiful Arne Gessner Institut für pharmazeutische Biologie und Biotechnologie Albert-Ludwigs-Universität Freiburg Streptomyces calvus is most prominently known for producing the fluorinated compound nucleocidin. S. calvus is also a non-sporulating strain, an unusual property for Streptomycetes, which is reflected in the Latin word for bald, calvus. Examination of a draft sequence of the genome of this strain revealed a polyketide-biosynthesis gene cluster that has high sequence similarity to known polyene-biosynthesis clusters like those for Nystatin or Pimaricin, which are valuable natural products that are therapeutically used to treat fungal infections in humans and animals. A leucine in the loading domain of a PKS in this biosynthesis cluster is encoded by a TTA-codon. Such codons are extremely rare in the GC-rich genomes of Streptomycetes. The corresponding Leu-tRNA is encoded by the blda gene. Sequence alignment of the S. calvus blda gene with blda genes from other Streptomyces species showed a point mutation that is predicted to encode a mis-folded and most likely non-functional Leu-tRNA (TTA). So it was hypothetisized that complementation of S. calvus with a functional copy of the blda gene would not only restore sporulation but could also activate the cryptic polyene cluster. The S. calvus blda(+) strain did indeed regain the ability to sporulate. Additionally, LC-DAD-MS analysis of an extract from a seven-day production culture revealed a new peak that showed an UV-spectrum typical for a polyene. The corresponding polyene annimycin was purified and the structure elucidated by 1 H-, 13 C-, HSQC, HMBC and ROESY NMR spectroscopy. Disruption of PKS genes are currently underway to define the biosynthetic cluster for annimycin. 14

15 UNRAVELING THE BIOSYNTHESIS OF KOTANIN AND ITS MONOMERIC PRECURSOR 7- DEMETHYLSIDERIN IN ASPERGILLUS NIGER C. Gil Girol, W. Hüttel, M. Müller Institute for Pharmaceutical Sciences, University of Freiburg A. niger shows an intermolecular stereo- and regioselective oxidative phenol coupling of the coumarin derivative 7-demethylsiderin (2), forming orlandin (5). Final O-methylation leads to kotanin (6) (Fig.1). 1 The biosynthesis of kotanin (6) in A. niger and its absolute configuration was elucidated through feeding experiments and stereoselective synthesis. 1, 2 Up to now there is no evidence for an alternative biosynthetic route to 6 by oxidative coupling of 3,7-dihydroxycoumarin (1) leading to the bicoumarin 4 and subsequent O-methylation. CH 3 OH CH 3 O 13 CH 3 CH 3 O 13 CH 3 HO 13 C O O HO 13 C O O H 3 CO C O O? CH 3 OH CH 3 O 13 CH 3 CH 3 O 13 CH 3 HO HO 13 C O O O 13 C O? HO HO 13 C O O O 13 C O H 3 CO H 3 CO 13 C O O O 13 C O CH 3 OH CH 3 OCH 3 CH 3 OCH Figure 1: Biosynthesis of kotanin (6) elucidated through feeding experiments and stereoselective synthesis. 1, 2 Here, we report the verification of this biosynthetical pathway on genomic level by a gene targeting approach. In preliminary feeding experiments the polyketidic orign of kotanin was proven, an in silico analysis of the A. niger genome 3 revealed putative PKS clusters coding for the monomeric precursor 2. Subsequent disruption of the genes led to the PKS responsible for kotanin (6) biosynthesis. Furthermore disruption of an O-methyl transferase of the cluster provided evidence for absence of an alternative route to 6 via 1 and Hüttel, W. & Müller, M. Regio- and stereoselective intermolecular oxidative phenol coupling in kotanin biosynthesis by Aspergillus niger. Chembiochem 8, (2007). 2. Hüttel, W., Nieger, M. & Müller, M. A short and efficient total synthesis of the naturally occurring coumarins siderin, kotanin, isokotanin A and desertorin C. Synthesis, (2003). 3. Pel, H.J. et al. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS Nature Biotechnology 25, (2007). 15

16 GAP: A Genome Annotation Pipeline Grüning BA, Erxleben A, Senger C, Flemming S, Günther S* Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, University of Freiburg, Germany * stefan.guenther[at]pharmazie.uni-freiburg.de Introduction: Processing the exploding number of new sequence data requires efficient implementation of several specialised tools on a powerful hardware infrastructure. Employed methods include genome assembly, genome annotation, pathway reconstruction, data visualisation, and pathway modelling. Galaxy is a workflow management system for data processing ideally suited to the combination of various software tools. Furthermore, it ensures data and process reproducibility in terms of repeatability and traceability. Accessibility via web interface facilitates the integration of Galaxy into genome annotation projects. Methods and Results: Based on Galaxy, we have developed the comprehensive Genome Annotation Pipeline (GAP) focused on processing newly sequenced bacterial genomes. Currently, the pipeline includes several publicly available and self-developed tools: Glimmer3 for the prediction of ORFs, similarity searches in NCBI databases and UniProt, InterProScan for the functional annotation of gene products, SignalP for the prediction of protein localisation, Aragorn for trna and tmrna detection within the genome and many more. The pipeline is implemented on a high-performance computer and allows a very fast complete annotation of an average microbial genome. GAP has been successfully applied for the annotation of Streptomyces TÜ6071. This is a bacterium which has a highly-active isoprenoid biosynthesis and produces the industrial important terpene Phenalinolactone which has anti-bacterial activity against several Gram-positive bacteria. The annotated genome sequence of Streptomyces TÜ6071 is now available under the NCBI accession number AFHJ Future Prospects: Additional sequence analysis tools and and interfaces for complex data visualisation will be implemented. GAP will soon be publicly available for genome annotation and systems biology for the scientific community. 16

17 Strukturelle Charakterisierung von Br 9 - -Anionen Heike Haller, Mathias Ellwanger, Sebastian Riedel* Institut für Anorganische und Analytische Chemie Uni Freiburg Seit Jahrzehnten ist eine Vielzahl von Polyiodidanionen bekannt und strukturell untersucht. Im Bereich der niedrigeren Homologen kennt man deutlich weniger Beispiele. So sind bei den Polybromiden mehrere Kristallstrukturen bekannt wie zum Beispiel Br 2-10, (Br - ) 2 (Br 2-4 ) und 2- ein unendliches 2D Polybromidnetzwerk. Anfang diesen Jahres wurde von Br 20 als bisher bromreichste bekannte Verbindung berichtet [1]. Jedoch ist im Bereich der Polybromidmonoanionen lediglich Br - 3 seit als Kristallstruktur bekannt. Zu Br - 5, Br - 7 und Br 9 - gibt es ausführliche ramanspektroskopische Untersuchungen [2], eine genauere kristallographische Untersuchung gelang jedoch bislang nicht. Uns gelang erstmals NMe 4 Br 9 sowie NEt 4 Br 9 mittels Einkristallstrukturanalyse zu charakterisieren. [1] Wolff, M.; Meyer, J.; Feldmann, C.; Angewandte Chemie 2011,123, [2] Chen, X.; Rickard, M.; Hull Jr., J.; Zheng, C.; Leugers, A.; Simoncic, P.; Inorganic Chemistry 2010, 49,

18 Gallium(I) Chemistry and the Synthesis of Highly Reactive Polyisobutylene From Fundamentals to Applications Higelin, A. and Lichtenthaler, M. R., Freiburg i. Br. / D Prof. Dr. Ingo Krossing, Albert-Ludwigs-Universität Freiburg, Alberstraße 21, Freiburg i. Br. / D In 2010 a simple route to univalent gallium salts of weakly coordinating anions (WCAs) was developed by SLATTERY et al. [1] Herein the gallium(i)-cations are solely coordinated by aromatic solvent molecules (e.g. toluene or fluorobenzene) in a bent sandwich fashion. As only one Ga-F contact is shorter than the sum of the van der Waals radii (3.34 Å) the interaction between the gallium(i)-cations and the WCAs is very weak (Figure 1).These novel salts are therefore ideal starting materials for further gallium(i) chemistry. The solvent molecules can be replaced by a variety of σ-donor ligands, like phosphanes and ethers, leading to an entirely new class of coordination compounds Figure 1: Molecular Structure of [Ga(C 6 H 5 Me) 2 ] + [Al(OC(C(CF 3 ) 3 ) 4 ]. which were inaccessible with previously known Ga(I) starting materials. The study of these exciting new compounds and their exotic bonding situations, in conjunction with quantum chemical investigations, gives fundamental insights into the nature of the chemical bond. On the applied side, the variation of the ligands offers an elegant method of tuning the reactivity of the gallium(i)-cations. The latter namely are a promising species for a variety of applications, e.g. initiating or catalyzing the synthesis of highly reactive Polyisobutylene (HR-PIB). Depending on its molecular weight Polyisobutylene (PIB) has been used in many versatile applications. Thus high molecular weight PIB has gradually substituted natural chicle as the main chewing gum base. The application of low molecular weight PIB however relies on the PIB being highly reactive. PIB is classified as highly reactive as soon as the content of terminal double bonds exceeds 60%. Being sterically exposed, the latter can easily be functionalized. Therefore HR-PIB represents an essential intermediate in manufacturing additives for lubricants and fuels. [2] Up to this day most syntheses of HR-PIB show a lack in at least one point. May it be low reaction temperatures down to 100 C, dichloromethane as solvent or relatively high concentrations of the initiating or catalyzing species all these factors sum up to a negative [3], [4] economic and environmental balance. Recently a number of reactions showed the superior quality of the univalent gallium salts initiating or catalyzing the polymerization of isobutylene. Thus the synthesis of HR-PIB can be carried out at relatively high reaction temperatures up to 0 C, in a non carcinogenic and non water-hazardous solvent, i.e. toluene, as well as using relatively low concentrations of the initiating or catalyzing species, down to mol%. The experimental results were backed by quantum-chemical calculations giving a first hint on a coordinative polymerization mechanism. [1] J. M. Slattery, A. Higelin, T. Bayer, I. Krossing, Angew. Chem. Int. Ed., 2010, 49, [2] M. Vierle, Y. Zhang, E. Herdtweck, M. Bohnenpoll, O. Nuyken, F. E. Kühn, Angew. Chem. Int Ed. 2003, 42, [3] A. Guerrero, K. Kulbaba, M. Bochmann, Macromol. Chem. and Phys. 2008, 209, [4] Y. Li, H. Y. Yeong, E. Herdtweck, B. Voit, F. E. Kühn, Eur. J. Inorg. Chem. 2010,

19 Characterization of airborne dust particles in the coal mining area of Cam Pha, northern Viet Nam T.B. HOÀNG-HÒA 1*, R. GIERÉ 1, V. DIETZE 2, U. KAMINSKI 2 AND P. STILLE 3 1 Albert-Ludwigs-Universität, D Freiburg, Germany (*correspondence: 2 German Meteorological Service, Research Center Human Biometeorology, Stefan-Meier-Str. 4, D-79104, Freiburg, Germany 3 École et Observatoire des Sciences de la Terre, Université de Strasbourg, F Strasbourg, France Cam Pha, located in Quang Ninh province, is one of the largest coal mining areas in Viet Nam (reserves ~10 Gt). This study focuses on the mineralogical and chemical characterization of airborne dust. Exposure to dust is a major challenge for the population living near the mines, especially the open-pit mines. Additional major dust sources comprise mine dumps containing the overburden, a coal-processing facility, a coal-shipping harbour, mining traffic, and various industries, including coal-fired power stations. Coarse particles (dp >2.5 µm) have been collected with the passive sampler device Sigma-2 on transparent adhesive collection plates for subsequent single-particle analysis by automated optical microscopy according to VDI guideline 2119 [1]. Select specimens, sampled during different meteorological conditions, were investigated further by SEM-EDX single-particle analysis and by determining their bulk chemical and isotopic composition (ICP-MS and MC-ICP-MS, respectively). Wind directions indicate that the particles are mainly derived from the open-pit mines, consistent with bulk chemical and isotopic data ( 87 Sr/ 86 Sr = ; ε Nd = ; 206 Pb/ 207 Pb = ), which suggest that the dust contains mostly natural materials (coal, silicate minerals from sedimentary rocks). Relative to the coal, the bulk airborne dust is enriched in Na, Mg, K, and Ca, but depleted in most other components. Element-ratio plots reveal some systematic differences between the dust samples and specimens of coal and overburden, pointing to an additional, yet unknown particle source. To verify the hypothesis of an additional dust source and to provide quantitative data on the mineralogical composition of the dust samples, we are currently optimizing the automated SEM-EDX single-particle analysis technique. [1] VDI (1997): VDI guideline 2119, part 4. 19

20 Towards the Total Synthesis of β-lipomycin: A Highly Convergent and Adaptable Double Stille-Coupling Strategy for the Synthesis of 3-(Polyenoyl)tetramic Acids Max Hofferberth and Reinhard Brückner* Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstraße 21, Freiburg, Germany; 3-( -Hydroxymethylidene)pyrrolidine-2,4-diones constitute the major tautomer of structures commonly referred to as acyltetramic acids. Compounds in which acyl equals polyenoyl define a class of natural products, which continues to evoke interest both in the synthetic [1] and biosynthetic community [2]. We synthesized a prototypical (polyenoyl)tetramic acid, namely β-lipomycin (9), [3] or possibly a stereoisomer thereof, since the 3 D structure of 9 still awaits elucidation. Employing a novel approach, which is variable and convergent the naturally occurring stereoisomer plus chain-extended or chain-altered derivatives thereof should become readily accessible. [1] R. Schobert, A. Schlenk, Bioorg. Med. Chem. 2008, 16, and literature cited therein. [2] E. g.: C. Bihlmaier, E. Welle, C. Hofmann, K. Welzel, A. Vente, E. Breitling, M. Müller, S. Glaser, A. Bechthold, Antimicrob. Agents Chemother. 2006, 50, [3] B. Kunze, K. Schabacher, H. Zähner, A. Zeeck, Arch. Mikobiol. 1972, 86, [4] First synthesis and applications of 6: A. Sorg, R. Brückner, Angew. Chem. 2004, 116, ; Angew. Chem. Int. Ed. 2004, 43, ; J. Burghart, R. Brückner, Eur. J. Org. Chem. 2011, ; J. Burghart, A. Sorg, R. Brückner, Chem. Eur. J. 2011, 17,

21 Chorismatases: Characterizing a new group of enzymes F. Hubrich, J. Andexer Institut für Pharmazeutische Wissenschaften, Pharmazeutische und Medizinische Chemie, Albertstr. 25, Freiburg Chorismatases are enzymes catalyzing the hydrolysis of chorismic acid 1 to pyruvat and a cyclic carboxylic acid. The level of saturation of the carboxylic acid depends on the type of enzyme catalyzing this hydrolysis. Enzymes of the FkbO-type produce 1,5-diene-3,4-dihydroxycyclohexanoic acid (DHCHC) 3, enzymes of the Hyg5-type produce the aromatic 3-hydroxybenzoic acid (3HBA) 2. 1 These products are precursor molecules for the synthesis of natural products like ascomycin 5, rapamycin 2, brasilicardin 3 and xanthomonadin 4. FkbO and Hyg5 are kinetically characterized for chorismate, but both the structure and the reaction mechanism of these enzymes are still unknown. Structural modeling will be difficult, because there is no sequence similarity between chorismatases and other chorismate using enzymes. Phylogenetic analysis 1 and sequence alignments (BLAST) show additional genes in different organisms (Streptomyces and Xanthomonas), that are probably encoding for chorismatases. To show that these genes products are chorismatases, the target genes are introduced into E. coli expression vectors and strains. The already purified protein FkbO and Hyg5 are used in crystallization experiments to get a crystal structure of a chorismatase. 21

22 Lawsone and Tetrahydroxynaphthalene Reductase Syed Masood Husain, Michael Schätzle, Michael Richter, Michael Müller Institut für Pharmazeutische Wissenschaften der Albert-Ludwigs-Universität Freiburg, Albertstr. 25, D Freiburg im Breisgau, Lawsone (2-hydroxy-1,4-naphthoquinone), is a red-orange dye present in the leaves of the henna plant (Lawsonia inermis). Humans have used henna extracts containing lawsone as hair and skin pigments for more than 5000 years. We have used this natural product as a substrate, which on reduction catalyzed by the enzyme called tetrahydroxynaphthalene reductase (T 4 HNR) from Magnaprothe grisea, gave cis-ketodiol with high yield (95%) and high ee (99%). O O T 4 HNR HO NADPH HO O OH Lawsone cis-keto-diol Lawsone was also used extensively to study the mechanism of T 4 HNR-catalyzed reduction that has led to the formation of a cis-keto-diol. 22

23 Stereoselectivity of the Ketoreductase Tyl-KR1 from Streptomyces fradiae A VCD spectroscopy analysis Matthias Häckh, Michael Müller, and Steffen Lüdeke Institut für Pharmazeutische Wissenschaften der Albert-Ludwigs-Universität Freiburg, Albertstr. 25, D Freiburg, Germany Enzyme-catalysed reactions are best-known for their high stereoselectivity. Biocatalysis benefits from these outstanding properties making chiral building blocks accessible that can be used for drug syntheses. [1] Oxidoreductases play an important role in polyketide chemistry, especially those with rarely observed anti-prelog type selectivity, since oxidoreductase-catalysed reduction of ketones generally leads to products with Prelog type configuration. [2] The stereoselectivity of many enzymes is substrate-specific and might be decreased or even converted for non-physiological substrates. Exact determination of the absolute configuration of different products formed out of different substrates is therefore very important for the useful application of enzymes in biocatalysis. A switch between anti-prelog type and Prelog type - selectivity seems to be possible. The ketoreductase Tyl-KR1 from Streptomyces fradiae is known to reduce racemic 2- methyl-3-oxopentanoic acid N-acetylcysteamine thioester (1) enantioselectively to anti-(2r,3r)-3-hydroxy-2-methylpentanoic acid N-acetylcysteamine thioester (2). [3] This anti-prelog type anti-configuration is rarely found in natural products. O O CH 3 H TYL KR 1 OH O N S R R "anti-prelog type"-reduction S O CH anti-r,r Figure 1: Anti-Prelog type -reduction catalysed by Tyl-KR1. H N O We used VCD spectroscopy and quantum chemical calculations to determine the absolute configurations of four different polyketide analogues reduced by Tyl-KR1. References [1] M. Müller, Angew. Chem. Int. Ed. 2005, 44, 362. [2] K. Faber, Biotransformations in Organic Chemistry, 5th ed., Springer, [3] A. P. Siskos, A. Baerga-Ortiz, S. Bali, V. Stein, H. Mamdani, D. Spiteller, B. Popovic, J. B. Spencer, J. Staunton, K. J. Weissman, P. F. Leadlay, Chem. Biol. 2005, 12,

24 Engineering an aryl-c-glycoside biocatalyst J. Härle 1, M. Weber 1, B. Lauinger 1, S. Günther 2, B. Kammerer 3, A. Luzhetskyy 1, A. Bechthold 1 * (1) Department of Pharmaceutical Biology und Biotechnology (2) Department of Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, Albert-Ludwigs- Universität Freiburg, Freiburg, Germany. (3) Zentrum für Biosystemanalytik,Albert-Ludwigs-Universität Freiburg, Freiburg, Germany. Before a natural product potentially becomes a therapeutic agent properties influencing the pharmacological or pharmacokinetic qualities might have to be improved. As sugar substituents play an essentiell role in respect to bioactivity and solubility, they represent a valuable address for modification (Harle and Bechthold, 2009).Since the sugar moieties are primarily O-linked to the natural product core the acid sensitivity strictly limits a principal therapeutical application. A practical alternative is to improve the molecule utilizability by replacing the labile O-aryl bond with an enzymatical and chemical stable C- glycosidic bond. The resulting structural difference might not influence the bioactivity but raises enormously the rigidity. The observed flexibility of UrdGT2 catalyzing C- and O-glycosidic bonds (Durr et al., 2004) brought up the idea to engineer LanGT2, a strictly O-glycosyltransferase involved in the biosynthesis of the anticancer agent landomycin A (Luzhetskyy et al., 2005),towards a C-glycosylating enzyme. By integrating computational assistance with multiple target amino acid replacement experiments, we interconverted the naturally O-glycosylating enzyme LanGT2 towards a glycosyltransferase evolved to catalyzes the sugar attachment by a C-glycosidic bond. Elucidated by alanin substitutions and visulized by in silico protein modeling we illustrate the assumed catalytic mechanism determining the C- and O- glycosylation respectively. The achievement in overcoming natural limitations by protein engineering might document a general strategy in gaining further chemical diversity in the field of combinatorial biosynthesis. References: Durr,C., Hoffmeister,D., Wohlert,S.E., Ichinose,K., Weber,M., Von Mulert,U., Thorson,J.S., and Bechthold,A. (2004). The glycosyltransferase UrdGT2 catalyzes both C- and O-glycosidic sugar transfers. Angew. Chem. Int. Ed Engl. 43, Harle,J. and Bechthold,A. (2009). Chapter 12. The power of glycosyltransferases to generate bioactive natural compounds. Methods Enzymol. 458, Luzhetskyy,A., Taguchi,T., Fedoryshyn,M., Durr,C., Wohlert,S.E., Novikov,V., and Bechthold,A. (2005). LanGT2 Catalyzes the First Glycosylation Step during landomycin A biosynthesis. Chembiochem. 6,

25 Master Thesis: The Influence of Mechanical Defects on the Lattice of silicon T. Jauss 1, J. Wittge 1, A.N. Danilewsky 1, A. Cröll 1, J. Garagorri 2, R. M. Elizalde 2, D. Allen 3, P. McNally 3 1 Universität Freiburg, Kristallographie, Geowissenschaftliches Institut, Freiburg, Germany 2 Centro de Estudios e Investigaciones Tecnicas de Gipuzkoa, CEIT and Tecnun (University of Navarra), San Sebastian, Spain 3 Dublin City University, The RINCE Institute, Dublin, Ireland Correspondence The aim of this Master was thesis to examine the impact of mechanical damage to the silicon lattice. For this reason controlled damage was applied to silicon wafers with a boron doped layer by nanoindentation [Gar10]. A diamond Vickers tip on an Agilent Nanoindenter II has been used for indentation and the resulting damage has been characterized by differential interference contrast microscopy (NIC) and high resolution X-ray diffraction (HRXRD). Damage by loads of 1N 5N is compared. Rocking curves (RC) and reciprocal space maps (RSM) were recorded and analyzed with respect to full width at half maximum and lattice plane spacing by the method of Bond. The volume of the disturbed crystal material around the indents is very small compared to the undisturbed volume. Therefore a line of seven indents with 1N indentation load is oriented in a way that it lies parallel to the line focus of the X-ray beam in order to increase the signal intensity of the disturbed crystal. The RSM of the undisturbed crystal volume is regarded as a reference, the sharp RC are confirmed by the sharp confined peaks in the RSM. Only artefact streaks of the monochromator and the analyzer are also clearly visible, as well as the dynamical streak of the specimen (Fig. 1a). Despite the low count rate, a clear anisotropic intensity distribution around the layer related peak is visible at the damaged area (Fig. 1b). Fig. 1: Reciprocal space maps of the 004 reflection. Two peaks produced by the lattice mismatch between the silicon substrate and the boron doped layer can be observed in both cases. a) Undisturbed area: sharp confined peaks of the silicon substrate and the B-doped layer, as well as the apparatus induced artefact streaks and the dynamical specimen streak. b) Disturbed area: an anisotropic broadening of the peak bases is clearly visible, but mainly concentrated around the layer related peak. [Gar10] Garagorri, J., Gorostegui-Colinas, E., Elizalde, M.R., Allen, D., McNally, P. (2010) Nanoindentation induced silicon fracture and 3D modelling, Anales de Mecánica de la Fractura, 27, pages

26 Biomonitoring of atmospheric particles on cypress leaves - sampled in the vicinity of a nuclear plant- R. KALTENMEIER 1*, R. GIERÉ 1 AND L. POURCELOT² 1 Albert-Ludwigs-Universität, D Freiburg, Germany (*correspondence: ²Institut de Radioprotection et de Sûreté Nucléaire, Cadarache, F St Paul lez Durance, France Environmental pollution can be assessed and evaluated by plants as biological monitors. Their use can be selected depending on the investigation objective, by their ability to reflect past and/ or current environmental conditions as well as temporal changes (Wolterbeek 2002). Coniferous trees belong to the best passive bioindicators for air, soil and water pollution (Saito et al. 2004). For cypress leaves (Chamaecyparis nootkatensis), sampled in the vicinity of the Malvesi unranium processing facility, SW France, increased activity of actinides and some of their decay products has been reported (Figure 1). Ejection via smokestacks and artificial ponds inside the facility are the source of these enhanced activities. Air dried leaf samples were examined systematically by scanning electron microscopy (SEM) in secondary and backscattered electron mode in combination with energydispersive X-ray spectrometry (EDX), in order to characterize particulate matter deposited on leaf surfaces and to verify the existence of radioactive particles. For the interpretation of qualitative EDX spectra of individual particles trapped on the leaf surfaces, signals resulting from C or AU coating as well as the background spectra of the cypress leaves themselves were taken into account (Figure 2). Particle sizes ranging from <200 nm to ~40 μm were found. The boundaries between facial and lateral leaves showed a greater abundance of particles compared to the adaxial leaf surfaces (Figure 3). According to the most prominent peaks in the EDX spectra, roughly 80% of all examined particles were chemically classified as the following five classes: carbonates, silicates, sulfates, oxides/ hydroxides, and halides (Figure 4). The remaining particles include Fe alloys, scheelite-group phases, phosphates, sulfides and fly ash spheres. Most importantly, U-rich particles, particularly U-oxides, except one being a U-oxide-fluorite-particle, could be identified (Figure 5). Without dispute these particles were ejected into the atmosphere by the nuclear facility, prior to their deposition on the leaf surfaces. Most of the U-rich particles are 1 µm in diameter and are therefore respirable. Once inhaled, particles containing alpha emitting isotopes, are a long term source of ionizing radiation, and can potentially cause severe lung damages. Therefore the releases of the Malvési facility pose a threat to the health of people living nearby. 26

27 Carbamates as a new prodrug concept for HDACs Keller, K. [a], Stolfa, D.A., [a,d] Schlimme, S., [b] Hauser, A-T., [a] Carafa, V., [c] Heinke, R., [b] Kannan, S., [b] Cellamare, S., [d] Carotti, A., [d] Altucci, L., [c] Jung, M., * [a] and Sippl, W., * [b] [a] Albert-Ludwigs-Universität Freiburg, Albertstr. 25, Freiburg [b] Martin-Luther-Universität, Wolfgang-Langenbeck-Str. 4, Halle/Saale [c] Seconda Università di Napoli, Vico L. De Crecchio 7, Napoli [d] Università degli Studi Aldo Moro, Via Orabona 4, 7012 Bari Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are responsible for maintaining the acetylation equilibrium. HDACs are amidohydrolases that cleave the acetamide bond by a zinc-dependent mechanism. Inhibitors of HDACs have shown great promise in the development as new anticancer agents. Hence, a prodrug principle for HDAC inhibitors is a valuable concept to optimize cellular activity. Our experimental results validate the general applicability of the carbamate group as a prodrug for hydroxamates, as compound 2 is inducing cellular hyperacetylation in a similar range of concentration as compared to the parent hydroxamate 1. These results demonstrate that the introduction of a carbamate group is a valuable concept for the design of new HDAC inhibitors with improved pharmacokinetic properties. Introducing a carbamate group on the hydroxamic acid function of SAHA (suberoylanilide hydroxamic acid), a drug already approved as a HDAC inhibitor, led to further prodrugs, such as compound 3. We synthesized further carbamates from SAHA with different moieties to further investigate stability, cellular activity and to study the impact of different substitution patterns by considering pharmacokinetic aspects like solubility. 3 1 Literatur: S. Schlimme et al., ChemMedChem 2011, 6 (4) 27

28 STABILIZATION OF DIALKYL METAL COMPOUNDS OF GROUP 13 (R 2 E) 2 B 12 Cl 12 (E = Al, Ga, In) USING THE WEAKLY COORDINATING DIANION [B 12 Cl 12 ] 2- Mathias Keßler, Ardiana Zogaj, Carsten Knapp Institut für Anorganische und Analytische Chemie Albert-Ludwigs-Universität Freiburg, Freiburg i. Br., Germany; The perchlorinated closo-dodecaborate [B 12 Cl 12 ] 2- is a chemically very robust weakly coordinating dianion, for which improved synthesis have been published recently.[1] It was used for the syntheses of trialkyl silylium compounds (R 3 Si)B 12 Cl 12 and the methylating agent Me 2 B 12 Cl 12 which indicate its potential to stabilize electrophilic cations.[2] The stabilization of ion-like dialkyl metal compounds of group 13 [R 2 E] + (E = Al, Ga, In) is a challenging task. Bochmann et al. showed that the tetrakis(pentafluorophenyl)borate [B(C 6 F 5 ) 4 ] anion is not suitable as counterion because degradation occurs during the reaction.[3] In 2002 Reed et al. succeeded in the characterization of (Et 2 Al)(HCB 11 H 5 X 6 ) (X = Cl, Br) using partly halogenated carborane anions.[4] The reactions of the trityl salt [CPh 3 ] 2 [B 12 Cl 12 ] with trialkyl metal compounds R 3 E of group 13 (E = Al, In) and Et 3 Ga (OEt 2 ) leading to (R 2 E) 2 B 12 Cl 12 (E = Al, In; R = Me, Et) and [Et 2 Ga(OEt 2 ) 2 ] 2 [B 12 Cl 12 ] will be discussed. Characterization of the compounds using NMR- and Raman spectroscopy and X-Ray diffraction will be presented.[5] Fig. 1 Part of the crystal structure of (Me 2 Al) 2 B 12 Cl 12. References: [1] a) Knapp, C.; Guttsche, K.; Geis, V.; Scherer, H.; Uzun, R. Dalton Trans. 2009, b) Gu, W.; Ozerov, O. V. Inorg.Chem. 2011, 50, [2] a) Kessler, M.; Knapp, C.; Sagawe, V.; Scherer, H.; Uzun, R. Inorg. Chem. 2010, 49, b) Bolli, C.; Derendorf, J.; Keßler, M.; Knapp, C.; Scherer, H.; Schulz, C.; Warneke, J. Angew. Chem. 2010, 122, ; Angew. Chem. Int. Ed. 2010, 49, [3] Bochmann, M.; Sarsfield, M. J. Organometallics 1998, 17, [4] Kim, K. C.; Reed, C. A.; Long, G. S.; Sen, A. J. Am. Chem. Soc. 2002, 124, [5] Kessler, M.; Knapp, C.; Zogaj, A. Organometallics 2011, accepted. 28

29 Untersuchung des Einflusses von Nanofüllstoffen auf die Trocknung und die Eigenschaften von Polymerfilmen mittels forcierter Rayleighstreuung Kiessling, Andy, Bartsch, Eckhard, Beschichtungen, welche auf der Verwendung von leicht flüchtigen organischen Substanzen basieren, tragen u.a. zum bodennahen Ozon bei. Dieses verursacht eine Reizung des respiratorischen Systems, welches bestehende Atemwegserkrankungen wie Asthma verschlimmert. Im Gegensatz dazu entstehen bei der Herstellung von Beschichtungen aus wässrigen Polymerdispersionen keine schädlichen Emissionen. Trotz ihrer breiten Anwendung ist die Filmbildung aus wässrigen Polymerdispersionen mechanistisch nicht in allen Details verstanden. Einer der wichtigsten Schritte dieser Filmbildung ist die Teilchenkoaleszenz. Dabei lösen sich durch Interdiffusion der Polymerketten die Teilchengrenzen auf und ein mechanisch stabiler Film entsteht. Dieser Prozess wird in unserer Gruppe mit der Methode der forcierten Rayleighstreuung (FRS) auf molekularer Ebene verfolgt. Hierbei wird die Diffusion eines Tracers über verschiedene Weglängen beobachtet, indem durch die Überlagerung zweier Laserstrahlen ein holographisches Gitter eingebleicht wird. Dessen Zerfall durch Farbstoffdiffusion wird über das zeitliche Abklingen eines optischen Braggstreusignals detektiert. Aus der Interpretation und Modellierung des Signals gewinnt man Informationen über die Mobilität des Tracers in den verschiedenen Filmkompartimenten, welche durch Diffusionslängen und Diffusionskoeffizienten charakterisiert wird. Aktuell wird der Einfluss innerer und äußerer Partikel-Grenzflächen anhand von Kern-Schale- Systemen untersucht. [1] Diese Untersuchungen sollen Aufschluss über den molekularen Ursprung der makroskopisch beobachteten besonderen Eigenschaften wie Kratzfestigkeit geben, die bei Beschichtungen aus Materialien komplementärer Eigenschaften auftreten. Dafür werden die Schalendicke, die Kerngröße, die Art des Kerns und der Schale variiert. Neben der Natur des Systems haben die Filmbildungsbedingungen (Temperatur, Tensidkonzentration, Trocknungsgeschwindigkeit) enormen Einfluss auf die Eigenschaften der gebildeten Beschichtung. Daher sind die Filmbildungsbedingungen ein weiterer wichtiger Teil der Untersuchungen. Links: Stadien der Filmbildung einer Latex-Dispersion, Mitte: elektronenmikroskopische Aufnahme der Teilchenkoaleszenz, [2] Rechts: schematische Darstellung des FRS-Experiments. [1] K. Suresh, E. Bartsch, J. Polym. Sci. B. 2007, 45, [2] Kolloide Vorstoß in die Nanowelt, Topics in Chemistry, BASF AG, Ludwigshafen. 29

30 In vivo conversion of trans-3-hydroxy-l-proline by heterologously overexpressed microbial trans-4-prolinehydroxylase Christian Klein, Michael Müller and Wolfgang Hüttel Lehrstuhl für Pharmazeutische und Medizinische Chemie, Albert-Ludwigs-Universität Freiburg, Germany Heterologously overexpressed proline hydroxylases provide the possibilities of enzymatic conversions of L-proline for the regio- and stereospecific generation of hydroxyprolines, useful chiral synthons for chemical synthesis of pharmaceuticals. [1,2] It was also found that proline hydroxylases are not strictly substrate specific but accept a set of proline congeners. [1,3] Among several so far undiscovered reactions, proline-4-hydroxylase showed activity with trans-3-hydroxy-l-proline resulting in the trans-2,3-cis-3,4-dihydroxyproline isomer exclusively. Since in vitro conversion with the enzyme suffers from several drawbacks, an in vivo approach was established. Product concentrations of up to 4 mm were obtained in the fermentation broth of simple shake flask cultures and the product was isolated via ionexchange chromatography in >90% yield. References: [1] C. Klein, W. Hüttel, Adv. Synth. Catal. 2011, 353, [2] P. Remuzon, Tetrahedron 1996, 52, [3] T. Shibasaki, W. Sakuri, A. Hasegawa, Y. Uosaki, H. Mori, M. Yoshida, A. Ozaki, Tetrahedron Lett. 1999, 40,

eurex rundschreiben 094/10

eurex rundschreiben 094/10 eurex rundschreiben 094/10 Datum: Frankfurt, 21. Mai 2010 Empfänger: Alle Handelsteilnehmer der Eurex Deutschland und Eurex Zürich sowie Vendoren Autorisiert von: Jürg Spillmann Weitere Informationen zur

Mehr

Lehrstuhl für Allgemeine BWL Strategisches und Internationales Management Prof. Dr. Mike Geppert Carl-Zeiß-Str. 3 07743 Jena

Lehrstuhl für Allgemeine BWL Strategisches und Internationales Management Prof. Dr. Mike Geppert Carl-Zeiß-Str. 3 07743 Jena Lehrstuhl für Allgemeine BWL Strategisches und Internationales Management Prof. Dr. Mike Geppert Carl-Zeiß-Str. 3 07743 Jena http://www.im.uni-jena.de Contents I. Learning Objectives II. III. IV. Recap

Mehr

ISO 15504 Reference Model

ISO 15504 Reference Model Prozess Dimension von SPICE/ISO 15504 Process flow Remarks Role Documents, data, tools input, output Start Define purpose and scope Define process overview Define process details Define roles no Define

Mehr

Fluid-Particle Multiphase Flow Simulations for the Study of Sand Infiltration into Immobile Gravel-Beds

Fluid-Particle Multiphase Flow Simulations for the Study of Sand Infiltration into Immobile Gravel-Beds 3rd JUQUEEN Porting and Tuning Workshop Jülich, 2-4 February 2015 Fluid-Particle Multiphase Flow Simulations for the Study of Sand Infiltration into Immobile Gravel-Beds Tobias Schruff, Roy M. Frings,

Mehr

Algorithms for graph visualization

Algorithms for graph visualization Algorithms for graph visualization Project - Orthogonal Grid Layout with Small Area W INTER SEMESTER 2013/2014 Martin No llenburg KIT Universita t des Landes Baden-Wu rttemberg und nationales Forschungszentrum

Mehr

Technical Thermodynamics

Technical Thermodynamics Technical Thermodynamics Chapter 1: Introduction, some nomenclature, table of contents Prof. Dr.-Ing. habil. Egon Hassel University of Rostock, Germany Faculty of Mechanical Engineering and Ship Building

Mehr

Extended Ordered Paired Comparison Models An Application to the Data from Bundesliga Season 2013/14

Extended Ordered Paired Comparison Models An Application to the Data from Bundesliga Season 2013/14 Etended Ordered Paired Comparison Models An Application to the Data from Bundesliga Season 2013/14 Gerhard Tutz & Gunther Schauberger Ludwig-Maimilians-Universität München Akademiestraße 1, 80799 München

Mehr

In situ SEM as a tool for investigating micro and nanoscale processes in materials research

In situ SEM as a tool for investigating micro and nanoscale processes in materials research In situ SEM as a tool for investigating micro and nanoscale processes in materials research Reiner Mönig Institut for Materials Research II Electrical Mechanical Heating Electrochemical Experiments Projektbüro

Mehr

Evidence of strobilurine resistant isolates of A. solani and A. alternata in Germany

Evidence of strobilurine resistant isolates of A. solani and A. alternata in Germany Technische Universität München Evidence of strobilurine resistant isolates of A. solani and A. alternata in Germany H. Hausladen, B. Adolf and J. Leiminger outline introduction material and methods results

Mehr

Ingenics Project Portal

Ingenics Project Portal Version: 00; Status: E Seite: 1/6 This document is drawn to show the functions of the project portal developed by Ingenics AG. To use the portal enter the following URL in your Browser: https://projectportal.ingenics.de

Mehr

Influence of dust layer thickness. on specific dust resistivity

Influence of dust layer thickness. on specific dust resistivity on specific dust resistivity D. Pieloth, M. Majid, H. Wiggers, P. Walzel Chair of Mechanical Process Engineering, TU Dortmund, Dortmund/Germany Outline 2 Motivation Measurement of specific dust resistivity

Mehr

Customer-specific software for autonomous driving and driver assistance (ADAS)

Customer-specific software for autonomous driving and driver assistance (ADAS) This press release is approved for publication. Press Release Chemnitz, February 6 th, 2014 Customer-specific software for autonomous driving and driver assistance (ADAS) With the new product line Baselabs

Mehr

Bayerisches Landesamt für Statistik und Datenverarbeitung Rechenzentrum Süd. z/os Requirements 95. z/os Guide in Lahnstein 13.

Bayerisches Landesamt für Statistik und Datenverarbeitung Rechenzentrum Süd. z/os Requirements 95. z/os Guide in Lahnstein 13. z/os Requirements 95. z/os Guide in Lahnstein 13. März 2009 0 1) LOGROTATE in z/os USS 2) KERBEROS (KRB5) in DFS/SMB 3) GSE Requirements System 1 Requirement Details Description Benefit Time Limit Impact

Mehr

Group and Session Management for Collaborative Applications

Group and Session Management for Collaborative Applications Diss. ETH No. 12075 Group and Session Management for Collaborative Applications A dissertation submitted to the SWISS FEDERAL INSTITUTE OF TECHNOLOGY ZÜRICH for the degree of Doctor of Technical Seiences

Mehr

1.9 Dynamic loading: τ ty : torsion yield stress (torsion) τ sy : shear yield stress (shear) In the last lectures only static loadings are considered

1.9 Dynamic loading: τ ty : torsion yield stress (torsion) τ sy : shear yield stress (shear) In the last lectures only static loadings are considered 1.9 Dynaic loading: In the last lectures only static loadings are considered A static loading is: or the load does not change the load change per tie N Unit is 10 /sec 2 Load case Ι: static load (case

Mehr

USBASIC SAFETY IN NUMBERS

USBASIC SAFETY IN NUMBERS USBASIC SAFETY IN NUMBERS #1.Current Normalisation Ropes Courses and Ropes Course Elements can conform to one or more of the following European Norms: -EN 362 Carabiner Norm -EN 795B Connector Norm -EN

Mehr

Welche Rolle kann gemeinwohlorientierte Wissenschaft/Forschungspolitik für die Entwicklung und Umsetzung einer zukunftsfähigen Green Economy spielen?

Welche Rolle kann gemeinwohlorientierte Wissenschaft/Forschungspolitik für die Entwicklung und Umsetzung einer zukunftsfähigen Green Economy spielen? Welche Rolle kann gemeinwohlorientierte Wissenschaft/Forschungspolitik für die Entwicklung und Umsetzung einer zukunftsfähigen Green Economy spielen? - In welcher Verbindung stehen gemeinwohlorientierte

Mehr

CHAMPIONS Communication and Dissemination

CHAMPIONS Communication and Dissemination CHAMPIONS Communication and Dissemination Europa Programm Center Im Freistaat Thüringen In Trägerschaft des TIAW e. V. 1 CENTRAL EUROPE PROGRAMME CENTRAL EUROPE PROGRAMME -ist als größtes Aufbauprogramm

Mehr

Exercise (Part II) Anastasia Mochalova, Lehrstuhl für ABWL und Wirtschaftsinformatik, Kath. Universität Eichstätt-Ingolstadt 1

Exercise (Part II) Anastasia Mochalova, Lehrstuhl für ABWL und Wirtschaftsinformatik, Kath. Universität Eichstätt-Ingolstadt 1 Exercise (Part II) Notes: The exercise is based on Microsoft Dynamics CRM Online. For all screenshots: Copyright Microsoft Corporation. The sign ## is you personal number to be used in all exercises. All

Mehr

PART 3: MODELLING BUSINESS PROCESSES EVENT-DRIVEN PROCESS CHAINS (EPC)

PART 3: MODELLING BUSINESS PROCESSES EVENT-DRIVEN PROCESS CHAINS (EPC) Information Management II / ERP: Microsoft Dynamics NAV 2009 Page 1 of 5 PART 3: MODELLING BUSINESS PROCESSES EVENT-DRIVEN PROCESS CHAINS (EPC) Event-driven Process Chains are, in simple terms, some kind

Mehr

IPEK. Institut für Produktentwicklung. Institut für Produktentwicklung Universität Karlsruhe (TH) Prof. A. Albers

IPEK. Institut für Produktentwicklung. Institut für Produktentwicklung Universität Karlsruhe (TH) Prof. A. Albers Bead Optimization with respect to acoustical behavior - o.prof.dr.-ing.dr.h.c.a.albers Institute of Product Development University of Karlsruhe (TH) 2007 Alle Rechte beim Karlsruhe. Jede Institute of Product

Mehr

Titelbild1 ANSYS. Customer Portal LogIn

Titelbild1 ANSYS. Customer Portal LogIn Titelbild1 ANSYS Customer Portal LogIn 1 Neuanmeldung Neuanmeldung: Bitte Not yet a member anklicken Adressen-Check Adressdaten eintragen Customer No. ist hier bereits erforderlich HERE - Button Hier nochmal

Mehr

Labour law and Consumer protection principles usage in non-state pension system

Labour law and Consumer protection principles usage in non-state pension system Labour law and Consumer protection principles usage in non-state pension system by Prof. Dr. Heinz-Dietrich Steinmeyer General Remarks In private non state pensions systems usually three actors Employer

Mehr

Support Technologies based on Bi-Modal Network Analysis. H. Ulrich Hoppe. Virtuelles Arbeiten und Lernen in projektartigen Netzwerken

Support Technologies based on Bi-Modal Network Analysis. H. Ulrich Hoppe. Virtuelles Arbeiten und Lernen in projektartigen Netzwerken Support Technologies based on Bi-Modal Network Analysis H. Agenda 1. Network analysis short introduction 2. Supporting the development of virtual organizations 3. Supporting the development of compentences

Mehr

Inequality Utilitarian and Capabilities Perspectives (and what they may imply for public health)

Inequality Utilitarian and Capabilities Perspectives (and what they may imply for public health) Inequality Utilitarian and Capabilities Perspectives (and what they may imply for public health) 1 Utilitarian Perspectives on Inequality 2 Inequalities matter most in terms of their impact onthelivesthatpeopleseektoliveandthethings,

Mehr

SAP PPM Enhanced Field and Tab Control

SAP PPM Enhanced Field and Tab Control SAP PPM Enhanced Field and Tab Control A PPM Consulting Solution Public Enhanced Field and Tab Control Enhanced Field and Tab Control gives you the opportunity to control your fields of items and decision

Mehr

DAS METABOLOM: ERNÄHRUNGSSTATUS, METABOLISMUS, METABOLITEN

DAS METABOLOM: ERNÄHRUNGSSTATUS, METABOLISMUS, METABOLITEN DAS METABOLOM: ERNÄHRUNGSSTATUS, METABOLISMUS, METABOLITEN Das Metabolom Extrinsiche Faktoren Ernährung (Nährstoffe und nicht nutritive Lebensmittelinhaltsstoffe) Arzneimittel Physische Aktivität Darmflora

Mehr

Introducing PAThWay. Structured and methodical performance engineering. Isaías A. Comprés Ureña Ventsislav Petkov Michael Firbach Michael Gerndt

Introducing PAThWay. Structured and methodical performance engineering. Isaías A. Comprés Ureña Ventsislav Petkov Michael Firbach Michael Gerndt Introducing PAThWay Structured and methodical performance engineering Isaías A. Comprés Ureña Ventsislav Petkov Michael Firbach Michael Gerndt Technical University of Munich Overview Tuning Challenges

Mehr

Prediction Market, 28th July 2012 Information and Instructions. Prognosemärkte Lehrstuhl für Betriebswirtschaftslehre insbes.

Prediction Market, 28th July 2012 Information and Instructions. Prognosemärkte Lehrstuhl für Betriebswirtschaftslehre insbes. Prediction Market, 28th July 2012 Information and Instructions S. 1 Welcome, and thanks for your participation Sensational prices are waiting for you 1000 Euro in amazon vouchers: The winner has the chance

Mehr

Dossier AD586. Limited edition

Dossier AD586. Limited edition Dossier AD586 Market study of Holst Porzellan GmbH regarding the online trading volume of European manufacturers from 15.08.2012 until 29.08.2012 on the Internet platform ebay in the Federal Republic of

Mehr

Einsatz einer Dokumentenverwaltungslösung zur Optimierung der unternehmensübergreifenden Kommunikation

Einsatz einer Dokumentenverwaltungslösung zur Optimierung der unternehmensübergreifenden Kommunikation Einsatz einer Dokumentenverwaltungslösung zur Optimierung der unternehmensübergreifenden Kommunikation Eine Betrachtung im Kontext der Ausgliederung von Chrysler Daniel Rheinbay Abstract Betriebliche Informationssysteme

Mehr

p^db=`oj===pìééçêíáåñçêã~íáçå=

p^db=`oj===pìééçêíáåñçêã~íáçå= p^db=`oj===pìééçêíáåñçêã~íáçå= Error: "Could not connect to the SQL Server Instance" or "Failed to open a connection to the database." When you attempt to launch ACT! by Sage or ACT by Sage Premium for

Mehr

Accounting course program for master students. Institute of Accounting and Auditing http://www.wiwi.hu-berlin.de/rewe

Accounting course program for master students. Institute of Accounting and Auditing http://www.wiwi.hu-berlin.de/rewe Accounting course program for master students Institute of Accounting and Auditing http://www.wiwi.hu-berlin.de/rewe 2 Accounting requires institutional knowledge... 3...but it pays: Lehman Bros. Inc.,

Mehr

An Introduction to Monetary Theory. Rudolf Peto

An Introduction to Monetary Theory. Rudolf Peto An Introduction to Monetary Theory Rudolf Peto 0 Copyright 2013 by Prof. Rudolf Peto, Bielefeld (Germany), www.peto-online.net 1 2 Preface This book is mainly a translation of the theoretical part of my

Mehr

Simulation of Longitudinal Beam Dynamics

Simulation of Longitudinal Beam Dynamics Fachgebiet Theoretische Elektrotechnik und Numerische Feldberechnung PD Dr. Markus Clemens DESY Beam Dynamics Meeting Simulation of Longitudinal Beam Dynamics, Markus Clemens Chair for Theory in Electrical

Mehr

Security Planning Basics

Security Planning Basics Einführung in die Wirtschaftsinformatik VO WS 2009/2010 Security Planning Basics Gerald.Quirchmayr@univie.ac.at Textbook used as basis for these slides and recommended as reading: Whitman, M. E. & Mattord,

Mehr

Exercise (Part XI) Anastasia Mochalova, Lehrstuhl für ABWL und Wirtschaftsinformatik, Kath. Universität Eichstätt-Ingolstadt 1

Exercise (Part XI) Anastasia Mochalova, Lehrstuhl für ABWL und Wirtschaftsinformatik, Kath. Universität Eichstätt-Ingolstadt 1 Exercise (Part XI) Notes: The exercise is based on Microsoft Dynamics CRM Online. For all screenshots: Copyright Microsoft Corporation. The sign ## is you personal number to be used in all exercises. All

Mehr

Strategies for Random Contract-Based Testing

Strategies for Random Contract-Based Testing DISS. ETH NO. 18143 Strategies for Random Contract-Based Testing A dissertation submitted to ETH ZURICH for the degree of Doctor of Sciences presented by ILINCA CIUPA Dipl. Eng., Technical University of

Mehr

Using TerraSAR-X data for mapping of damages in forests caused by the pine sawfly (Dprion pini) Dr. Klaus MARTIN klaus.martin@slu-web.

Using TerraSAR-X data for mapping of damages in forests caused by the pine sawfly (Dprion pini) Dr. Klaus MARTIN klaus.martin@slu-web. Using TerraSAR-X data for mapping of damages in forests caused by the pine sawfly (Dprion pini) Dr. Klaus MARTIN klaus.martin@slu-web.de Damages caused by Diprion pini Endangered Pine Regions in Germany

Mehr

Controlling the Surface Properties of Nanoparticles Bioorganically modified Nanoparticles for Cell Signaling (NANOCYTES)

Controlling the Surface Properties of Nanoparticles Bioorganically modified Nanoparticles for Cell Signaling (NANOCYTES) Surfaces and Interfaces NANCYTES Engineering at the Nanoscale, DECHEMA, 9. März 2005 Controlling the Surface Properties of Nanoparticles Bioorganically modified Nanoparticles for Cell Signaling (NANCYTES)

Mehr

Chemical heat storage using Na-leach

Chemical heat storage using Na-leach Hilfe2 Materials Science & Technology Chemical heat storage using Na-leach Robert Weber Empa, Material Science and Technology Building Technologies Laboratory CH 8600 Dübendorf Folie 1 Hilfe2 Diese Folie

Mehr

ReadMe zur Installation der BRICKware for Windows, Version 6.1.2. ReadMe on Installing BRICKware for Windows, Version 6.1.2

ReadMe zur Installation der BRICKware for Windows, Version 6.1.2. ReadMe on Installing BRICKware for Windows, Version 6.1.2 ReadMe zur Installation der BRICKware for Windows, Version 6.1.2 Seiten 2-4 ReadMe on Installing BRICKware for Windows, Version 6.1.2 Pages 5/6 BRICKware for Windows ReadMe 1 1 BRICKware for Windows, Version

Mehr

Understanding and Improving Collaboration in Distributed Software Development

Understanding and Improving Collaboration in Distributed Software Development Diss. ETH No. 22473 Understanding and Improving Collaboration in Distributed Software Development A thesis submitted to attain the degree of DOCTOR OF SCIENCES of ETH ZURICH (Dr. sc. ETH Zurich) presented

Mehr

Kongsberg Automotive GmbH Vehicle Industry supplier

Kongsberg Automotive GmbH Vehicle Industry supplier Kongsberg Automotive GmbH Vehicle Industry supplier Kongsberg Automotive has its HQ in Hallbergmoos, 40 locations worldwide and more than 10.000 employees. We provide world class products to the global

Mehr

Introduction to the diploma and master seminar in FSS 2010. Prof. Dr. Armin Heinzl. Sven Scheibmayr

Introduction to the diploma and master seminar in FSS 2010. Prof. Dr. Armin Heinzl. Sven Scheibmayr Contemporary Aspects in Information Systems Introduction to the diploma and master seminar in FSS 2010 Chair of Business Administration and Information Systems Prof. Dr. Armin Heinzl Sven Scheibmayr Objective

Mehr

The poetry of school.

The poetry of school. International Week 2015 The poetry of school. The pedagogy of transfers and transitions at the Lower Austrian University College of Teacher Education(PH NÖ) Andreas Bieringer In M. Bernard s class, school

Mehr

GIPS 2010 Gesamtüberblick. Dr. Stefan J. Illmer Credit Suisse. Seminar der SBVg "GIPS Aperitif" 15. April 2010 Referat von Stefan Illmer

GIPS 2010 Gesamtüberblick. Dr. Stefan J. Illmer Credit Suisse. Seminar der SBVg GIPS Aperitif 15. April 2010 Referat von Stefan Illmer GIPS 2010 Gesamtüberblick Dr. Stefan J. Illmer Credit Suisse Agenda Ein bisschen Historie - GIPS 2010 Fundamentals of Compliance Compliance Statement Seite 3 15.04.2010 Agenda Ein bisschen Historie - GIPS

Mehr

Software development with continuous integration

Software development with continuous integration Software development with continuous integration (FESG/MPIfR) ettl@fs.wettzell.de (FESG) neidhardt@fs.wettzell.de 1 A critical view on scientific software Tendency to become complex and unstructured Highly

Mehr

RailMaster New Version 7.00.p26.01 / 01.08.2014

RailMaster New Version 7.00.p26.01 / 01.08.2014 RailMaster New Version 7.00.p26.01 / 01.08.2014 English Version Bahnbuchungen so einfach und effizient wie noch nie! Copyright Copyright 2014 Travelport und/oder Tochtergesellschaften. Alle Rechte vorbehalten.

Mehr

Role Play I: Ms Minor Role Card. Ms Minor, accountant at BIGBOSS Inc.

Role Play I: Ms Minor Role Card. Ms Minor, accountant at BIGBOSS Inc. Role Play I: Ms Minor Role Card Conversation between Ms Boss, CEO of BIGBOSS Inc. and Ms Minor, accountant at BIGBOSS Inc. Ms Boss: Guten Morgen, Frau Minor! Guten Morgen, Herr Boss! Frau Minor, bald steht

Mehr

Applying Pléiades in the ASAP project HighSens

Applying Pléiades in the ASAP project HighSens Applying Pléiades in the ASAP project HighSens Highly versatile, new satellite Sensor applications for the Austrian market and International Development (Contract number: 833435) Dr. Eva Haas, GeoVille

Mehr

Extract of the Annotations used for Econ 5080 at the University of Utah, with study questions, akmk.pdf.

Extract of the Annotations used for Econ 5080 at the University of Utah, with study questions, akmk.pdf. 1 The zip archives available at http://www.econ.utah.edu/ ~ ehrbar/l2co.zip or http: //marx.econ.utah.edu/das-kapital/ec5080.zip compiled August 26, 2010 have the following content. (they differ in their

Mehr

HARTNAGEL Etikettiermaschinen für Verpackungsbecher und Automation. Etikettierautomat - EMR 8-200 / EMR 8-400

HARTNAGEL Etikettiermaschinen für Verpackungsbecher und Automation. Etikettierautomat - EMR 8-200 / EMR 8-400 Etikettierautomat - EMR 8-200 / EMR 8-400 Die Firma Hartnagel, begann vor über 15 Jahren den ersten Etikettierautomaten zu entwickeln und zu bauen. Geleitet von der Idee, das hinsichtlich der Produktführung

Mehr

1. General information... 2 2. Login... 2 3. Home... 3 4. Current applications... 3

1. General information... 2 2. Login... 2 3. Home... 3 4. Current applications... 3 User Manual for Marketing Authorisation and Lifecycle Management of Medicines Inhalt: User Manual for Marketing Authorisation and Lifecycle Management of Medicines... 1 1. General information... 2 2. Login...

Mehr

AS Path-Prepending in the Internet And Its Impact on Routing Decisions

AS Path-Prepending in the Internet And Its Impact on Routing Decisions (SEP) Its Impact on Routing Decisions Zhi Qi ytqz@mytum.de Advisor: Wolfgang Mühlbauer Lehrstuhl für Netzwerkarchitekturen Background Motivation BGP -> core routing protocol BGP relies on policy routing

Mehr

City Development Plan for Vienna 2005 www.wien.at / stadtentwicklung / step

City Development Plan for Vienna 2005 www.wien.at / stadtentwicklung / step Lebensqualität City Development Plan for Vienna 2005 wwwwienat / stadtentwicklung / step Results of COMET Project which will be part of the new City Development Plan Vienna 2005 Suggestions in the draft-version

Mehr

Medical Image Processing MediGRID. GRID-Computing für Medizin und Lebenswissenschaften

Medical Image Processing MediGRID. GRID-Computing für Medizin und Lebenswissenschaften Medical Image Processing in Medical Image Processing Image Processing is of high importantance for medical research, diagnosis and therapy High storage capacity Volume data, high resolution images, screening

Mehr

Working Sets for the Principle of Least Privilege in Role Based Access Control (RBAC) and Desktop Operating Systems DISSERTATION

Working Sets for the Principle of Least Privilege in Role Based Access Control (RBAC) and Desktop Operating Systems DISSERTATION UNIVERSITÄT JOHANNES KEPLER LINZ JKU Technisch-Naturwissenschaftliche Fakultät Working Sets for the Principle of Least Privilege in Role Based Access Control (RBAC) and Desktop Operating Systems DISSERTATION

Mehr

VPPR Stab Sicherheit, Gesundheit und Umwelt Safety, Security, Health and Environment. Laser which rules apply in Switzerland?

VPPR Stab Sicherheit, Gesundheit und Umwelt Safety, Security, Health and Environment. Laser which rules apply in Switzerland? Laser which rules apply in Switzerland? ETH Zürich KT/07.07.2008 When in danger say STOP! VPPR Laser classes Class 1 Eye safe < 0.39 mw Class 1M Eye safe without optical instruments 400 700 nm < 0.39 mw

Mehr

SARA 1. Project Meeting

SARA 1. Project Meeting SARA 1. Project Meeting Energy Concepts, BMS and Monitoring Integration of Simulation Assisted Control Systems for Innovative Energy Devices Prof. Dr. Ursula Eicker Dr. Jürgen Schumacher Dirk Pietruschka,

Mehr

Christ Water Technology Group

Christ Water Technology Group Christ Water Technology Group 1 / 10.10.2002 / Schmitt G. THREE DIVISIONS OF BWT GROUP BWT AG Christ Water Technology Group Aqua Ecolife Technologies FuMA-Tech (Industrial & Municipal Division) (Household

Mehr

Delivering services in a user-focussed way - The new DFN-CERT Portal -

Delivering services in a user-focussed way - The new DFN-CERT Portal - Delivering services in a user-focussed way - The new DFN-CERT Portal - 29th TF-CSIRT Meeting in Hamburg 25. January 2010 Marcus Pattloch (cert@dfn.de) How do we deal with the ever growing workload? 29th

Mehr

H. Enke, Sprecher des AK Forschungsdaten der WGL

H. Enke, Sprecher des AK Forschungsdaten der WGL https://escience.aip.de/ak-forschungsdaten H. Enke, Sprecher des AK Forschungsdaten der WGL 20.01.2015 / Forschungsdaten - DataCite Workshop 1 AK Forschungsdaten der WGL 2009 gegründet - Arbeit für die

Mehr

MANAGEMENT AND FEDERATION OF STREAM PROCESSING APPLICATIONS

MANAGEMENT AND FEDERATION OF STREAM PROCESSING APPLICATIONS DISS. ETH NO. 20172 MANAGEMENT AND FEDERATION OF STREAM PROCESSING APPLICATIONS A dissertation submitted to ETH ZURICH for the degree of Doctor of Sciences presented by MICHAEL ALEXANDER DULLER Master

Mehr

DATA ANALYSIS AND REPRESENTATION FOR SOFTWARE SYSTEMS

DATA ANALYSIS AND REPRESENTATION FOR SOFTWARE SYSTEMS DATA ANALYSIS AND REPRESENTATION FOR SOFTWARE SYSTEMS Master Seminar Empirical Software Engineering Anuradha Ganapathi Rathnachalam Institut für Informatik Software & Systems Engineering Agenda Introduction

Mehr

Messer und Lochscheiben Knives and Plates

Messer und Lochscheiben Knives and Plates Messer und Lochscheiben Knives and Plates Quality is the difference Seit 1920 Since 1920 Quality is the difference Lumbeck & Wolter Qualität, kontinuierlicher Service und stetige Weiterentwicklung zeichnen

Mehr

Wie agil kann Business Analyse sein?

Wie agil kann Business Analyse sein? Wie agil kann Business Analyse sein? Chapter Meeting Michael Leber 2012-01-24 ANECON Software Design und Beratung G.m.b.H. Alser Str. 4/Hof 1 A-1090 Wien Tel.: +43 1 409 58 90 www.anecon.com office@anecon.com

Mehr

A Practical Approach for Reliable Pre-Project Effort Estimation

A Practical Approach for Reliable Pre-Project Effort Estimation A Practical Approach for Reliable Pre-Project Effort Estimation Carl Friedrich Kreß 1, Oliver Hummel 2, Mahmudul Huq 1 1 Cost Xpert AG, Augsburg, Germany {Carl.Friedrich.Kress,Mahmudul.Huq}@CostXpert.de

Mehr

Disclaimer & Legal Notice. Haftungsausschluss & Impressum

Disclaimer & Legal Notice. Haftungsausschluss & Impressum Disclaimer & Legal Notice Haftungsausschluss & Impressum 1. Disclaimer Limitation of liability for internal content The content of our website has been compiled with meticulous care and to the best of

Mehr

PRESS RELEASE. Kundenspezifische Lichtlösungen von MENTOR

PRESS RELEASE. Kundenspezifische Lichtlösungen von MENTOR Kundenspezifische Lichtlösungen von MENTOR Mit Licht Mehrwert schaffen. Immer mehr Designer, Entwicklungsingenieure und Produktverantwortliche erkennen das Potential innovativer Lichtkonzepte für ihre

Mehr

SAFETY CONSIDERATIONS ON LIQUID HYDROGEN (PART 2)

SAFETY CONSIDERATIONS ON LIQUID HYDROGEN (PART 2) SAFETY CONSIDERATIONS ON LIQUID HYDROGEN (PART 2) Karl Verfondern Research Center Jülich, Germany 2 nd European Summer School on Hydrogen Safety Belfast, July 30 August 8, 2007 Types of Cryogen Release

Mehr

The Single Point Entry Computer for the Dry End

The Single Point Entry Computer for the Dry End The Single Point Entry Computer for the Dry End The master computer system was developed to optimize the production process of a corrugator. All entries are made at the master computer thus error sources

Mehr

Capillary interactions, shear thickening and liquid migration in wet granular media

Capillary interactions, shear thickening and liquid migration in wet granular media Diss. ETH No. 21809 Capillary interactions, shear thickening and liquid migration in wet granular media A dissertation submitted to ETH Zurich for the degree of Doctor of Sciences presented by Roman Andri

Mehr

3. BvD Transfer Pricing Day BEPS und die Auswirkungen auf das operationale Verrechnungspreis-Management

3. BvD Transfer Pricing Day BEPS und die Auswirkungen auf das operationale Verrechnungspreis-Management 3. BvD Transfer Pricing Day BEPS und die Auswirkungen auf das operationale Verrechnungspreis-Management Agenda Einführung Operationales Verrechnungspreis- Management Was bedeutet BEPS für Unternehmen?

Mehr

Infrastructure as a Service (IaaS) Solutions for Online Game Service Provision

Infrastructure as a Service (IaaS) Solutions for Online Game Service Provision Infrastructure as a Service (IaaS) Solutions for Online Game Service Provision Zielsetzung: System Verwendung von Cloud-Systemen für das Hosting von online Spielen (IaaS) Reservieren/Buchen von Resources

Mehr

Distributed testing. Demo Video

Distributed testing. Demo Video distributed testing Das intunify Team An der Entwicklung der Testsystem-Software arbeiten wir als Team von Software-Spezialisten und Designern der soft2tec GmbH in Kooperation mit der Universität Osnabrück.

Mehr

XML Template Transfer Transfer project templates easily between systems

XML Template Transfer Transfer project templates easily between systems Transfer project templates easily between systems A PLM Consulting Solution Public The consulting solution XML Template Transfer enables you to easily reuse existing project templates in different PPM

Mehr

Total Security Intelligence. Die nächste Generation von Log Management and SIEM. Markus Auer Sales Director Q1 Labs.

Total Security Intelligence. Die nächste Generation von Log Management and SIEM. Markus Auer Sales Director Q1 Labs. Total Security Intelligence Die nächste Generation von Log Management and SIEM Markus Auer Sales Director Q1 Labs IBM Deutschland 1 2012 IBM Corporation Gezielte Angriffe auf Unternehmen und Regierungen

Mehr

An Open Innovation Technology Transfer Concept - R&D Cooperation for breakthrough Technologies between Academic Spin-Offs and established Industry

An Open Innovation Technology Transfer Concept - R&D Cooperation for breakthrough Technologies between Academic Spin-Offs and established Industry Diss ETH NO. 20731 An Open Innovation Technology Transfer Concept - R&D Cooperation for breakthrough Technologies between Academic Spin-Offs and established Industry A dissertation submitted to ETH ZURICH

Mehr

LIFE SCIENCES Forschung & Entwicklung

LIFE SCIENCES Forschung & Entwicklung LIFE SCIENCES Forschung & Entwicklung Vol. 9 RHOMBOS Bibliografische Information der Deutschen Nationalbibliothek Die Deutsche Nationalbibliothek verzeichnet diese Publikation in der Deutschen Nationalbibliografie;

Mehr

Beschwerdemanagement / Complaint Management

Beschwerdemanagement / Complaint Management Beschwerdemanagement / Complaint Management Structure: 1. Basics 2. Requirements for the implementation 3. Strategic possibilities 4. Direct Complaint Management processes 5. Indirect Complaint Management

Mehr

Config & Change Management of Models

Config & Change Management of Models Config & Change Management of Models HOOD GmbH Keltenring 7 82041 Oberhaching Germany Tel: 0049 89 4512 53 0 www.hood-group.com -1- onf 2007 -Config & Change Management of models Speaker HOOD Group Keltenring

Mehr

Implementation of GMP in the manufacturing of Herbal APIs (Extracts) Dr. Frank Waimer GA Workshop GACP/GMP Münster, 03/09/2013

Implementation of GMP in the manufacturing of Herbal APIs (Extracts) Dr. Frank Waimer GA Workshop GACP/GMP Münster, 03/09/2013 Implementation of GMP in the manufacturing of Herbal APIs (Extracts) Dr. Frank Waimer GA Workshop GACP/GMP Münster, 03/09/2013 1 EU-GMP Guideline Part II (since 2005) Transfer of ICH Q7A (2000) Detailed

Mehr

Field Librarianship in den USA

Field Librarianship in den USA Field Librarianship in den USA Bestandsaufnahme und Zukunftsperspektiven Vorschau subject librarians field librarians in den USA embedded librarians das amerikanische Hochschulwesen Zukunftsperspektiven

Mehr

Modellfreie numerische Prognosemethoden zur Tragwerksanalyse

Modellfreie numerische Prognosemethoden zur Tragwerksanalyse Modellfreie numerische Prognosemethoden zur Tragwerksanalyse Zur Erlangung des akademischen Grades Doktor-Ingenieur (Dr.-Ing.) an der Fakultät Bauingenieurwesen der Technischen Universität Dresden eingereichte

Mehr

Product Lifecycle Manager

Product Lifecycle Manager Product Lifecycle Manager ATLAS9000 GmbH Landauer Str. - 1 D-68766 Hockenheim +49(0)6205 / 202730 Product Lifecycle Management ATLAS PLM is powerful, economical and based on standard technologies. Directory

Mehr

MHG - Modular Humidity Generator

MHG - Modular Humidity Generator MHG - Modular Humidity Generator Humidity Control Kontrollierte Luftfeuchtigkeit To provide reliable and reproducible results, an increasing number of analytical test methods require controlled environmental

Mehr

Klausur Verteilte Systeme

Klausur Verteilte Systeme Klausur Verteilte Systeme SS 2005 by Prof. Walter Kriha Klausur Verteilte Systeme: SS 2005 by Prof. Walter Kriha Note Bitte ausfüllen (Fill in please): Vorname: Nachname: Matrikelnummer: Studiengang: Table

Mehr

O N E SOLUTION. VIS//ON Overview Module Datacenter and Cablemanagement. VIS//ON Übersicht Module Datacenter und Kabelmanagement

O N E SOLUTION. VIS//ON Overview Module Datacenter and Cablemanagement. VIS//ON Übersicht Module Datacenter und Kabelmanagement O N E SOLUTION VIS//ON Overview Module Datacenter and Cablemanagement VIS//ON Übersicht Module Datacenter und Kabelmanagement Ü B E R S C H R I F T A R T I K E L I N N E N S E I T E C O M PA N Y OVERV

Mehr

Employment and Salary Verification in the Internet (PA-PA-US)

Employment and Salary Verification in the Internet (PA-PA-US) Employment and Salary Verification in the Internet (PA-PA-US) HELP.PYUS Release 4.6C Employment and Salary Verification in the Internet (PA-PA-US SAP AG Copyright Copyright 2001 SAP AG. Alle Rechte vorbehalten.

Mehr

Veräußerung von Emissionsberechtigungen in Deutschland

Veräußerung von Emissionsberechtigungen in Deutschland Veräußerung von Emissionsberechtigungen in Deutschland Monatsbericht September 2008 Berichtsmonat September 2008 Die KfW hat im Zeitraum vom 1. September 2008 bis zum 30. September 2008 3,95 Mio. EU-Emissionsberechtigungen

Mehr

A central repository for gridded data in the MeteoSwiss Data Warehouse

A central repository for gridded data in the MeteoSwiss Data Warehouse A central repository for gridded data in the MeteoSwiss Data Warehouse, Zürich M2: Data Rescue management, quality and homogenization September 16th, 2010 Data Coordination, MeteoSwiss 1 Agenda Short introduction

Mehr

Cooperation Project Sao Paulo - Bavaria. Licensing of Waste to Energy Plants (WEP/URE)

Cooperation Project Sao Paulo - Bavaria. Licensing of Waste to Energy Plants (WEP/URE) Cooperation Project Sao Paulo - Bavaria Licensing of Waste to Energy Plants (WEP/URE) SMA 15.10.2007 W. Scholz Legal framework Bayerisches Staatsministerium für European Directive on Waste incineration

Mehr

Der RIA von ICN eignet sich zur Überwachung der Lutealphase.

Der RIA von ICN eignet sich zur Überwachung der Lutealphase. 6 Zusammenfassung Das Ziel der vorliegenden Arbeit bestand darin die Eignung von gering invasiven Methoden (Messung der Körperinnentemperatur, Gewinnung von Vaginalsekret zur Bestimmung von ph-wert und

Mehr

Robotino View Kommunikation mit OPC. Communication with OPC DE/EN 04/08

Robotino View Kommunikation mit OPC. Communication with OPC DE/EN 04/08 Robotino View Kommunikation mit OPC Robotino View Communication with OPC 1 DE/EN 04/08 Stand/Status: 04/2008 Autor/Author: Markus Bellenberg Festo Didactic GmbH & Co. KG, 73770 Denkendorf, Germany, 2008

Mehr

SpraySpy. Innovative Droplet and Particle Characterisation Innovative Tropfen und Partikel Charakterisierung

SpraySpy. Innovative Droplet and Particle Characterisation Innovative Tropfen und Partikel Charakterisierung SpraySpy Innovative Droplet and Particle Characterisation Innovative Tropfen und Partikel Charakterisierung SpraySpy : The real time spray control The characterization of drops and particles in flows is

Mehr

Abteilung Internationales CampusCenter

Abteilung Internationales CampusCenter Abteilung Internationales CampusCenter Instructions for the STiNE Online Enrollment Application for Exchange Students 1. Please go to www.uni-hamburg.de/online-bewerbung and click on Bewerberaccount anlegen

Mehr

Workflows, Ansprüche und Grenzen der GNSS- Datenerfassung im Feld

Workflows, Ansprüche und Grenzen der GNSS- Datenerfassung im Feld Workflows, Ansprüche und Grenzen der GNSS- Datenerfassung im Feld Alexander Fischer Senior Application Engineer Asset Collection & GIS 1 Leica Zeno GIS Agenda Erfassung im Feld VS Erfassung im Office Validierung

Mehr

Possible Solutions for Development of Multilevel Pension System in the Republic of Azerbaijan

Possible Solutions for Development of Multilevel Pension System in the Republic of Azerbaijan Possible Solutions for Development of Multilevel Pension System in the Republic of Azerbaijan by Prof. Dr. Heinz-Dietrich Steinmeyer Introduction Multi-level pension systems Different approaches Different

Mehr

Parameter-Updatesoftware PF-12 Plus

Parameter-Updatesoftware PF-12 Plus Parameter-Updatesoftware PF-12 Plus Mai / May 2015 Inhalt 1. Durchführung des Parameter-Updates... 2 2. Kontakt... 6 Content 1. Performance of the parameter-update... 4 2. Contact... 6 1. Durchführung

Mehr