![]() Raus, Tonia ![]() Doctoral thesis (2010) Detailed reference viewed: 100 (8 UL)![]() Meyers, Christian ![]() Conference given outside the academic context (2010) Detailed reference viewed: 33 (0 UL)![]() Dentzer, Thomas ![]() Doctoral thesis (2010) An estimated 170 million people are infected with hepatitis C virus (HCV). 15-30% of HCV-induced chronic hepatitis progresses to cirrhosis within years to decades after infection, and 3-4% of them will ... [more ▼] An estimated 170 million people are infected with hepatitis C virus (HCV). 15-30% of HCV-induced chronic hepatitis progresses to cirrhosis within years to decades after infection, and 3-4% of them will develop hepatocellular carcinoma. There is no vaccine available, and current HCV therapy of pegylated interferon-! in combination with ribavirin leads to a sustained response only in about 50% of infected patients. The HCV non-structural protein NS2 (MW 23 kDa) is a dimeric multifunctional hydrophobic protein with an essential but poorly understood role in infectious virus production. The N terminal region of NS2 interacts with membranes whereas the Cterminal region, together with the N-terminal third of NS3, forms the NS2-3 protease. NS2 is not required for RNA synthesis, although cleavage at the NS2/3 junction is necessary for replication. Further, NS2 has been shown to interact with a number of viral and host proteins; it has been reported to activate transcription factors, inhibit apoptosis, and is a substrate for host kinase phosphorylation and proteosomic degradation. NS2 determinants and their respective function in the HCV life cycle were investigated. Based on the crystal structure of the post-cleavage form of the NS2 protease domain, we mutated conserved features and analyzed the effects of these changes on polyprotein processing, replication, and infectious virus production. We found that mutations around the protease active site inhibit viral RNA replication by preventing NS2/3 cleavage. Supplementary assays indicated a dimerization defect for these mutant constructs, which prevented cleavage and RNA replication. In contrast, alterations in the dimer interface and at the C-terminal region did not affect replication, NS2 stability, or NS2 protease activity, but decreased infectious virus production. Analysis of the NS2/3 cleavage site revealed an additional function for several residues besides cleavage, notably in infectious virus production. A more comprehensive deletion and mutagenesis analysis of the C-terminal end of NS2 revealed the importance of its C-terminal residue in infectious particle production. Structural data suggests that the C-terminal leucine is locked in the active site, and mutation or deletion of this residue could therefore alter the NS2 folding and disrupt potential protein-protein interactions important for infectious particle production. Further, we established an NS2- 3 interaction model based on the solved NS2pro and NS3 crystal structures and assessed the importance of proximal residues for viral propagation. We were able to show genetic interactions between the viral proteins NS2 and E1 as well as NS2 and NS3. Additionally a pull down assay of strep-tagged NS2 followed by a mass spectrometry analysis divulged the physical interactions between NS2-E2, and NS2- NS3. Numerous host cell proteins could be identified to interact with NS2, involved in various pathways such as membrane trafficking, actin/myosin interactions or actin polymerization. In this study we dissected the residues of NS2 involved in its multiple essential roles and interactions in the HCV life cycle and established NS2 as a new viable target for HCV-specific inhibitors for future anti-viral therapeutics. [less ▲] Detailed reference viewed: 93 (4 UL)![]() Lippert, Sarah ![]() Doctoral thesis (2010) Detailed reference viewed: 123 (5 UL)![]() Bungard, Volker ![]() Doctoral thesis (2010) The thesis deals with the non-destructive condition assessment of civil engineering structures made of reinforced and prestressed concrete as well as bridges and concentrates on a comparison of static and ... [more ▼] The thesis deals with the non-destructive condition assessment of civil engineering structures made of reinforced and prestressed concrete as well as bridges and concentrates on a comparison of static and dynamic investigation methods. The main questions discuss the sensitivity of changes in static as well as in dynamic properties during the mechanical lifetime of those types of structures under laboratory conditions, the sensitivity of these changes when testing in-situ and the dimension of undesired environmental influences on the dynamic properties. Therefore, a gradually loaded laboratory reinforced concrete beam (cp. chapter 7) and a reinforced as well as a prestressed concrete slab (cp. chapter 8) are investigated for changes in their static and dynamic parameters until reaching their ultimate loads. Furthermore, a successively damaged and stepwise loaded laboratory reinforced concrete slab and a prestressed concrete slab (cp. also chapter 8) are under investigation and also compared in changes in their static as well as in dynamic properties during their lifetimes. By means of static and dynamic tests on a successively damaged and stepwise loaded prestressed concrete bridge (cp. chapter 9) it was possible to investigate the amount of changes in static and dynamic properties for a real in-situ object. A long-term measurement of a composite bridge (cp. chapter 10) demonstrates the environmental influences on the static and dynamic properties of a system which have to be considered when conducting comparative non-destructive condition assessment techniques on real objects. All tests are calculated respectively simulated by the method of the integration of stress (cp. chapter 6) or the finite element method by using the softwares ANSYS and SOFISTIK. Furthermore, measured eigenfrequencies and modeshapes are used to adapt finite element models with the aim to improve the model or to locate and quantify damaged areas. The work is a contribution to the application of non-destructive static and dynamic condition assessment methods on civil engineering structures made of concrete in the sector of civil engineering. [less ▲] Detailed reference viewed: 235 (14 UL)![]() Hemmer, Marc ![]() Doctoral thesis (2010) IK9 was recently reported to be a potent inhibitor of cancer cell invasion and angiogenesis. It markedly reduced in vitro invasion of human HT1080 fibrosarcoma cells through collagen-coated porous ... [more ▼] IK9 was recently reported to be a potent inhibitor of cancer cell invasion and angiogenesis. It markedly reduced in vitro invasion of human HT1080 fibrosarcoma cells through collagen-coated porous membranes (Boyden chamber assay) and in vivo tumour growth in athymic nude mice. It was furthermore able to decrease angiogenesis ex vivo in a rat aortic ring assay and in vivo in a choroidal neovascularisation mice model. It nevertheless presents some water solubility and stability problems, which should be taken into account for further investigations. In the first part of the project, we synthesized original IK9 derivatives, modulated at the 3- and 6-positions, by introducing functional groups able to improve water solubility and metabolic stability. Their in vitro anti-invasive potency was screened and the generated results highlighted some structure-activity relationships. A second part of the project was devoted to the elucidation of the actually unknown mechanism of action of IK9. Anti-invasive or anti-proliferative effects against endothelial cells, main actors of the angiogenic process, were not emphasised. We showed that IK9 acts likely not as an inhibitor of receptor tyrosine kinases (EGFR, PDGFR and VEGFR). The compound generates a weak decrease of mRNA coding for MMP 2 and 9, and on the other hand a substantial diminution of MMP 2 and 9 secretions by HT1080 fibrosarcoma cells. In conclusion, the consideration of anti-invasive properties together with the worked out solubility and stability profiles highlights several series, notably 6-hydroxycoumarins, 6-hydroxymethylcoumarins and coumarin-3-sulfonamides, whose interest as potential successors to IK9 is undeniable. [less ▲] Detailed reference viewed: 115 (2 UL)![]() ; Kalesaki, Efterpi ![]() in Journal of Applied Physics (2010), 108 GaN quantum dots (QDs) grown in semipolar (11-22) AlN by plasma-assisted molecular-beam epitaxy were studied by transmission electron microscopy (TEM) and scanning transmission electron microscopy ... [more ▼] GaN quantum dots (QDs) grown in semipolar (11-22) AlN by plasma-assisted molecular-beam epitaxy were studied by transmission electron microscopy (TEM) and scanning transmission electron microscopy techniques. The embedded (11-22)-grown QDs exhibited pyramidal or truncated-pyramidal morphology consistent with the symmetry of the nucleating plane, and were delimited by nonpolar and semipolar nanofacets. It was also found that, in addition to the (11-22) surface, QDs nucleated at depressions comprising {10-11} facets. This was justified by ab initio density functional theory calculations showing that such GaN/AlN facets are of lower energy compared to (11-22). Based on quantitative high-resolution TEM strain measurements, the three-dimensional QD strain state was analyzed using finite-element simulations. The internal electrostatic field was then estimated, showing small potential drop along the growth direction, and limited localization at most QD interfaces. [less ▲] Detailed reference viewed: 114 (0 UL)![]() Lickova, Magdalena ![]() Speeches/Talks (2010) Detailed reference viewed: 36 (1 UL)![]() Biryukov, Maria ![]() Doctoral thesis (2010) Due to intensive growth of the electronically available publications, bibliographic databases have become widespread. They cover a large variety of knowledge fields and provide a fast access to the wide ... [more ▼] Due to intensive growth of the electronically available publications, bibliographic databases have become widespread. They cover a large variety of knowledge fields and provide a fast access to the wide variety of data. At the same time they contain a wealth of hidden knowledge that requires steps of extra processing in order to infer it. In this work we focus on extraction of such meta knowledge from the research bibliographic databases by looking at them from sociolinguistic, text mining and bibliometric perspectives. We choose the Digital Library and Bibliographic Database as a testbed for our experiments. In the framework of the sociolinguistic analysis we build a statistical system for the language identification of personal names. We show also that extension of a purely statistical model with the co-authors network boosts the system's performance. In the text mining scenario, we perform a number of experiments that focus on topic identification and ranking. While our topic detection approach remains generic and can be used for any kind of textual data, the topic ranking metrics are built upon the information provided by the bibliographic databases. The goal of our bibliometric study is to create a researcher's profile on DBLP and analyze some of the research communities defined by the different conferences, in terms of the publication activity, interdisciplinarity of research, collaboration trends and population stability. We also aim at exploring to what extent these aspects correlate with the conference rank. Each of the above topics constitutes a method of meta information extraction from bibliographic databases and other similarly structured data sources. [less ▲] Detailed reference viewed: 343 (103 UL)![]() ![]() Nienaber, Birte ![]() ![]() Scientific Conference (2010, November 11) Detailed reference viewed: 67 (1 UL)![]() Ratti, Luca ![]() Presentation (2010, November 10) Detailed reference viewed: 88 (0 UL)![]() Selinger, Christian ![]() Doctoral thesis (2010) P ([0, 1])) with respect to the Skorohod topology. In the last chapter we restrict ourselves to the space of histograms on the unit interval. We calculate the Wasserstein distances numerically and obtain ... [more ▼] P ([0, 1])) with respect to the Skorohod topology. In the last chapter we restrict ourselves to the space of histograms on the unit interval. We calculate the Wasserstein distances numerically and obtain a Riemannian metric on the simplex. We investigate explosion behaviour of the respective diffusion processes in dimension 1 and 2. [less ▲] Detailed reference viewed: 188 (15 UL)![]() ![]() ; Meyers, Christian ![]() Article for general public (2010) Detailed reference viewed: 27 (1 UL)![]() Dale, Phillip ![]() ![]() Patent (2010) Detailed reference viewed: 128 (3 UL)![]() Guigou, Jean-Daniel ![]() ![]() Article for general public (2010) Detailed reference viewed: 58 (6 UL)![]() ; Picard, Pierre M. ![]() in International Economic Review (2010), 51(4), 1097-1125 This article presents a market design for the management of noise pollution created by aircraft traffic around airports. A local market for noise licenses allows noise generators to compensate noise ... [more ▼] This article presents a market design for the management of noise pollution created by aircraft traffic around airports. A local market for noise licenses allows noise generators to compensate noise victims and to meet social acceptability. We show that the market allows the market designer to implement the social planner's optimal allocation of flights as long as the latter does not put too high a weight in his/her objective function on firms' profits compared to the disutility of noise pollution. The fact that local representatives of noise victims may be strategic players does not fundamentally alter this finding. Because of the market auctioneer's information constraints, noise licenses are likely to distribute windfall gains to residents, which alters the urban structure in the long run. [less ▲] Detailed reference viewed: 114 (9 UL)![]() ![]() Steffgen, Georges ![]() Scientific Conference (2010, November) Detailed reference viewed: 106 (2 UL)![]() Weth, Constanze ![]() in IMIS Beiträge (2010), 37 Detailed reference viewed: 280 (10 UL)![]() Weth, Constanze ![]() in IMIS Beiträge (2010), 37 Detailed reference viewed: 208 (3 UL)![]() ; Picard, Pierre M. ![]() in Journal of International Economics (2010), 82(2), 230-237 Empirical research on strategic alliances has focused on the idea that alliance partners are selected on the basis of social capital considerations. In this paper we emphasize instead the role of ... [more ▼] Empirical research on strategic alliances has focused on the idea that alliance partners are selected on the basis of social capital considerations. In this paper we emphasize instead the role of complementary knowledge stocks (broadly defined) in partner selection, arguing not only that knowledge complementarity should not be overlooked, but that it may be the true causal force behind alliance formation. To marshal evidence on this point, we design a simple model of partner selection in which firms ally for the purpose of learning and innovating, and in doing so create an industry network. We abstract completely from network-based structural and strategic motives for partner selection and focus instead on the idea that firms’ knowledge bases must “fit” in order for joint leaning and innovation to be possible, and thus for an alliance to be feasible. The striking result is that while containing no social capital considerations, this simple model replicates the firm conduct, network structure, and contingent effects of network position on performance observed and discussed in the empirical literature. [less ▲] Detailed reference viewed: 128 (5 UL) |
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