Erfassung und Bewertung unerwünschter Arzneimittelwirkungen nach Anwendung von Impfstoffen : Diskussion der Spontanerfassungsdaten des Paul-Ehrlich-Instituts 1987 bis 1995

Im Rahmen der vorliegenden Arbeit wurden alle UAW-Verdachtsfallberichte nach Anwendung von Impfstoffen, die dem Paul-Ehrlich-Institut im Zeitraum von 1987 bis 1995 zugingen, nochmals aufgearbeitet und für jeden Impfstoff ein Nebenwirkungsprofil (PEI-UAW-PROFIL) erstellt. In diesem Zusammenhang wurden die derzeit gebräuchlichen Systeme zur Arzneimittelüberwachung und Kausalitätsbewertung vorgestellt und diskutiert. Alle derzeit von der ständigen Impfkommission (STIKO) empfohlenen Schutzimpfungen wurden kurz beschrieben und die verfügbaren Impfstoffe mitsamt ihres UAW-Profils charakterisiert. Abschließend wurden Möglichkeiten der Optimierung des derzeit gebräuchlichen passiven Spontanerfassungssystems aufgezeigt.All ADR-reports concerning application of vaccines received by the Paul-Ehrlich- Institut in the years 1987 up to 1995 were reassessed and integrated to get an ADR-profile of each vaccine or vaccine-combination. Due to this, actual pharmacovigilance systems used for collection and assessment of ADR-data are introduced and discussed. All vaccines currently recommended in Germany are shortly characterized including their ADR-profile. Finally, possibilities to optimize the passiv spontaneous reporting system actually used in Germany for vaccine surveillance are discussed

S-wave experiments for the exploration of a deep geothermal carbonate reservoir in the German Molasse Basin

There are many successful geothermal projects that exploit the Upper Jurassic aquifer at 2–3 km depth in the German Molasse Basin. However, up to now, only P-wave seismic exploration has been carried out. In an experiment in the Greater Munich area, we recorded S-waves that were generated by the conventional P-wave seismic survey, using 3C receivers. From this, we built a 3D volume of P- to S-converted (PS) waves using the asymptotic conversion point approach. By combining the P-volume and the resulting PS-seismic volume, we were able to derive the spatial distribution of the vp/vs ratio of both the Molasse overburden and the Upper Jurassic reservoir. We found that the vp/vs ratios for the Molasse units range from 2.0 to 2.3 with a median of 2.15, which is much higher than previously assumed. This raises the depth of hypocenters of induced earthquakes in surrounding geothermal wells. The vp/vs ratios found in the Upper Jurassic vary laterally between 1.5 and 2.2. Since no boreholes are available for verification, we test our results against an independently derived facies classification of the conventional 3D seismic volume and found it correlates well. Furthermore, we see that low vp/vs ratios correlate with high vp and vs velocities. We interpret the latter as dolomitized rocks, which are connected with enhanced permeability in the reservoir. We conclude that 3C registration of conventional P-wave surveys is worthwhile

Supplementary data for article: Molloy, S.; Nikodinović-Runić, J.; Martin, L. B.; Hartmann, H.; Solano, F.; Decker, H.; O’Connor, K. E. Engineering of a Bacterial Tyrosinase for Improved Catalytic Efficiency towards D-Tyrosine Using Random and Site Directed Mutagenesis Approaches. Biotechnology and Bioengineering 2013, 110 (7), 1849–1857. https://doi.org/10.1002/bit.24859

Supporting information for: [https://doi.org/10.1002/bit.24859]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1359]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3491

Nonequilibrium Electron Distribution in Presence of Kondo Impurities

We study the energy relaxation of quasiparticles in voltage biased mesoscopic wires in presence of magnetic impurities. The renormalization of the exchange interaction of Kondo impurities coupled to conduction electrons is extended to the case of a nonequilibrium electron distribution, which is determined self-consistently from a Boltzmann equation with a collision term due to Kondo impurity mediated electron-electron scattering. The approach leads to predictions in quantitative agreement with recent experiments by Pothier et al. [Phys. Rev. Lett. 79, 3490 (1997)].Comment: 4 pages, 3 figure

Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein

Background: Proteolytic processing of the prion protein (PrPC) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous system and in brain diseases. Shedding of almost full-length PrPC into the extracellular space by the metalloprotease ADAM10 is of peculiar relevance since soluble PrP stimulates axonal outgrowth and is protective in neurodegenerative conditions such as Alzheimer’s and prion disease. However, molecular determinates and mechanisms regulating the shedding of PrP are entirely unknown. Methods: We produced an antibody recognizing the neo-epitope of shed PrP generated by ADAM10 in biological samples and used it to study structural and mechanistic aspects affecting the shedding. For this, we investigated genetically modified cellular and murine models by biochemical and morphological approaches. Results: We show that the novel antibody specifically detects shed PrP in cell culture supernatants and murine brain. We demonstrate that ADAM10 is the exclusive sheddase of PrPC in the nervous system and reveal that the glycosylation state and type of membrane-anchorage of PrPC severely affect its shedding. Furthermore, we provide evidence that PrP shedding can be modulated by pharmacological inhibition and stimulation and present data suggesting that shedding is a relevant part of a compensatory network ensuring PrPC homeostasis of the cell. Conclusions: With the new antibody, our study introduces a new tool to reliably investigate PrP-shedding. In addition, this study provides novel and important insight into the regulation of this cleavage event, which is likely to be relevant for diagnostic and therapeutic approaches even beyond neurodegeneration

Supplementary data for article: Molloy, S.; Nikodinović-Runić, J.; Martin, L. B.; Hartmann, H.; Solano, F.; Decker, H.; O’Connor, K. E. Engineering of a Bacterial Tyrosinase for Improved Catalytic Efficiency towards D-Tyrosine Using Random and Site Directed Mutagenesis Approaches. Biotechnology and Bioengineering 2013, 110 (7), 1849–1857. https://doi.org/10.1002/bit.24859

Supporting information for: [https://doi.org/10.1002/bit.24859]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1359]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3491

Variability of the transitional T Tauri star T Chamaeleontis

We characterize the physical properties of T Chamaeleontis, a transitional T Tauri star showing UX Ori-type variability, and of its associated disc, and probe possible effects of disc clearing processes. Different spectral diagnostics are examined, based on a rich collection of optical high- and low-resolution spectra. We determine radial and projected rotational velocities, and measure equivalent widths of the Li I (6708 A) line and of the most prominent emission lines (e.g. Ha, Hb and [OI] 6300A); we analyse shape changes of photospheric lines via bisector-method, while variability in Ha and Hb is inspected through line-profile correlation matrices. The strength of the Ha and Hb emission is highly variable and well correlated with that of the [OI] lines, as well as with Av variations of over three magnitudes. Variations up to nearly 10 km/s in the radial velocity of the star are measured on analogous time-scale, but with no apparent periodicity. SED modelling confirms the existence of a gap in the disc. Variable circumstellar extinction is pointed out as responsible for the conspicuous variations observed in the stellar continuum flux and for concomitant changes in the emission features by contrast effect. Clumpy structures, incorporating large dust grains and orbiting the star within a few tenths of AU, obscure episodically the star and, eventually, part of the inner circumstellar zone, while the bulk of the hydrogen lines emitting zone and outer low-density wind region traced by the [OI] remain unaffected. Coherently with this scenario, the detected radial velocity changes are also explainable in terms of clumpy materials transiting and partially obscuring the star.Comment: 38 pages, 32 figures. To appear in the Astronomy and Astrophysics main journa